Zn-finger in ubiquitin-hydrolases and other protein;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1768748606 317 CFECGVQENLWICLICGHIGCGRYVSRHAYKHFEETQHTYAMQLTNHRVWDYAGDNYVHRLVA 379
Cdd:pfam02148   1 CSLCGNTSNLWLCLTCGHVGCGRYQNSHALEHYEETGHPLAVNLSTLTVYCYPCDDYVHDPSL 63

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768748606 413 TSQLESQRIYWENKIVRIEKDTAEEVHSAEHESGQTHHGAQRGTGDEQVFASQPSPPA---EQAEGGGEDVKGDLRPEGP 489
Cdd:PHA03169   52 TTSGPQVRAVAEQGHRQTESDTETAEESRHGEKEERGQGGPSGSGSESVGSPTPSPSGsaeELASGLSPENTSGSSPESP 131

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1768748606 490 ADHRDPGAAAGRhvlPGDaAEDQPPARRDAAGNPGG 525
Cdd:PHA03169  132 ASHSPPPSPPSH---PGP-HEPAPPESHNPSPNQQP 163

BRCA1-associated protein 2; These proteins include BRCA1-associated protein 2 (BRAP2), which binds nuclear localization signals (NLSs) in vitro and in yeast two-hybrid screening. These proteins share a region of sequence similarity at their N terminus. They also have pfam02148 at the C terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768748606 158 RRSAMLCILTVPATMTSHDLMKFVAPFNEVIEQMKIIRDSTPNQYMVLIKFSAQADADSFYMACNGRQFNSIEDDVCQLV 237
Cdd:pfam07576   1 GRSTLLCILAVPNYMSPADFLQFCGSFLEHISHIRIIRDGMENRYMVLIKFDDQNSADEFYEEFNGKPFSSLEPEVCHVL 80

                          90
                  ....*....|...
gi 1768748606 238 YVERAEVLKSEDG 250
Cdd:pfam07576  81 FVKSVEYTESAEI 93

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
                  ....*....|....*....|....*....|....*....|....
gi 1768748606 262 PKCTVCLERMDESVNGILTTLCNHSFHSQCLQRWDDTTCPVCRY 305
Cdd:cd16457     1 PTCPVCLERMDESVSGILTILCNHSFHCSCLSKWGDSSCPVCRY 44

Ring finger domain;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMDESVNgILTTLCNHSFHSQCLQRWDDT--TCPVCR 304
Cdd:pfam13639   3 CPICLEEFEEGDK-VVVLPCGHHFHRECLDKWLRSsnTCPLCR 44

N1R/p28-like protein; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1768748606 257 DLTELPKCTVCLER-----MDESVNGILTTlCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:PHA02929  170 NRSKDKECAICMEKvydkeIKNMYFGILSN-CNHVFCIECIDIWkkEKNTCPVCR 223

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1768748606 254 PVMDLTelPKCTVCLERMDESVngILTTLCNHSFHSQCLQRWDDT--TCPVCR 304
Cdd:COG5194    29 HIMGTC--PECQFGMTPGDECP--VVWGVCNHAFHDHCIYRWLDTkgVCPLDR 77

BRCA1-associated protein 2; These proteins include BRCA1-associated protein 2 (BRAP2), which binds nuclear localization signals (NLSs) in vitro and in yeast two-hybrid screening. These proteins share a region of sequence similarity at their N terminus. They also have pfam02148 at the C terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768748606 158 RRSAMLCILTVPATMTSHDLMKFVAPFNEVIEQMKIIRDSTPNQYMVLIKFSAQADADSFYMACNGRQFNSIEDDVCQLV 237
Cdd:pfam07576   1 GRSTLLCILAVPNYMSPADFLQFCGSFLEHISHIRIIRDGMENRYMVLIKFDDQNSADEFYEEFNGKPFSSLEPEVCHVL 80

                          90
                  ....*....|...
gi 1768748606 238 YVERAEVLKSEDG 250
Cdd:pfam07576  81 FVKSVEYTESAEI 93

Zn-finger in ubiquitin-hydrolases and other protein;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1768748606 317 CFECGVQENLWICLICGHIGCGRYVSRHAYKHFEETQHTYAMQLTNHRVWDYAGDNYVHRLVA 379
Cdd:pfam02148   1 CSLCGNTSNLWLCLTCGHVGCGRYQNSHALEHYEETGHPLAVNLSTLTVYCYPCDDYVHDPSL 63

RNA recognition motif (RRM) found in yeast RING finger protein ETP1 and similar proteins; This subgroup corresponds to the RRM of ETP1, also termed BRAP2 homolog, or ethanol tolerance protein 1, the yeast homolog of BRCA1-associated protein (BRAP2) found in vertebrates. It may be involved in ethanol and salt-induced transcriptional activation of the NHA1 promoter and heat shock protein genes (HSP12 and HSP26), and participate in ethanol-induced turnover of the low-affinity hexose transporter Hxt3p. ETP1 contains an N-terminal RNA recognition motif (RRM), also termed RBD (RNA binding domain) or RNP (ribonucleoprotein domain), followed by a C3HC4-type ring finger domain and a UBP-type zinc finger.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1768748606 162 MLCILTVPATMTSHDLMKFVAP-FNEVIEQMKIIRDSTPNQYMVLIKFSAQADADSFYMACNGRQFNSIEDDVCQLVYV 239
Cdd:cd12717     1 TLAILAVPSYMTPSDLLGFVGGaTLEQVSHFRLIRTSRPNRYMVLLKFRDAKSAKEFQKEFNGKKFNSIDPETCHVVFI 79

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
                  ....*....|....*....|....*....|....*....|....
gi 1768748606 264 CTVCLERMDESVNGILTTlCNHSFHSQCLQRW---DDTTCPVCR 304
Cdd:cd16448     1 CVICLEEFEEGDVVRLLP-CGHVFHLACILRWlesGNNTCPLCR 43

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMDESVNgILTTLCNHSFHSQCLQRWDDT--TCPVCR 304
Cdd:cd16480     2 CTICSDFFDNSRD-VAAIHCGHTFHYDCLLQWFDTsrTCPQCR 43

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)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1768748606  264 CTVCLERMDESVngiLTTLCNHSFHSQCLQRWDDT---TCPVC 303
Cdd:smart00184   1 CPICLEEYLKDP---VILPCGHTFCRSCIRKWLESgnnTCPIC 40

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        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 263 KCTVCLERMDESVNGILTTlCNHSFHSQCLQRWDDTT--CPVCRY 305
Cdd:cd16669     1 KCPICLLEFEEGETVKQLP-CKHSFHSDCILPWLGKTnsCPLCRH 44

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 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. RNF6 also 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 binds and upregulates the Inha promoter, and functions as a transcription regulatory protein in the mouse sertoli cell. It 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 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. Both RNF6 and RNF12 contain a well conserved C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1768748606 263 KCTVCLERMDESvNGILTTLCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16467     1 ECTICLGEYETG-EKLRRLPCSHEFHSECVDRWlkENSSCPICR 43

RING finger, H2 subclass, found in RING finger proteins RNF38, RNF44, and similar proteins; This subfamily 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 to 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1768748606 262 PKCTVCLerMDESVNGILTTL-CNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16472     3 TQCVVCM--CDYEKRQLLRVLpCSHEFHAKCIDKWlkTNRTCPICR 46

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 the degradation from the ER. AMFR contains an N-terminal RING-H2 finger and a C-terminal ubiquitin-associated (UBA)-like CUE domain.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1768748606 263 KCTVCLERMDESvngiLTTLCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16455     2 DCAICWESMQSA----RKLPCGHLFHNSCLRSWleQDTSCPTCR 41

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        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMDESvNGILTTLCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16674     3 CSVCITEYTEG-NKLRKLPCSHEYHVHCIDRWlsENSTCPICR 44

RING finger, H2 subclass, found in Arabidopsis thaliana protein WAV3 homolog 2 (WAVH2) and similar proteins; WAVH2, also known as RING-type E3 ubiquitin transferase WAVH2, is a probable E3 ubiquitin-protein ligase involved in the regulation of root growth. It acts as a positive regulator of root gravitropism. WAVH2 contains a C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1768748606 263 KCTVCLERMDESVN-GILTTLCNHSFHSQCLQRWDDTT---CPVCR 304
Cdd:cd23114     6 ECSICLETMKPGSGhAIFTAECSHSFHFECIAGNVRHGnlrCPVCR 51

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 combinatorial 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMdESVNGILTTLCNHSFHSQCLQRWDD--TTCPVCR 304
Cdd:cd16460     3 CVICHEAF-SDGDRLLVLPCAHKFHTQCIGPWLDgqQTCPTCR 44

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        40
                  ....*....|....*....|....*....|....*....|..
gi 1768748606 264 CTVCLERMDESVngilTTLCNHSFHSQCLQRW--DDTTCPVC 303
Cdd:cd16476     3 CAICYQEMKEAR----ITPCNHFFHGLCLRKWlyVQDTCPLC 40

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 AMPA-type glutamate receptor subunit 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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1768748606 264 CTVCLERMDESvNGILTTLCNHSFHSQCLQRW---DDTTCPVCR 304
Cdd:cd16797     3 CAICLDEYEEG-DKLRVLPCSHAYHSKCVDPWltqTKKTCPVCK 45

RING finger, H2 subclass, found in RING finger proteins RNF126, RNF115, and similar proteins; This subfamily 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; this inhibition increases the efficacy of metformin in breast cancer cells. It also functions as a cofactor 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), AKT-phosphorylation sites, and a C-terminal C3H2C3-type RING-H2 finger.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 264 CTVCLERM--DESVngiLTTLCNHSFHSQCLQRWDD--TTCPVCR 304
Cdd:cd16667     2 CAVCKEDFevGEEV---RQLPCKHLFHPDCIVPWLElhNSCPVCR 43

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.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMDESVNGILTTLCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16461     2 CAICLSDYENGEELRRLPECKHAFHKECIDEWlkSNSTCPLCR 44

Zinc finger, C3HC4 type (RING finger);

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1768748606 263 KCTVClerMDESVNGILTTLCNHSFHSQCLQRW--DDTTCPVC 303
Cdd:pfam13923   1 MCPIC---MDMLKDPSTTTPCGHVFCQDCILRAlrAGNECPLC 40

hypothetical protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1768748606 413 TSQLESQRIYWENKIVRIEKDTAEEVHSAEHESGQTHHGAQRGTGDEQVFASQPSPPA---EQAEGGGEDVKGDLRPEGP 489
Cdd:PHA03169   52 TTSGPQVRAVAEQGHRQTESDTETAEESRHGEKEERGQGGPSGSGSESVGSPTPSPSGsaeELASGLSPENTSGSSPESP 131

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1768748606 490 ADHRDPGAAAGRhvlPGDaAEDQPPARRDAAGNPGG 525
Cdd:PHA03169  132 ASHSPPPSPPSH---PGP-HEPAPPESHNPSPNQQP 163

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        40
                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 264 CTVCLErmDESVNGILTTL-CNHSFHSQCLQRW---DDTTCPVCR 304
Cdd:cd16473     7 CAICLE--NYQNGDLLRGLpCGHVFHQNCIDVWlerDNHCCPVCR 49

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        40
                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 263 KCTVCLERMDESvNGILTTLCNHSFHSQCLQRW---DDTTCPVCR 304
Cdd:cd16486     1 QCRICLKAFQLG-QHVRTLPCRHKFHRDCIDNWllhSRNSCPIDG 44

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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1768748606 264 CTVCLERMDESVN-GILTtlCNHSFHSQCLQRWDDTTCpVCRYCQTP 309
Cdd:cd16676     3 CAVCLEDFKTKDElGVLP--CQHAFHRKCLVKWLEIRC-VCPMCNKP 46

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 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 is regulated by histone deacetylases.

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                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 264 CTVCLERMDES-VNGILTtlCNHSFHSQCLQRW--DDTTCPVCRY 305
Cdd:cd16802     3 CAVCIEPYKPNdVVRILT--CNHLFHKNCIDPWllEHRTCPMCKC 45

RING finger, HC subclass, found in tripartite motif-containing protein 77 (TRIM77) and similar proteins; TRIM77 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including two consecutive zinc-binding domains, a C3HC4-type RING-HC finger and Bbox2, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1768748606 264 CTVCLERMDESVngilTTLCNHSFHSQCLQR-WDDT----TCPVCRYCQTPEP 311
Cdd:cd16543     6 CSICLDLLKDPV----TIPCGHSFCMNCITLlWDRKqgvpSCPQCRESFPPRP 54

RING finger, H2 subclass, found in protein E3 ubiquitin-protein ligase Praja-1, Praja-2, and similar proteins; This 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 the 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. Praja-1 also regulates the transcription function of the homeodomain protein Dlx5 by controlling the stability of Dlxin-1, via a ubiquitin-dependent degradation pathway. Praja-2, also known as RING finger protein 131, 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. Together with the AMPK-related kinase SIK2 and the CDK5 activator CDK5R1/p35, it forms a SIK2-p35-PJA2 complex that plays an essential role for glucose homeostasis in pancreatic beta cell functional compensation. 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.

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                  ....*....|....*....|....*....|....*....|....*..
gi 1768748606 264 CTVCLER--MDEsvngILTTL-CNHSFHSQCLQRW--DDTTCPVCRY 305
Cdd:cd16465     2 CPICCSEyvKDE----IATELpCHHLFHKPCITAWlqKSGTCPVCRH 44

RING finger, HC subclass, found in tripartite motif-containing protein 69 (TRIM69) and similar proteins; TRIM69, also known as RFP-like domain-containing protein trimless or RING finger protein 36 (RNF36), is a testis E3 ubiquitin-protein ligase that plays a specific role in apoptosis and may also play an important role in germ cell homeostasis during spermatogenesis. TRIM69 belongs to the C-IV subclass of the 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1768748606 258 LTELPKCTVCLERMDESVngILTtlCNHSFHSQCLQRW-----DDTTCPVCRY-CQT 308
Cdd:cd16611     1 LTEELHCPLCLDFFRDPV--MLS--CGHNFCQSCITGFwelqaEDTTCPECRElCQY 53

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

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 1768748606 254 PVMDLTelPKCTVCLERMDESVngILTTLCNHSFHSQCLQRWDDT--TCPVCR 304
Cdd:COG5194    29 HIMGTC--PECQFGMTPGDECP--VVWGVCNHAFHDHCIYRWLDTkgVCPLDR 77

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. RNF111 also 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, an 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.

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                  ....*....|....*....|....*....|....*....|....
gi 1768748606 263 KCTVCLERMDESVNgILTTLCNHSFHSQCLQRW--DDTTCPVCR 304
Cdd:cd16681    12 KCTICLSILEEGED-VRRLPCMHLFHQVCVDQWliTNKKCPICR 54

zinc-RING finger domain;

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                  ....*....|....*....|....*....|....*....|...
gi 1768748606 263 KCTVCLERMDESVNGILTTlCNHSFHSQCLQRW-DDTTCPVCR 304
Cdd:pfam14634   1 HCNKCFKELSKTRPFYLTS-CGHIFCEECLTRLlQERQCPICK 42

RING finger, HC subclass, found in topoisomerase I-binding arginine/serine-rich protein (Topors) and similar proteins; Topors, also known as topoisomerase I-binding RING finger protein, tumor suppressor p53- binding protein 3, or p53-binding protein 3 (p53BP3), is a ubiquitously expressed nuclear E3 ubiquitin-protein ligase that can ligate both ubiquitin and small ubiquitin-like modifier (SUMO) to substrate proteins in the nucleus. It contains an N-terminal C3HC4-type RING-HC finger which ligates ubiquitin to its target proteins including DNA topoisomerase I, p53, NKX3.1, H2AX, and the AAV-2 Rep78/68 proteins. As a RING-dependent E3 ubiquitin ligase, Topors works with the E2 enzymes UbcH5a, UbcH5c, and UbcH6, but not with UbcH7, CDC34, or UbcH2b. Topors acts as a tumor suppressor in various malignancies. It regulates p53 modification, suggesting it may be responsible for astrocyte elevated gene-1 (AEG-1, also known as metadherin, or LYRIC) ubiquitin modification. Plk1-mediated phosphorylation of Topors inhibits Topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. It also functions as a negative regulator of the prostate tumor suppressor NKX3.1. Moreover, Topors is associated with promyelocytic leukemia nuclear bodies, and may be involved in the cellular response to camptothecin. It also plays a key role in the turnover of H2AX protein, discriminating the type of DNA damaging stress. Furthermore, Topors is a cilia-centrosomal protein associated with autosomal dominant retinal degeneration. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa (adRP).

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                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 262 PKCTVCLERMDESVnGILTTlCNHSFHSQCLQRWDD--TTCPVCR 304
Cdd:cd16574     2 SSCPICLDRFENEK-AFLDG-CFHAFCFTCILEWSKvkNECPLCK 44

RING finger, HC subclass, found in the makorin (MKRN) proteins; The MKRN protein subfamily includes ribonucleoproteins that are characterized by a variety of zinc-finger motifs, including typical arrays of one to four C3H1-type zinc fingers and a C3HC4-type RING-HC finger. Another motif rich in Cys and His residues (CH), with so far unknown function, is also generally present in MKRN proteins. MKRN proteins may have E3 ubiquitin ligase activity.

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                  ....*....|....*....|....*....|....*....|....*....|..
gi 1768748606 264 CTVCLERM--DESVNGILTTlCNHSFHSQCLQRWDDT---------TCPVCR 304
Cdd:cd16521     3 CGICMEVVleKERRFGILSN-CNHVFCLECIREWRSSkdfensivrSCPICR 53

RING finger, H2 subclass, found in 43 kDa receptor-associated protein of the synapse (Rapsyn) and similar proteins; Rapsyn, also known as acetylcholine receptor (AChR)-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 AChR in the postsynaptic membrane of the motor endplate. 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 AChR 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.

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                  ....*....|....*....|....*....|....*....|....*
gi 1768748606 264 CTVCLERMDEsVNGILTTL-CNHSFHSQCLQ---RWDDTTCPVCR 304
Cdd:cd16478     4 CGMCGESIGE-KNEQLQALpCSHIFHLKCLQtnlRGGTRGCPNCR 47

RING finger, H2 subclass, found in Arabidopsis thaliana protein ABA INSENSITIVE RING PROTEIN 1 (AIRP1) and similar proteins; This subfamily includes Arabidopsis thaliana AIRP1 and RING-H2 finger B1a (RHB1A). AIRP1, also known as RING-type E3 ubiquitin transferase AIRP1, possesses E3 ubiquitin-protein ligase activity in vitro when associated with the E2 enzyme UBC8. It plays combinatory roles with AIRP2 in the positive regulation of the abscisic acid-mediated drought stress response. RHB1A is a probable E3 ubiquitin-protein ligase. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

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                  ....*....|....*....|....*....|....*....|..
gi 1768748606 264 CTVCLERMDESvNGILTTLCNHSFHSQCLQRWDD--TTCPVC 303
Cdd:cd23116     5 CPTCLEGYTEE-NPKLLTKCGHHFHLACIYEWMErsERCPVC 45

RING finger, HC subclass, found in RING finger protein 5 (RNF5) and similar proteins; RNF5, also known as protein G16 or Ram1, is an E3 ubiquitin-protein ligase anchored to the outer membrane of the endoplasmic reticulum (ER). It acts at early stages of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) biosynthesis and functions as a target for therapeutic modalities to antagonize mutant CFTR proteins in CF patients carrying the F508del allele. It also regulates the turnover of specific G protein-coupled receptors by ubiquitinating JNK-associated membrane protein (JAMP) and preventing proteasome recruitment. RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection through the regulation of ATG4B stability. It is also involved in the degradation of Pendrin, a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. RNF5 plays an important role in cell adhesion and migration. It can modulate cell migration by ubiquitinating paxillin. Furthermore, RNF5 interacts with virus-induced signaling adaptor (VISA) at mitochondria in a viral infection-dependent manner, and further targets VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection. It also negatively regulates virus-triggered signaling by targeting MITA, also known as STING, for ubiquitination and degradation at the mitochondria. In addition, RNF5 determines breast cancer response to ER stress-inducing chemotherapies through the regulation of the L-glutamine carrier proteins SLC1A5 and SLC38A2 (SLC1A5/38A2). It also has been implicated in muscle organization and in recognition and processing of misfolded proteins. RNF5 contains a C3HC4-type RING-HC finger.

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gi 1768748606 263 KCTVCLERMDESVngilTTLCNHSFHSQCLQRWDDT-----TCPVCR 304
Cdd:cd16743     2 ECNICLETARDAV----VSLCGHLFCWPCLHQWLETrperqECPVCK 44

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 1768748606 283 CNHSFHSQCLQRW----DDTTCPVCR 304
Cdd:cd16491    25 CKNKFHSACLYKWfrssNKSTCPLCR 50

HC subclass of RING (RING-HC) finger 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 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 the HC subclass of RING (RING-HC) fingers 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 fingers 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.

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                  ....*....|....*....|....*....|....*....|....
gi 1768748606 263 KCTVCLERMDESVngilTTLCNHSFHSQCLQRW---DDTTCPVC 303
Cdd:cd16449     2 ECPICLERLKDPV----LLPCGHVFCRECIRRLlesGSIKCPIC 41