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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 307
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789927 308 FSPCLPNEGTNTDPLIIC 325
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 307
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789927 308 FSPCLPNEGTNTDPLIIC 325
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

SPRY-associated domain; PRY is a 50-60 amino acids domain associated with SPRY domains, adjacent to its N-terminal. PRY and SPRY domains are structurally very similar and consist of a beta sandwich fold. Distant homologs are domains in butyrophilin/marenostrin/pyrin, evolutionarily more ancient than SPRY/B30.2 counterpart.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1039789927 151 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIF 199
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDERQNVPDNPERFDSWPCVLGSEGF 49

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKIGDDYSLWVS--SPLkgqHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 307
Cdd:cd13733    81 KITLSPENGYWTVGLRNGNEYKALTSpsTPL---SLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDC-FTEKLYPY 156

                         170
                  ....*....|....*...
gi 1039789927 308 FSPCLPNEGTNTDPLIIC 325
Cdd:cd13733   157 FSPCLNDGGKNSAPLIIC 174

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 149 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 228
Cdd:cd15813     9 VNVTLDPETAHPNLIFSDDLKSVRLGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRK 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 229 GNLPKPPGDLFSLIGLKIGDDYSLWVSSPLKGQhVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRPIF 308
Cdd:cd15813    89 GSMTLSPENGYWVVMMTKRNEYQASTSPPTRLW-LREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSFSSSGPLQPIF 167

                         170
                  ....*....|....*..
gi 1039789927 309 SPCLPNEGTNTDPLIIC 325
Cdd:cd15813   168 SPGTHDGGKNMDPLTIC 184

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 1039789927 149 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 228
Cdd:cd15819     2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 229 GNLPKPPGDLFSLIGLkIGDDYslW-VSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRPI 307
Cdd:cd15819    82 GRVTLSPENGFWAIRL-YGNEY--WaLTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTAFSGPLRPF 158

                         170
                  ....*....|....*...
gi 1039789927 308 FspCLPNEGTNtdPLIIC 325
Cdd:cd15819   159 F--RLWSSDSG--PLTIC 172

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 1039789927 151 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKGN 230
Cdd:cd15818    15 ITLDPKTAHPNLILSEDLTCVWHGDTKQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGN 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 231 LPKPPGDLFSLIGLKIGDDYSLwVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPIFSP 310
Cdd:cd15818    95 CPLSPEDGFWLLRLRNQNELKA-LDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDT-FTEKIYPYFCP 172

                         170
                  ....*....|....
gi 1039789927 311 CLPNEGTNTDPLII 324
Cdd:cd15818   173 CLNDSGENKEPLKI 186

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVRRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLP-KPPGDLFSLIglKIGDDYSlWVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPF-HEALRPI 307
Cdd:cd12888    81 EISfSPEEGIWAVG--QWGGQYW-ALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFaGERIFPW 157

                  .
gi 1039789927 308 F 308
Cdd:cd12888   158 F 158

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd15829    20 DVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTKA 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKiGDDYSLW--VSSPLKGQhvrEPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPI 307
Cdd:cd15829   100 RRPPSGQQGCWRIQLQ-GGDYDAPgaVPPPLLLE---VKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDT-FSGPLRPY 174

                         170
                  ....*....|....*...
gi 1039789927 308 FspCLpneGTNTDPLIIC 325
Cdd:cd15829   175 F--YV---GPDSKPLRIC 187

PRY/SPRY domain in tripartite motif-binding protein 58 (TRIM58), also known as BIA2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM58, also known as BIA2. TRIM58 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins.It is implicated by genome-wide association studies (GWAS) to regulate erythrocyte traits, including cell size and number. Trim58 facilitates erythroblast enucleation by inducing proteolytic degradation of the microtubule motor dynein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 N-LPKPPGDLFSLIGLKiGDDYSLWVSSPLKGQHVREPvHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPIF 308
Cdd:cd15816    81 EtTPSPENGVWAVWLLK-GNEYMVLASPSVPLLQLRRP-RRVGVFLDYEAGEISFYNVTAGSHIYTFRQL-FSGILRPYF 157

                         170
                  ....*....|....*.
gi 1039789927 309 SPClpnegtNTDPLII 324
Cdd:cd15816   158 FVC------DTTPLTL 167

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 1039789927 149 ADITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 228
Cdd:cd12905     4 APLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQ 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 229 GNLPKPPGDLFSLIGLKIGDDYSLwVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALrPIF 308
Cdd:cd12905    84 ARVKLCPENGYWTLRLRNGDEYWA-GTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQGPRGKVF-PFF 161

                         170
                  ....*....|....*..
gi 1039789927 309 SPCLPNEGTNTDPLIIC 325
Cdd:cd12905   162 STCFSDDGQNAEPMRLL 178

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd15828    11 DVTLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRNW 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKIGDDYSlwVSSPLKGQHVrePV---HKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRP 306
Cdd:cd15828    91 SNQPSVQDGLWAIGRYSESNYV--ALGPKKIQLL--PKvrpSKIGIFLDYELGEVSFYNMNDRSLLYTFSDS-FTGTLWP 165

                         170
                  ....*....|....*....
gi 1039789927 307 IFSpclpnEGTNTDPLIIC 325
Cdd:cd15828   166 YFY-----TGTDSEPLKIC 179

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKG 229
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 230 NLPKPPGDLFSLIGLKIgDDYSLWVSSPLKGQHVREPvHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRPIFS 309
Cdd:cd15817    81 QDPPSPLGGCWQIGRYM-SGYVASGPKTTQLLPVVKP-SRIGIFLDYELGEVSFYNMNDRSHLYTFTDT-FTGKLIPYFY 157

                         170
                  ....*....|....*.
gi 1039789927 310 PclpneGTNTDPLIIC 325
Cdd:cd15817   158 V-----GPDSEPLTIC 168

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 1039789927 153 LDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKGNLP 232
Cdd:cd13743    16 LDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLN 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 233 KPPGDLFSLIGLKIGDDYSLWVSS----PLKGqhvrePVHKVGVFLDYDSGHIAFYNA--TDE-SLIYSFpPTPFHEALR 305
Cdd:cd13743    96 KSPENGVWLIGLKEGRVYEAFANPrvplPLST-----RPQRIGVFLDYEKGELTFYNAdsPDElVPIYTF-QAEFQGKLY 169

                         170
                  ....*....|....*....
gi 1039789927 306 PIFSPCLPNEGTNTDPLII 324
Cdd:cd13743   170 PLLDVCWHERGANKLPIIL 188

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 1039789927 151 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEV--GKKTEWEVGICKDSVNRK 228
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 229 GNLPKPPGD-LFSLIGLKIGddysLWVS-SPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTpFHEALRP 306
Cdd:cd15826    82 GEMGLSAEDgVWAVILSHQQ----CWAStSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTAS-FSGKVFP 156

                  ..
gi 1039789927 307 IF 308
Cdd:cd15826   157 FF 158

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 1039789927 151 ITLDPATANAYLLLSEDLKSVRYGGTRQQLPDNPERFDQSaTVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRKGN 230
Cdd:cd12891     1 LTLDPNTAHNNLALSGDLKTVTCSSENQHYPDSPERFTHS-QVLSTQSFSSGRHYWEVEVSESGGWSVGVAYPSIERKGD 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 231 LpkppgdlfSLIGL--------KIGDDYSLW---VSSPLKGQhvrePVHKVGVFLDYDSGHIAFYNATD-ESLIYSFPPT 298
Cdd:cd12891    80 E--------SRIGRndkswcleWQDKSFSAWhnnEETPLPSV----SSRRLGVYLDYEAGRLSFYELSDpIRHLHTFTAT 147

                         170
                  ....*....|
gi 1039789927 299 pFHEALRPIF 308
Cdd:cd12891   148 -FTEPLHPAF 156

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGGTRQQL-PDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTEWEVGICKDSVNRK 228
Cdd:cd13742    13 NLTFDPDTAHPYLVVSSDGKRVECADQKQAVsSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGRK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 229 GNLPKPPGDLFSLIGLKIGDDYSLWVSS--PlKGQHVREPVHKVGVFLDYDSGHIAFYNATDE-SLIYSFpptPFHE--- 302
Cdd:cd13742    93 GRLHALPSNGFWLLGCKEGKVYEAHVEHkeP-RALRVEGRPTRIGVYLSFSDGVLSFYDASDEdNLVQLF---AFHErfp 168

                         170       180
                  ....*....|....*....|....
gi 1039789927 303 -ALRPIFSPCLPNEGTNTDPLIIC 325
Cdd:cd13742   169 gPLYPFFDVCWHDKGKNSQPLKIF 192

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 1039789927 150 DITLDPATANAYLLLSEDLKSVRYGG---TRQQLPDNPERFDqsatVLGAQIFTCGRHYWEVEVGKKTEWEVGIC----- 221
Cdd:cd15810     1 DVTLNPVNISLNIVISEDQRQVRIVPpqtSGQALTNNNYDFG----VLGSQYFSSGKHYWEVDVSKKSAWILGVCshkrs 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 222 ---KDSVNRKGNLPK-----PPGDLFSLIGLKIGDDYSLWVSSPLKGQHVRE-----PVHKVGVFLDYDSGHIAFYNATD 288
Cdd:cd15810    77 damTKSNANQINHQNvysryQPQYGYWVIGLQNESEYNAFEDSSSFNPHVLTlsvtvPPHRVGVFLDYEAGTVSFFNVTN 156

                         170       180
                  ....*....|....*....|....
gi 1039789927 289 E-SLIYSFPPTPFHEALRPIFSPC 311
Cdd:cd15810   157 HgSLIYKFSKCCFSTTVCPYFNPW 180

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 1039789927 150 DITLDPATANAYLLLSEDlKSVRYGGT-RQQLPDNPERFDQSATVLGAQIFTCGRHYWEVEVGKKTE--WEVGICKDSVN 226
Cdd:cd15812     1 DVVPDPSTAYPYLLLYES-RQRRYLSTpPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDalWALGVCRDNVS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039789927 227 RKGNLPKPPGDLFSLIGLKIGDDYsLWVSSPLKGQHVREPVHKVGVFLDYDSGHIAFYNATDESLIYSFPPTPFHEALRP 306
Cdd:cd15812    80 RKDRVPKSPENGFWVVQLSKGKKY-LSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQP 158

                         170
                  ....*....|
gi 1039789927 307 IFSPCLPNEG 316
Cdd:cd15812   159 FFCLGAPKSG 168