Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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SPRY Domain in SPla and the RYanodine Receptor.

SMART accession number:	SM00449
Description:	Domain of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin homologues.
Interpro abstract (IPR018355):	The SPRY domain is of unknown function. Distant homologues are domains in butyrophilin/marenostrin/pyrin [(PUBMED:9204703)]. Ca2+-release from the sarcoplasmic or endoplasmic reticulum, the intracellular Ca2+ store, is mediated by the ryanodine receptor (RyR) and/or the inositol trisphosphate receptor (IP3R).
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 2359 SPRY domains in 2054 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a SPRY domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with SPRY domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Hilton DJ et al.
  • Twenty proteins containing a C-terminal SOCS box form five structural classes.
  • Proc Natl Acad Sci U S A. 1998; 95: 114-9
  • Display abstract

  • The four members of the recently identified suppressor of cytokines signaling family (SOCS-1, SOCS-2, SOCS-3, and CIS, where CIS is cytokine-inducible SH2-containing protein) appear, by various means, to negatively regulate cytokine signal transduction. Structurally, the SOCS proteins are composed of an N-terminal region of variable length and amino acid composition, a central SH2 domain, and a previously unrecognized C-terminal motif that we have called the SOCS box. By using the SOCS box amino acid sequence consensus, we have searched DNA databases and have identified a further 16 proteins that contain this motif. These proteins fall into five classes based on the protein motifs found N-terminal of the SOCS box. In addition to four new SOCS proteins (SOCS-4 to SOCS-7) containing an SH2 domain and a SOCS box, we describe three new families of proteins that contain either WD-40 repeats (WSB-1 and -2), SPRY domains (SSB-1 to -3) or ankyrin repeats (ASB-1 to -3) N-terminal of the SOCS box. In addition, we show that a class of small GTPases also contains a SOCS box. The expression of representative members of each class of proteins differs markedly, as does the regulation of expression by cytokines. The function of the WSB, SSB, and ASB protein families remains to be determined.

  • Ponting C, Schultz J, Bork P
  • SPRY domains in ryanodine receptors (Ca(2+)-release channels).
  • Trends Biochem Sci. 1997; 22: 193-4
• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the SPRY domain.

  Protein	Disease
  Pyrin (O15553) (SMART)	OMIM:249100: Familial Mediterranean fever

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 45.83 map04020 Calcium signaling pathway 25.00 map04120 Ubiquitin mediated proteolysis 12.50 map00380 Tryptophan metabolism 12.50 map04730 Long-term depression 4.17 map00230 Purine metabolism This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with SPRY domain which could be assigned to a KEGG orthologous group, and not all proteins containing SPRY domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of SPRY domains in PDB

  PDB code	Main view	Title
  2afj		Spry domain-containing socs box protein 2 (ssb-2)
  2fbe		Crystal structure of the pryspry-domain
  2fnj		Crystal structure of a b30.2/spry domain-containing protein gustavus in complex with elongin b and elongin c
  2ihs		Crystal structure of the b30.2/spry domain of gustavus in complex with a 20-residue vasa peptide
  2iwg		Complex between the pryspry domain of trim21 and igg fc
  2jk9		The structure of spla-ryanodine receptor domain and socs box containing 1 in complex with a par-4 peptide
  2v24		Structure of the human spry domain-containing socs box protein ssb-4
  2vok		Murine trim21
  2vol		Murine trim21 in complex with murine igg fc
  2wl1		Pyrin pryspry domain
  2yyo		Crystal sturcture of human spry domain
  3ek9		Spry domain-containing socs box protein 2: crystal structure and residues critical for protein binding
  3emw		Crystal structure of human spla/ryanodine receptor domain and socs box containing 2 (spsb2) in complex with a 20- residue vasa peptide
  3f2o		Crystal structure of human spla/ryanodine receptor domain and socs box containing 1 (spsb1) in complex with a 20- residue vasa peptide

• Links (links to other resources describing this domain)

• PFAM	SPRY
  INTERPRO	IPR018355

Send comments to Ivica Letunic