RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 133505096  29 FKEELLCAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQTTPSCPVCKERAVPGELRTNHTLNNLVE 94
Cdd:cd16599    1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

Synaptonemal complex protein 1 (SCP-1); Synaptonemal complex protein 1 (SCP-1) is the major component of the transverse filaments of the synaptonemal complex. Synaptonemal complexes are structures that are formed between homologous chromosomes during meiotic prophase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096  144 QEHRVQpikdtAQDFRAKcknMEHVLREKAKSFWALRRTYEAIAKHNEVQTTWLEGRIRDEFDKLRD--FLRVEEQATVD 221
Cdd:pfam05483 200 EELRVQ-----AENARLE---MHFKLKEDHEKIQHLEEEYKKEINDKEKQVSLLLIQITEKENKMKDltFLLEESRDKAN 271

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 133505096  222 AMKEESRkkhlLAEEKMKQLAEQTEALAREIERLQMEMK 260
Cdd:pfam05483 272 QLEEKTK----LQDENLKELIEKKDHLTKELEDIKMSLQ 306

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 133505096  29 FKEELLCAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQTTPSCPVCKERAVPGELRTNHTLNNLVE 94
Cdd:cd16599    1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

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 133505096  370 HSWEVDVGGL--PSWRVGVVRVqahaqaqaqaDVGGEGHSHSCyhdTRSGFWYLCRTQGVDGDHcmTSDTATAPLVQAMP 447
Cdd:pfam00622   2 HYFEVEIFGQdgGGWRVGWATK----------SVPRKGERFLG---DESGSWGYDGWTGKKYWA--STSPLTGLPLFEPG 66

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 133505096  448 RRLRVELECEEGELSFYDSErHCHLYTFH--AHFGEVRPYFYLGASRG 493
Cdd:pfam00622  67 DVIGCFLDYEAGTISFTKNG-KSLGYAFRdvPFAGPLFPAVSLGAGEG 113

Ring finger; E3 ubiquitin-protein ligase activity is intrinsic to the RING domain of c-Cbl and is likely to be a general function of this domain; Various RING fingers exhibit binding activity towards E2 ubiquitin-conjugating enzymes (Ubc' s)

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 133505096    35 CAVCYDPF-RDAVTLRCGHNFCRRCVSGCWEvQTTPSCPVC 74
Cdd:smart00184   1 CPICLEEYlKDPVILPCGHTFCRSCIRKWLE-SGNNTCPIC 40

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|..
gi 133505096   35 CAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQ--TTPSCPVC 74
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPdgESLLCPQC 42

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 133505096   110 RSPRPCRAHR-APLTLFCVEDKELLCCACQAdARHQEHRVQPI 151
Cdd:smart00336   1 QRAPKCDSHGdEPAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 133505096  112 PRPCRAH-RAPLTLFCVEDKELLCCACQADArHQEHRVQPI 151
Cdd:pfam00643   3 ERLCPEHeEEPLTLYCNDCQELLCEECSVGE-HRGHTVVPL 42

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 133505096 317 PFSLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRVqahaqa 395
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARE------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 396 qaqaDVGGEGhshSCYHDTRSGFWYLCRTqgvDGDHCMTSDTATAPLVQAM-PRRLRVELECEEGELSFYDSERHCHLYT 474
Cdd:cd13733   75 ----SVNRKG---KITLSPENGYWTVGLR---NGNEYKALTSPSTPLSLREkPQKVGVFLDYEEGQVSFYNVDDGSHIYT 144

                        170       180       190
                 ....*....|....*....|....*....|
gi 133505096 475 FHAHF-GEVRPYFYLGASRGDGPPEPLRIC 503
Cdd:cd13733  145 FTDCFtEKLYPYFSPCLNDGGKNSAPLIIC 174

PRY/SPRY domain in tripartite motif-binding protein 39 (TRIM39) and TRIM39-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of pyrin, several tripartite motif-containing proteins (TRIMs), including E3 ubiquitin-protein ligase (TRIM21), RET finger protein (RFP)/tripartite motif protein 27 (TRIM27), as well as butyrophilin (Btns) and butyrophilin-like (Btnl) family members, with the exception of Btnl2. Btn and Btnl family members are novel regulators of immune responses, with many of the genes located within the MHC. They are implicated in T-cell inhibition and modulation of epithelial cell-T cell interactions. TRIM21 (also known as RO52, SSA1 or RNF81) is a major autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Sjorgen's syndrome. TRIM27 (also known as Ret finger protein, RFP or RNF76) negatively regulates CD4 T-cells by ubiquitinating and inhibiting the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta), a kinase critical for KCa3.1 channel activation. The PRY/SPRY domain of Pyrin, which is mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 320 LDPNTAAGWLKVADDLTSVInHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRvqahaqaqa 397
Cdd:cd13745    7 LDPDTAHPNLVLSEDRKSVR-HGDTRQdlPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCR--------- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 398 qADVGGEGHSHScyhDTRSGFWYLCrtqgVDGDHCMTSDTATAPL-VQAMPRRLRVELECEEGELSFYDSERHCHLYTFH 476
Cdd:cd13745   77 -ESVSRKGEVTL---SPENGYWTVW----LRDGKYEALTSPPTPLpVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFT 148

                        170       180
                 ....*....|....*....|....*....
gi 133505096 477 AHF-GEVRPYFYLGASRGDGPPEPLRICH 504
Cdd:cd13745  149 DTFsGTLRPYFYPGLNAGGKNAAPLIICP 177

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 320 LDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRVQAHAQAQAQ 398
Cdd:cd15829   23 LDPETAHPNLLVSEDKKCVTFTKKKQRVpDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTKARRP 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 399 ADVggeghshscyhdtRSGFWylcRTQGVDGDhCMTSDTATAPLV-QAMPRRLRVELECEEGELSFYDSERHCHLYTFHA 477
Cdd:cd15829  103 PSG-------------QQGCW---RIQLQGGD-YDAPGAVPPPLLlEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTD 165

                        170       180
                 ....*....|....*....|....*..
gi 133505096 478 HFGEV-RPYFYLGASrgdgpPEPLRIC 503
Cdd:cd15829  166 TFSGPlRPYFYVGPD-----SKPLRIC 187

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 133505096 317 PFSLDPNTAAGWLKVADDLTSVINHGY-RVQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRvqahaqa 395
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEmQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVAS------- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 396 qaqADVGGEGHSHSCyhdTRSGFWYLcRTQgvDGDHCMTSDTATAPL-VQAMPRRLRVELECEEGELSFYDSERHCHLYT 474
Cdd:cd12905   78 ---ESVDRQARVKLC---PENGYWTL-RLR--NGDEYWAGTQPWTRLrVTSRPQRIGVFLDCEERKVSFYNADDMSLLYS 148

                        170       180       190
                 ....*....|....*....|....*....|
gi 133505096 475 FH-AHFGEVRPYFYLGASRGDGPPEPLRIC 503
Cdd:cd12905  149 FHqGPRGKVFPFFSTCFSDDGQNAEPMRLL 178

PRY/SPRY domain of tripartite motif-binding protein 60 and 75 (TRIM60 and TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60 and TRIM75, both composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM60 domain is also known as RING finger protein 33 (RNF33) or 129 (RNF129). Based on its expression profile, RNF33 likely plays an important role in the spermatogenesis process, the development of the pre-implantation embryo, and in testicular functions; Rnf33 is temporally transcribed in the unfertilized egg and the pre-implantation embryo, and is permanently silenced before the blastocyst stage. Mice experiments have shown that RNF33 associates with the cytoplasmic motor proteins, kinesin-2 family members 3A (KIF3A) and 3B (KIF3B), suggesting possible contribution to cargo movement along the microtubule in the expressed sites. TRIM75, also known as Gm794, has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 320 LDPNTAAGWLKVADDLTSVInhgYRVQVEN----PERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRVQAHAQA 395
Cdd:cd15817    4 LDPETAHPNLIVSEDRKAVR---YRRMKPNcpydPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 396 QAQADVGGeghshscyhdtrsGFWYLcrTQGVDGDHcmTSDTATAPLV-QAMPRRLRVELECEEGELSFYDSERHCHLYT 474
Cdd:cd15817   81 QDPPSPLG-------------GCWQI--GRYMSGYV--ASGPKTTQLLpVVKPSRIGIFLDYELGEVSFYNMNDRSHLYT 143

                        170       180       190
                 ....*....|....*....|....*....|
gi 133505096 475 FHAHF-GEVRPYFYLGASRgdgppEPLRIC 503
Cdd:cd15817  144 FTDTFtGKLIPYFYVGPDS-----EPLTIC 168

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 133505096 315 SVPFSLDPNTAAGWLKVADDLTSViNHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRvqah 392
Cdd:cd15814    1 SVDVTLDPDTAYPSLILSDNLRQV-RYSYLQQdlPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCE---- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 393 aqaqaqADVGGEGHSHSCyhdTRSGFWYLCRTQGVDGdHCMTSDTATAPLVQAMpRRLRVELECEEGELSFYDSERHCHL 472
Cdd:cd15814   76 ------DSVCRKGGVTSA---PQNGFWAVSLWYGKEY-WALTSPMTALPLRTPL-QRVGIFLDYDAGEVSFYNVTERCHT 144

                        170       180       190
                 ....*....|....*....|....*....|...
gi 133505096 473 YTF-HAHF-GEVRPYFYLGASRGDGPPePLRIC 503
Cdd:cd15814  145 FTFsHATFcGPVRPYFSLSYSGGKSAA-PLIIC 176

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 133505096 316 VPFSLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRvqahaq 394
Cdd:cd12900    3 VHITLDPDTANPWLILSKDRRQVRLGDTHQNVpENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCR------ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 395 aqaqADVGGEGHSHScyhDTRSGFWYLCRTQGVdgdhcmtSDTATAPL----VQAMPRRLRVELECEEGELSFYDSERHC 470
Cdd:cd12900   77 ----DSVRRKGQFLL---SPENGFWTIWLWNKK-------YEAGTSPQttlhLQVPPCQVGIFLDYEAGVVSFYNITDHG 142

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 133505096 471 HL-YTFH--AHFGEVRPYFYLGASRGDGPPEPLRICHL 505
Cdd:cd12900  143 SLiYTFSecAFTGPLRPFFNPGFNDSGGNAAPLTLCPL 180

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 133505096 319 SLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRVQAHAQAQA 397
Cdd:cd15811    3 TLDPDTANPELVLSEDRRSVRRGDLRQALpDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKEKG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 398 QADVGgeghshscyhdtrSGFWYLCRTqgvdGDHCMTSDTATAPLVQAmPRRLRVELECEEGELSFYDSERHCHLYTFH- 476
Cdd:cd15811   83 ELSAG-------------NGFWILVFL----GNYYSSERRTFAPLRDP-PRRVGIFLDYEAGHLSFYSATDGSLLFIFPe 144

                        170       180
                 ....*....|....*....|....*...
gi 133505096 477 -AHFGEVRPYFylgaSRGDGPPEPLRIC 503
Cdd:cd15811  145 tPFSGTLRPLF----SPLSSSPTPMTIC 168

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. 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 133505096 318 FSLDPNTAAGWLKVADDLTSVINHGYR---VQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRvqahAQ 394
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYDPEGskdQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAY----KS 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 395 AQAQADVGgeghshscyHDTRSgfWYLCRTQGV-----DGDHCMtsdtataPLVQAMPRRLRVELECEEGELSFYDSERH 469
Cdd:cd13734   77 APRDEDLG---------KNSTS--WCLSRDNNRytarhDGKVVD-------LRVTGHPARIGVLLDYDNGTLSFYDAESK 138

                        170       180
                 ....*....|....*....|.
gi 133505096 470 CHLYTFHAHFGE-VRPYFYLG 489
Cdd:cd13734  139 QHLYTFHVDFEGpVCPAFAVW 159

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 133505096 315 SVPFSLDPNTAAGWLKVADDLTSV-INHGYRVQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPSWRVGVVRVqaha 393
Cdd:cd15813    8 AVNVTLDPETAHPNLIFSDDLKSVrLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKA---- 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 394 qaqaqaDVGGEGhshSCYHDTRSGFWYLCRTQGvdGDHCMTSDTATAPLVQAMPRRLRVELECEEGELSFYDSERHCHLY 473
Cdd:cd15813   84 ------SVSRKG---SMTLSPENGYWVVMMTKR--NEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIY 152

                        170       180       190
                 ....*....|....*....|....*....|..
gi 133505096 474 TFHAHF--GEVRPYFYLGASRGDGPPEPLRIC 503
Cdd:cd15813  153 TFTSFSssGPLQPIFSPGTHDGGKNMDPLTIC 184

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 133505096 319 SLDPNTAAGWLKVADDLTSVINHG-YRVQVENPERFSSAPCLLGSQVFSKGSHSWEVDV--GGLPSWRVGVVRVQAHAQa 395
Cdd:cd15826    3 TLDPQTASGSLVLSEDRKSVRYTRqKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 396 qaqadvGGEGHShscyhdTRSGFWYLCRTQgvDGDHCMTSDTATAPLVQaMPRRLRVELECEEGELSFYDSERHCHLYTF 475
Cdd:cd15826   82 ------GEMGLS------AEDGVWAVILSH--QQCWASTSPGTDLPLSE-IPRRVGVALDYEAGTVTLTNAETQEPIFTF 146

                        170
                 ....*....|....
gi 133505096 476 HAHF-GEVRPYFYL 488
Cdd:cd15826  147 TASFsGKVFPFFAV 160

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. 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. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 304 RVWKKMLGSVESVpfSLDPNTAAGWLKVADDLTSViNHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPS 381
Cdd:cd13743    2 RLHRKVLPAPELL--KLDPLTAHPMLELSKGNTVV-ECGLLAQrlPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 382 WRVGVVRvqahaqaqaqadvGGEGHSHSCYHDTRSGFWYLCRTQGVDGDhCMTSDTATAPLvQAMPRRLRVELECEEGEL 461
Cdd:cd13743   79 WRLGLIK-------------GTTSRKGKLNKSPENGVWLIGLKEGRVYE-AFANPRVPLPL-STRPQRIGVFLDYEKGEL 143

                        170       180
                 ....*....|....*....|....*....
gi 133505096 462 SFYDSERHCHL---YTFHAHF-GEVRPYF 486
Cdd:cd13743  144 TFYNADSPDELvpiYTFQAEFqGKLYPLL 172

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or MG53) 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. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 304 RVWKKMLGSVESVPFslDPNTAAGWLKVADDLTSV--INHGYRVQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPS 381
Cdd:cd13742    2 KMFRALMPALENLTF--DPDTAHPYLVVSSDGKRVecADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133505096 382 WRVGVVrvqahaqaqaQADVGGEGHSHSCyhdTRSGFWYL-CRtqgvDGDHCMTSDTATAPLV---QAMPRRLRVELECE 457
Cdd:cd13742   80 WALGVI----------SAEAGRKGRLHAL---PSNGFWLLgCK----EGKVYEAHVEHKEPRAlrvEGRPTRIGVYLSFS 142

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|
gi 133505096 458 EGELSFYDS---ERHCHLYTFHAHF-GEVRPYFYLGASRGDGPPEPLRIC 503
Cdd:cd13742  143 DGVLSFYDAsdeDNLVQLFAFHERFpGPLYPFFDVCWHDKGKNSQPLKIF 192

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 133505096  28 SFKEELLCAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQ--TTPSCPVCKE--RAVPgELRTNHTLNNLVE 94
Cdd:cd16597    1 DLEEELTCSICLELFKDPVTLPCGHNFCGVCIEKTWDSQhgSEYSCPQCRAtfPRRP-ELHKNTVLRNIVE 70