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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 477
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789917 478 FSPCLPNEGTNTDPLIIC 495
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917  20 LTCFICLDYFSSPVTTECGHSFCLMCLLKSWEEHNtplSCPECWRTLGAPHFQANERLGRLANIGRQLRSQVLQSedeqs 99
Cdd:TIGR00599  27 LRCHICKDFFDVPVLTSCSHTFCSLCIRRCLSNQP---KCPLCRAEDQESKLRSNWLVSEIVESFKNLRPSLLEF----- 98

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039789917 100 icGRMPGPSWVFSDDEQSvinVSPPSQGTNKACFSSEAEEQHKEKLQDIINILRKKKKEVQA 161
Cdd:TIGR00599  99 --LRIPKTTPVENPDLAG---PENSSKIELIEESESDGVDAEDEDLQRSATSSRALAARSTA 155

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 477
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789917 478 FSPCLPNEGTNTDPLIIC 495
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

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 1039789917 321 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIF 369
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDERQNVPDNPERFDSWPCVLGSEGF 49

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 1039789917  22 CFICLDYFSSPVTTECGHSFCLMCLLKSWEE-HNTPLSCPEC 62
Cdd:pfam15227   1 CPICLDYLEKPVSIECGHSFCLSCINSLQKEpDGESLLCPQC 42

RING-finger-containing E3 ubiquitin ligase [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 1039789917  22 CFICLDYFSSPVTTECGHSFCLMCLLKSWEEhNTPLSCPEC 62
Cdd:COG5574   218 CFLCLEEPEVPSCTPCGHLFCLSCLLISWTK-KKYEFCPLC 257

E3 ubiquitin-protein ligase RMA2; Provisional

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1039789917  19 ELTCFICLDYFSSPVTTECGHSFCLMCLLK-------------SWEEHNTPLSCPEC 62
Cdd:PLN03208   18 DFDCNICLDQVRDPVVTLCGHLFCWPCIHKwtyasnnsrqrvdQYDHKREPPKCPVC 74

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 477
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789917 478 FSPCLPNEGTNTDPLIIC 495
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

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 1039789917 319 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 398
Cdd:cd15813     9 VNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 399 GNLPKPPGDLFSLIGLKIGDDYSLWVSSPLKGQhVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRPIF 478
Cdd:cd15813    89 GSMTLSPENGYWVVMMTKRNEYQASTSPPTRLW-LREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPLQPIF 167

                         170
                  ....*....|....*..
gi 1039789917 479 SPCLPNEGTNTDPLIIC 495
Cdd:cd15813   168 SPGTHDGGKNMDPLTIC 184

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 1039789917 319 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 398
Cdd:cd15819     2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 399 GNLPKPPGDLFSLIGLkIGDDYslW-VSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRPI 477
Cdd:cd15819    82 GRVTLSPENGFWAIRL-YGNEY--WaLTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPF 158

                         170
                  ....*....|....*...
gi 1039789917 478 FspCLPNEGTNtdPLIIC 495
Cdd:cd15819   159 F--RLWSSDSG--PLTIC 172

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRkg 399
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNR-- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 nlpKPPGDLFSLIGLKIGDDYSLWVSSPLKG-QHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRPIF 478
Cdd:cd15811    79 ---KEKGELSAGNGFWILVFLGNYYSSERRTfAPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPLF 155

                         170
                  ....*....|....*..
gi 1039789917 479 SPClpneGTNTDPLIIC 495
Cdd:cd15811   156 SPL----SSSPTPMTIC 168

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLP-KPPGDLFSLIglKIGDDYSlWVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPF-HEALRPI 477
Cdd:cd12888    81 EISfSPEEGIWAVG--QWGGQYW-ALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFaGERIFPW 157

                  .
gi 1039789917 478 F 478
Cdd:cd12888   158 F 158

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd15829    20 DVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTKA 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKiGDDYSLW--VSSPLKGQhvrEPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 477
Cdd:cd15829   100 RRPPSGQQGCWRIQLQ-GGDYDAPgaVPPPLLLE---VKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDT-FSGPLRPY 174

                         170
                  ....*....|....*...
gi 1039789917 478 FspCLpneGTNTDPLIIC 495
Cdd:cd15829   175 F--YV---GPDSKPLRIC 187

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 N-LPKPPGDLFSLIGLKiGDDYSLWVSSPLKGQHVREPvHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPIF 478
Cdd:cd15816    81 EtTPSPENGVWAVWLLK-GNEYMVLASPSVPLLQLRRP-RRVGVFLDYEAGEISFYNVTAGSHIYTFRQL-FSGILRPYF 157

                         170
                  ....*....|....*.
gi 1039789917 479 SPClpnegtNTDPLII 494
Cdd:cd15816   158 FVC------DTTPLTL 167

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 1039789917 319 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 398
Cdd:cd12905     4 APLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 399 GNLPKPPGDLFSLIGLKIGDDYSLwVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALrPIF 478
Cdd:cd12905    84 ARVKLCPENGYWTLRLRNGDEYWA-GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVF-PFF 161

                         170
                  ....*....|....*..
gi 1039789917 479 SPCLPNEGTNTDPLIIC 495
Cdd:cd12905   162 STCFSDDGQNAEPMRLL 178

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 321 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKGN 400
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 401 LPKPPGDLFSLiGLKI-GDDYSLWVSSPLKGQHVREPvHKVGVFLDYDSGHIAFYNATD-ESLIYSFpPTPFHEALRPIF 478
Cdd:cd12874    81 MSNLGRNNGSW-CLEWrENEFSAWHNNPETRLPVTPP-RRLGVFLDCDGGSLSFYGVTDgVQLLYTF-KAKFTEPLYPAF 157

                  ...
gi 1039789917 479 SPC 481
Cdd:cd12874   158 WLG 160

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKIgDDYSLWVSSPLKGQHVREPvHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPIFS 479
Cdd:cd15817    81 QDPPSPLGGCWQIGRYM-SGYVASGPKTTQLLPVVKP-SRIGIFLDYELGEVSFYNMNDRSHLYTFTDT-FTGKLIPYFY 157

                         170
                  ....*....|....*.
gi 1039789917 480 PclpneGTNTDPLIIC 495
Cdd:cd15817   158 V-----GPDSEPLTIC 168

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 1039789917 323 LDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKGNLP 402
Cdd:cd13743    16 LDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLN 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 403 KPPGDLFSLIGLKIGDDYSLWVSS----PLKGqhvrePVHKVGVFLDYDSGHIAFYNA--TDE-SLIYSFpPTPFHEALR 475
Cdd:cd13743    96 KSPENGVWLIGLKEGRVYEAFANPrvplPLST-----RPQRIGVFLDYEKGELTFYNAdsPDElVPIYTF-QAEFQGKLY 169

                         170
                  ....*....|....*....
gi 1039789917 476 PIFSPCLPNEGTNTDPLII 494
Cdd:cd13743   170 PLLDVCWHERGANKLPIIL 188

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 1039789917 321 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEV--GKKTEWEVGICKDSVNRK 398
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 399 GNLPKPPGD-LFSLIGLKIGddysLWVS-SPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRP 476
Cdd:cd15826    82 GEMGLSAEDgVWAVILSHQQ----CWAStSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTAS-FSGKVFP 156

                  ..
gi 1039789917 477 IF 478
Cdd:cd15826   157 FF 158

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 399
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTHHKE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 400 NLPKPPGDLFSLIGLKIGDDYSLWVSSPLKGQHVREPV---------------------------HKVGVFLDYDSGHIA 452
Cdd:cd13741    81 KVGSGGSSVSSGDASSSRHHHRRRRLHLPQQPLLQREVwcvgtngkryqaqssteqtllspsekpRRFGVYLDYEAGRLG 160

                         170       180
                  ....*....|....*....|....*.
gi 1039789917 453 FYNATDESLIYSFPPTPFHEALRPIF 478
Cdd:cd13741   161 FYNAETLAHVHTFSAAFLGERVFPFF 186

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 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGGTRQQL-PDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 398
Cdd:cd13742    13 NLTFDPDTAHPYLVVSSDGKRVECADQKQAVsSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGRK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 399 GNLPKPPGDLFSLIGLKIGDDYSLWVSS--PlKGQHVREPVHKVGVFLDYDSGHIAFYNATDE-SLIYSFpptPFHE--- 472
Cdd:cd13742    93 GRLHALPSNGFWLLGCKEGKVYEAHVEHkeP-RALRVEGRPTRIGVYLSFSDGVLSFYDASDEdNLVQLF---AFHErfp 168

                         170       180
                  ....*....|....*....|....
gi 1039789917 473 -ALRPIFSPCLPNEGTNTDPLIIC 495
Cdd:cd13742   169 gPLYPFFDVCWHDKGKNSQPLKIF 192

PRY/SPRY domain of tripartite motif-binding protein 5, 6, 22 and 34 (TRIM5, TRIM6, TRIM22 and TRIM34); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of very close paralogs, TRIM5, TRIM6, TRIM22 and TRIM34. These domains are composed of RING/B-box/coiled-coil core and are also known as RBCC proteins. They form a locus of four closely related TRIM genes within an olfactory receptor-rich region on chromosome 11 of the human genome. Genetic analysis of this locus indicates that these four genes have evolved by gene duplication from a common ancestral gene. All genes in the TRIM6/TRIM34/TRIM5/TRIM22 locus are type I interferon inducible, with TRIM5 and TRIM22 possessing antiviral properties. TRIM5 promotes innate immune signaling by activating the TAK1 kinase complex by cooperating with the heterodimeric E2, UBC13/UEV1A. It also stimulates NFkB and AP-1 signaling, and the transcription of inflammatory cytokines and chemokines, amplifying these activities upon retroviral infection. Interaction of its PRY-SPRY or cyclophilin domains with the retroviral capsid lattice stimulates the formation of a complementary lattice by TRIM5, with greatly increased TRIM5 E3 activity, and host cell signal transduction. TRIM6 is selectively expressed in embryonic stem (ES) cells and interacts with the proto-oncogene product Myc, maintaining the pluripotency of the ES cells. TRIM6, together with E2 Ubiquitin conjugase (UbE2K) and K48-linked poly-Ub chains, is critical for the IkappaB kinase epsilon (IKKepsilon) branch of type I interferon (IFN-I) signaling pathway and subsequent establishment of a protective antiviral response. TRIM22 plays an integral role in the host innate immune response to viruses; it has been shown to inhibit the replication of a number of viruses, including HIV-1, hepatitis B, and influenza A. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. While the PRY-SPRY domain of TRIM5a provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789917 320 DITLDPATANAYLLLSEDLKSVRYGG---TRQQLPDNPERFDqsatVLGAQIFTCGRHYWEVEVGKKTEWEVGIC----- 391
Cdd:cd15810     1 DVTLNPVNISLNIVISEDQRQVRIVPpqtSGQALTNNNYDFG----VLGSQYFSSGKHYWEVDVSKKSAWILGVCshkrs 76