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 890769858  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90
                 ....*....|....*.
gi 890769858 115 KNRLpaNSLPQEGDVV 130
Cdd:cd12880   81 IHKL--KQLVEEGDVI 94

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 890769858  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90
                 ....*....|....*.
gi 890769858 115 KNRLpaNSLPQEGDVV 130
Cdd:cd12880   81 IHKL--KQLVEEGDVI 94

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 890769858  35 MGTDVVIVKNGRRICGTGGCLASAPLHQNKSYFEFKIQSTGIWGIGVATQKVNLNQIPLGRDMHSLVMRNDGALYHNNEE 114
Cdd:cd12880    1 MGPDVVIVKNGRRICGTGAALANAPIVQDKAYFEVKIQSTGVWGVGLATRKTDLNRVPLGNDAESWVLRSDGTIWHNGEV 80

                         90
                 ....*....|....*.
gi 890769858 115 KNRLpaNSLPQEGDVV 130
Cdd:cd12880   81 IHKL--KQLVEEGDVI 94

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 890769858  31 DTQHMGTDVVIVKNGRRI-------CGTGGCLASAPLHQNKSYFEFKIqSTGIWG----IGVATQKVNLNQI------PL 93
Cdd:cd12876    5 DERDKSPAVQLSDNNREVyfhpdysCGTAAVRGTKPLTNGQHYWEIKM-SSPVYGtdmmVGVGTKKADLHAYryefcsLL 83

                         90       100
                 ....*....|....*....|...
gi 890769858  94 GRDMHSLVMRNDGALYHNNEEKN 116
Cdd:cd12876   84 GEDEESWGLSYKGLLWHDGQSRP 106

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 890769858  66 YFEFKIQSTG----IwGIGVATQKVNLNQIPlGRDMHS 99
Cdd:cd12909   28 YFEVKIISKGrdgyI-GIGFSTKDVNLNRLP-GWEPHS 63