chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 310772223     7 RIQTEFNQLRNILDRVEQR--ELKKLEQEEKKGLRIIEEAENDLVHQTQSLRELISDLERRCQGSTMELLQ 75
Cdd:TIGR02168  870 ELESELEALLNERASLEEAlaLLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGLEVRIDN 940

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 310772223   177 SGKHYWEVDVAKKTAWILGVCSNSlGPTFSFNHFAQNHsaysryqpqsGYWVIGLQHNHEYRAYEdsSPSLLLSMTVPPR 256
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKS-VPRGYFALLGEDK----------GSWGYDGDGGKKYHNST--GPEYGLPLQEPGD 67

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 310772223   257 RVGVFLDYEAGTVSFYNVTNHgFPIYTFSKYYFPTTLCPYF---NPCNCVI 304
Cdd:smart00449  68 VIGCFLDLEAGTISFYKNGKY-LHGLAFFDVKFSGPLYPAFslgSGNSVRL 117

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 310772223     7 RIQTEFNQLRNILDRVEQR--ELKKLEQEEKKGLRIIEEAENDLVHQTQSLRELISDLERRCQGSTMELLQ 75
Cdd:TIGR02168  870 ELESELEALLNERASLEEAlaLLRSELEELSEELRELESKRSELRRELEELREKLAQLELRLEGLEVRIDN 940

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 310772223 127 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCS--NSLGPT 204
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCShkRSDAMT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 205 FSFNHFAQNHSAYSRYQPQSGYWVIGLQHNHEYRAYEDSS----PSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFP 280
Cdd:cd15810   81 KSNANQINHQNVYSRYQPQYGYWVIGLQNESEYNAFEDSSsfnpHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVTNHGSL 160

                        170       180
                 ....*....|....*....|....*....
gi 310772223 281 IYTFSKYYFPTTLCPYFNPCNCVIPMTLR 309
Cdd:cd15810  161 IYKFSKCCFSTTVCPYFNPWNCPVPMTLC 189

PRY/SPRY domain in tripartite motif-containing protein 22 (TRIM22), also known as RING finger protein 94 (RNF94) or Stimulated trans-acting factor of 50 kDa (STAF50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM22, also known as RING finger protein 94 (RNF94) or STAF50 (Stimulated trans-acting factor of 50 kDa). TRIM6 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM22 is an interferon-induced protein, predominantly expressed in peripheral blood leukocytes, in lymphoid tissue such as spleen and thymus, and in the ovary.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. TRIM22 inhibits influenza A virus (IAV) infection by targeting the viral nucleoprotein for degradation; it represents a novel restriction factor up-regulated upon IAV infection that curtails its replicative capacity in epithelial cells. Altered TRIM22 expression has also been associated with multiple sclerosis, cancer, and autoimmune disease. A large number of high-risk non-synonymous (ns)SNPs have been identified in the highly polymorphic TRIM22 gene, most of which are located in the SPRY domain and could possibly alter critical regions of the SPRY structural and functional residues, including several sites that undergo post-translational modification. TRIM22 is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. It is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines; p53 dysfunction may be one of the mechanisms for its down-regulation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 124 YWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGP 203
Cdd:cd15824    1 YWVDVMLNPVNAVSNVVVSADQRQVTVVHICMFRNSNPCDFSAFDVLGCQYFSSGKYYWEVDVSGKIAWILGVYSKRNNL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 204 T------FSFNHFAQNHSAYSRYQPQSGYWVIGLQHNHEYRAYEDSSPS----LLLSMTVPPRRVGVFLDYEAGTVSFYN 273
Cdd:cd15824   81 NkrkssgFAFDPNVNHPNVYSRYRPQNGYWVIGLQNESEYNAFEDSSSSdpkvLTLSMAVPPHRVGVFLDYEAGTVSFFN 160

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 310772223 274 VTNHGFPIYTFSKYYFPTTLCPYFNPCNCVIPMTLRRP 311
Cdd:cd15824  161 VTNHGSLIYKFSKCCFSQPVYPYFNPWNCPAPMTLCPP 198

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 310772223 127 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSlgptf 205
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCvCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARES----- 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 206 sfnhfaQNHSAYSRYQPQSGYWVIGLQHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGFPIYTFS 285
Cdd:cd13733   76 ------VNRKGKITLSPENGYWTVGLRNGNEYKAL--TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDD-GSHIYTFT 146

                        170
                 ....*....|....*
gi 310772223 286 KyYFPTTLCPYFNPC 300
Cdd:cd13733  147 D-CFTEKLYPYFSPC 160

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 310772223 118 LTDVQSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGV 196
Cdd:cd15813    1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCiIVLGSPSFTSGRHYWEVEVGDKTGWILGV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 197 CSNSLgptfsfnhfaqNHSAYSRYQPQSGYWVIGLQHNHEYRAyeDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTN 276
Cdd:cd15813   81 CKASV-----------SRKGSMTLSPENGYWVVMMTKRNEYQA--STSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTA 147

                        170       180
                 ....*....|....*....|....
gi 310772223 277 HGFpIYTFSKYYFPTTLCPYFNPC 300
Cdd:cd15813  148 KSH-IYTFTSFSSSGPLQPIFSPG 170

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 310772223 126 VDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK--HYDCsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSL-- 201
Cdd:cd15819    2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERfdSLPC-VLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVmr 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 202 --GPTFSfnhfaqnhsaysryqPQSGYWVIGLqHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGF 279
Cdd:cd15819   81 kgRVTLS---------------PENGFWAIRL-YGNEYWAL--TSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTD-GS 141

                        170
                 ....*....|....*...
gi 310772223 280 PIYTFSKYYFPTTLCPYF 297
Cdd:cd15819  142 HIYTFPQTAFSGPLRPFF 159

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 310772223 126 VDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYD--CsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSL-- 201
Cdd:cd15821    4 VDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDalC-VLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVnr 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 202 -GPTfsfnhfaqnhsaysRYQPQSGYWVIGLQHNHEYRAyeDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGFP 280
Cdd:cd15821   83 qGPI--------------ELSPEHGFWTVSLRDGSVFFA--STVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSD-GSH 145

                        170       180
                 ....*....|....*....|..
gi 310772223 281 IYTFSKYYFPTTLCPYFNPCNC 302
Cdd:cd15821  146 IFTFTKISAEEPLRPFFAPANP 167

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 310772223 121 VQSYWVDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPScLEKHYDCS--VLGSQHFSSGKHYWEVDVAKKTAWILGVCS 198
Cdd:cd15829   14 IKKFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPD-SPKRFTVNpvVLGFPGFHSGRHFWEVEVGDKPEWAVGVCK 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 199 NSLgptfsfnhfaqnhSAYSRYQP--QSGYWVIGLQhNHEYRAyEDSSPSLLLSmTVPPRRVGVFLDYEAGTVSFYNVTN 276
Cdd:cd15829   93 DSL-------------STKARRPPsgQQGCWRIQLQ-GGDYDA-PGAVPPPLLL-EVKPRGIGVFLDYELGEISFYNMPE 156

                        170       180
                 ....*....|....*....|...
gi 310772223 277 --HgfpIYTFSKyYFPTTLCPYF 297
Cdd:cd15829  157 ksH---IHTFTD-TFSGPLRPYF 175

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 310772223 127 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKhYD---CsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGP 203
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPER-FDpgpC-VLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 204 TFSFNHFAQNhsaysryqpqsGYWVIGLQHNheyraYEDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGFPIYT 283
Cdd:cd15811   79 KEKGELSAGN-----------GFWILVFLGN-----YYSSERRTFAPLRDPPRRVGIFLDYEAGHLSFYSATD-GSLLFI 141

                        170       180
                 ....*....|....*....|....*...
gi 310772223 284 FSKYYFPTTLCPYFNPCNCV-IPMTLRR 310
Cdd:cd15811  142 FPETPFSGTLRPLFSPLSSSpTPMTICR 169

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 310772223 128 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCS-VLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLGPtfs 206
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFFECWqVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPR--- 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 207 fnhfaqnHSAYSRYQPQSGYWVIGLQHNhEYRAYEDSSPSLLLSmtVPPRRVGVFLDYEAGTVSFYNVTNHGFPIYTFsK 286
Cdd:cd12874   78 -------KGKMSNLGRNNGSWCLEWREN-EFSAWHNNPETRLPV--TPPRRLGVFLDCDGGSLSFYGVTDGVQLLYTF-K 146

                        170
                 ....*....|....*.
gi 310772223 287 YYFPTTLCPYFNPCNC 302
Cdd:cd12874  147 AKFTEPLYPAFWLGEG 162

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 310772223 128 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLgptfs 206
Cdd:cd12905    6 LTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCvNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESV----- 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 207 fnhfaqNHSAYSRYQPQSGYWVIGLQHNHEYRAyeDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIYTFSK 286
Cdd:cd12905   81 ------DRQARVKLCPENGYWTLRLRNGDEYWA--GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSL-LYSFHQ 151

                        170
                 ....*....|....
gi 310772223 287 YYfPTTLCPYFNPC 300
Cdd:cd12905  152 GP-RGKVFPFFSTC 164

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 310772223 127 DVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDC-SVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLgPTf 205
Cdd:cd15817    1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYpAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSL-PR- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 206 sfnhfaqnhSAYSRYQPQSGYWVIGLQHNhEYRAYEDSSPSLLlsMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIYTFS 285
Cdd:cd15817   79 ---------NAQDPPSPLGGCWQIGRYMS-GYVASGPKTTQLL--PVVKPSRIGIFLDYELGEVSFYNMNDRSH-LYTFT 145

                        170
                 ....*....|..
gi 310772223 286 KyYFPTTLCPYF 297
Cdd:cd15817  146 D-TFTGKLIPYF 156

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 310772223 126 VDVTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKH--YDCsVLGSQHFSSGKHYWEVDVAKKTAWILGVCSNSLgp 203
Cdd:cd15814    2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFnlFPC-VLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSV-- 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 204 tfsfnhfAQNHSAYSryQPQSGYWVIGLQHNHEYRAYedSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIYT 283
Cdd:cd15814   79 -------CRKGGVTS--APQNGFWAVSLWYGKEYWAL--TSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCH-TFT 146

                        170
                 ....*....|....*
gi 310772223 284 FSKYYFPTTLCPYFN 298
Cdd:cd15814  147 FSHATFCGPVRPYFS 161

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 310772223 128 VTLNPHTANLNLVLAKNRRQVRFVGAKVSGPScLEKHYDC--SVLGSQHFSSGKHYWEVDVAKKT--AWILGVCSNSL-- 201
Cdd:cd15826    2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPD-SPLRFDGlpAVLGSPGFSSGRHRWQVEVQLGDggGCTVGVAGESVrr 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 202 --GPTFSfnhfaqnhsaysryqPQSGYWVIGLQHNheyRAYEDSSPSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGf 279
Cdd:cd15826   81 kgEMGLS---------------AEDGVWAVILSHQ---QCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQE- 141

                        170
                 ....*....|....*...
gi 310772223 280 PIYTFSKyYFPTTLCPYF 297
Cdd:cd15826  142 PIFTFTA-SFSGKVFPFF 158

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 310772223 127 DVTLNPHTANLNLVLAKNRrQVRFVGAKVSGPSCLEKH---YDCSVlGSQHFSSGKHYWEV--DVAKKTAWILGVCSNsl 201
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESR-QRRYLSTPPDGTPCSKDRflaYPCAV-GQETFSSGRHYWEVgmNLTGDALWALGVCRD-- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 202 gptfsfnhfaqNHSAYSRY--QPQSGYWVIGLQHNHEYRAYEDSSPSLLLsmTVPPRRVGVFLDYEAGTVSFYNVTNhGF 279
Cdd:cd15812   77 -----------NVSRKDRVpkSPENGFWVVQLSKGKKYLSAMSALTPVTL--TEPPSHMGIFLDFEAGEVSFYSVND-GS 142

                        170
                 ....*....|....*...
gi 310772223 280 PIYTFSKYYFPTTLCPYF 297
Cdd:cd15812  143 HLHTYSQAAFPGPLQPFF 160

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 165 YDCSVLGSQHFSSGKHYWEVDVAKKTAWILGVCSnslGPTFSFNHFAQNhsaysryqPQSGYWVIGLQHNHEYRAYedSS 244
Cdd:cd13743   52 YSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIK---GTTSRKGKLNKS--------PENGVWLIGLKEGRVYEAF--AN 118

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 310772223 245 PSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHG--FPIYTFsKYYFPTTLCPYFNPC 300
Cdd:cd13743  119 PRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDelVPIYTF-QAEFQGKLYPLLDVC 175

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 310772223 100 RSMFRA--PDLKRMlrvcreltdvqsywvdvTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEKHYDCS--VLGSQHF 175
Cdd:cd13742    1 RKMFRAlmPALENL-----------------TFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKAncVVSHQSF 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 176 SSGKHYWEVDVAKKTAWILGVCSNSLGPTFSFNHFaqnhsaysryqPQSGYWVIGLQHNHEYRAYEDSSPSLLLSMTVPP 255
Cdd:cd13742   64 SEGEHYWEVIVGDKPRWALGVISAEAGRKGRLHAL-----------PSNGFWLLGCKEGKVYEAHVEHKEPRALRVEGRP 132

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 310772223 256 RRVGVFLDYEAGTVSFYNVTNHG--FPIYTFSKyYFPTTLCPYFNPC 300
Cdd:cd13742  133 TRIGVYLSFSDGVLSFYDASDEDnlVQLFAFHE-RFPGPLYPFFDVC 178

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as 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. 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 310772223 100 RSMFRA--PDLKRMlrvcreltdvqsywvdvTLNPHTANLNLVLAKNRRQVRFVGAKVSGPSCLEK-HYDCSVLGSQHFS 176
Cdd:cd12897    1 RKMFRAlmPALESL-----------------TFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERfDKSTCVVASQGFS 63