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 261599039 345 NFTLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCREGVER 417
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpdnperfDTCVCVLGSEGFSSGRHYWEVEVGGKTD--WDLGVARESVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 418 KGCFSECPEKGFWTVG-QSSSGYWAYvDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEAsFSGTLLPY 496
Cdd:cd13733   79 KGKITLSPENGYWTVGlRNGNEYKAL-TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                 ...
gi 261599039 497 FRL 499
Cdd:cd13733  157 FSP 159

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 261599039 149 SAPEVYI---KGPEDGGVCVVCMASGWYPEP-QVHWRDSRGEDLP 189
Cdd:cd21029    1 VKPRVRLssrPSPGDGHLQLSCHVTGFYPRPiEVTWLRDGQEQMD 45

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 261599039 345 NFTLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCREGVER 417
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpdnperfDTCVCVLGSEGFSSGRHYWEVEVGGKTD--WDLGVARESVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 418 KGCFSECPEKGFWTVG-QSSSGYWAYvDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEAsFSGTLLPY 496
Cdd:cd13733   79 KGKITLSPENGYWTVGlRNGNEYKAL-TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                 ...
gi 261599039 497 FRL 499
Cdd:cd13733  157 FSP 159

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 261599039  391 RYYWEVKLRNRDSSTWTLGVCREGVERKGCFSECPEKGFWTVgQSSSG--YWAyVDSGRDSLSIRQAPQSVGVFVDYDER 468
Cdd:pfam00622   1 RHYFEVEIFGQDGGGWRVGWATKSVPRKGERFLGDESGSWGY-DGWTGkkYWA-STSPLTGLPLFEPGDVIGCFLDYEAG 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 261599039  469 NISFYNMSdKSHLFSFHEASFSGTLLPYFRLKSGNISMT 507
Cdd:pfam00622  79 TISFTKNG-KSLGYAFRDVPFAGPLFPAVSLGAGEGLKF 116

Immunoglobulin V-set domain; This domain is found in antibodies as well as neural protein P0 and CTL4 amongst others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039   36 PSDPVVAAPGREAILPCSVSPAMSVENMEeLRWFR------TRFSQAVFVYRDQEEQKEEQlpqYSWRTSLVKdqfheGK 109
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTS-VYWYRqppgkgPTFLIAYYSNGSEEGVKKGR---FSGRGDPSN-----GD 72

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 261599039  110 AAVRIQNVQESDSGIYVCH-FKQGHFREEAILELKV 144
Cdd:pfam07686  73 GSLTIQNLTLSDSGTYTCAvIPSGEGVFGKGTRLTV 108

Immunoglobulin domain of Cluster of Differentiation (CD) 1; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin domain of Cluster of Differentiation (CD) 1. CD1 family of transmembrane glycoproteins, are structurally related to the major histocompatibility complex (MHC) proteins and form heterodimers with beta-2-microglobulin. They mediate the presentation of primarily lipid and glycolipid antigens of self or microbial origin to T cells. The human genome contains five CD1 family genes (CD1a, CD1b, CD1c, CD1d, and CD1e) organized in a cluster on chromosome 1. The CD1 family members are thought to differ in their cellular localization and specificity for particular lipid ligands. CD1a localizes to the plasma membrane and to recycling vesicles of the early endocytic system. Alternative splicing results in multiple transcript variants. Immunoglobulin (Ig) domain of major histocompatibility complex (MHC) class I alpha chain. Class I MHC proteins bind antigenic peptide fragments and present them to CD8+ T lymphocytes. Class I molecules consist of a transmembrane alpha chain and a small chain called the beta-2-microglobulin. The alpha chain contains three extracellular domains, two of which fold together to form the peptide-binding cleft (alpha1 and alpha2), and one which has an Ig fold (alpha3). Peptide binding to class I molecules occurs in the endoplasmic reticulum (ER) and involves both chaperones and dedicated factors to assist in peptide loading. Class I MHC molecules are expressed on most nucleated cells. C1-set Ig domains have one beta sheet that is formed by strands A, B, E, and D and the other strands by G, F, C, and C'.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 261599039 149 SAPEVYI---KGPEDGGVCVVCMASGWYPEP-QVHWRDSRGEDLP 189
Cdd:cd21029    1 VKPRVRLssrPSPGDGHLQLSCHVTGFYPRPiEVTWLRDGQEQMD 45

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 261599039 345 NFTLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCREGVER 417
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLpdnperfDTCVCVLGSEGFSSGRHYWEVEVGGKTD--WDLGVARESVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 418 KGCFSECPEKGFWTVG-QSSSGYWAYvDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEAsFSGTLLPY 496
Cdd:cd13733   79 KGKITLSPENGYWTVGlRNGNEYKAL-TSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                 ...
gi 261599039 497 FRL 499
Cdd:cd13733  157 FSP 159

Immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG); The members here are composed of the immunoglobulin (Ig)-like domain of myelin oligodendrocyte glycoprotein (MOG). MOG, a minor component of the myelin sheath, is an important CNS-specific autoantigen, linked to the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). It is a transmembrane protein having an extracellular Ig domain. MOG is expressed in the CNS on the outermost lamellae of the myelin sheath, and on the surface of oligodendrocytes, and may participate in the completion, compaction, and/or maintenance of myelin. This group also includes butyrophilin (BTN). BTN is the most abundant protein in bovine milk-fat globule membrane (MFGM).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039  31 FRVFGPSDPVVAAPGREAILPCSVSPAMSVENMEeLRWFRTRFSQAVFVYRDQEEQKEEQLPQYSWRTSLVKDQFHEGKA 110
Cdd:cd05713    1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHME-VRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSV 79

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 261599039 111 AVRIQNVQESDSGIYVCHFKQGHFREEAILELKVA 145
Cdd:cd05713   80 ALRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 261599039 341 FQACNFTLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCRE 413
Cdd:cd15820    1 FQPADVILDPDTANPILLISEDQRSLQWADEPQNLpdnpkrfDWHYCVLGCKSFTSGRHFWEVEVGDRKE--WYVGVCRE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 414 GVERKGCFSECPEKGFWTVGQS-SSGYWAYVDSgRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEASFSGT 492
Cdd:cd15820   79 NVERKLWVKMAPENGFWTIGLSdGNDYQALTDP-RTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSGP 157

                 ....*....
gi 261599039 493 LLPYFRLKS 501
Cdd:cd15820  158 LYPVFRLLS 166

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 261599039 345 NFTLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCREGVER 417
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLpdnperfDTWPCVLGCEGFTSGRHYWEVEVGDGGG--WAVGVARESVRR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 418 KGCFSECPEKGFWTVGQSSSGYWAyVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEASFSG-TLLPY 496
Cdd:cd12888   79 KGEISFSPEEGIWAVGQWGGQYWA-LTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAGeRIFPW 157

                 ....*.
gi 261599039 497 FRLKSG 502
Cdd:cd12888  158 FWVGKG 163

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 261599039 347 TLDPASAHPILNVSQDRMRV-------TRKDTTMCLDDLFCVLGTNGISSGRYYWEVKLRNrdSSTWTLGVCREGVERKG 419
Cdd:cd15821    7 TLDVDTANNYLIISEDLRSVrcgcfrqNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGT--STEWDLGVCRESVNRQG 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 261599039 420 CFSECPEKGFWTVG-QSSSGYWAYVdSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEASFSGTLLPYF 497
Cdd:cd15821   85 PIELSPEHGFWTVSlRDGSVFFAST-VPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEPLRPFF 162

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 261599039 338 KEHFQAcNFTLDPASAHPILNVSQDRMRVT---RKDTTMCLDDLF----CVLGTNGISSGRYYWEVKLRnrDSSTWTLGV 410
Cdd:cd15829   14 IKKFRV-DVTLDPETAHPNLLVSEDKKCVTftkKKQRVPDSPKRFtvnpVVLGFPGFHSGRHFWEVEVG--DKPEWAVGV 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 411 CREGVERKGCFSECPEKGFWTVGQSSSGYWAyVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEaSFS 490
Cdd:cd15829   91 CKDSLSTKARRPPSGQQGCWRIQLQGGDYDA-PGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTD-TFS 168

                 ....*....
gi 261599039 491 GTLLPYFRL 499
Cdd:cd15829  169 GPLRPYFYV 177

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 261599039 345 NFTLDPASAHPILNVSQDRMRVTRKDTTMCLDDL-------FCVLGTNGISSGRYYWEVKLRNRdsSTWTLGVCREGVER 417
Cdd:cd15818   14 LITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNperfdssVAVLGSEGFTSGKHYWEVEVAKK--TKWTLGVVRESINR 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 418 KGCFSECPEKGFWTVGQSSSGYWAYVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEaSFSGTLLPYF 497
Cdd:cd15818   92 KGNCPLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSD-TFTEKIYPYF 170

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 261599039 347 TLDPASAHPILNVSQDRMRVTRKDTTMCLDD-----LFCV--LGTNGISSGRYYWEVKLRNRdsSTWTLGVCREGVERKG 419
Cdd:cd12905    7 TFDPETAHPSLILSRDLTAVTESDEMQPYPRspkrfLQCVnvLASQGFQSGRHYWEVWVGSK--TKWDLGVASESVDRQA 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 420 CFSECPEKGFWTVG-QSSSGYWAYVdSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEASfSGTLLPYFR 498
Cdd:cd12905   85 RVKLCPENGYWTLRlRNGDEYWAGT-QPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGP-RGKVFPFFS 162

                        170       180
                 ....*....|....*....|....
gi 261599039 499 lksgnismtvssmACVSEGQQGEE 522
Cdd:cd12905  163 -------------TCFSDDGQNAE 173

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 261599039 346 FTLDPASAHPILNVSQDRMRVTR-KDTTMCLDDL--F----CVLGTNGISSGRYYWEVKLRnrDSSTWTLGVCREGVERK 418
Cdd:cd12893    2 VTLDPNTAHPWLSLSEDLTSVRYsSEKQQLPDNPerFdpypCVLGSEGFTSGKHSWDVEVG--DNTSWMLGVAKESVQRK 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 419 GCFSECPEKGFWTVGQSSSGY-WAYVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHeASFSGTLLPYF 497
Cdd:cd12893   80 GKFTLSPESGFWTIGFSEGKYsARTSPEPRTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFT-HTFTERVFPYF 158

                        170
                 ....*....|.
gi 261599039 498 RLKSGNISMTV 508
Cdd:cd12893  159 YTGCKSEPLRI 169

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 261599039 347 TLDPASAHPILNVSQDRMRVTRKDTTMCL-------DDLFCVLGTNGISSGRYYWEVKLRNRDSstWTLGVCREGVERKG 419
Cdd:cd12900    6 TLDPDTANPWLILSKDRRQVRLGDTHQNVpeneerfDNYPMVLGAQRFNSGKHYWEVDVTGKEA--WDLGVCRDSVRRKG 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 261599039 420 CFSECPEKGFWTVGQSSSGYWAYVdSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHL-FSFHEASFSGTLLPYF 497
Cdd:cd12900   84 QFLLSPENGFWTIWLWNKKYEAGT-SPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDHGSLiYTFSECAFTGPLRPFF 161

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 261599039 343 ACNFTLDPASAHPILNVSQDRMRVTRKDTTMCLDD------LF-CVLGTNGISSGRYYWEVKLRnrDSSTWTLGVCREGV 415
Cdd:cd15814    1 SVDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDnperfnLFpCVLGSPCFIAGRHYWEVEVG--DKAKWTIGVCEDSV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 416 ERKGCFSECPEKGFWTVG-QSSSGYWAyVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHEASFSGTLL 494
Cdd:cd15814   79 CRKGGVTSAPQNGFWAVSlWYGKEYWA-LTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVR 157

                 ....*
gi 261599039 495 PYFRL 499
Cdd:cd15814  158 PYFSL 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 261599039 345 NFTLDPASAHPILNVSQDRMRVT-RKDTTM---CLDDLFC--VLGTNGISSGRYYWEVKLRNRdsSTWTLGVC------- 411
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRiVPPQTSgqaLTNNNYDfgVLGSQYFSSGKHYWEVDVSKK--SAWILGVCshkrsda 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 412 -----REGVERKGCFSEC-PEKGFWTVG-QSSSGYWAYVDSGRDS-----LSIRQAPQSVGVFVDYDERNISFYNMSDK- 478
Cdd:cd15810   79 mtksnANQINHQNVYSRYqPQYGYWVIGlQNESEYNAFEDSSSFNphvltLSVTVPPHRVGVFLDYEAGTVSFFNVTNHg 158

                        170       180
                 ....*....|....*....|....*....
gi 261599039 479 SHLFSFHEASFSGTLLPYFRLKSGNISMT 507
Cdd:cd15810  159 SLIYKFSKCCFSTTVCPYFNPWNCPVPMT 187

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 261599039 346 FTLDPASAHPILNVSQDRMRVTRKDTTM---------CLDDLFCVLGTNGISSGRYYWEVKLrnrDSSTW-TLGVCREGV 415
Cdd:cd13734    1 FKLDPKTAHRKLRLSNDNLTVEYDPEGSkdqaavlprRFTGSPAVLGDVAISSGRHYWEVSV---SRSTSyRVGVAYKSA 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 416 ERKGCFSEcpEKGFWTVGQSSSGYWAYVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDKSHLFSFHeASFSGTLLP 495
Cdd:cd13734   78 PRDEDLGK--NSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFH-VDFEGPVCP 154

                        170
                 ....*....|
gi 261599039 496 YFRLKSGNIS 505
Cdd:cd13734  155 AFAVWNGSLT 164

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 261599039 378 LFCVLGTNGISSGRYYWEVKlrNRDSSTWTLGVCREGVERKGCFSE-CPEKGFWTVGQSSSGYWAYVDSGRDSLSIRQAP 456
Cdd:cd15809   63 LPCVLGKNVFTSGKHYWEVE--NRDSLEIAVGVCREDVMGITDGSEmSPHVGIWAICWSSAGYRPLTSSPVSPTKQEPAL 140

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 261599039 457 QSVGVFVDYDERNISFYNMSDKSHLFSFhEASFSGTLLPYFRL 499
Cdd:cd15809  141 HRVGVFLDHGAGEVSFYSAVDGVHLHTF-SCPLVSRLRPFFWL 182

PRY/SPRY domain of tripartite motif-binding protein 14 (TRIM14); This is a TRIM14 domain family 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. TRIM14 domains have yet to be characterized. These B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. It belongs to Class IV TRIM protein family which has members involved in antiviral immunity at various levels of interferon signaling cascade.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 347 TLDPASAHPILNVSQDRMRVT---RKDTTMC----LDDLFCVLGTNGISSGRYYWEVKLRNRdSSTWTLGVCREGVERKG 419
Cdd:cd13738    2 TLEPDTLHPRLRLSDDRLTVScgwLGTLGLCppqrFDKLWQVLSRDSFFSGRHYWEVDLQEA-GAGWWVGAAYPSIGRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 261599039 420 CfSECPEKGF----WTVGQSSSGYWAYVDSGRDSLSIRQAPQSVGVFVDYDERNISFYNMSDK-SHLFSFHeASFSGTLL 494
Cdd:cd13738   81 D-SEAARLGWnrqsWCLKRYDLEYWAFHDGQRSRLRPEDDPDRLGVFLDYEAGILSFYDVTGGmTHLHTFR-ATFQEPLY 158

                        170
                 ....*....|..
gi 261599039 495 PYFRLKSGNISM 506
Cdd:cd13738  159 PALRLWEGSISI 170

PRY/SPRY domain in tripartite motif-binding protein 41 (TRIM41); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 41 (TRIM41). TRIM41 (also known as RING finger-interacting protein with C kinase or RINCK) is localized to speckles in the cytoplasm and nucleus, and functions as an E3 ligase that catalyzes the ubiquitin-mediated degradation of protein kinase C.