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 94957742 289 EVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRrK 366
Cdd:cd13733   1 DVTLDPDTAHPNLILSeDLKSVRYGDKRQNLPDNPERFdTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR-K 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 367 EYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIeY 446
Cdd:cd13733  80 GKITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF-S 158

                       170
                ....*....|....*.
gi 94957742 447 PSYNE--QNGTPIVIC 460
Cdd:cd13733 159 PCLNDggKNSAPLIIC 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 94957742 289 EVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRrK 366
Cdd:cd13733   1 DVTLDPDTAHPNLILSeDLKSVRYGDKRQNLPDNPERFdTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR-K 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 367 EYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIeY 446
Cdd:cd13733  80 GKITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF-S 158

                       170
                ....*....|....*.
gi 94957742 447 PSYNE--QNGTPIVIC 460
Cdd:cd13733 159 PCLNDggKNSAPLIIC 174

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 94957742    339 GKHYWEVDGGHNKRWRVGVCRDDVDRRKEyVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTI 418
Cdd:smart00449   2 GRHYFEVEIGDGGHWRVGVATKSVPRGYF-ALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 94957742    419 SFFNINDQSLIYT-LTCRFEGLLRPYIeypSYNEQNGTPIVICP 461
Cdd:smart00449  81 SFYKNGKYLHGLAfFDVKFSGPLYPAF---SLGSGNSVRLNFGP 121

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 94957742    24 PDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFR---GQFSSVVHLYRDGKDQPFMQMPQYQGRtklvkDSIAEGRISLR 100
Cdd:pfam07686   2 TPREVTVALGGSVTLPCTYSSSMSEASTSVYWYRqppGKGPTFLIAYYSNGSEEGVKKGRFSGR-----GDPSNGDGSLT 76

                          90       100
                  ....*....|....*....|.
gi 94957742   101 LENITVLDAGLYGCRISSQSY 121
Cdd:pfam07686  77 IQNLTLSDSGTYTCAVIPSGE 97

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 94957742 289 EVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRrK 366
Cdd:cd13733   1 DVTLDPDTAHPNLILSeDLKSVRYGDKRQNLPDNPERFdTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNR-K 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 367 EYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIeY 446
Cdd:cd13733  80 GKITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYF-S 158

                       170
                ....*....|....*.
gi 94957742 447 PSYNE--QNGTPIVIC 460
Cdd:cd13733 159 PCLNDggKNSAPLIIC 174

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 94957742  19 WQVFGPDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFRGQFSSVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRIS 98
Cdd:cd05713   1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                        90       100       110
                ....*....|....*....|....*....|....
gi 94957742  99 LRLENITVLDAGLYGCRISSQSYYQKAIWELQVS 132
Cdd:cd05713  81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 94957742 287 AVEVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRFTRKS-VVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVdR 364
Cdd:cd15819   1 AVNVTLDPDTAHPALILSeDGRSVTWGETRQDLPENPERFDSLPcVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNV-M 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 365 RKEYVTLSPDHGYWVLRL-NGEhlYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLT-CRFEGLLRP 442
Cdd:cd15819  80 RKGRVTLSPENGFWAIRLyGNE--YWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPqTAFSGPLRP 157

                       170
                ....*....|....*...
gi 94957742 443 YIEYPSYNEqngTPIVIC 460
Cdd:cd15819 158 FFRLWSSDS---GPLTIC 172

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 94957742 284 RKHAVEVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRFTRKSVV-ASQSFQAGKHYWEVDGGHNKRWRVGVCRDD 361
Cdd:cd15829  15 KKFRVDVTLDPETAHPNLLVSeDKKCVTFTKKKQRVPDSPKRFTVNPVVlGFPGFHSGRHFWEVEVGDKPEWAVGVCKDS 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 362 VDRrKEYVTLSPDHGYWVLRLNGEHlYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLR 441
Cdd:cd15829  95 LST-KARRPPSGQQGCWRIQLQGGD-YDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLR 172

                ..
gi 94957742 442 PY 443
Cdd:cd15829 173 PY 174

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 94957742 290 VTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRFTRK-SVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRRKE 367
Cdd:cd12905   6 LTFDPETAHPSLILSrDLTAVTESDEMQPYPRSPKRFLQCvNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQAR 85

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 368 yVTLSPDHGYWVLRL-NGEHLYFTLNPRfISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTltcrFEGLLRPYIeY 446
Cdd:cd12905  86 -VKLCPENGYWTLRLrNGDEYWAGTQPW-TRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYS----FHQGPRGKV-F 158

                       170       180
                ....*....|....*....|
gi 94957742 447 P------SYNEQNGTPIVIC 460
Cdd:cd12905 159 PffstcfSDDGQNAEPMRLL 178

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 94957742 285 KHAVEVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDV 362
Cdd:cd15821   1 KFQVDMTLDVDTANNYLIISeDLRSVRCGCFRQNRKELAERFdDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 363 dRRKEYVTLSPDHGYWVLRLNGEHLYF--TLNPRFISVFPRtpPTKIGVFLDYECGTISFFNINDQSLIYTLTCRF-EGL 439
Cdd:cd15821  81 -NRQGPIELSPEHGFWTVSLRDGSVFFasTVPLTVLWVNPR--LHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISaEEP 157

                       170       180
                ....*....|....*....|.
gi 94957742 440 LRPYIEYPSYNEQNGTPIVIC 460
Cdd:cd15821 158 LRPFFAPANPYGDDQGVLSIC 178

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 94957742 290 VTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRRKE 367
Cdd:cd15818  15 ITLDPKTAHPNLILSeDLTCVWHGDTKQMLPDNPERFdSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGN 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 368 YvTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIeYP 447
Cdd:cd15818  95 C-PLSPEDGFWLLRLRNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTFSDTFTEKIYPYF-CP 172

                       170
                ....*....|....
gi 94957742 448 SYNE--QNGTPIVI 459
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 94957742 289 EVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRF-TRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVdRRK 366
Cdd:cd12888   1 NVTLDPDTAHPRLVLSeDRKSVRWGDTRQDLPDNPERFdTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESV-RRK 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 94957742 367 EYVTLSPDHGYWVLRLNGEhLYFTLNprfiSVFPRTP----PTKIGVFLDYECGTISFFNINDQSLIYTLT 433
Cdd:cd12888  80 GEISFSPEEGIWAVGQWGG-QYWALT----SPETPLPlsevPRRIRVYLDYEGGQVAFFDADNEAPIFTFP 145

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 94957742 284 RKHAVEVTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRFT-RKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDD 361
Cdd:cd15815   9 RRHQVSVTLDPDTAHPELTLSkDQRQVTYGRCQENLDASPKRFTvLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLEN 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 362 VDRRKEyVTLSPDHGYWVLRLNGEHLYFTLNPrfisvfPRTP------PTKIGVFLDYECGTISFFNINDQSLIYTL-TC 434
Cdd:cd15815  89 VQRGFG-MKQEPEFGFWTIRLCEEDGYVALTS------PPTPlplrekPLVVGVFLDYEAGLVSFYNMTTGSHIFTFpKA 161

                ....*....
gi 94957742 435 RFEGLLRPY 443
Cdd:cd15815 162 SFSDTLRPY 170

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 94957742 287 AVEVTLDPETAHPKLCVSD-LKTVTHRKAPQEVPHSEKRFTR-KSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVdR 364
Cdd:cd15814   1 SVDVTLDPDTAYPSLILSDnLRQVRYSYLQQDLPDNPERFNLfPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSV-C 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 365 RKEYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLT-CRFEGLLRPY 443
Cdd:cd15814  80 RKGGVTSAPQNGFWAVSLWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFShATFCGPVRPY 159

                       170
                ....*....|....*...
gi 94957742 444 IEYPSYNEQNGTPIVICP 461
Cdd:cd15814 160 FSLSYSGGKSAAPLIICP 177

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 94957742 290 VTLDPETAHPKLCVS-DLKTVTHRKAPQEVPHSEKRFT-RKSVVASQSFQAGKHYWEVD--GGHNKRWRVGVCRDDVdRR 365
Cdd:cd15826   2 VTLDPQTASGSLVLSeDRKSVRYTRQKQNLPDSPLRFDgLPAVLGSPGFSSGRHRWQVEvqLGDGGGCTVGVAGESV-RR 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 94957742 366 KEYVTLSPDHGYWVLRLNGEHLYFTLNPRfISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYI 444
Cdd:cd15826  81 KGEMGLSAEDGVWAVILSHQQCWASTSPG-TDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFF 158

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 94957742 279 ELRDARKHAVEVTLDPETAHPKLCVSDLKTVTHRKaPQEVPHSEKRFTRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVC 358
Cdd:cd15822   3 ELTDVQRYWVHVTLDPSNNKNIVISEDRRQVRYVR-KQQRYNSNGNNEDYGVLGSPSITSGKHYWEVDVSKKRAWILGVC 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 359 -------------RDDVDRRKEYVTLSPDHGYWVLRLNGEHLY------FTLNPRFISVFPRTPPTKIGVFLDYECGTIS 419
Cdd:cd15822  82 ggkypnstlkdfnKQGKNNQKQCSNYQPKYGYWVIGLQNKSEYnafedsSSSDPLILTLSLTVPPCRVGVFLDYEAGTVS 161

                       170       180
                ....*....|....*....|....*.
gi 94957742 420 FFNI-NDQSLIYTL-TCRFEGLLRPY 443
Cdd:cd15822 162 FFNVtNHGFLIYKFsSCSFSQEVFPY 187

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain provides specificity and the capsid recognition motif to retroviral restriction, TRIM34 binds HIV-1 capsid but does not restrict HIV-1 infection.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 288 VEVTLDPETAHPKLCVSDlktvTHRKApQEVPHSEKRFTRKSVVASQSFQAGKHYWEVDGGHNKRWRVGV-CR------D 360
Cdd:cd15825   2 VDFTLNPVNLNLNLVLSE----DQRQV-TSVPIWPFKCYNYGILGSQYFSSGKHYWEVDVSKKTAWILGVyCRkrsrtfK 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 361 DVDRRKE----YVTLSPDHGYWVLRLNGEHLYF------TLNPRFISVFPRTPPTKIGVFLDYECGTISFFNI-NDQSLI 429
Cdd:cd15825  77 YVRQGKNhpnvYSRYRPQYGYWVIGLQNKSEYYafedssTSDPKVLTLSVATPPHRVGVFLDYEAGTVSFFNVtNHGSLI 156

                       170       180       190
                ....*....|....*....|....*....|....
gi 94957742 430 YTLT-CRFEGLLRPYieypsYNEQN-GTPIVICP 461
Cdd:cd15825 157 YKFSkCCFSQPVYPY-----FNPWNcPAPMTLCP 185

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 94957742 291 TLDPETAHPKLCVS-DLKTVTH---RKAPQEVPHSEKRFTRKSVVASQSFQAGKHYWEVDGGHNKRWRVGVCRDDVDRRK 366
Cdd:cd13734   2 KLDPKTAHRKLRLSnDNLTVEYdpeGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRDE 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 94957742 367 EyvtLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRP 442
Cdd:cd13734  82 D---LGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPARIGVLLDYDNGTLSFYDAESKQHLYTFHVDFEGPVCP 154

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 94957742 289 EVTLDPETAHPKLCVSDLKTVTHRKAPQE-VPHSEKRF-TRKSVVASQSFQAGKHYWEV--DGGHNKRWRVGVCRDDVDR 364
Cdd:cd15812   1 DVVPDPSTAYPYLLLYESRQRRYLSTPPDgTPCSKDRFlAYPCAVGQETFSSGRHYWEVgmNLTGDALWALGVCRDNVSR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 94957742 365 rKEYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVFPRTPPTKIGVFLDYECGTISFFNINDQSLIYTLT-CRFEGLLRPY 443
Cdd:cd15812  81 -KDRVPKSPENGFWVVQLSKGKKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSqAAFPGPLQPF 159