RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2118037398 3975 GLKPCPICMGDPTEPVNLPCDHVYCHSCIKVWLvPERMQCPLCLTKVPED 4024
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDD 49

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2118037398 3975 GLKPCPICMGDPTEPVNLPCDHVYCHSCIKVWLvPERMQCPLCLTKVPED 4024
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDD 49

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2118037398 3979 CPICMGDPTEPVN-LPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:pfam00097    1 CPICLEEPKDPVTlLPCGHLFCSKCIRSWLESGNVTCPLC 40

ATPases associated with a variety of cellular activities; AAA - ATPases associated with a variety of cellular activities. This profile/alignment only detects a fraction of this vast family. The poorly conserved N-terminal helix is missing from the alignment.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2118037398  2422 GIPVVLMGETGCGKTRLIKFLC-ELRRSGAP---------ANNMKLVKVHGGTTADAIYDKVRDVEAIAIANMQQFQFGt 2491
Cdd:smart00382    2 GEVILIVGPPGSGKTTLARALArELGPPGGGviyidgediLEEVLDQLLLIIVGGKKASGSGELRLRLALALARKLKPD- 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*
gi 2118037398  2492 ILFFDEANT-TEAVSSIKEVLCDHTVEGEPLKHNSGLQIIAACNP 2535
Cdd:smart00382   81 VLILDEITSlLDAEQEALLLLLEELRLLLLLKSEKNLTVILTTND 125

RING finger, HC subclass, found in RING finger protein 213 (RNF213) and similar proteins; RNF213, also known as ALK lymphoma oligomerization partner on chromosome 17 or Moyamoya steno-occlusive disease-associated AAA+ and RING finger protein (mysterin), is an intracellular soluble protein that functions as an E3 ubiquitin-protein ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. It plays a unique role in endothelial cells for proper gene expression in response to inflammatory signals from the environment. Mutations in RNF213 may be associated with Moyamoya disease (MMD), an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. It also acts as a nuclear marker for acanthomorph phylogeny. RNF213 contains two tandem enzymatically active AAA+ ATPase modules and a C3HC4-type RING-HC finger. It can form a huge ring-shaped oligomeric complex.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 2118037398 3975 GLKPCPICMGDPTEPVNLPCDHVYCHSCIKVWLvPERMQCPLCLTKVPED 4024
Cdd:cd16561      1 GEQECSICLEDLNDPVKLPCDHVFCEECIRQWL-PGQMSCPLCRTELPDD 49

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 2118037398  3979 CPICMGD-PTEPVNLPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:smart00184    1 CPICLEEyLKDPVILPCGHTFCRSCIRKWLESGNNTCPIC 40

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2118037398 3979 CPICMGDPTEPVN-LPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:pfam00097    1 CPICLEEPKDPVTlLPCGHLFCSKCIRSWLESGNVTCPLC 40

RING finger, HC subclass, found in RING finger protein 146 (RNF146) and similar proteins; RNF146, also known as dactylidin, or iduna, is a cytoplasmic E3 ubiquitin-protein ligase that is responsible for PARylation-dependent ubiquitination (PARdU). It displays neuroprotective property due to its inhibition of Parthanatos, a PAR dependent cell death, via binding with Poly(ADP-ribose) (PAR). It also modulates PAR polymerase-1 (PARP-1)-mediated oxidative cell injury in cardiac myocytes. Moreover, RNF146 mediates tankyrase-dependent degradation of axin, thereby positively regulating Wnt signaling. It also facilitates DNA repair and protects against cell death induced by DNA damaging agents or gamma-irradiation by translocating to the nucleus after cellular injury and promoting the ubiquitination and degradation of various nuclear proteins involved in DNA damage repair. Furthermore, RNF146 is implicated in neurodegenerative disease and cancer development. It regulates the development and progression of non-small cell lung cancer (NSCLC) by enhancing cell growth, invasion, and survival. RNF146 contains an N-terminal C3HC4-type RING-HC finger followed by a WWE domain with a poly(ADP-ribose) (PAR) binding motif at the tail.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIK-VWLVPERmqCPLCLTKVPEDY 4025
Cdd:cd16546      3 CPICLQTCIHPVKLPCGHIFCYLCVKgVAWQSKR--CALCRQEIPEDF 48

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2118037398 3961 RQCKEAVSLifcryglkpCPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMqCPLCLT 4019
Cdd:cd16741      8 RQCSEADDI---------CAICQAEFRKPILLICQHVFCEECISLWFNREKT-CPLCRT 56

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:cd16509      6 CAICLDSLTNPVITPCAHVFCRRCICEVIQREKAKCPMC 44

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIK-VWLVPE--RMQCPLCLTKVPE 4023
Cdd:cd16609      6 CSICLGLYQDPVTLPCQHSFCRACIEdHWRQKDegSFSCPECRAPFPE 53

RING finger, HC subclass, found in Saccharomyces cerevisiae POB3/SPT16 histone-associated protein 1 (ScPSH1) and similar proteins; ScPSH1 is a Cse4-specific E3 ubiquitin ligase that interacts with the kinetochore protein Pat1 and targets the degradation of budding yeast centromeric histone H3 variant, CENP-ACse4, which is essential for faithful chromosome segregation. ScPSH1 contains a C3HC4-type RING-HC finger and a DNA directed RNA polymerase domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPER-MQCPLCLTKV 4021
Cdd:cd16568      7 CIICHEYLYEPMVTTCGHTYCYTCLNTWFKSNRsLSCPDCRTKI 50

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCI-KVWLVPE-RMQCPLCLTKVPEDYTPT 4028
Cdd:cd16594      8 CPICLDYFTDPVTLDCGHSFCRACIaRCWEEPEtSASCPQCRETCPQRNLRP 59

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).

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2118037398 3979 CPICMGDPTEPVNL--PCDHVYCHSCIKVWLVPERMqCPLC 4017
Cdd:cd16574      4 CPICLDRFENEKAFldGCFHAFCFTCILEWSKVKNE-CPLC 43

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMQCPLCLTKV 4021
Cdd:cd16550      3 CPICLEILVEPVTLPCNHTLCMPCFQSTVEKASLCCPLCRLRI 45

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 2118037398 3979 CPICMgdptEP---------VNLPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:cd16450      5 CPICF----EPwtssgehrlVSLKCGHLFGYSCIEKWLKGKGKKCPQC 48

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEpVNLPCDHVYCHSCIKVWLVPERmQCPLC 4017
Cdd:cd16545      3 CCICMDRKAD-LILPCAHSYCQKCIDKWSDRHR-TCPIC 39

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2118037398 3979 CPICMGDPTEP---VNLPCDHVYCHSCIKVWLVPERMQCPLCLTKVP 4022
Cdd:COG5540    326 CAICMSNFIKNdrlRVLPCDHRFHVGCVDKWLLGYSNKCPVCRTAIP 372

RING finger, HC subclass, found in breast cancer type 1 susceptibility protein (BRCA1) and similar proteins; BRCA1, also known as RING finger protein 53 (RNF53), is a RING finger protein encoded by the tumor suppressor gene BRCA1 that regulates all DNA double-strand break (DSB) repair pathways. BRCA1 is frequently mutated in patients with hereditary breast and ovarian cancer (HBOC). Its mutation is also associated with an increased risk of pancreatic, stomach, laryngeal, fallopian tube, and prostate cancer. It plays an important role in the DNA damage response signaling and has been implicated in various cellular processes such as cell cycle regulation, transcriptional regulation, chromatin remodeling, DNA DSBs, and apoptosis. BRCA1 contains an N-terminal C3HC4-type RING-HC finger, and two BRCT (BRCA1 C-terminus domain) repeats at the C-terminus.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWL--VPERMQCPLCLTKV 4021
Cdd:cd16498     19 CPICLELLKEPVSTKCDHQFCRFCILKLLqkKKKPAPCPLCKKSV 63

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMQCP 4015
Cdd:cd16643      4 CPICLMALREPVQTPCGHRFCKACILKSIREAGHKCP 40

RING finger, HC subclass, found in peroxin-10 (PEX10) and similar proteins; PEX10, also known as peroxisome biogenesis factor 10, peroxisomal biogenesis factor 10, peroxisome assembly protein 10, or RING finger protein 69 (RNF69), is an integral peroxisomal membrane protein with two transmembrane regions and a C3HC4-type RING-HC finger within its cytoplasmically exposed C-terminus. It plays an essential role in peroxisome assembly, import of target substrates, and recycling or degradation of protein complexes and amino acids. It is an essential component of the spinal locomotor circuit, and thus its mutations may be involved in peroxisomal biogenesis disorders (PBD). Mutations in human PEX10 also result in autosomal recessive ataxia. Moreover, PEX10 functions as an E3-ubiquitin ligase with an E2, UBCH5C. It mono- or poly-ubiquitinates PEX5, a key player in peroxisomal matrix protein import, in a UBC4-dependent manner, to control PEX5 receptor recycling or degradation. It also links the E2 ubiquitin conjugating enzyme PEX4 to the protein import machinery of the peroxisome.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVpERMQCPLC 4017
Cdd:cd16527      3 CSLCLEERRHPTATPCGHLFCWSCITEWCN-EKPECPLC 40

zinc finger of C3HC4-type, RING; This is a family of primate-specific Ret finger protein-like (RFPL) zinc-fingers of the C3HC4 type. Ret finger protein-like proteins are primate-specific target genes of Pax6, a key transcription factor for pancreas, eye and neocortex development. This domain is likely to be DNA-binding. This zinc-finger domain together with the RDM domain, pfam11002, forms a large zinc-finger structure of the RING/U-Box superfamily. RING-containing proteins are known to exert an E3 ubiquitin protein ligase activity with the zinc-finger structure being mandatory for binding to the E2 ubiquitin-conjugating enzyme.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVW---LVPERMQCPLC 4017
Cdd:pfam15227    1 CPICLDYLEKPVSIECGHSFCLSCINSLqkePDGESLLCPQC 42

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2118037398 3979 CPICMGDPTEPVNL-PCDHVYCHSCIKVWLVPERMQCPLCLTKV 4021
Cdd:cd16503      5 CSICQDLLHDCVSLqPCMHNFCAACYSDWMERSNTECPTCRATV 48

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPIC---MGDPTEPVNLPCDHVYCHSCIKVWLVPERMQCPLC 4017
Cdd:cd00162      1 CPICreeMNDRRPVVLLSCGHTFSRSAIARWLEGSKQKCPFC 42

RING finger, HC subclass, found in tripartite motif-containing protein 47 (TRIM47) and similar proteins; TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), 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, a B-box, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. It plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. This subfamily also includes RING finger protein 135 (RNF135). RNF135, also known as RIG-I E3 ubiquitin ligase (REUL) or Riplet, is a widely expressed E3 ubiquitin-protein ligase that consists of an N-terminal C3HC4-type RING-HC finger and C-terminal B30.2/SPRY and PRY motifs, but lacks the B-box and coiled-coil domains that are also typically present in TRIM proteins. RNF135 serves as a specific retinoic acid-inducible gene-I (RIG-I)-interacting protein that ubiquitinates RIG-I and specifically stimulates RIG-I-mediated innate antiviral activity to produce antiviral type-I interferon (IFN) during the early phase of viral infection. It also has been identified as a bio-marker and therapy target of glioblastoma. It associates with the ERK signal transduction pathway and plays a role in glioblastoma cell proliferation, migration and cell cycle.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCI-KVWLVPE--RMQCPLC 4017
Cdd:cd16604      3 CPICLDLLKDPVTLPCGHSFCMGCLgALWGAGRggRASCPLC 44

RING finger, HC subclass, found in RING finger protein 10 (RNF10) and similar proteins; RNF10 is an E3 ubiquitin-protein ligase that interacts with mesenchyme Homeobox 2 (MEOX2) transcription factor, a regulator of the proliferation, differentiation and migration of vascular smooth muscle cells and cardiomyocytes; it enhances Meox2 activation of the p21 promoter. It also regulates the expression of myelin-associated glycoprotein (MAG) genes and is required for myelin production in Schwann cells of the peripheral nervous system. Moreover, RNF10 regulates retinoic acid-induced neuronal differentiation and the cell cycle exit of P19 embryonic carcinoma cells. RNF10 contains a C3HC4-type RING-HC finger and three putative nuclear localization signals.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWL-VPERMQ--CPLC 4017
Cdd:cd16536      3 CPICLEPPVAPRITRCGHIFCWPCILRYLsLSEKKWrkCPIC 44

RING finger, HC subclass, found in Arabidopsis thaliana BRCA1-associated RING domain protein 1 (AtBARD1) and similar proteins; AtBARD1, also called protein REPRESSOR OF WUSCHEL 1, binds specifically to H3K4me3 regions of target gene (e.g. WUS and WOX5) promoters to repress their transcription via chromatin remodeling. It is required for the shoot apical meristem (SAM) organization and maintenance, by confining WUS expression to the organizing center, and for the quiescent center (QC) development in the root apical meristem (RAM), by repressing WOX5 expression in the root proximal meristem. AtBARD1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBARD1 contains a typical C3HC4-type RING-HC finger.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPeRMQCPLC 4017
Cdd:cd23146      7 CPICLKLLNRPVLLPCDHIFCSSCITDSTKV-GSDCPVC 44

RING finger, HC subclass, found in Ret finger protein-like 4B (RFPL4B) and similar proteins; RFPL4B, also called RING finger protein 211 (RNF211), is an uncharacterized RING finger protein containing a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPE---RMQCPLC 4017
Cdd:cd16623     11 CPICLDFFSHPISLSCAHIFCFDCIQKWMTKRedsILTCPLC 52

Zinc finger, C3HC4 type (RING finger);

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 2118037398 3977 KPCPICMGDPTEPVNLPCDH-VYCHSCIKvWLVPERMQCPLCLTKV 4021
Cdd:pfam13920    3 LLCVICLDRPRNVVLLPCGHlCLCEECAE-RLLRKKKKCPICRQPI 47

RING finger, HC subclass, found in Saccharomyces cerevisiae increased recombination centers protein 20 (IRC20) and similar proteins; IRC20 is an uncharacterized ATP-dependent helicase that is probably involved in a pathway contributing to genomic integrity. IRC20 contains a typical C3HC4-type RING-HC finger.

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLvPERMQCPLC 4017
Cdd:cd23135      6 CSICFSEIRSGAILKCGHFFCLSCIASWL-REKSTCPLC 43

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERmQCPLCLTKV 4021
Cdd:cd16547      6 CSICHGVLRCPVRLSCSHIFCKKCILQWLKRQE-TCPCCRKEV 47

RING finger, HC subclass, found in ligand of numb protein X 4 (LNX4); LNX4, also known as PDZ domain-containing RING finger protein 4 (PDZRN4), or SEMACAP3-like protein (SEMCAP3L), is an E3 ubiquitin-protein ligase responsible for the ubiquitination and degradation of Numb, a component of the Notch signaling pathway that functions in the specification of cell fates during development and is known to control cell numbers during neurogenesis in vertebrates. LNX4 contains an N-terminal C3HC4-type RING-HC finger, two PDZ domains, and a C-terminal LNX3 homology (LNX3H) domain.

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMqCPL 4016
Cdd:cd16719      7 CKLCGKVLEEPLSTPCGHVFCAGCLLPWAVQRRL-CPL 43

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

                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVpERMQCPL 4016
Cdd:cd16512      3 CKLCLGVLEEPLATPCGHVFCAGCVLPWVV-RNGSCPL 39

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

                           10        20        30
                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLP-CDHVYCHSCIKVWLVPERMqCPL 4016
Cdd:cd16634      4 CPICSGVLEEPLQAPhCEHAFCNACITEWLSRQQT-CPV 41

RING finger, HC subclass, found in tripartite motif-containing protein 10 (TRIM10) and similar proteins; TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM10 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWL------VPERMQCPLC 4017
Cdd:cd16593      8 CPICQGTLREPVTIDCGHNFCRACLTRYCeipgpdLEEPPTCPLC 52

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWL--VPERMQCPLC 4017
Cdd:cd16745      3 CNICLDLAQDPVVTLCGHLFCWPCLHKWLrrQSSQPECPVC 43

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of 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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKV-WLVPERMQCPLC 4017
Cdd:cd16599      7 CPICYEPFREAVTLRCGHNFCKGCVSRsWERQPRAPCPVC 46

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.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIK-VWlvpERMQ----CPLCLTKVP 4022
Cdd:cd16543      6 CSICLDLLKDPVTIPCGHSFCMNCITlLW---DRKQgvpsCPQCRESFP 51

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.

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                   ....*....|....*....|....*....|....*....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPErMQCPLC 4017
Cdd:cd16476      3 CAICYQEMKEARITPCNHFFHGLCLRKWLYVQ-DTCPLC 40

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 2118037398 3978 PCPICMGD---PTEPVNLPCDHVYCHSCIKVWLVpERMQCPLC 4017
Cdd:cd16667      1 ECAVCKEDfevGEEVRQLPCKHLFHPDCIVPWLE-LHNSCPVC 42

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

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                   ....*....|....*....|....*....|....*....|...
gi 2118037398 3978 PCPIC---MGDPTEPVNLPCDHVYCHSCIKVWLVpERMQCPLC 4017
Cdd:cd16454      1 TCAICleeFKEGEKVRVLPCNHLFHKDCIDPWLE-QHNTCPLC 42

RING finger, HC subclass, found in really interesting new gene proteins RING1, RING2 and similar proteins; RING1, also known as polycomb complex protein RING1, RING finger protein 1 (RNF1), or RING finger protein 1A (RING1A), is a transcriptional repressor that is associated with the Polycomb group (PcG) protein complex involved in stable repression of gene activity. RING2, also known as huntingtin-interacting protein 2-interacting protein 3, HIP2-interacting protein 3, protein DinG, RING finger protein 1B (RING1B), RING finger protein 2 (RNF2), or RING finger protein BAP-1, is an E3 ubiquitin-protein ligase that interacts with both nucleosomal DNA and an acidic patch on histone H4 to achieve the specific monoubiquitination of K119 on histone H2A (H2AK119ub), thereby playing a central role in histone code and gene regulation. Both RING1 and RING2 are core components of polycomb repressive complex 1 (PRC1) that functions as an E3-ubuiquitin ligase transferring the mono-ubuiquitin mark to the C-terminal tail of Histone H2A at K118/K119. PRC1 is also capable of chromatin compaction, a function not requiring histone tails, and this activity appears important in gene silencing. RING2 acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity. Members of this family contain a C3HC4-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....*
gi 2118037398 3979 CPICMGDPTEP-VNLPCDHVYCHSCIKVWLVPERMQCPLCLTKVP 4022
Cdd:cd16531      4 CPICLGIIKNTmTVKECLHRFCAECIEKALRLGNKECPTCRKHLP 48

RING finger, HC subclass, found in tripartite motif-containing protein 36 (TRIM36) and similar proteins; TRIM36, the human ortholog of mouse Haprin, also known as RING finger protein 98 (RNF98) or zinc-binding protein Rbcc728, is an E3 ubiquitin-protein ligase expressed in the germ plasm. It has been implicated in acrosome reaction, fertilization, and embryogenesis, as well as in carcinogenesis. TRIM36 functions upstream of Wnt/beta-catenin activation, and plays a role in controlling the stability of proteins regulating microtubule polymerization during cortical rotation, and subsequently dorsal axis formation. It is also potentially associated with chromosome segregation by interacting with the kinetochore protein centromere protein-H (CENP-H), and colocalizing with the microtubule protein alpha-tubulin. Its overexpression may cause chromosomal instability and carcinogenesis. It is, thus, a novel regulator affecting cell cycle progression. Moreover, TRIM36 plays a critical role in the arrangement of somites during embryogenesis. TRIM36 belongs to the C-I 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, Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVpeRMQCPLCLTKV 4021
Cdd:cd16756      6 CPSCKELFTHPLILPCQHSVCHKCVKELLT--TFPCPGCQHDV 46

RING finger, HC subclass, found in Arabidopsis thaliana protein BREAST CANCER SUSCEPTIBILITY 1 homolog (AtBRCA1) and similar proteins; AtBRCA1 plays a role in DNA repair and in cell-cycle control. It is required for the repair of DNA double-strand breaks (DSBs), both natural and induced by genotoxic stress, by homologous recombination (HR). AtBRCA1 contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIKVWLVPERMqCPLCltKVP 4022
Cdd:cd23147      7 CPICLSLFKSAANLSCNHCFCAGCIGESLKLSAI-CPVC--KIP 47

RING finger, HC subclass, found in Saccharomyces cerevisiae radiation sensitivity protein 18 (RAD18) and similar proteins; RAD18, also called RING-type E3 ubiquitin transferase RAD18, acts as a postreplication repair E3 ubiquitin-protein ligase that associates with the E2 ubiquitin conjugating enzyme UBC2/RAD6 to form the UBC2-RAD18 ubiquitin ligase complex involved in postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. RAD18 is an E3 RING-finger protein belonging to the UBC2/RAD6 epistasis group. It contains a typical C3HC4-type RING-HC finger.

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                   ....*....|....*....|....*....|....*....|....*...
gi 2118037398 3976 LKPCPICMGDPTEPVNLPCDHVYCHSCIKVWLVpERMQCPLCLTKVPE 4023
Cdd:cd23148      3 ALRCHICKDLLKAPMRTPCNHTFCSFCIRTHLN-NDARCPLCKAEVTE 49

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 2118037398 3979 CPICMGDPT--EPV-NLPCDHVYCHSCIKVWLvPERMQCPLC 4017
Cdd:cd16801      2 CPVCKEDYTvgENVrQLPCNHLFHNDCIVPWL-EQHDTCPVC 42

RING finger, HC subclass, found in Candida albicans transcriptional regulator of yeast form adherence 3 (TRY3) and similar proteins; TRY3 acts as a transcription factor required for yeast cell adherence to silicone substrate. It contains a typical C3HC4-type RING-HC finger.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 2118037398 3979 CPICMGDPTEPVNLPCDHVYCHSCIkVWLVPERM-QCPLCLTKV 4021
Cdd:cd23137      5 CPICMNVAWKPVRLECSHVFCLRCL-VKAQKQKKdNCPLCRAKG 47

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

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gi 2118037398 3979 CPICMGDPTE-PVNLPCDHVYCHSCIKVWLvpERMQ-CPLC 4017
Cdd:cd16479      4 CIICREEMTVgAKKLPCGHIFHLSCLRSWL--QRQQtCPTC 42