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 1390157523  33 FLVLGPPHPLLAIVGQDKELPCKLSLNISAEGMELRWYRDKPSSVVHVYKNGEDVYDEQMVEYKGRTSFNGSHVARGEAA 112
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1390157523 113 VKIHNVTVFDNGTYHCVFKEYTSHSQATLWLKVA 146
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 1390157523  33 FLVLGPPHPLLAIVGQDKELPCKLSLNISAEGMELRWYRDKPSSVVHVYKNGEDVYDEQMVEYKGRTSFNGSHVARGEAA 112
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1390157523 113 VKIHNVTVFDNGTYHCVFKEYTSHSQATLWLKVA 146
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 1390157523 355 RHYWEVEVGDRR--AWILGVCLESLVREGRIPKSPQHGLWALE-FYKKKLQALSYPRTCLSPPEPLRRVGILLDFEAGQI 431
Cdd:pfam00622   1 RHYFEVEIFGQDggGWRVGWATKSVPRKGERFLGDESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEAGTI 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 1390157523 432 SFYNstNG-SLIYVFSGFSFSGPLQPFFCL 460
Cdd:pfam00622  81 SFTK--NGkSLGYAFRDVPFAGPLFPAVSL 108

Immunoglobulin V-Type;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523   51 ELPCKLSLNiSAEGMELRWYRDKPSS---VVHVYKNGEDVYDEQmvEYKGRTSFNGSHvARGEAAVKIHNVTVFDNGTYH 127
Cdd:smart00406   3 TLSCKFSGS-TFSSYYVSWVRQPPGKgleWLGYIGSNGSSYYQE--SYKGRFTISKDT-SKNDVSLTISNLRVEDTGTYY 78

                   ...
gi 1390157523  128 CVF 130
Cdd:smart00406  79 CAV 81

Second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and Necl-5), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig) domain of poliovirus receptor (PVR, also known as CD155 and nectin-like protein 5 (Necl-5)) and similar proteins. Poliovirus (PV) binds to its cellular receptor (PVR/CD155) to initiate infection. CD155 is a membrane-anchored, single-span glycoprotein; its extracellular region has three Ig-like domains. There are four different isotypes of CD155 (referred to as alpha, beta, gamma, and delta), these result from alternate splicing of the CD155 mRNA, and have identical extracellular domains. CD155-beta and CD155-gamma are secreted, while CD155-alpha and CD155-delta are membrane-bound and function as PV receptors. The virus recognition site is contained in the amino-terminal domain, D1. Having the virus attachment site on the receptor distal from the plasma membrane may be important for successful initiation of infection of cells by the virus. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. This group also includes the second Ig-like domain of nectin-1, also known as poliovirus receptor related protein(PVRL)1 or CD111.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 159 TQDKGIRAECTSAGWYPEPKVEWL-DLKGQPVSAEshfsVSASTGLVALLS--IVTPQDTAVG-GLTCSISNPLLPEKVT 234
Cdd:cd05719    14 GGEPTLVATCISANGKPPASVTWEtDLKGEASTTQ----VRGSNGTVTVTSryRLVPSREADGqPLTCVVEHPSLEKDQR 89

                  ....*
gi 1390157523 235 ETYLL 239
Cdd:cd05719    90 ISVTL 94

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 1390157523 303 LSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREGR 382
Cdd:cd13733     2 VTLDPDTAHPNLILSEDLKSVRYGDKRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGKTDWDLGVARESVNRKGK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 383 IPKSPQHGLWALEFYK-KKLQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGfSFSGPLQPFFCLW 461
Cdd:cd13733    82 ITLSPENGYWTVGLRNgNEYKALTSPSTPLSLREKPQKVGVFLDYEEGQVSFYNVDDGSHIYTFTD-CFTEKLYPYFSPC 160

                         170
                  ....*....|....
gi 1390157523 462 THD----PRPLTIC 471
Cdd:cd13733   161 LNDggknSAPLIIC 174

PRY/SPRY domain of butyrophilin 3 (BTN3), includes BTN3A1, BTN3A2, BTN3A3 as well as BTN-like 3 (BTNL3); BTN3A also known as CD277; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of butyrophilin family 3A (BTN3A); duplication events have led to three paralogs in primates: BTN3A1, BTN3A2, and BTN3A3. BTNs belong to receptor glycoproteins of immunoglobulin (Ig) superfamily, characterized by the presence of extracellular Ig-like domains (IgV and/or IgC). BTN3 transcripts are ubiquitously present in all immune cells (T cells, B cells, NK cells, monocytes, dendritic cells, and hematopoietic precursors) with different expression levels; BTN3A1 and BTN3A2 are expressed mainly by CD4+ and CD8+ T cells, BTN3A2 is the major form expressed in NK cells, and BTN3A3 is poorly expressed in these immune cells. The PRY/SPRY domain of the BTN3A1 isoform mediates phosphoantigen (pAg)-induced activation by binding directly to the pAg.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 305 LDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREGRIP 384
Cdd:cd15820     8 LDPDTANPILLISEDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVGDRKEWYVGVCRENVERKLWVK 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 385 KSPQHGLWALEFY-KKKLQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPFFCLWTH 463
Cdd:cd15820    88 MAPENGFWTIGLSdGNDYQALTDPRTKLTIANPPQRVGVFLDYETGEVSFYNAMDGSHIYTFPHTSFSGPLYPVFRLLSW 167

                  ....*...
gi 1390157523 464 DPRPLTIC 471
Cdd:cd15820   168 DPTALTIC 175

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 1390157523 299 FHVSLSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLV 378
Cdd:cd15821     2 FQVDMTLDVDTANNYLIISEDLRSVRCGCFRQNRKELAERFDDALCVLGSPRFTSGRHYWEVDVGTSTEWDLGVCRESVN 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 379 REGRIPKSPQHGLWALEFYKKK-LQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPF 457
Cdd:cd15821    82 RQGPIELSPEHGFWTVSLRDGSvFFASTVPLTVLWVNPRLHRVGIFLDMEMGTISFYDVSDGSHIFTFTKISAEEPLRPF 161

                         170
                  ....*....|....*..
gi 1390157523 458 FC---LWTHDPRPLTIC 471
Cdd:cd15821   162 FApanPYGDDQGVLSIC 178

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 1390157523  33 FLVLGPPHPLLAIVGQDKELPCKLSLNISAEGMELRWYRDKPSSVVHVYKNGEDVYDEQMVEYKGRTSFNGSHVARGEAA 112
Cdd:cd05713     1 FSVIGPTEPILALVGEDAELPCHLSPKMSAEHMEVRWFRSQFSPVVHLYRDGQDQEEEQMPEYRGRTELLKDAIAEGSVA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1390157523 113 VKIHNVTVFDNGTYHCVFKEYTSHSQATLWLKVA 146
Cdd:cd05713    81 LRIHNVRPSDEGQYTCFFRSGSFYEEATLELKVA 114

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 1390157523 303 LSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREGR 382
Cdd:cd15811     2 VTLDPDTANPELVLSEDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNRKEK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 383 IPKSPQHGLWALEFYKkklQALSYPRTCLSP-PEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPFFCLW 461
Cdd:cd15811    82 GELSAGNGFWILVFLG---NYYSSERRTFAPlRDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPLFSPL 158

                         170
                  ....*....|
gi 1390157523 462 THDPRPLTIC 471
Cdd:cd15811   159 SSSPTPMTIC 168

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 1390157523 299 FHVSLSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLV 378
Cdd:cd15815    11 HQVSVTLDPDTAHPELTLSKDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLENVQ 90

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 379 REGRIPKSPQHGLWALEFYKKK-LQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPF 457
Cdd:cd15815    91 RGFGMKQEPEFGFWTIRLCEEDgYVALTSPPTPLPLREKPLVVGVFLDYEAGLVSFYNMTTGSHIFTFPKASFSDTLRPY 170

                  ....*...
gi 1390157523 458 FCLWTHDP 465
Cdd:cd15815   171 FQVYQYSP 178

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 1390157523 303 LSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREGR 382
Cdd:cd15817     2 LILDPETAHPNLIVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRNAQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 383 IPKSPQHGLWALEFYKKKLQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGfSFSGPLQPFFCLWT 462
Cdd:cd15817    82 DPPSPLGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNMNDRSHLYTFTD-TFTGKLIPYFYVGP 160

                  ....*....
gi 1390157523 463 hDPRPLTIC 471
Cdd:cd15817   161 -DSEPLTIC 168

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 1390157523 301 VSLSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVRE 380
Cdd:cd15814     2 VDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCVLGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 381 GRIPKSPQHGLWALE-FYKKKLQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPFFC 459
Cdd:cd15814    82 GGVTSAPQNGFWAVSlWYGKEYWALTSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYFS 161

                         170
                  ....*....|....*
gi 1390157523 460 LWTHDPR---PLTIC 471
Cdd:cd15814   162 LSYSGGKsaaPLIIC 176

PRY/SPRY domain in tripartite motif-containing protein 35 (TRIM35); This PRY/SPRY domain is found at the C-terminus of the overall domain architecture of tripartite motif 35, TRIM35 (also known as hemopoietic lineage switch protein), which includes a RING finger domain (RING) and a B-box motif (BBOX). TRIM35 may play a role as a tumor suppressor and is implicated in the cell death mechanism.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 304 SLDPETASPKLMVSEDQKSV-----KRLLFDqdvfpSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLV 378
Cdd:cd12893     3 TLDPNTAHPWLSLSEDLTSVrysseKQQLPD-----NPERFDPYPCVLGSEGFTSGKHSWDVEVGDNTSWMLGVAKESVQ 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 379 REGRIPKSPQHGLWALEFYKKKLQALS--YPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGfSFSGPLQP 456
Cdd:cd12893    78 RKGKFTLSPESGFWTIGFSEGKYSARTspEPRTPLRVKQKPQRIRVQLDWDRGKVSFSDPDTNTHIHTFTH-TFTERVFP 156

                         170
                  ....*....|....*
gi 1390157523 457 FFCLWTHDPrPLTIC 471
Cdd:cd12893   157 YFYTGCKSE-PLRIL 170

zinc-binding protein A33-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69 and TRIM proteins NF7 and bloodthirsty (bty). TRIM69 is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. TRIM protein NF7, which also contains a chromodomain (CHD) at the N-terminus and an RFP (Ret finger protein)-like domain at the C-terminus, is required for its association with transcriptional units of RNA polymerase II which is mediated by a trimeric B box. In Xenopus oocyte, xNF7 has been identified as a nuclear microtubule-associated protein (MAP) whose microtubule-bundling activity, but not E3-ligase activity, contributes to microtubule organization and spindle integrity. Bloodthirsty (bty) is a novel gene identified in zebrafish and has been shown to likely play a role in in regulation of the terminal steps of erythropoiesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 302 SLSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREG 381
Cdd:cd12905     5 PLTFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCVNVLASQGFQSGRHYWEVWVGSKTKWDLGVASESVDRQA 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 382 RIPKSPQHGLWALEFYK-KKLQALSYPRTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGfSFSGPLQPFF-- 458
Cdd:cd12905    85 RVKLCPENGYWTLRLRNgDEYWAGTQPWTRLRVTSRPQRIGVFLDCEERKVSFYNADDMSLLYSFHQ-GPRGKVFPFFst 163

                         170
                  ....*....|....*
gi 1390157523 459 CLWTH--DPRPLTIC 471
Cdd:cd12905   164 CFSDDgqNAEPMRLL 178

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 1390157523 306 DPETASPKLMVSEDQKsvKRLLFD--QDVFPSSRRFNQDPCILAQERFEAGRHYWEVEV---GDRrAWILGVCLESLVRE 380
Cdd:cd15812     5 DPSTAYPYLLLYESRQ--RRYLSTppDGTPCSKDRFLAYPCAVGQETFSSGRHYWEVGMnltGDA-LWALGVCRDNVSRK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 381 GRIPKSPQHGLWALEFYKKKLQALSYP-RTCLSPPEPLRRVGILLDFEAGQISFYNSTNGSLIYVFSGFSFSGPLQPFFC 459
Cdd:cd15812    82 DRVPKSPENGFWVVQLSKGKKYLSAMSaLTPVTLTEPPSHMGIFLDFEAGEVSFYSVNDGSHLHTYSQAAFPGPLQPFFC 161

                  .
gi 1390157523 460 L 460
Cdd:cd15812   162 L 162

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 1390157523 305 LDPETASPKLMVSEDQKSVkRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVC--------LES 376
Cdd:cd15810     4 LNPVNISLNIVISEDQRQV-RIVPPQTSGQALTNNNYDFGVLGSQYFSSGKHYWEVDVSKKSAWILGVCshkrsdamTKS 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 377 LVREGRIPK-----SPQHGLWALEFYKK-KLQALSYPRTC------LSPPEPLRRVGILLDFEAGQISFYNSTN-GSLIY 443
Cdd:cd15810    83 NANQINHQNvysryQPQYGYWVIGLQNEsEYNAFEDSSSFnphvltLSVTVPPHRVGVFLDYEAGTVSFFNVTNhGSLIY 162

                         170       180
                  ....*....|....*....|....*...
gi 1390157523 444 VFSGFSFSGPLQPFFCLWtHDPRPLTIC 471
Cdd:cd15810   163 KFSKCCFSTTVCPYFNPW-NCPVPMTLC 189

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 1390157523 303 LSLDPETASPKLMVSEDQKSVKRLLFDQDVFPSSRRFNQDPCILAQERFEAGRHYWEVEVGDRRAWILGVCLESLVREGR 382
Cdd:cd13740     2 LTLDPDSANPRLILSLDLKSVRLGERAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVGSKDGWAFGVARESVRRKGL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1390157523 383 IPKSPQHGLWALEFYKKKLQALSYP-RTCLSPPEpLRRVGILLDFEAGQISFYNSTNGSLIYVFSgFSFSGPLQPFFclw 461
Cdd:cd13740    82 TPFTPEEGVWALQLNGGQYWAVTSPeRTPLSCGH-LSRVRVALDLEVGAVSFYAAEDMRHIYTFR-VNFQERVFPLF--- 156

                         170
                  ....*....|....
gi 1390157523 462 thdprplTICSVVT 475
Cdd:cd13740   157 -------SVCSTGT 163