RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has 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 the mitochondria.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 301601615   4 EDIQEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 64
Cdd:cd16590    1 EDIQEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 61

RING finger, HC subclass, found in tripartite motif-containing protein TRIM4 and similar proteins; TRIM4 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, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM4, also known as RING finger protein 87 (RNF87), is a cytoplasmic E3 ubiquitin-protein ligase that has 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 the mitochondria.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 301601615   4 EDIQEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 64
Cdd:cd16590    1 EDIQEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 61

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 301601615   12 CPICLDYFQDPVSIECGHNFCRGCLHRNW-APGGGPFPCPEC 52
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQkEPDGESLLCPQC 42

SPRY domain; SPRY Domain is named from SPla and the RYanodine Receptor and it is found in many eukaryotic proteins with a wide range of functions. It is a protein-interaction module involved in many important signalling pathways like RNA processing, regulation of histone H3 methylation, innate immunity or embryonic development. It can be divided into 11 subfamilies based on amino acid sequence similarity or the presence of additional protein domains. The greater SPRY family is divided into the SPRY/B30.2 (which contains a PRY extension at the N-terminal) and SPRY-only sub-families which are preceded by a subdomain that is structurally similar to the PRY region. SPRY/B30.2 structures revealed a bent beta-sandwich fold comprised of two beta-sheets. Distant homologs are domains in butyrophilin/ marenostrin/pyrin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615  379 KHYWEVE--SRDSLEVAVGVCREDVMGiTDRSKMSPDVGIWAiYWSAAG--YWPLIGFP-GTPTQQEPalHRVGVYLDRG 453
Cdd:pfam00622   1 RHYFEVEifGQDGGGWRVGWATKSVPR-KGERFLGDESGSWG-YDGWTGkkYWASTSPLtGLPLFEPG--DVIGCFLDYE 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 301601615  454 TGNVSFYsaVDGVHL-HTFS-CSSVSRLRPFFWLSPLASLVI 493
Cdd:pfam00622  77 AGTISFT--KNGKSLgYAFRdVPFAGPLFPAVSLGAGEGLKF 116

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 301601615   10 LTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGpfpCPECRHPSAPAALRPNWALARLTE 72
Cdd:TIGR00599  27 LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQPK---CPLCRAEDQESKLRSNWLVSEIVE 86

RING-finger-containing E3 ubiquitin ligase [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 301601615  10 LTCPICLDYFQDPVSIECGHNFCRGCLHRNWapGGGPFpCPECRHPSAPAALRPNWALARLTEKTQRRR 78
Cdd:COG5432   26 LRCRICDCRISIPCETTCGHTFCSLCIRRHL--GTQPF-CPVCREDPCESRLRGSSGSREINESHARNR 91

E3 ubiquitin-protein ligase RMA2; Provisional

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 301601615   9 ELTCPICLDYFQDPVSIECGHNFCRGCLHRnWAPGGG--------------PFPCPECRHPSAPAALRP 63
Cdd:PLN03208  18 DFDCNICLDQVRDPVVTLCGHLFCWPCIHK-WTYASNnsrqrvdqydhkrePPKCPVCKSDVSEATLVP 85

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM5, TRIM6, TRIM7, TRIM10, TRIM11, TRIM17, TRIM20, TRIM21, TRIM27, TRIM35, TRIM38, TRIM41, TRIM50, TRIM58, TRIM60, TRIM62, TRIM69, TRIM72, NF7 and bloodthirsty; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class IV TRIM proteins, including TRIM7, TRIM35, TRIM41, TRIM50, TRIM62, TRIM69, TRIM72, TRIM protein NF7 and bloodthirsty (bty). TRIM7 interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism. TRIM41 is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. TRIM62 is involved in the morphogenesis of the mammary gland; loss of TRIM62 gene expression in breast is associated with increased risk of recurrence in early-onset breast cancer. TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis. TRIM72 has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 309 VNLAEDTAHPKLVFSQEGRYVKNTASASSWPVfssawnyfagwrNPqktafvERFQHLPCVLGKNVFTSGKHYWEVESRD 388
Cdd:cd13733    2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPD------------NP------ERFDTCVCVLGSEGFSSGRHYWEVEVGG 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 389 SLEVAVGVCREDVMGItDRSKMSPDVGIWAI-YWSAAGYWPLIGFPgTPTQQEPALHRVGVYLDRGTGNVSFYSAVDGVH 467
Cdd:cd13733   64 KTDWDLGVARESVNRK-GKITLSPENGYWTVgLRNGNEYKALTSPS-TPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSH 141

                        170       180       190
                 ....*....|....*....|....*....|...
gi 301601615 468 LHTFSCSSVSRLRPFFWLSP------LASLVIP 494
Cdd:cd13733  142 IYTFTDCFTEKLYPYFSPCLndggknSAPLIIC 174

butyrophilin subfamily member A1 and A2 (BTN1A and BTN2A); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 1A and 2A (BTN1A and BTN2A). BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN1A plays a role in the secretion, formation and stabilization of milk fat globules. The B30.2 domain of BTN1A1 binds the enzyme xanthine oxidoreductase (XOR) in order to participate in milk fat globule secretion; this interaction may lead to the production of reactive oxygen species, which have immunomodulatory and antimicrobial functions. Duplication events have led to three paralogs of BTN2A in primates: BTN2A1, BTN2A2, and BTN2A3. In humans, only BTN2A1 has been functionally characterized; it has been detected on epithelial cells and leukocytes, and identified as a novel ligand of dendritic cell-specific ICAM-3 grabbing nonintegrin (DCSIGN), a C-type lectin receptor that acts as an internalization receptor for HIV-1, HCV, and other pathogens. BTN2A2 mRNA has been shown to be expressed in circulating human immune cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 307 VAVNLAEDTAHPKLVFSQEGRYVKntasasswpvfssawnyfagWRN-----PQKTafvERFQHLPCVLGKNVFTSGKHY 381
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVT--------------------WGEtrqdlPENP---ERFDSLPCVLGQEGFTSGRHY 58

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 382 WEVESRDSLEVAVGVCREDVM---GITdrskMSPDVGIWAIYWSAAGYWPLIGfPGTPTQQEPALHRVGVYLDRGTGNVS 458
Cdd:cd15819   59 WEVEVGDRTSWDLGVCRDNVMrkgRVT----LSPENGFWAIRLYGNEYWALTS-PETPLTLKEPPRRVGIFLDYEAGDVS 133

                        170       180
                 ....*....|....*....|....*...
gi 301601615 459 FYSAVDGVHLHTFSCSSVS-RLRPFFWL 485
Cdd:cd15819  134 FYNMTDGSHIYTFPQTAFSgPLRPFFRL 161

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7)-like, including TRIM7, TRIM10, TRIM15, TRIM26, TRIM39, TRIM41; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several tripartite motif-containing (TRIM) proteins, including TRIM7 (also referred to as glycogenin-interacting protein, RING finger protein 90 or RNF90), TRIM10, TRIM15, TRIM26, TRIM39 and TRIM41. TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. TRIM10 (also known as hematopoietic RING finger 1 (HERF1) or TRIM10/HERF1) plays a key role in definitive erythroid development; downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival. Antiviral activity of TRIM15 is dependent on the ability of its B-box to interact with the MLV Gag precursor protein; downregulation of TRIM15, along with TRIM11, enhances virus release suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. Tripartite motif-containing 26 (TRIM26) function is as yet unknown; however, since it is localized in the human histocompatibility complex (MHC) class I region, TRIM26 may play a role in immune response although studies show no association between TRIM26 polymorphisms and the risk of aspirin-exacerbated respiratory disease. TRIM39 is a MOAP-1 (Modulator of Apoptosis)-binding protein that stabilizes MOAP-1 through inhibition of its poly-ubiquitination process. TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 309 VNLAEDTAHPKLVFSQEGRYVKntasasswpvFSSAWNYFagWRNPqktafvERFQHLPCVLGKNVFTSGKHYWEVESRD 388
Cdd:cd12888    2 VTLDPDTAHPRLVLSEDRKSVR----------WGDTRQDL--PDNP------ERFDTWPCVLGCEGFTSGRHYWEVEVGD 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 389 SLEVAVGVCREDVmgitdRSK----MSPDVGIWAIYWSAAGYWPLiGFPGTPTQQEPALHRVGVYLDRGTGNVSFYSAVD 464
Cdd:cd12888   64 GGGWAVGVARESV-----RRKgeisFSPEEGIWAVGQWGGQYWAL-TSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADN 137

                        170       180
                 ....*....|....*....|....*....
gi 301601615 465 GVHLHTFSCSSVS--RLRPFFWLSPLASL 491
Cdd:cd12888  138 EAPIFTFPPASFAgeRIFPWFWVGKGSQL 166

PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM38 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3). The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 299 KEMLKRFQVAVNLAEDTAHPKLVFSQEGRYVKNtasasswpvfssawnyfagwRNPQK--TAFVERFQHLPCVLGKNVFT 376
Cdd:cd15815    5 KKMLRRHQVSVTLDPDTAHPELTLSKDQRQVTY--------------------GRCQEnlDASPKRFTVLPCVLGCEGFT 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 377 SGKHYWEVESRDSLEVAVGVCREDVMGITDRsKMSPDVGIWAIYWSA-AGYWPLIGfPGTPT--QQEPALhrVGVYLDRG 453
Cdd:cd15815   65 SGRHYFEVDVGEGTGWDVGVCLENVQRGFGM-KQEPEFGFWTIRLCEeDGYVALTS-PPTPLplREKPLV--VGVFLDYE 140

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 301601615 454 TGNVSFYSAVDGVHLHTFSCSSVS-RLRPFFWLSPLASLVIP 494
Cdd:cd15815  141 AGLVSFYNMTTGSHIFTFPKASFSdTLRPYFQVYQYSPLFLP 182

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 309 VNLAEDTAHPKLVFSQEGRYVKNTAsasswpvfssawnyfaGWRNPQktAFVERFQHLPCVLGKNVFTSGKHYWEVESRD 388
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGD----------------ISQHPP--EPPPRFFECWQVLGSQSFSSGRHYWEVDVQD 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 389 SLEVAVGVCREDVMGITDRSKMSPDVGIWAIYWSAAGYWPLIGFPGTPTQQEPaLHRVGVYLDRGTGNVSFYSAVDGV-H 467
Cdd:cd12874   63 DSSWYVGVTYKSLPRKGKMSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVTP-PRRLGVFLDCDGGSLSFYGVTDGVqL 141

                        170       180
                 ....*....|....*....|....*..
gi 301601615 468 LHTFSCSSVSRLRPFFWLSPLASLVIP 494
Cdd:cd12874  142 LYTFKAKFTEPLYPAFWLGEGSTLSIC 168

PRY/SPRY domain of tripartite motif-binding protein 11 (TRIM11), also known as RING finger protein 92 (RNF92); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM11, also known as RING finger protein 92 (RNF92) or BIA1. TRIM11 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It localizes to the nucleus and the cytoplasm; it is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 increases expression of dopamine beta-hydroxylase gene by interacting with the homeodomain transcription factor, PHOX2B, via the B30.2/SPRY domain, thus playing a potential role in the specification of noradrenergic (NA) neuron phenotype. It has also been shown that TRIM11 plays a critical role in the clearance of mutant PHOX2B, which causes congenital central hypoventilation syndrome, via the proteasome. TRIM11 binds a key component of the activator-mediated cofactor complex (ARC105), and destabilizes it, through the ubiquitin-proteasome system; ARC105 mediates chromatin-directed transcription activation and is a key regulatory factor for transforming growth factor beta (TGFbeta) signaling.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 309 VNLAEDTAHPKLVFSQEGRYVKNTASASSWPvfssawnyfagwRNPqktafvERFQHLPCVLGKNVFTSGKHYWEVESRD 388
Cdd:cd15811    2 VTLDPDTANPELVLSEDRRSVRRGDLRQALP------------DSP------ERFDPGPCVLGRERFTSGRHYWEVEVGD 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 389 SLEVAVGVCREDVmGITDRSKMSPDVGIWA-IYWSAAGYWPLIGFpgTPTQQEPalHRVGVYLDRGTGNVSFYSAVDGVH 467
Cdd:cd15811   64 RTSWALGVCKENV-NRKEKGELSAGNGFWIlVFLGNYYSSERRTF--APLRDPP--RRVGIFLDYEAGHLSFYSATDGSL 138

                        170       180
                 ....*....|....*....|....*...
gi 301601615 468 LHTFSCSSVS-RLRPFFwlSPLASLVIP 494
Cdd:cd15811  139 LFIFPETPFSgTLRPLF--SPLSSSPTP 164

RING finger, HC subclass, found in tripartite motif-containing proteins, TRIM7, TRIM11 and TRIM27, and similar proteins; TRIM7, TRIM11 and TRIM27, closely related tripartite motif-containing proteins, belong to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox2, and a coiled coil region, as well as a SPRY/B30.2 domain positioned C-terminal to the RBCC domain. TRIM7, also known as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90), is an E3 ubiquitin-protein ligase that mediates c-Jun/AP-1 activation by Ras signalling. Its phosphorylation and activation by MSK1 in response to direct activation by the Ras-Raf-MEK-ERK pathway can stimulate TRIM7 E3 ubiquitin ligase activity in mediating Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilization. Moreover, TRIM7 binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis. TRIM11, also known as protein BIA1, or RING finger protein 92 (RNF92), is an E3 ubiquitin-protein ligase involved in the development of the central nervous system. It is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. TRIM11 acts as a potential therapeutic target for congenital central hypoventilation syndrome (CCHS) by mediating the degradation of CCHS-associated polyalanine-expanded Phox2b. TRIM11 modulates the function of neurogenic transcription factor Pax6 through the ubiquitin-proteosome system, and thus plays an essential role for Pax6-dependent neurogenesis. It also binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105), humanin, a neuroprotective peptide against Alzheimer's disease-relevant insults, and further regulates ARC105 function in transforming growth factor beta (TGFbeta) signaling. Moreover, TRIM11 negatively regulates retinoic acid-inducible gene-I (RIG-I)-mediated interferon-beta (IFNbeta) production and antiviral activity by targeting TANK-binding kinase-1 (TBK1). It may contribute to the endogenous restriction of retroviruses in cells. It enhances N-tropic murine leukemia virus (N-MLV) entry by interfering with Ref1 restriction. It also suppresses the early steps of human immunodeficiency virus HIV-1 transduction, resulting in decreased reverse transcripts. TRIM27, also known as RING finger protein 76 (RNF76), RET finger protein (RFP), or zinc finger protein RFP, is a nuclear E3 ubiquitin-protein ligase that is highly expressed in testis and in various tumor cell lines. Expression of TRIM27 is associated with prognosis of colon and endometrial cancers. TRIM27 was first identified as a fusion partner of the RET receptor tyrosine kinase. It functions as a transcriptional repressor and associates with several proteins involved in transcriptional activity, such as enhancer of polycomb 1 (Epc1), a member of the Polycomb group proteins, and Mi-2beta, a main component of the nucleosome remodeling and deacetylase (NuRD) complex, and the cell cycle regulator retinoblastoma protein (RB1). It also interacts with HDAC1, leading to downregulation of thioredoxin binding protein 2 (TBP-2), which inhibits the function of thioredoxin. Moreover, TRIM27 mediates Pax7-induced ubiquitination of MyoD in skeletal muscle atrophy. In addition, it inhibits muscle differentiation by modulating serum response factor (SRF) and Epc1. TRIM27 promotes a non-canonical polyubiquitination of PTEN, a lipid phosphatase that catalyzes PtdIns(3,4,5)P3 (PIP3) to PtdIns(4,5)P2 (PIP2). It is an IKKepsilon-interacting protein that regulates IkappaB kinase (IKK) function and negatively regulates signaling involved in the antiviral response and inflammation. TRIM27 also forms a protein complex with MBD4 or MBD2 or MBD3, and thus plays an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis. It is a component of an estrogen receptor 1 (ESR1) regulatory complex that is involved in estrogen receptor-mediated transcription in MCF-7 cells.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 301601615   7 QEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPSAPAALRPN 64
Cdd:cd16594    3 QEELTCPICLDYFTDPVTLDCGHSFCRACIARCWEEPETSASCPQCRETCPQRNLRPN 60

PRY/SPRY domain in tripartite motif-containing protein 27 (TRIM27), also known as RING finger protein 76 (RNF76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM27, also known as RING finger protein 76 (RNF76) or RET finger protein (RFP). TRIM27 domain is composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in the spleen, thymus and in cells of the hematopoietic compartment. TRIM27 exhibits either nuclear or cytosolic localization depending on the cell type. TRIM27 negatively regulates nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated signaling by proteasomal degradation of NOD2, suggesting that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases such as Crohn's. High expression of TRIM27 is observed in several human cancers, including breast and endometrial cancer, where elevated TRIM27 expression predicts poor prognosis. Also, TRIM27 forms an oncogenic fusion protein with Ret proto-oncogene. It is involved in different stages of spermatogenesis and its significant expression in male germ cells and seminomas, suggests that TRIM27 may be associated with the regulation of testicular germ cell proliferation and histological-type of germ cell tumors. TRIM27 could also be a predictive marker for chemoresistance in ovarian cancer patients. In the neurotoxin model of Parkinson's disease (PD), deficiency of TRIM27 decreases apoptosis and protects dopaminergic neurons, making TRIM27 an effective potential target during the treatment of PD.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 307 VAVNLAEDTAHPKLVFSQEGRYVKNTASASSWPvfssawnyfagwRNPqktafvERFQHLPCVLGKNVFTSGKHYWEVES 386
Cdd:cd15814    2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLP------------DNP------ERFNLFPCVLGSPCFIAGRHYWEVEV 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 387 RDSLEVAVGVCREDVM---GITDrskmSPDVGIWAI-YWSAAGYWPLIGfPGTPTQQEPALHRVGVYLDRGTGNVSFYSA 462
Cdd:cd15814   64 GDKAKWTIGVCEDSVCrkgGVTS----APQNGFWAVsLWYGKEYWALTS-PMTALPLRTPLQRVGIFLDYDAGEVSFYNV 138

                        170       180       190
                 ....*....|....*....|....*....|....*....
gi 301601615 463 VDGVHLHTFSCSS-VSRLRPFFWLS-----PLASLVIPP 495
Cdd:cd15814  139 TERCHTFTFSHATfCGPVRPYFSLSysggkSAAPLIICP 177

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 303 KRFQVAVNLAEDTAHPKLVFSQEGRYVKntasasswpvFSSAWNyfagwRNPQKTafvERFQHLPCVLGKNVFTSGKHYW 382
Cdd:cd15813    5 QAHAVNVTLDPETAHPNLIFSDDLKSVR----------LGNKWD-----RLPDNP---ERFDSCIIVLGSPSFTSGRHYW 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 383 EVESRDSLEVAVGVCREDV--MGITDrskMSPDVGIWAIYWSAAGYWPLIGFPGTPTQ-QEPAlHRVGVYLDRGTGNVSF 459
Cdd:cd15813   67 EVEVGDKTGWILGVCKASVsrKGSMT---LSPENGYWVVMMTKRNEYQASTSPPTRLWlREPP-RRVGIFLDYEAGDISF 142

                        170       180
                 ....*....|....*....|....*....
gi 301601615 460 YSAVDGVHLHTF-SCSSVSRLRPFFwlSP 487
Cdd:cd15813  143 YNVTAKSHIYTFtSFSSSGPLQPIF--SP 169

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 313 EDTAHPKLVFSQEGRYVKNTASASSWPvfssawnyfagwRNPQktafveRFQHLPCVLGKNVFTSGKHYWEVESRDSLEV 392
Cdd:cd12905   10 PETAHPSLILSRDLTAVTESDEMQPYP------------RSPK------RFLQCVNVLASQGFQSGRHYWEVWVGSKTKW 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 393 AVGVCREDVmgitDRS---KMSPDVGIWAI-------YWSAAGywpligfPGTPTQQEPALHRVGVYLDRGTGNVSFYSA 462
Cdd:cd12905   72 DLGVASESV----DRQarvKLCPENGYWTLrlrngdeYWAGTQ-------PWTRLRVTSRPQRIGVFLDCEERKVSFYNA 140

                        170       180
                 ....*....|....*....|.
gi 301601615 463 VDGVHLHTFSCSSVSRLRPFF 483
Cdd:cd12905  141 DDMSLLYSFHQGPRGKVFPFF 161

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 309 VNLAEDTAHPKLVFSQEGRYVKNTASASSWPVfssawnyfagwrNPQktafveRFQHLPCVLGKNVFTSGKHYWEVE-SR 387
Cdd:cd15826    2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPD------------SPL------RFDGLPAVLGSPGFSSGRHRWQVEvQL 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 388 DSLE-VAVGVCREDVMGITDRSkMSPDVGIWAIYWSAAGYWPLIGfPGT--PTQQEPalHRVGVYLDRGTGNVSFYSAVD 464
Cdd:cd15826   64 GDGGgCTVGVAGESVRRKGEMG-LSAEDGVWAVILSHQQCWASTS-PGTdlPLSEIP--RRVGVALDYEAGTVTLTNAET 139

                        170       180
                 ....*....|....*....|.
gi 301601615 465 GVHLHTFSCSSVSRLRPFFWL 485
Cdd:cd15826  140 QEPIFTFTASFSGKVFPFFAV 160

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 298 MKEMLKRFQVAVNLAEDTAHPKLVFSQEGRYVKNTASASSWPvfssawnyfagwRNPqktafvERFQHLPCVLGKNVFTS 377
Cdd:cd15818    4 MKSILNPGLSLITLDPKTAHPNLILSEDLTCVWHGDTKQMLP------------DNP------ERFDSSVAVLGSEGFTS 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 378 GKHYWEVESRDSLEVAVGVCREDVM---GITdrskMSPDVGIWAIYWSAAGYWPLIGFPGTPTQQEPALHRVGVYLDRGT 454
Cdd:cd15818   66 GKHYWEVEVAKKTKWTLGVVRESINrkgNCP----LSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEG 141

                        170       180
                 ....*....|....*....|....*....
gi 301601615 455 GNVSFYSAVDGVHLHTFSCSSVSRLRPFF 483
Cdd:cd15818  142 GQVSFYNANTMSHIYTFSDTFTEKIYPYF 170

RING finger, HC subclass, found in tripartite motif-containing protein TRIM17 and similar proteins; 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 the mitotic spindle checkpoint, and negatively regulates cell proliferation. TRIM17 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 301601615   6 IQEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPG---------GGPFPCPECRHPSAPAALRPN 64
Cdd:cd16595    2 LQEEATCSICLDYFTDPVMTTCGHNFCRACIQLSWEKArgkkgrrkqKGSFPCPECREMSPQRNLRPN 69

RING finger, HC subclass, found in tripartite motif-containing protein 26 (TRIM26) and similar proteins; 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. TRIM26 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 301601615   6 IQEELTCPICLDYFQDPVSIECGHNFCRGCL---HRNWAPGGGPFpCPECRHPSAPAALRPNWAL 67
Cdd:cd16598    1 LEEEVTCSICLDYLRDPVTIDCGHNFCRSCItdyCPISGGHERPV-CPLCRKPFKKENIRPNWQL 64

RING finger, HC subclass, found in tripartite motif-containing protein TRIM65 and similar proteins; TRIM65 is an E3 ubiquitin-protein ligase that interacts with the innate immune receptor MDA5, enhancing its ability to stimulate interferon-beta signaling. It functions as a potential oncogenic protein that negatively regulates p53 through ubiquitination, providing insight into the development of novel approaches targeting TRIM65 for non-small cell lung carcinoma (NSCLC) treatment, and also overcoming chemotherapy resistance. Moreover, TRIM65 negatively regulates microRNA-driven suppression of mRNA translation by targeting TNRC6 proteins for ubiquitination and degradation. TRIM65 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 301601615   7 QEELTCPICLDYFQDPVSIECGHNFCRGCLHRNWA-PGGGPFPCPECRHP 55
Cdd:cd16609    1 EEELTCSICLGLYQDPVTLPCQHSFCRACIEDHWRqKDEGSFSCPECRAP 50

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 305 FQVAVNLAEDTAHPKLVFSQEGRYVKNTASASSWPVFSsawnyfagwrnpqktafvERFQHLPCVLGKNVFTSGKHYWEV 384
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENE------------------ERFDNYPMVLGAQRFNSGKHYWEV 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 301601615 385 ESRDSLEVAVGVCREDVmgitdRSK----MSPDVGIWAIyWSAAGYWPLIGFPGTPTQ-QEPALhRVGVYLDRGTGNVSF 459
Cdd:cd12900   63 DVTGKEAWDLGVCRDSV-----RRKgqflLSPENGFWTI-WLWNKKYEAGTSPQTTLHlQVPPC-QVGIFLDYEAGVVSF 135

                        170       180
                 ....*....|....*....|....*.
gi 301601615 460 YSAVD-GVHLHTFS-CSSVSRLRPFF 483
Cdd:cd12900  136 YNITDhGSLIYTFSeCAFTGPLRPFF 161

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 301601615   9 ELTCPICLDYFQDPVSIECGHNFCRGCLHRNWAPGGGPFPCPECRHPS 56
Cdd:cd16607    1 EASCPICLDYLKDPVTINCGHNFCRSCISMSWKDLQDTFPCPVCRFCC 48

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.

                         10        20        30
                 ....*....|....*....|....*....|....*....
gi 301601615  85 GLCGRHWEPLRLFCEDDQRPVCLVCRESQEHQTHAMAPI 123
Cdd:cd19760    1 GLCEKHQEPLKLFCEEDEALICVICRESRAHRAHTVVPI 39

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 301601615  85 GLCGRHWEPLRLFCEDDQRPVCLVCRESQEHQTHAMAPIDEA 126
Cdd:cd19762    1 GVCEKHQEPLKLFCKEDKRPICVVCDRSREHRHHTVLPVEEA 42

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 301601615  85 GLCGRHWEPLRLFCEDDQRPVCLVCRESQEHQTHAMAPIDEAFE 128
Cdd:cd19766    1 GLCGKHREPLKLFCKDHEALLCVVCERSREHWGHRVVPAEEAAQ 44