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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 142 FRVDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK---SECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCnny 218
Cdd:cd15821    2 FQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERfddALCVL--GSPRFTSGRHYWEVDVGTSTEWDLGVC--- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 219 wKEK--RQND-KIDGEEGLFLLGCVKEDTHCSlfTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCS 295
Cdd:cd15821   77 -RESvnRQGPiELSPEHGFWTVSLRDGSVFFA--STVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKIS 153

                        170
                 ....*....|
gi 119594094 296 FSPPLRPIFC 305
Cdd:cd15821  154 AEEPLRPFFA 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 119594094 142 FRVDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK---SECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCnny 218
Cdd:cd15821    2 FQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERfddALCVL--GSPRFTSGRHYWEVDVGTSTEWDLGVC--- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 219 wKEK--RQND-KIDGEEGLFLLGCVKEDTHCSlfTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCS 295
Cdd:cd15821   77 -RESvnRQGPiELSPEHGFWTVSLRDGSVFFA--STVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKIS 153

                        170
                 ....*....|
gi 119594094 296 FSPPLRPIFC 305
Cdd:cd15821  154 AEEPLRPFFA 163

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 119594094  197 KYYWEVHMG--DSWNWAFGVCnnYWKEKRQNDKIDG-EEGLFLL-GCvkeDTHCSLFTTSPLVVQYVPRPTSTVGLFLDC 272
Cdd:pfam00622   1 RHYFEVEIFgqDGGGWRVGWA--TKSVPRKGERFLGdESGSWGYdGW---TGKKYWASTSPLTGLPLFEPGDVIGCFLDY 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 119594094  273 EGRTVSFVDVDQsSLIYTIPNCSFSPPLRPIFCCSH 308
Cdd:pfam00622  76 EAGTISFTKNGK-SLGYAFRDVPFAGPLFPAVSLGA 110

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 119594094 142 FRVDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK---SECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCnny 218
Cdd:cd15821    2 FQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERfddALCVL--GSPRFTSGRHYWEVDVGTSTEWDLGVC--- 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 219 wKEK--RQND-KIDGEEGLFLLGCVKEDTHCSlfTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCS 295
Cdd:cd15821   77 -RESvnRQGPiELSPEHGFWTVSLRDGSVFFA--STVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKIS 153

                        170
                 ....*....|
gi 119594094 296 FSPPLRPIFC 305
Cdd:cd15821  154 AEEPLRPFFA 163

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 119594094 145 DFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK-SECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywKE-- 221
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERfDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVA----REsv 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 222 KRQ-NDKIDGEEGLFLLGCVKEDTHCSLFTTS-PLVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCsFSPP 299
Cdd:cd13733   77 NRKgKITLSPENGYWTVGLRNGNEYKALTSPStPLSLREKPQ---KVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEK 152

                 ....*.
gi 119594094 300 LRPIFC 305
Cdd:cd13733  153 LYPYFS 158

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 119594094 142 FRVDFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECF-LVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWK 220
Cdd:cd12900    1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYpMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 221 EKRQNdKIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRptsTVGLFLDCEGRTVSFVDV-DQSSLIYTIPNCSFSPP 299
Cdd:cd12900   81 RKGQF-LLSPENGFWTIWLWNKKYEAGTSPQTTLHLQVPPC---QVGIFLDYEAGVVSFYNItDHGSLIYTFSECAFTGP 156

                 ....*
gi 119594094 300 LRPIF 304
Cdd:cd12900  157 LRPFF 161

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 119594094 145 DFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECF-LVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYwKEKR 223
Cdd:cd15820    5 DVILDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHyCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCREN-VERK 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 224 QNDKIDGEEGLFLLGCVKEDTHCSLftTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPLRPI 303
Cdd:cd15820   84 LWVKMAPENGFWTIGLSDGNDYQAL--TDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSGPLYPV 161

                 .
gi 119594094 304 F 304
Cdd:cd15820  162 F 162

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 119594094 145 DFTLQPERANSHIFLCGDLRSMNVGCDPQ---DDPDITGKSECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWKE 221
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLRQalpDSPERFDPGPCVL--GRERFTSGRHYWEVEVGDRTSWALGVCKENVNR 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 222 KRQNDKIDGeEGLFLLGCVKEDTHCSLFTTSPLvvqyvPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPLR 301
Cdd:cd15811   79 KEKGELSAG-NGFWILVFLGNYYSSERRTFAPL-----RDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLR 152

                 ...
gi 119594094 302 PIF 304
Cdd:cd15811  153 PLF 155

PRY/SPRY domain of tripartite motif-binding protein 38 (TRIM38), also known as Ring finger protein 15 (RNF15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM38, which is also known as RING finger protein 15 (RNF15) or RORET. TRIM38 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM38 has been shown to act as a suppressor in TOLL-like receptor (TLR)-mediated interferon (IFN)-beta induction by promoting degradation of TRAF6 and NAP1 through the ubiquitin-proteasome system. Another study has shown that TRIM38 may act as a novel negative regulator for TLR3-mediated IFN-beta signaling by targeting TRIF for degradation. TRIM38 has been identified as a critical negative regulator in TNFalpha- and IL-1beta-triggered activation of NF-kappaB and MAP Kinases (MAPKs); it causes degradation of two essential cellular components, TGFbeta-associated kinase 1 (TAK1)-associating chaperones 2 and 3 (TAB2/3). The degradation is promoted through a lysosomal-dependent pathway, which requires the C-terminal PRY-SPRY of TRIM38. Enterovirus 71 infection induces degradation of TRIM38, suggesting that TRIM38 may play a role in viral infections.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 139 LSGFRVDFTLQPERANSHIFLCGDLRSMNVGCdPQDDPDITGK----SECFLvwGAQAFTSGKYYWEVHMGDSWNWAFGV 214
Cdd:cd15815    8 LRRHQVSVTLDPDTAHPELTLSKDQRQVTYGR-CQENLDASPKrftvLPCVL--GCEGFTSGRHYFEVDVGEGTGWDVGV 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 215 CnnywKEKRQND---KIDGEEGLFLLGCVKEDTHCSLfTTSPLVVQYVPRPTsTVGLFLDCEGRTVSFVDVDQSSLIYTI 291
Cdd:cd15815   85 C----LENVQRGfgmKQEPEFGFWTIRLCEEDGYVAL-TSPPTPLPLREKPL-VVGVFLDYEAGLVSFYNMTTGSHIFTF 158

                        170
                 ....*....|....
gi 119594094 292 PNCSFSPPLRPIFC 305
Cdd:cd15815  159 PKASFSDTLRPYFQ 172

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 119594094 144 VDFTLQPERANSHIFLCGDLRSMNVGCDPQ----DDPDITGksecFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVC---N 216
Cdd:cd15824    3 VDVMLNPVNAVSNVVVSADQRQVTVVHICMfrnsNPCDFSA----FDVLGCQYFSSGKYYWEVDVSGKIAWILGVYskrN 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 217 NYWKEK-----------RQN--DKIDGEEGLFLLGCVKEDTHCSL---FTTSPLVVQ-YVPRPTSTVGLFLDCEGRTVSF 279
Cdd:cd15824   79 NLNKRKssgfafdpnvnHPNvySRYRPQNGYWVIGLQNESEYNAFedsSSSDPKVLTlSMAVPPHRVGVFLDYEAGTVSF 158

                        170       180
                 ....*....|....*....|....*.
gi 119594094 280 VDV-DQSSLIYTIPNCSFSPPLRPIF 304
Cdd:cd15824  159 FNVtNHGSLIYKFSKCCFSQPVYPYF 184

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 119594094 146 FTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGK-SECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywKEKRQ 224
Cdd:cd12893    2 VTLDPNTAHPWLSLSEDLTSVRYSSEKQQLPDNPERfDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVA----KESVQ 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 225 -NDKIDG--EEGL----FLLGCVKEDThcSLFTTSPLVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIPNcSFS 297
Cdd:cd12893   78 rKGKFTLspESGFwtigFSEGKYSART--SPEPRTPLRVKQKPQ---RIRVQLDWDRGKVSFSDPDTNTHIHTFTH-TFT 151

                 ....*....
gi 119594094 298 PPLRPIFCC 306
Cdd:cd12893  152 ERVFPYFYT 160

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 119594094 146 FTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKS-ECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnYWKEKRQ 224
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPEPPPRFfECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVT--YKSLPRK 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 225 NDKID-GEEGLFLLGCVKEDThcslFTTSPLVVQYV--PRPTSTVGLFLDCEGRTVSFVDV-DQSSLIYTIpNCSFSPPL 300
Cdd:cd12874   79 GKMSNlGRNNGSWCLEWRENE----FSAWHNNPETRlpVTPPRRLGVFLDCDGGSLSFYGVtDGVQLLYTF-KAKFTEPL 153

                 ....
gi 119594094 301 RPIF 304
Cdd:cd12874  154 YPAF 157

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 119594094 142 FRVDFTLQPERANSHIFLCGDLRSMN-VGCDPQDDPDITGKSECFlVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNN--- 217
Cdd:cd15823    1 YWVDVTLNPHTANLNLVLSKNRRQVRfVGAKLSGPSYLEEHYDCS-VLGSQHFSSGKHYWEVDVTKKTAWILGVCSHslg 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 218 -------YWKEKRQNDKIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSL-IY 289
Cdd:cd15823   80 ptfsfnqYAQNHNAYSRYQPQSGYWVIGLQHNHEYRAYEDSSTSLLLSMTVPPRRVGVFLDYEAGTVSFYNVTNHGFpIY 159

                        170
                 ....*....|....*
gi 119594094 290 TIPNCSFSPPLRPIF 304
Cdd:cd15823  160 TFSKYYFPTTLCPYF 174

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 119594094 189 GAQAFTSGKYYWEVHM---GDSWnWAFGVCNNYWKEKRQNDKIDgEEGLFLLGCVKEDTHCSLFTTSPLVVqyVPRPTST 265
Cdd:cd15812   46 GQETFSSGRHYWEVGMnltGDAL-WALGVCRDNVSRKDRVPKSP-ENGFWVVQLSKGKKYLSAMSALTPVT--LTEPPSH 121

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 119594094 266 VGLFLDCEGRTVSFVDVDQSSLIYTIPNCSFSPPLRPIFC 305
Cdd:cd15812  122 MGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPFFC 161

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 119594094 147 TLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSECFL-VWGAQAFTSGKYYWEVHMGDSWNWAFGVCnnywKE---K 222
Cdd:cd15818   16 TLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVaVLGSEGFTSGKHYWEVEVAKKTKWTLGVV----REsinR 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 223 RQNDKIDGEEGLFLLGCVKE------DTH-CSLFTTSPLvvqyvprptSTVGLFLDCEGRTVSFVDVDQSSLIYTIpNCS 295
Cdd:cd15818   92 KGNCPLSPEDGFWLLRLRNQnelkalDVPsFSLTLTSNL---------NKVGIYLDYEGGQVSFYNANTMSHIYTF-SDT 161

                        170
                 ....*....|
gi 119594094 296 FSPPLRPIFC 305
Cdd:cd15818  162 FTEKIYPYFC 171

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 119594094 145 DFTLQPERANSHIFLCGD-----LRSMNVGCdPQDDPDITgksECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYW 219
Cdd:cd15817    1 DLILDPETAHPNLIVSEDrkavrYRRMKPNC-PYDPRRFT---VYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSL 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 220 KEKRQnDKIDGEEGLFLLGCVKEDTHCSLFTTSPLVVQYVPRptsTVGLFLDCEGRTVSFVDVDQSSLIYTIPNCsFSPP 299
Cdd:cd15817   77 PRNAQ-DPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPS---RIGIFLDYELGEVSFYNMNDRSHLYTFTDT-FTGK 151

                 ....*
gi 119594094 300 LRPIF 304
Cdd:cd15817  152 LIPYF 156

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 119594094   195 SGKYYWEVHMGDSWNWAFGVCnnYWKEKRQNDKIDGEE----GLFLLGCVKedTHCSLFTTSPLVVQYVPRptsTVGLFL 270
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVA--TKSVPRGYFALLGEDkgswGYDGDGGKK--YHNSTGPEYGLPLQEPGD---VIGCFL 73

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 119594094   271 DCEGRTVSFVDVDQSSLIYTIPNCSFSPPLRPIFCCS 307
Cdd:smart00449  74 DLEAGTISFYKNGKYLHGLAFFDVKFSGPLYPAFSLG 110

PRY/SPRY domain in tripartite motif-binding protein 5 (TRIM5), also known as RING finger protein 88 (RNF88); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM5 which is also known as RING finger protein 88 (RNF88) or TRIM5alpha (TRIM5a), an antiretroviral restriction factor and a retrovirus capsid sensor in immune signaling. TRIM5 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. It blocks retrovirus infection soon after the virion core enters the cell cytoplasm by recognizing the capsid protein lattice that encases the viral genomic RNA; the SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. TRIM5a, an E3 ubiquitin ligase, 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, and amplifies 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 144 VDFTLQPERaNSHIFLCGDLRSMNVgCDPQDDPDITGKSECFLVWGAQAFTSGKYYWEVHMGDSWNWAFGVC-------- 215
Cdd:cd15822   12 VHVTLDPSN-NKNIVISEDRRQVRY-VRKQQRYNSNGNNEDYGVLGSPSITSGKHYWEVDVSKKRAWILGVCggkypnst 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 216 -NNYWKEKRQNDKIDG----EEGLFLLGC---------VKEDTHCSLFTTSPLVVqyvprPTSTVGLFLDCEGRTVSFVD 281
Cdd:cd15822   90 lKDFNKQGKNNQKQCSnyqpKYGYWVIGLqnkseynafEDSSSSDPLILTLSLTV-----PPCRVGVFLDYEAGTVSFFN 164

                        170       180
                 ....*....|....*....|....
gi 119594094 282 VDQS-SLIYTIPNCSFSPPLRPIF 304
Cdd:cd15822  165 VTNHgFLIYKFSSCSFSQEVFPYF 188

PRY/SPRY domain in tripartite motif-binding protein 7 (TRIM7); 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 7 (TRIM7), also referred to as glycogenin-interacting protein (GNIP) or RING finger protein 90 (RNF90). TRIM7 or GNIP interacts with glycogenin and stimulates its self-glucosylating activity via its SPRY domain. The GNIP gene encodes at least four distinct isoforms of GNIP, of which three (GNIP1, GNIP2, and GNIP3) have the B30.2 domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 145 DFTLQPERANSHIFLCGDLRSMNVGCDPQDDPDITGKSEC-FLVWGAQAFTSGKYYWEVHMGDSWNWAFGVCNNYWKEKR 223
Cdd:cd13740    1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTnTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 224 QNdKIDGEEGLFllgCVKEDTHCSLFTTSPLVVQYVPRPTSTVGLFLDCEGRTVSFVDVDQSSLIYTIpNCSFSPPLRPI 303
Cdd:cd13740   81 LT-PFTPEEGVW---ALQLNGGQYWAVTSPERTPLSCGHLSRVRVALDLEVGAVSFYAAEDMRHIYTF-RVNFQERVFPL 155

                 ....*
gi 119594094 304 F-CCS 307
Cdd:cd13740  156 FsVCS 160

PRY/SPRY domain in tripartite motif-containing domain 65 (TRIM65); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM65 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). The SPRY/PRY combination is a possible component of immune defense. This protein family has not been characterized.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 139 LSGFRVDFTLQPERANSHIFL-CGDLRSMNVGCDPQDDPditGKSECFLVWG---AQAFTSGKYYWEVHMGDSWNwAFGV 214
Cdd:cd12896    5 LWKDYRNLTFDPRTANKYLELsRQNRRAKHGRSAARGVP---ASPGSFELWQvqcTQSFQHGHHYWEVEVSSHSV-TLGV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 119594094 215 CNNYWKEKRQNDKID--GEEGLFLLGCVKEDTHCSLFTTSPlvvQYVPRPTST-VGLFLDCEGRTVSFVDV-DQSSLIYT 290
Cdd:cd12896   81 TYPGLPRHKQGGHKDniGRNPCSWGLQIQEDSLQAWHNGRA---QKLQGVSYRlLGVDLDLEAGTLTFYGLePGTQRLHT 157

                        170
                 ....*....|....
gi 119594094 291 IpNCSFSPPLRPIF 304
Cdd:cd12896  158 F-HAIFTQPLYPVF 170