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 26344696    240 RGTYYWEVEIIE-GWVSVGVMaegfspQEPYDRGR---LGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSP-TVGVCLE 314
Cdd:smart00449   1 SGRHYFEVEIGDgGHWRVGVA------TKSVPRGYfalLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGdVIGCFLD 74

                           90
                   ....*....|.
gi 26344696    315 YADHALAFYAV 325
Cdd:smart00449  75 LEAGTISFYKN 85

PRY/SPRY domain in tripartite motif-containing (TRIM) proteins, including TRIM14-like, TRIM16-like, TRIM25-like, TRIM47-like, TRIM65 and RNF135, and stonustoxin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM14, TRIM16 and TRIM25, TRIM47 as well as RING finger protein RNF135 and stonustoxin, a secreted poisonous protein of the stonefish Synanceja horrida. TRIM16 (also known as estrogen-responsive B box protein or EBBP) has E3 ubiquitin ligase activity. It is a regulator of keratinocyte differentiation and a tumor suppressor in retinoid-sensitive neuroblastoma. TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function. TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100), is highly expressed in kidney tubular cells, but low expressed in most tissue. It is overexpressed in astrocytoma tumor cells and plays an important role in the process of dedifferentiation that is associated with astrocytoma tumorigenesis. RNF135 ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Stonustoxin (STNX) is a hypotensive and lethal protein factor that also possesses other biological activities such as species-specific hemolysis (due to its ability to form pores in the cell membrane) and platelet aggregation, edema-induction, and endothelium-dependent vasorelaxation (mediated by the nitric oxide pathway and activation of potassium channels). 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 26344696 191 VDLDSDTADKFLQLFGTKgvKRVLCPIN---YPESPTRFTHCeQVLGEGALDRGTYYWEVEIIE-GWVSVGVMAEGFSPQ 266
Cdd:cd12891   1 LTLDPNTAHNNLALSGDL--KTVTCSSEnqhYPDSPERFTHS-QVLSTQSFSSGRHYWEVEVSEsGGWSVGVAYPSIERK 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 267 epYDRGRLGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSPTVGVCLEYADHALAFYAVRDgKLSLLRRLKASRPrrsga 346
Cdd:cd12891  78 --GDESRIGRNDKSWCLEWQDKSFSAWHNNEETPLPSVSSRRLGVYLDYEAGRLSFYELSD-PIRHLHTFTATFT----- 149

                       170
                ....*....|...
gi 26344696 347 laSPTDPFQSRLD 359
Cdd:cd12891 150 --EPLHPAFWVLE 160

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 26344696 193 LDSDTADKFLQLFgtKGVKRV-LCPI--NYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE-GWVSVGVMAEGFSPQEP 268
Cdd:cd12874   3 FDPDTAHLNLILS--DDLRSVrVGDIsqHPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDdSSWYVGVTYKSLPRKGK 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 26344696 269 YDRgrLGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSPTVGVCLEYADHALAFYAVRDGKlSLLRRLKAS 339
Cdd:cd12874  81 MSN--LGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVTDGV-QLLYTFKAK 148

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM25 proteins (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 216 PINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE-GWVSVGVMAEGFSPQEPydRGRLGRNAHSCCLQWNGRGFSVWF 294
Cdd:cd13736  27 PQNYREHPQRFTYCSQVLGLHCFKQGIHYWEVELQKnNFCGVGICYGSMDRQGP--ESRLGRNSESWCVEWFNVKISAWH 104

                        90       100       110
                ....*....|....*....|....*....|....
gi 26344696 295 CGLEAPLPHAFSPTVGVCLEyADHALA-FYAVRD 327
Cdd:cd13736 105 NNVEKTLPSTKATRVGVLLN-CDHGFViFFAVQD 137

PRY/SPRY domain in tripartite motif-containing domain 25 (TRIM25)-like; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of proteins similar to TRIM25 (composed of RING/B-box/coiled-coil core and also known as RBCC proteins). TRIM25 (also called Efp) ubiquitinates the N terminus of the viral RNA receptor retinoic acid-inducible gene-I (RIG-I) in response to viral infection, leading to activation of the RIG-I signaling pathway, thus resulting in type I interferon production to limit viral replication. It has been shown that the influenza A virus targets TRIM25 and disables its antiviral function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 191 VDLDSDTADKFLQLFgtKGVKRVL----CPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEGWVSVGVMaegFSPQ 266
Cdd:cd13737   1 LNFDPNTASEELFLF--KETHSVLnmgiLLESFFGPCQGFNHWPQVLCTRSLCEGCHYWEAEVSNSWVCLGVT---YSYS 75

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 26344696 267 EPYDRGR----LGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSPTVGVCLEYADHALAFYAVrDGKLSLLRRLKAS 339
Cdd:cd13737  76 HPTGKSCifylIGRNPYSWCLEWDSLKFSVWHNNIQTVVHGSYYKTIGVLLDYAAGSLTFYGV-ANTMNLIYRFLTT 151

PRY/SPRY domain in tripartite motif-containing proteins 1, 9, 18, 36, 46, 67,76 (TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67, TRIM76); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several Class I TRIM proteins, including TRIM1, TRIM9, TRIM18, TRIM36, TRIM46, TRIM67 and TRIM76. TRIM1 (also known as MID2) and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. Their coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in TRIM18 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects. TRIM9 is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. Its immunoreactivity is severely decreased in affected brain areas in Parkinson's disease and dementia with Lewy bodies, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM36 interacts with centromere protein-H, one of the kinetochore proteins and possibly associates with chromosome segregation; an excess of TRIM36 may cause chromosomal instability. TRIM46 has not yet been characterized. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It is possibly involved in protein kinase A signaling as well as vesicular trafficking. It has also been implicated in Duchenne muscular dystrophy and cardiac disease. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 193 LDSDTADKFLQLFgtKGVKRVLCPINYPE-----SPTRFTHCEQVLGEGALDRGTYYWEVEIIEG-WVSVGVmAEGFSPQ 266
Cdd:cd13734   3 LDPKTAHRKLRLS--NDNLTVEYDPEGSKdqaavLPRRFTGSPAVLGDVAISSGRHYWEVSVSRStSYRVGV-AYKSAPR 79

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 26344696 267 EPydrgRLGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSPT-VGVCLEYADHALAFYAVRDGKL 330
Cdd:cd13734  80 DE----DLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHPArIGVLLDYDNGTLSFYDAESKQH 140

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 26344696 191 VDLDSDTADKFLQLF-GTKGVKRVLCPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE--GWvSVGVMAEGFSPQE 267
Cdd:cd15811   2 VTLDPDTANPELVLSeDRRSVRRGDLRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDrtSW-ALGVCKENVNRKE 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 26344696 268 pydRGRLGRNahscclqwNGRGFSVWFCGLEAPLPHAFSP------TVGVCLEYADHALAFYAVRDGKL 330
Cdd:cd15811  81 ---KGELSAG--------NGFWILVFLGNYYSSERRTFAPlrdpprRVGIFLDYEAGHLSFYSATDGSL 138

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 26344696 191 VDLDSDTADKFLQLF-GTKGVKRVLCPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEG--WVsVGVMAE------ 261
Cdd:cd12888   2 VTLDPDTAHPRLVLSeDRKSVRWGDTRQDLPDNPERFDTWPCVLGCEGFTSGRHYWEVEVGDGggWA-VGVAREsvrrkg 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 26344696 262 --GFSPQEpydrgrlGRNAhsccLQWNGrGFSVWFCGLEAPLPHAFSPT-VGVCLEYADHALAFYAVRDGKL 330
Cdd:cd12888  81 eiSFSPEE-------GIWA----VGQWG-GQYWALTSPETPLPLSEVPRrIRVYLDYEGGQVAFFDADNEAP 140

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 26344696    240 RGTYYWEVEIIE-GWVSVGVMaegfspQEPYDRGR---LGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSP-TVGVCLE 314
Cdd:smart00449   1 SGRHYFEVEIGDgGHWRVGVA------TKSVPRGYfalLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGdVIGCFLD 74

                           90
                   ....*....|.
gi 26344696    315 YADHALAFYAV 325
Cdd:smart00449  75 LEAGTISFYKN 85

PRY/SPRY domain of tripartite motif-binding protein 60 (TRIM60) also known as RING finger protein 33 (RNF33); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM60, which is also known as RING finger protein 33 (RNF33) or 129 (RNF129). TRIM60 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 191 VDLDSDTADKflQLFGTKGVKRVLC---PINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEG--WVsVGVMAEGFsp 265
Cdd:cd15828  12 VTLDPETAHP--QLTVSEDRKSVLYgemKQNVCYNPRRFYLCPAVLGSEGFHSGRQYWEVEVGDKpeWT-LGVCQDCL-- 86

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 26344696 266 qePYDRGR----------LGRNAHSCCLQWNGRGFSVwfcgleapLPHAFSPTVGVCLEYADHALAFYAVRDGklSLL 333
Cdd:cd15828  87 --PRNWSNqpsvqdglwaIGRYSESNYVALGPKKIQL--------LPKVRPSKIGIFLDYELGEVSFYNMNDR--SLL 152

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 26344696 191 VDLDSDTADKFLQLfgTKGVKRVLC---PINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE--GWvSVGVMAE---- 261
Cdd:cd13733   2 VTLDPDTAHPNLIL--SEDLKSVRYgdkRQNLPDNPERFDTCVCVLGSEGFSSGRHYWEVEVGGktDW-DLGVAREsvnr 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 26344696 262 -GFSPQEPyDRG--RLGRnahscclqWNGRGFSVWFCgLEAPLPHAFSPT-VGVCLEYADHALAFYAVRDG 328
Cdd:cd13733  79 kGKITLSP-ENGywTVGL--------RNGNEYKALTS-PSTPLSLREKPQkVGVFLDYEEGQVSFYNVDDG 139

SPRY domain; SPRY domains, first identified in the SP1A kinase of Dictyostelium and rabbit Ryanodine receptor (hence the name), are homologous to B30.2. SPRY domains have been identified in at least 11 protein families, covering a wide range of functions, including regulation of cytokine signaling (SOCS), RNA metabolism (DDX1 and hnRNP), immunity to retroviruses (TRIM5alpha), intracellular calcium release (ryanodine receptors or RyR) and regulatory and developmental processes (HERC1 and Ash2L). B30.2 also contains residues in the N-terminus that form a distinct PRY domain structure; i.e. 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 or RBCC core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). TRIM/RBCC proteins are involved in a variety of processes, including apoptosis, cell cycle regulation, cell growth, senescence, viral response, meiosis, cell differentiation, and vesicular transport. Genes belonging to this family are implicated in several human diseases that vary from cancer to rare genetic syndromes. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site. 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. Mutations found in the SPRY-containing proteins have shown to cause Mediterranean fever and Opitz syndrome.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 241 GTYYWEVEIIEGWVS---VGVMAEGFSPQepyDRGRLGRNAHSCClqWNGRGFSVWFCGLEAPLPHAFSP--TVGVCLEY 315
Cdd:cd11709   1 GKWYWEVRVDSGNGGliqVGWATKSFSLD---GEGGVGDDEESWG--YDGSRLRKGHGGSSGPGGRPWKSgdVVGCLLDL 75

                ....*...
gi 26344696 316 ADHALAFY 323
Cdd:cd11709  76 DEGTLSFS 83

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 26344696 191 VDLDSDTADKFLQLF-GTKGVKRVLCPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEG--WvSVGVMAE----GF 263
Cdd:cd15815  15 VTLDPDTAHPELTLSkDQRQVTYGRCQENLDASPKRFTVLPCVLGCEGFTSGRHYFEVDVGEGtgW-DVGVCLEnvqrGF 93

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 26344696 264 S-PQEPyDRG----RLGRNAHSCCLQWngrgfsvwfcgLEAPLPHAFSP-TVGVCLEYADHALAFYAVRDG 328
Cdd:cd15815  94 GmKQEP-EFGfwtiRLCEEDGYVALTS-----------PPTPLPLREKPlVVGVFLDYEAGLVSFYNMTTG 152

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 26344696 193 LDSDTADKFLQLFGTKGVKRVLC-PINYPESPTRFTHCEQVLGEGALDRGTYYWEVEI--IEGWvSVGVMAEG------- 262
Cdd:cd13740   4 LDPDSANPRLILSLDLKSVRLGErAQDLPNHPCRFDTNTRVLASCGFSSGRHHWEVEVgsKDGW-AFGVARESvrrkglt 82

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 26344696 263 -FSPQEpydrgrlGRNAhsccLQWNGRGFSVWFCGLEAPLPHAFSPTVGVCLEYADHALAFYAVRD 327
Cdd:cd13740  83 pFTPEE-------GVWA----LQLNGGQYWAVTSPERTPLSCGHLSRVRVALDLEVGAVSFYAAED 137

PRY/SPRY domain containing protein 4 (SPRYD4); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain and is encoded by the SPRYD4 gene. SPRYD4 (SPRY containing domain 4) is ubiquitously expressed in many human tissues, most strongly in kidney, bladder, brain, thymus and stomach. Subcellular localization demonstrates that SPRYD4 protein is localized in the nucleus when overexpressed in COS-7 green monkey cell. It has remained uncharacterized thus far.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 193 LDSDTADKFLQLF-GTKGVK-RVLC--PINYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEGW-VSVGVMAEGFSPQE 267
Cdd:cd12903   3 LDERTAHSSLDLFkKDTGVIyRMLGvdPTKVPQNPERFRDWAVVLGDTPVTSGRHYWEVTVKRSQeFRIGVADVDMSRDE 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 26344696 268 PydrgrLGRNAHSCCLQWNGRGFSVWFCGLEAPLPHAFSPT-VGVCLEYADHALAFyaVRDGKLSLLRRLKA 338
Cdd:cd12903  83 C-----IGTNESSWVFAYAQRKWYAMVANETVPVPLVGKPDrVGLLLDYEAGKLSL--VDVEKNSVVHTMSA 147

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76)-like; This domain is similar to the distinct PRY/SPRY subdomain found at the C-terminus of TRIM76, a Class I TRIM protein. TRIM76 (also known as cardiomyopathy-associated protein 5 or CMYA5 or myospryn or SPRYD2) is a muscle-specific member of the TRIM superfamily, but lacks the RING domain. It has been suggested that TRIM76 is involved in two distinct processes, protein kinase A signaling and vesicular trafficking.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 26344696 220 PESPTRFTHCEQVLGEGALDRGTYYWEVEIIEGW-VSVGVMAEGFSPQepydrGRLGRNAHSCCLQ 284
Cdd:cd12899  35 SFSDNSFTRCVAVMGSLIPVRGKHYWEVEVDEQTeYRVGVAFEDTQRN-----GYLGANNTSWCMR 95

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 26344696 193 LDSDTADKFLQLfgTKGVKRVLCPINY---PESPTRFTHCEQVLGEGALDRGTYYWEVE----------IIEGWVSvgvm 259
Cdd:cd13743  16 LDPLTAHPMLEL--SKGNTVVECGLLAqrlPSNPERFDYSNCVLASRGFSSGKHYWEVVvgskskwrlgLIKGTTS---- 89

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 26344696 260 aegfspqepyDRGRLGRNAHscclqwNGrgfsVWFCGL------EA------PLPHAFSPT-VGVCLEYADHALAFY 323
Cdd:cd13743  90 ----------RKGKLNKSPE------NG----VWLIGLkegrvyEAfanprvPLPLSTRPQrIGVFLDYEKGELTFY 146

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 26344696 191 VDLDSDTADKFLQLF-GTKGVKRVLCPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEI--IEGWvSVGVMAE 261
Cdd:cd15820   6 VILDPDTANPILLISeDQRSLQWADEPQNLPDNPKRFDWHYCVLGCKSFTSGRHFWEVEVgdRKEW-YVGVCRE 78

PRY/SPRY domain in tripartite motif-binding protein 69 (TRIM69), also known as RING finger protein 36 (RNF36); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM69, which is also known as RING finger protein 36 (RNF36) or testis-specific ring finger (Trif). TRIM69 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is a novel testis E3 ubiquitin ligase that may function to ubiquitinate its particular substrates during spermatogenesis. In humans, TRIM69 localizes in the cytoplasm and nucleus, and requires an intact RING finger domain to function. The mouse ortholog of this gene is specifically expressed in germ cells at the round spermatid stages during spermatogenesis and, when overexpressed, induces apoptosis. TRIM69 has been shown to be a novel regulator of mitotic spindle assembly in tumor cells; it associates with spindle poles and promotes centrosomal clustering, and is therefore essential for formation of a bipolar spindle.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 218 NYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIE--GWvSVGVMAEG--------FSPQEPYDRGRLgRNAHScclqwng 287
Cdd:cd15818  43 MLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKktKW-TLGVVRESinrkgncpLSPEDGFWLLRL-RNQNE------- 113

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 26344696 288 rgfsvwfcgLEAPLPHAFSPT-------VGVCLEYADHALAFYAVRD 327
Cdd:cd15818 114 ---------LKALDVPSFSLTltsnlnkVGIYLDYEGGQVSFYNANT 151

PRY/SPRY domain of tripartite motif-binding protein 1 (TRIM1) or MID2; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM1 (also known as MID2 or midline 2). MID2 and its close homolog, TRIM18 (also known as MID1), both contain a B30.2-like domain at their C-terminus and a single fibronectin type III (FN3) motif between it and their N-terminal RBCC domain. MID2 and MID1 coiled-coil motifs mediate both homo- and heterodimerization, a prerequisite for association of the rapamycin-sensitive PP2A regulatory subunit Alpha 4 with microtubules. Mutations in MID1 have shown to cause Opitz syndrome, a disorder causing congenital anomalies such as cleft lip and palate as well as heart defects.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 26344696 222 SPTRF--THCEQVLGEGALDRGTYYWEVEI-IEGWVSVGVmAEGFSPQEPYdrgrLGRNAHSCCLQWNGRGFSVWFCGLE 298
Cdd:cd13739  33 TPERFsgTGCYGAAGNIFIDSGCHYWEVVVgSSTWYAIGI-AYKSAPKNEW----IGKNSSSWVFSRCNNNFVVRHNNKE 107

                        90       100
                ....*....|....*....|....*..
gi 26344696 299 APL--PHAFSpTVGVCLEYADHALAFY 323
Cdd:cd13739 108 MLVdvPPQLK-RLGVLLDYDNNMLSFY 133

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 26344696 190 IVDLDSDTADKFLQLF-GTKGVKRVLCPINYPESPTRFTHCEQVLGEGALDRGTYYWEVEII---EGWVSVGVMAEG 262
Cdd:cd15826   1 SVTLDPQTASGSLVLSeDRKSVRYTRQKQNLPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgdGGGCTVGVAGES 77