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 of the E2 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-terminal Pro-rich region. Both the RING-H2 finger and the C-terminal regions of RNF25 are necessary for transcriptional activation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34878787 131 PHGQCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQHMEQELKAqGQEQEQERQHATTKQKAVGVQCPVCREPL 205
Cdd:cd16470   1 PHGQCVICLYGFQEGDAFTKTPCYHYFHSHCLARYIQHMEENLKE-EQEEQEERPRAQTEQEQFQVLCPVCREPL 74

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 of the E2 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-terminal Pro-rich region. Both the RING-H2 finger and the C-terminal regions of RNF25 are necessary for transcriptional activation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34878787 131 PHGQCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQHMEQELKAqGQEQEQERQHATTKQKAVGVQCPVCREPL 205
Cdd:cd16470   1 PHGQCVICLYGFQEGDAFTKTPCYHYFHSHCLARYIQHMEENLKE-EQEEQEERPRAQTEQEQFQVLCPVCREPL 74

RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. The function of this domain is unknown. GCN2 is the alpha-subunit of the only translation initiation factor (eIF2 alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787    19 EVEVLESIYLDELQVIKgNGRTSPWEIYITLHPATAEDQDSQYVCFTLVLQVPAEYPHEVPQISIRNPRGLSDEQIHTIL 98
Cdd:pfam05773   6 ELEALESIYPDEFEVIS-DSPYESLEIEIKLSLDSDESDSSHLPPLVLKFTLPEDYPDEPPKISLSSPWNLSDEQVLSLL 84

                          90       100
                  ....*....|....*....|....*..
gi 34878787    99 QVLGHVAKAGLGTAMLYELIEKGKEIL 125
Cdd:pfam05773  85 EELEELAEENLGEVMIFELIEWLQENL 111

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   264 SLQQPPAPAEPESAVD-----VSKGSQPPSTLAAELSTSPAVQSTLPPPLPVATQHICEKIPGtrSNQQRLGETQKAMLD 338
Cdd:PHA03247 2797 SLPSPWDPADPPAAVLapaaaLPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPG--GDVRRRPPSRSPAAK 2874

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   339 PPKPSRGPWRQPERrhpkggechaPKGTRDTQELP-PPEGPLKEPM-DLKPEPHSQG-VEGPPQEKGPGSWQGPPPRRTR 415
Cdd:PHA03247 2875 PAAPARPPVRRLAR----------PAVSRSTESFAlPPDQPERPPQpQAPPPPQPQPqPPPPPQPQPPPPPPPRPQPPLA 2944

                         170       180       190
                  ....*....|....*....|....*....|
gi 34878787   416 DCVRWERSKGRTPGSSYPRLprgqGAYRPG 445
Cdd:PHA03247 2945 PTTDPAGAGEPSGAVPQPWL----GALVPG 2970

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 of the E2 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-terminal Pro-rich region. Both the RING-H2 finger and the C-terminal regions of RNF25 are necessary for transcriptional activation.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34878787 131 PHGQCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQHMEQELKAqGQEQEQERQHATTKQKAVGVQCPVCREPL 205
Cdd:cd16470   1 PHGQCVICLYGFQEGDAFTKTPCYHYFHSHCLARYIQHMEENLKE-EQEEQEERPRAQTEQEQFQVLCPVCREPL 74

RWD domain; This domain was identified in WD40 repeat proteins and Ring finger domain proteins. The function of this domain is unknown. GCN2 is the alpha-subunit of the only translation initiation factor (eIF2 alpha) kinase that appears in all eukaryotes. Its function requires an interaction with GCN1 via the domain at its N-terminus, which is termed the RWD domain after three major RWD-containing proteins: RING finger-containing proteins, WD-repeat-containing proteins, and yeast DEAD (DEXD)-like helicases. The structure forms an alpha + beta sandwich fold consisting of two layers: a four-stranded antiparallel beta-sheet, and three side-by-side alpha-helices.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787    19 EVEVLESIYLDELQVIKgNGRTSPWEIYITLHPATAEDQDSQYVCFTLVLQVPAEYPHEVPQISIRNPRGLSDEQIHTIL 98
Cdd:pfam05773   6 ELEALESIYPDEFEVIS-DSPYESLEIEIKLSLDSDESDSSHLPPLVLKFTLPEDYPDEPPKISLSSPWNLSDEQVLSLL 84

                          90       100
                  ....*....|....*....|....*..
gi 34878787    99 QVLGHVAKAGLGTAMLYELIEKGKEIL 125
Cdd:pfam05773  85 EELEELAEENLGEVMIFELIEWLQENL 111

RWD, DRWD, and ELF domain family; The family includes the RWD, double-RWD (DRWD), and ELF domains. They belong to the ubiquitin-conjugating (UBC) superfamily that represents a structural domain with an alpha-beta(4)-alpha(3) core fold. The RWD domain (named after three major RWD-containing proteins: RING finger, WD-repeat-containing proteins and DEXD-like helicases) mediates protein-protein interactions in a variety of pathways in eukaryotes. The DRWD domain is responsible for substrate binding. It is involved in interactions with other kinetochore proteins. The ELF (N-terminal E2-like fold) domain is found in all Fanconi anemia group L protein (FANCL) homologs. It is required to promote efficient DNA damage-induced FANCD2 (Fanconi anemia group D2 protein) monoubiquitination in vertebrate cells.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787  22 VLESIYLDELQVIKGNGRTSpWEIYITLHPataedqDSQYVCFTLVLQVPAEY-PHEVPQISIRNPRGLSDEQIHTILQV 100
Cdd:cd11605   1 ALESIYGDELEVLSDDSPLR-FSIRLSPEE------EEDDPPLELEFTLPPGYpPEEPPLITLRSPKLSSAERLSLLKLE 73

                        90
                ....*....|....*....
gi 34878787 101 LGHVAKAGLGTAMLYELIE 119
Cdd:cd11605  74 LEEAAEENLGEPMLFDLVE 92

H2 subclass of RING (RING-H2) fingers and its variants; The 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 different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (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 the 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34878787 135 CVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQHMEQelkaqgqeqeqerqhattkqkavgvQCPVCR 202
Cdd:cd16448   1 CVICLEEFEEGDVVRLLPCGHVFHLACILRWLESGNN-------------------------TCPLCR 43

RWD domain of RWD domain-containing protein 4 (RWDD4) and related proteins; RWDD4, also called protein FAM28A, is a target of the tumor suppressor MicroRNA (MiR)-506 in bladder cancer cells. Downregulation of RWDD4 suppresses bladder cancer cell proliferation, migration and invasion. RWDD4 has also been identified as a modifier of metastasis in human prostate cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787  19 EVEVLESIYldelqviKGNgrtspwEIYITLHPATAE---DQDSQYVCFTLVLQVPAEYPHEVPQISIR---NpRGLSDE 92
Cdd:cd23817   3 ELEVLLSIY-------EGD------ENFKQISDTTFQykyGEDGDPKSFLLEISWPENYPEEPPIINLDafyN-KHISSS 68

                        90       100       110
                ....*....|....*....|....*....|.
gi 34878787  93 QIHTILQVLGHVAKAGLGTAMLYELIEKGKE 123
Cdd:cd23817  69 VKEKIVSKLNEEAEQNLGSAMTYTLFEWAKE 99

RWD domain of RWD domain-containing protein 3 (RWDD3) and related proteins; RWDD3, also called RWD domain-containing sumoylation enhancer (RSUME), acts as an enhancer of SUMO conjugation and has no effect on ubiquitination. It increases protein sumoylation (a dynamic ubiquitin-like post translational modification) of several proteins including HIF1alpha and I-kappa-B, through direct interaction with UBC9. Its RWD domain is required for the sumoylation enhancement activity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787  19 EVEVLESIYL--DELQVIKGNGRTSPweiyITLHPATAEDQDSQYVCFTLVLQVPAEYPHEVPQISIRNPRgLSDEQIHT 96
Cdd:cd23819   2 ELSVLQAIFCgpGEFEVLSSSETSDG----VSFKIQISVEGFDEDIVLKLTFHLSPNYPSSLPDISVSSEQ-LTRAQCND 76

                        90       100
                ....*....|....*....|...
gi 34878787  97 ILQVLGHVAKAGLGTAMLYELIE 119
Cdd:cd23819  77 LQDSLLEYANSLLGEPMVLELVL 99

RWD domain of Saccharomyces cerevisiae putative ATP-dependent RNA helicase YLR419W and related proteins; YLR419W (EC 3.6.4.13) may act as an ATP-binding RNA helicase. The RWD domain may mediate protein-protein interactions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787  19 EVEVLESIYLDELQVIKGNGrtspWEIYITLHPATAEDqdsqyvcftLVLQV--PAEYPHEVPQISIRNPRGL-SDEQIH 95
Cdd:cd23827   4 EIEALEAIYGEKFEVISDDS----CEITLNSPTKTKPS---------LKLKFykSSSYPNSLPGIFISSSDKLpAYIKLA 70

                        90       100       110
                ....*....|....*....|....*....|..
gi 34878787  96 TILQVLGHVAKAGLGTAMLYELIEKGKEILTD 127
Cdd:cd23827  71 IIRQLLQYARDNLLGDPMIFSIVEWLEENIEE 102

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   264 SLQQPPAPAEPESAVD-----VSKGSQPPSTLAAELSTSPAVQSTLPPPLPVATQHICEKIPGtrSNQQRLGETQKAMLD 338
Cdd:PHA03247 2797 SLPSPWDPADPPAAVLapaaaLPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPG--GDVRRRPPSRSPAAK 2874

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   339 PPKPSRGPWRQPERrhpkggechaPKGTRDTQELP-PPEGPLKEPM-DLKPEPHSQG-VEGPPQEKGPGSWQGPPPRRTR 415
Cdd:PHA03247 2875 PAAPARPPVRRLAR----------PAVSRSTESFAlPPDQPERPPQpQAPPPPQPQPqPPPPPQPQPPPPPPPRPQPPLA 2944

                         170       180       190
                  ....*....|....*....|....*....|
gi 34878787   416 DCVRWERSKGRTPGSSYPRLprgqGAYRPG 445
Cdd:PHA03247 2945 PTTDPAGAGEPSGAVPQPWL----GALVPG 2970

RWD domain of protein IMPACT and related proteins; IMPACT, also imprinted and ancient gene protein homolog, acts as a translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment, and glucose deprivation. It plays a role as a negative regulator of EIF2AK4/GCN2 kinase activity. It impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. IMPACT may be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, IMPACT plays a role in differentiation of neuronal cells by stimulating neurite outgrowth.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787  19 EVEVLESIYLDELQVIKGNGRTspWEIYItlhpataEDQDSQYVCFTLVLQVPAEYP-HEVPQISIRNPRgLSDEQIHTI 97
Cdd:cd23821   3 EIEALEAIYGEDFVVIDESARS--FVIRI-------ELDGPHLPPLVLRVHLPPDYPsHSPPIFELSAPW-LSGEERSEL 72

                        90       100
                ....*....|....*....|....*...
gi 34878787  98 LQVLGHVAKAGLGTAMLYELIEKGKEIL 125
Cdd:cd23821  73 CAELDEIWEENAGEPVLFQWVEWLREYL 100

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 by 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.

                        10        20        30
                ....*....|....*....|....*....|
gi 34878787 133 GQCVICLYGFQEKEAFTKTPCYHYFHCHCL 162
Cdd:cd16473   5 EECAICLENYQNGDLLRGLPCGHVFHQNCI 34

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. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the 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.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 34878787 135 CVIClygFQEKEAFTKTPCYHYFHCHCLAR--YIQ 167
Cdd:cd16476   3 CAIC---YQEMKEARITPCNHFFHGLCLRKwlYVQ 34

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 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 model corresponds to the second RING-H2 finger, which is not a canonical C3H2C3-type, but a modified C3H2C2D-type.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 34878787 134 QCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQH 168
Cdd:cd16486   1 QCRICLKAFQLGQHVRTLPCRHKFHRDCIDNWLLH 35

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. RNF12 also acts as a co-regulator for 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 signaling of type I receptors from the transforming growth factor beta (TGF-beta) superfamily. 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.

                        10        20        30
                ....*....|....*....|....*....|..
gi 34878787 135 CVICLYGFQEKEAFTKTPCYHYFHCHCLARYI 166
Cdd:cd16674   3 CSVCITEYTEGNKLRKLPCSHEYHVHCIDRWL 34

RING finger, H2 subclass, found in Arabidopsis thaliana RING-H2 finger A1a (RHA1A), A1b (RHA1B) and similar proteins; This subfamily includes Arabidopsis thaliana RHA1A, RHA1B and XERICO. RHA1A is a probable E3 ubiquitin-protein ligase that may possess E3 ubiquitin ligase activity in vitro. RHA1B possesses E3 ubiquitin-protein ligase activity when associated with the E2 enzyme UBC8 in vitro. XERICO functions on abscisic acid homeostasis at post-translational level, probably through ubiquitin/proteasome-dependent substrate-specific degradation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34878787 135 CVICLYGFQEKEAFTKTP-CYHYFHCHCLARYIQhmeqelkaqgqeqeqerqhaTTKQKavgvqCPVCREPL 205
Cdd:cd23121   4 CAICLSDFNSDEKLRQLPkCGHIFHHHCLDRWIR--------------------YNKIT-----CPLCRADL 50

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.

                        10        20
                ....*....|....*....|....*....
gi 34878787 134 QCVICLYGFQEKEAFTKTPCYHYFHCHCL 162
Cdd:cd16669   1 KCPICLLEFEEGETVKQLPCKHSFHSDCI 29

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, Arkadia2, or Ark2C, is an E3 ubiquitin ligase with homology to the C-terminal half of RNF111. It is expressed specifically in the nervous system, and can serve to amplify neuronal responses to specific signals. It 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.

                        10        20        30
                ....*....|....*....|....*....|...
gi 34878787 135 CVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQ 167
Cdd:cd16474   3 CTICLSDFEEGEDVRRLPCMHLFHQECVDQWLS 35

RING finger, H2 subclass, found in Arabidopsis thaliana RING-type E3 ubiquitin transferase BIG BROTHER (BB) and similar proteins; BB (also known as protein ENHANCER OF DA1-1 or EOD1) is an E3 ubiquitin-protein ligase that limits organ size, and possibly seed size, in a dose-dependent manner. It negatively regulates the duration of cell proliferation in leaves and petals independently of the major phytohormones (e.g. auxin, cytokinin, gibberellin, brassinosteroids, ethylene, abscisic acid, jasmonic acid), probably by targeting growth stimulators for degradation. It limits the proliferation of root meristematic cells. BB polyubiquitinates DA1. It is involved in the promotion of leaf senescence, in addition to its function in restricting plant growth. BB-related is an E3 ubiquitin-ligase probably involved in organ size regulation. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                        10        20        30
                ....*....|....*....|....*....|....*
gi 34878787 134 QCVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQH 168
Cdd:cd23115   6 RCVICRLEYEEGEDLLTLPCKHCYHSECIQQWLQI 40

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 undergo 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.

                        10        20        30
                ....*....|....*....|....*....|...
gi 34878787 135 CVICLYGFQEKEAFTKTPCYHYFHCHCLARYIQ 167
Cdd:cd16676   3 CAVCLEDFKTKDELGVLPCQHAFHRKCLVKWLE 35

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 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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 34878787 133 GQCVICLYGFQEKEAFTKT-PCYHYFHCHCLARYIQHmeqelkaqgqeqeqerqhattkqkavgvQCPVCRE 203
Cdd:cd16457   1 PTCPVCLERMDESVSGILTiLCNHSFHCSCLSKWGDS----------------------------SCPVCRY 44

EBNA-3C; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   208 DLASLKAAPEPQQPMELYQPSAESLRQQEERKRLYQRQQErggiidleaernryfisLQQPPAPA-----EPESAVDVSK 282
Cdd:PHA03377  599 QQAKCKDGPPASGPHEKQPPSSAPRDMAPSVVRMFLRERL-----------------LEQSTGPKpksfwEMRAGRDGSG 661

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   283 GSQPPSTlaaelSTSPAVQSTLPPPLPVATQHICEKIPGTRSnqQRLGETQKAMLDPPKPSRgpwrqperrHPKGGECHA 362
Cdd:PHA03377  662 IQQEPSS-----RRQPATQSTPPRPSWLPSVFVLPSVDAGRA--QPSEESHLSSMSPTQPIS---------HEEQPRYED 725

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34878787   363 PKGTRDTqELPPPEGPLKEPMDLKPephsqGVEGPPQEKGP--GSWQGPPPRRTRDCVRWERSKG----RTPGSSYPRLP 436
Cdd:PHA03377  726 PDDPLDL-SLHPDQAPPPSHQAPYS-----GHEEPQAQQAPypGYWEPRPPQAPYLGYQEPQAQGvqvsSYPGYAGPWGL 799

                  ...
gi 34878787   437 RGQ 439
Cdd:PHA03377  800 RAQ 802