Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 24665272  11 FLNCPICCNEFAASQRCPVSLGCGHTICKLCLTTLYNRQCPFDQ 54
Cdd:cd16638   1 FLSCPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLHRKQCPFDQ 44

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24665272     2 PIQAPSWTDFLNCPI-CCNEFAASQRC---------PVSLGCGHTICKLCLTTLYNRQ--CPfdqTVIVSDIDN-LPINH 68
Cdd:TIGR00599   3 ELDITDSSDWLTTPIpSLYPLDTSLRChickdffdvPVLTSCSHTFCSLCIRRCLSNQpkCP---LCRAEDQESkLRSNW 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 24665272    69 ALLQLVKD-----SELLELAPPPPSVQKLEPE 95
Cdd:TIGR00599  80 LVSEIVESfknlrPSLLEFLRIPKTTPVENPD 111

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 24665272  11 FLNCPICCNEFAASQRCPVSLGCGHTICKLCLTTLYNRQCPFDQ 54
Cdd:cd16638   1 FLSCPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLHRKQCPFDQ 44

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 24665272     14 CPICCNEFaasQRCPVSLGCGHTICKLCLTTLY---NRQCPF 52
Cdd:smart00184   1 CPICLEEY---LKDPVILPCGHTFCRSCIRKWLesgNNTCPI 39

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24665272     2 PIQAPSWTDFLNCPI-CCNEFAASQRC---------PVSLGCGHTICKLCLTTLYNRQ--CPfdqTVIVSDIDN-LPINH 68
Cdd:TIGR00599   3 ELDITDSSDWLTTPIpSLYPLDTSLRChickdffdvPVLTSCSHTFCSLCIRRCLSNQpkCP---LCRAEDQESkLRSNW 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 24665272    69 ALLQLVKD-----SELLELAPPPPSVQKLEPE 95
Cdd:TIGR00599  80 LVSEIVESfknlrPSLLEFLRIPKTTPVENPD 111

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-1, Roquin-2, and similar proteins; The ROQUIN family includes Roquin-1, Roquin-2, and similar proteins, which localize to the cytoplasm and upon stress, are concentrated in stress granules. They may play essential roles in preventing T-cell-mediated autoimmune disease and in microRNA-mediated repression of inducible costimulator (Icos) mRNA. They function as E3 ubiquitin ligases consisting of an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 activity, a highly conserved ROQ domain required for RNA binding and localization to stress granules, and a CCCH-type zinc finger involved in RNA recognition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....
gi 24665272  11 FLNCPICCNEFAASQRCPVSLGCGHTICKLCLTTLYNRQCPFDQ 54
Cdd:cd16638   1 FLSCPVCTNEFDGTQRKPISLGCGHTVCKTCLSKLHRKQCPFDQ 44

Modified RING finger, HC subclass (C3HC3D-type), found in Roquin-2; Roquin-2, also known as membrane-associated nucleic acid-binding protein (MNAB), RING finger and CCCH-type zinc finger domain-containing protein 2 (RC3H2), or RING finger protein 164 (RNF164), is an E3 ubiquitin ligase that is localized to the cytoplasm and upon stress, is concentrated in stress granules. It is required for reactive oxygen species (ROS)-induced ubiquitination and degradation of apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5). Roquin-2 interacts with the 3'UTR of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and tumor-necrosis factor-alpha (TNFalpha), and modulates immune responses. Moreover, Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation. Roquin-2 contains an N-terminal modified C3HC3D-type RING-HC finger with a potential E3 ubiquitin-ligase function, a highly conserved ROQ domain required for RNA binding and localization to stress granules, a coiled-coil (CC1), and a CCCH-type zinc finger that is involved in RNA recognition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 24665272   8 WTDFLNCPICCNEFAASQRCPVSLGCGHTICKLCLTTLYNRQCPFDQT 55
Cdd:cd16782   2 WTEFLSCPICYNEFDENVHKPISLGCSHTVCKTCLNKLHRKACPFDQT 49

RING finger, HC subclass, found in tripartite motif-containing protein 32 (TRIM32) and similar proteins; TRIM32, also known as 72 kDa Tat-interacting protein, zinc finger protein HT2A, or BBS11, is an E3 ubiquitin-protein ligase that promotes degradation of several targets, including actin, PIASgamma, Abl interactor 2, dysbindin, X-linked inhibitor of apoptosis (XIAP), p73 transcription factor, thin filaments and Z-bands during fasting. It plays important roles in neuronal differentiation of neural progenitor cells, as well as in controlling cell fate in skeletal muscle progenitor cells. It reduces PI3K-Akt-FoxO signaling in muscle atrophy by promoting plakoglobin-PI3K dissociation. It also functions as a pluripotency-reprogramming roadblock that facilitates cellular transition towards differentiation by modulating the levels of Oct4 and cMyc. Moreover, TRIM32 is an intrinsic influenza A virus (IAV) restriction factor which senses and targets the polymerase basic protein 1 (PB1) for ubiquitination and protein degradation. It also plays a significant role in mediating the biological activity of the HIV-1 Tat protein in vivo, binds specifically to the activation domain of HIV-1 Tat, and can also interact with the HIV-2 and EIAV Tat proteins in vivo. Furthermore, TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2 (N-myc downstream-regulated gene). It negatively regulates tumor suppressor p53 to promote tumorigenesis. It also facilitates degradation of MYCN on spindle poles and induces asymmetric cell division in human neuroblastoma cells. In addition, TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress. It also plays a role in regeneration by affecting satellite cell cycle progression via modulation of the SUMO ligase PIASy (PIAS4). Defects in TRIM32 leads to limb-girdle muscular dystrophy type 2H (LGMD2H), sarcotubular myopathies (STM) and Bardet-Biedl syndrome. TRIM32 belongs to the C-VII subclass of the TRIM (tripartite motif)-NHL family that is defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil domain, as well as a NHL (named after proteins NCL-1, HT2A and Lin-41 that contain repeats folded into a six-bladed beta propeller) repeat domain positioned C-terminal to the RBCC domain. The NHL domain mediates the interaction with Argonaute proteins and consequently allows TRIM32 to modulate the activity of certain miRNAs.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 24665272  12 LNCPICCNEFAASQRCPVSLGCGHTICKLCLTTLYNR------QCPF 52
Cdd:cd16587   1 LECPICLESFDEGQLRPKLLHCGHTICEQCLEKLLASlsingvRCPF 47

Modified RING finger, HC subclass (C3HC3D-type), found in Caenorhabditis elegans putative GTP-binding protein trim-23 homolog (arc-1) and similar proteins; arc-1, also called RING-type E3 ubiquitin transferase arc-1, is an E3 ubiquitin-protein ligase that mediates E2-dependent protein ubiquitination. arc-1 contains a modified C3HC3D-type RING-HC finger.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24665272  11 FLNCPICCNEFAA--SQRCPVSL-GCGHTICKLCLTTLYNRQ-----CPFDQTV 56
Cdd:cd23124   1 ELECGICQQEYSAddPLLIPRILtECGHTICTNCAGTILGQSsgsifCPFDRIV 54

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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 24665272  12 LNCPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNRQ----CPFDQTviVSDIDNLPINHALLQLVK 75
Cdd:cd16599   5 LLCPICYEPF----REAVTLRCGHNFCKGCVSRSWERQprapCPVCKE--ASSSDDLRTNHTLNNLVE 66

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 24665272    14 CPICCNEFAasqRCPVSLGCGHTICKLCLTTLY---NRQCP 51
Cdd:pfam00097   1 CPICLEEPK---DPVTLLPCGHLFCSKCIRSWLesgNVTCP 38

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.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 24665272  12 LNCPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNRQ-----CP 51
Cdd:cd16611   5 LHCPLCLDFF----RDPVMLSCGHNFCQSCITGFWELQaedttCP 45

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
                ....*....|....*....|....*....|....*....|....*.
gi 24665272  14 CPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNRQ--CPFDQTVI 57
Cdd:cd16741  17 CAICQAEF----RKPILLICQHVFCEECISLWFNREktCPLCRTVI 58

Modified RING finger, HC subclass (C3HC3D-type), found in tripartite motif-containing protein 23 (TRIM23) and similar proteins; TRIM23, also known as ADP-ribosylation factor domain-containing protein 1, GTP-binding protein ARD-1, or RING finger protein 46 (RNF46), is an E3 ubiquitin-protein ligase belonging to the C-IX subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a modified C3HC3D-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as C-terminal ADP ribosylation factor (ARF) domains. TRIM23 is involved in nuclear factor (NF)-kappaB activation. It mediates atypical lysine 27 (K27)-linked polyubiquitin conjugation to NF-kappaB essential modulator NEMO, also known as IKKgamma, which plays an important role in the NF-kappaB pathway, and this conjugation is essential for TLR3- and RIG-I/MDA5-mediated antiviral innate and inflammatory responses. It also regulates adipocyte differentiation via stabilization of the adipogenic activator peroxisome proliferator-activated receptor gamma (PPARgamma) through atypical ubiquitin conjugation to PPARgamma. Moreover, TRIM23 interacts with and polyubiquitinates yellow fever virus (YFV) NS5 to promote its binding to STAT2 and trigger type I interferon (IFN-I) signaling inhibition.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 24665272  12 LNCPICCNEFAAS-QRCPVSLGCGHTICKLCLTTLYNR----QCPFDQT 55
Cdd:cd16645   2 LECGVCEDVFSLQgDKVPRLLLCGHTVCHDCLTRLPLHgravRCPFDRQ 50

RING finger, HC subclass, found in tripartite motif-containing protein 62 (TRIM62) and similar proteins; TRIM62, also known as Ductal Epithelium Associated Ring Chromosome 1 (DEAR1), is a cytoplasmic E3 ubiquitin-protein ligase that was identified as a dominant regulator of acinar morphogenesis in the mammary gland. It is implicated in the inflammatory response of immune cells by regulating the Toll-like receptor 4 (TLR4) signaling pathway, leading to increased activity of the activator protein 1 (AP-1) transcription factor in primary macrophages. It is also involved in muscular protein homeostasis, especially during inflammation-induced atrophy, and may play a role in the pathogenesis of ICU-acquired weakness (ICUAW) by activating and maintaining inflammation in myocytes. Moreover, TRIM62 facilitates K27-linked poly-ubiquitination of CARD9 and also regulates CARD9-mediated anti-fungal immunity and intestinal inflammation. It also functions as a chromosome 1p35 tumor suppressor and negatively regulates transforming growth factor beta (TGFbeta)-driven epithelial-mesenchymal transition (EMT) by binding to and promoting the ubiquitination of SMAD3, a major effector of TGFbeta-mediated EMT. TRIM62 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 24665272   7 SWTDFLNCPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNRQ----CP 51
Cdd:cd16608   2 SLKDELLCSICLSIY----QDPVSLGCEHYFCRQCITEHWSRSehrdCP 46

RING finger, HC subclass, found in malin and similar proteins; Malin ("mal" for seizure in French), also known as NHL repeat-containing protein 1 (NHLRC1), or EPM2B, is a nuclear E3 ubiquitin-protein ligase that ubiquitinates and promotes the degradation of laforin (EPM2A encoding protein phosphatase). Malin and laforin operate as a functional complex that play key roles in regulating cellular functions such as glycogen metabolism, unfolded cellular stress response, and proteolytic processes. They act as pro-survival factors that negatively regulate the Hipk2-p53 cell death pathway. They also negatively regulate cellular glucose uptake by preventing plasma membrane targeting of glucose transporters. Moreover, they degrade polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase. Furthermore, they, together with Hsp70, form a new functional complex that suppress the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. Defects in either malin or laforin may cause Lafora disease (LD), a fatal form of teenage-onset autosomal recessive progressive myoclonus epilepsy. In addition, malin may have function, independent of laforin, in lysosomal biogenesis and/or lysosomal glycogen disposal. Malin contains six NHL-repeat protein-protein interaction domains and a C3HC4-type RING-HC finger.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*..
gi 24665272  12 LNCPICCNEFA-ASQRCPVSLGCGHTICKLCLTTLYNR-----QCPF 52
Cdd:cd16516   1 LECKVCFEKYShQQEHRPRNLPCGHVLCRECVTALAHPrrsklECPF 47

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 24665272   9 TDFLNCPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNRQ-----CP 51
Cdd:cd16543   1 EDQLTCSICLDLL----KDPVTIPCGHSFCMNCITLLWDRKqgvpsCP 44

RING finger, HC subclass, found in RING finger protein 182 (RNF182) and similar proteins; RNF182 is a brain-enriched E3 ubiquitin-protein ligase that stimulates E2-dependent polyubiquitination in vitro. It is upregulated in Alzheimer"s disease (AD) brains and neuronal cells exposed to injurious insults. It interacts with ATP6V0C and promotes its degradation by the ubiquitin-proteosome pathway, suggesting a very specific role in controlling the turnover of an essential component of the neurotransmitter release machinery. RNF182 contains an N-terminal C3HC4-type RING-HC finger, and a C-terminal transmembrane domain.

                        10        20        30
                ....*....|....*....|....*....|.
gi 24665272  12 LNCPICCNEFAASQRCPVSLGCGHTICKLCL 42
Cdd:cd16555   2 LECKICYNRYDLRQRRPKVLECCHRVCAKCL 32

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
                ....*....|....*....|....*....|..
gi 24665272  12 LNCPICCNEFaasqRCPVSLGCGHTICKLCLT 43
Cdd:cd16594   6 LTCPICLDYF----TDPVTLDCGHSFCRACIA 33

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

                        10        20        30
                ....*....|....*....|....*....|....
gi 24665272  12 LNCPICCNEFAASQRCPVSLGCGHTICKLCLTTL 45
Cdd:cd16557   2 LECLVCRNPYSCFVRKPKLLACQHAFCAICLKLI 35

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 24665272  12 LNCPICCnEFAasqRCPVSLGCGHTICKLCLTTLYNR-----QCP 51
Cdd:cd16498  17 LECPICL-ELL---KEPVSTKCDHQFCRFCILKLLQKkkkpaPCP 57

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        50
                ....*....|....*....|....*....|....*....|....*....|...
gi 24665272  12 LNCPICCnefaasQRC--PVSLGCGHTICKLCLTTLYNRQ--CPFDQTVIVSD 60
Cdd:cd16546   1 PECPICL------QTCihPVKLPCGHIFCYLCVKGVAWQSkrCALCRQEIPED 47

DNA repair protein rad18; All proteins in this family for which functions are known are involved in nucleotide excision repair.This family is based on the phylogenomic analysis of JA Eisen (1999, Ph.D. Thesis, Stanford University). [DNA metabolism, DNA replication, recombination, and repair]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24665272     2 PIQAPSWTDFLNCPI-CCNEFAASQRC---------PVSLGCGHTICKLCLTTLYNRQ--CPfdqTVIVSDIDN-LPINH 68
Cdd:TIGR00599   3 ELDITDSSDWLTTPIpSLYPLDTSLRChickdffdvPVLTSCSHTFCSLCIRRCLSNQpkCP---LCRAEDQESkLRSNW 79

                          90       100       110
                  ....*....|....*....|....*....|..
gi 24665272    69 ALLQLVKD-----SELLELAPPPPSVQKLEPE 95
Cdd:TIGR00599  80 LVSEIVESfknlrPSLLEFLRIPKTTPVENPD 111

RING finger, HC subclass, found in tripartite motif-containing protein 72 (TRIM72) and similar proteins; TRIM72, also known as Mitsugumin-53 (MG53), is a muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at muscle injury sites. It is required in repair of alveolar epithelial cells under plasma membrane stress failure. It interacts with dysferlin to regulate sarcolemmal repair. Upregulation of TRIM72 develops obesity, systemic insulin resistance, dyslipidemia, and hyperglycemia, as well as induces diabetic cardiomyopathy through transcriptional activation of the peroxisome proliferation-activated receptor alpha (PPAR-alpha) signaling pathway. Compensation for the absence of AKT signaling by ERK signaling during TRIM72 overexpression leads to pathological hypertrophy. Moreover, TRIM72 functions as a novel negative feedback regulator of myogenesis by targeting insulin receptor substrate-1 (IRS-1). It is transcriptionally activated by the synergism of myogenin (MyoD) and myocyte enhancer factor 2 (MEF2). TRIM72 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 24665272  12 LNCPICCNEFaasqRCPVSLGCGHTICKLCLT 43
Cdd:cd16612   5 LSCPLCLKLF----QSPVTTECGHTFCQDCLS 32

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

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gi 24665272  12 LNCPICCNEFAASqrcpVSLGCGHTICKLCLTTLYNR--QCPFDQTVIVSDIDNLPINHALLQLV 74
Cdd:cd16535   2 LQCSICSELFIEA----VTLNCSHSFCSYCITEWMKRkkECPICRKPITSKTRSLVLDNCIDKMV 62

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM43, TRIM48, TRIM49, TRIM51, TRIM64 and similar proteins; The family includes a group of closely related uncharacterized tripartite motif-containing proteins, TRIM43, TRIM43B, TRIM48/RNF101, TRIM49/RNF18, TRIM49B, TRIM49C/TRIM49L2, TRIM49D/TRIM49L, TRIM51/SPRYD5, TRIM64, TRIM64B, and TRIM64C, whose biological function remain unclear. TRIM49, also known as testis-specific RING-finger protein, has moderate similarity with SS-A/Ro52 antigen, suggesting it may be one of the target proteins of autoantibodies in the sera of patients with these autoimmune disorders. All family members 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 as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. In RBCC region, they all have a C3HC4-type RING-HC finger.

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gi 24665272  12 LNCPICCNEFAAsqrcPVSLGCGHTICKLCL 42
Cdd:cd16603   5 LTCPICMNYFID----PVTIDCGHSFCRPCL 31

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.

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gi 24665272  12 LNCPICCNEFaasqRCPVSLGCGHTICKLCLTTLYNR 48
Cdd:cd16604   1 LSCPICLDLL----KDPVTLPCGHSFCMGCLGALWGA 33

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

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gi 24665272  16 ICCNEFAASqrcPVSLGCGHTICKLCLT 43
Cdd:cd16613   4 ICCQELVYK---PITTPCKHNICKSCLQ 28

RING finger, HC subclass, found in RING finger protein 152 (RNF152) and similar proteins; RNF152 is a lysosome-anchored E3 ubiquitin-protein ligase involved in apoptosis. It is polyubiquitinated through K48 linkage. It negatively regulates the activation of the mTORC1 pathway by targeting RagA GTPase for K63-linked ubiquitination. It interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The ubiquitination of RagA recruits its inhibitor GATOR1, a GAP complex for Rag GTPases, to the Rag complex, thereby inactivating mTORC1 signaling. RNF152 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal transmembrane domain, both of which are responsible for its E3 ligase activity.

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gi 24665272  12 LNCPICCNEFAASQRcPVSLGCGHTICKLCLTTLYNRQ----CPF 52
Cdd:cd16548   1 LECQICFNYYSPRRR-PKLLDCKHTCCSVCLQQMRTSQkdlrCPW 44

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.

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gi 24665272  14 CPICCNEFAAsqrcPVSLGCGHTICKLC-LTTLYNRQ--CPF 52
Cdd:cd16550   3 CPICLEILVE----PVTLPCNHTLCMPCfQSTVEKASlcCPL 40

first RING finger, HC subclass, found in the LON peptidase N-terminal domain and RING finger protein family; The LON peptidase N-terminal domain and RING finger protein family includes LONRF1 (also known as RING finger protein 191 or RNF191), LONRF2 (also known as RING finger protein 192, RNF192, or neuroblastoma apoptosis-related protease), LONRF3 (also known as RING finger protein 127 or RNF127), which are characterized by containing two C3HC4-type RING-HC fingers, four tetratricopeptide (TPR) repeats, and an ATP-dependent protease La (LON) substrate-binding domain at the C-terminus. Their biological functions remain unclear. This model corresponds to the first RING-HC finger.

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gi 24665272  10 DFLNCPICCNEFAAsqrcPVSLGCGHTICKLCL 42
Cdd:cd16513   1 DLLSCPLCRGLLFE----PVTLPCGHTFCKRCL 29