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 563127   314 SVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVEREGwsedeeegdeeeege 393
Cdd:cd15826   1 SVTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGD--------------- 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagyGDGyddwetdedeeslgdeeeeeeeeeeevlesCMVGVARDSVKRKGDLSLRPEDGVWALRLSSSGIWAN 473
Cdd:cd15826  66 ----------GGG------------------------------CTVGVAGESVRRKGEMGLSAEDGVWAVILSHQQCWAS 105

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 563127   474 TSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWLKWPGTRLLLR 538
Cdd:cd15826 106 TSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVWKKGSRLTLK 170

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 563127   100 KLCERHREKLHYYCEDDGKLLCVMCRESREHRPHTAVLM 138
Cdd:cd19765   1 TLCEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

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 563127   314 SVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVEREGwsedeeegdeeeege 393
Cdd:cd15826   1 SVTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGD--------------- 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagyGDGyddwetdedeeslgdeeeeeeeeeeevlesCMVGVARDSVKRKGDLSLRPEDGVWALRLSSSGIWAN 473
Cdd:cd15826  66 ----------GGG------------------------------CTVGVAGESVRRKGEMGLSAEDGVWAVILSHQQCWAS 105

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 563127   474 TSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWLKWPGTRLLLR 538
Cdd:cd15826 106 TSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVWKKGSRLTLK 170

B-box-type 2 zinc finger found in tripartite motif-containing proteins, TRIM10, TRIM15, TRIM26, TRIM31 and similar proteins; This family includes TRIM10, TRIM15, TRIM26 and TRIM31. TRIM10, also known as B30-RING finger protein (RFB30), RING finger protein 9 (RNF9), or hematopoietic RING finger 1 (HERF1), is a novel hematopoiesis-specific RING finger protein required for terminal differentiation of erythroid cells. TRIM15, also termed RING finger protein 93 (RNF93), or zinc finger protein 178 (ZNF178), or zinc finger protein B7 (ZNFB7), is a focal adhesion protein that regulates focal adhesion disassembly. It localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. TRIM15 can also associate with coronin 1B, cortactin, filamin binding LIM protein1, and vasodilator-stimulated phosphoprotein, which are involved in actin cytoskeleton dynamics. As an additional component of the integrin adhesome, it regulates focal adhesion turnover and cell migration. TRIM26, also known as acid finger protein (AFP), RING finger protein 95 (RNF95), or zinc finger protein 173 (ZNF173), is an E3 ubiquitin-protein ligase that negatively regulates interferon-beta production and antiviral response through polyubiquitination and degradation of nuclear transcription factor IRF3. It functions as an important regulator for RNA virus-triggered innate immune response by bridging TBK1 to NEMO (NF-kappaB essential modulator, also known as IKKgamma) and mediating TBK1 activation. It also acts as a novel tumor suppressor of hepatocellular carcinoma by regulating cancer cell proliferation, colony forming ability, migration, and invasion. TRIM31 is an E3 ubiquitin-protein ligase that primarily localizes to the cytoplasm, but is also associated with the mitochondria. It can negatively regulate cell proliferation and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis. TRIM31 is downregulated in non-small cell lung cancer and serves as a potential tumor suppressor. It interacts with p52 (Shc) and inhibits Src-induced anchorage-independent growth. TRIM10, TRIM15 and TRIM26 belong to the C-IV subclass of TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a RING finger, Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain. TRIM31 belongs to the C-V subclass of TRIM family of proteins. The type 2 B-box (Bbox2) zinc finger is characterized by a CHC3H2 zinc-binding consensus motif.

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 563127   100 KLCERHREKLHYYCEDDGKLLCVMCRESREHRPHTAVLM 138
Cdd:cd19765   1 TLCEEHGEKIHFFCEDDGKFLCVVCRESREHRTHTVSLL 39

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 563127     437 CMVGVARDSVKRKGDLSLRPEDGVWALRLSS-SGIWANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAEsQELIYTFT 515
Cdd:pfam00622  16 WRVGWATKSVPRKGERFLGDESGSWGYDGWTgKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTISFTKNG-KSLGYAFR 94

                          90
                  ....*....|....*..
gi 563127     516 -ATFTRRLVPFLWLKWP 531
Cdd:pfam00622  95 dVPFAGPLFPAVSLGAG 111

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 563127       16 CSICLD-YLRDPVTIDCGHVFCRSCTTdvRPISGSRPVCPLC 56
Cdd:smart00184   1 CPICLEeYLKDPVILPCGHTFCRSCIR--KWLESGNNTCPIC 40

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 563127       3 TSAP-LRSLEEEVTCSICLDYLRDPVTIDCGHVFCRSCttdVRPISGSRPVCPLCKKPFKKENIRPVWQLASLVE 76
Cdd:TIGR00599  15 TPIPsLYPLDTSLRCHICKDFFDVPVLTSCSHTFCSLC---IRRCLSNQPKCPLCRAEDQESKLRSNWLVSEIVE 86

B-box zinc finger;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 563127      97 QDAKLCERH-REKLHYYCEDDGKLLCVMCRESrEHRPHTAVLM 138
Cdd:pfam00643   1 SKERLCPEHeEEPLTLYCNDCQELLCEECSVG-EHRGHTVVPL 42

ATP-dependent Clp protease, ATP-binding subunit ClpA [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   173 DILAALKKLQDQRQYIVAEFEQGHQflrEREEHLLEQLAKLEQELTEGREKFKSR--GVGELARLALVISELEGKAQQPA 250
Cdd:COG0542 415 ELERRLEQLEIEKEALKKEQDEASF---ERLAELRDELAELEEELEALKARWEAEkeLIEEIQELKEELEQRYGKIPELE 491

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 563127   251 AELMQDTRDFLNRYPRKKFWVGKP-IARVVKKKTG---------EfSDKLLSLQRGLRE 299
Cdd:COG0542 492 KELAELEEELAELAPLLREEVTEEdIAEVVSRWTGipvgkllegE-REKLLNLEEELHE 549

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 563127   314 SVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVEREGwsedeeegdeeeege 393
Cdd:cd15826   1 SVTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQLGD--------------- 65

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagyGDGyddwetdedeeslgdeeeeeeeeeeevlesCMVGVARDSVKRKGDLSLRPEDGVWALRLSSSGIWAN 473
Cdd:cd15826  66 ----------GGG------------------------------CTVGVAGESVRRKGEMGLSAEDGVWAVILSHQQCWAS 105

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 563127   474 TSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWLKWPGTRLLLR 538
Cdd:cd15826 106 TSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFFAVWKKGSRLTLK 170

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 563127   315 VTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEV-EREGWSedeeegdeeeege 393
Cdd:cd13733   2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVgGKTDWD------------- 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRLSSSGI-WA 472
Cdd:cd13733  69 ---------------------------------------------LGVARESVNRKGKITLSPENGYWTVGLRNGNEyKA 103

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 563127   473 NTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWLKWP 531
Cdd:cd13733 104 LTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYFSPCLN 162

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 563127   313 VSVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVE-REGWSedeeegdeeee 391
Cdd:cd15819   2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGdRTSWD----------- 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   392 geeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRLSSSGIW 471
Cdd:cd15819  71 -----------------------------------------------LGVCRDNVMRKGRVTLSPENGFWAIRLYGNEYW 103

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 563127   472 ANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFT-ATFTRRLVPFLWLkWP 531
Cdd:cd15819 104 ALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPqTAFSGPLRPFFRL-WS 163

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 563127   314 SVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVERE-GWSedeeegdeeeeg 392
Cdd:cd15818  14 LITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKtKWT------------ 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   393 eeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRL-SSSGIW 471
Cdd:cd15818  82 ----------------------------------------------LGVVRESINRKGNCPLSPEDGFWLLRLrNQNELK 115

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 563127   472 ANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPF 525
Cdd:cd15818 116 ALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTEKIYPY 169

Ret finger protein-like (RFPL), includes RFP1, 2, 3, 4; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of RFPL protein family, which includes RFPL1, RFPL2, RFPL3 and RFPL4. In humans, RFPL transcripts can be detected at the onset of neurogenesis in differentiating human embryonic stem cells, and in the developing human neocortex. The human RFPL1, 2, 3 genes have a role in neocortex development. RFPL1 is a primate-specific target gene of Pax6, a key transcription factor for pancreas, eye and neocortex development; human RFPL1 decreases cell number through its RFPL-defining motif (RDM) and SPRY domains. The RFPL4 (also known as RFPL4A) gene encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells and interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   313 VSVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVER-EGWSedeeegdeeee 391
Cdd:cd15821   4 VDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTsTEWD----------- 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   392 geeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRLSSSGI- 470
Cdd:cd15821  73 -----------------------------------------------LGVCRESVNRQGPIELSPEHGFWTVSLRDGSVf 105

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 563127   471 WANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRR-LVPF 525
Cdd:cd15821 106 FASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEpLRPF 161

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 563127   286 FSDKLLSLQRGLREFQgkllrdleyktVSVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTW 365
Cdd:cd15829   3 FPPQYSALQKIIKKFR-----------VDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHS 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   366 GKVYWEVEVEREG-WsedeeegdeeeegeeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescMVGVARD 444
Cdd:cd15829  72 GRHFWEVEVGDKPeW----------------------------------------------------------AVGVCKD 93

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   445 SVKRKGDLSLRPEDGVWALRLSSSGIWANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVP 524
Cdd:cd15829  94 SLSTKARRPPSGQQGCWRIQLQGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLRP 173

                ....
gi 563127   525 FLWL 528
Cdd:cd15829 174 YFYV 177

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   315 VTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVEREgwsedeeegdeeeegee 394
Cdd:cd15816   2 VKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEK----------------- 64

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   395 eeeeeeAGYGdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWAL-RLSSSGIWAN 473
Cdd:cd15816  65 ------AEWG----------------------------------LGVCQDSAPRKGETTPSPENGVWAVwLLKGNEYMVL 104

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 563127   474 TSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWL 528
Cdd:cd15816 105 ASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFV 159

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 563127   310 YKTVSVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEV-EREGWsedeeegde 388
Cdd:cd15820   1 FQPADVILDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVgDRKEW--------- 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   389 eeegeeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescMVGVARDSVKRKGDLSLRPEDGVWALRLSSS 468
Cdd:cd15820  72 -------------------------------------------------YVGVCRENVERKLWVKMAPENGFWTIGLSDG 102

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 563127   469 GIW-ANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTAT-FTRRLVP-FLWLKWPGTRLLLRP 539
Cdd:cd15820 103 NDYqALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTsFSGPLYPvFRLLSWDPTALTICP 176

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; 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 TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). 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 563127   315 VTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPgVLGSKGFTWGKVYWEVEVEREGWsedeeegdeeeegee 394
Cdd:cd12891   1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHSQ-VLSTQSFSSGRHYWEVEVSESGG--------------- 64

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   395 eeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlesCMVGVARDSVKRKGDLS-LRPEDGVWALRLSSSGIWAN 473
Cdd:cd12891  65 ------------------------------------------WSVGVAYPSIERKGDESrIGRNDKSWCLEWQDKSFSAW 102

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 563127   474 TSPEAELFPALRPRRVGIALDYEGGTVTFTN-AESQELIYTFTATFTRRLVPFLWLKWPGT 533
Cdd:cd12891 103 HNNEETPLPSVSSRRLGVYLDYEAGRLSFYElSDPIRHLHTFTATFTEPLHPAFWVLEGGW 163

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 563127   313 VSVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEV-EREGWSedeeegdeeee 391
Cdd:cd12900   3 VHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVtGKEAWD----------- 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   392 geeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRLSSSGIW 471
Cdd:cd12900  72 -----------------------------------------------LGVCRDSVRRKGQFLLSPENGFWTIWLWNKKYE 104

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 563127   472 ANTSPEAELFPALRPRRVGIALDYEGGTVTFTN-AESQELIYTFT-ATFTRRLVPFL 526
Cdd:cd12900 105 AGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNiTDHGSLIYTFSeCAFTGPLRPFF 161

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 563127   314 SVTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEV-EREGWSedeeegdeeeeg 392
Cdd:cd12905   5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVgSKTKWD------------ 72

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   393 eeeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRL-SSSGIW 471
Cdd:cd12905  73 ----------------------------------------------LGVASESVDRQARVKLCPENGYWTLRLrNGDEYW 106

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....
gi 563127   472 ANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPF 525
Cdd:cd12905 107 AGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVFPF 160

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 563127   315 VTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVE-REGWSEDEEEGDEEEEGE 393
Cdd:cd13741   2 LTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGgRRGWAVGAARESTHHKEK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 EEEEEEEAGYGDGYDDWETDEdeeslgdeeeeeeeeeeevlescmvgvardsvKRKGDLSLRP--EDGVWALRLSSSGIW 471
Cdd:cd13741  82 VGSGGSSVSSGDASSSRHHHR--------------------------------RRRLHLPQQPllQREVWCVGTNGKRYQ 129

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   472 ANTSPEAELF-PALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATF-TRRLVPFLWLKWPGTRLLLRP 539
Cdd:cd13741 130 AQSSTEQTLLsPSEKPRRFGVYLDYEAGRLGFYNAETLAHVHTFSAAFlGERVFPFFRVLSKGTRIKLCP 199

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 563127   316 TLDPQSASGYLQLSEDWKCVTY--TSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEVEREGWsedeeegdeeeege 393
Cdd:cd13734   2 KLDPKTAHRKLRLSNDNLTVEYdpEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTS-------------- 67

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagygdgYDdwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRkgDLSLRPEDGVWALRLSSSGIWA- 472
Cdd:cd13734  68 -------------YR------------------------------VGVAYKSAPR--DEDLGKNSTSWCLSRDNNRYTAr 102

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 563127   473 -NTSPEAeLFPALRPRRVGIALDYEGGTVTFTNAESQELIYTFTATFTRRLVPFLWLkWPGT 533
Cdd:cd13734 103 hDGKVVD-LRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCPAFAV-WNGS 162

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 563127   315 VTLDPQSASGYLQLSEDWKCVTYTSLYKSAYLHPQQFDCEPGVLGSKGFTWGKVYWEVEV-EREGWSedeeegdeeeege 393
Cdd:cd15811   2 VTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVgDRTSWA------------- 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127   394 eeeeeeeagygdgyddwetdedeeslgdeeeeeeeeeeevlescmVGVARDSVKRKGDLSLRPEDGVWALRLSSSgiwAN 473
Cdd:cd15811  69 ---------------------------------------------LGVCKENVNRKEKGELSAGNGFWILVFLGN---YY 100

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 563127   474 TSPEAELFPaLR--PRRVGIALDYEGGTVTFTNAESQELIYTFTAT-FTRRLVPFL 526
Cdd:cd15811 101 SSERRTFAP-LRdpPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETpFSGTLRPLF 155

Domain in SPla and the RYanodine Receptor; Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 563127      437 CMVGVARDSVKRKGDLSLRPEDGVWALRLSS-SGIWANTSPEAELFPALRPRRVGIALDYEGGTVTFTNAESQELIYTF- 514
Cdd:smart00449  16 WRVGVATKSVPRGYFALLGEDKGSWGYDGDGgKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTISFYKNGKYLHGLAFf 95