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Conserved domains on  [gi|21539663|ref|NP_071763|]
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E3 ubiquitin-protein ligase Praja-1 isoform c [Homo sapiens]

Protein Classification

RING-H2_PJA1_2 domain-containing protein (domain architecture ID 11613365)

RING-H2_PJA1_2 domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
RING-H2_PJA1_2 cd16465
RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and ...
406-451 1.11e-31

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; The family includes two highly similar E3 ubiquitin-protein ligases Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Furthermore, Praja-1 regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1, via an ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, or NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP) dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Moreover, Praja-2, together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Furthermore, Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.


:

Pssm-ID: 319379 [Multi-domain]  Cd Length: 46  Bit Score: 114.78  E-value: 1.11e-31
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:cd16465   1 CCPICCCEYVKDEIATELPCHHLFHKLCITAWLQKSGTCPVCRHVL 46
 
Name Accession Description Interval E-value
RING-H2_PJA1_2 cd16465
RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and ...
406-451 1.11e-31

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; The family includes two highly similar E3 ubiquitin-protein ligases Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Furthermore, Praja-1 regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1, via an ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, or NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP) dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Moreover, Praja-2, together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Furthermore, Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.


Pssm-ID: 319379 [Multi-domain]  Cd Length: 46  Bit Score: 114.78  E-value: 1.11e-31
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:cd16465   1 CCPICCCEYVKDEIATELPCHHLFHKLCITAWLQKSGTCPVCRHVL 46
zf-RING_2 pfam13639
Ring finger domain;
407-448 9.15e-15

Ring finger domain;


Pssm-ID: 338865 [Multi-domain]  Cd Length: 44  Bit Score: 67.80  E-value: 9.15e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 21539663   407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:pfam13639   3 CPICLEEFEEGDKVVILPCGHHFHRECLDKWLRSSNTCPLCR 44
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
407-447 6.23e-10

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 54.05  E-value: 6.23e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 21539663    407 CPICCSEYVKgeVATELPCHHYFHKPCVSIWL-QKSGTCPVC 447
Cdd:smart00184   1 CPICLEEYLK--DPVILPCGHTFCRSCIRKWLeSGNNTCPIC 40
COG5540 COG5540
RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, ...
407-454 1.80e-09

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227827 [Multi-domain]  Cd Length: 374  Bit Score: 58.85  E-value: 1.80e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWL-QKSGTCPVCRCMFPPP 454
Cdd:COG5540 326 CAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLlGYSNKCPVCRTAIPPP 374
PHA02929 PHA02929
N1R/p28-like protein; Provisional
425-451 8.45e-03

N1R/p28-like protein; Provisional


Pssm-ID: 222944  Cd Length: 238  Bit Score: 37.45  E-value: 8.45e-03
                         10        20
                 ....*....|....*....|....*..
gi 21539663  425 CHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:PHA02929 200 CNHVFCIECIDIWKKEKNTCPVCRTPF 226
 
Name Accession Description Interval E-value
RING-H2_PJA1_2 cd16465
RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and ...
406-451 1.11e-31

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; The family includes two highly similar E3 ubiquitin-protein ligases Praja-1 and Praja-2. Praja-1, also known as RING finger protein 70, is a RING-H2 finger ubiquitin ligase encoded by gene PJA1, a novel human X chromosome gene abundantly expressed in brain. It has been implicated in bone and liver development, as well as memory formation and X-linked mental retardation (MRX). Praja-1 interacts with and activates the ubiquitin-conjugating enzyme UbcH5B, and shows E2-dependent E3 ubiquitin ligase activity. It is a 3-deazaneplanocin A (DZNep)-induced ubiquitin ligase that directly ubiquitinates individual polycomb repressive complex 2 (PRC2) subunits in a cell free system, which leads to their proteasomal degradation. It also plays an important role in neuronal plasticity, which is the basis for learning and memory. Moreover, Praja-1 ubiquitinates embryonic liver fodrin (ELF) and Smad3, but not Smad4, in a transforming growth factor-beta (TGF-beta)-dependent manner. It controls ELF abundance through ubiquitin-mediated degradation, and further regulates TGF-beta signaling, which plays a key role in the suppression of gastric carcinoma. Furthermore, Praja-1 regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1, via an ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, or NEURODAP1, or KIAA0438, is an E2-dependent E3 ubiquitin ligase that interacts with and activates the ubiquitin-conjugating enzyme UbcH5B. It functions as an A-kinase anchoring protein (AKAP)-like E3 ubiquitin ligase that plays a critical role in controlling cyclic AMP (cAMP) dependent PKA activity and pro-survival signaling, and further promotes cell proliferation and growth. Praja-2 is also involved in protein sorting at the postsynaptic density region of axosomatic synapses and possibly plays a role in synaptic communication and plasticity. Moreover, Praja-2, together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. Furthermore, Praja-2 ubiquitylates and degrades Mob, a core component of NDR/LATS kinase and a positive regulator of the tumor-suppressor Hippo signaling. Both Praja-1 and Praja-2 contain a potential nuclear localization signal (NLS) and a C-terminal C3H2C3-type RING-H2 motif.


Pssm-ID: 319379 [Multi-domain]  Cd Length: 46  Bit Score: 114.78  E-value: 1.11e-31
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:cd16465   1 CCPICCCEYVKDEIATELPCHHLFHKLCITAWLQKSGTCPVCRHVL 46
RING-H2_PA-TM-RING cd16454
RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING ...
406-448 8.97e-18

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3 which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.


Pssm-ID: 319368 [Multi-domain]  Cd Length: 43  Bit Score: 76.19  E-value: 8.97e-18
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16454   1 TCAICLEEFEDGEEVRVLPCNHLFHSNCIDPWLEQHATCPLCR 43
RING-H2_EL5_like cd16461
RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; ...
407-448 6.54e-15

RING finger, H2 subclass, found in rice E3 ubiquitin-protein ligase EL5 and similar proteins; EL5, also known as protein ELICITOR 5, is an E3 ubiquitin-protein ligase containing an N-terminal transmembrane domain and a C3H2C3-type RING-H2 finger that is a binding site for ubiquitin-conjugating enzyme (E2). It can be rapidly induced by N-acetylchitooligosaccharide elicitor. EL5 catalyzes polyubiquitination via the Lys48 residue of ubiquitin, and thus plays a crucial role as a membrane-anchored E3 in the maintenance of cell viability after the initiation of root primordial formation in rice. It also acts as an anti-cell death enzyme that might be responsible for mediating the degradation of cytotoxic proteins produced in root cells after the actions of phytohormones. Moreover, EL5 interacts with UBC5b, a rice ubiquitin carrier protein, through its RING-H2 finger. EL5 is an unstable protein, and its degradation is regulated by the C3H2C3-type RING-H2 finger in a proteasome-independent manner.


Pssm-ID: 319375 [Multi-domain]  Cd Length: 43  Bit Score: 68.11  E-value: 6.54e-15
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16461   2 CPICLEDFEDGELVRLLKCGHVFHKECIDLWLRSHSTCPLCR 43
zf-RING_2 pfam13639
Ring finger domain;
407-448 9.15e-15

Ring finger domain;


Pssm-ID: 338865 [Multi-domain]  Cd Length: 44  Bit Score: 67.80  E-value: 9.15e-15
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 21539663   407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:pfam13639   3 CPICLEEFEEGDKVVILPCGHHFHRECLDKWLRSSNTCPLCR 44
mRING-H2-C3H2C2D_ZSWM2 cd16486
Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing ...
406-448 2.04e-14

Modified RING finger, H2 subclass (C3H2C2D-type), found in zinc finger SWIM domain-containing protein 2 (ZSWIM2) and similar proteins; ZSWIM2, also known as MEKK1-related protein X (MEX) or ZZ-type zinc finger-containing protein 2, is a testis-specific E3 ubiquitin ligase that promotes death receptor-induced apoptosis through Fas, death receptor (DR) 3 and DR4 signaling. ZSWIM2 is self-ubiquitinated and targeted for degradation through the proteasome pathway. It also acts as an E3 ubiquitin ligase, through the E2, Ub-conjugating enzymes UbcH5a, UbcH5c, or UbcH6. ZSWIM2 contains four putative zinc-binding domains including an N-terminal SWIM (SWI2/SNF2 and MuDR) domain critical for its ubiquitination, and two modified RING-H2 fingers separated by a ZZ zinc finger domain, which was required for interaction with UbcH5a and its self-association. This family corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.


Pssm-ID: 319400 [Multi-domain]  Cd Length: 44  Bit Score: 66.87  E-value: 2.04e-14
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSG-TCPVCR 448
Cdd:cd16486   1 QCRICLRDFQAGQVLRKLPCKHKFHRDCIDSWLTHSRpTCPLCG 44
RING-H2_RNF181 cd16669
RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; ...
407-448 2.99e-14

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.


Pssm-ID: 319583 [Multi-domain]  Cd Length: 46  Bit Score: 66.63  E-value: 2.99e-14
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16669   2 CPVCLLEFEEGEEVKEMPCKHSFHSGCILPWLKKTNSCPLCR 43
RING-H2_RNF126_like cd16667
RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; ...
407-448 3.92e-13

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; The family includes RING finger proteins RNF126, RNF115, and similar proteins. RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. RNF115 and RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. Both of them contain an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319581 [Multi-domain]  Cd Length: 43  Bit Score: 63.11  E-value: 3.92e-13
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16667   2 CAVCKEDFKVGEKVRQLPCNHVFHPDCIVPWLEQHNTCPVCR 43
RING-H2 cd16448
H2 subclass of RING (RING-H2) finger and its variants; RING finger is a specialized type of ...
407-448 2.22e-12

H2 subclass of RING (RING-H2) finger and its variants; RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized as two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have different Cys/His pattern. Some lack a single Cys or His residues at typical Zn ligand positions. Especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well. This family corresponds to H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 319362 [Multi-domain]  Cd Length: 44  Bit Score: 60.93  E-value: 2.22e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 407 CPICCSEYVKGE-VATELPCHHYFHKPCVSIWLQ-KSGTCPVCR 448
Cdd:cd16448   1 CAICLEEFEEGDcPVRLLPCGHVFHKSCIDKWLEsGNRTCPLCR 44
RING-H2_RNF115 cd16800
RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; ...
407-448 2.23e-12

RING finger, H2 subclass, found in RING finger protein 115 (RNF115) and similar proteins; RNF115, also known as Rab7-interacting ring finger protein (Rabring 7), or zinc finger protein 364 (ZNF364), or breast cancer-associated gene 2 (BCA2), is an E3 ubiquitin-protein ligase that is an endogenous inhibitor of adenosine monophosphate-activated protein kinase (AMPK) activation and its inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a co-factor in the restriction imposed by tetherin on HIV-1, and targets HIV-1 Gag for lysosomal degradation, impairing virus assembly and release, in a tetherin-independent manner. Moreover, RNF115 is a Rab7-binding protein that stimulates c-Myc degradation through mono-ubiquitination of MM-1. It also plays crucial roles as a Rab7 target protein in vesicle traffic to late endosome/lysosome and lysosome biogenesis. Furthermore, RNF115 and the related protein, RNF126 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF115 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319714 [Multi-domain]  Cd Length: 47  Bit Score: 61.16  E-value: 2.23e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16800   3 CPVCKEDYTVEEQVRQLPCNHFFHSDCIVPWLELHDTCPVCR 44
RING-H2_RNF126 cd16801
RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; ...
407-448 2.54e-12

RING finger, H2 subclass, found in RING finger protein 126 (RNF126) and similar proteins; RNF126 is a Bag6-dependent E3 ubiquitin ligase that is involved in the mislocalized protein (MLP) pathway of quality control. It regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor (CI-MPR). Moreover, RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation, and could be a novel therapeutic target in breast and prostate cancers. It is also able to ubiquitylate cytidine deaminase (AID), a poorly soluble protein that is essential for antibody diversification. In addition, RNF126 and the related protein, RNF115 associate with the epidermal growth factor receptor (EGFR) and promote ubiquitylation of EGFR, suggesting they play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. RNF126 contains an N-terminal BCA2 Zinc-finger domain (BZF), the AKT-phosphorylation sites, and the C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319715 [Multi-domain]  Cd Length: 44  Bit Score: 61.12  E-value: 2.54e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16801   2 CPVCKEDYAVGENVRQLPCNHLFHNDCIVPWLEQHDTCPVCR 43
RING-H2_GRAIL cd16668
RING finger, H2 subclass, found in the GRAIL transmembrane proteins family; The GRAIL ...
406-449 7.16e-12

RING finger, H2 subclass, found in the GRAIL transmembrane proteins family; The GRAIL transmembrane proteins family includes RING finger proteins RNF128 (also known as GRAIL), RNF130, RNF133, RNF148, RNF149, and RNF150, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence. RNF128 is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128. It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression regulated by histone deacetylases. RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that induces the ubiquitination of wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) and promotes its proteasome-dependent degradation. RNF150 is a RING finger protein that its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. The family also includes Drosophila melanogaster protein goliath (d-goliath), also known as protein g1, which is one of the funding members of the family. It was originally identified as a transcription factor involved in the embryo mesoderm formation.


Pssm-ID: 319582 [Multi-domain]  Cd Length: 48  Bit Score: 59.67  E-value: 7.16e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 406 CCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRC 449
Cdd:cd16668   1 QCAVCIEPYKPGDVVRILPCKHIFHKSCVDPWLLEHRTCPMCKL 44
RING-H2_RNF111_like cd16474
RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; ...
407-450 8.70e-12

RING finger, H2 subclass, found in RING finger proteins RNF111, RNF165, and similar proteins; The family includes RING finger proteins RNF111, RNF165, and similar proteins. RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It also interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. The N-terminal half of RNF111 harbors three SUMO-interacting motifs (SIMs). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). RNF165, also known as Arkadia-like 2, or Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It thus acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. Both RNF165 and RNF111 contain a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319388 [Multi-domain]  Cd Length: 46  Bit Score: 59.63  E-value: 8.70e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCM 450
Cdd:cd16474   3 CTICLSEFEDGEEVRRLPCMHLFHQACVDQWLATNKRCPICRVD 46
RING-H2_RNF6 cd16673
RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 ...
407-448 9.12e-12

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6 and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. Furthermore, RNF6 acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF6 contains an N-terminal coiled-coil domain, a Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL) motif, and a C-terminal C3H2C3-type RING-H2 finger which is responsible for its ubiquitin ligase activity. The KIL motif is present in a subset of RING-H2 proteins from organisms as evolutionarily diverse as human, mouse, chicken, Drosophila, Caenorhabditis elegans, and Arabidopsis thaliana.


Pssm-ID: 319587 [Multi-domain]  Cd Length: 45  Bit Score: 59.27  E-value: 9.12e-12
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16673   3 CSVCINEYATGNKLRRLPCAHEFHIHCIDRWLSENSTCPICR 44
RING-H2_RNF11 cd16468
RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 ...
407-447 3.06e-11

RING finger, H2 subclass, found in RING finger protein 11 (RNF11) and similar proteins; RNF11 is an E3 ubiquitin-protein ligase that acts both as an adaptor and a modulator of itch-mediated control of ubiquitination events underlying membrane traffic. It is the downstream of an enzymatic cascade for the ubiquitination of specific substrates. It is also a molecular adaptor of homologous to E6-associated protein C-terminus (HECT)-type ligases. RNF11 has been implicated in the regulation of several signaling pathways. It enhances the transforming growth factor receptor (TGFR) signaling by both abrogating Smurf2-mediated receptor ubiquitination and by promoting the Smurf2-mediated degradation of AMSH (associated molecule with the SH3 domain of STAM), a de-ubiquitinating enzyme that enhances transforming growth factor-beta (TGF-beta) signaling and epidermal growth factor receptor (EGFR) endosomal recycling. It also acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signaling. Moreover, RNF11 functions as a critical component of the A20 ubiquitin-editing protein complex that negatively regulates tumor necrosis factor (TNF)-mediated nuclear factor (NF)-kappaB activation. It also interacts with Smad anchor for receptor activation (SARA) and the endosomal sorting complex required for transport (ESCRT)-0 complex, thus participating in the regulation of lysosomal degradation of EGFR. Furthermore, RNF11 acts as a novel GGA cargo actively participating in regulating the ubiquitination of the GGA protein family. In addition, RNF11 functions together with TAX1BP1 to target TANK-binding kinase 1 (TBK1)/IkappaB kinase IKKi, and further restricts antiviral signaling and type I interferon (IFN)-beta production. RNF11 contains an N-terminal PPPY motif that binds WW domain-containing proteins such as AIP4/itch, Nedd4 and Smurf1/2 (SMAD-specific E3 ubiquitin-protein ligase 1/2), and a C-terminal C3H2C3-type RING-H2 finger that functions as a scaffold for the coordinated transfer of ubiquitin to substrate proteins together with the E2 enzymes UbcH527 and Ubc13.


Pssm-ID: 319382 [Multi-domain]  Cd Length: 43  Bit Score: 57.83  E-value: 3.06e-11
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16468   2 CVICMNDFVYGDPIRFLPCMHIYHKDCIDDWLMRSFTCPSC 42
RING-H2_RNF6_like cd16467
RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar ...
407-448 1.87e-10

RING finger, H2 subclass, found in E3 ubiquitin-protein ligase RNF6, RNF12, and similar proteins; RNF6 is an androgen receptor (AR)-associated protein that induces AR ubiquitination and promotes AR transcriptional activity. RNF6-induced ubiquitination may regulate AR transcriptional activity and specificity through modulating cofactor recruitment. RNF6 is overexpressed in hormone-refractory human prostate cancer tissues and required for prostate cancer cell growth under androgen-depleted conditions. Moreover, RNF6 regulates local serine/threonine kinase LIM kinase 1 (LIMK1) levels in axonal growth cones. RNF6-induced LIMK1 polyubiquitination is mediated via K48 of ubiquitin and leads to proteasomal degradation of the kinase. RNF6 also binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. Furthermore, RNF6 acts as a potential tumor suppressor gene involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). RNF12, also known as LIM domain-interacting RING finger protein, or RING finger LIM domain-binding protein (R-LIM), is E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.


Pssm-ID: 319381 [Multi-domain]  Cd Length: 43  Bit Score: 55.60  E-value: 1.87e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16467   2 CSVCISEYVTGNKLRKLPCSHEFHVHCIDRWLSENSTCPICR 43
RING-H2_RNF24_like cd16469
RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; ...
407-447 1.94e-10

RING finger, H2 subclass, found in RING finger proteins RNF24, RNF122, and similar proteins; The family includes RNF24, RNF122, and similar proteins. RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, ?3, ?4, ?5, ?6, and ?7, and affects TRPC intracellular trafficking without affecting their activity. RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergoes degradation through its RING finger in a proteasome-dependent manner. Both RNF24 and RNF122 contain an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319383 [Multi-domain]  Cd Length: 47  Bit Score: 55.54  E-value: 1.94e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16469   3 CAVCLEDFKKKEELGVCPCGHAFHRKCLLKWLEVRNVCPMC 43
RING-H2_RNF128_like cd16802
RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This ...
407-449 3.63e-10

RING finger, H2 subclass, found in RING finger protein 128 (RNF128) and similar proteins; This subfamily includes RING finger proteins RNF128, RNF133, RNF148, and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence. RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL), is a type 1 transmembrane E3 ubiquitin-protein ligase that is a critical regulator of adaptive immunity and development. It inhibits cytokine gene transcription is expressed in anergic CD4+ T cells, and has been implicated in primary T cell activation, survival, and differentiation, as well as in T cell anergy and oral tolerance. It induces T cell anergy through the ubiquitination activity of its cytosolic RING finger. It regulates expression of the costimulatory molecule CD40L on CD4 T cells, and ubiquitinates the costimulatory molecule CD40 ligand (CD40L) during the induction of T cell anergy. Moreover, RNF128 interacts with the luminal/extracellular portion of both CD151 and the related tetraspanin CD81 via its PA domain, which promoted ubiquitination of cytosolic lysine residues. It also down-modulates the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. Furthermore, Rho guanine dissociation inhibitor (RhoGDI) has been identified as a potential substrate of RNF128, suggesting a role for Rho effector molecules in T cell anergy. In addition, RNF128 plays a role in environmental stress responses. It promotes environmental salinity tolerance in euryhaline tilapia. RNF133 is a testis-specific endoplasmic reticulum-associated E3 ubiquitin ligase that is mainly present in the cytoplasm of elongated spermatids. It may play a role in sperm maturation through an ER-associated degradation (ERAD) pathway. RNF148 is a testis-specific E3 ubiquitin ligase that is abundantly expressed in testes and slightly expressed in pancreas. Its expression regulated by histone deacetylases.


Pssm-ID: 319716 [Multi-domain]  Cd Length: 49  Bit Score: 54.83  E-value: 3.63e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRC 449
Cdd:cd16802   3 CAVCIEPYKPNDVVRILTCNHFFHKSCIDPWLLEHRTCPMCKC 45
RING-H2_RNF130 cd16803
RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; ...
407-448 5.50e-10

RING finger, H2 subclass, found in RING finger protein 130 (RNF130) and similar proteins; RNF130, also known as Goliath homolog (H-Goliath), is a paralog of RNF128, also known as gene related to anergy in lymphocytes protein (GRAIL). It is a transmembrane E3 ubiquitin-protein ligase expressed in leukocytes. It has a self-ubiquitination property, and controls the development of T cell clonal anergy by ubiquitination. RNF130 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319717 [Multi-domain]  Cd Length: 49  Bit Score: 54.59  E-value: 5.50e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16803   3 CAVCIEGYKQNDVVRILPCKHVFHKSCVDPWLNEHCTCPMCK 44
RING smart00184
Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and ...
407-447 6.23e-10

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)


Pssm-ID: 214546 [Multi-domain]  Cd Length: 40  Bit Score: 54.05  E-value: 6.23e-10
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 21539663    407 CPICCSEYVKgeVATELPCHHYFHKPCVSIWL-QKSGTCPVC 447
Cdd:smart00184   1 CPICLEEYLK--DPVILPCGHTFCRSCIRKWLeSGNNTCPIC 40
RING-H2_TTC3 cd16481
RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar ...
407-448 7.85e-10

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, or TPR repeat protein D, or TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. TTC3 contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It also affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. TTC3 contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.


Pssm-ID: 319395 [Multi-domain]  Cd Length: 42  Bit Score: 53.89  E-value: 7.85e-10
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATeLPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16481   2 CSICHEELKPGTVRK-LDCGHRFHKGCIRQWLKEQSTCPTCR 42
RING-H2_RNF103 cd16473
RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; ...
407-448 1.53e-09

RING finger, H2 subclass, found in RING finger protein 103 (RNF103) and similar proteins; RNF103, also known as KF-1, or zinc finger protein 103 homolog (Zfp-103), is an endoplasmic reticulum (ER)-resident E3 ubiquitin-protein ligase that is widely expressed in many different organs, including brain, heart, kidney, spleen, and lung. It is involved in the ER-associated degradation (ERAD) pathway through interacting with components of the ERAD pathway, including Derlin-1 and VCP. RNF103 contains several hydrophobic regions at its N-terminal and middle regions, as well as a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319387 [Multi-domain]  Cd Length: 46  Bit Score: 53.07  E-value: 1.53e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKS-GTCPVCR 448
Cdd:cd16473   2 CVICLENYEEGCLLCGLPCGHVFHQNCIDVWLTRDnHCCPVCR 44
COG5540 COG5540
RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, ...
407-454 1.80e-09

RING-finger-containing ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227827 [Multi-domain]  Cd Length: 374  Bit Score: 58.85  E-value: 1.80e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWL-QKSGTCPVCRCMFPPP 454
Cdd:COG5540 326 CAICMSNFIKNDRLRVLPCDHRFHVGCVDKWLlGYSNKCPVCRTAIPPP 374
RING-H2_RNF43_like cd16666
RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; ...
407-448 2.15e-09

RING finger, H2 subclass, found in RING finger proteins RNF43, ZNRF3, and similar proteins; RNF43 and ZNRF3 (also known as RNF203) are transmembrane E3 ubiquitin-protein ligases that belong to the PA-TM-RING ubiquitin ligases family, which has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger domain followed by a long C-terminal region. Both RNF43 and RNF203 function as tumor suppressors involved in the regulation of Wnt/beta-catenin signaling. They negatively regulate Wnt signaling through interacting with complexes of frizzled receptors (FZD) and low-density lipoprotein receptor-related protein (LRP) 5/6, which leads to ubiquitination of Frizzled receptors (FZD) and endocytosis of the Wnt receptor. Dishevelled (DVL), a positive Wnt regulator, is required for ZNRF3/RNF43-mediated ubiquitination and degradation of FZD. They also associate with R-spondin 1 (RSPO1). This interaction may block Frizzled ubiquitination and enhances Wnt signaling.


Pssm-ID: 319580 [Multi-domain]  Cd Length: 45  Bit Score: 52.83  E-value: 2.15e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16666   2 CAICLEEFKDGQELRVLPCSHEFHRHCVDPWLLQNRTCPLCL 43
RING-H2_RNF38_like cd16472
RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; ...
404-448 2.38e-09

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; The family includes RING finger proteins RNF38, RNF44, and similar proteins. RNF38 is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38. Both RNF38 and RNF44 contain a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger. In addition, RNF38 harbors two potential nuclear localization signals.


Pssm-ID: 319386 [Multi-domain]  Cd Length: 45  Bit Score: 52.48  E-value: 2.38e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 404 EMCCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16472   1 QTSCVVCMCDFEARQLLRVLPCSHEFHAKCVDKWLKTNRTCPICR 45
RING-H2_RNF167 cd16797
RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; ...
407-448 3.16e-09

RING finger, H2 subclass, found in RING finger protein 167 (RNF167) and similar proteins; RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It ubiquitinates GluA2 and regulates its surface expression, and thus acts as a selective regulator of AMPAR-mediated neurotransmission. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA, also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. RNF167 is widely conserved in metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, two transmembrane domains (TM1 and TM2), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319711 [Multi-domain]  Cd Length: 46  Bit Score: 52.35  E-value: 3.16e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKS-GTCPVCR 448
Cdd:cd16797   3 CAICLDEYEEGDKLRVLPCSHAYHSKCVDPWLTQTkKTCPVCK 45
mRING-CH-C4HC2H_ZNRF cd16489
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; This ZNRF family ...
407-446 3.58e-09

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in the ZNRF family; This ZNRF family includes zinc/RING finger proteins ZNRF1, ZNRF2, and similar proteins. It has been characterized by containing a unique combination zinc finger-RING finger motif in the C-terminal region, which is evolutionarily conserved in a wide range of species, including Caenorhabditis elegans and Drosophila. The ZNRF family of proteins function as an E3 ubiquitin ligase and are highly expressed in central nervous system (CNS) and peripheral nervous system (PNS) neurons, particularly during development and in adulthood. In neurons, ZNRF1 and ZNRF2 are differentially localized within the synaptic region. ZNRF1 is associated with synaptic vesicle membranes, whereas ZNRF2 is present in presynaptic plasma membranes. They are N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts. ZNRF proteins may play a role in the establishment and maintenance of neuronal transmission and plasticity via their ubiquitin ligase activity, as well as in regulating Ca2+-dependent exocytosis. The RING fingers found in ZNRF proteins are modified as C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger.


Pssm-ID: 319403 [Multi-domain]  Cd Length: 43  Bit Score: 51.90  E-value: 3.58e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPV 446
Cdd:cd16489   2 CVICLEELLAGDTIARLPCLCIYHKKCIDDWFEVNRSCPE 41
RING-H2_RNF43 cd16798
RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 ...
407-447 8.33e-09

RING finger, H2 subclass, found in RING finger protein 43 (RNF43) and similar proteins; RNF43 is a transmembrane E3 ubiquitin-protein ligase that plays an important role in frizzled-dependent regulation of the Wnt/beta-catenin pathway. It functions as a tumor suppressor that inhibits Wnt/beta-catenin signaling by ubiquitinating Frizzled receptor and targeting it to the lysosomal pathway for degradation. miR-550a-5p directly targeted the 3?-UTR of gene RNF43 and regulated its expression. Moreover, RNF43 interacts with NEDD-4-like ubiquitin-protein ligase-1 (NEDL1) and regulates p53-mediated transcription. It may also be involved in cell growth control potentially through the interaction with HAP95, a chromatin-associated protein interfacing the nuclear envelope. Mutations of RNF43 have been identified in various tumors, including colorectal cancer (CRC), endometrial cancer, mucinous ovarian tumors, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, liver fluke-associated cholangiocarcinoma, hepatocellular carcinoma, and glioma. RNF43 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger domain followed by a long C-terminal region.


Pssm-ID: 319712 [Multi-domain]  Cd Length: 47  Bit Score: 51.09  E-value: 8.33e-09
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16798   3 CAICLEEFSEGQELRIISCAHEFHRECVDPWLHQHRTCPLC 43
zf-C3HC4 pfam00097
Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a ...
407-447 1.01e-08

Zinc finger, C3HC4 type (RING finger); The C3HC4 type zinc-finger (RING finger) is a cysteine-rich domain of 40 to 60 residues that coordinates two zinc ions, and has the consensus sequence: C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C where X is any amino acid. Many proteins containing a RING finger play a key role in the ubiquitination pathway.


Pssm-ID: 333836 [Multi-domain]  Cd Length: 40  Bit Score: 50.43  E-value: 1.01e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 21539663   407 CPICCSEYVkgEVATELPCHHYFHKPCV-SIWLQKSGTCPVC 447
Cdd:pfam00097   1 CPICLEEPK--DPVTILPCGHLFCSKCIlSWLESGNVTCPLC 40
RING-H2_AMFR cd16455
RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar ...
407-451 1.37e-08

RING finger, H2 subclass, found in autocrine motility factor receptor (AMFR) and similar proteins; AMFR, also known as AMF receptor, or RING finger protein 45, or ER-protein gp78, is an internalizing cell surface glycoprotein localized in both plasma membrane caveolae and the endoplasmic reticulum (ER). It is involved in the regulation of cellular adhesion, proliferation, motility and apoptosis, as well as in the process of learning and memory. AMFR also functions as a RING finger-dependent ubiquitin protein ligase (E3) implicated in degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.


Pssm-ID: 319369 [Multi-domain]  Cd Length: 44  Bit Score: 50.45  E-value: 1.37e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICcseYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:cd16455   3 CAIC---WESMQTARKLPCGHLFHNSCLRSWLEQDTSCPTCRRSL 44
RING-H2_ZNRF3 cd16799
RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ...
407-448 1.40e-08

RING finger, H2 subclass, found in zinc/RING finger protein 3 (ZNRF3) and similar proteins; ZNRF3, also known as RING finger protein 203 (RNF203), is a homolog of Ring finger protein 43 (RNF43). It is a transmembrane E3 ubiquitin-protein ligase that is associated with the Wnt receptor complex, and negatively regulates Wnt signaling by promoting the turnover of frizzled and lipoprotein receptor-related protein LRP6 in an R-spondin-sensitive manner. It inhibits gastric cancer cell growth and promotes the cell apoptosis by affecting the Wnt/beta-catenin/TCF signaling pathway. ZNRF3 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C3H2C3-type RING-H2 finger domain followed by a long C-terminal region.


Pssm-ID: 319713 [Multi-domain]  Cd Length: 45  Bit Score: 50.41  E-value: 1.40e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16799   2 CAICLEKYIDGEELRVIPCTHRFHKKCVDPWLLQHHTCPHCR 43
RING-H2_RNF12 cd16674
RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, ...
407-448 1.46e-08

RING finger, H2 subclass, found in RING finger protein 12 (RNF12) and similar proteins; RNF12, also known as LIM domain-interacting RING finger protein or RING finger LIM domain-binding protein (R-LIM), is an E3 ubiquitin-protein ligase encoded by gene RLIM that is crucial for normal embryonic development in some species and for normal X inactivation in mice. It thus functions as a major sex-specific epigenetic regulator of female mouse nurturing tissues. RNF12 is widely expressed during embryogenesis, and mainly localizes to the cell nucleus, where it regulates the levels of many proteins, including CLIM, LMO, HDAC2, TRF1, SMAD7, and REX1, by proteasomal degradation. Its functional activity is regulated by phosphorylation-dependent nucleocytoplasmic shuttling. It is negatively regulated by pluripotency factors in embryonic stem cells. p53 represses its transcription through Sp1. RNF12 is the primary factor responsible for X chromosome inactivation (XCI) in female placental mammals. It is an indispensable factor in up-regulation of Xist transcription, thereby leading to initiation of random XCI. It also targets REX1, an inhibitor of XCI, for proteasomal degradation. Moreover, RNF12 acts as a co-regulator of a range of transcription factors, particularly those containing a LIM homeodomain, and modulates the formation of transcriptional multiprotein complexes. It is a negative regulator of Smad7, which in turn negatively regulates the type I receptors in transforming growth factor beta (TGF-beta) superfamily signaling. In addition, paternal RNF12 is a critical survival factor for milk-producing alveolar cells. RNF12 contains an nuclear localization signal (NLS) and a C3H2C3-type RING-H2 finger.


Pssm-ID: 319588 [Multi-domain]  Cd Length: 45  Bit Score: 50.45  E-value: 1.46e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16674   3 CSVCITEYTEGNKLRKLPCSHEYHVHCIDRWLSENSTCPICR 44
RING-HC_RNFT1_like cd16532
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein ...
406-448 4.14e-08

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein RNFT1, RNFT2, and similar proteins; Both RNFT1 and RNFT2 are multi-pass membrane proteins containing a C3HC4-type RING-HC finger. Their biological roles remain unclear.


Pssm-ID: 319446 [Multi-domain]  Cd Length: 40  Bit Score: 48.82  E-value: 4.14e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 406 CCPICCSEYVKgevATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16532   1 LCPICQDEFKD---PIKLRCKHIFCEDCVSEWFDRERTCPLCR 40
RING-H2_synoviolin cd16479
RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as ...
407-448 4.69e-08

RING finger, H2 subclass, found in synoviolin and similar proteins; Synoviolin, also known as synovial apoptosis inhibitor 1 (Syvn1), Hrd1, or Der3, is an endoplasmic reticulum (ER)-anchoring E3 ubiquitin ligase that functions as a suppressor of ER stress-induced apoptosis and plays a role in homeostasis maintenance. It also targets tumor suppressor gene p53 for proteasomal degradation, suggesting the crosstalk between ER associated degradation (ERAD) and p53 mediated apoptotic pathway under ER stress. Moreover, Synoviolin controls body weight and mitochondrial biogenesis through negative regulation of the thermogenic coactivator peroxisome proliferator-activated receptor coactivator (PGC)-1beta. It upregulates amyloid beta production by targeting a negative regulator of gamma-secretase, Retention in endoplasmic reticulum 1 (Rer1), for degradation. It is also involved in the degradation of endogenous immature nicastrin, and affects amyloid beta-protein generation. Moreover, Synoviolin is highly expressed in rheumatoid synovial cells and may be involved in the pathogenesis of rheumatoid arthritis (RA). It functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of RA. It promotes inositol-requiring enzyme 1 (IRE1) ubiquitination and degradation in synovial fibroblasts with collagen-induced arthritis. Furthermore, the upregulation of Synoviolin may represent a protective response against neurodegeneration in Parkinson"s disease (PD). In addition, Synoviolin is involved in liver fibrogenesis. Synoviolin contains a C3H2C2-type RING-H2 finger.


Pssm-ID: 319393 [Multi-domain]  Cd Length: 43  Bit Score: 48.83  E-value: 4.69e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGevATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16479   4 CIICREEMVSG--AKKLPCGHIFHLSCLRSWLQRQQTCPTCR 43
RING-H2_DZIP3 cd16460
RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) ...
409-448 6.18e-08

RING finger, H2 subclass, found in DAZ (deleted in azoospermia)-interacting protein 3 (DZIP3) and similar proteins; DZIP3, also known as RNA-binding ubiquitin ligase of 138 kDa (RUL138) or 2A-HUB protein, is an RNA-binding E3 ubiquitin-protein ligase that interacts with coactivator-associated arginine methyltransferase 1 (CARM1) and acts as a transcriptional coactivator of estrogen receptor (ER) alpha. It is also a histone H2A ubiquitin ligase that catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for repressing a specific chemokine gene expression program, critically modulating migratory responses to Toll-like receptors (TLR) activation. DZIP3 contains a C3H2C3-type RING-H2 finger at the C-terminus.


Pssm-ID: 319374 [Multi-domain]  Cd Length: 43  Bit Score: 48.48  E-value: 6.18e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|
gi 21539663 409 ICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16460   4 VICHENLSPENLSVLPCAHKFHSQCIRPWLMQQRTCPTCR 43
zf-rbx1 pfam12678
RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be ...
404-448 6.31e-08

RING-H2 zinc finger domain; There are 8 cysteine/ histidine residues which are proposed to be the conserved residues involved in zinc binding. The protein, of which this domain is the conserved region, participates in diverse functions relevant to chromosome metabolism and cell cycle control.


Pssm-ID: 315369 [Multi-domain]  Cd Length: 55  Bit Score: 48.85  E-value: 6.31e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 21539663   404 EMCCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:pfam12678  11 EEPCPECQAPGDDECPVVWGECGHAFHLHCISRWLKTNNTCPLCR 55
RING-H2_RNF215 cd16670
RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This ...
407-448 6.65e-08

RING finger, H2 subclass, found in RING finger protein 215 (RNF215) and similar proteins; This family includes uncharacterized protein RNF215 and similar proteins. Although its biological function remains unclear, RNF215 shares high sequence similarity with PA-TM-RING ubiquitin ligases, which have been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain.


Pssm-ID: 319584 [Multi-domain]  Cd Length: 50  Bit Score: 48.74  E-value: 6.65e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16670   3 CAVCLDQFHKNQCLRVLPCLHEFHRDCVDPWLLLQQTCPLCK 44
RING-H2_RNF149 cd16804
RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; ...
407-448 7.22e-08

RING finger, H2 subclass, found in RING finger protein 149 (RNF149) and similar proteins; RNF149, also known as DNA polymerase-transactivated protein 2, is an E3 ubiquitin-protein ligase that interacts with wild-type v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), a RING domain-containing E3 ubiquitin ligase involved in control of gene transcription, translation, cytoskeletal organization, cell adhesion, and epithelial development. RNF149 induces the ubiquitination of wild-type BRAF and promotes its proteasome-dependent degradation. Mutated RNF149 has been found in some human breast, ovarian, and colorectal cancers. RNF149 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319718 [Multi-domain]  Cd Length: 48  Bit Score: 48.35  E-value: 7.22e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16804   2 CAVCIENYKPKDVVRILPCKHIFHRICIDPWLLEHRTCPMCK 43
RING-H2_RNF165 cd16682
RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; ...
407-448 7.58e-08

RING finger, H2 subclass, found in RING finger protein 165 (RNF165) and similar proteins; RNF165, also known as Arkadia-like 2, or Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It thus acts as a positive regulator of bone morphogenetic protein (BMP)-Smad signaling that is involved in motor neuron (MN) axon elongation. RNF165 contains two serine rich domains, a nuclear localization signal, a NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is responsible for the enhancement of BMP-Smad1/5/8 signaling in the spinal cord.


Pssm-ID: 319596 [Multi-domain]  Cd Length: 51  Bit Score: 48.54  E-value: 7.58e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16682   3 CTICLSMLEDGEDVRRLPCMHLFHQLCVDQWLAMSKKCPICR 44
RING-H2_RNF44 cd16680
RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 ...
407-448 7.68e-08

RING finger, H2 subclass, found in RING finger protein 44 (RNF44) and similar proteins; RNF44 is an uncharacterized RING finger protein that shows high sequence similarity with RNF38, which is a nuclear E3 ubiquitin protein ligase that plays a role in regulating p53. RNF44 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C2-type RING-H2 finger.


Pssm-ID: 319594 [Multi-domain]  Cd Length: 45  Bit Score: 48.13  E-value: 7.68e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16680   4 CVVCFSDFESRQLLRVLPCNHEFHTKCVDKWLKTNRTCPICR 45
RING-H2_RNF111 cd16681
RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; ...
407-448 8.64e-08

RING finger, H2 subclass, found in RING finger protein 111 (RNF111) and similar proteins; RNF111, also known as Arkadia, is a nuclear E3 ubiquitin-protein ligase that targets intracellular effectors and modulators of transforming growth factor beta (TGF-beta)/Nodal-related signaling for polyubiquitination and proteasome-dependent degradation. It acts as an amplifier of Nodal signals, and enhances the dorsalizing activity of limiting amounts of Xnr1, a Nodal homolog, and requires Nodal signaling for its function. The loss of RNF111 results in early embryonic lethality, with defects attributed to compromised Nodal signaling. Moreover, RNF111 regulates tumor metastasis by modulation of the TGF-beta pathway. Its ubiquitination can be modulated by the four and a half LIM-only protein 2 (FHL2) that activates TGF-beta signal transduction. Furthermore, RNF111 interacts with the clathrin-adaptor 2 (AP2) complex and regulates endocytosis of certain cell surface receptors, leading to modulation of epidermal growth factor (EGF) and possibly other signaling pathways. In addition, RNF111 has been identified as a small ubiquitin-like modifier (SUMO)-binding protein with clustered SUMO-interacting motifs (SIMs) that together form a SUMO-binding domain (SBD). It thus functions as a SUMO-targeted ubiquitin ligase (STUbL) that directly links nonproteolytic ubiquitylation and SUMOylation in the DNA damage response, as well as triggers degradation of signal-induced polysumoylated proteins, such as the promyelocytic leukemia protein (PML). The N-terminal half of RNF111 harbors three SIMs. Its C-terminal half show high sequence similarity with RING finger protein 165 (RNF165), where it contains two serine rich domains, two nuclear localization signals, a NRG-TIER domain, and a C-terminal C3H2C3-type RING-H2 finger that is required for polyubiqutination and proteasome-dependent degradation of phosphorylated forms of Smad2/3 and three major negative regulators of TGF-beta signaling, Smad7, SnoN and c-Ski.


Pssm-ID: 319595 [Multi-domain]  Cd Length: 46  Bit Score: 48.15  E-value: 8.64e-08
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16681   3 CTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICR 44
RING-H2_RNF13_like cd16665
RING finger, H2 subclass, found in RING finger protein 13 (RNF13), RING finger protein 167 ...
407-448 1.34e-07

RING finger, H2 subclass, found in RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), and similar proteins; This subfamily includes RING finger protein 13 (RNF13), RING finger protein 167 (RNF167), Zinc/RING finger protein 4 (ZNRF4), and similar proteins, which belong to a larger PA-TM-RING ubiquitin ligase family that has been characterized by containing an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane domain (TM), and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence. RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. RNF167, also known as RING105, is an endosomal/lysosomal E3 ubiquitin-protein ligase involved in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) ubiquitination. It acts as an endosomal membrane protein which ubiquitylates vesicle-associated membrane protein 3 (VAMP3) and regulates endosomal trafficking. Moreover, RNF167 plays a role in the regulation of TSSC5 (tumor-suppressing subchromosomal transferable fragment cDNA; also known as ORCTL2/IMPT1/BWR1A/SLC22A1L), which can function in concert with the ubiquitin-conjugating enzyme UbcH6. ZNRF4, also known as RING finger protein 204 (RNF204), or Nixin, is an endoplasmic reticulum (ER) membrane-anchored ubiquitin ligase that physically interacts with the ER-localized chaperone calnexin in a glycosylation-independent manner, induces calnexin ubiquitination, and p97-dependent degradation, indicating an ER-associated degradation-like mechanism of calnexin turnover. The murine protein sperizin (spermatid-specific ring zinc finger) is a homolog of human ZNRF4. It is specifically expressed in Haploid germ cells and involved in spermatogenesis.


Pssm-ID: 319579 [Multi-domain]  Cd Length: 46  Bit Score: 47.79  E-value: 1.34e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWL-QKSGTCPVCR 448
Cdd:cd16665   3 CAICLDDYEEGDKLRILPCSHAYHCKCIDPWLtQNRRTCPVCK 45
RING-HC_RNFT1 cd16741
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 ...
407-448 1.42e-07

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 1 (RNFT1); RNFT1, also known as protein PTD016, is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.


Pssm-ID: 319655 [Multi-domain]  Cd Length: 40  Bit Score: 47.24  E-value: 1.42e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKgevATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16741   2 CPICQAEFQK---PILLICQHIFCEECISLWFNREKTCPLCR 40
RING-H2_RNF139 cd16683
RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; ...
407-447 1.63e-07

RING finger, H2 subclass, found in RING finger protein 139 (RNF139) and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. The mutation of RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF139 physically and functionally interacts with von Hippel-Lindau (VHL), which is part of an SCF related E3-ubiquitin ligase complex with "gatekeeper" function in renal carcinoma and is defective in most sporadic clear-cell renal cell carcinomas (ccRCC). It suppresses growth and functions with VHL in a common pathway. RNF139 also suppresses tumorigenesis through targeting heme oxygenase-1 for ubiquitination and degradation. Moreover, RNF139 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells, suggesting a role of RNF139 in dysgerminoma. Furthermore, RNF139 physically and functionally interacts with von Hippel-Lindau (VHL), which is part of an SCF related E3-ubiquitin ligase complex with "gatekeeper" function in renal carcinoma and is defective in most sporadic clear-cell renal cell carcinomas (ccRCC). It suppresses growth and functions with VHL in a common pathway. In addition, RNF139 forms an integral part of a novel multi-protein ER complex, containing MHC I, US2, and signal peptide peptidase, which is associated with ER-associated degradation (ERAD) pathway. It is required for the ubiquitination of MHC class I molecules before dislocation from the ER. As a novel sterol-sensing ER membrane protein, RNF139 hinders sterol regulatory element-binding protein-2 (SREBP-2) processing through interaction with SREBP-2 and SREBP cleavage-activated protein (SCAP), regulating its own turnover rate via its E3 ubiquitin ligase activity. RNF139 shows two regions of similarity with the receptor for sonic hedgehog (SHH), Patched. The first region corresponds to the second extracellular domain of Patched, which is involved in binding SHH. The second region is a putative sterol-sensing domain (SSD). In addition, the C-terminal half of RNF139 contains a C3H2C3-type RING-H2 finger with E3-ubiquitin ligase activity in vitro.


Pssm-ID: 319597 [Multi-domain]  Cd Length: 42  Bit Score: 47.29  E-value: 1.63e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYvkGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16683   3 CAICYQEF--TTSARITPCNHYFHALCLRKWLYIQDTCPMC 41
RING-H2_RNF38 cd16679
RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 ...
403-448 1.69e-07

RING finger, H2 subclass, found in RING finger protein 38 (RNF38) and similar proteins; RNF38 is a nuclear E3 ubiquitin protein ligase that is widely expressed throughout the body in human, especially highly expressed in the heart, brain, placenta and the testis. It recognizes p53 as a substrate for ubiquitination, and thus plays a role in regulating p53. The overexpression of RNF38 increases p53 ubiquitination and alters p53 localization. It is also capable of autoubiquitination. Moreover, RNF38 expression is negatively regulated by the serotonergic system. Induction of RNF38 may be involved in the anxiety-like behavior or non-cell autonomous by the decline of serotonin (5-HT) levels. RNF38 contains a coiled-coil motif, a KIL motif (Lys-X2-Ile/Leu-X2-Ile/Leu, X can be any amino acid), and a C3H2C3-type RING-H2 finger, as well as two potential nuclear localization signals.


Pssm-ID: 319593 [Multi-domain]  Cd Length: 49  Bit Score: 47.36  E-value: 1.69e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 403 QEMCCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16679   1 EQTLCVVCMCDFESRQLLRVLPCNHEFHAKCVDKWLKANRTCPICR 46
RING-H2_RNF150 cd16805
RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; ...
407-448 2.47e-07

RING finger, H2 subclass, found in RING finger protein 150 (RNF150) and similar proteins; RNF150 is a RING finger protein that its polymorphisms may be associated with chronic obstructive pulmonary disease (COPD) risk in the Chinese population. Further studies with larger numbers of participants worldwide are needed for validation of the relationships between RNF150 genetic variants and the pathogenesis of COPD. RNF150 contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319719 [Multi-domain]  Cd Length: 49  Bit Score: 46.94  E-value: 2.47e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16805   3 CAVCIEGYKPNDVVRILPCRHLFHKSCVDPWLLDHRTCPMCK 44
mRING-HC-C3HC3D_PHRF1 cd16635
Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger ...
407-448 4.71e-07

Modified RING finger, HC subclass (C3HC3D-type), found in PHD and RING finger domain-containing protein 1(PHRF1) and similar proteins; PHRF1, also known as KIAA1542, or CTD-binding SR-like protein rA9, is a ubiquitin ligase which induces the ubiquitination of TGIF (TG-interacting factor) at lysine 130. It acts as a tumor suppressor that promotes the transforming growth factor (TGF)-beta cytostatic program through selective release of TGIF-driven promyelocytic leukemia protein (PML) inactivation. PHRF1 contains a plant homeodomain (PHD) finger and a modified C3HC3D-type RING-HC finger.


Pssm-ID: 319549 [Multi-domain]  Cd Length: 44  Bit Score: 45.89  E-value: 4.71e-07
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16635   3 CPICLNEFTDQAVGTPESCDHYFCLDCILEWSKNVNTCPVDR 44
zf-RING_5 pfam14634
zinc-RING finger domain;
407-448 8.94e-07

zinc-RING finger domain;


Pssm-ID: 339304 [Multi-domain]  Cd Length: 43  Bit Score: 45.11  E-value: 8.94e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 21539663   407 CPICCSEYVKGEVATELPCHHYFHKPCVSIwLQKSGTCPVCR 448
Cdd:pfam14634   2 CNKCFKPLSKTRPFYLTSCGHIFCEECLTK-LLKERQCPICR 42
RING-H2_RNF13 cd16796
RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RING ...
407-448 1.01e-06

RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins; RING finger, H2 subclass, found in RING finger protein 13 (RNF13) and similar proteins RNF13 is a widely expressed membrane-associated E3 ubiquitin-protein ligase that is functionally significant in the regulation of cancer development, muscle cell growth, and neuronal development. Its expression is developmentally regulated during myogenesis and is upregulated in various tumors. RNF13 negatively regulates cell proliferation through its E3 ligase activity. It functions as an important regulator of Inositol-requiring transmembrane kinase/endonuclease IRE1alpha, mediating endoplasmic reticulum (ER) stress-induced apoptosis through the activation of the IRE1alpha-TRAF2-JNK signaling pathway. Moreover, RNF13 is involved in the regulation of the soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex via the ubiquitination of snapin, a SNAP25-interacting protein, which thereby controls synaptic function. In addition, RNF13 participates in regulating the function of satellite cells by modulating cytokine composition. RNF13 is evolutionarily conserved among many metazoans and contains an N-terminal signal peptide, a protease-associated (PA) domain, a transmembrane (TM) domain and a C-terminal C3H2C3-type RING-H2 finger domain followed by a putative PEST sequence.


Pssm-ID: 319710 [Multi-domain]  Cd Length: 49  Bit Score: 45.42  E-value: 1.01e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKS-GTCPVCR 448
Cdd:cd16796   4 CAICLDEYEEGDKLRILPCSHAYHCKCVDPWLTKTkKTCPVCK 46
RING-HC_TRIM13_like_C-V cd16581
RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and ...
404-448 1.95e-06

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.


Pssm-ID: 319495 [Multi-domain]  Cd Length: 45  Bit Score: 44.37  E-value: 1.95e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21539663 404 EMCCPICCSEYVKGEVateLPCHHYFHKPCVSIWLQKSGT--CPVCR 448
Cdd:cd16581   2 KLTCSICLDIFNDPRV---LPCLHTFCKNCLEGRAAESGPlkCPTCR 45
zf-RING_11 pfam17123
RING-like zinc finger;
407-434 3.08e-06

RING-like zinc finger;


Pssm-ID: 339895 [Multi-domain]  Cd Length: 29  Bit Score: 43.27  E-value: 3.08e-06
                          10        20
                  ....*....|....*....|....*...
gi 21539663   407 CPICCSEYVKGEVATELPCHHYFHKPCV 434
Cdd:pfam17123   2 CSICLDEFEPGQALRVLPCSHVFHYKCI 29
zf-C3HC4_2 pfam13923
Zinc finger, C3HC4 type (RING finger);
407-447 3.53e-06

Zinc finger, C3HC4 type (RING finger);


Pssm-ID: 316445 [Multi-domain]  Cd Length: 40  Bit Score: 43.56  E-value: 3.53e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 21539663   407 CPICCSEYVKGEVATelPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:pfam13923   2 CPICLDMLKDPSTTT--PCGHVFCQKCILRALRSGNECPLC 40
RING-HC_RNF219 cd16562
RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; ...
404-448 3.95e-06

RING finger, HC subclass, found in RING finger protein 219 (RNF219) and similar proteins; RNF219 may function as a modulator of late-onset Alzheimer"s disease (LOAD) associated amyloid beta A4 precursor protein (APP) endocytosis and metabolism. It genetically interacts with apolipoprotein E epsilon4 allele (APOE4). Thus a genetic variant within RNF219 was found to affect amyloid deposition in human brain and LOAD age-of-onset. Moreover, common genetic variants at the RNF219 locus had been associated with alternations in lipid metabolism, cognitive performance and central nervous system ventricle volume. RNF219 contains a C3HC4-type RING-HC finger.


Pssm-ID: 319476 [Multi-domain]  Cd Length: 42  Bit Score: 43.52  E-value: 3.95e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 404 EMCCPICCSEyVKGEVATelPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16562   1 PISCHICLGK-VKQPVIC--PNNHVFCSSCMDLWLKRNNQCPACR 42
RING-H2_RNF139_like cd16476
RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; ...
407-447 4.15e-06

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. The mutation of RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.


Pssm-ID: 319390 [Multi-domain]  Cd Length: 41  Bit Score: 43.23  E-value: 4.15e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVAtelPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16476   3 CAICYQEMKNARIT---PCQHYFHGVCLRKWLYVQDRCPLC 40
RING-H2_BRAP2 cd16457
RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; ...
407-448 5.01e-06

RING finger, H2 subclass, found in BRCA1-associated protein (BRAP2) and similar proteins; BRAP2, also known as impedes mitogenic signal propagation (IMP), RING finger protein 52, or renal carcinoma antigen NY-REN-63, is a novel cytoplasmic protein interacting with the two functional nuclear localization signal (NLS) motifs of BRCA1, a nuclear protein linked to breast cancer. It also binds to the SV40 large T antigen NLS motif and the bipartite NLS motif found in mitosin. BRAP2 serves as a cytoplasmic retention protein and plays a role in in the regulation of nuclear protein transport. It contains an N-terminal RNA recognition motif (RRM), also known as RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3H2C3-type RING-H2 finger and a UBP-type zinc finger.


Pssm-ID: 319371 [Multi-domain]  Cd Length: 44  Bit Score: 43.04  E-value: 5.01e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICC---SEYVKGEVATElpCHHYFHKPCVSIWLQksGTCPVCR 448
Cdd:cd16457   3 CPVCLermDESVSGILTIL--CNHSFHCDCLKRWGD--STCPVCR 43
RING-HC cd16449
HC subclass of RING (RING-HC) finger and its variants; RING finger is a specialized type of ...
407-447 6.15e-06

HC subclass of RING (RING-HC) finger and its variants; RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to HC subclass of RING (RING-HC) finger proteins that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 319363 [Multi-domain]  Cd Length: 39  Bit Score: 42.84  E-value: 6.15e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYvkgEVATELPCHHYFHKPCVSIWLQKSG-TCPVC 447
Cdd:cd16449   1 CPICLELL---KDPVLLPCGHTFCRSCLRRLLKEGKkKCPIC 39
RING-HC_RNF141 cd16545
RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; ...
406-448 6.61e-06

RING finger, HC subclass, found in RING finger protein 141 (RNF141) and similar proteins; RNF141, also known as zinc finger protein 230 (ZNF230), is a RING finger protein present primarily in the nuclei of spermatogonia, the acrosome, and the tail of spermatozoa. It may have a broad function during early development of vertebrates. It plays an important role in spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization. It also exhibits DNA binding activity. RNF141 corresponding ZNF230 gene mutation may be associated with azoospermia. RNF141 contains a C3HC4-type RING finger domain that may function as an activator module in transcription.


Pssm-ID: 319459 [Multi-domain]  Cd Length: 39  Bit Score: 42.78  E-value: 6.61e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 406 CCpICcseyVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16545   2 CC-IC----MDRKPDTILPCAHSFCQKCIDKWSVRHRTCPICR 39
RING-HC_LNX3_like cd16512
RING finger, HC subclass, found in ligand of Numb protein LNX3, LNX4, and similar proteins; ...
407-448 9.11e-06

RING finger, HC subclass, found in ligand of Numb protein LNX3, LNX4, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4, or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for the substrate-binding. This family corresponds to LNX3/LNX4-like proteins, which contains a typical C3HC4-type RING-HC finger and two PDZ domains.


Pssm-ID: 319426 [Multi-domain]  Cd Length: 41  Bit Score: 42.50  E-value: 9.11e-06
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYvkgEVATELPCHHYFHKPCVSIWLQKSGTCPV-CR 448
Cdd:cd16512   2 CSICLEVL---EDPLTTPCGHVFCSGCILPWLVQNGSCPVkCR 41
RING-HC_RNF8 cd16535
RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is ...
404-448 1.33e-05

RING finger, HC subclass, found in RING finger protein 8 (RNF8) and similar proteins; RNF8 is a telomere-associated E3 ubiquitin-protein ligase that plays an important role in DNA double-strand break (DSB) repair via histone ubiquitination. It is localized in the nucleus and interacts with class III E2s (UBE2E2, UbcH6, and UBE2E3), but not with other E2s (UbcH5, UbcH7, UbcH10, hCdc34, and hBendless). It recruits UBC13 for lysine 63-based self polyubiquitylation. Its deficiency causes neuronal pathology and cognitive decline, and its loss results in neuron degeneration. RNF8, together with RNF168, catalyzes a series of ubiquitylation events on substrates such as H2A and H2AX, with the H2AK13/15 ubiquitylation being particularly important for recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of DSBs. Specially, RNF8 mediates the ubiquitination of gammaH2AX, and recruits 53BP1 and BRCA1 to DNA damage sites which promotes DNA damage response (DDR) and inhibits chromosomal instability. Moreover, RNF8 interacts with retinoid X receptor alpha (RXR alpha) and enhances its transcription-stimulating activity. It also regulates the rate of exit from mitosis and cytokinesis. RNF8 contains an N-terminal forkhead-associated (FHA) domain and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 319449 [Multi-domain]  Cd Length: 42  Bit Score: 42.03  E-value: 1.33e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 404 EMCCPICCSEYVKgevATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16535   1 ELQCSICSELFIE---AVTLNCSHSFCSYCITEWMKRKKECPICR 42
RING-H2_Rapsyn cd16478
RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) ...
404-449 2.01e-05

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor-associated 43 kDa protein or RING finger protein 205 (RNF205), is a 43 kDa postsynaptic protein that plays an essential role in the clustering and maintenance of acetylcholine receptor (AChR) in the postsynaptic membrane of the motor endplate (EP). AChRs enable the transport of rapsyn from the Golgi complex to the plasma membrane through a molecule-specific interaction. Rapsyn also mediates subsynaptic anchoring of protein kinase A (PKA) type I in close proximity to the postsynaptic membrane, which is essential for synapse maintenance. Its mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. Rapsyn contains an N-terminal myristoylation signal required for membrane association, seven tetratricopeptide repeats (TPRs) that subserve rapsyn self-association, a coiled-coil domain responsible for the binding of determinants within the long cytoplasmic loop of each AChR subunit, a C3H2C3-type RING-H2 finger that binds to the cytoplasmic domain of beta-dystroglycan and to S-NRAP and links rapsyn to the subsynaptic cytoskeleton, and a serine phosphorylation site.


Pssm-ID: 319392 [Multi-domain]  Cd Length: 47  Bit Score: 41.65  E-value: 2.01e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21539663 404 EMCCPICCSEY-VKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCRC 449
Cdd:cd16478   1 ELYCGMCGESIgEKNESLQALPCSHIFHLKCLQTNLNGTRGCPNCRR 47
RING-H2_RNF145 cd16684
RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; ...
407-447 3.23e-05

RING finger, H2 subclass, found in RING finger protein 145 (RNF145) and similar proteins; RNF145 is an uncharacterized RING finger protein encoded by RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139, an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. Like RNF139, RNF145 contains a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.


Pssm-ID: 319598 [Multi-domain]  Cd Length: 43  Bit Score: 40.81  E-value: 3.23e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEyVKGEVATelPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16684   5 CSICYQD-MKSAVIT--PCSHFFHAGCLKKWLYVQETCPLC 42
mRING-CH-C4HC2H_ZNRF1 cd16694
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) ...
407-445 4.17e-05

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 1 (ZNRF1) and similar proteins; ZNRF1, also known as Nerve injury-induced gene 283 protein (nin283), or peripheral nerve injury protein (PNIP), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is associated with synaptic vesicle membranes. It is N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts, suggesting it may participate in ubiquitin-mediated protein modification. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. ZNRF1 regulates Schwann cell differentiation by proteasomal degradation of glutamine synthetase (GS). It also mediates regulation of neuritogenesis via interaction with beta-tubulin type 2 (Tubb2). Moreover, ZNRF1 promotes Wallerian degeneration by degrading AKT to induce glycogen synthase kinase-3beta (GSK3B)-dependent CRMP2 phosphorylation. Furthermore, ZNRF1 and its sister protein ZNRF2 regulate the ubiquitous Na+/K+ pump (Na+/K+ATPase). In addition, ZNRF1 may be associated with leukemogenesis of acute lymphoblastic leukemia (ALL) with paired box domain gene 5 (PAX5) alteration.


Pssm-ID: 319608 [Multi-domain]  Cd Length: 46  Bit Score: 40.73  E-value: 4.17e-05
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCP 445
Cdd:cd16694   3 CVICLEELLQGDTIARLPCLCIYHKSCIDSWFEVNRSCP 41
RING1-H2_RNF32 cd16677
RING finger 1, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; ...
407-448 4.97e-05

RING finger 1, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, the protein with double RING-H2 fingers may act as a scaffold for binding several proteins that function in the same pathway. This family corresponds to the first RING-H2 finger.


Pssm-ID: 319591 [Multi-domain]  Cd Length: 44  Bit Score: 40.39  E-value: 4.97e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICCSE-YVKGEVAteLPCHHYFHKPCVSIWLQKSG--TCPVCR 448
Cdd:cd16677   2 CVICKEDfGLQQQVL--LSCSHVFHRACLESFERFSGkkTCPMCR 44
RING-H2_RNF122 cd16676
RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; ...
407-447 5.65e-05

RING finger, H2 subclass, found in RING finger protein 122 (RNF122) and similar proteins; RNF122 is a RING finger protein associated with HEK 293T cell viability. It is localized to the endoplasmic reticulum (ER) and the Golgi apparatus, and overexpressed in anaplastic thyroid cancer cells. RNF122 functions as an E3 ubiquitin ligase that can ubiquitinate itself and undergoes degradation through its RING finger in a proteasome-dependent manner. It interacts with calcium-modulating cyclophilin ligand (CAML), which is not a substrate, but a stabilizer of RNF122. RNF122 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319590 [Multi-domain]  Cd Length: 47  Bit Score: 40.39  E-value: 5.65e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16676   3 CAVCLEDFKVKDELGVLPCQHAFHRKCLVKWLEVRCVCPMC 43
RING-HC_CHFR cd16503
RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein ...
403-448 5.72e-05

RING finger, HC subclass, found in checkpoint with forkhead and RING finger domains protein (CHFR); CHFR, also known as RING finger protein 196 (RNF196), is a checkpoint protein that delays entry into mitosis in response to stress. It functions as an E3 ubiquitin ligase that ubiquitinates and degrades its target proteins, such as Aurora-A, Plk1, Kif22, and PARP-1, which are critical for proper mitotic transitions. It also plays an important role in cell cycle progression and tumor suppression, and is negatively regulated by SUMOylation-mediated proteasomal ubiquitylation. Moreover, CHFR is involved in the early stage of the DNA damage response, which mediates the crosstalk between ubiquitination and poly-ADP-ribosylation. CHFR contains a fork head associated- (FHA) and a C3HC4-type RING-HC finger.


Pssm-ID: 319417 [Multi-domain]  Cd Length: 44  Bit Score: 40.09  E-value: 5.72e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 403 QEMCCPICcsEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16503   1 ETLLCSIC--QDLLHDCVSLQPCMHNFCAGCYSEWMERSSLCPQCR 44
RING-CH-C4HC3_LTN1 cd16491
RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and ...
406-448 6.04e-05

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), whick mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.


Pssm-ID: 319405 [Multi-domain]  Cd Length: 50  Bit Score: 40.34  E-value: 6.04e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 21539663 406 CCPICCSeyVKGEVATELP------CHHYFHKPCVSIWLQKSG--TCPVCR 448
Cdd:cd16491   2 ECPICYS--VIHGSNHSLPklkcktCKNKFHSACLYKWFSSSNksTCPLCR 50
RING-HC_TRIM40-C-V cd16583
RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar ...
407-448 6.45e-05

RING finger, HC subclass, found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also known as probable E3 NEDD8-protein ligase or RING finger protein 35 (RNF35), is highly expressed in the gastrointestinal tract including the stomach, small intestine, and large intestine. It enhances neddylation of inhibitor of nuclear factor kappaB kinase subunit gamma (IKKgamma), inhibits the activity of nuclear factor-kappaB (NF-kappaB)-mediated transcription, and thus prevents inflammation-associated carcinogenesis in the gastrointestinal tract. TRIM40 belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region , as well as an uncharacterized region positioned C-terminal to the RBCC domain.


Pssm-ID: 319497 [Multi-domain]  Cd Length: 46  Bit Score: 39.88  E-value: 6.45e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21539663 407 CPICCSEyVKGEVATelPCHHYFHKPCVSIWLQKSG-----TCPVCR 448
Cdd:cd16583   2 CPICLDP-LKEPVST--TCGHVFCRGCIAQHLEKASvsgvlCCPVCR 45
RING-HC_RNFT2 cd16742
RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2 ...
407-448 6.76e-05

RING finger, HC subclass, found in RING finger and transmembrane domain-containing protein 2(RNFT2); RNFT2, also known as transmembrane protein 118 (TMEM118), is a multi-pass membrane protein containing a C3HC4-type RING-HC finger. Its biological role remains unclear.


Pssm-ID: 319656 [Multi-domain]  Cd Length: 41  Bit Score: 39.80  E-value: 6.76e-05
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVateLPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16742   3 CAICQAEFREPLI---LICQHVFCEECLCLWFDRERTCPLCR 41
HRD1 COG5243
HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein ...
407-448 7.52e-05

HRD ubiquitin ligase complex, ER membrane component [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 227568 [Multi-domain]  Cd Length: 491  Bit Score: 44.96  E-value: 7.52e-05
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYV----------KGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:COG5243 290 CTICMDEMFhpdheplprgLDMTPKRLPCGHILHLHCLKNWLERQQTCPICR 341
RING-HC_RNF151 cd16547
RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; ...
423-448 8.22e-05

RING finger, HC subclass, found in RING finger protein 151 (RNF151) and similar proteins; RNF151 is a testis-specific RING finger protein that interacts with dysbindin, a synaptic and microtubular protein that binds brain snapin, a SNARE-binding protein that mediated intracellular membrane fusion in both neuronal and non-neuronal cells. Thus, it may be involved in acrosome formation of spermatids through interacting with multiple proteins participating in membrane biogenesis and microtubule organization. RNF151 contains a C3HC4-type RING finger domain, a putative nuclear localization signal (NLS), and a TNF receptor associated factor (TRAF)-type zinc finger domain.


Pssm-ID: 319461 [Multi-domain]  Cd Length: 39  Bit Score: 39.42  E-value: 8.22e-05
                        10        20
                ....*....|....*....|....*.
gi 21539663 423 LPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16547  14 LPCSHIFCKKCILQWLKRQETCPCCR 39
mRING-C3HGC3_RFWD3 cd16450
Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing ...
405-448 1.05e-04

Modified RING finger, C3HGC3-type, found in RING finger and WD repeat domain-containing protein 3 (RFWD3) and similar proteins; RFWD3, also known as RING finger protein 201 (RNF201) or FLJ10520, is an E3 ubiquitin-protein ligase that forms a complex with Mdm2 and p53 to synergistically ubiquitinate p53 and acts as a positive regulator of p53 stability in response to DNA damage. It is phosphorylated by checkpoint kinase ATM/ATR and the phosphorylation mutant fails to stimulate p53 ubiquitination. RFWD3 also functions as a novel replication protein A (RPA)-associated protein involved in DNA replication checkpoint control. RFWD3 contains an N-terminal SQ-rich region followed by a RING finger domain that exhibits robust E3 ubiquitin ligase activity toward p53, a coiled-coil domain and three WD40 repeats in the C-terminus, the latter two of which may be responsible for protein-protein interaction. The RING finger in this family is a modified C3HGC3-type RING finger, but not a canonical C3H2C3-type RING-H2 finger or C3HC4-type RING-HC finger.


Pssm-ID: 319364 [Multi-domain]  Cd Length: 49  Bit Score: 39.57  E-value: 1.05e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 21539663 405 MCCPICCSEYVKG---EVATeLPCHHYFHKPCVSIWLQKSG-TCPVCR 448
Cdd:cd16450   3 DTCPICFEPWTNSgshRLCS-LKCGHLFGRSCIEKWLKGQGgKCPQCN 49
RING-HC_TRIM35_C-IV cd16599
RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar ...
404-448 1.40e-04

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 319513 [Multi-domain]  Cd Length: 44  Bit Score: 39.15  E-value: 1.40e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 404 EMCCPICcseYVKGEVATELPCHHYFHKPCVS-IWLQKSGTCPVCR 448
Cdd:cd16599   1 ELLCPIC---YDPFREAVTLRCGHNFCKGCVSrSWEVRSHTCPVCK 43
RING-H2_RNF214 cd16477
RING finger, H2 subclass, found in RING finger protein 214 (RNF214) and similar proteins; ...
411-447 2.04e-04

RING finger, H2 subclass, found in RING finger protein 214 (RNF214) and similar proteins; RNF214 is an uncharacterized RING finger protein containing a C3H2C3-type RING-H2 finger, suggesting possible E3-ubiquitin ligase activity.


Pssm-ID: 319391  Cd Length: 45  Bit Score: 38.73  E-value: 2.04e-04
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 21539663 411 CSEYVKGEVATELPCHHYFHKPCVSIWLQ--KSGTCPVC 447
Cdd:cd16477   6 CQKLVQPNEVHPMACSHTVHKECIKFWAQsnKNSTCPFC 44
RING-H2_RNF25 cd16470
RING finger, H2 subclass, found in RING finger protein 25 (RNF25) and similar proteins; RNF25, ...
407-448 2.08e-04

RING finger, H2 subclass, found in RING finger protein 25 (RNF25) and similar proteins; RNF25, also known as AO7, is a putative E3 ubiquitin-protein ligase that was initially identified as an interacting protein with an ubiquitin-conjugating enzyme, Ubc5B. It is ubiquitously expressed in various tissues and predominantly localized in the nucleus. RNF25 activates the nuclear factor (NF)-kappaB-dependent gene expression upon stimulation with Interleukin-1 beta (IL-1beta), or tumor necrosis factor (TNF), or overexpression of NF-kappaB-inducing kinase. It interacts with the p65 transactivation domain (TAD) and modulates its transcriptional activity. RNF25 contains an N-terminal RWD domain, a C3H2C3-type RING-H2 finger, and a C-termial Pro-rich region. Both the RING-H2 finger and the C-terminal regions of RNF25 are necessary for the transcriptional activation.


Pssm-ID: 319384 [Multi-domain]  Cd Length: 68  Bit Score: 39.29  E-value: 2.08e-04
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWL------------------------QKSGTCPVCR 448
Cdd:cd16470   2 CVICLYGFQEGDVFTKTPCYHYFHCHCLARYInhmltqlkaeqeeqeqqknqkeqpEEQVLCPVCR 67
RING-HC_TRIM13_C-V cd16762
RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar ...
403-448 2.15e-04

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for its degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates lanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs to the C-V subclass of TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM13 contains a C-terminal transmembrane domain.


Pssm-ID: 319676 [Multi-domain]  Cd Length: 57  Bit Score: 38.81  E-value: 2.15e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 21539663 403 QEMCCPICCSEYVKGEVateLPCHHYFHKPCV----------SIWLQKSGTCPVCR 448
Cdd:cd16762   2 EDLTCPICCSLFDDPRV---LPCSHNFCKKCLegilegnvrnMLWRPAPFKCPTCR 54
RING-HC_TRIM17_C-IV cd16595
RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar ...
404-448 2.29e-04

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 belongs to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.


Pssm-ID: 319509 [Multi-domain]  Cd Length: 48  Bit Score: 38.59  E-value: 2.29e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 21539663 404 EMCCPICCsEYVKGEVATElpCHHYFHKPCVSIWLQKSG------TCPVCR 448
Cdd:cd16595   1 ELCCSICL-DYFKDPVILR--CGHNFCRACITQFWEKQGglqgklTCPECR 48
RING-HC_UHRF cd16613
RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing ...
405-448 2.47e-04

RING finger, HC subclass, found in ubiquitin-like PHD and RING finger domain-containing proteins, UHRF1 and UHRF2, and similar proteins; UHRF1 is a unique chromatin effector protein that integrates the recognition of both histone PTMs and DNA methylation. It is essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas, such as laryngeal squamous cell carcinoma (LSCC), gastric cancer (GC), esophageal squamous cell carcinoma (ESCC), colorectal cancer, prostate cancer, and breast cancer. UHRF1 acts as a transcriptional repressor through its binding to histone H3 when it is unmodified at Arg2. Its overexpression in human lung fibroblasts results in downregulation of expression of the tumor suppressor pRB. It also plays a role in transcriptional repression of the cell cycle regulator p21. Moreover, UHRF1-dependent repression of transcription factors can facilitate the G1-S transition. It interacts with Tat-interacting protein of 60 kDa (TIP60) and induces degradation-independent ubiquitination of TIP60. It is also an N-methylpurine DNA glycosylase (MPG)-interacting protein that binds MPG in a p53 status-independent manner in the DNA base excision repair (BER) pathway. In addition, UHRF1 functions as an epigenetic regulator that is important for multiple aspects of epigenetic regulation, including maintenance of DNA methylation patterns and recognition of various histone modifications. UHRF2 was originally identified as a ubiquitin ligase acting as a small ubiquitin-like modifier (SUMO) E3 ligase that enhances zinc finger protein 131 (ZNF131) SUMOylation, but does not enhance ZNF131 ubiquitination. It also ubiquitinates PCNP, a PEST-containing nuclear protein. Moreover, UHRF2 functions as a nuclear protein involved in cell-cycle regulation and has been implicated in tumorigenesis. It interacts with cyclins, CDKs, p53, pRB, PCNA, HDAC1, DNMTs, G9a, methylated histone H3 lysine 9, and methylated DNA. It interacts with the cyclin E-CDK2 complex, ubiquitinates cyclins D1 and E1, induces G1 arrest, and is involved in the G1/S transition regulation. Furthermore, UHRF2 is a direct transcriptional target of the transcription factor E2F-1 in the induction of apoptosis. It recruits HDAC1 and binds to methyl-CpG. UHRF2 also participates in the maturation of Hepatitis B virus (HBV) by interacting with the HBV core protein and promoting its degradation. Both UHRF1 and UHRF2 contain an N-terminal ubiquitin-like domain (UBL), a tandem Tudor domain (TTD), a plant homeodomain (PHD) finger, a SET- and RING-associated (SRA) domain, and a C-terminal C3HC4-type RING-HC finger.


Pssm-ID: 319527 [Multi-domain]  Cd Length: 46  Bit Score: 38.53  E-value: 2.47e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21539663 405 MCcpICCSEYVKGEVATelPCHHYFHKPCvsiwLQKS-----GTCPVCR 448
Cdd:cd16613   2 TC--ICCQEVVYQPITT--PCQHNVCKGC----LQRSfkaevYSCPACR 42
RING-HC_RNF168 cd16550
RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; ...
407-448 2.62e-04

RING finger, HC subclass, found in RING finger protein 168 (RNF168) and similar proteins; RNF168 is an E3 ubiquitin-protein ligase that promotes noncanonical K27 ubiquitination to signal DNA damage. It, together with RNF8, functions as a DNA damage response (DDR) factor that promotes a series of ubiquitylation events on substrates, such as H2A and H2AX with H2AK13/15 ubiquitylation, facilitates recruitment of repair factors p53-binding protein 1 (53BP1) or the RAP80-BRCA1 complex to sites of double-strand breaks (DSBs), and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. RNF168 also promotes H2A neddylation, which antagonizes ubiquitylation of H2A and regulates DNA damage repair. Moreover, RNF168 forms a functional complex with RAD6A or RAD6B during the DNA damage response. RNF168 contains an N-terminal C3HC4-type RING-HC finger that catalyzes H2A-K15ub and interacts with H2A, and two MIU (motif interacting with ubiquitin) domains responsible for the interaction with K63 linked poly-ubiquitin.


Pssm-ID: 319464 [Multi-domain]  Cd Length: 42  Bit Score: 38.04  E-value: 2.62e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 407 CPICCSEYVkgEVATeLPCHHYFHKPCVSIWLQKSG-TCPVCR 448
Cdd:cd16550   1 CPICLEILV--EPVT-LPCKHELCLPCFQQTVEKANlCCPLCR 40
RING-H2_RNF32 cd16471
RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 ...
407-448 2.93e-04

RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, the protein with double RING-H2 fingers may act as a scaffold for binding several proteins that function in the same pathway.


Pssm-ID: 319385 [Multi-domain]  Cd Length: 49  Bit Score: 38.36  E-value: 2.93e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21539663 407 CPICCSEYVKGEVATeLPCHHYFHKPCVSIWLQKSG-------TCPVCR 448
Cdd:cd16471   2 CPICLEEFDQDSQAR-LSCSHVFHQACFLSYLAYSHservsqtQCPMCR 49
mRING-CH-C4HC2H_ZNRF2 cd16695
Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) ...
407-445 3.04e-04

Modified RING-CH finger, H2 subclass (C4HC2H-type), found in zinc/RING finger protein 2 (ZNRF2) and similar proteins; ZNRF2, also known as protein Ells2 or RING finger protein 202 (RNF202), is an E3 ubiquitin-protein ligase that is highly expressed in the nervous system during development and is present in presynaptic plasma membranes. It is N-myrisotoylated and also located in the endosome-lysosome compartment in fibroblasts. It contains an N-terminal MAGE domain, and a special C-terminal domain that combines a zinc finger and a modified C4HC2H-type RING-CH finger, rather than the typical C4HC3-type RING-CH finger, which is a variant of RING-H2 finger. Only the RING finger of the zinc finger-RING finger motif is required for its E3 ubiquitin ligase activity. Together with its sister protein ZNRF1, ZNRF2 regulates the ubiquitous Na+/K+ pump (Na+/K+ATPase).


Pssm-ID: 319609 [Multi-domain]  Cd Length: 45  Bit Score: 38.08  E-value: 3.04e-04
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCP 445
Cdd:cd16695   2 CAICLEELQQGDTIARLPCLCIYHKGCIDEWFEVNRSCP 40
mRING-HC-C3HC3D_SCAF11 cd16636
Modified RING finger, HC subclass (C3HC3D-type), found in SR-related and CTD-associated factor ...
407-448 3.66e-04

Modified RING finger, HC subclass (C3HC3D-type), found in SR-related and CTD-associated factor 11 (SCAF11) and similar proteins; SCAF11, also known as CTD-associated SR protein 11 (CASP11), renal carcinoma antigen NY-REN-40, SC35-interacting protein 1 (Sip1), Serine/arginine-rich splicing factor 2 (SRSF2)-interacting protein, or splicing regulatory protein 129 (SRrp129), is a novel arginine-serine-rich (RS) domain-containing protein essential for pre-mRNA splicing. It functions as an auxiliary splice factor interacting with spliceosomal component SC35 promoting RNAPII elongation. In addition to SR proteins, such as SC35, ASF/SF2, SRp75, and SRp20, SCAF11 also associates with U1-70K and U2AF65, proteins associated with 5' and 3' splice sites, respectively. SCAF11 contains an N-terminal modified C3HC3D-type RING-HC finger, an internal serine-arginine rich domain (SR domain), and a C-terminal SRI domain.


Pssm-ID: 319550  Cd Length: 43  Bit Score: 37.85  E-value: 3.66e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16636   2 CPICLNCLLEQEVAFPENCSHVFCLTCILKWAETLTSCPVDR 43
RING-H2_RNF24 cd16675
RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 ...
407-447 3.79e-04

RING finger, H2 subclass, found in RING finger protein 24 (RNF24) and similar proteins; RNF24 is an intrinsic membrane protein localized in the Golgi apparatus. It specifically interacts with the ankyrin-repeats domains (ARDs) of TRPC1, ?3, ?4, ?5, ?6, and ?7, and affects TRPC intracellular trafficking without affecting their activity. RNF24 contains an N-terminal transmembrane domain and a C-terminal C3H2C3-type RING-H2 finger.


Pssm-ID: 319589 [Multi-domain]  Cd Length: 47  Bit Score: 38.06  E-value: 3.79e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|.
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16675   3 CAVCLEEFKPKDELGICPCKHAFHRKCLIKWLEVRKVCPLC 43
APC11 COG5194
Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational ...
406-448 4.28e-04

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];


Pssm-ID: 227521 [Multi-domain]  Cd Length: 88  Bit Score: 39.05  E-value: 4.28e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 21539663 406 CCPICCSEYVKGEvatELP-----CHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:COG5194  33 TCPECQFGMTPGD---ECPvvwgvCNHAFHDHCIYRWLDTKGVCPLDR 77
RING-H2_TRAIP cd16480
RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; ...
407-448 5.24e-04

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.


Pssm-ID: 319394 [Multi-domain]  Cd Length: 45  Bit Score: 37.53  E-value: 5.24e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQK--SGTCPVCR 448
Cdd:cd16480   2 CTICSDFFDNSRDVAAIHCGHTFHYECLLQWFETapSRTCPQCR 45
zf-C3HC4_3 pfam13920
Zinc finger, C3HC4 type (RING finger);
403-448 5.36e-04

Zinc finger, C3HC4 type (RING finger);


Pssm-ID: 339001 [Multi-domain]  Cd Length: 48  Bit Score: 37.36  E-value: 5.36e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*..
gi 21539663   403 QEMCCPICCSEYVkgEVATeLPCHHY-FHKPCVSIWLQKSGTCPVCR 448
Cdd:pfam13920   1 EDRLCVICLDRPR--NVVL-LPCGHLcLCEECAERLRKKKKKCPICR 44
RING-HC_HLTF cd16509
RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar ...
407-448 6.48e-04

RING finger, HC subclass, found in helicase-like transcription factor (HLTF) and similar proteins; HLTF, also known as DNA-binding protein/plasminogen activator inhibitor 1 regulator, or HIP116, or RING finger protein 80, or SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 3, or sucrose nonfermenting protein 2-like 3, is a yeast RAD5 homolog found in mammals. It has both E3 ubiquitin ligase and DNA helicase activities, and plays a pivotal role in the template-switching pathway of DNA damage tolerance. It is involved in Lys-63-linked poly-ubiquitination of proliferating cell nuclear antigen (PCNA) at Lys-164 and in the regulation of DNA damage tolerance. It shows double-stranded DNA translocase activity with 3'-5' polarity, thereby facilitating regression of the replication fork. HLTF contains an N-terminal HIRAN (HIP116 and RAD5 N-terminal) domain, a SWI/SNF helicase domain that is divided into N- and C-terminal parts by an insertion of a C3HC4-type RING-HC finger involved in the poly-ubiquitination of PCNA.


Pssm-ID: 319423 [Multi-domain]  Cd Length: 43  Bit Score: 37.28  E-value: 6.48e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 407 CPICCsEYVKGEVATelPCHHYFHKPCVSIWLQKSG--TCPVCR 448
Cdd:cd16509   3 CPICL-DSLKDPVIT--PCAHVFCRGCIEQVIQREPnaKCPLCR 43
zf-RING_UBOX pfam13445
RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.
407-445 6.61e-04

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.


Pssm-ID: 338747 [Multi-domain]  Cd Length: 38  Bit Score: 36.98  E-value: 6.61e-04
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 21539663   407 CPICCSEYVKgevaTELPCHHYFHKPCV---SIWLQKSGTCP 445
Cdd:pfam13445   1 CPICLELFTD----PVLPCGHTFCRECLeemSLLKGGRFKCP 38
RING-HC_ScPSH1_like cd16568
RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated ...
406-448 8.00e-04

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1), Arabidopsis thaliana Protein KEEP ON GOING (AtKEG) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain. AtKEG is an E3 ubiquitin ligase essential for Arabidopsis growth and development. It maintains low levels of ABSCISIC ACID-INSENSITIVE5 (ABI5) in the absence of stress and thus functions as a negative regulator of abscisic acid (ABA) signaling. AtKEG is a multidomain protein that includes a C3HC4-type RING-HC finger, a kinase domain, ankyrin repeats, and 12 HERC2-like (for HECT and RCC1-like) repeats.


Pssm-ID: 319482 [Multi-domain]  Cd Length: 45  Bit Score: 37.09  E-value: 8.00e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21539663 406 CCPICCSEYvkGEVATELPCHHYFHKPCVSIWL----QKSGTCPVCR 448
Cdd:cd16568   1 VCSVCHDRL--NEVPMMLPCGHGFCKKCLNKMFstssDKRLACPTCR 45
RING_Ubox cd00162
The superfamily of RING finger (Really Interesting New Gene) domain and U-box domain; RING ...
407-447 8.08e-04

The superfamily of RING finger (Really Interesting New Gene) domain and U-box domain; RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized as two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have different Cys/His pattern. Some lack a single Cys or His residues at typical Zn ligand positions. Especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well. C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC finger. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are close to RING-H2 finger. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerated RING fingers from Siz/PIAS RING (SP-RING) family proteins and sporulation protein RMD5, are characterized by lacking the second, fifth, and sixth Zn2+ ion-coordinating residues. They bind only one Zn2+ ion. On the other hand, the RING fingers of the human APC11 and RBX1 proteins can bind a third Zn atom since they harbor four additional Zn ligands. U-box is a modified form of the RING finger domain that lacks metal chelating Cys and His. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms. RING finger/U-box-containing proteins are a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.


Pssm-ID: 319361 [Multi-domain]  Cd Length: 40  Bit Score: 36.67  E-value: 8.08e-04
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVAteLPCHHYFHKPCVSIWLQKSG-TCPVC 447
Cdd:cd00162   1 CPICRELMKDPVVL--PSCGHTFCYSCIARWLESSDqTCPFC 40
COG5219 COG5219
Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];
407-452 8.44e-04

Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];


Pssm-ID: 227544  Cd Length: 1525  Bit Score: 41.96  E-value: 8.44e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 21539663  407 CPICCSeyVKGEVATELP------CHHYFHKPCVSIWLQKSG--TCPVCRCMFP 452
Cdd:COG5219 1472 CAICYS--VLDMVDRSLPskrcatCKNKFHTRCLYKWFASSArsNCPLCRSEIT 1523
RING-H2_PHR cd16463
RING finger, H2 subclass, found in the PHR protein family; The PHR protein family represents ...
407-448 8.67e-04

RING finger, H2 subclass, found in the PHR protein family; The PHR protein family represents an evolutionally conserved family of large proteins including human E3 ubiquitin ligase protein associated with Myc (Pam) and its homologs, Phr1 (for Pam/Highwire/RPM-1) in mouse, Highwire (HIW) in Drosophila, RPM-1 (regulator of presynaptic morphology 1) in Caenorhabditis elegans, and Esrom in zebrafish. Those proteins are large E3 ubiquitin ligases containing regulator of chromosome condensation (RCC) homology domains (RHD-1 and RHD-2) with inferred guanine exchange factor (GEF) activity, a Myc-binding domain, a B-box zinc finger, and a C-terminal C3H2C3-type RING-H2 finger with E3 ubiquitin (Ub) ligase activity. They play an important role in axon guidance and synaptogenesis. They regulate synapse formation and growth in mammals, zebrafish, Drosophila, and Caenorhabditis elegans, and may control a variety of signaling pathways, including cAMP signaling in mammalian cells, JNK/p38 MAPK signaling in Drosophila and C. elegans, and bone morphogenetic protein signaling in Drosophila. Pam also known as Myc-binding protein 2 (MYCBP2), or Pam/highwire/rpm-1 protein (PHR1), negatively regulates neuronal growth, synaptogenesis and synaptic plasticity by modulating several signaling pathways including the p38 MAPK signaling cascade. It also participates in receptor and ion channel internalization, such as regulating internalization of transient receptor potential vanilloid receptor 1 (TRPV1) in peripheral sensory neurons, as well as duration of thermal hyperalgesia through p38 MAPK. It interacts with neuron-specific electroneutral potassium (K+) and chloride (Cl-) cotransporter KCC2 and modulates its function. Moreover, Pam genetically interacts with Robo2 to modulate axon guidance in the olfactory system. It also associates with tuberous sclerosis complex (TSC) proteins, ubiquitinating TSC2 and regulating mammalian/mechanistic target of rapamycin (mTOR) signaling. Furthermore, Pam is the longest lasting nontranscriptional regulator of adenylyl cyclase activity, and can mediate sustained inhibition of cAMP signaling by sphingosine-1-phosphate. It is also involved in spinal nociceptive processing. Phr1 is an essential regulator of retinal ganglion cell projection during both dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) topographic map development. RPM-1 positively regulates a Rab GTPase pathway to promote vesicular trafficking via late endosomes, thereby regulating synapse formation and axon termination. Esrom has E3 ligase activity and modulates the amount of phosphorylated Tuberin, a tumor suppressor, in growth cones. It is required in formation of the retinotectal projection.


Pssm-ID: 319377  Cd Length: 55  Bit Score: 37.29  E-value: 8.67e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVATELPCHHYFHKPCVSIWLQKSGT----------CPVCR 448
Cdd:cd16463   4 CMICFTEALSAAPAIQLQCGHVFHLHCCRRVLEKRWPgpritfgflkCPICK 55
RING-HC_DTX3 cd16711
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3) and similar ...
407-448 1.06e-03

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3) and similar proteins; DTX3, also known as RING finger protein 154 (RNF154), is an E3 ubiquitin-protein ligase that belongs to the Deltex (DTX) family. In contrast to other DTXs, DTX3 does not contain N-terminal two Notch-binding WWE domains, but a short unique N-terminal domain, suggesting it does not interact with intracellular domain of Notch. Its C-terminal region includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain.


Pssm-ID: 319625 [Multi-domain]  Cd Length: 41  Bit Score: 36.64  E-value: 1.06e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEvaTELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16711   2 CPICLGEIQNKK--TLDKCKHSFCEDCITRALQVKKACPMCG 41
RING-HC_DTX3L cd16712
RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, ...
406-447 1.24e-03

RING finger, HC subclass, found in protein Deltex-3-like (DTX3L) and similar proteins; DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), is a RING-domain E3 ubiquitin-protein ligase that regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. DTX3L has a unique N-terminus, but lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex (DTX) family members, such as DTX1, DTX2, and DTX4. Moreover, its C-terminal region is highly homologous to DTX3. It includes a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N-terminus and further enhance self-ubiquitination.


Pssm-ID: 319626 [Multi-domain]  Cd Length: 41  Bit Score: 36.27  E-value: 1.24e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 21539663 406 CCPICCSEYVKGEVateLP-CHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16712   1 KCPICMDKVSDPKV---LPkCKHVFCAACIDEAFKHKPVCPVC 40
RING-H2_Vps cd16484
RING finger, H2 subclass, found in vacuolar protein sorting-associated proteins Vps8, Vps11, ...
407-448 1.25e-03

RING finger, H2 subclass, found in vacuolar protein sorting-associated proteins Vps8, Vps11, Vps18, Vps41, and similar proteins; This family corresponds to a group of vacuolar protein sorting-associated proteins containing a C-terminal C3H2C3-type RING-H2 finger, which includes Vps8, Vps11, Vps18, and Vps41. Vps11 and Vps18 associate with Vps16 and Vps33 to form a Class C Vps core complex that is required for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE)-mediated membrane fusion at the lysosome-like yeast vacuole. The core complex, together with two additional compartment-specific subunits, forms the tethering complexes HOPS (homotypic vacuole fusion and protein sorting) and CORVET (class C core vacuole/endosome transport) protein complexes. CORVET contains the additional Vps3 and Vps8 subunits. It operates at endosomes, controls traffic into late endosomes and interacts with the Rab5/Vps21-GTP form. HOPS contains the additional Vps39 and Vps41 subunits. It operates at the lysosomal vacuole, controls all traffic from late endosomes into the vacuole and interacts with the Rab7/Ypt7-GTP form.


Pssm-ID: 319398  Cd Length: 46  Bit Score: 36.32  E-value: 1.25e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICCSEYVKGEVATEL---PCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16484   2 CSICNKPLKERGRADPVvvfFCGHMYHETCLENYERSRATCPICS 46
RING-H2_RNF121_like cd16475
RING finger, H2 subclass, found in RING finger proteins RNF121, RNF175 and similar proteins; ...
402-448 1.27e-03

RING finger, H2 subclass, found in RING finger proteins RNF121, RNF175 and similar proteins; The family includes RNF121, RNF175 and similar proteins. RNF121 is an E3-ubiquitin ligase present in the endoplasmic reticulum (ER) and cis-Golgi compartments. It is a novel regulator of apoptosis. It also facilitates the degradation and membrane localization of voltage-gated sodium (NaV) channels, and thus plays a role in the quality control of NaV channels during their synthesis and subsequent transport to the membrane. Moreover, RNF121 acts as a broad regulator of nuclear factor kappaB (NF-kappaB) signaling since its silencing also dampens NF-kappaB activation following stimulation of toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I-like Receptors (RLRs) or after DNA damages. RNF121 contains five conserved transmembrane (TM) domains and a C3H2C2-type RING-H2 finger. RNF175 is an uncharacterized RING finger protein that shows high sequence similarity with RNF121. This family also includes Arabidopsis RING finger E3 ligase RHA2A, RHA2B, and their homologs. RHA2A is a novel positive regulator of abscisic acid (ABA) signaling during seed germination and early seedling development. RHA2B may play a role in the ubiquitin-dependent proteolysis pathway that respond to proteasome inhibition. All family members contain a C3H2C3-type RING-H2 finger, which is responsible for E3-ubiquitin ligase activity.


Pssm-ID: 319389 [Multi-domain]  Cd Length: 55  Bit Score: 36.50  E-value: 1.27e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 21539663 402 GQEMCcpICCSEYVKGEVATELPCHHYFHKPCVSIW--LQKSGTCPVCR 448
Cdd:cd16475   7 GQELD--VDDNEEGIIEKTYQLSCGHVFHEFCIRGWciVGKKQTCPYCK 53
zf-ANAPC11 pfam12861
Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the ...
406-451 1.54e-03

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.


Pssm-ID: 289620 [Multi-domain]  Cd Length: 85  Bit Score: 37.46  E-value: 1.54e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 21539663   406 CCPIC------CSeYVKGEvatelpCHHYFHKPCVSIWLQKS---GTCPVCRCMF 451
Cdd:pfam12861  34 TCPDCkfpgddCP-LVWGK------CSHNFHMHCILKWLHTEtskGLCPMCRQTF 81
RING-HC_RNF224_like cd16565
RING finger, HC subclass, found in RING finger protein RNF224, RNF225 and similar proteins; ...
407-448 1.79e-03

RING finger, HC subclass, found in RING finger protein RNF224, RNF225 and similar proteins; Both RNF224 and RNF225 are uncharacterized C3HC4-type RING-HC finger-containing proteins. They may function as an E3 ubiquitin-protein ligase.


Pssm-ID: 319479 [Multi-domain]  Cd Length: 49  Bit Score: 35.98  E-value: 1.79e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 21539663 407 CPICCSEY-VKGEVATELPCHHYFHKPCV-----SIWLQKSGTCPVCR 448
Cdd:cd16565   2 CIICLSSYdLSGRLPRRLYCGHTFCQACLkrldtVTNEQRWIPCPQCR 49
RING-HC_Cbl_like cd16502
RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor ...
407-448 2.07e-03

RING finger, HC subclass, found in Casitas B-lineage lymphoma (Cbl) proteins; The Cbl adaptor proteins family contains a small class of RING-type E3 ubiquitin ligases with oncogenic activity, which is represented by three mammalian members, c-Cbl, Cbl-b and Cbl-c, as well as two invertebrate Cbl-family proteins, D-Cbl in Drosophila and Sli-1 in C. elegans. Cbl proteins function as potent negative regulators of various signaling cascades in a wide range of cell types. They play roles in ubiquitinating the activated tyrosine kinases and targeting them for degradation. D-Cbl associates with the Drosophila epidermal growth factor receptor (EGFR) and overexpression of D-Cbl in the eye of Drosophila embryos inhibits EGFR dependent photoreceptor cell development. Sli-1 is a negative regulator of the Let-23 receptor tyrosine kinase, an EGFR homolog, in vulva development. Cbl proteins in this family consist of a highly conserved N-terminal half that includes a tyrosine-kinase-binding domain (TKB, also known as the phosphotyrosine binding PTB domain, is composed of a four helix-bundle, a Ca2+ binding EF-hand and a highly variant SH2 domain) and a C3HC4-type RING-HC finger, both of which are required for Cbl-mediated downregulation of RTKs, and a divergent C-terminal region.


Pssm-ID: 319416 [Multi-domain]  Cd Length: 43  Bit Score: 35.79  E-value: 2.07e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICCSEY--VKGEvatelPCHHYFHKPCVSIWLQKSG-TCPVCR 448
Cdd:cd16502   4 CKICAENDkdVRIE-----PCGHLLCTPCLTSWQDSDGqTCPFCR 43
RINGv smart00744
The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and ...
406-448 2.80e-03

The RING-variant domain is a C4HC3 zinc-finger like motif found in a number of cellular and viral proteins; Some of these proteins have been shown both in vivo and in vitro to have ubiquitin E3 ligase activity. The RING-variant domain is reminiscent of both the RING and the PHD domains and may represent an evolutionary intermediate. To describe this domain the term PHD/LAP domain has been used in the past. Extended description: The RING-variant (RINGv) domain contains a C4HC3 zinc-finger-like motif similar to the PHD domain, while some of the spacing between the Cys/His residues follow a pattern somewhat closer to that found in the RING domain. The RINGv domain, similar to the RING, PHD and LIM domains, is thought to bind two zinc ions co-ordinated by the highly conserved Cys and His residues. RING variant domain: C-x (2) -C-x(10-45)-C-x (1) -C-x (7) -H-x(2)-C-x(11-25)-C-x(2)-C As opposed to a PHD: C-x(1-2) -C-x (7-13)-C-x(2-4)-C-x(4-5)-H-x(2)-C-x(10-21)-C-x(2)-C Classical RING domain: C-x (2) -C-x (9-39)-C-x(1-3)-H-x(2-3)-C-x(2)-C-x(4-48) -C-x(2)-C


Pssm-ID: 128983  Cd Length: 49  Bit Score: 35.35  E-value: 2.80e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 21539663    406 CCPICcseYVKGEVATEL--PCH-----HYFHKPCVSIWLQKSG--TCPVCR 448
Cdd:smart00744   1 ICRIC---HDEGDEGDPLvsPCRckgslKYVHQECLERWINESGnkTCEICK 49
RING-HC_PCGF1 cd16733
RING finger, HC subclass, found in polycomb group RING finger protein 1 (PCGF1) and similar ...
404-447 2.87e-03

RING finger, HC subclass, found in polycomb group RING finger protein 1 (PCGF1) and similar proteins; PCGF1, also known as nervous system Polycomb-1 (NSPc1) or RING finger protein 68 (RNF68), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) and serves as the core component of a noncanonical Polycomb repressive complex 1 (PRC1)-like BCOR complex that also contains RING1, RNF2, RYBP, SKP1, as well as the BCL6 co-repressor BCOR and the histone demethylase KDM2B, and is required to maintain the transcriptionally repressive state of some genes, such as Hox genes, BCL6 and the cyclin-dependent kinase inhibitor, CDKN1A. PCGF1 promotes cell cycle progression and enhances cell proliferation as well. It is a cell growth regulator that acts as a transcriptional repressor of p21Waf1/Cip1 via the retinoid acid response element (RARE element). Moreover, PCGF1 functions as an epigenetic regulator involved in hematopoietic cell differentiation. It cooperates with the transcription factor runt-related transcription factor 1 (Runx1) in regulating differentiation and self-renewal of hematopoietic cells. Furthermore, PCGF1 represents a physical and functional link between Polycomb function and pluripotency. PCGF1 contains a C3HC4-type RING-HC finger.


Pssm-ID: 319647 [Multi-domain]  Cd Length: 43  Bit Score: 35.35  E-value: 2.87e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 21539663 404 EMCCPICCSEYVKGEVATElpCHHYFHKPCVSIWLQKSGTCPVC 447
Cdd:cd16733   1 HIVCILCAGYFIDATTITE--CLHTFCKSCIVKYLQTSKYCPMC 42
RING-HC_TRIM8_C-V cd16580
RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar ...
405-447 3.09e-03

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V subclass of nuclear TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.


Pssm-ID: 319494 [Multi-domain]  Cd Length: 44  Bit Score: 35.32  E-value: 3.09e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*.
gi 21539663 405 MCCPICCSEYVKgevATELPCHHYFHKPCVS-IWLQKSGT--CPVC 447
Cdd:cd16580   1 LICPICLHVFVE---PVQLPCKHNFCRGCIGeAWAKEAGLvrCPEC 43
RING-H2_RBX2 cd16466
RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also ...
425-448 4.20e-03

RING finger, H2 subclass, found in RING-box protein 2 (RBX2) and similar proteins; RBX2, also known as CKII beta-binding protein 1 (CKBBP1), RING finger protein 7 (RNF7), regulator of cullins 2 (ROC2), or sensitive to apoptosis gene protein (SAG), is an E3 ubiquitin-protein ligase that protects cells from apoptosis, confers radioresistance, and plays an essential and non-redundant role in embryogenesis and vasculogenesis. It promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1alpha, IkappaBalpha, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes. RBX2 is necessary for ubiquitin ligation activity of the multimeric cullin (Cul)-RING E3 ligases (CRLs). RBX2-containing CRLs are involved in NEDD8 pathway and RBX2 specifically regulate NEDD8ylation of Cul5. It can bind and activate HIV-1 Vif-Cullin5 E3 ligase complex in vitro. It is also a substrate of NEDD4-1 E3 ubiquitin ligase and mediates NEDD4-1 induced chemosensitization. The inactivation of RBX2 E3 ubiquitin ligase activity triggers senescence and inhibits Kras-induced immortalization. Endothelial deletion of RBX2 causes embryonic lethality and blocks tumor angiogenesis, suggesting a way for anti-angiogenesis therapy of human cancer. Moreover, as a component of Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. Furthermore, RBX2 functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. RBX2 contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.


Pssm-ID: 319380 [Multi-domain]  Cd Length: 60  Bit Score: 35.19  E-value: 4.20e-03
                        10        20
                ....*....|....*....|....
gi 21539663 425 CHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16466  34 CNHSFHNCCMSLWVKQNNRCPLCQ 57
mRING-HC-C3HC3D_LNX1_like cd16637
Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, ...
404-448 4.59e-03

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, and similar proteins; The ligand of Numb protein X (LNX) family, also known as PDZ and RING (PDZRN) family, includes LNX1-5, which can interact with Numb, a key regulator of neurogenesis and neuronal differentiation. LNX5 (also known as PDZK4 or PDZRN4L) shows high sequence homology to LNX3 and LNX4, but it lacks the RING domain. LNX1-4 proteins function as E3 ubiquitin ligases and have a unique domain architecture consisting of an N-terminal RING-HC finger for E3 ubiquitin ligase activity and either two or four PDZ domains necessary for the substrate-binding. This family corresponds to LNX1/LNX2-like proteins, which contains a modified C3HC3D-type RING-HC finger and four PDZ domains.


Pssm-ID: 319551 [Multi-domain]  Cd Length: 42  Bit Score: 34.62  E-value: 4.59e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 404 EMCCPICCSEYVKgevATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16637   1 DLICHICLQPLVD---PLDTPCGHTFCSRCLKNYLKVQKFCPIDR 42
RING-HC_SH3RF2 cd16749
RING finger, HC subclass, found in SH3 domain-containing RING finger protein 2 (SH3RF2) and ...
407-448 5.10e-03

RING finger, HC subclass, found in SH3 domain-containing RING finger protein 2 (SH3RF2) and similar proteins; SH3RF2, also known as heart protein phosphatase 1-binding protein (HEPP1), plenty of SH3s (POSH)-eliminating RING protein (POSHER), protein phosphatase 1 regulatory subunit 39, or RING finger protein 158 (RNF158), is a putative E3 ubiquitin-protein ligase that acts as an anti-apoptotic regulator for the c-Jun N-terminal kinase (JNK) pathway by binding to and promoting the proteasomal degradation of SH3RF1 (or POSH), a scaffold protein that is required for pro-apoptotic JNK activation. It may also play a role in cardiac functions together with protein phosphatase 1. SH3RF2 contains an N-terminal C3HC4-type RING-HC finger responsible for the E3 ligase activity and four Src Homology 3 (SH3) domains that are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs.


Pssm-ID: 319663 [Multi-domain]  Cd Length: 48  Bit Score: 34.91  E-value: 5.10e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICcseYVKGEV-ATELPCHHYFHKPCVSIWL--QKSGTCPVCR 448
Cdd:cd16749   5 CPVC---FEKLDVtAKVLPCQHTFCKPCLQRIFkaRKELRCPECR 46
RING-HC_AtRMA_like cd16745
RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) ...
407-448 5.19e-03

RING finger, HC subclass, found in Arabidopsis thaliana RING membrane-anchor proteins (AtRMAs) and similar proteins; AtRMAs, including AtRma1, AtRma2, and AtRma3, are endoplasmic reticulum (ER)-localized Arabidopsis homologs of human outer membrane of the ER-anchor E3 ubiquitin-protein ligase, RING finger protein 5 (RNF5). AtRMAs possess E3 ubiquitin ligase activity, and may play a role in the growth and development of Arabidopsis. The AtRMA1 and AtRMA3 genes are predominantly expressed in major tissues, such as cotyledons, leaves, shoot-root junction, roots, and anthers, while AtRMA2 expression is restricted to the root tips and leaf hydathodes. AtRma1 probably functions with the Ubc4/5 subfamily of E2. AtRma2 is likely involved in the cellular regulation of ABP1 expression levels through interacting with auxin binding protein 1 (ABP1). AtRMA proteins contain an N-terminal C3HC4-type RING-HC finger and a trans-membrane-anchoring domain in their extreme C-terminal region.


Pssm-ID: 319659 [Multi-domain]  Cd Length: 45  Bit Score: 34.59  E-value: 5.19e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 407 CPICCsEYVKGEVATelPCHHYFHKPCVSIWLQKSG---TCPVCR 448
Cdd:cd16745   3 CNICL-DLASDPVVT--LCGHLFCWPCLYRWLQRHSenrECPVCK 44
mRING-HC-C3HC3D_Nrdp1 cd16634
Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation ...
404-448 5.24e-03

Modified RING finger, HC subclass (C3HC3D-type), found in neuregulin receptor degradation protein-1 (Nrdp1) and similar proteins; Nrdp1 (referred to as FLRF in mice), also known as RING finger protein 41 (RNF41), is an E3 ubiquitin-protein ligase that plays a critical role in the regulation of cell growth and apoptosis, inflammation and production of reactive oxygen species (ROS), as well as in doxorubicin (DOX)-induced cardiac injury. It promoten and degradation of the epidermal growth factor receptor (EGFR/ErbB) family member, ErbB3, which is independent of growth factor stimulation. It also promotes M2 macrophage polarization by ubiquitinating and activating transcription factor CCAAT/enhancer-binding Protein beta (C/EBPbeta) via Lys-63-linked ubiquitination. Moreover, Nrdp1 interacts with and modulates activity of Parkin, a causative protein for early onset recessive juvenile parkinsonism (AR-JP). It also interacts with ubiquitin-specific protease 8 (USP8), which is involved in trafficking of various transmembrane proteins. Furthermore, Nrdp1 inhibits basal lysosomal degradation and enhances ectodomain shedding of JAK2-associated cytokine receptors. Its phosphorylation by the kinase Par-1b (also known as MARK2) is required for epithelial cell polarity. Nrdp1 contains an N-terminal modified C3HC3D-type RING-HC finger required for enhancing ErbB3 degradation, a B-box, a coiled-coil domain responsible for Nrdp1 oligomerization, and a C-terminal ErbB3-binding domain.


Pssm-ID: 319548 [Multi-domain]  Cd Length: 43  Bit Score: 34.71  E-value: 5.24e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 21539663 404 EMCCPICCSeyVKGEVATELPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16634   1 ELICPICSG--VLEEPLQAPHCEHAFCNACITEWLSRQQTCPVDR 43
RING-H2_APC11 cd16456
RING finger, H2 subclass, found in anaphase-promoting complex subunit 11 (APC11) and similar ...
406-448 5.56e-03

RING finger, H2 subclass, found in anaphase-promoting complex subunit 11 (APC11) and similar proteins; APC11, also known as cyclosome subunit 11, or hepatocellular carcinoma-associated RING finger protein, is a C3H2C3-type RING-H2 protein that facilitates ubiquitin chain formation by recruiting ubiquitin-charged ubiquitin conjugating enzymes (E2) through its RING-H2 domain. APC11 and its partner the cullin-like subunit APC2 form the dynamic catalytic core of the gigantic, multisubunit 1.2-MDa anaphase-promoting complex/cyclosome (APC), also known as the cyclosome, which is a ubiquitin-protein ligase (E3) composed of at least 12 subunits and controls cell division by ubiquitinating cell cycle regulators, such as cyclin B and securin, to drive their timely degradation. APC11 can be inhibited by hydrogen peroxide, which may contributes to the delay in cell cycle progression through mitosis that is characteristic of cells subjected to oxidative stress. APC11 contains a canonical RING-H2-finger domain, which includes one histidine and seven cysteine residues that coordinate two Zn2+ ions. In addition, it contains a third Zn2+-binding site and the third Zn2+ ion is not essential for its ligase activity.


Pssm-ID: 319370 [Multi-domain]  Cd Length: 63  Bit Score: 34.94  E-value: 5.56e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 21539663 406 CCPIC------CSeYVKGEvatelpCHHYFHKPCVSIWL---QKSGTCPVCR 448
Cdd:cd16456  14 CCPDCkfpgddCP-LVWGK------CSHAFHMHCILKWLnsqQVQQQCPMCR 58
RING-HC_RNF186 cd16557
RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; ...
404-448 5.72e-03

RING finger, HC subclass, found in RING finger protein 186 (RNF186) and similar proteins; RNF186 is an E3 ubiquitin-protein ligase with an N-terminal C3HC4-type RING-HC finger and two putative C-terminal transmembrane domains which enable it to localize in a certain organelle. It regulates RING-dependent self-ubiquitination, as well as endoplasmic reticulum (ER) stress-mediated apoptosis through interaction with the Bcl-2 family protein BNip1.


Pssm-ID: 319471 [Multi-domain]  Cd Length: 51  Bit Score: 34.81  E-value: 5.72e-03
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 21539663 404 EMCCPICCSEYVKGEVATELPCHHYFHKPCVSIWLQK-----SGTCPVCR 448
Cdd:cd16557   1 DLECLVCFNSYEFVRKPKLLACQHAFCAICLKLILEEkdntwVITCPLCR 50
RING-HC_DTX3_like cd16506
RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like ...
407-448 7.90e-03

RING finger, HC subclass, found in E3 ubiquitin-protein ligase Deltex3 (DTX3), Deltex-3-like (DTX3L) and similar proteins; The family contains Deltex3 (DTX3) and Deltex-3-like (DTX3L), both of which are E3 ubiquitin-protein ligases belonging to the Deltex (DTX) family. DTX3, also known as RING finger protein 154 (RNF154), has a biological function that remains unclear. DTX3L, also known as B-lymphoma- and BAL-associated protein (BBAP) or Rhysin-2 (Rhysin2), regulates endosomal sorting of the G protein-coupled receptor CXCR4 from endosomes to lysosomes. It also regulates subcellular localization of its partner protein, B aggressive lymphoma (BAL), by a dynamic nucleocytoplasmic trafficking mechanism. In contrast to other DTXs, both DTX3 and DTX3L contain a C3HC4-type RING-HC finger, and a previously unidentified C-terminal domain. DTX3L can associate with DTX1 through its unique N termini and further enhance self-ubiquitination.


Pssm-ID: 319420 [Multi-domain]  Cd Length: 41  Bit Score: 34.03  E-value: 7.90e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|..
gi 21539663 407 CPICCSEYVKGEVAteLPCHHYFHKPCVSIWLQKSGTCPVCR 448
Cdd:cd16506   2 CPICLDTISNKKVL--LKCKHSFCAPCINKALTVKPICPICQ 41
RING-HC_RNF208 cd16559
RING finger, HC subclass, found in RING finger protein 208 (RNF208) and similar proteins; ...
407-448 8.40e-03

RING finger, HC subclass, found in RING finger protein 208 (RNF208) and similar proteins; RNF208 is an E3 ubiquitin-protein ligase whose activity can be modulated by S-nitrosylation. It contains a C3HC4-type RING-HC finger.


Pssm-ID: 319473 [Multi-domain]  Cd Length: 50  Bit Score: 34.38  E-value: 8.40e-03
                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 21539663 407 CPICCSEYVKGEVateLPCHHYFHKPCVSIWLQKSG-----TCPVCR 448
Cdd:cd16559   4 CPLCGETYNRPRI---LSCLHSFCEPCLQKLYESCPkykfiSCPTCK 47
PHA02929 PHA02929
N1R/p28-like protein; Provisional
425-451 8.45e-03

N1R/p28-like protein; Provisional


Pssm-ID: 222944  Cd Length: 238  Bit Score: 37.45  E-value: 8.45e-03
                         10        20
                 ....*....|....*....|....*..
gi 21539663  425 CHHYFHKPCVSIWLQKSGTCPVCRCMF 451
Cdd:PHA02929 200 CNHVFCIECIDIWKKEKNTCPVCRTPF 226
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.17
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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