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 188595645   8 CLRCCRDGG-TGHIPLKEMPA---VQLdtQHMGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEEKNRLpaNS 83
Cdd:cd12880   11 GRRICGTGAaLANAPIVQDKAyfeVKI--QSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEVIHKL--KQ 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 188595645  84 LPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQIF 157
Cdd:cd12880   87 LVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQSLL 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 188595645   8 CLRCCRDGG-TGHIPLKEMPA---VQLdtQHMGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEEKNRLpaNS 83
Cdd:cd12880   11 GRRICGTGAaLANAPIVQDKAyfeVKI--QSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEVIHKL--KQ 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 188595645  84 LPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQIF 157
Cdd:cd12880   87 LVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQSLL 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 188595645   28 VQLDTQHMGIWGIGVATQKVNL-NQIPLGRDMHSLVMRND-GALYHNNEEKNRLPANSlpQEGDVVGITYDHV--ELNVY 103
Cdd:pfam00622   6 VEIFGQDGGGWRVGWATKSVPRkGERFLGDESGSWGYDGWtGKKYWASTSPLTGLPLF--EPGDVIGCFLDYEagTISFT 83

                          90       100
                  ....*....|....*....|....*
gi 188595645  104 LNGKNMHCPASGIR--GTVYPVVYV 126
Cdd:pfam00622  84 KNGKSLGYAFRDVPfaGPLFPAVSL 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 188595645   8 CLRCCRDGG-TGHIPLKEMPA---VQLdtQHMGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEEKNRLpaNS 83
Cdd:cd12880   11 GRRICGTGAaLANAPIVQDKAyfeVKI--QSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEVIHKL--KQ 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 188595645  84 LPQEGDVVGITYDHVELNVYLNGKNMHCPASGIRGTVYPVVYVDDSAILDCQFSEFYHTPPPGFEKILFEQQIF 157
Cdd:cd12880   87 LVEEGDVIGVTYDHVELNFYLNGKPLDCPITGIKGTVYPVVYVDDGAILDVQFSNFYHPPPSGFEEIMFEQSLL 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 188595645  28 VQLDTQHMGIWGIGVATQKVNLN-QIPLGRDMHSLVMrnDGALYHNNEEKNRLPANSLPQEGDVVGITYD--HVELNVYL 104
Cdd:cd11709    7 VRVDSGNGGLIQVGWATKSFSLDgEGGVGDDEESWGY--DGSRLRKGHGGSSGPGGRPWKSGDVVGCLLDldEGTLSFSL 84

                         90       100       110
                 ....*....|....*....|....*....|....
gi 188595645 105 NGKNMHCPASGI---RGTVYPVVYVDDSAILDCQ 135
Cdd:cd11709   85 NGKDLGVAFTNLflkGGGLYPAVSLGSGQGVTIN 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 188595645  40 IGVATQKVNLNQI------PLGRDMHSLVMRNDGALYHNNEEKNRlpANSLPQEGDVVGITYD--HVELNVYLNGKNMHC 111
Cdd:cd12876   63 VGVGTKKADLHAYryefcsLLGEDEESWGLSYKGLLWHDGQSRPY--TSPFGNQGTIIGVHLDmwRGTLTFYKNGKPLGV 140

                         90
                 ....*....|....*
gi 188595645 112 PASGIRG--TVYPVV 124
Cdd:cd12876  141 AFTGLNGvkPLYPMV 155

SPRY domain in HERC1; This SPRY domain is found in the HERC1, a large protein related to chromosome condensation regulator RCC1. It is widely expressed in many tissues, playing an important role in intracellular membrane trafficking in the cytoplasm as well as Golgi apparatus. HERC1 also interacts with tuberous sclerosis 2 (TSC2, tuberin), which suppresses cell growth, and results in the destabilization of TSC2. However, the biological function of HERC1 has yet to be defined.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 188595645  30 LDTQHMGIWG--IGVATQKVNLNQIplgRDMHSLVMRN--DGALYHNNEEKNRLpaNSLPQEGDVVGITYDHVE--LNVY 103
Cdd:cd12881   50 LVKENRGNEGtcVGVSRKPVTDFNY---RTSSDMWLYRayNGNLYHNGEQLLRL--SSKFHQGDYITVVLDMEEgtLSFG 124

                         90       100
                 ....*....|....*....|....*...
gi 188595645 104 LNGKNMHCPASGIRGT-VYPVVYVDDSA 130
Cdd:cd12881  125 KNGEEPGVAFEDVDATeLYPCVMFYSSG 152