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.

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                 ....*....|....*....|....*....|....*....|....*...
gi 922580982   1 MEYTVNDRkriyQDDSMAFTNMPrGLYYPAFSVNANSSITVHTGLSSP 48
Cdd:cd12889  130 LSFYVNDE----PQGPIAFRNLP-GVFYPAVSLNRNVQVTLHTGLEPP 172

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

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                 ....*....|....*....|....*....|....*....|....*...
gi 922580982   1 MEYTVNDRkriyQDDSMAFTNMPrGLYYPAFSVNANSSITVHTGLSSP 48
Cdd:cd12889  130 LSFYVNDE----PQGPIAFRNLP-GVFYPAVSLNRNVQVTLHTGLEPP 172

PRY/SPRY domain in tripartite motif-containing proteins, TRIM9 and TRIM67; This domain, consisting of the distinct N-terminal PRY subdomain followed by the SPRY subdomain, is found at the C-terminus of TRIM9 proteins. TRIM9 protein is expressed mainly in the cerebral cortex, and functions as an E3 ubiquitin ligase. It has been shown that TRIM9 is localized to the neurons in the normal human brain and its immunoreactivity in affected brain areas in Parkinson's disease and dementia with Lewy bodies is severely decreased, possibly playing an important role in the regulation of neuronal function and participating in pathological process of Lewy body disease through its ligase. TRIM67 negatively regulates Ras activity via degradation of 80K-H, leading to neural differentiation, including neuritogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 922580982   1 MEYTVNDRkriyQDDSMAFTNMPrGLYYPAFSVNANSSITVHTGLSSP 48
Cdd:cd12889  130 LSFYVNDE----PQGPIAFRNLP-GVFYPAVSLNRNVQVTLHTGLEPP 172