SPRY domain-containing protein 3; This family contains SPRY domain-containing protein 3 (SPRYD3). In humans, it is highly expressed in most tissues, including brain, kidney, heart, intestine, skeletal muscle, and testis. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 220 WGRLHDVRVCGTLLEYLGKGksIVDVGLAQARHPLSTRSHYFEVEIVDPGEKCYIALGLARKDYPKNRHPGWSRGSVAYH 299
Cdd:cd12908    1 WERLNDVRVNGDVLEYHGRG--IGDVGLAQARRPLSPDNHYFEVEIVDPGVRCYIAIGLAPQDYPLDRHPGWNPGSVAYH 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 300 ADDGKIFHGSGVGDPFGPRCYKGDIMGCGIMFPRDYILDSEGDSDDscdtvilsptaravrnvrnvmylhqegeeeeeee 379
Cdd:cd12908   79 ADDGKLFKGSGVGDQFGPRCTKGDRMGCGIRFPRDYDTDSEDQGDE---------------------------------- 124

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160420333 380 eeeedgeeieqeHEGKKVVVFFTRNGKIIGKKDAVVPSGGFFPTIGMLSCGEKVKVDLH 438
Cdd:cd12908  125 ------------EEGRTVQVFFTRNGKEVGRTEVPLPPGGFYPAVGMHSEGEKVRVDLH 171

SPRY domain-containing protein 3; This family contains SPRY domain-containing protein 3 (SPRYD3). In humans, it is highly expressed in most tissues, including brain, kidney, heart, intestine, skeletal muscle, and testis. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 220 WGRLHDVRVCGTLLEYLGKGksIVDVGLAQARHPLSTRSHYFEVEIVDPGEKCYIALGLARKDYPKNRHPGWSRGSVAYH 299
Cdd:cd12908    1 WERLNDVRVNGDVLEYHGRG--IGDVGLAQARRPLSPDNHYFEVEIVDPGVRCYIAIGLAPQDYPLDRHPGWNPGSVAYH 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 300 ADDGKIFHGSGVGDPFGPRCYKGDIMGCGIMFPRDYILDSEGDSDDscdtvilsptaravrnvrnvmylhqegeeeeeee 379
Cdd:cd12908   79 ADDGKLFKGSGVGDQFGPRCTKGDRMGCGIRFPRDYDTDSEDQGDE---------------------------------- 124

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160420333 380 eeeedgeeieqeHEGKKVVVFFTRNGKIIGKKDAVVPSGGFFPTIGMLSCGEKVKVDLH 438
Cdd:cd12908  125 ------------EEGRTVQVFFTRNGKEVGRTEVPLPPGGFYPAVGMHSEGEKVRVDLH 171

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 160420333    80 YFEVSIVDSGVrgtIAVGLVPQYYSLDHQ--PGWLPDSVAYHADDGKLYNGRaKGRQFGSKC-NSGDRIGCGIepvsfDV 156
Cdd:smart00449   5 YFEVEIGDGGH---WRVGVATKSVPRGYFalLGEDKGSWGYDGDGGKKYHNS-TGPEYGLPLqEPGDVIGCFL-----DL 75

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 160420333   157 QTAQIFFTKNGKRV-GSTIMPMSPDG-LFPAVGMHS 190
Cdd:smart00449  76 EAGTISFYKNGKYLhGLAFFDVKFSGpLYPAFSLGS 111

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 160420333   80 YFEVsIVDSGVRGTIAVGLV-PQYYSLDHQ-PGWLPDSVAYHADDGKLYNGRaKGRQFGSKCN-SGDRIGCGIEpvsFDV 156
Cdd:pfam00622   3 YFEV-EIFGQDGGGWRVGWAtKSVPRKGERfLGDESGSWGYDGWTGKKYWAS-TSPLTGLPLFePGDVIGCFLD---YEA 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 160420333  157 QTaqIFFTKNGKRVGSTI-MPMSPDGLFPAVGMHSlGEEVRLHL 199
Cdd:pfam00622  78 GT--ISFTKNGKSLGYAFrDVPFAGPLFPAVSLGA-GEGLKFNF 118

SPRY domain-containing protein 3; This family contains SPRY domain-containing protein 3 (SPRYD3). In humans, it is highly expressed in most tissues, including brain, kidney, heart, intestine, skeletal muscle, and testis. It also has cross-species conservation, suggesting that it is likely to carry out important cellular processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 220 WGRLHDVRVCGTLLEYLGKGksIVDVGLAQARHPLSTRSHYFEVEIVDPGEKCYIALGLARKDYPKNRHPGWSRGSVAYH 299
Cdd:cd12908    1 WERLNDVRVNGDVLEYHGRG--IGDVGLAQARRPLSPDNHYFEVEIVDPGVRCYIAIGLAPQDYPLDRHPGWNPGSVAYH 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 300 ADDGKIFHGSGVGDPFGPRCYKGDIMGCGIMFPRDYILDSEGDSDDscdtvilsptaravrnvrnvmylhqegeeeeeee 379
Cdd:cd12908   79 ADDGKLFKGSGVGDQFGPRCTKGDRMGCGIRFPRDYDTDSEDQGDE---------------------------------- 124

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160420333 380 eeeedgeeieqeHEGKKVVVFFTRNGKIIGKKDAVVPSGGFFPTIGMLSCGEKVKVDLH 438
Cdd:cd12908  125 ------------EEGRTVQVFFTRNGKEVGRTEVPLPPGGFYPAVGMHSEGEKVRVDLH 171

SPRY domain in Ran binding proteins, SSH4, HECT E3 and SPRYD3; This family includes SPRY domains found in Ran binding proteins (RBP or RanBPM) 9 and 10, SSH4 (suppressor of SHR3 null mutation protein 4), SPRY domain-containing protein 3 (SPRYD3) as well as HECT, a C-terminal catalytic domain of a subclass of ubiquitin-protein ligase (E3). RanBP9 and RanBP10 act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. SPRYD3 is highly expressed in most tissues in humans, possibly involved in important cellular processes. HECT E3 mediates the direct transfer of ubiquitin from E2 to substrate.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333  66 GCYVASRPL--TKDSNYFEVSIVDSGVRGTIAVGLVPQYYSLDHQPGWLPDSVAYHADDGKLYNGRAKGRQFGSKCNSGD 143
Cdd:cd12885    1 GSVRADHPIppKVPVFYFEVTILDLGEKGIVSIGFCTSGFPLNRMPGWEDGSYGYHGDDGRVYLGGGEGENYGPPFGTGD 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 160420333 144 RIGCGIepvsfDVQTAQIFFTKNGKRVGSTIMPMSPDGLFPAVGMHSLGEEVRLHL 199
Cdd:cd12885   81 VVGCGI-----NFKTGEVFFTKNGELLGTAFENVVKGRLYPTVGLGSPGVKVRVNF 131

SPRY domain in Ran binding proteins, SSH4, HECT E3 and SPRYD3; This family includes SPRY domains found in Ran binding proteins (RBP or RanBPM) 9 and 10, SSH4 (suppressor of SHR3 null mutation protein 4), SPRY domain-containing protein 3 (SPRYD3) as well as HECT, a C-terminal catalytic domain of a subclass of ubiquitin-protein ligase (E3). RanBP9 and RanBP10 act as androgen receptor (AR) coactivators. Both consist of the N-terminal proline- and glutamine-rich regions, the SPRY domain, and LisH-CTLH and CRA motifs. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. SPRYD3 is highly expressed in most tissues in humans, possibly involved in important cellular processes. HECT E3 mediates the direct transfer of ubiquitin from E2 to substrate.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 249 QARHPLST--RSHYFEVEIVDPGEKCYIALGLARKDYPKNRHPGWSRGSVAYHADDGKIFHGSGVGDPFGPRCYKGDIMG 326
Cdd:cd12885    4 RADHPIPPkvPVFYFEVTILDLGEKGIVSIGFCTSGFPLNRMPGWEDGSYGYHGDDGRVYLGGGEGENYGPPFGTGDVVG 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 327 CGIMFPRdyildsegdsddscdtvilsptaravrnvrnvmylhqegeeeeeeeeeeedgeeieqeheGKkvvVFFTRNGK 406
Cdd:cd12885   84 CGINFKT------------------------------------------------------------GE---VFFTKNGE 100

                        170       180
                 ....*....|....*....|....*....
gi 160420333 407 IIGKKDAVVPSGGFFPTIGMLSCGEKVKV 435
Cdd:cd12885  101 LLGTAFENVVKGRLYPTVGLGSPGVKVRV 129

SPRY domain in SSH4 and similar proteins; This family includes SPRY domain in SSH4 (suppressor of SHR3 null mutation protein 4) and similar proteins. SSH4 is a component of the endosome-vacuole trafficking pathway that regulates nutrient transport and may be involved in processes determining whether plasma membrane proteins are degraded or routed to the plasma membrane. The SPRY domain in SSH4 may be involved in cargo recognition, either directly or by combination with other adaptors, possibly leading to a higher selectivity. In yeast, SSH4 and the homologous protein EAR1 (endosomal adapter of RSP5) recruit Rsp5p, an essential ubiquitin ligase of the Nedd4 family, and assist it in its function at multivesicular bodies by directing the ubiquitylation of specific cargoes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333  62 SGEVGCYVASRPLTKDSN---YFEVSIVDSGVR--GTIAVGLVPQYYSLDHQPGWLPDSVAYHADDGKLY-NGRAKGRQF 135
Cdd:cd12910   37 SLPLYSVQTNLPLPTGRPktiYFEVKIFELPRAddTSVAIGFATKPYPPFRLPGWHRGSLAVHSDDGHRYiNDPFGGKDF 116

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 160420333 136 GSKCNSGDRIGCGIEPvsfdvQTAQIFFTKNGKRVGS-------------TIMPMSPDGLFPAVGmhSLGEEVRLHLN 200
Cdd:cd12910  117 TPPFREGDTIGIGYRF-----SSGTIFFTRNGKRLGGwdlgeeldaeddgVTGLEGFHDLYAAIG--VFGGECEVHVN 187

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 160420333  79 NYFEVsIVDSGVRGTIAVGLVPQYYSLDHQPGWLPDSVAYHADDGKLYNG-RAKGRQFGSKCNSGDRIGCGIepvsfDVQ 157
Cdd:cd11709    3 WYWEV-RVDSGNGGLIQVGWATKSFSLDGEGGVGDDEESWGYDGSRLRKGhGGSSGPGGRPWKSGDVVGCLL-----DLD 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 160420333 158 TAQIFFTKNGKRVG--STIMPMSPDGLFPAVGMHSlGEEVRLH 198
Cdd:cd11709   77 EGTLSFSLNGKDLGvaFTNLFLKGGGLYPAVSLGS-GQGVTIN 118

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 160420333  259 HYFEVEIvDPGEKCYIALGLARKDYP--KNRHPGWSRGSVAYHADDGKIFHgSGVGDPFGPRCY-KGDIMGCGI 329
Cdd:pfam00622   2 HYFEVEI-FGQDGGGWRVGWATKSVPrkGERFLGDESGSWGYDGWTGKKYW-ASTSPLTGLPLFePGDVIGCFL 73

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 160420333   259 HYFEVEIVDPGekcYIALGLARKDYP--KNRHPGWSRGSVAYHADDGKIFHGSGVGDPFGPRCYKGDIMGCGIMFPRDYI 336
Cdd:smart00449   4 HYFEVEIGDGG---HWRVGVATKSVPrgYFALLGEDKGSWGYDGDGGKKYHNSTGPEYGLPLQEPGDVIGCFLDLEAGTI 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160420333 259 HYFEVEIVDPGEKCyIALGLARKDYPKN--RHPGWSRGSVAYHADdgKIFHGSGVGDPFGPRCYK-GDIMGC 327
Cdd:cd11709    3 WYWEVRVDSGNGGL-IQVGWATKSFSLDgeGGVGDDEESWGYDGS--RLRKGHGGSSGPGGRPWKsGDVVGC 71

SPRY domain-like in bacteria; This family contains SPRY-like domains that are found only in bacterial and are mostly uncharacterized. 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 eukaryotic 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).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333  80 YFEVSIVDSGVRGTIAVGLVPQYYSLDHQPGWLPDS---VAYHADDGKLYNGRAKGRQFGSKCNSGDRIGcgiepVSFDV 156
Cdd:cd12886    4 YWEVTVVSSAASTYAGIGVANAAATGNNGLNGIELSsigYSLGVYSGNKLSNGSSVATYGAGFTAGDVIG-----VALDL 78

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 160420333 157 QTAQIFFTKNGKRVGS------TIMPMSPDGLFPAVG 187
Cdd:cd12886   79 DAGKIWFYKNGVWQGGgdpapgTNPAFAGTAMYPAVT 115

SPRY domain in HECT E3; This domain consists of the SPRY subdomain similar to those found at the N-terminus of the HECT (homologous to the E6AP carboxyl terminus) protein, a C-terminal catalytic domain of a subclass of ubiquitin-protein ligase (E3). HECT E3 binds specific ubiquitin-conjugating enzymes (E2), accepts ubiquitin from E2, transfers ubiquitin to substrate lysine side chains, and transfers additional ubiquitin molecules to the end of growing ubiquitin chains. It has a prominent role in protein trafficking and immune response, and is involved in crucial signaling pathways implicated in tumorigenesis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160420333 253 PLSTRSHYFEVEIVDPGEK-----CYIALGLARKDYPKNRHPGWSRGSVAYHaDDGKIFHGSGVGDPFGPRCY------K 321
Cdd:cd13735   12 PAQAPSFYWEVEVVSLGETddsdgPIISVGFAPPAEDRDGAWTNPVGTCLFH-NNGRAVHYRGSSLTQWKSIRtdvtlsI 90

                 ....*..
gi 160420333 322 GDIMGCG 328
Cdd:cd13735   91 GDVAGCG 97