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 1130413390 298 RYYFEVEIF---GAGTYVGLTCKGIDRKGEERNSCisgNNFSWSLQ-WNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPG 373
Cdd:pfam00622   1 RHYFEVEIFgqdGGGWRVGWATKSVPRKGERFLGD---ESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1130413390 374 GILSFYGVEydtMTLVHKFA-CKFSEPVYAAFWLSKKENAIRIVDLG 419
Cdd:pfam00622  78 GTISFTKNG---KSLGYAFRdVPFAGPLFPAVSLGAGEGLKFNFGLR 121

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 1130413390 245 ITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPdLPSRFLHWRQVLSQQSLYLHRYYFEVEIFG-AGTYVGLTCKGIDRKG 323
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQHPPE-PPPRFFECWQVLGSQSFSSGRHYWEVDVQDdSSWYVGVTYKSLPRKG 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 324 EerNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEyDTMTLVHKFACKFSEPVYAA 403
Cdd:cd12874    80 K--MSNLGRNNGSWCLEWRENEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVT-DGVQLLYTFKAKFTEPLYPA 156

                         170
                  ....*....|...
gi 1130413390 404 FWLSkKENAIRIV 416
Cdd:cd12874   157 FWLG-EGSTLSIC 168

Stonustoxin subunit alpha or SNTX subunit alpha; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of Stonustoxin alpha proteins. Stonustoxin (SNTX) is a multifunctional lethal protein isolated from venom elaborated by the stonefish. It comprises two subunits, termed alpha and beta. SNTX elicits an array of biological responses, particularly a potent hypotension and respiratory difficulties.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 235 REQFLQYAYDITFDPDTAHKYLRLQEENRKVTNtTPWEHPYPDLPSRFLHWRQVLSQQSLyLHRYYFEVEIFGAGTYVGL 314
Cdd:cd16040     1 REEFLKYACQLTLDPNTAHRNLSLSEGNRKVTR-VKEEQPYPDHPERFDYWPQVLCREGL-SGRCYWEVEWSGGGVDIAV 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 315 TCKGIDRKGEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKA--GPFRRLGVYIDFPGGILSFYGVeYDTMTLVHKF 392
Cdd:cd16040    79 AYKGISRKGDGDDSRFGYNDKSWSLECSPSGYSFWHNNKKTEISVpsSSSSRVGVYLDHSAGTLSFYSV-SDTMTLLHTV 157

                         170
                  ....*....|....
gi 1130413390 393 ACKFSEPVYAAFWL 406
Cdd:cd16040   158 QTTFTEPLYPGFGV 171

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 1130413390 244 DITFDPDTAHKYLRLQEENRKVTNTTPWEHPyPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIfGAGT--YVGLTCKGIDR 321
Cdd:cd13733     1 DVTLDPDTAHPNLILSEDLKSVRYGDKRQNL-PDNPERFDTCVCVLGSEGFSSGRHYWEVEV-GGKTdwDLGVARESVNR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 322 KGEERNSciSGNNFsWSLQ-WNGKEFTAWySDMETPLK-AGPFRRLGVYIDFPGGILSFYGVeyDTMTLVHKFACKFSEP 399
Cdd:cd13733    79 KGKITLS--PENGY-WTVGlRNGNEYKAL-TSPSTPLSlREKPQKVGVFLDYEEGQVSFYNV--DDGSHIYTFTDCFTEK 152

                         170
                  ....*....|..
gi 1130413390 400 VYAAFWLSKKEN 411
Cdd:cd13733   153 LYPYFSPCLNDG 164

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 1130413390 298 RYYFEVEIF---GAGTYVGLTCKGIDRKGEERNSCisgNNFSWSLQ-WNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPG 373
Cdd:pfam00622   1 RHYFEVEIFgqdGGGWRVGWATKSVPRKGERFLGD---ESGSWGYDgWTGKKYWASTSPLTGLPLFEPGDVIGCFLDYEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1130413390 374 GILSFYGVEydtMTLVHKFA-CKFSEPVYAAFWLSKKENAIRIVDLG 419
Cdd:pfam00622  78 GTISFTKNG---KSLGYAFRdVPFAGPLFPAVSLGAGEGLKFNFGLR 121

PRY/SPRY domain in tripartite motif-containing protein 47 (TRIM47), also known as RING finger protein 100 (RNF100) or Gene overexpressed in astrocytoma protein (GOA); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM47, also known as GOA (Gene overexpressed in astrocytoma protein) or RNF100 (RING finger protein 100). TRIM47 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. It is highly expressed in kidney tubular cells, but lowly 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; astrocytoma, also known as cerebral astrocytoma, is a malignant glioma that arises from astrocytes. Genome wide studies on white matter lesions have identified a novel locus on chromosome 17q25 harboring several genes such as TRIM47 and TRIM65 which pinpoints to possible novel mechanisms leading to these lesions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 238 FLQYAYDITFDPDTAHKYLRLQeeNRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCK 317
Cdd:cd15808     3 FLKFAFIVDLDSDTADKFLQLF--GTKGVKRVLCPISYPESPTRFTHCEQVLGEGALDRGTYYWEVEIIEGWVSVGVMAE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 318 GIDRKGEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEYDTMTLVHKFacKFS 397
Cdd:cd15808    81 DFSPREPYDRGRLGRNAHSCCLQWNGRNFSVWFHGLEAPLPHPFSPTVGVCLEYADRALAFYAVRDGKVSLLRRL--KAS 158

                  ..
gi 1130413390 398 EP 399
Cdd:cd15808   159 RP 160

PRY/SPRY domain in RING finger protein RNF135; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of the RING finger protein RNF135 (also known as Riplet/RNF135), which ubiquitinates RIG-I (retinoic acid-inducible gene-I) to promote interferon-beta induction during the early phase of viral infection. Normally, RIG-I is activated by TRIM25 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. However, RNF135, consisting of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs and showing sequence similarity to TRIM25, acts as an alternative factor that promotes RIG-I activation independent of TRIM25.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 246 TFDPDTAHKYLRLQEENRKVTnTTPWEHPYPDLPSRFlHWRQVLSQQSLYLHRYYFEVEI-FGAGTYVGLTCKGIDRK-- 322
Cdd:cd12902     2 TFDLRSLSCSLEVSEDSRKVT-VSHGPQAYAWSPDRF-SISQVLCSQAFSSGQHYWEVDTrQCSHWAVGVASWEMSRDqm 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 323 -GEERNScisgnnfsWSLQWNGK-EFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEyDTMTLVHKFACKFSEPV 400
Cdd:cd12902    80 lGRTMDS--------WCIEWKGTgQLSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSVA-NQERLLHECEVSASSPL 150

                  ....*.
gi 1130413390 401 YAAFWL 406
Cdd:cd12902   151 HPAFWL 156

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 1130413390 242 AYDITFDPDTAHKYLRLQEENRKVTnttpWEHPYPDLPS---RFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCK 317
Cdd:cd15819     1 AVNVTLDPDTAHPALILSEDGRSVT----WGETRQDLPEnpeRFDSLPCVLGQEGFTSGRHYWEVEVGDRTSWdLGVCRD 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 318 GIDRKGEernSCISGNNFSWSLQWNGKEFTAWYSdMETPLK-AGPFRRLGVYIDFPGGILSFYgveydTMT---LVHKFA 393
Cdd:cd15819    77 NVMRKGR---VTLSPENGFWAIRLYGNEYWALTS-PETPLTlKEPPRRVGIFLDYEAGDVSFY-----NMTdgsHIYTFP 147

                         170
                  ....*....|....
gi 1130413390 394 -CKFSEPVYAAFWL 406
Cdd:cd15819   148 qTAFSGPLRPFFRL 161

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 1130413390 245 ITFDPDTAHKYLRLQEENRKVT-NTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTckgidRK 322
Cdd:cd13734     1 FKLDPKTAHRKLRLSNDNLTVEyDPEGSKDQAAVLPRRFTGSPAVLGDVAISSGRHYWEVSVSRSTSYrVGVA-----YK 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 323 GEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKAGPF-RRLGVYIDFPGGILSFYGVEydTMTLVHKFACKFSEPVY 401
Cdd:cd13734    76 SAPRDEDLGKNSTSWCLSRDNNRYTARHDGKVVDLRVTGHpARIGVLLDYDNGTLSFYDAE--SKQHLYTFHVDFEGPVC 153

                  ...
gi 1130413390 402 AAF 404
Cdd:cd13734   154 PAF 156

SPRY domain in Ro-Ret family; This domain, named BSPRY, has been identified in the Ro-Ret family, since the protein is composed of a B-box, an alpha-helical coiled coil and a SPRY domain. The gene for BSPRY resides on human chromosome 9 and is specifically expressed in testis. The function of BSPRY is not known, but several related proteins of the RING-Box-coiled-coil (RBCC) family have been implicated in cell transformation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 245 ITFDPDTAHKYLRLQEENRKVT-NTTPWEHPYPDLPSRFLHWRQVLSQQSLY--LHRYYFEVEIFGAgtY-VGLTCKGID 320
Cdd:cd12904     1 LRFDERTVSPLLSLSEDRRTLTfSPKKARQSPPDDPERFDHWPNALASLSFSsgTHAWVVDVGKSCA--YkVGVCYGSLE 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 321 RKGEERNSCISGNNFSWSLQWNGKEFTAWYSDMETPLKA--GPfRRLGVYIDFPGGILSFYgvEYDTMTLVHKFACKFSE 398
Cdd:cd12904    79 RKGSGNEARLGYNAFSWVFSRYDGEFSFSHNGQHVPLELlkCP-ARVGVLLDWPSQELLFY--DPDSCTVLHSHREAFAA 155

                  ....*.
gi 1130413390 399 PVYAAF 404
Cdd:cd12904   156 PLLPVF 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 244 DITFDPDTAHKYLRLQEENRKVtNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFG-AGTYVGLTCKGIDRK 322
Cdd:cd13741     1 DLTLDPDTAHPALLLSPDRRGV-RLAERRQEVPEHPKRFSADCCVLGAQGFRSGRHYWEVEVGGrRGWAVGAARESTHHK 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 323 ---GEERNSCISGNNFS----------------------WSLQWNGKEFTAWYSDMETPLKAG--PfRRLGVYIDFPGGI 375
Cdd:cd13741    80 ekvGSGGSSVSSGDASSsrhhhrrrrlhlpqqpllqrevWCVGTNGKRYQAQSSTEQTLLSPSekP-RRFGVYLDYEAGR 158

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 1130413390 376 LSFYGVEydTMTLVHKFACKF-SEPVYAAFWLSKKENAIRI 415
Cdd:cd13741   159 LGFYNAE--TLAHVHTFSAAFlGERVFPFFRVLSKGTRIKL 197

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 1130413390 245 ITFDPDTAHKYLRLQEENRKVTNTTPwEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCKGIDRKG 323
Cdd:cd15818    15 ITLDPKTAHPNLILSEDLTCVWHGDT-KQMLPDNPERFDSSVAVLGSEGFTSGKHYWEVEVAKKTKWtLGVVRESINRKG 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 324 eerNSCISGNNFSWSLQW-NGKEFTAwysdMETPLKA----GPFRRLGVYIDFPGGILSFYgvEYDTMTLVHKFACKFSE 398
Cdd:cd15818    94 ---NCPLSPEDGFWLLRLrNQNELKA----LDVPSFSltltSNLNKVGIYLDYEGGQVSFY--NANTMSHIYTFSDTFTE 164

                  ....*.
gi 1130413390 399 PVYAAF 404
Cdd:cd15818   165 KIYPYF 170

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 1130413390 244 DITFDPDTAHKYLRLQEENRKVTNTTpWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCK-GIDRK 322
Cdd:cd15811     1 DVTLDPDTANPELVLSEDRRSVRRGD-LRQALPDSPERFDPGPCVLGRERFTSGRHYWEVEVGDRTSWALGVCKeNVNRK 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1130413390 323 geERNSCISGNNFsWSLQWngkeFTAWYSDME---TPLKAGPfRRLGVYIDFPGGILSFYGV 381
Cdd:cd15811    80 --EKGELSAGNGF-WILVF----LGNYYSSERrtfAPLRDPP-RRVGIFLDYEAGHLSFYSA 133

SPRY-associated domain; PRY is a 50-60 amino acids domain associated with SPRY domains, adjacent to its N-terminal. PRY and SPRY domains are structurally very similar and consist of a beta sandwich fold. Distant homologs are domains in butyrophilin/marenostrin/pyrin, evolutionarily more ancient than SPRY/B30.2 counterpart.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1130413390 245 ITFDPDTAHKYLRLQEENRKVTNTTPWeHPYPDLPSRFLHWRQVLSQQSL 294
Cdd:pfam13765   1 VTLDPNTAHPSLVLSEDLKSVRYGDER-QNVPDNPERFDSWPCVLGSEGF 49

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 1130413390 245 ITFDPDTAHKYLRLQEENRKVTNTTPWEHpYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIF---GAGTYVGLTCKGIDR 321
Cdd:cd15826     2 VTLDPQTASGSLVLSEDRKSVRYTRQKQN-LPDSPLRFDGLPAVLGSPGFSSGRHRWQVEVQlgdGGGCTVGVAGESVRR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 322 KGEERNSCISGnnfSWSLQWNGKEFTAWYS-DMETPLKAGPfRRLGVYIDFPGGILSFYGVEydTMTLVHKFACKFSEPV 400
Cdd:cd15826    81 KGEMGLSAEDG---VWAVILSHQQCWASTSpGTDLPLSEIP-RRVGVALDYEAGTVTLTNAE--TQEPIFTFTASFSGKV 154

                  ....*....
gi 1130413390 401 YAAFWLSKK 409
Cdd:cd15826   155 FPFFAVWKK 163

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 1130413390 244 DITFDPDTAHKYLRLQEENRKVTNTTPWEHpYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIfGAGTYVGL-TCK-GIDR 321
Cdd:cd15816     1 DVKLDPATAHPSLLLTADLRSVQDGELWRD-VPGNPERFDTWPCVLGLQSFSSGRHYWEVAV-GEKAEWGLgVCQdSAPR 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 322 KGEernSCISGNNFSWSLqW--NGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYGVEYDTMtlVHKFACKFSEP 399
Cdd:cd15816    79 KGE---TTPSPENGVWAV-WllKGNEYMVLASPSVPLLQLRRPRRVGVFLDYEAGEISFYNVTAGSH--IYTFRQLFSGI 152

                  ....*..
gi 1130413390 400 VYAAFWL 406
Cdd:cd15816   153 LRPYFFV 159

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 1130413390 244 DITFDPDTAHKYLRLQEENRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTY-VGLTCKGIDRK 322
Cdd:cd13742    13 NLTFDPDTAHPYLVVSSDGKRVECADQKQAVSSDDPNRFDKANCVVSHQSFSEGEHYWEVIVGDKPRWaLGVISAEAGRK 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 323 GeeRNSCISGNNFsWSLQW-NGKEFTAwYSDMETP----LKAGPfRRLGVYIDFPGGILSFY-GVEYDTMTLVHKFACKF 396
Cdd:cd13742    93 G--RLHALPSNGF-WLLGCkEGKVYEA-HVEHKEPralrVEGRP-TRIGVYLSFSDGVLSFYdASDEDNLVQLFAFHERF 167

                         170
                  ....*....|....*....
gi 1130413390 397 SEPVYAAF---WLSKKENA 412
Cdd:cd13742   168 PGPLYPFFdvcWHDKGKNS 186

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 1130413390 244 DITFDPDTAHKYLrLQEENRKVTNTTPWEHPYPDLPSRFLHWRQVLSQQSLYLHRYYFEVEIFGAGTYVGLTCKGIDRKG 323
Cdd:cd15817     1 DLILDPETAHPNL-IVSEDRKAVRYRRMKPNCPYDPRRFTVYPAVLGSEGFDSGRHFWEVEVGGKGEWILGVCKDSLPRN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1130413390 324 EERNSCIsgNNFSWSLQWNGKEFTAWYSDMETPLKAGPFRRLGVYIDFPGGILSFYgvEYDTMTLVHKFACKFSEPVYAA 403
Cdd:cd15817    80 AQDPPSP--LGGCWQIGRYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFY--NMNDRSHLYTFTDTFTGKLIPY 155

                         170
                  ....*....|..
gi 1130413390 404 FWLSKKENAIRI 415
Cdd:cd15817   156 FYVGPDSEPLTI 167