SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. 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 or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. 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. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 134 KKMFRALMPELEELTFDPSSAHPSLVVSASGRRVECSEQKAPPAGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRW 213
Cdd:cd13742     1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 214 ALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPERpPARIGLYLSFADGVLTFYDASNTDALTP 293
Cdd:cd13742    81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEGR-PTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958648220 294 LFSFHERLPGPVYPMFDVCWHDKGKNSQPLLLV 326
Cdd:cd13742   160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 1958648220 134 KKMFRALMPELEELTFDPSSAHPSLVVSASGRRVECSEQKAPPAGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRW 213
Cdd:cd13742     1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 214 ALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPERpPARIGLYLSFADGVLTFYDASNTDALTP 293
Cdd:cd13742    81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEGR-PTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958648220 294 LFSFHERLPGPVYPMFDVCWHDKGKNSQPLLLV 326
Cdd:cd13742   160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 1958648220 201 HYWEVEVG--DKPRWALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAhveAKEPRALRTPERPPARIGLYLSFADG 278
Cdd:pfam00622   2 HYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWA---STSPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1958648220 279 VLTFYDasNTDALTPLFSfHERLPGPVYPMFDVCWHDKGKN 319
Cdd:pfam00622  79 TISFTK--NGKSLGYAFR-DVPFAGPLFPAVSLGAGEGLKF 116

Chromosome segregation protein NDC80, interacts with SMC proteins [Cell cycle control, cell division, chromosome partitioning];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220   2 RKEKSVAVLEHQLVEVEETVRQFRGAVGEQLGKMRMFLAALESSL---DREAERvrgeagvaLRRELSSLNSYLEQLRQM 78
Cdd:COG5185   371 ELSKSSEELDSFKDTIESTKESLDEIPQNQRGYAQEILATLEDTLkaaDRQIEE--------LQRQIEQATSSNEEVSKL 442

                          90
                  ....*....|....*
gi 1958648220  79 EKVLEEVADKPQTEF 93
Cdd:COG5185   443 LNELISELNKVMREA 457

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 1958648220 134 KKMFRALMPELEELTFDPSSAHPSLVVSASGRRVECSEQKAPPAGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRW 213
Cdd:cd13742     1 RKMFRALMPALENLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRW 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 214 ALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPERpPARIGLYLSFADGVLTFYDASNTDALTP 293
Cdd:cd13742    81 ALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVEHKEPRALRVEGR-PTRIGVYLSFSDGVLSFYDASDEDNLVQ 159

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1958648220 294 LFSFHERLPGPVYPMFDVCWHDKGKNSQPLLLV 326
Cdd:cd13742   160 LFAFHERFPGPLYPFFDVCWHDKGKNSQPLKIF 192

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 1958648220 134 KKMFRALMPELEELTFDPSSAHPSLVVSASGRRVECS--EQKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKP 211
Cdd:cd13743     1 KRLHRKVLPAPELLKLDPLTAHPMLELSKGNTVVECGllAQRLPSNPE---RFDYSNCVLASRGFSSGKHYWEVVVGSKS 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 212 RWALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPerpPARIGLYLSFADGVLTFYDASNTDAL 291
Cdd:cd13743    78 KWRLGLIKGTTSRKGKLNKSPENGVWLIGLKEGRVYEAFANPRVPLPLSTR---PQRIGVFLDYEKGELTFYNADSPDEL 154

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958648220 292 TPLFSFHERLPGPVYPMFDVCWHDKGKNSQPLLL 325
Cdd:cd13743   155 VPIYTFQAEFQGKLYPLLDVCWHERGANKLPIIL 188

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 1958648220 142 PELEELTFDPSSAHPSLVVSASGRRV-ECSEQKapPAGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAA 220
Cdd:cd12905     1 PGPAPLTFDPETAHPSLILSRDLTAVtESDEMQ--PYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 221 DASRRGRLHAVPSQGLWLLGLRDGKILEAhveAKEPRALRTPERPPARIGLYLSFADGVLTFYDAsntDALTPLFSFHER 300
Cdd:cd12905    79 SVDRQARVKLCPENGYWTLRLRNGDEYWA---GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNA---DDMSLLYSFHQG 152

                         170       180
                  ....*....|....*....|....*
gi 1958648220 301 LPGPVYPMFDVCWHDKGKNSQPLLL 325
Cdd:cd12905   153 PRGKVFPFFSTCFSDDGQNAEPMRL 177

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 1958648220 146 ELTFDPSSAHPSLVVSASGRRVECseqkappagEDTCQ--------FDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGV 217
Cdd:cd13745     4 DVTLDPDTAHPNLVLSEDRKSVRH---------GDTRQdlpdnperFDTYPCVLGAEGFTGGRHYWEVEVGDKTEWTLGV 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 218 MAADASRRGRLHAVPSQGLWLLGLRDGKIleahveakepRALRTPERP------PARIGLYLSFADGVLTFYDAsnTDAl 291
Cdd:cd13745    75 CRESVSRKGEVTLSPENGYWTVWLRDGKY----------EALTSPPTPlpvsvrPSRVGIFLDYEAGEVSFYNV--TDR- 141

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1958648220 292 TPLFSFHERLPGPVYPMFDVCWHDKGKNSQPLLL 325
Cdd:cd13745   142 SHLFTFTDTFSGTLRPYFYPGLNAGGKNAAPLII 175

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 1958648220 148 TFDPSSAHPSLVVSASGRRVECSE--QKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADASRR 225
Cdd:cd15813    12 TLDPETAHPNLIFSDDLKSVRLGNkwDRLPDNPE---RFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 226 GRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRtpeRPPARIGLYLSFADGVLTFYdasNTDALTPLFSF-HERLPGP 304
Cdd:cd15813    89 GSMTLSPENGYWVVMMTKRNEYQASTSPPTRLWLR---EPPRRVGIFLDYEAGDISFY---NVTAKSHIYTFtSFSSSGP 162

                         170
                  ....*....|....*....
gi 1958648220 305 VYPMFDVCWHDKGKNSQPL 323
Cdd:cd15813   163 LQPIFSPGTHDGGKNMDPL 181

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 1958648220 148 TFDPSSAHPSLVVSASGRRVECSE--QKAPpagEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADASRR 225
Cdd:cd15819     5 TLDPDTAHPALILSEDGRSVTWGEtrQDLP---ENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 226 GRLHAVPSQGLWLLGLRDGkileahveakEPRALRTPER------PPARIGLYLSFADGVLTFYdaSNTDAlTPLFSF-H 298
Cdd:cd15819    82 GRVTLSPENGFWAIRLYGN----------EYWALTSPETpltlkePPRRVGIFLDYEAGDVSFY--NMTDG-SHIYTFpQ 148

                         170
                  ....*....|....*....
gi 1958648220 299 ERLPGPVYPMFDVCWHDKG 317
Cdd:cd15819   149 TAFSGPLRPFFRLWSSDSG 167

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 1958648220 147 LTFDPSSAHPSLVVSASGRRVEC--SEQKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADASR 224
Cdd:cd12900     5 ITLDPDTANPWLILSKDRRQVRLgdTHQNVPENEE---RFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVRR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 225 RGRLHAVPSQGLWLLGLRDGKiLEAHVEAKEPRALRTperPPARIGLYLSFADGVLTFYDASNTDALtpLFSFHE-RLPG 303
Cdd:cd12900    82 KGQFLLSPENGFWTIWLWNKK-YEAGTSPQTTLHLQV---PPCQVGIFLDYEAGVVSFYNITDHGSL--IYTFSEcAFTG 155

                         170       180
                  ....*....|....*....|..
gi 1958648220 304 PVYPMFDVCWHDKGKNSQPLLL 325
Cdd:cd12900   156 PLRPFFNPGFNDSGGNAAPLTL 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 1958648220 146 ELTFDPSSAHPSLVVSASGRRVECSE--QKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADAS 223
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDtrQDLPDNPE---RFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 224 RRGRLHAVPSQGLWLLGLRDGKIleahveakepRALRTPERP------PARIGLYLSFADGVLTFYDASNtdaLTPLFSF 297
Cdd:cd12888    78 RKGEISFSPEEGIWAVGQWGGQY----------WALTSPETPlplsevPRRIRVYLDYEGGQVAFFDADN---EAPIFTF 144

                         170       180
                  ....*....|....*....|..
gi 1958648220 298 ------HERlpgpVYPMFDVCW 313
Cdd:cd12888   145 ppasfaGER----IFPWFWVGK 162

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 1958648220 146 ELTFDPSSAHPSLVVSASGRRVECS--EQKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADAS 223
Cdd:cd15814     3 DVTLDPDTAYPSLILSDNLRQVRYSylQQDLPDNPE---RFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVC 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 224 RRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPERppaRIGLYLSFADGVLTFYdasNTDALTPLFSF-HERLP 302
Cdd:cd15814    80 RKGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQ---RVGIFLDYDAGEVSFY---NVTERCHTFTFsHATFC 153

                         170       180
                  ....*....|....*....|...
gi 1958648220 303 GPVYPMFDVCWhDKGKNSQPLLL 325
Cdd:cd15814   154 GPVRPYFSLSY-SGGKSAAPLII 175

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 1958648220 146 ELTFDPSSAHPSLVVSASGRRVECSE--QKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADAS 223
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGElwRDVPGNPE---RFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 224 RRGRLHAVPSQGLWLLGLRDGKilEAHVEAKEPRALRTPERpPARIGLYLSFADGVLTFYDASNTdalTPLFSFHERLPG 303
Cdd:cd15816    78 RKGETTPSPENGVWAVWLLKGN--EYMVLASPSVPLLQLRR-PRRVGVFLDYEAGEISFYNVTAG---SHIYTFRQLFSG 151

                         170       180
                  ....*....|....*....|..
gi 1958648220 304 PVYPMFDVCwhdkgkNSQPLLL 325
Cdd:cd15816   152 ILRPYFFVC------DTTPLTL 167

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 1958648220 148 TFDPSSAHPSLVVSASGRRVECSEQKAPP-AGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADASRRG 226
Cdd:cd13734     2 KLDPKTAHRKLRLSNDNLTVEYDPEGSKDqAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRDE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 227 RLHAvpSQGLWLLgLRDGKILEAHVEAKEPRaLRTPERpPARIGLYLSFADGVLTFYDAsntDALTPLFSFHERLPGPVY 306
Cdd:cd13734    82 DLGK--NSTSWCL-SRDNNRYTARHDGKVVD-LRVTGH-PARIGVLLDYDNGTLSFYDA---ESKQHLYTFHVDFEGPVC 153

                  ....*...
gi 1958648220 307 PMFDVcWH 314
Cdd:cd13734   154 PAFAV-WN 160

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 1958648220 145 EELTFDPSSAHPSLVVSASGRRVEC--SEQKAPPAGEdtcQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADA 222
Cdd:cd15820     4 ADVILDPDTANPILLISEDQRSLQWadEPQNLPDNPK---RFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 223 SRRGRLHAVPSQGLWLLGLRDGKILEAhveAKEPRALRTPERPPARIGLYLSFADGVLTFYDASNTdalTPLFSF-HERL 301
Cdd:cd15820    81 ERKLWVKMAPENGFWTIGLSDGNDYQA---LTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDG---SHIYTFpHTSF 154

                         170
                  ....*....|....
gi 1958648220 302 PGPVYPMFDVCWHD 315
Cdd:cd15820   155 SGPLYPVFRLLSWD 168

PRY/SPRY domain of tripartite motif-binding protein 17 (TRIM17), also known as testis RING finger protein (terf); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM17, also known as RING finger protein 16 (RNF16) or testis RING finger protein (terf). TRIM17 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein, expressed almost exclusively in the testis. It exhibits E3 ligase activity, causing protein degradation of ZW10 interacting protein (ZWINT), a known component of the kinetochore complex required for the mitotic spindle checkpoint, and negatively regulates proliferation of breast cancer cells. TRIM17 undergoes ubiquitination in COS7 fibroblast-like cells but is inhibited and stabilized by TRIM44.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 150 DPSSAHPSLVVSASGRRVECSeqkaPPAGEDTCQFDKTVA---VVAKQLLSQGEHYWEVEV---GDKpRWALGVMAADAS 223
Cdd:cd15812     5 DPSTAYPYLLLYESRQRRYLS----TPPDGTPCSKDRFLAypcAVGQETFSSGRHYWEVGMnltGDA-LWALGVCRDNVS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 224 RRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRtpeRPPARIGLYLSFADGVLTFYDASNTDALtPLFSfHERLPG 303
Cdd:cd15812    80 RKDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLT---EPPSHMGIFLDFEAGEVSFYSVNDGSHL-HTYS-QAAFPG 154

                  ....*.
gi 1958648220 304 PVYPMF 309
Cdd:cd15812   155 PLQPFF 160

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 1958648220 147 LTFDPSSAHPSLVVSASGRRVECSEQK----APPAGEDTCQfdktvaVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADA 222
Cdd:cd12891     1 LTLDPNTAHNNLALSGDLKTVTCSSENqhypDSPERFTHSQ------VLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSI 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 223 SRRGrlhavPSQGL------WLLGLRDGKILEAHveakEPRALRTPERPPARIGLYLSFADGVLTFYDASNTdaLTPLFS 296
Cdd:cd12891    75 ERKG-----DESRIgrndksWCLEWQDKSFSAWH----NNEETPLPSVSSRRLGVYLDYEAGRLSFYELSDP--IRHLHT 143

                         170
                  ....*....|...
gi 1958648220 297 FHERLPGPVYPMF 309
Cdd:cd12891   144 FTATFTEPLHPAF 156

PRY/SPRY domain in tripartite motif-binding protein 6 (TRIM6), also known as RING finger protein 89 (RNF89); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM6, also known as RING finger protein 89 (RNF89). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 146 ELTFDPSSAHPSLVVSASGRRVEC--SEQKAPPAGEDtcQFDktVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADAS 223
Cdd:cd15823     4 DVTLNPHTANLNLVLSKNRRQVRFvgAKLSGPSYLEE--HYD--CSVLGSQHFSSGKHYWEVDVTKKTAWILGVCSHSLG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958648220 224 RRGRLHAV-----------PSQGLWLLGLRDGKILEAHvEAKEPRALRTPERPPARIGLYLSFADGVLTFYDASNTDalT 292
Cdd:cd15823    80 PTFSFNQYaqnhnaysryqPQSGYWVIGLQHNHEYRAY-EDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHG--F 156

                         170       180
                  ....*....|....*....|.
gi 1958648220 293 PLFSFHE-RLPGPVYPMFDVC 312
Cdd:cd15823   157 PIYTFSKyYFPTTLCPYFNPC 177