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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66807465    1 MKVTIKSiWNTVSAWHWDV-NEECCGICRMAFDGCCVDCKIPGDDCPPVWGVCNHAFHMHCILKWLNANELQ-QCPMCRS 78
Cdd:pfam12861  1 MKVKIKE-WNAVATWLWDVpSDDVCGICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSKgLCPMCRQ 79

                 ....*
gi 66807465   79 EWRFK 83
Cdd:pfam12861 80 TFKFA 84

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66807465    1 MKVTIKSiWNTVSAWHWDV-NEECCGICRMAFDGCCVDCKIPGDDCPPVWGVCNHAFHMHCILKWLNANELQ-QCPMCRS 78
Cdd:pfam12861  1 MKVKIKE-WNAVATWLWDVpSDDVCGICRVSFDGTCPDCKFPGDDCPLVWGKCSHNFHMHCILKWLHTETSKgLCPMCRQ 79

                 ....*
gi 66807465   79 EWRFK 83
Cdd:pfam12861 80 TFKFA 84

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 66807465   22 ECCGICRMAFDGCCVDCKIPGDD-CPPVWGVCNHAFHMHCILKWLNANelQQCPMCR 77
Cdd:pfam12678  1 DTCAICRNPFMEPCPECQAPGDDeCPVVWGECGHAFHLHCISRWLKTN--NTCPLCR 55

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

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 66807465    7 SIWNTVSAWHWDVNE-----ECCGICRMAFDGccVDCKIPGDDCPpvwgVCNHAFHMHCILKWLNANELQQCPMCRSEWR 81
Cdd:COG5219 1450 SFMDLLGLWKKNIDEkfsghEECAICYSVLDM--VDRSLPSKRCA----TCKNKFHTRCLYKWFASSARSNCPLCRSEIT 1523

                 .
gi 66807465   82 F 82
Cdd:COG5219 1524 F 1524

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 the NEDD8 pathway and RBX2 specifically regulates NEDD8ylation of Cul5. It can bind and activate the 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, and may have potential use in anti-angiogenesis therapy of human cancers. Moreover, as a component of the Cullin 5-RING E3 ubiquitin ligase (CRL5) complex, RBX2 regulates neuronal migration through different CRL5 adaptors, such as SOCS7. RBX2 also functions as a redox inducible antioxidant protein that scavenges oxygen radicals by forming inter- and intra-molecular disulfide bonds when acting alone. It contains a C-terminal C3H2C3-type RING-H2 finger that is essential for its ligase activity.

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               ....*....|....*....|....*....|....*....|....*....|....*....
gi 66807465 24 CGICRMAFDGCCVDCK--IPGDDCPPVWGVCNHAFHMHCILKWLNANelQQCPMCRSEW 80
Cdd:cd16466  4 CAICRVQVMDACLRCQaeNKQEDCVVVWGECNHSFHNCCMSLWVKQN--NRCPLCQQDW 60

RING finger (Really Interesting New Gene) domain and U-box domain superfamily; 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). C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type RING fingers are closely related to RING-HC fingers. In contrast, C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type RING fingers are more closely related to RING-H2 fingers. However, not all RING finger-containing proteins display regular RING finger features, and the RING finger family has turned out to be multifarious. The degenerate RING fingers of the 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 residues. 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 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 enable efficient transfer of ubiquitin from E2 to the substrates.

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               ....*....|....*....|....*....|....*....|....*....|...
gi 66807465 24 CGICRMAFDGCCvdckipgddcPPVWGVCNHAFHMHCILKWLNAnELQQCPMC 76
Cdd:cd00162  1 CPICREEMNDRR----------PVVLLSCGHTFSRSAIARWLEG-SKQKCPFC 42

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.

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               ....*....|....*....|....*...
gi 66807465 52 CNHAFHMHCILKWLNANelQQCPMCRSE 79
Cdd:cd16680 28 CNHEFHTKCVDKWLKTN--RTCPICRAD 53

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), which 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.

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               ....*....|....*....|....*....|....*....|....*....|....*.
gi 66807465 22 ECCGICRMAFDGccVDCKIPGDDCPpvwgVCNHAFHMHCILKWLNANELQQCPMCR 77
Cdd:cd16491  1 EECPICYSVIHG--SNHSLPKLKCK----TCKNKFHSACLYKWFRSSNKSTCPLCR 50

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

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               ....*....|....*....|....*....
gi 66807465 51 VCNHAFHMHCILKWLNANELQQCPMCRSE 79
Cdd:cd23120 20 DCGHEFHLTCIREWHNKSGNLDCPICRVE 48

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.

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gi 66807465 52 CNHAFHMHCILKWLNANelQQCPMCR 77
Cdd:cd16674 21 CSHEYHVHCIDRWLSEN--STCPICR 44

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 by 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. RNF6 also 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.

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gi 66807465 52 CNHAFHMHCILKWLNANelQQCPMCR 77
Cdd:cd16673 21 CAHEFHIHCIDRWLSEN--STCPICR 44

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.

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gi 66807465 52 CNHAFHMHCILKWLNANelQQCPMCR 77
Cdd:cd16461 21 CKHAFHKECIDEWLKSN--STCPLCR 44