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 1622935185  31 FIVVGPTDPILATVGENTTLRCHLSPEKNAEDMEVRWFRSQFFPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVA 110
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622935185 111 LVIHNVTAQENGTYRCYFQEGRSYDEAILHLVVA 144
Cdd:cd05713    81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 1622935185  31 FIVVGPTDPILATVGENTTLRCHLSPEKNAEDMEVRWFRSQFFPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVA 110
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622935185 111 LVIHNVTAQENGTYRCYFQEGRSYDEAILHLVVA 144
Cdd:cd05713    81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 1622935185 312 KHYWEVEVENVI--EWTVGVCRDSVERKEEVLLLPQNGFWTLDMHKGQ-YRALSSPKRILPLKESLCRVGVFLDYEAGDV 388
Cdd:pfam00622   1 RHYFEVEIFGQDggGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKkYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100
                  ....*....|....*....|....*..
gi 1622935185 389 SFYNMrDRSHIYTCPRSAFSVPVRPFF 415
Cdd:pfam00622  81 SFTKN-GKSLGYAFRDVPFAGPLFPAV 106

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622935185   49 TLRCHLSPEKNAeDMEVRWFRSQFFPAV-FVYKGGRERTEEQMEEYRGRTTFvSKDISRGSVALVIHNVTAQENGTYRC 126
Cdd:smart00406   3 TLSCKFSGSTFS-SYYVSWVRQPPGKGLeWLGYIGSNGSSYYQESYKGRFTI-SKDTSKNDVSLTISNLRVEDTGTYYC 79

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRCPLRhlgESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKR---QNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLDMHKG-QYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPF 414
Cdd:cd13733    78 RKGKITLSPENGYWTVGLRNGnEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTF-TDCFTEKLYPY 156

                         170
                  ....*....|....*...
gi 1622935185 415 FRIGSDDR-----PIFIC 427
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 1622935185 247 WRRTVLHAVDVVLDPDTAHPDLLLSEDRRSVRrcpLRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWT 326
Cdd:cd15813     1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVR---LGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWI 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 327 VGVCRDSVERKEEVLLLPQNGFWTLDMHKG-QYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRS 405
Cdd:cd15813    78 LGVCKASVSRKGSMTLSPENGYWVVMMTKRnEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSF 157

                         170       180
                  ....*....|....*....|....*..
gi 1622935185 406 AFSVPVRPFFRIGSDDR-----PIFIC 427
Cdd:cd15813   158 SSSGPLQPIFSPGTHDGgknmdPLTIC 184

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRCPLRHlgeSVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd12888     1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQ---DLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLDMHKGQYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVP-VRPF 414
Cdd:cd12888    78 RKGEISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAGErIFPW 157

                  ....
gi 1622935185 415 FRIG 418
Cdd:cd12888   158 FWVG 161

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 1622935185  31 FIVVGPTDPILATVGENTTLRCHLSPEKNAEDMEVRWFRSQFFPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVA 110
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1622935185 111 LVIHNVTAQENGTYRCYFQEGRSYDEAILHLVVA 144
Cdd:cd05713    81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 1622935185 253 HAVDVVLDPDTAHPDLLLSEDRRSVRRcplRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRD 332
Cdd:cd15815    11 HQVSVTLDPDTAHPELTLSKDQRQVTY---GRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 333 SVERKEEVLLLPQNGFWTLDMHKGQ-YRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPV 411
Cdd:cd15815    88 NVQRGFGMKQEPEFGFWTIRLCEEDgYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSDTL 167

                  ....*.
gi 1622935185 412 RPFFRI 417
Cdd:cd15815   168 RPYFQV 173

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRCPLRhlgESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGDLR---QALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVN 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLdMHKGQYRalSSPKRIL-PLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVRPF 414
Cdd:cd15811    78 RKEKGELSAGNGFWIL-VFLGNYY--SSERRTFaPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPL 154

                         170
                  ....*....|....
gi 1622935185 415 FR-IGSDDRPIFIC 427
Cdd:cd15811   155 FSpLSSSPTPMTIC 168

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRcplRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQD---GELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLDMHKG-QYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPF 414
Cdd:cd15816    78 RKGETTPSPENGVWAVWLLKGnEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTF-RQLFSGILRPY 156

                         170
                  ....*....|...
gi 1622935185 415 FrigsddrpiFIC 427
Cdd:cd15816   157 F---------FVC 160

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 1622935185 257 VVLDPDTAHPDLLLSEDRRSVRRCPLRHLgesVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVER 336
Cdd:cd15818    15 ITLDPKTAHPNLILSEDLTCVWHGDTKQM---LPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINR 91

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 337 KEEVLLLPQNGFWTLDM-HKGQYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPFF 415
Cdd:cd15818    92 KGNCPLSPEDGFWLLRLrNQNELKALDVPSFSLTLTSNLNKVGIYLDYEGGQVSFYNANTMSHIYTF-SDTFTEKIYPYF 170

                         170
                  ....*....|....*
gi 1622935185 416 rigsddrpifiCPAL 430
Cdd:cd15818   171 -----------CPCL 174

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRrcpLRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd15817     1 DLILDPETAHPNLIVSEDRKAVR---YRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLP 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLDMHKGQYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPFF 415
Cdd:cd15817    78 RNAQDPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTF-TDTFTGKLIPYF 156

                         170
                  ....*....|..
gi 1622935185 416 RIGSDDRPIFIC 427
Cdd:cd15817   157 YVGPDSEPLTIC 168

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 1622935185 257 VVLDPDTAHPDLLLSEDRRSVRRCPLrhlGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVER 336
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDI---SQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 337 KEEVLLL-PQNGFWTLDMHKGQYRALSS-PKRILPLKEsLCRVGVFLDYEAGDVSFYNMRD-RSHIYTCpRSAFSVPVRP 413
Cdd:cd12874    78 KGKMSNLgRNNGSWCLEWRENEFSAWHNnPETRLPVTP-PRRLGVFLDCDGGSLSFYGVTDgVQLLYTF-KAKFTEPLYP 155

                         170
                  ....*....|....
gi 1622935185 414 FFRIGSdDRPIFIC 427
Cdd:cd12874   156 AFWLGE-GSTLSIC 168

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRCPLRhlgESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGVRLAERR---QEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGRRGWAVGAARESTH 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEV-----------------------LLLPQNGF-----WTLDMHKGQYRALSSPKR-ILPLKESLCRVGVFLDYEAG 386
Cdd:cd13741    78 HKEKVgsggssvssgdasssrhhhrrrrLHLPQQPLlqrevWCVGTNGKRYQAQSSTEQtLLSPSEKPRRFGVYLDYEAG 157

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1622935185 387 DVSFYNMRDRSHIYTCPRSAFSVPVRPFFRIGSDDRPIFICP 428
Cdd:cd13741   158 RLGFYNAETLAHVHTFSAAFLGERVFPFFRVLSKGTRIKLCP 199

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRrcpLRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 335
Cdd:cd13740     1 ELTLDPDSANPRLILSLDLKSVR---LGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 336 RKEEVLLLPQNGFWTLDMHKGQYRALSSPKRIlPLK-ESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPF 414
Cdd:cd13740    78 RKGLTPFTPEEGVWALQLNGGQYWAVTSPERT-PLScGHLSRVRVALDLEVGAVSFYAAEDMRHIYTF-RVNFQERVFPL 155

                         170
                  ....*....|....
gi 1622935185 415 FRIGSDDRPIFICP 428
Cdd:cd13740   156 FSVCSTGTYLRIWP 169

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 257 VVLDPDTAHPDLLLSEDrrsvrrCPLRHLGESVP----DNPERFDSEPCVLGRESFASGKHYWEVEVENVIEWTVGVCRD 332
Cdd:cd13744    14 LTLDPVTAHQRLILSDD------CTIVAYGNLHPqplqDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 333 SVERKEEVLLLPQNGFWTLDMHKG-QYRALSSPKRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPV 411
Cdd:cd13744    88 AVSRKGSIQIQPGRGFYCIVMHDGnQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTF-REKFPGKL 166

                  ....*..
gi 1622935185 412 RPFFRIG 418
Cdd:cd13744   167 CSYFSPG 173

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 1622935185 256 DVVLDPDTAHPDLLLSEDRRSVRRCPLRHLGESVPDNPERFDsepcVLGRESFASGKHYWEVEVENVIEWTVGVC----- 330
Cdd:cd15810     1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFG----VLGSQYFSSGKHYWEVDVSKKSAWILGVCshkrs 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 331 ---RDSVERKEEVL-----LLPQNGFWTLDM-HKGQYRAL----SSPKRILPLKESLC--RVGVFLDYEAGDVSFYNMRD 395
Cdd:cd15810    77 damTKSNANQINHQnvysrYQPQYGYWVIGLqNESEYNAFedssSFNPHVLTLSVTVPphRVGVFLDYEAGTVSFFNVTN 156

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1622935185 396 R-SHIYTCPRSAFSVPVRPFFRIGSDDRPIFIC 427
Cdd:cd15810   157 HgSLIYKFSKCCFSTTVCPYFNPWNCPVPMTLC 189

PRY/SPRY domain of tripartite motif-binding protein 10 (TRIM10) also known as hematopoietic RING finger 1 (HERF1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM10, also known as RING finger protein 9 (RNF9) or hematopoietic RING finger 1 (HERF1). TRIM10 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. TRIM10/HERF1 is predominantly expressed during definitive erythropoiesis and in embryonic liver, and minimally expressed in adult liver, kidney, and colon. It is critical for erythroid cell differentiation and its down-regulation leads to cell death; inhibition of TRIM10 expression blocks terminal erythroid differentiation, while its over-expression in erythroid cells induces beta-major globin expression and erythroid differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 257 VVLDPDTAHPDLLLSEDRRSVRrcpLRHLGESVPDNPERFDSEPCVLGRESFASGKHYWEVEVENVI--EWTVGVCRDSV 334
Cdd:cd15827     4 ISLDPQTSHPKLLLSEDHQRAR---FSYKWQNSPDNPQRFDRATCVLAHDGFTGGRHTWVVSVDLAHggSCTVGVVSEDV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622935185 335 ERKEEVLLLPQNGFWTLDMHKGQYRALSS-PKRiLPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSaFSVPVRP 413
Cdd:cd15827    81 RRKGELRLRPEEGVWAVRLAWGFVSALGSfPTR-LALEEQPRQVRVSLDYEVGWVTFVNAVTQEPIYTFTAS-FTQKVFP 158