B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. 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. TRIM27, also termed RING finger protein 76 (RNF76), or 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. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes 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. In addition, TRIM27 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 also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

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                  ....*....|....*....|....*....|....*....|...
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEEAVQ 140
Cdd:cd19762     2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEAAQ 44

B-box-type 2 zinc finger found in tripartite motif-containing proteins TRIM7, TRIM27 and similar proteins; The family includes TRIM7 and TRIM27, both of which belong to the C-IV subclass of 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. 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. TRIM27, also termed RING finger protein 76 (RNF76), or 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. It also inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. Furthermore, TRIM27 promotes 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. In addition, TRIM27 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 also a component of an estrogen receptor 1 (ESR1) regulatory complex, and is involved in estrogen receptor-mediated transcription in MCF-7 cells. Meanwhile, TRIM27 interacts with the hinge region of chromosome 3 protein (SMC3), a component of the multimeric cohesin complex that holds sister chromatids together and prevents their premature separation during mitosis.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEEAVQ 140
Cdd:cd19762     2 VCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEAAQ 44

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1034558989   94 QKQDLCQEHH-EPLKLFCQKDQSPICVVCRESrEHRLHRVLP 134
Cdd:smart00336   1 QRAPKCDSHGdEPAEFFCEECGALLCRTCDEA-EHRGHTVVL 41

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)

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                   ....*....|....*....|....*....|....*....|....*....|.
gi 1034558989   16 CSICLDYF-TDPVMTTCGHNFCRACIQLSWEkargkkgrrkrKGSFPCPEC 65
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLE-----------SGNNTCPIC 40

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558989  16 CSICLDYFTDPVMTTCGHNFCRACIQ--LSWEKArgkkgrrkrkgsfpCPECREMSPQRNLLPNRLLTKVAE 85
Cdd:TIGR00599  29 CHICKDFFDVPVLTSCSHTFCSLCIRrcLSNQPK--------------CPLCRAEDQESKLRSNWLVSEIVE 86

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKArgkkgrrkrKGSFPCPECREMSPQRNLLPNR 78
Cdd:cd16594     2 LQEELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEP---------ETSASCPQCRETCPQRNLRPNR 61

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM41, TRIM52 and similar proteins; TRIM41 and TRIM52, two closely related tripartite motif-containing proteins, have dramatically expanded RING domains compared with the rest of the TRIM family proteins. TRIM41 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of the TRIM family that contains only RBCC domains. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  11 QEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWekargkkgrrkrkgSFPCPECREMSPQRNLLPN 77
Cdd:cd16602     1 QEEAVCAICLDYFKDPVSIGCGHNFCRVCVTQLW--------------GFTCPQCRKSFPRRSFRPN 53

RING finger, HC subclass, found in tripartite motif-containing protein TRIM25 and similar proteins; TRIM25, also known as estrogen-responsive finger protein (EFP), RING finger protein 147 (RNF147), or RING-type E3 ubiquitin transferase, is an E3 ubiquitin/ISG15 ligase that is induced by estrogen and is therefore particularly abundant in placenta and uterus. TRIM25 regulates various cellular processes through E3 ubiquitin ligase activity, transferring ubiquitin and ISG15 to target proteins. It mediates K63-linked polyubiquitination of retinoic acid inducible gene I (RIG-I) that is crucial for downstream antiviral interferon signaling. It is also required for melanoma differentiation-associated gene 5 (MDA5) and mitochondrial antiviral signaling (MAVS, also known as IPS-1, VISA, Cardiff) mediated activation of nuclear factor-kappaB (NF-kappaB) and interferon production. Upon UV irradiation, TRIM25 interacts with mono-ubiquitinated PCNA and promotes its ISG15 modification (ISGylation), suggesting a crucial role in termination of error-prone translesion DNA synthesis. TRIM25 also functions as a novel regulator of p53 and Mdm2. It enhances p53 and Mdm2 abundance by inhibiting their ubiquitination and degradation in 26S proteasomes. Meanwhile, it inhibits p53's transcriptional activity and dampens the response to DNA damage, and is essential for medaka development and this dependence is rescued by silencing of p53. Moreover, TRIM25 is involved in the host cellular innate immune response against retroviral infection. It interferes with the late stage of feline leukemia virus (FeLV) replication. Furthermore, TRIM25 acts as an oncogene in gastric cancer. Its blockade by RNA interference inhibits migration and invasion of gastric cancer cells through transforming growth factor-beta (TGF-beta) signaling, suggesting it presents a novel target for the detection and treatment of gastric cancer. In addition, TRIM25 acts as an RNA-specific activator for Lin28a/TuT4-mediated uridylation. TRIM25 belongs to the C-IV subclass of 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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEkargkkgrRKRKGSFPCPECREMSPQR-NLLPNRLLTKVAE 85
Cdd:cd16597     2 LEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWD--------SQHGSEYSCPQCRATFPRRpELHKNTVLRNIVE 70

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM4, TRIM17, TRIM41, TRIM52 and similar proteins; This family includes a group of tripartite motif-containing proteins, including TRIM4, TRIM17, TRIM41 and TRIM52. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that recently evolved and is present only in higher mammals. It transiently interacts with mitochondria, induces mitochondrial aggregation and sensitizes the cells to hydrogen peroxide (H2O2) induced death. Its interaction with peroxiredoxin 1 (PRX1) is critical for the regulation of H2O2 induced cell death. Moreover, TRIM4 functions as a positive regulator of RIG-I-mediated type I interferon induction. It regulates the K63-linked ubiquitination of RIG-1 and assembly of antiviral signaling complex at mitochondria. TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (Terf), is a crucial E3 ubiquitin ligase that is necessary and sufficient for neuronal apoptosis and contributes to Mcl-1 ubiquitination in cerebellar granule neurons (CGNs). It interacts in a SUMO-dependent manner with nuclear factor of activated T cell NFATc3 transcription factor, and thus inhibits the activity of NFATc3 by preventing its nuclear localization. In contrast, it binds to and inhibits NFATc4 transcription factor in a SUMO-independent manner. Moreover, TRIM17 stimulates degradation of kinetochore protein ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM41, also known as RING finger-interacting protein with C kinase (RINCK), is an E3 ubiquitin-protein ligase that promotes the ubiquitination of protein kinase C (PKC) isozymes in cells. It specifically recognizes the C1 domain of PKC isozymes. It controls the amplitude of PKC signaling by controlling the amount of PKC in the cell. TRIM52, also known as RING finger protein 102 (RNF102), is encoded by a novel, noncanonical antiviral TRIM52 gene in primate genomes with unique specificity determined by the rapidly evolving RING domain. TRIM4, TRIM17 and TRIM41 belong to the C-IV subclass of 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 RING finger, 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. In contrast, TRIM52 lacks the putative viral recognition SPRY/B30.2 domain, and thus has been classified to the C-V subclass of TRIM family that contains only RBCC domains. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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                  ....*....|....*....|....*....|....*...
gi 1034558989  97 DLCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLP 134
Cdd:cd19760     1 GLCEKHQEPLKLFCEEDEALICVICRESRAHRAHTVVP 38

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM60, TRIM61, TRIM75 and similar proteins; TRIM60, also known as RING finger protein 129 (RNF129) or RING finger protein 33 (RNF33), is a cytoplasmic protein expressed in the testis. It may play an important role in the spermatogenesis process, the development of the preimplantation embryo, and in testicular functions. RNF33 interacts with the cytoplasmic kinesin motor proteins KIF3A and KIF3B suggesting possible contribution to cargo movement along the microtubule in the expressed sites. It is also involved in spermatogenesis in Sertoli cells under the regulation of nuclear factor-kappaB (NF-kappaB). TRIM75 mainly localizes within spindles, suggesting it may function in spindle organization and thereby affect meiosis. Both TRIM60 and TRIM75 belong 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 B2-box, and two coiled coil domains, as well as a PRY domain and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. In contrast, TRIM61 belongs to the C-V subclass of the TRIM family that contains RBCC domains only. Its biological function remains unclear.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034558989  13 EATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKargkkgrrkRKGSFPCPECR 66
Cdd:cd16607     1 EASCPICLDYLKDPVTINCGHNFCRSCISMSWKD---------LQDTFPCPVCR 45

B-box-type 2 zinc finger found in tripartite motif-containing protein 11 (TRIM11) and similar proteins; 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) through 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. TRIM11 belongs to the C-IV subclass of 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 RING finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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                  ....*....|....*....|....*....|....*....|...
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEEAVQ 140
Cdd:cd19766     2 LCGKHREPLKLFCKDHEALLCVVCERSREHWGHRVVPAEEAAQ 44

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034558989  11 QEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGrrkrkgsfpCPECREMSPQR 72
Cdd:cd16543     1 EDQLTCSICLDLLKDPVTIPCGHSFCMNCITLLWDRKQGVPS---------CPQCRESFPPR 53

B-box-type 2 zinc finger found in Xenopus laevis nuclear factor 7 (xNF7) and similar proteins; xNF7 is a maternally expressed novel zinc finger nuclear phosphoprotein. It acts as a transcription factor that determines dorsal-ventral body axis. xNF7 harbors a B-box motif that shows high sequence similarity with B-Box-type zinc finger 2 found in tripartite motif-containing proteins (TRIMs). The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

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                  ....*....|....*....|....*....|....*...
gi 1034558989  97 DLCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLP 134
Cdd:cd19800     1 EVCSEHDEPLKLFCKDDKRLICVICRDSRKHRGHRFLP 38

RING finger, HC subclass, found in tripartite motif-containing protein 38 (TRIM38) and similar proteins; TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates Tumor necrosis factor alpha (TNF-alpha)- and interleukin-1beta-triggered Nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome. TRIM38 belongs 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1034558989   9 KLQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKargKKGRRKRKGSFPCPECR 66
Cdd:cd16600     1 KMREEATCSICLQLMTEPVSINCGHSYCKRCIVSFLEN---QSQLEPGLETFSCPQCR 55

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKgrrkrkgsfpCPECR 66
Cdd:cd16608     3 LKDELLCSICLSIYQDPVSLGCEHYFCRQCITEHWSRSEHRD----------CPECR 49

B-box-type 2 zinc finger found in tripartite motif-containing protein 68 (TRIM68) and similar proteins; TRIM68, also known as RING finger protein 137 (RNF137) or SSA protein SS-56 (SS-56), is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems. It also functions as a cofactor for androgen receptor-mediated transcription by regulating ligand-dependent transcription of androgen receptor in prostate cancer cells. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogren's syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE. TRIM68 belongs the C-IV subclass of 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 RING finger, Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 1034558989  96 QDLCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEEAV 139
Cdd:cd19795     1 EDLCERHKEKLNLFCEEDQELLCVVCEQSPEHKAHTVVPVEEAA 44

RING finger, HC subclass, found in tripartite motif-containing protein 8 (TRIM8) and similar proteins; TRIM8, also known as glioblastoma-expressed RING finger protein (GERP) or RING finger protein 27 (RNF27), is a probable E3 ubiquitin-protein ligase that may promote proteasomal degradation of suppressor of cytokine signaling 1 (SOCS1) and further regulate interferon-gamma signaling. It functions as a new p53 modulator that stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation. TRIM8 deficit dramatically impairs p53 stabilization and activation in response to chemotherapeutic drugs. TRIM8 also modulates tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta)-triggered nuclear factor-kappaB (NF- kappa B) activation by targeting transforming growth factor beta (TGFbeta) activated kinase 1 (TAK1) for K63-linked polyubiquitination. Moreover, TRIM8 modulates translocation of phosphorylated STAT3 into the nucleus through interaction with Hsp90beta and consequently regulates transcription of Nanog in embryonic stem cells. It also interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. TRIM8 belongs to the C-V 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 domain, as well as an uncharacterized region positioned C-terminal to the RBCC domain. The coiled coil domain is required for homodimerization and the region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGrrkrkgsfpCPECREMSPQR 72
Cdd:cd16580     8 FEEELICPICLHVFVEPVQLPCKHNFCRGCIGEAWAKDAGLVR---------CPECNQAYNQK 61

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        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1034558989   9 KLQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKargkkgrrkRKGSFPCPECREMSPQRNLLPN 77
Cdd:cd16498    12 AMQKNLECPICLELLKEPVSTKCDHQFCRFCILKLLQK---------KKKPAPCPLCKKSVTKRSLQES 71

HC subclass of RING (RING-HC) finger and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers. Some have a different Cys/His pattern. Some lack a single Cys or His residue at typical Zn ligand positions, especially, the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can chelate Zn in a RING finger as well. This family corresponds to the HC subclass of RING (RING-HC) fingers that are characterized by containing C3HC4-type canonical RING-HC fingers or noncanonical RING-HC finger variants, including C4C4-, C3HC3D-, C2H2C4-, and C3HC5-type modified RING-HC fingers. The canonical RING-HC finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-C-X2-C-X(4-48)-C-X2-C. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-HC fingers can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle, and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serve as scaffolds for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034558989  15 TCSICLDYFTDPVMTTCGHNFCRACIQLSWEkargkkgrrkrKGSFPCPEC 65
Cdd:cd16449     2 ECPICLERLKDPVLLPCGHVFCRECIRRLLE-----------SGSIKCPIC 41

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. 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. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong to the C-IV subclass of 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 RING finger, 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. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 1034558989  97 DLCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLP 134
Cdd:cd19765     1 TLCEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSL 38

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM16, TRIM29, TRIM47 and similar proteins; This family includes a group of tripartite motif-containing proteins, such as TRIM16, TRIM29 and TRIM47. TRIM16, also termed estrogen-responsive B box protein (EBBP), is a regulator that may play a role in the regulation of keratinocyte differentiation. It may also act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcinogenesis. TRIM29, also termed ataxia telangiectasia group D-associated protein (ATDC), plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. TRIM47, also known as gene overexpressed in astrocytoma protein (GOA) or RING finger protein 100 (RNF100), plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. TRIM16 and TRIM29 belong to an unclassified TRIM (tripartite motif) family of proteins that do not have RING fingers and thus lack the characteristic tripartite (RING (R), B-box, and coiled coil (CC)) RBCC motif. TRIM47 belongs to the C-IV subclass of TRIM family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox1 and Bbox2, and two coiled coil domains, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESrEHRLHRVLPAEEAVQGYK 143
Cdd:cd19769     2 VCPIHKKPLELFCRTDQMCICELCAKE-EHRGHDVVTVEEEREKKE 46

RING-type zinc-finger; This zinc-finger is a typical RING-type of plant ubiquitin ligases.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1034558989  16 CSICLDYFTDPVmTTCGHNFCRACIQLSWEKargkkgrrkRKGSFPCP 63
Cdd:pfam13445   1 CPICLELFTDPV-LPCGHTFCRECLEEMSQK---------KGGKFKCP 38

B-box-type 2 zinc finger 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 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEE 137
Cdd:cd19777     5 LCRLHGETLKLFCLDDKELLCCACQSSKQHQGHRVYPVKE 44

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        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034558989  16 CSICLDYFTDPV-MTTCGHNFCRACIQLSWEKargkkgrrkrkGSFPCPEC 65
Cdd:pfam00097   1 CPICLEEPKDPVtLLPCGHLFCSKCIRSWLES-----------GNVTCPLC 40

RING finger, HC subclass, found in RING finger protein 138 (RNF138) and similar proteins; RNF138, also known as Nemo-like kinase-associated RING finger protein (NARF) or NLK-associated RING finger protein, is an E3 ubiquitin-protein ligase that plays an important role in glioma cell proliferation, apoptosis, and cell cycle. It specifically cooperates with the E2 conjugating enzyme E2-25K (Hip-2/UbcH1), regulates the ubiquitylation and degradation of T cell factor/lymphoid enhancer factor (TCF/LEF), and further suppresses Wnt-beta-catenin signaling. RNF138, together with three closely related proteins: RNF114, RNF125 and RNF166, forms a novel family of ubiquitin ligases with a C3HC4-type RING-HC finger, a C2HC-, and two C2H2-type zinc fingers, as well as a ubiquitin interacting motif (UIM).

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  12 EEATCSICLDYFTDPVMT-TCGHNFCRACIQLSWEKargkkgrrkrkGSFPCPECRE 67
Cdd:cd16544     1 AELTCPVCQEVLKDPVELpPCRHIFCKACILLALRS-----------SGARCPLCRG 46

B-box-type 2 zinc finger found in tripartite motif-containing protein 40 (TRIM40) and similar proteins; TRIM40, also termed probable E3 NEDD8-protein ligase, or RING finger protein 35, may function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway. It promotes neddylation of IKBKG/NEMO, stabilizing NFKBIA, and inhibiting NF-kappaB nuclear translocation and activity. TRIM40 belongs to the C-V subclass of 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 RING finger, Bbox2, and a coiled coil region. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1034558989  98 LCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAEEA 138
Cdd:cd19781     4 LCQLHEKKVEWFCEEDQVLLCEECLKSPEHQSHHVLTIEDA 44

RING finger, HC subclass, found in tripartite motif-containing proteins TRIM13, TRIM59 and similar proteins; TRIM13 and TRIM59, two closely related tripartite motif-containing proteins, belong to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, followed by a C-terminal transmembrane domain. TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1034558989  12 EEATCSICLDYFTDPVMTTCGHNFCRACIQlswekARGKKGRRKRKGSFPCPECR 66
Cdd:cd16581     1 EELTCSICYNIFDDPKILPCSHTFCKNCLE-----KLLAASGYYLLASLKCPTCR 50

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        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034558989  12 EEATCSICLDYFTDPVMTT-CGHNFCRACIQLSWEKARGKkgrrkrkgsfpCPECR 66
Cdd:cd16503     1 ENLTCSICQDLLHDCVSLQpCMHNFCAACYSDWMERSNTE-----------CPTCR 45

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1034558989   94 QKQDLCQEHH-EPLKLFCQKDQSPICVVCRESrEHRLHRVLP 134
Cdd:smart00336   1 QRAPKCDSHGdEPAEFFCEECGALLCRTCDEA-EHRGHTVVL 41

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM5, TRIM6, TRIM22, TRIM34, TRIM38 and similar proteins; The family includes TRIM5, TRIM6, TRIM22, TRIM34, and TRIM38, all of which 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 RING finger, 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. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif. TRIM5, also termed RING finger protein 88 (RNF88), is a capsid-specific restriction factor that prevents infection from non-host-adapted retroviruses in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. Its retroviral restriction activity correlates with the ability to activate TAK1-dependent innate immune signaling. TRIM5 also acts as a pattern recognition receptor that activates innate immune signaling in response to the retroviral capsid lattice. Moreover, TRIM5 plays a role in regulating autophagy through activation of autophagy regulator BECN1 by causing its dissociation from its inhibitors BCL2 and TAB2. It also plays a role in autophagy by acting as a selective autophagy receptor which recognizes and targets HIV-1 capsid protein p24 for autophagic destruction. TRIM6, also termed RING finger protein 89 (RNF89), is an E3-ubiquitin ligase that cooperates with the E2-ubiquitin conjugase UbE2K to catalyze the synthesis of unanchored K48-linked polyubiquitin chains, and further stimulates the interferon-I kappa B kinase epsilon (IKKepsilon) kinase-mediated antiviral response. It also regulates the transcriptional activity of Myc during the maintenance of embryonic stem (ES) cell pluripotency, and may act as a novel regulator for Myc-mediated transcription in ES cells. TRIM22, also termed 50 kDa-stimulated trans-acting factor (Staf-50), or RING finger protein 94 (RNF94), is an E3 ubiquitin-protein ligase that plays an integral role in the host innate immune response to viruses. It has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. TRIM22 acts as a suppressor of basal HIV-1 long terminal repeat (LTR)-driven transcription by preventing transcription factor specificity protein 1 (Sp1) binding to the HIV-1 promoter. It also controls FoxO4 activity and cell survival by directing Toll-like receptor 3 (TLR3)-stimulated cells toward type I interferon (IFN) type I gene induction or apoptosis. Moreover, TRIM22 can activate the noncanonical nuclear factor-kappaB (NF-kappaB) pathway by activating I kappa B kinase alpha (IKKalpha). It also regulates nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-kappaB. TRIM34, also termed interferon-responsive finger protein 1, or RING finger protein 21 (RNF21), may function as an antiviral protein that contributes to the defense against retroviral infections. TRIM38, also known as RING finger protein 15 (RNF15) or zinc finger protein RoRet, is an E3 ubiquitin-protein ligase that promotes K63- and K48-linked ubiquitination of cellular proteins and also catalyzes self-ubiquitination. It negatively regulates tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta-triggered nuclear factor-kappaB (NF-kappaB) activation by mediating lysosomal-dependent degradation of transforming growth factor beta (TGFbeta)-activated kinase 1 (TAK1)-binding protein (TAB)2/3, two critical components of the TAK1 kinase complex. It also inhibits TLR3/4-mediated activation of NF-kappaB and interferon regulatory factor 3 (IRF3) by mediating ubiquitin-proteasomal degradation of TNF receptor-associated factor 6 (Traf6) and NAK-associated protein 1 (Nap1), respectively. Moreover, TRIM38 negatively regulates TLR3-mediated interferon beta (IFN-beta) signaling by targeting ubiquitin-proteasomal degradation of TIR domain-containing adaptor inducing IFN-beta (TRIF). It functions as a valid target for autoantibodies in primary Sjogren's Syndrome.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|
gi 1034558989  97 DLCQEHHEPLKLFCQKDQSPICVVCRESREHRLHRVLPAE 136
Cdd:cd19761     1 DHCEHHGEKLLLFCQEDGKVICWLCERSQEHRGHHTFLLE 40

RING finger, HC subclass, found in tripartite motif-containing protein 59 (TRIM59) and similar proteins; TRIM59, also known as RING finger protein 104 (RNF104) or tumor suppressor TSBF-1, is a putative E3 ubiquitin-protein ligase that functions as a novel multiple cancer biomarker for immunohistochemical detection of early tumorigenesis. It is upregulated in gastric cancer and promotes gastric carcinogenesis by interacting with and targeting the P53 tumor suppressor for its ubiquitination and degradation. It also acts as a novel accessory molecule involved in cytotoxicity of BCG-activated macrophages (BAM). Moreover, TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways. It interacts with ECSIT and negatively regulates nuclear factor-kappaB (NF- kappa B) and interferon regulatory factor (IRF)-3/7-mediated signal pathways. TRIM59 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM59 contains a C-terminal transmembrane domain.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1034558989  11 QEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGRRKRKGSFPCPECR 66
Cdd:cd16763     1 EEDLTCSVCYSLFEDPRVLPCSHTFCRNCLENILQVSGNFSIWRPLRPPLKCPNCR 56

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 1034558989  94 QKQDLCQEHH-EPLKLFCQKDQSPICVVCRESrEHRLHRVLP 134
Cdd:pfam00643   1 SKERLCPEHEeEPLTLYCNDCQELLCEECSVG-EHRGHTVVP 41

Modified RING finger, HC subclass (C3HC3D-type), found in ligand of Numb protein LNX1, LNX2, 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 substrate-binding. LNX1/LNX2-like proteins contain a modified C3HC3D-type RING-HC finger and four PDZ domains. This model corresponds to the RING finger.

                          10        20
                  ....*....|....*....|....*.
gi 1034558989  15 TCSICLDYFTDPVMTTCGHNFCRACI 40
Cdd:cd16637     3 TCHICLQPLVEPLDTPCGHTFCYKCL 28

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.

                          10        20
                  ....*....|....*....|....*
gi 1034558989  16 CSICLDYFTDPVMTTCGHNFCRACI 40
Cdd:cd16644     8 CPLCQRVFKDPVITSCGHTFCRRCA 32

RING finger, HC subclass, found in midline-1 (MID1) and similar proteins; MID1, also known as midin, midline 1 RING finger protein, putative transcription factor XPRF, RING finger protein 59 (RNF59), or tripartite motif-containing protein 18 (TRIM18), is a microtubule-associated E3 ubiquitin-protein ligase implicated in epithelial-mesenchymal differentiation, cell migration and adhesion, and programmed cell death along specific regions of the ventral midline during embryogenesis. It monoubiquinates the alpha4 subunit of protein phosphatase 2A (PP2A), promoting proteosomal degradation of the catalytic subunit of PP2A (PP2Ac) and preventing the A and B subunits from forming an active complex. It promotes allergen and rhinovirus-induced asthma through the inhibition of PP2A activity. It is strongly upregulated in cytotoxic lymphocytes (CTLs) and directs lytic granule exocytosis and cytotoxicity of killer T cells. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (XLOS) syndrome characterized by defective midline development during embryogenesis. MID1 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, Bbox1 and Bbox2, and a coiled coil region, as well as a COS (carboxyl-terminal subgroup one signature) box, a fibronectin type III (FN3) domain, and a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. MID1 hetero-dimerizes in vitro with its paralog MID2.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGRRKRKGSFPCPECR 66
Cdd:cd16753     2 LESELTCPICLELFEDPLLLPCAHSLCFNCAHRILVSHCASNESVESITAFQCPTCR 58

RING finger, HC subclass, found in RING finger proteins RNF113A, RNF113B, and similar proteins; RNF113A, also known as zinc finger protein 183 (ZNF183), is an E3 ubiquitin-protein ligase that physically interacts with the E2 protein, UBE2U. A nonsense mutation in RNF113A is associated with an X-linked trichothiodystrophy (TTD). Its yeast ortholog Cwc24p is predicted to have a spliceosome function and acts in a complex with Cef1p to participate in pre-U3 snoRNA splicing, indirectly affecting pre-rRNA processing. It is also important for the U2 snRNP binding to primary transcripts and co-migrates with spliceosomes. Moreover, the ortholog of RNF113A in fruit flies may also act as a spliceosome and is hypothesized to be involved in splicing, namely within the central nervous system. The ortholog in Caenorhabditis elegans is involved in DNA repair of inter-strand crosslinks. RNF113B, also known as zinc finger protein 183-like 1, shows high sequence similarity with RNF113A. Both RNF113A and RNF113B contain a CCCH-type zinc finger, which is commonly found in RNA-binding proteins involved in splicing, and a C3HC4-type RING-HC finger, which is frequently found in E3 ubiquitin ligases.

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                  ....*....|....*....|....*....|..
gi 1034558989  15 TCSICLDYFTDPVMTTCGHNFCRACIQLSWEK 46
Cdd:cd16539     7 ACFICRKPFKNPVVTKCGHYFCEKCALKHYRK 38

RING finger, HC subclass, found in tripartite motif-containing protein 13 (TRIM13) and similar proteins; TRIM13, also known as B-cell chronic lymphocytic leukemia tumor suppressor Leu5, leukemia-associated protein 5, putative tumor suppressor RFP2, RING finger protein 77 (RNF77), or Ret finger protein 2, is an endoplasmic reticulum (ER) membrane anchored E3 ubiquitin-protein ligase that interacts with proteins localized to the ER, including valosin-containing protein (VCP), a protein indispensable for ER-associated degradation (ERAD). It also targets the known ER proteolytic substrate CD3-delta, but not the N-end rule substrate Ub-R-YFP (yellow fluorescent protein) for degradation. Moreover, TRIM13 regulates ubiquitination and degradation of NEMO to suppress tumor necrosis factor (TNF) induced nuclear factor-kappaB (NF- kappa B) activation. It is also involved in NF-kappaB p65 activation and nuclear factor of activated T-cells (NFAT)-dependent activation of c-Rel upon T-cell receptor engagement. Furthermore, TRIM13 negatively regulates melanoma differentiation-associated gene 5 (MDA5)-mediated type I interferon production. It also regulates caspase-8 ubiquitination, translocation to autophagosomes, and activation during ER stress induced cell death. Meanwhile, TRIM13 enhances ionizing radiation-induced apoptosis by increasing p53 stability and decreasing AKT kinase activity through MDM2 and AKT degradation. TRIM13 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region. In addition, TRIM13 contains a C-terminal transmembrane domain.

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gi 1034558989  11 QEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKArgkKGRRKRKGSFPCPECRE 67
Cdd:cd16762     1 EEDLTCPICCCLFDDPRVLPCSHNFCKKCLEGILEGN---VRTMLWRPPFKCPTCRK 54

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 1034558989  10 LQEEATCSICLDYFTDPVMTTCGHNFCRACI 40
Cdd:cd16612     1 MHQDLSCPLCLKLFQSPVTTECGHTFCQDCL 31

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.

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                  ....*....|....*....|....*....|....*....|....*....|.
gi 1034558989  16 CSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKkgrrkrkgsfpCPECR 66
Cdd:cd16509     6 CAICLDSLTNPVITPCAHVFCRRCICEVIQREKAK-----------CPMCR 45

RING finger, HC subclass, found in RING finger protein 180 (RNF180) and similar proteins; RNF180, also known as Rines, is a membrane-bound E3 ubiquitin-protein ligase well conserved among vertebrates. It is a critical regulator of the monoaminergic system, as well as emotional and social behavior. It interacts with brain monoamine oxidase A (MAO-A) and targets it for ubiquitination and degradation. It also functions as a novel tumor suppressor in gastric carcinogenesis. The hypermethylated CpG site count of the RNF180 DNA promoter can be used to predict survival of gastric cancer. RNF180 contains a novel conserved dual specificity protein phosphatase Rines conserved (DSPRC) domain, a basic coiled-coil domain, a C3HC4-type RING-HC finger, and a C-terminal hydrophobic region that is predicted to be a transmembrane domain.

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                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034558989  12 EEATCSICLDYFTDPVMTT-CGHNFCRACIQLswekargkkGRRKRKGSFPCPECRE 67
Cdd:cd16554     1 ESLTCPVCLDLYYDPYMCYpCGHIFCEPCLRQ---------LAKSSPKNTPCPLCRT 48

RING finger, HC subclass, found in tripartite motif-containing protein 68 (TRIM68) and similar proteins; TRIM68, also known as RING finger protein 137 (RNF137) or SSA protein SS-56 (SS-56), is an E3 ubiquitin-protein ligase that negatively regulates Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I interferon production by degrading TRK fused gene (TFG), a novel driver of IFN-beta downstream of anti-viral detection systems. It also functions as a cofactor for androgen receptor-mediated transcription by regulating ligand-dependent transcription of androgen receptor in prostate cancer cells. Moreover, TRIM68 is a cellular target of autoantibody responses in Sjogre's syndrome (SS), as well as systemic lupus erythematosus (SLE). It is also an auto-antigen for T cells in SS and SLE. TRIM68 belongs 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.

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                  ....*....|....*....|....*....|....*....|....*....|....
gi 1034558989  13 EATCSICLDYFTDPVMTTCGHNFCRACIQLSWEkargkKGRRKRKGSFPCPECR 66
Cdd:cd16610     1 EVACPICMTFLREPVSIDCGHSFCHSCLSGLWE-----VPGESQNWGYTCPLCR 49

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 1034558989  14 ATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKArgkkgrrkrkgSFPCPECR 66
Cdd:cd16550     1 CLCPICLEILVEPVTLPCNHTLCMPCFQSTVEKA-----------SLCCPLCR 42

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.

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gi 1034558989  16 CSICLDYFTDPVMTTCGHNFCRACIQLS 43
Cdd:cd16643     4 CPICLMALREPVQTPCGHRFCKACILKS 31

RING finger, HC subclass, found in tripartite motif-containing protein 31 (TRIM31) and similar proteins; TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM31 belongs to the C-V subclass of the TRIM (tripartite motif) family of proteins that are defined by an N-terminal RBCC (RING, Bbox, and coiled coil) domain, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as an uncharacterized region positioned C-terminal to the RBCC domain.

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                  ....*....|....*....|....*...
gi 1034558989  13 EATCSICLDYFTDPVMTTCGHNFCRACI 40
Cdd:cd16582     1 EVICPICLDILQKPVTIDCGHNFCLQCI 28

RING finger, HC subclass, found in RING finger protein 169 (RNF169) and similar proteins; RNF169 is an uncharacterized E3 ubiquitin-protein ligase paralogous to RNF168. It functions as a negative regulator of the DNA damage signaling cascade. RNF169 recognizes polyubiquitin structures but does not itself contribute to double-strand break (DSB)-induced chromatin ubiquitylation. It contributes to regulation of the DSB repair pathway utilization via functionally competing with recruiting repair factors, 53BP1 and RAP80-BRCA1, for association with RNF168-modified chromatin independent of its catalytic activity, limiting the magnitude of the RNF8/RNF168-dependent signaling response to DSBs. RNF169 contains an N-terminal C3HC4-type RING-HC finger and a C-terminal MIU (motif interacting with ubiquitin) domain.

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gi 1034558989  13 EATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKARGKKGrrkrkgsfpCPECR 66
Cdd:cd16551     1 ELTCAGCLEVPVEPATLPCGHTLCRGCANRALDAAEAGPT---------CPRCR 45

RING finger, HC subclass, found in RING finger protein 170 (RNF170) and similar proteins; RNF170, also known as putative LAG1-interacting protein, is an endoplasmic reticulum (ER) membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination-dependent degradation of type-I inositol 1,4,5-trisphosphate (IP3) receptors (ITPR1) via the endoplasmic-reticulum-associated protein degradation (ERAD) pathway. A point mutation (arginine to cysteine at position 199) in the RNF170 gene is linked with autosomal-dominant sensory ataxia (ADSA), a disease characterized by neurodegeneration in the posterior columns of the spinal cord. RNF170 contains a C3HC4-type RING-HC finger.

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gi 1034558989  15 TCSICLDYFTDPVMTTCGHNFCRACIQLSWEkargkkgRRKRKGSFPCPECREM 68
Cdd:cd16553     3 ECPICLQDARFPVETNCGHLFCGPCIITYWR-------HGSWLGAVSCPVCRQT 49

second 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 second RING-HC finger.

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gi 1034558989  16 CSICLDYFTDPVMTTCGHNFCRACIQLSWEkargkkgrrkrkGSFPCPECRE 67
Cdd:cd16514     4 CSLCLRLLYEPVTTPCGHTFCRACLERCLD------------HSPKCPLCRT 43

RING finger found in polycomb group RING finger protein 5 (PCGF5) and similar proteins; PCGF5, also known as RING finger protein 159 (RNF159), is one of six PcG RING finger (PCGF) homologs (PCGF1/NSPc1, PCGF2/Mel-18, PCGF3, PCGF4/BMI1, PCGF5, and PCGF6/MBLR) and serves as the core component of a Polycomb repressive complex 1 (PRC1). Like other PCGF homologs, PCGF5 associates with ring finger protein 2 (RNF2) to form a RNF2-PCGF heterodimer, which is catalytically competent as an E3 ubiquitin transferase and is the scaffold for the assembly of additional components. PCGF5 contains a C3HC4-type RING-HC finger.

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gi 1034558989   6 LARKLQEEATCSICLDYFTDP-VMTTCGHNFCRACIQLSWEKARGkkgrrkrkgsfpCPEC----REMSPQRNLLPNRLL 80
Cdd:cd16737     3 LVRDFNPYITCRICKGYLIKPtTVTECLHTFCKSCIVQHFEDSND------------CPECgiqvHETNPLEMLRLDNTL 70

                          90       100
                  ....*....|....*....|....
gi 1034558989  81 TKVaeMAQQHPGLQKQDlCQEHHE 104
Cdd:cd16737    71 EEI--IFKLVPGLRERE-LQREAE 91