Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495    1 MDYLWEINQETRNNLNQETS---TFHSLKDYVSVRKRIITIQYQKMPIFLDEEE--QRHLQALER---EAEELFQQLQDS 72
Cdd:pfam05557  82 KKYLEALNKKLNEKESQLADareVISCLKNELSELRRQIQRAELELQSTNSELEelQERLDLLKAkasEAEQLRQNLEKQ 161

                          90
                  ....*....|....*...
gi 767970495   73 QVRMTQHLERMKDMYREL 90
Cdd:pfam05557 162 QSSLAEAEQRIKELEFEI 179

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 767970495   195 SGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFLISSKRSNHYSLSTnSPPLIQYVQRPLGRVGVFLDYDNGS 274
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKKYHNST-GPEYGLPLQEPGDVIGCFLDLEAGT 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 767970495   275 VSFFDVSKGSLIYGFPPSSFSSPLRPFFCFG 305
Cdd:smart00449  80 ISFYKNGKYLHGLAFFDVKFSGPLYPAFSLG 110

Mitotic checkpoint protein; This family consists of several eukaryotic mitotic checkpoint (Mitotic arrest deficient or MAD) proteins. The mitotic spindle checkpoint monitors proper attachment of the bipolar spindle to the kinetochores of aligned sister chromatids and causes a cell cycle arrest in prometaphase when failures occur. Multiple components of the mitotic spindle checkpoint have been identified in yeast and higher eukaryotes. In S.cerevisiae, the existence of a Mad1-dependent complex containing Mad2, Mad3, Bub3 and Cdc20 has been demonstrated.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495    1 MDYLWEINQETRNNLNQETS---TFHSLKDYVSVRKRIITIQYQKMPIFLDEEE--QRHLQALER---EAEELFQQLQDS 72
Cdd:pfam05557  82 KKYLEALNKKLNEKESQLADareVISCLKNELSELRRQIQRAELELQSTNSELEelQERLDLLKAkasEAEQLRQNLEKQ 161

                          90
                  ....*....|....*...
gi 767970495   73 QVRMTQHLERMKDMYREL 90
Cdd:pfam05557 162 QSSLAEAEQRIKELEFEI 179

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 767970495 156 YISLSEDVRYVIFGDDHLSAPTDPQGVDSFA-VWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFF 234
Cdd:cd13733   12 NLILSEDLKSVRYGDKRQNLPDNPERFDTCVcVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKGKITLSPENGYW 91

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767970495 235 LISSKRSNHYSLSTnSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFFC 303
Cdd:cd13733   92 TVGLRNGNEYKALT-SPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTF-TDCFTEKLYPYFS 158

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 767970495 159 LSEDVRYVIFGDDHLSAPTDPQGVDSFA-VWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFLIS 237
Cdd:cd15819   17 LSEDGRSVTWGETRQDLPENPERFDSLPcVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRKGRVTLSPENGFWAIR 96

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767970495 238 SKRSNHYSLStnSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFPPSSFSSPLRPFFC 303
Cdd:cd15819   97 LYGNEYWALT--SPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPFFR 160

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 767970495 142 FRVDSALSTEMIPCYISLSEDVRYVIFGDDHLSAPTDPQGVDSFA-VWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRT 220
Cdd:cd13745    1 FAVDVTLDPDTAHPNLVLSEDRKSVRHGDTRQDLPDNPERFDTYPcVLGAEGFTGGRHYWEVEVGDKTEWTLGVCRESVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 221 ADANFVIDSDERFFLISSKRSNHYSLSTNSPPLIQYVqRPlGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRP 300
Cdd:cd13745   81 RKGEVTLSPENGYWTVWLRDGKYEALTSPPTPLPVSV-RP-SRVGIFLDYEAGEVSFYNVTDRSHLFTF-TDTFSGTLRP 157

                 ....*
gi 767970495 301 FFCFG 305
Cdd:cd13745  158 YFYPG 162

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 767970495 145 DSALSTEMIPCYISLSEDVRYVIFGDDHLSAPTDPQGVDSFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRT-ADA 223
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRSdAMT 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 224 NFVIDSDER------------FFLI-----SSKRSNHYSLSTNSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSK-GSL 285
Cdd:cd15810   81 KSNANQINHqnvysryqpqygYWVIglqneSEYNAFEDSSSFNPHVLTLSVTVPPHRVGVFLDYEAGTVSFFNVTNhGSL 160

                        170
                 ....*....|....*..
gi 767970495 286 IYGFPPSSFSSPLRPFF 302
Cdd:cd15810  161 IYKFSKCCFSTTVCPYF 177

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 154 PCyISLSEDVRYVIFGDDHLSAPTDPQGVDSFA-VWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDER 232
Cdd:cd12893   11 PW-LSLSEDLTSVRYSSEKQQLPDNPERFDPYPcVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQRKGKFTLSPESG 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767970495 233 FFLIsSKRSNHYSLSTNSPPLIQY-VQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFFCFGCT 307
Cdd:cd12893   90 FWTI-GFSEGKYSARTSPEPRTPLrVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTF-THTFTERVFPYFYTGCK 163

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 159 LSEDVRYVIFGDDHLSAPTDPQGVD-SFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFLIS 237
Cdd:cd15818   28 LSEDLTCVWHGDTKQMLPDNPERFDsSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGNCPLSPEDGFWLLR 107

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767970495 238 SKRSNHYSlSTNSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFFC 303
Cdd:cd15818  108 LRNQNELK-ALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTF-SDTFTEKIYPYFC 171

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain 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 767970495 143 RVDSALSTEMIPCYISLSEDVRYVIfgddhlSAPTDPQGVDSFAVWGAQAFTSGKHYWEVDVTLSSNWILGV-CRdSRTA 221
Cdd:cd15825    1 WVDFTLNPVNLNLNLVLSEDQRQVT------SVPIWPFKCYNYGILGSQYFSSGKHYWEVDVSKKTAWILGVyCR-KRSR 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 222 DANFVIDSDER------------FFLISSKRSNHYSL---STNSPP--LIQYVQRPLGRVGVFLDYDNGSVSFFDVSK-G 283
Cdd:cd15825   74 TFKYVRQGKNHpnvysryrpqygYWVIGLQNKSEYYAfedSSTSDPkvLTLSVATPPHRVGVFLDYEAGTVSFFNVTNhG 153

                        170
                 ....*....|....*....
gi 767970495 284 SLIYGFPPSSFSSPLRPFF 302
Cdd:cd15825  154 SLIYKFSKCCFSQPVYPYF 172

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 767970495 155 CYISLSEDVRYVIFGDDHLSAPTDPQGVDS-FAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDS--RTADANFviDSDE 231
Cdd:cd12888   11 PRLVLSEDRKSVRWGDTRQDLPDNPERFDTwPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESvrRKGEISF--SPEE 88

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767970495 232 RfflISSKRSNH--YSLSTNSPPLIQYVQRPlGRVGVFLDYDNGSVSFFDVSKGSLIYGFPPSSFSSP-LRPFFCFG 305
Cdd:cd12888   89 G---IWAVGQWGgqYWALTSPETPLPLSEVP-RRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAGErIFPWFWVG 161

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 767970495 142 FRVDSALSTEMIPCYISLSEDVRYVIFGDDHLSAPTDPQGVDSFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTA 221
Cdd:cd15823    1 YWVDVTLNPHTANLNLVLSKNRRQVRFVGAKLSGPSYLEEHYDCSVLGSQHFSSGKHYWEVDVTKKTAWILGVCSHSLGP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 222 DANFVIDSDER-----------FFLISSKRSNHY-SLSTNSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSK-GSLIYG 288
Cdd:cd15823   81 TFSFNQYAQNHnaysryqpqsgYWVIGLQHNHEYrAYEDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNhGFPIYT 160

                        170
                 ....*....|....
gi 767970495 289 FPPSSFSSPLRPFF 302
Cdd:cd15823  161 FSKYYFPTTLCPYF 174

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 767970495 156 YISLSEDVRYVIFGDDHLSAPTDPQGVDS-FAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFF 234
Cdd:cd12874   11 NLILSDDLRSVRVGDISQHPPEPPPRFFEcWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGKMSNLGRNNGS 90

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767970495 235 LISSKRSNHYSLSTNSPPLIQYVqRPLGRVGVFLDYDNGSVSFFDVS-KGSLIYGFpPSSFSSPLRPFF 302
Cdd:cd12874   91 WCLEWRENEFSAWHNNPETRLPV-TPPRRLGVFLDCDGGSLSFYGVTdGVQLLYTF-KAKFTEPLYPAF 157

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 767970495 141 NFRVDSALSTEMIPCYISLSEDVRYVIFGDDHLSAPTDPQG-VDSFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSR 219
Cdd:cd15829   16 KFRVDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRfTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSL 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 220 TADANFVIDSDERFFLIsSKRSNHYSLSTNSPPLIQYVQRPlGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLR 299
Cdd:cd15829   96 STKARRPPSGQQGCWRI-QLQGGDYDAPGAVPPPLLLEVKP-RGIGVFLDYELGEISFYNMPEKSHIHTF-TDTFSGPLR 172

                 ....*..
gi 767970495 300 PFFCFGC 306
Cdd:cd15829  173 PYFYVGP 179

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 767970495 144 VDSALSTEMIPCYISLSEDVRYVIFGDDHLSAPTDPQGVDSF-AVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTAD 222
Cdd:cd15814    2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFpCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 223 ANFVIDSDERFFLISSKRSNHYsLSTNSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFPPSSFSSPLRPFF 302
Cdd:cd15814   82 GGVTSAPQNGFWAVSLWYGKEY-WALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYF 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 767970495 156 YISLSEDVRYVIFGDDHLSAPTDPQGVDSFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDS--RTADANFVIDSDERF 233
Cdd:cd12891   11 NLALSGDLKTVTCSSENQHYPDSPERFTHSQVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSieRKGDESRIGRNDKSW 90

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767970495 234 FLisSKRSNHYSLSTNSppliqyVQRPL-----GRVGVFLDYDNGSVSFFDVSKG-SLIYGFpPSSFSSPLRPFF 302
Cdd:cd12891   91 CL--EWQDKSFSAWHNN------EETPLpsvssRRLGVYLDYEAGRLSFYELSDPiRHLHTF-TATFTEPLHPAF 156

PRY/SPRY domain in tripartite motif-binding protein 62 (TRIM62); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM62. It is also called DEAR1 ductal epithelium (associated RING chromosome 1) and 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 and thus, making TRIM62 a predictive biomarker. Non-small cell lung cancer lesions show a step-wise loss of TRIM62 levels during disease progression, indicating that it may play a role in the evolution of lung cancer. Decreased levels of TRIM62 also represent an independent adverse prognostic factor in AML.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 159 LSEDVRYVIFGDDHLSAPTD-PQGVD-SFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFLI 236
Cdd:cd13744   27 LSDDCTIVAYGNLHPQPLQDsPKRFDvEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHEAVSRKGSIQIQPGRGFYCI 106

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767970495 237 SSKRSNHYSLSTnSPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFFCFG 305
Cdd:cd13744  107 VMHDGNQYSACT-EPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTF-REKFPGKLCSYFSPG 173

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 767970495 156 YISLSEDVRYVIFGDDHLSAPTDPQGVDSF-AVWGAQAFTSGKHYWEVDVTLS--SNWILGVCRDSRTADANFVIDSDER 232
Cdd:cd15826   12 SLVLSEDRKSVRYTRQKQNLPDSPLRFDGLpAVLGSPGFSSGRHRWQVEVQLGdgGGCTVGVAGESVRRKGEMGLSAEDG 91

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767970495 233 FFLIsskRSNHYSLSTNSPPLIQY--VQRPLgRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFF 302
Cdd:cd15826   92 VWAV---ILSHQQCWASTSPGTDLplSEIPR-RVGVALDYEAGTVTLTNAETQEPIFTF-TASFSGKVFPFF 158

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 767970495 156 YISLSEDVRYVIFGDDHLSAPTDPQGVD-SFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFF 234
Cdd:cd12897   24 LLVVSSGGTVVECGLQKQRRASQPERFDkSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKGKLHASPSHGVW 103

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767970495 235 LISSKRSNHYSLST--NSPPLIQYVQRPlGRVGVFLDYDNGSVSFFDVSKGS---LIYGFpPSSFSSPLRPFF 302
Cdd:cd12897  104 LIGLKEGKVYEAHGepKEPRPLRVAGRP-HRIGVYLSFEDGVLSFFDASDPDdlrTLYTF-QERFQGKLYPFF 174

PRY/SPRY domain in tripartite motif-binding protein 4 (TRIM4), also known as RING finger protein 87 (RNF87); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM4 which is also known as RING finger protein 87 (RNF87). TRIM4 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It is a positive regulator of RIG-I-mediated interferon (IFN) induction. It regulates virus-induced IFN induction and cellular antiviral innate immunity by targeting RIG-I for K63-linked poly-ubiquitination. Over-expression of TRIM4 enhances virus-triggered activation of transcription factors IRF3 and NF-kappaB, as well as IFN-beta induction. Expression of TRIM4 differs significantly in Huntington's Disease (HD) neural cells when compared with wild-type controls, possibly impacting down-regulation of the Huntingtin (HTT) gene, which is involved in the regulation of diverse cellular activities that are impaired in Huntington's Disease (HD) cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 187 VWGAQAFTSGKHYWEVDVTLSSNWILGVCRDsrtaDANFVIDSDER-----FFLISSKRSNHYSLStnSPPLIQYVQRP- 260
Cdd:cd15809   66 VLGKNVFTSGKHYWEVENRDSLEIAVGVCRE----DVMGITDGSEMsphvgIWAICWSSAGYRPLT--SSPVSPTKQEPa 139

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767970495 261 LGRVGVFLDYDNGSVSFFDVSKGSLIYGFpPSSFSSPLRPFF 302
Cdd:cd15809  140 LHRVGVFLDHGAGEVSFYSAVDGVHLHTF-SCPLVSRLRPFF 180

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 767970495 157 ISLSEDVRYVIFGDDHLSAPTDPQGVD-SFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFL 235
Cdd:cd13743   25 LELSKGNTVVECGLLAQRLPSNPERFDySNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLNKSPENGVWL 104

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 236 ISSKRSNHYSLSTNsPPLIQYVQRPLGRVGVFLDYDNGSVSFFDVSKGS---LIYGFpPSSFSSPLRPFF 302
Cdd:cd13743  105 IGLKEGRVYEAFAN-PRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDelvPIYTF-QAEFQGKLYPLL 172

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767970495 175 APTDPQGVD-SFAVWGAQAFTSGKHYWEVDVTLSSNWILGVCRDSRTADANFVIDSDERFFLISSKRSNHYSLST--NSP 251
Cdd:cd13742   44 SSDDPNRFDkANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGRKGRLHALPSNGFWLLGCKEGKVYEAHVehKEP 123