PROSITE documentation PDOC50188

B30.2/SPRY domain profile

The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the human class I major histocompatibility complex region [1], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors [2]. The SPRY domains are shorter at the N-terminus than the B30.2 domains and appear as a subdomain of the latter. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [3].

The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains [3]. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) [4]. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short α-helices at the N-terminus (see <PDB:2FNJ>). The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement [3]. The 5th β-strand corresponding to WEVE motif [5]. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [3].

Some proteins known to contain a B30.2/SPRY domain are listed below:

• Dictyostelium discoideum splA, a dual-specificity kinase that regulates spore cell differentiation.
• Ryanodine receptors (RyRs), involved in the release of Ca2+ ions from intracellular stores.
• SPRY domain-containing proteins with a SOCS boc (SSB). The SOCS proteins appear to form part of a classical negative feedback loop that regulates cytokine signal transduction.
• Proteins of the RBCC (RING-finger, B-box and coiled-coil domain) family, such as Sjoegren syndrom type-A or Ro/SS-A antigen, Xenopus nuclear factor 7 (Xnf7) and pyrin/marenostrin.
• Proteins of the butyrophilin-related family. Butyrophilin is a membrane protein expressed in milk fat globule membrane. Its SPRY domain is linked to two external immunoglobulin-like motifs by a single transmembrane segment.
• Enterophilins, a family of leucine zipper proteins associated with enterocyte differentiation.
• The α and β subunits of stonustoxin (STNX), a secreted protein that was purified from the venom of stonefish (Synanceja horrida).

The profile we developed covers the entire B30.2/SPRY domain.