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 109821743  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDVHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109821743 115 KNRLpaNSLPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQ 194
Cdd:cd12880   81 IHKL--KQLVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQS 158

                 ..
gi 109821743 195 IF 196
Cdd:cd12880  159 LL 160

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 109821743  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDVHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109821743 115 KNRLpaNSLPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQ 194
Cdd:cd12880   81 IHKL--KQLVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQS 158

                 ..
gi 109821743 195 IF 196
Cdd:cd12880  159 LL 160

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 109821743   64 KSYFEFKI--QSTGIWGIGVATQKVNL-NQIPLGRDVHSLVMRND-GALYHNNEEKNRLPANSlpQEGDVVGITYDHV-- 137
Cdd:pfam00622   1 RHYFEVEIfgQDGGGWRVGWATKSVPRkGERFLGDESGSWGYDGWtGKKYWASTSPLTGLPLF--EPGDVIGCFLDYEag 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 109821743  138 ELNVYLNGKNMHCPASGIR--GTVYPVVYV 165
Cdd:pfam00622  79 TISFTKNGKSLGYAFRDVPfaGPLFPAVSL 108

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 109821743  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDVHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 109821743 115 KNRLpaNSLPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQ 194
Cdd:cd12880   81 IHKL--KQLVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQS 158

                 ..
gi 109821743 195 IF 196
Cdd:cd12880  159 LL 160

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 109821743  64 KSYFEFKIQST--GIWGIGVATQKVNLN-QIPLGRDVHSLVMrnDGALYHNNEEKNRLPANSLPQEGDVVGITYD--HVE 138
Cdd:cd11709    2 KWYWEVRVDSGngGLIQVGWATKSFSLDgEGGVGDDEESWGY--DGSRLRKGHGGSSGPGGRPWKSGDVVGCLLDldEGT 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 109821743 139 LNVYLNGKNMHCPASGI---RGTVYPVVYVDDSAILDCQ 174
Cdd:cd11709   80 LSFSLNGKDLGVAFTNLflkGGGLYPAVSLGSGQGVTIN 118

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 109821743  31 DTQHMGTDVVIVKNGRRI-------CGTGGCLASAPLHQNKSYFEFKIqSTGIWG----IGVATQKVNLNQI------PL 93
Cdd:cd12876    5 DERDKSPAVQLSDNNREVyfhpdysCGTAAVRGTKPLTNGQHYWEIKM-SSPVYGtdmmVGVGTKKADLHAYryefcsLL 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 109821743  94 GRDVHSLVMRNDGALYHNNEEKNRlpANSLPQEGDVVGITYD--HVELNVYLNGKNMHCPASGIRG--TVYPVV 163
Cdd:cd12876   84 GEDEESWGLSYKGLLWHDGQSRPY--TSPFGNQGTIIGVHLDmwRGTLTFYKNGKPLGVAFTGLNGvkPLYPMV 155

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 109821743  36 GTDVVIVKNGRRICGT------GGCLASAPLHQNkSYFEFKIQSTGI-W----GIGVATQKVNLNQIP---LGRDVHSLV 101
Cdd:cd12887    7 GKNIRLSNDGRTATRVkasfnnGVVFSSRPLRPG-ELFEVRIDKLVDrWsgslEIGVTTLNPETLDLPpsaTDLKSGTWI 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 109821743 102 MRNDGALYHNNEEKNRLPAN-SLPQEGDVVGITYDHV-ELNVYLNGKNMHCPASGIRGTVYPVV 163
Cdd:cd12887   86 LSGSSVFKNGNKIRENYGPDlDRLRVGDRVGVMRTSDgTLHFYVNGEDQGVAASNVPQPVYAVV 149

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
                 ....*....|....*....|....*....|....*...
gi 109821743  66 YFEFKIQSTG----IwGIGVATQKVNLNQIPlGRDVHS 99
Cdd:cd12909   28 YFEVKIISKGrdgyI-GIGFSTKDVNLNRLP-GWEPHS 63