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 19923536  39 VALLGGTAELLCPLSlwpgtvPK------EVRWLRSPFpqrSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDA-QEGSVTL 111
Cdd:cd05713  11 LALVGEDAELPCHLS------PKmsaehmEVRWFRSQF---SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAiAEGSVAL 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 19923536 112 QILDVRLEDQGSYRCLIQVGNLSKEDTVILQVA 144
Cdd:cd05713  82 RIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 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 19923536  39 VALLGGTAELLCPLSlwpgtvPK------EVRWLRSPFpqrSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDA-QEGSVTL 111
Cdd:cd05713  11 LALVGEDAELPCHLS------PKmsaehmEVRWFRSQF---SPVVHLYRDGQDQEEEQMPEYRGRTELLKDAiAEGSVAL 81

                        90       100       110
                ....*....|....*....|....*....|...
gi 19923536 112 QILDVRLEDQGSYRCLIQVGNLSKEDTVILQVA 144
Cdd:cd05713  82 RIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 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 19923536   293 HYWEVYVG--DKTKWILGVCSESVSRKGKVTASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVIS 370
Cdd:pfam00622   2 HYFEVEIFgqDGGGWRVGWATKSVPRKGERFLGDESGSWGYDGWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTIS 81

                          90       100
                  ....*....|....*....|....*.
gi 19923536   371 FYNVtNKSHIFTFTH-NFSGPLRPFF 395
Cdd:pfam00622  82 FTKN-GKSLGYAFRDvPFAGPLFPAV 106

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536     45 TAELLCplSLWPGTVPK-EVRWLRSPfpQRSQAVHIFRDGKDQDEDLMPEYKGRTVLVRDAQEGSVTLQILDVRLEDQGS 123
Cdd:smart00406   1 SVTLSC--KFSGSTFSSyYVSWVRQP--PGKGLEWLGYIGSNGSSYYQESYKGRFTISKDTSKNDVSLTISNLRVEDTGT 76

                   ....*
gi 19923536    124 YRCLI 128
Cdd:smart00406  77 YYCAV 81

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 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKGK 319
Cdd:cd13733   2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKGK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 320 VTASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHNFSGPLRPFFEPCL 399
Cdd:cd13733  82 ITLSPENGYWTVGLRNGNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTDCFTEKLYPYFSPCL 161

                       170
                ....*....|...
gi 19923536 400 HDGGKNTAPLVIC 412
Cdd:cd13733 162 NDGGKNSAPLIIC 174

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 19923536 238 VAVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRK 317
Cdd:cd15819   2 VNVTLDPDTAHPALILSEDGRSVTWGETRQDLPENPERFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWDLGVCRDNVMRK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 318 GKVTASPANGHWLLRQSrGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHN-FSGPLRPFFE 396
Cdd:cd15819  82 GRVTLSPENGFWAIRLY-GNEYWALTSPETPLTLKEPPRRVGIFLDYEAGDVSFYNMTDGSHIYTFPQTaFSGPLRPFFR 160

                       170
                ....*....|....*.
gi 19923536 397 PCLHDGGkntaPLVIC 412
Cdd:cd15819 161 LWSSDSG----PLTIC 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 19923536 238 VAVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRK 317
Cdd:cd15829  19 VDVTLDPETAHPNLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPVVLGFPGFHSGRHFWEVEVGDKPEWAVGVCKDSLSTK 98

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 318 GKVTASPANGHWLLRQsRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHNFSGPLRPFFep 397
Cdd:cd15829  99 ARRPPSGQQGCWRIQL-QGGDYDAPGAVPPPLLLEVKPRGIGVFLDYELGEISFYNMPEKSHIHTFTDTFSGPLRPYF-- 175

                       170
                ....*....|....*
gi 19923536 398 CLhdgGKNTAPLVIC 412
Cdd:cd15829 176 YV---GPDSKPLRIC 187

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKGK 319
Cdd:cd15816   2 VKLDPATAHPSLLLTADLRSVQDGELWRDVPGNPERFDTWPCVLGLQSFSSGRHYWEVAVGEKAEWGLGVCQDSAPRKGE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 320 VTASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHNFSGPLRPFFEPCl 399
Cdd:cd15816  82 TTPSPENGVWAVWLLKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSHIYTFRQLFSGILRPYFFVC- 160

                       170
                ....*....|..
gi 19923536 400 hdggkNTAPLVI 411
Cdd:cd15816 161 -----DTTPLTL 167

PRY/SPRY domain in tripartite motif-binding protein 21 (TRIM21) also known as 52kD Ribonucleoprotein Autoantigen (Ro52); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM21, which is also known as Sjogren Syndrome Antigen A (SSA), SSA1, 52kD Ribonucleoprotein Autoantigen (Ro52, Ro/SSA, SS-A/Ro) or RING finger protein 81 (RNF81). TRIM21 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. As an E3 ligase, TRIM21 mediates target specificity in ubiquitination; it regulates type 1 interferon and proinflammatory cytokines via ubiquitination of interferon regulatory factors (IRFs). It is up-regulated at the site of autoimmune inflammation, such as cutaneous lupus lesions, indicating a central role in the tissue destructive inflammatory process. It interacts with auto-antigens in patients with Sjogren syndrome and systemic lupus erythematosus, a chronic systemic autoimmune disease characterized by the presence of autoantibodies against the protein component of the human intracellular ribonucleoprotein-RNA complexes and more specifically TRIM21, Ro60/TROVE2 and La/SSB proteins. It binds the Fc part of IgG molecules via its PRY-SPRY domain with unexpectedly high affinity.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 236 HFVAVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVS 315
Cdd:cd12900   1 HMVHITLDPDTANPWLILSKDRRQVRLGDTHQNVPENEERFDNYPMVLGAQRFNSGKHYWEVDVTGKEAWDLGVCRDSVR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 316 RKGKVTASPANGHWLLRQSRGnEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTN-KSHIFTFTH-NFSGPLRP 393
Cdd:cd12900  81 RKGQFLLSPENGFWTIWLWNK-KYEAGTSPQTTLHLQVPPCQVGIFLDYEAGVVSFYNITDhGSLIYTFSEcAFTGPLRP 159

                       170
                ....*....|....*....
gi 19923536 394 FFEPCLHDGGKNTAPLVIC 412
Cdd:cd12900 160 FFNPGFNDSGGNAAPLTLC 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 19923536 238 VAVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRK 317
Cdd:cd15821   4 VDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVNRQ 83

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 318 GKVTASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHNF-SGPLRPFFE 396
Cdd:cd15821  84 GPIELSPEHGFWTVSLRDGSVFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISaEEPLRPFFA 163

                       170
                ....*....|....*.
gi 19923536 397 PCLHDGGkNTAPLVIC 412
Cdd:cd15821 164 PANPYGD-DQGVLSIC 178

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 19923536 234 RLHFVAVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSES 313
Cdd:cd15815   9 RRHQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLEN 88

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 314 VSRKGKVTASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHN-FSGPLR 392
Cdd:cd15815  89 VQRGFGMKQEPEFGFWTIRLCEEDGYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKAsFSDTLR 168

                ....*...
gi 19923536 393 PFFEPCLH 400
Cdd:cd15815 169 PYFQVYQY 176

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 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKGK 319
Cdd:cd15811   2 VTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKEK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 320 VTASPANGHWLLrQSRGNEYealTSPQTSFR-LKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHN-FSGPLRPFFEP 397
Cdd:cd15811  82 GELSAGNGFWIL-VFLGNYY---SSERRTFApLRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETpFSGTLRPLFSP 157

                       170
                ....*....|....*
gi 19923536 398 ClhdgGKNTAPLVIC 412
Cdd:cd15811 158 L----SSSPTPMTIC 168

PRY/SPRY domain in tripartite motif-binding protein 72 (TRIM72); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM72. Muscle-specific TRIM72 (also known as Mitsugumin 53 or MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM72 interacts with dysferlin, a sarcolemmal protein whose deficiency causes Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B); this coordination plays an important role in the repair of sarcolemma damage.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPV-PDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKG 318
Cdd:cd13742  14 LTFDPDTAHPYLVVSSDGKRVECADQKQAVsSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWALGVISAEAGRKG 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 319 KVTASPANGHWLLRQSRGNEYEALTSPQT--SFRLKEPPRCVGIFLDYEAGVISFYNVT---NKSHIFTFTHNFSGPLRP 393
Cdd:cd13742  94 RLHALPSNGFWLLGCKEGKVYEAHVEHKEprALRVEGRPTRIGVYLSFSDGVLSFYDASdedNLVQLFAFHERFPGPLYP 173

                       170
                ....*....|....*....
gi 19923536 394 FFEPCLHDGGKNTAPLVIC 412
Cdd:cd13742 174 FFDVCWHDKGKNSQPLKIF 192

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKGK 319
Cdd:cd12897  14 LTFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTCVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKGK 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 320 VTASPANGHWLLRQSRGNEYEALTSPQT--SFRLKEPPRCVGIFLDYEAGVISFYNVTNKSH---IFTFTHNFSGPLRPF 394
Cdd:cd12897  94 LHASPSHGVWLIGLKEGKVYEAHGEPKEprPLRVAGRPHRIGVYLSFEDGVLSFFDASDPDDlrtLYTFQERFQGKLYPF 173

                       170
                ....*....|....*..
gi 19923536 395 FEPCLHDGGKNTAPLVI 411
Cdd:cd12897 174 FDVCWHDKGKNSQPLVL 190

PRY/SPRY domain in tripartite motif-binding protein 50 (TRIM50); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM50. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23. It is specifically expressed in gastric parietal cells and may play an essential role in tubulovesicular dynamics. It also interacts with and increases the level of p62, a multifunctional adaptor protein that is implicated in various cellular processes such as the autophagy clearance of polyubiquitinated protein aggregates.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 242 LDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKGKVT 321
Cdd:cd13743  16 LDPLTAHPMLELSKGNTVVECGLLAQRLPSNPERFDYSNCVLASRGFSSGKHYWEVVVGSKSKWRLGLIKGTTSRKGKLN 95

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 322 ASPANGHWLLRQSRGNEYEALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSH---IFTFTHNFSGPLRPFFEPC 398
Cdd:cd13743  96 KSPENGVWLIGLKEGRVYEAFANPRVPLPLSTRPQRIGVFLDYEKGELTFYNADSPDElvpIYTFQAEFQGKLYPLLDVC 175

                       170
                ....*....|...
gi 19923536 399 LHDGGKNTAPLVI 411
Cdd:cd13743 176 WHERGANKLPIIL 188

PRY/SPRY domain in tripartite motif-binding protein 15 (TRIM15); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of tripartite motif-containing protein 15 (TRIM15), also referred to as RING finger protein 93 (RNF93) or Zinc finger protein B7 or 178 (ZNFB7 or ZNF178). TRIM15 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. The PRY and SPRY/B30.2 domains can function as immune defense components and in pathogen sensing. TRIM15 has been shown to regulate inflammatory and innate immune signaling, in addition to displaying antiviral activities. Down-regulation of TRIM15, as well as TRIM11, enhances virus release, suggesting that these proteins contribute to the endogenous restriction of retroviruses in cells. TRIM15 is also a regulatory component of focal adhesion turnover and cell migration.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 240 VTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYV--GDKTKWILGVCSESVSRK 317
Cdd:cd15826   2 VTLDPQTASGSLVLSEDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVqlGDGGGCTVGVAGESVRRK 81

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 19923536 318 GKVTASPANGHWLLRQSRGNEYeALTSPQTSFRLKEPPRCVGIFLDYEAGVISFYNVTNKSHIFTFTHNFSGPLRPFF 395
Cdd:cd15826  82 GEMGLSAEDGVWAVILSHQQCW-ASTSPGTDLPLSEIPRRVGVALDYEAGTVTLTNAETQEPIFTFTASFSGKVFPFF 158

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 19923536 239 AVTLDPDTAHPKLILSEDQRCVRLGDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVSRKG 318
Cdd:cd13740   1 ELTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 319 KVTASPANGHWLLRQSrGNEYEALTSPQTSfrlkepPRCVG------IFLDYEAGVISFYNVTNKSHIFTFTHNFSGPLR 392
Cdd:cd13740  81 LTPFTPEEGVWALQLN-GGQYWAVTSPERT------PLSCGhlsrvrVALDLEVGAVSFYAAEDMRHIYTFRVNFQERVF 153

                ....*.
gi 19923536 393 PFFEPC 398
Cdd:cd13740 154 PLFSVC 159

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 19923536 240 VTLDPDTAHPKLILSEDQRCVRLgDRRQPVPDNPQRFDFVVSILGSEYFTTGCHYWEVYVGDKTKWILGVCSESVS--RK 317
Cdd:cd15810   2 VTLNPVNISLNIVISEDQRQVRI-VPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCSHKRSdaMT 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 19923536 318 GKVTAS-----------PANGHWLLRQSRGNEYEALTSPQTS------FRLKEPPRCVGIFLDYEAGVISFYNVTNK-SH 379
Cdd:cd15810  81 KSNANQinhqnvysryqPQYGYWVIGLQNESEYNAFEDSSSFnphvltLSVTVPPHRVGVFLDYEAGTVSFFNVTNHgSL 160

                       170       180       190
                ....*....|....*....|....*....|....
gi 19923536 380 IFTFTH-NFSGPLRPFFEPClhdggKNTAPLVIC 412
Cdd:cd15810 161 IYKFSKcCFSTTVCPYFNPW-----NCPVPMTLC 189