SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also 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. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 189 YKGHGKTPKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTG 268
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767939010 269 QPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPP-NLYPTVGLQTPGEVVDANFGQ 331
Cdd:cd12909   81 KPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIKKgNLYPTVGLRTPGEHVEANFGQ 144

Lissencephaly type-1-like homology motif; Alpha-helical motif present in Lis1, treacle, Nopp140, some katanin p60 subunits, muskelin, tonneau, LEUNIG and numerous WD40 repeat-containing proteins. It is suggested that LisH motifs contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 767939010   364 EWQTMIQKMVSSYLVHHGYCATAEAFARSTDQTV 397
Cdd:smart00667   1 ISRSELNRLILEYLLRNGYEETAETLQKESGLSL 34

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also 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. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 189 YKGHGKTPKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTG 268
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767939010 269 QPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPP-NLYPTVGLQTPGEVVDANFGQ 331
Cdd:cd12909   81 KPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIKKgNLYPTVGLRTPGEHVEANFGQ 144

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 767939010  214 IYYFEVKIVSKGrDGYMGIGLSAQGVNM--NRLPGWDKHSYGYHGDDGHSFCSSgTGQPYG-PTFTTGDVIGCCVNLINN 290
Cdd:pfam00622   1 RHYFEVEIFGQD-GGGWRVGWATKSVPRkgERFLGDESGSWGYDGWTGKKYWAS-TSPLTGlPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767939010  291 TCFYTKNGHSLGIAFTDLP--PNLYPTVGLQtPGEVVDANFGQH 332
Cdd:pfam00622  79 TISFTKNGKSLGYAFRDVPfaGPLFPAVSLG-AGEGLKFNFGLR 121

CT11-RanBPM; protein-protein interaction domain present in crown eukaryotes (plants, animals, fungi)

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010   526 AIERMIHFGRELQAMSEqlrrdcGKNTANKKMLKDAFSLLAYSDP-WNSPVGNQLDPIQREPVCSALNSAILET-HNLPK 603
Cdd:smart00757   2 KIEEALAYARELLAPFA------KEHEKFLKELEKTMALLAYPDPtEPSPYKELLSPSQREKLAEELNSAILELlHGKSS 75

                           90
                   ....*....|....*
gi 767939010   604 QPPLALAMGQATQCL 618
Cdd:smart00757  76 ESPLEILLSAGLAAL 90

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|....
gi 767939010  368 MIQKMVSSYLVHHGYCATAEAFAR 391
Cdd:pfam08513   1 ELNRLIYDYLVKEGYEETAEAFEK 24

SPRY domain in Ran binding proteins 9 and 10; This family includes SPRY domain in Ran binding protein (RBP or RanBPM) 9 and 10, and similar proteins. RanBP9 (also known as RanBPM), a binding partner of Ran, is a small Ras-like GTPase that exerts multiple functions via interactions with various proteins. RanBP9 and RanBP10 also 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. SPRY domain of RanBPM forms a complex with CD39, a prototypic member of the NTPDase family, thus down-regulating activity substantially. RanBP10 enhances the transcriptional activity of AR in a ligand-dependent manner and exhibits a protein expression pattern different from RanBPM in various cell lines. RanBP10 is highly expressed in AR-positive prostate cancer LNCaP cells, while RanBPM is abundant in WI-38 and MCF-7 cells.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 189 YKGHGKTPKDAASVRATHPIPAACGIYYFEVKIVSKGRDGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCSSGTG 268
Cdd:cd12909    1 YKGPGKTDKDAAAVRANHPIPPQCGIYYFEVKIISKGRDGYIGIGFSTKDVNLNRLPGWEPHSWGYHGDDGHSFCSSGTG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767939010 269 QPYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPP-NLYPTVGLQTPGEVVDANFGQ 331
Cdd:cd12909   81 KPYGPTFTTGDVIGCGINFRDNTAFYTKNGVNLGIAFRDIKKgNLYPTVGLRTPGEHVEANFGQ 144

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 767939010   212 CGIYYFEVKIVSKGrdgYMGIGLSAQGVN--MNRLPGWDKHSYGYHGDDGHsFCSSGTGQPYGPTFT-TGDVIGCCVNLI 288
Cdd:smart00449   1 SGRHYFEVEIGDGG---HWRVGVATKSVPrgYFALLGEDKGSWGYDGDGGK-KYHNSTGPEYGLPLQePGDVIGCFLDLE 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 767939010   289 NNTCFYTKNGHSLGI-AFTDLPPN--LYPTVGLQtPGEVVDANFGQ 331
Cdd:smart00449  77 AGTISFYKNGKYLHGlAFFDVKFSgpLYPAFSLG-SGNSVRLNFGP 121

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 767939010  214 IYYFEVKIVSKGrDGYMGIGLSAQGVNM--NRLPGWDKHSYGYHGDDGHSFCSSgTGQPYG-PTFTTGDVIGCCVNLINN 290
Cdd:pfam00622   1 RHYFEVEIFGQD-GGGWRVGWATKSVPRkgERFLGDESGSWGYDGWTGKKYWAS-TSPLTGlPLFEPGDVIGCFLDYEAG 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 767939010  291 TCFYTKNGHSLGIAFTDLP--PNLYPTVGLQtPGEVVDANFGQH 332
Cdd:pfam00622  79 TISFTKNGKSLGYAFRDVPfaGPLFPAVSLG-AGEGLKFNFGLR 121

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 767939010 201 SVRATHPIPaaCGI---YYFEVKIVSKGR--DGYMGIGLSAQGVNMNRLPGWDKHSYGYHGDDGHSFCS-SGTGQPYGPT 274
Cdd:cd12910   42 SVQTNLPLP--TGRpktIYFEVKIFELPRadDTSVAIGFATKPYPPFRLPGWHRGSLAVHSDDGHRYINdPFGGKDFTPP 119

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767939010 275 FTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPP--------------NLYPTVGL-QTPGEVVdANFGQ 331
Cdd:cd12910  120 FREGDTIGIGYRFSSGTIFFTRNGKRLGGWDLGEELdaeddgvtglegfhDLYAAIGVfGGECEVH-VNPGQ 190

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 767939010 213 GIYYFEVKIVSkGRDGYMGIGLSAQGVNMN--RLPGWDKHSYGYHGDDGHSfCSSGTGQPYGPTFTTGDVIGCCVNLINN 290
Cdd:cd11709    1 GKWYWEVRVDS-GNGGLIQVGWATKSFSLDgeGGVGDDEESWGYDGSRLRK-GHGGSSGPGGRPWKSGDVVGCLLDLDEG 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 767939010 291 TCFYTKNGHSLGIAFTDL---PPNLYPTVGLqTPGEVVDAN 328
Cdd:cd11709   79 TLSFSLNGKDLGVAFTNLflkGGGLYPAVSL-GSGQGVTIN 118

SPRY domain associated with DEAD box gene DDX1; This SPRY domain is associated with the DEAD box gene, DDX1, an RNA-dependent ATPase involved in HIV-1 Rev function and virus replication. It is suggested that DDX1 acts as a cellular cofactor by promoting oligomerization of Rev on the Rev response element (RRE). DDX1 RNA is overexpressed in breast cancer, data showing a strong and independent association between poor prognosis and deregulation of the DEAD box protein DDX1, thus potentially serving as an effective prognostic biomarker for early recurrence in primary breast cancer. DDX1 also interacts with RelA and enhances nuclear factor kappaB-mediated transcription. DEAD-box proteins are associated with all levels of RNA metabolism and function, and have been implicated in translation initiation, transcription, RNA splicing, ribosome assembly, RNA transport, and RNA decay.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 169 WSPKDKFSYIGLSQNNL----RVHYKGHGktpkdaasVRATHPIPAAcGIYYFEVKIVSKG--RdgymgIGLSAQGVNMN 242
Cdd:cd12873    1 MNPYDRDAALAISPDGLlcqsREEKGWQG--------CRATKGVKGK-GKYYYEVTVTDEGlcR-----VGWSTEDASLD 66

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 243 RlpGWDKHSYGYHGDDGHSFCSSGTGqpYGPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFtDLPPN-----LYPTVG 317
Cdd:cd12873   67 L--GTDKFGFGYGGTGKKSHGRQFDD--YGEPFGLGDVIGCYLDLDNGTISFSKNGKDLGKAF-DIPPHlrnsaLFPAVC 141

                        170
                 ....*....|....*.
gi 767939010 318 LQTpGEVVdANFGQHP 333
Cdd:cd12873  142 LKN-AEVE-FNFGDKP 155

SPRY domain in the suppressor of cytokine signaling 3 (SOCS3) family; The SPRY domain-containing SOCS box protein family (SPSB1-4, also known as SSB-1 to -4) is composed of a central SPRY protein interaction domain and a C-terminal SOCS box. All four SPSB proteins interact with c-Met, the hepatocyte growth factor receptor, but SOCS3 regulates cellular response to a variety of cytokines such as leukemia inhibitory factor (LIF) and interleukin 6. SOCS3, along with SOCS1, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS. In non-small cell lung cancer (NSCLC), SOCS3 is silenced and proline-rich tyrosine kinase 2 (Pyk2) is over-expressed; it has been suggested that SOCS3 could be an effective way to prevent the progression of NSCLC due to its role in regulating Pyk2 expression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 168 SWSPKDKFSYIGLSQNNLRVHYkgHGKTPKDAASVRATHPIPAacGIYYFEVKIVSK--GRDgyMGIGLSAQGVNMNR-- 243
Cdd:cd12876    3 TWDERDKSPAVQLSDNNREVYF--HPDYSCGTAAVRGTKPLTN--GQHYWEIKMSSPvyGTD--MMVGVGTKKADLHAyr 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 244 -----LPGWDKHSYGY-------HGddghsfcssGTGQPYGPTFTT-GDVIGCCVNLINNTCFYTKNGHSLGIAFTDLP- 309
Cdd:cd12876   77 yefcsLLGEDEESWGLsykgllwHD---------GQSRPYTSPFGNqGTIIGVHLDMWRGTLTFYKNGKPLGVAFTGLNg 147

                 ....*...
gi 767939010 310 -PNLYPTV 316
Cdd:cd12876  148 vKPLYPMV 155

SPRY domain at N-terminus of ring finger protein 123; This SPRY domain is found at the N-terminus of RING finger protein 123 domain (also known as E3 ubiquitin-protein ligase RNF123). The ring finger domain motif is present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. RNF123 displays E3 ubiquitin ligase activity toward the cyclin-dependent kinase inhibitor p27 (Kip1).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 201 SVRAThpipaAC---GIYYFEVKIVSKGrdgYMGIGLSAQGVNMNRLPG-WDKH-SYGYhgdDGHSFCS-SGTGQPYGPT 274
Cdd:cd12882    1 SIRAN-----ACvykGKWMYEVTLGTKG---IMQIGWATISCRFTQEEGvGDTRdSYAY---DGNRVRKwNVSTQKYGEP 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 275 FTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLP--PNL--YPTVGLQTpGEVVDANFG 330
Cdd:cd12882   70 WVAGDVIGCCIDLDKGTISFYRNGRSLGVAFDNVRrgPGLayFPAVSLSF-GERLELNFG 128

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 767939010 200 ASVRATHPIPAACGIYYFEVKIVSKGRDG-----YMGIGLSAQGVNMNRLPGWDKHSYGYHgDDGHSFCSSGTGQPYGPT 274
Cdd:cd13735    3 VFVYANSPIPAQAPSFYWEVEVVSLGETDdsdgpIISVGFAPPAEDRDGAWTNPVGTCLFH-NNGRAVHYRGSSLTQWKS 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767939010 275 FTT------GDVIGC-----CVNLINNTCFYTKNGHSLGIAFTDLPPNLYPTVGLQTPGEVVDANFG 330
Cdd:cd13735   82 IRTdvtlsiGDVAGCgwertDTPPAKGRVYFTHNGQRLPRSLQDVSGGLWPVVHVQKKNTRVRANFG 148

SPRY domain in the F-box family Fbxo45; Fbxo45 is a novel synaptic E3 and ubiquitin ligase, related to the suppressor of cytokine signaling (SOCS) proteins and located N-terminal to a SPRY (SPla and the ryanodine receptor) domain. Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1, via the SPRY domain, thus playing an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse. F-box motifs are found in proteins that function as the substrate recognition component of SCF E3 complexes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 168 SWSPKDKFSYIGLSQNNLRVHykghgKTPKDAASVRATHPIPAACGIYYFEVKIvskgrDGYMG----IGLSAQGVNMN- 242
Cdd:cd12907    2 AWNPNDCSRNIYIKPNGFTLH-----RNPVAQSTDGARGKIGFSSGRHAWEVWW-----EGPLGtvavVGIATKHAPLQc 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 243 ----RLPGWDKHSYGYHGDDGHSFCSSGTGQPY-----GPTFTTGDVIGCCVNLINNTCFYTKNGHSLGIAFTDLPP-NL 312
Cdd:cd12907   72 qgyvALLGSDDQSWGWNLVDNHLLHNGDSQGNYpqcnnAPKYQVGERIRVILDCEDNTLAFERGYEFLGVAFRGLPPtKL 151

                 ....
gi 767939010 313 YPTV 316
Cdd:cd12907  152 YPAV 155

SPRY domain-containing protein 7; This family contains SPRY domain-containing protein 7 (also known as SPRY domain-containing protein 7 or CLL deletion region gene 6 protein homolog or CLLD6 or chronic lymphocytic leukemia deletion region gene 6 protein homolog). In humans, CLLD6 is highly expressed in heart, skeletal muscle, and testis as well as cancer cell lines. 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 767939010 216 YFEVKIVSKGRdgyMGIGLSAQGVNMNRLPGwdkhsygyhGDDGHSF--CSSGT----GQPYG---PTFTTGDVIGCC-- 284
Cdd:cd12880   32 YFEVKIQSTGV---WGVGLATRKTDLNRVPL---------GNDAESWvlRSDGTiwhnGEVIHklkQLVEEGDVIGVTyd 99

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767939010 285 -VNLiNntcFYtKNGHSLGIAFTDLPPNLYPTVGLQTpGEVVDANF 329
Cdd:cd12880  100 hVEL-N---FY-LNGKPLDCPITGIKGTVYPVVYVDD-GAILDVQF 139

LisH; The LisH (lis homology) domain mediates protein dimerization and tetramerization. The LisH domain is found in Sif2, a component of the Set3 complex which is responsible for repressing meiotic genes. It has been shown that the LisH domain helps mediate interaction with components of the Set3 complex.

                          10        20
                  ....*....|....*....|....
gi 767939010  368 MIQKMVSSYLVHHGYCATAEAFAR 391
Cdd:pfam08513   1 ELNRLIYDYLVKEGYEETAEAFEK 24

SPRY domain 1 (SPRY1) of ryanodine receptor (RyR); This SPRY domain is the first of three structural repeats in all three isoforms of the ryanodine receptor (RyR), which are the major Ca2+ release channels in the membranes of sarcoplasmic reticulum (SR). There are three RyR genes in mammals; the skeletal RyR1, the cardiac RyR2 and the brain RyR3. The three SPRY domains are located in the N-terminal part of the cytoplasmic region of the RyRs, but no specific function has been found for this first SPRY domain of the RyRs.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 215 YYFEVKI------------------VSKGRDGYMGIGLSAQGVnmnrLPGWDKHSYGYhgdDGHSFCSSG----TGQPYG 272
Cdd:cd12877   20 WYFEVEVdhveqfthqpahlrvgwaNTSGYVPYPGGGEGWGGN----GVGDDLYSYGF---DGLHLWTGGrsrrVTSGTQ 92

                         90       100
                 ....*....|....*....|....*..
gi 767939010 273 PTFTTGDVIGCCVNLINNTCFYTKNGH 299
Cdd:cd12877   93 HLLKKGDVVGCCLDLSVPSISFRVNGR 119

SPRY domain in neuralized homology repeat; This family contains the neuralized homology repeat 1 (NHR1) domain similar to the SPRY domain (known to mediate specific protein-protein interactions) at the C-terminus of a conserved region within eukaryotic neuralized and neuralized-like proteins. In Drosophila, the neuralized protein (Neur) belongs to a group of ubiquitin ligases and is required in a subset of Notch pathway-mediated cell fate decisions during development of the nervous system. Neur binds to the Notch receptor ligand Delta through its first NHR1 domain and mediates its ubiquitination for endocytosis. Multiple copies of this region are found in some members of the family.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767939010 217 FEVKIVSKGRD--GYMGIGLSAQGVNMNRLP----GWDKHSYGYHGD----DGHSFCSSgtgqpYGPTF---TTGDVIGc 283
Cdd:cd12887   43 FEVRIDKLVDRwsGSLEIGVTTLNPETLDLPpsatDLKSGTWILSGSsvfkNGNKIREN-----YGPDLdrlRVGDRVG- 116

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 767939010 284 cVNLINNTC--FYTkNGHSLGIAFTDLPPNLYPTVGL 318
Cdd:cd12887  117 -VMRTSDGTlhFYV-NGEDQGVAASNVPQPVYAVVDL 151