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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728   1 MEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVALVIHNITAQENGTYRCYFQEGRSYDEAILHLV 80
Cdd:cd05713   33 MEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELK 112

                 ..
gi 308522728  81 VA 82
Cdd:cd05713  113 VA 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 308522728   1 MEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVALVIHNITAQENGTYRCYFQEGRSYDEAILHLV 80
Cdd:cd05713   33 MEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVALRIHNVRPSDEGQYTCFFRSGSFYEEATLELK 112

                 ..
gi 308522728  81 VA 82
Cdd:cd05713  113 VA 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 308522728  324 KHYWEVEVENVI--EWTVGVCRDSVERKGEVLLIPQNGFWTLEMHKGQ-YRAVSSPDRILPLKESLCRVGVFLDYEAGDV 400
Cdd:pfam00622   1 RHYFEVEIFGQDggGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKkYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 308522728  401 SFYNMrDRSHIYTCPRSAFSVPVRPFFRLG 430
Cdd:pfam00622  81 SFTKN-GKSLGYAFRDVPFAGPLFPAVSLG 109

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 308522728    1 MEVRWFR----SQFSPAVFVYKGGRerteeQMEEYRGRTTFvSKDISRGSVALVIHNITAQENGTYRCY-FQEGRSYDEA 75
Cdd:pfam07686  29 TSVYWYRqppgKGPTFLIAYYSNGS-----EEGVKKGRFSG-RGDPSNGDGSLTIQNLTLSDSGTYTCAvIPSGEGVFGK 102

                  ....*.
gi 308522728   76 ILHLVV 81
Cdd:pfam07686 103 GTRLTV 108

Synaptonemal complex central element protein 1; This family of proteins includes synaptonemal complex central element protein 1, a component of the synaptonemal complex involved in meiosis, and synaptonemal complex central element protein 1-like, which may be involved in meiosis.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 308522728  201 IAVCIYWINKLQKEKKILS---GEKEFERETREIALKELEKERVQKEEELQVKeklQEELR 258
Cdd:pfam15233   7 IEDLINRINELQQAKKKSSeelGEAQALWEALQRELDSLNGEKVHLEEVLNKK---QEALR 64

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRRCPFRhlgESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd13733    1 DVTLDPDTAHPNLILSEDLKSVRYGDKR---QNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVN 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 RKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPF 426
Cdd:cd13733   78 RKGKITLSPENGYWTVGLRNGnEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTF-TDCFTEKLYPY 156

                        170
                 ....*....|....*...
gi 308522728 427 FRLGCEDS-----PIFIC 439
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 308522728 259 WRRTFLHAVDVVLDPDTAHPDLFLSEDRRSVRrcpFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWT 338
Cdd:cd15813    1 LRAAQAHAVNVTLDPETAHPNLIFSDDLKSVR---LGNKWDRLPDNPERFDSCIIVLGSPSFTSGRHYWEVEVGDKTGWI 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 339 VGVCRDSVERKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRS 417
Cdd:cd15813   78 LGVCKASVSRKGSMTLSPENGYWVVMMTKRnEYQASTSPPTRLWLREPPRRVGIFLDYEAGDISFYNVTAKSHIYTFTSF 157

                        170       180
                 ....*....|....*....|....*..
gi 308522728 418 AFSVPVRPFFRLGCED-----SPIFIC 439
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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRRCPFRHlgeSVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd12888    1 NVTLDPDTAHPRLVLSEDRKSVRWGDTRQ---DLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGGGWAVGVARESVR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 RKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVP-VRPF 426
Cdd:cd12888   78 RKGEISFSPEEGIWAVGQWGGQYWALTSPETPLPLSEVPRRIRVYLDYEGGQVAFFDADNEAPIFTFPPASFAGErIFPW 157

                        170
                 ....*....|...
gi 308522728 427 FRLgCEDSPIFIC 439
Cdd:cd12888  158 FWV-GKGSQLKLC 169

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 308522728 266 AVDVVLDPDTAHPDLFLSEDRRSVRRCPFRhlgESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDS 345
Cdd:cd15821    3 QVDMTLDVDTANNYLIISEDLRSVRCGCFR---QNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRES 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 346 VERKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVR 424
Cdd:cd15821   80 VNRQGPIELSPEHGFWTVSLRDGsVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEPLR 159

                 ...
gi 308522728 425 PFF 427
Cdd:cd15821  160 PFF 162

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 308522728 266 AVDVVLDPDTAHPDLFLSEDRRSVRrcpFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDS 345
Cdd:cd15814    1 SVDVTLDPDTAYPSLILSDNLRQVR---YSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDS 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 346 VERKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVR 424
Cdd:cd15814   78 VCRKGGVTSAPQNGFWAVSLWYGkEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVR 157

                        170       180
                 ....*....|....*....|
gi 308522728 425 PFFRL----GCEDSPIFICP 440
Cdd:cd15814  158 PYFSLsysgGKSAAPLIICP 177

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRRcpfRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd15816    1 DVKLDPATAHPSLLLTADLRSVQD---GELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 RKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPF 426
Cdd:cd15816   78 RKGETTPSPENGVWAVWLLKGnEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTF-RQLFSGILRPY 156

                        170
                 ....*....|
gi 308522728 427 FRLgCEDSPI 436
Cdd:cd15816  157 FFV-CDTTPL 165

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRRCPFRhlgESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd15811    1 DVTLDPDTANPELVLSEDRRSVRRGDLR---QALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVN 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 RKGEVLLIPQNGFWTLEMHKGQYravSSPDRIL-PLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVRPF 426
Cdd:cd15811   78 RKEKGELSAGNGFWILVFLGNYY---SSERRTFaPLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPL 154

                        170
                 ....*....|....
gi 308522728 427 FR-LGCEDSPIFIC 439
Cdd:cd15811  155 FSpLSSSPTPMTIC 168

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRrcpFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd15817    1 DLILDPETAHPNLIVSEDRKAVR---YRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLP 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 RKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPVRPFF 427
Cdd:cd15817   78 RNAQDPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTF-TDTFTGKLIPYF 156

                        170
                 ....*....|..
gi 308522728 428 RLGCEDSPIFIC 439
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 308522728 269 VVLDPDTAHPDLFLSEDRRSVRRCPfrhLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVER 348
Cdd:cd12874    1 LTFDPDTAHLNLILSDDLRSVRVGD---ISQHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPR 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 349 KGEVLLI-PQNGFWTLEMHKGQYRA----VSSPDRILPLKeslcRVGVFLDYEAGDVSFYNMRD-RSHIYTCpRSAFSVP 422
Cdd:cd12874   78 KGKMSNLgRNNGSWCLEWRENEFSAwhnnPETRLPVTPPR----RLGVFLDCDGGSLSFYGVTDgVQLLYTF-KAKFTEP 152

                        170
                 ....*....|....*..
gi 308522728 423 VRPFFRLgCEDSPIFIC 439
Cdd:cd12874  153 LYPAFWL-GEGSTLSIC 168

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 308522728 268 DVVLDPDTAHPDLFLSEDRRsvrRCPFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIE--WTVGVCRDS 345
Cdd:cd15812    1 DVVPDPSTAYPYLLLYESRQ---RRYLSTPPDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMNLTGDalWALGVCRDN 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 346 VERKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSAFSVPVR 424
Cdd:cd15812   78 VSRKDRVPKSPENGFWVVQLSKGkKYLSAMSALTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQ 157

                        170
                 ....*....|
gi 308522728 425 PFFRLGCEDS 434
Cdd:cd15812  158 PFFCLGAPKS 167

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 308522728 269 VVLDPDTAHPDLFLSEDRRSVRrcpFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVE--NVIEWTVGVCRDSV 346
Cdd:cd15826    2 VTLDPQTASGSLVLSEDRKSVR---YTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgDGGGCTVGVAGESV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 347 ERKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCPRSaFSVPVRPF 426
Cdd:cd15826   79 RRKGEMGLSAEDGVWAVILSHQQCWASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTAS-FSGKVFPF 157

                 ...
gi 308522728 427 FRL 429
Cdd:cd15826  158 FAV 160

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRrcpfrhLGE---SVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRD 344
Cdd:cd13740    1 ELTLDPDSANPRLILSLDLKSVR------LGEraqDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 345 SVERKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRIlPLK-ESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPV 423
Cdd:cd13740   75 SVRRKGLTPFTPEEGVWALQLNGGQYWAVTSPERT-PLScGHLSRVRVALDLEVGAVSFYAAEDMRHIYTF-RVNFQERV 152

                        170
                 ....*....|....*..
gi 308522728 424 RPFFRLGCEDSPIFICP 440
Cdd:cd13740  153 FPLFSVCSTGTYLRIWP 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 308522728 269 VVLDPDTAHPDLFLSEDrrsvrrCPFRHLGESVP----DNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWTVGVCRD 344
Cdd:cd13744   14 LTLDPVTAHQRLILSDD------CTIVAYGNLHPqplqDSPKRFDVEVSVLGSEGFSGGVHYWEVVVSEKTQWMIGLAHE 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 345 SVERKGEVLLIPQNGFWTLEMHKG-QYRAVSSPDRILPLKESLCRVGVFLDYEAGDVSFYNMRDRSHIYTCpRSAFSVPV 423
Cdd:cd13744   88 AVSRKGSIQIQPGRGFYCIVMHDGnQYSACTEPWTRLNVKSKLEKVGVYLDYDKGLLIFYNADDMSWLYTF-REKFPGKL 166

                 ....*..
gi 308522728 424 RPFFRLG 430
Cdd:cd13744  167 CSYFSPG 173

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 308522728   322 SGKHYWEVEVENVIEWTVGVCRDSVERKGEVLLIPQNGFWTLEMHKGQ-YRAVSSPDRILPLKESLCRVGVFLDYEAGDV 400
Cdd:smart00449   1 SGRHYFEVEIGDGGHWRVGVATKSVPRGYFALLGEDKGSWGYDGDGGKkYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 308522728   401 SFYNMRDRSHIYTCPRSAFSVPVRPFFRLGCEDS-PIFICP 440
Cdd:smart00449  81 SFYKNGKYLHGLAFFDVKFSGPLYPAFSLGSGNSvRLNFGP 121

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 308522728 268 DVVLDPDTAHPDLFLSEDRRSVRRCPFRHLGESVPDNPERFDsqpcVLGRESFASGKHYWEVEVENVIEWTVGVCRDSVE 347
Cdd:cd15810    1 DVTLNPVNISLNIVISEDQRQVRIVPPQTSGQALTNNNYDFG----VLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRS 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308522728 348 ---RKGEVLLI----------PQNGFWTLEM-HKGQYRAV----SSPDRILPLKESLC--RVGVFLDYEAGDVSFYNMRD 407
Cdd:cd15810   77 damTKSNANQInhqnvysryqPQYGYWVIGLqNESEYNAFedssSFNPHVLTLSVTVPphRVGVFLDYEAGTVSFFNVTN 156