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 1370472446  80 PTFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 159
Cdd:cd12902     1 PTFDLRSLSCSLEVSEDSRKVTVSHGPQAYAWSPDRFSISQVLCSQAFSSGQHYWEVDTRQCSHWAVGVASWEMSRDQML 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GRTMDSCCVEWKGTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWLYGLH 239
Cdd:cd12902    81 GRTMDSWCIEWKGTGQLSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSVANQERLLHECEVSASSPLHPAFWLYGLE 160

                  ....*...
gi 1370472446 240 PGNYLIIK 247
Cdd:cd12902   161 PGNSLIIK 168

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 1370472446  80 PTFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 159
Cdd:cd12902     1 PTFDLRSLSCSLEVSEDSRKVTVSHGPQAYAWSPDRFSISQVLCSQAFSSGQHYWEVDTRQCSHWAVGVASWEMSRDQML 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GRTMDSCCVEWKGTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWLYGLH 239
Cdd:cd12902    81 GRTMDSWCIEWKGTGQLSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSVANQERLLHECEVSASSPLHPAFWLYGLE 160

                  ....*...
gi 1370472446 240 PGNYLIIK 247
Cdd:cd12902   161 PGNSLIIK 168

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 1370472446 131 KHYWEV--DTRNCSHWAVGVASWEMSR--DQVLGRTMDSCCVEwkGTSQLSAWH-MVKETVLGSDRPG-VVGIWLNLEEG 204
Cdd:pfam00622   1 RHYFEVeiFGQDGGGWRVGWATKSVPRkgERFLGDESGSWGYD--GWTGKKYWAsTSPLTGLPLFEPGdVIGCFLDYEAG 78

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1370472446 205 KLAFYsvDNQEKLLYECTI-SASSPLYPAFWLY 236
Cdd:pfam00622  79 TISFT--KNGKSLGYAFRDvPFAGPLFPAVSLG 109

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 1370472446  80 PTFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 159
Cdd:cd12902     1 PTFDLRSLSCSLEVSEDSRKVTVSHGPQAYAWSPDRFSISQVLCSQAFSSGQHYWEVDTRQCSHWAVGVASWEMSRDQML 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GRTMDSCCVEWKGTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWLYGLH 239
Cdd:cd12902    81 GRTMDSWCIEWKGTGQLSAWHMNKETVLGSDKPRVVGIWLDLEEGKLAFYSVANQERLLHECEVSASSPLHPAFWLYGLE 160

                  ....*...
gi 1370472446 240 PGNYLIIK 247
Cdd:cd12902   161 PGNSLIIK 168

PRY/SPRY domain, also known as B30.2; This domain contains residues in the N-terminus that form a distinct PRY domain structure such that the B30.2 domain consists of PRY and SPRY subdomains. B30.2 domains comprise the C-terminus of three protein families: BTNs (receptor glycoproteins of immunoglobulin superfamily); several TRIM proteins (composed of RING/B-box/coiled-coil core); Stonutoxin (secreted poisonous protein of the stonefish Synanceia horrida). While SPRY domains are evolutionarily ancient, B30.2 domains are a more recent adaptation where the SPRY/PRY combination is a possible component of immune defense. Among the TRIM proteins, also known as the N-terminal RING finger/B-box/coiled coil (RBCC) family, only Classes I and II contain the B30.2 domain that has evolved under positive selection. Class I TRIM proteins include multiple members involved in antiviral immunity at various levels of interferon signaling cascade. Among the 75 human TRIMs, roughly half enhance immune response, which they do at multiple levels in signaling pathways. The PRY-SPRY domain in these TRIM families is suggested to serve as the target binding site.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446  80 PTFNLKSLSCSLEVSKDSRTVTVSHRPQ-PYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQV 158
Cdd:cd12874     1 LTFDPDTAHLNLILSDDLRSVRVGDISQhPPEPPPRFFECWQVLGSQSFSSGRHYWEVDVQDDSSWYVGVTYKSLPRKGK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 159 ---LGRTMDSCCVEWKGtSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPAFWL 235
Cdd:cd12874    81 msnLGRNNGSWCLEWRE-NEFSAWHNNPETRLPVTPPRRLGVFLDCDGGSLSFYGVTDGVQLLYTFKAKFTEPLYPAFWL 159

                         170
                  ....*....|..
gi 1370472446 236 YGlhpGNYLIIK 247
Cdd:cd12874   160 GE---GSTLSIC 168

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 1370472446  82 FNL--KSLSCSLEVSKDSRTVTV-SHRPQPYRWSCERFST--SQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRD 156
Cdd:cd13734     1 FKLdpKTAHRKLRLSNDNLTVEYdPEGSKDQAAVLPRRFTgsPAVLGDVAISSGRHYWEVSVSRSTSYRVGVAYKSAPRD 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370472446 157 QVLGRTMDSCCVEWKGTSqLSAWHMVKETVLGSDR-PGVVGIWLNLEEGKLAFYSVDNQeKLLYECTISASSPLYPAF 233
Cdd:cd13734    81 EDLGKNSTSWCLSRDNNR-YTARHDGKVVDLRVTGhPARIGVLLDYDNGTLSFYDAESK-QHLYTFHVDFEGPVCPAF 156

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 1370472446  91 LEVSKDSRTVTVSHRPQPYRWSCERFST-SQVLCSQALSsGKHYWEVDtRNCSHWAVGVASWEMSR-----DQVLGRTMD 164
Cdd:cd16040    22 LSLSEGNRKVTRVKEEQPYPDHPERFDYwPQVLCREGLS-GRCYWEVE-WSGGGVDIAVAYKGISRkgdgdDSRFGYNDK 99

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370472446 165 SCCVEWKGTSqLSAWHMVKETVL-----GSDRpgvVGIWLNLEEGKLAFYSVDNQEKLLYecTISA--SSPLYPAFWLY 236
Cdd:cd16040   100 SWSLECSPSG-YSFWHNNKKTEIsvpssSSSR---VGVYLDHSAGTLSFYSVSDTMTLLH--TVQTtfTEPLYPGFGVG 172

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 1370472446  81 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTS-QVLCSQALSSGKHYWEVDTRNCSHWAVGVASwemsrDQVL 159
Cdd:cd12905     7 TFDPETAHPSLILSRDLTAVTESDEMQPYPRSPKRFLQCvNVLASQGFQSGRHYWEVWVGSKTKWDLGVAS-----ESVD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GRTMDSCCVE--------------WKGTsqlSAWhmVKETVlgSDRPGVVGIWLNLEEGKLAFYSVDNQeKLLYECTISA 225
Cdd:cd12905    82 RQARVKLCPEngywtlrlrngdeyWAGT---QPW--TRLRV--TSRPQRIGVFLDCEERKVSFYNADDM-SLLYSFHQGP 153

                  ....*...
gi 1370472446 226 SSPLYPAF 233
Cdd:cd12905   154 RGKVFPFF 161

PRY/SPRY domain of tripartite motif-binding protein 75 (TRIM75); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM75, also known as Gm794. TRIM75 domains are composed of RING/B-box/coiled-coil core and also known as RBCC proteins. TRIM75 has a single site of positive selection in its RING domain associated with E3 ubiquitin ligase activity. It has not been detectably expressed experimentally due to their constant turnover by the proteasome, and therefore not been characterized.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446  57 CPLPDQsHPALRR-ASRFAQWAI------HPtfnlkslscSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALS 128
Cdd:cd15829     1 CSFPPQ-YSALQKiIKKFRVDVTldpetaHP---------NLLVSEDKKCVTFTKKKQRVPDSPKRFTVNPvVLGFPGFH 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 129 SGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGRTMDSCC--VEWKGTSqLSAWHMVKETVLGSDRPGVVGIWLNLEEGKL 206
Cdd:cd15829    71 SGRHFWEVEVGDKPEWAVGVCKDSLSTKARRPPSGQQGCwrIQLQGGD-YDAPGAVPPPLLLEVKPRGIGVFLDYELGEI 149

                         170       180
                  ....*....|....*....|....*....
gi 1370472446 207 AFYSVdNQEKLLYECTISASSPLYPAFWL 235
Cdd:cd15829   150 SFYNM-PEKSHIHTFTDTFSGPLRPYFYV 177

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 1370472446 120 QVLCSQALSSGKHYWEVDTRNcSHWAVGVASWEMSRDQ------VLGRTMDSCCVEWKgTSQLSAWHMVKETVLGSDRPG 193
Cdd:cd13737    43 QVLCTRSLCEGCHYWEAEVSN-SWVCLGVTYSYSHPTGkscifyLIGRNPYSWCLEWD-SLKFSVWHNNIQTVVHGSYYK 120

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1370472446 194 VVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPA 232
Cdd:cd13737   121 TIGVLLDYAAGSLTFYGVANTMNLIYRFLTTFTEPLYPA 159

Fibronectin type III and SPRY containing 1 (FSD1) domain includes PRY at the N-terminus; This domain is part of the fibronectin type III and SPRY domain containing 1 (FSD1) and FSD1-like (FSD1L) proteins. These are centrosome-associated proteins that are characterized by an N-terminal coiled-coil region downstream of B-box (BBC) domain, a central fibronectin type III (FN3) domain, and C-terminal repeats in PRY/SPRY domain. The FSD1 protein associates with a subset of microtubules and may be involved in the stability and organization of microtubules during cytokinesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 105 RPQPYRWSCERFSTSQ--VLCSQALSSGKHYWEVD-TRNCSHWAVGVASWEMSRDQVLGRTMDSCCV---EWKGTSqLSA 178
Cdd:cd12901    58 RMPSARGGRDRFTAESytVLGDTLIDGGQHYWEVRaQKDSKAFSVGVAYRSLGKFDQLGKTNASWCLhvnNWLQNS-FAA 136

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370472446 179 WHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEkLLYECTISASSPLYPAF--WLYGLH 239
Cdd:cd12901   137 KHNNKAKTLDVPVPDRIGVYCDFDEGQLSFYNARTKQ-LLHTFKMKFTQPVLPAFmvWCGGLS 198

PRY/SPRY domain in tripartite motif-binding (TRIM) proteins TRIM50 and TRIM72; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of several TRIM proteins, including TRIM72 and TRIM50. TRIM72 (also known as MG53) has been shown to perform a critical function in membrane repair following acute muscle injury by nucleating the assembly of the repair machinery at injury sites. It is expressed specifically in skeletal muscle and heart, and tethered to the plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. TRIM50, an E3 ubiquitin ligase, is deleted in Williams-Beuren (WBS) syndrome, a multi-system neurodevelopmental disorder caused by the deletion of contiguous genes at chromosome region 7q11.23.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446  81 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 159
Cdd:cd12897    15 TFDPATAHPLLVVSSGGTVVECGLQKQRRASQPERFDKSTcVVASQGFSEGEHYWEVVVGDKPRWALGVIKGTASRKGKL 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GRTMDS--CCVEWKGTSQLSAWHMVKET-VLGS-DRPGVVGIWLNLEEGKLAFYSVDNQE--KLLYECTISASSPLYPAF 233
Cdd:cd12897    95 HASPSHgvWLIGLKEGKVYEAHGEPKEPrPLRVaGRPHRIGVYLSFEDGVLSFFDASDPDdlRTLYTFQERFQGKLYPFF 174

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 1370472446  91 LEVSKDSRTVTVSHRPQPYRWSCERFSTS-QVLCSQALSSGKHYWEVDTRNCSHWAVGVAswemsRDQVLGRTMDSCCVE 169
Cdd:cd15817    13 LIVSEDRKAVRYRRMKPNCPYDPRRFTVYpAVLGSEGFDSGRHFWEVEVGGKGEWILGVC-----KDSLPRNAQDPPSPL 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370472446 170 ---WK---GTSQLSAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVdNQEKLLYECTISASSPLYPAFWL 235
Cdd:cd15817    88 ggcWQigrYMSGYVASGPKTTQLLPVVKPSRIGIFLDYELGEVSFYNM-NDRSHLYTFTDTFTGKLIPYFYV 158

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 1370472446  81 TFNLKSLSCSLEVSKDSRTVTVSHRPQPYRWSCERFS-TSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRD--- 156
Cdd:cd15828    13 TLDPETAHPQLTVSEDRKSVLYGEMKQNVCYNPRRFYlCPAVLGSEGFHSGRQYWEVEVGDKPEWTLGVCQDCLPRNwsn 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 157 QVL--------GRTMDSCCVewkgtsqlsAWHMVKETVLGSDRPGVVGIWLNLEEGKLAFYSVDNQEkLLYECTISASSP 228
Cdd:cd15828    93 QPSvqdglwaiGRYSESNYV---------ALGPKKIQLLPKVRPSKIGIFLDYELGEVSFYNMNDRS-LLYTFSDSFTGT 162

                  ....*
gi 1370472446 229 LYPAF 233
Cdd:cd15828   163 LWPYF 167

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 1370472446 130 GKHYWEV--DTRNCSHWAVGVASWEMSRDQ--VLGRTMDSCCVEwkgTSQLSAWHMVKETVLGSD--RPGVVGIWLNLEE 203
Cdd:cd11709     1 GKWYWEVrvDSGNGGLIQVGWATKSFSLDGegGVGDDEESWGYD---GSRLRKGHGGSSGPGGRPwkSGDVVGCLLDLDE 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1370472446 204 GKLAFYSVDNQEKLLYECTISASSPLYPAFWLYG 237
Cdd:cd11709    78 GTLSFSLNGKDLGVAFTNLFLKGGGLYPAVSLGS 111

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 1370472446  90 SLEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDqvLGRTMDSCCV 168
Cdd:cd15815    25 ELTLSKDQRQVTYGRCQENLDASPKRFTVLPcVLGCEGFTSGRHYFEVDVGEGTGWDVGVCLENVQRG--FGMKQEPEFG 102

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370472446 169 EWkgtsqlsAWHMVKE----------TVLG-SDRPGVVGIWLNLEEGKLAFYSV 211
Cdd:cd15815   103 FW-------TIRLCEEdgyvaltsppTPLPlREKPLVVGVFLDYEAGLVSFYNM 149

PRY/SPRY domain in tripartite motif-containing protein 76 (TRIM76), also called cardiomyopathy-associated protein 5; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is 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. It has also been implicated in Duchenne muscular dystrophy and cardiac disease; gene polymorphism of TRIM76 is associated with left ventricular wall thickness in patients with hypertension while its interactions with M-band titin and calpain 3 link it to tibial and limb-girdle muscular dystrophies.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446  91 LEVSKDSRTVTVSHrpQPYRWSCERFSTSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGRTMDSCCVEW 170
Cdd:cd12898    15 LHISSDRGTVIYFH--ERRRKMSSLTECPSVLGEELPSCGQYYWETTVTRCPAYRLGICSSSASQAGALGEGSTSWCLHC 92

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370472446 171 KGTSQLSAWHMVKETVLGS----DRPGVVGIWLNLEEGKLAFYSVDNqEKLLYECTISASSPLYPAFWLYglHPGN 242
Cdd:cd12898    93 VPTSEPCRYTLLHSGIVSDvfvtERPARVGTLLDYNNGRLIFINAES-GQLLGIFRHRFAQPCHPAFALE--KPGK 165

PRY/SPRY domain in tripartite motif-containing protein 34 (TRIM34), also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1); This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM34, also known as RING finger protein 21 (RNF21) or interferon-responsive finger protein (IFP1). TRIM34 domain is composed of RING/B-box/coiled-coil core and also known as RBCC protein. The TRIM21 cDNA possesses at least three kinds of isoforms, due to alternative splicing, of which only the long and medium forms contain the SPRY domain. It is an interferon-induced protein, predominantly expressed in the testis, kidney, and ovary. The SPRY domain provides the capsid recognition motif that dictates specificity to retroviral restriction. While the PRY-SPRY domain 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 1370472446  81 TFNLKSLSCSLEVSKDSRTVT-VSHRPqpyrWSCERFStsqVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVL 159
Cdd:cd15825     5 TLNPVNLNLNLVLSEDQRQVTsVPIWP----FKCYNYG---ILGSQYFSSGKHYWEVDVSKKTAWILGVYCRKRSRTFKY 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 160 GR---TMDSCCVEWK--------GTSQLSAWHMVKETVLGSDR---------PGVVGIWLNLEEGKLAFYSVDNQEKLLY 219
Cdd:cd15825    78 VRqgkNHPNVYSRYRpqygywviGLQNKSEYYAFEDSSTSDPKvltlsvatpPHRVGVFLDYEAGTVSFFNVTNHGSLIY 157

                         170
                  ....*....|....*
gi 1370472446 220 E-CTISASSPLYPAF 233
Cdd:cd15825   158 KfSKCCFSQPVYPYF 172

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 1370472446  91 LEVSKDSRTVTVSHRPQPYRWSCERFSTSQ-VLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRdqvlgrtmdsccve 169
Cdd:cd15811    13 LVLSEDRRSVRRGDLRQALPDSPERFDPGPcVLGRERFTSGRHYWEVEVGDRTSWALGVCKENVNR-------------- 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 170 wKGTSQLSA----WHMVketVLGS-------------DRPGVVGIWLNLEEGKLAFYSVDNQEKLLYECTISASSPLYPA 232
Cdd:cd15811    79 -KEKGELSAgngfWILV---FLGNyysserrtfaplrDPPRRVGIFLDYEAGHLSFYSATDGSLLFIFPETPFSGTLRPL 154

                  .
gi 1370472446 233 F 233
Cdd:cd15811   155 F 155

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 1370472446  81 TFNLKSLSCSLEVSKDSRTVTVSHRP--QPYRWSCERF-STSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSR-- 155
Cdd:cd12904     2 RFDERTVSPLLSLSEDRRTLTFSPKKarQSPPDDPERFdHWPNALASLSFSSGTHAWVVDVGKSCAYKVGVCYGSLERkg 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446 156 ---DQVLGRTMDSccveW---KGTSQLSAWHMVKETVLG-SDRPGVVGIWLNLEEGKLAFYSVDNQeKLLYECTISASSP 228
Cdd:cd12904    82 sgnEARLGYNAFS----WvfsRYDGEFSFSHNGQHVPLElLKCPARVGVLLDWPSQELLFYDPDSC-TVLHSHREAFAAP 156

                  ....*
gi 1370472446 229 LYPAF 233
Cdd:cd12904   157 LLPVF 161

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 1370472446 114 ERFST-SQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGrtMDSCcvEWKGTSQLSAWH-MV---KETVLG 188
Cdd:cd12903    38 ERFRDwAVVLGDTPVTSGRHYWEVTVKRSQEFRIGVADVDMSRDECIG--TNES--SWVFAYAQRKWYaMVaneTVPVPL 113

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370472446 189 SDRPGVVGIWLNLEEGKLAFYSVDnQEKLLYECTISASSPLYPAFWLY 236
Cdd:cd12903   114 VGKPDRVGLLLDYEAGKLSLVDVE-KNSVVHTMSAEFRGPVVPAFALW 160

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 1370472446 114 ERFSTS-QVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGRT-MDSCCVEW-KGTSQLSAWHMVKETVLGSD 190
Cdd:cd15818    49 ERFDSSvAVLGSEGFTSGKHYWEVEVAKKTKWTLGVVRESINRKGNCPLSpEDGFWLLRlRNQNELKALDVPSFSLTLTS 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1370472446 191 RPGVVGIWLNLEEGKLAFYSVDNQEKlLYECTISASSPLYPAF 233
Cdd:cd15818   129 NLNKVGIYLDYEGGQVSFYNANTMSH-IYTFSDTFTEKIYPYF 170

PRY/SPRY domain in tripartite motif-binding protein 20 (TRIM20), also known as pyrin; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM20, which is also known as pyrin or marenostrin. Unlike TRIM domains that are composed of RING/B-box/coiled-coil core, the N-terminal RING domain in TRIM20 is exchanged by a PYRIN domain (PYD), a prime mediator of protein interactions necessary for apoptosis, inflammation and innate immune signaling pathway, and it also harbors a C-terminal B30.2 domain. Mutations in pyrin (TRIM20) are associated with familial Mediterranean fever (FMF), a recessively hereditary periodic fever syndrome, characterized by episodes of inflammation and fever. These mutations cluster in the C-terminal B30.2 domain and therefore it is assumed that pyrin plays a role in the innate immune system by possibly effecting caspase-1-dependent IL-1beta maturation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370472446  91 LEVSKDSRTVTVSHRPQPYRWSCERF-STSQVLCSQALSSGKHYWEVDTRNCSHWAVGVASWEMSRDQVLGRT------- 162
Cdd:cd15813    22 LIFSDDLKSVRLGNKWDRLPDNPERFdSCIIVLGSPSFTSGRHYWEVEVGDKTGWILGVCKASVSRKGSMTLSpengywv 101

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370472446 163 -MDSCCVEWKGTSQLSAWHMVKETvlgsdrPGVVGIWLNLEEGKLAFYSVDNQEkLLYECTISASS-PLYPAF 233
Cdd:cd15813   102 vMMTKRNEYQASTSPPTRLWLREP------PRRVGIFLDYEAGDISFYNVTAKS-HIYTFTSFSSSgPLQPIF 167