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 133506656  30 FKEELLCAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQTTPSCPVCKERAVPGELRTNHTLNNLVE 95
Cdd:cd16599    1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

Domain of unknown function (DUF4200); This family is found in eukaryotes. It is a coiled-coil domain of unknwon function.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 133506656  201 RIRDEFDKLRDFLRVEEQATLDAMK--EESRKKHLQAEEKMKQLAEQTEALAREIERLQ 257
Cdd:pfam13863  42 ELKEDLIKFDKFLKENDAKRRRALKkaEEETKLKKEKEKEIKKLTAQIEELKSEISKLE 100

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 133506656  30 FKEELLCAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQTTPSCPVCKERAVPGELRTNHTLNNLVE 95
Cdd:cd16599    1 FKEELLCPICYEPFREAVTLRCGHNFCKGCVSRSWERQPRAPCPVCKEASSSDDLRTNHTLNNLVE 66

SPRY-associated domain; PRY is a 50-60 amino acids domain associated with SPRY domains, adjacent to its N-terminal. PRY and SPRY domains are structurally very similar and consist of a beta sandwich fold. Distant homologs are domains in butyrophilin/marenostrin/pyrin, evolutionarily more ancient than SPRY/B30.2 counterpart.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 133506656  319 FSLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVF 366
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDERQNVpDNPERFDSWPCVLGSEGF 49

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 133506656    36 CAVCYDPF-RDAVTLRCGHNFCRRCVSGCWEvQTTPSCPVC 75
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 133506656   36 CAVCYDPFRDAVTLRCGHNFCRRCVSGCWEVQ--TTPSCPVC 75
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEPdgESLLCPQC 42

B-Box-type zinc finger;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 133506656   111 RSPRPCRAHR-APLTLFCLEDKELLCCACQAdARHQEHRVQPI 152
Cdd:smart00336   1 QRAPKCDSHGdEPAEFFCEECGALLCRTCDE-AEHRGHTVVLL 42

B-Box C-terminal domain; Coiled coil region C-terminal to (some) B-Box domains

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656   199 EGRIRDEFDKLRDFLRVEEQ---ATLDAMKEESRKKHLQAEEKMKQLAEQTEALAREIERLqmeMKEDDMT-FLMKHKSR 274
Cdd:smart00502  41 EAQIKAAFDELRNALNKRKKqllEDLEEQKENKLKVLEQQLESLTQKQEKLSHAINFTEEA---LNSGDPTeLLLSKKLI 117

                   ....
gi 133506656   275 KRRL 278
Cdd:smart00502 118 IERL 121

Uncharacterized conserved protein, contains a C-terminal ATPase domain [Function unknown];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656  141 DARHQEHRVQPIKDTAQDFRAKCKNMEHVLREKAKA-FWALRRTYEAIAKhnevqttwLEGRIRDEFDKLRdflrvEEQA 219
Cdd:COG4913   246 DAREQIELLEPIRELAERYAAARERLAELEYLRAALrLWFAQRRLELLEA--------ELEELRAELARLE-----AELE 312

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 133506656  220 TLDAMKEESRKKHLQAEEKMKQL-AEQTEALAREIERLQMEMKE 262
Cdd:COG4913   313 RLEARLDALREELDELEAQIRGNgGDRLEQLEREIERLERELEE 356

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 166 MEHVLREKAKAFWALRRTYEAIAKHNEVQTTwlegrIRDEFDKLRDFLRvEEQATLDAMKEESRKKHLQAEEKMKQLAEQ 245
Cdd:COG4942  141 LKYLAPARREQAEELRADLAELAALRAELEA-----ERAELEALLAELE-EERAALEALKAERQKLLARLEKELAELAAE 214

                         90
                 ....*....|....*..
gi 133506656 246 TEALAREIERLQMEMKE 262
Cdd:COG4942  215 LAELQQEAEELEALIAR 231

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 133506656 318 PFSLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRVqahaqa 396
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARE------ 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 397 qaqaDVGGEGhshSCYHDTRSGFWYLCRTqgvDGDHCMTSDTATAPLVQAM-PRRLRVELECEEGELSFYDSERHCHLYT 475
Cdd:cd13733   75 ----SVNRKG---KITLSPENGYWTVGLR---NGNEYKALTSPSTPLSLREkPQKVGVFLDYEEGQVSFYNVDDGSHIYT 144

                        170       180       190
                 ....*....|....*....|....*....|
gi 133506656 476 FHAHF-GEVRPYFYLGASRGDGPPEPLRIC 504
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 133506656 321 LDPNTAAGWLKVADDLTSVInHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqahaqaqa 398
Cdd:cd13745    7 LDPDTAHPNLVLSEDRKSVR-HGDTRQdlPDNPERFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGVCR--------- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 399 qADVGGEGHSHScyhDTRSGFWYLCrtqgVDGDHCMTSDTATAPL-VQAMPRRLRVELECEEGELSFYDSERHCHLYTFH 477
Cdd:cd13745   77 -ESVSRKGEVTL---SPENGYWTVW----LRDGKYEALTSPPTPLpVSVRPSRVGIFLDYEAGEVSFYNVTDRSHLFTFT 148

                        170       180
                 ....*....|....*....|....*....
gi 133506656 478 AHF-GEVRPYFYLGASRGDGPPEPLRICH 505
Cdd:cd13745  149 DTFsGTLRPYFYPGLNAGGKNAAPLIICP 177

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 133506656 320 SLDPNTAAGWLKVADDLTSViNHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqahaqaq 397
Cdd:cd12888    3 TLDPDTAHPRLVLSEDRKSV-RWGDTRQdlPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVAR-------- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 398 aqADVGGEGHSHscyHDTRSGFWYLcrtqGVDGDHC--MTSDTATAPLVQAmPRRLRVELECEEGELSFYDSERHCHLYT 475
Cdd:cd12888   74 --ESVRRKGEIS---FSPEEGIWAV----GQWGGQYwaLTSPETPLPLSEV-PRRIRVYLDYEGGQVAFFDADNEAPIFT 143

                        170       180       190
                 ....*....|....*....|....*....|..
gi 133506656 476 FHAHF--GE-VRPYFYLGASRgdgppePLRIC 504
Cdd:cd12888  144 FPPASfaGErIFPWFWVGKGS------QLKLC 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 133506656 318 PFSLDPNTAAGWLKVADDLTSVINHGY-RVQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqahaqa 396
Cdd:cd12905    5 PLTFDPETAHPSLILSRDLTAVTESDEmQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVAS------- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 397 qaqADVGGEGHSHSCyhdTRSGFWYLcRTQgvDGDHCMTSDTATAPL-VQAMPRRLRVELECEEGELSFYDSERHCHLYT 475
Cdd:cd12905   78 ---ESVDRQARVKLC---PENGYWTL-RLR--NGDEYWAGTQPWTRLrVTSRPQRIGVFLDCEERKVSFYNADDMSLLYS 148

                        170       180       190
                 ....*....|....*....|....*....|
gi 133506656 476 FH-AHFGEVRPYFYLGASRGDGPPEPLRIC 504
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 133506656 321 LDPNTAAGWLKVADDLTSVInhgYRVQVEN----PERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRVQAHAQA 396
Cdd:cd15817    4 LDPETAHPNLIVSEDRKAVR---YRRMKPNcpydPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 397 QAQADVGGeghshscyhdtrsGFWYLcrTQGVDGDHcmTSDTATAPLV-QAMPRRLRVELECEEGELSFYDSERHCHLYT 475
Cdd:cd15817   81 QDPPSPLG-------------GCWQI--GRYMSGYV--ASGPKTTQLLpVVKPSRIGIFLDYELGEVSFYNMNDRSHLYT 143

                        170       180       190
                 ....*....|....*....|....*....|
gi 133506656 476 FHAHF-GEVRPYFYLGASRgdgppEPLRIC 504
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 133506656 316 SVPFSLDPNTAAGWLKVADDLTSViNHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqah 393
Cdd:cd15814    1 SVDVTLDPDTAYPSLILSDNLRQV-RYSYLQQdlPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCE---- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 394 aqaqaqADVGGEGHSHSCyhdTRSGFWYLCRTQGVDGdHCMTSDTATAPLVQAMpRRLRVELECEEGELSFYDSERHCHL 473
Cdd:cd15814   76 ------DSVCRKGGVTSA---PQNGFWAVSLWYGKEY-WALTSPMTALPLRTPL-QRVGIFLDYDAGEVSFYNVTERCHT 144

                        170       180       190
                 ....*....|....*....|....*....|...
gi 133506656 474 YTF-HAHF-GEVRPYFYLGASRGDGPPePLRIC 504
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 133506656 317 VPFSLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqahaq 395
Cdd:cd12900    3 VHITLDPDTANPWLILSKDRRQVRLGDTHQNVpENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCR------ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 396 aqaqADVGGEGHSHScyhDTRSGFWYLCRTQGVdgdhcmtSDTATAPL----VQAMPRRLRVELECEEGELSFYDSERHC 471
Cdd:cd12900   77 ----DSVRRKGQFLL---SPENGFWTIWLWNKK-------YEAGTSPQttlhLQVPPCQVGIFLDYEAGVVSFYNITDHG 142

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 133506656 472 HL-YTFH--AHFGEVRPYFYLGASRGDGPPEPLRICHL 506
Cdd:cd12900  143 SLiYTFSecAFTGPLRPFFNPGFNDSGGNAAPLTLCPL 180

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); 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 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 320 SLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVR--VQAHAQA 396
Cdd:cd13741    3 TLDPDTAHPALLLSPDRRGVRLAERRQEVpEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAAResTHHKEKV 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 397 QAQADVGGEGHSHSCYHDTRSGFWYLCRTQ---------GVDGD--HCMTSDTATAPLVQAMPRRLRVELECEEGELSFY 465
Cdd:cd13741   83 GSGGSSVSSGDASSSRHHHRRRRLHLPQQPllqrevwcvGTNGKryQAQSSTEQTLLSPSEKPRRFGVYLDYEAGRLGFY 162

                        170       180
                 ....*....|....*....|....
gi 133506656 466 DSERHCHLYTFHAHF-GE-VRPYF 487
Cdd:cd13741  163 NAETLAHVHTFSAAFlGErVFPFF 186

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 133506656 320 SLDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRVQAHAQAQA 398
Cdd:cd15811    3 TLDPDTANPELVLSEDRRSVRRGDLRQALpDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKEKG 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 399 QADVGgeghshscyhdtrSGFWYLCRTqgvdGDHCMTSDTATAPLVQAmPRRLRVELECEEGELSFYDSERHCHLYTFH- 477
Cdd:cd15811   83 ELSAG-------------NGFWILVFL----GNYYSSERRTFAPLRDP-PRRVGIFLDYEAGHLSFYSATDGSLLFIFPe 144

                        170       180
                 ....*....|....*....|....*...
gi 133506656 478 -AHFGEVRPYFylgaSRGDGPPEPLRIC 504
Cdd:cd15811  145 tPFSGTLRPLF----SPLSSSPTPMTIC 168

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 321 LDPNTAAGWLKVADDLTSVINHGYRVQV-ENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPTWRVGVVRvqahaqaqaq 399
Cdd:cd15820    8 LDPDTANPILLISEDQRSLQWADEPQNLpDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCR---------- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 400 ADVGGEGHshsCYHDTRSGFWYLCRTQGvdGDHCMTSDTATAPLVQAMPRRLRVELECEEGELSFYDSERHCHLYTF-HA 478
Cdd:cd15820   78 ENVERKLW---VKMAPENGFWTIGLSDG--NDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFpHT 152

                        170       180
                 ....*....|....*....|....*..
gi 133506656 479 HF-GEVRPYFYLGASRgdgpPEPLRIC 504
Cdd:cd15820  153 SFsGPLYPVFRLLSWD----PTALTIC 175

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 133506656 320 SLDPNTAAGWLKVADDLTSVINHG-YRVQVENPERFSSAPCLLGSQVFSKGSHSWEVDV--GGLPTWRVGVVRVQAHAQa 396
Cdd:cd15826    3 TLDPQTASGSLVLSEDRKSVRYTRqKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK- 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 397 qaqadvGGEGHShscyhdTRSGFWYLCRTQgvDGDHCMTSDTATAPLVQaMPRRLRVELECEEGELSFYDSERHCHLYTF 476
Cdd:cd15826   82 ------GEMGLS------AEDGVWAVILSH--QQCWASTSPGTDLPLSE-IPRRVGVALDYEAGTVTLTNAETQEPIFTF 146

                        170
                 ....*....|....
gi 133506656 477 HAHF-GEVRPYFYL 489
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 133506656 305 RVWKKMLGSVESVpfSLDPNTAAGWLKVADDLTSViNHGYRVQ--VENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPT 382
Cdd:cd13743    2 RLHRKVLPAPELL--KLDPLTAHPMLELSKGNTVV-ECGLLAQrlPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 383 WRVGVVRvqahaqaqaqadvGGEGHSHSCYHDTRSGFWYLCRTQGVDGDhCMTSDTATAPLvQAMPRRLRVELECEEGEL 462
Cdd:cd13743   79 WRLGLIK-------------GTTSRKGKLNKSPENGVWLIGLKEGRVYE-AFANPRVPLPL-STRPQRIGVFLDYEKGEL 143

                        170       180
                 ....*....|....*....|....*....
gi 133506656 463 SFYDSERHCHL---YTFHAHF-GEVRPYF 487
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 133506656 305 RVWKKMLGSVESVPFslDPNTAAGWLKVADDLTSV--INHGYRVQVENPERFSSAPCLLGSQVFSKGSHSWEVDVGGLPT 382
Cdd:cd13742    2 KMFRALMPALENLTF--DPDTAHPYLVVSSDGKRVecADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPR 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 133506656 383 WRVGVVrvqahaqaqaQADVGGEGHSHSCyhdTRSGFWYL-CRtqgvDGDHCMTSDTATAPLV---QAMPRRLRVELECE 458
Cdd:cd13742   80 WALGVI----------SAEAGRKGRLHAL---PSNGFWLLgCK----EGKVYEAHVEHKEPRAlrvEGRPTRIGVYLSFS 142