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Review
, 116 (4), 411-7

Relationship Between SPRY and B30.2 Protein Domains. Evolution of a Component of Immune Defence?

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Review

Relationship Between SPRY and B30.2 Protein Domains. Evolution of a Component of Immune Defence?

David A Rhodes et al. Immunology.

Abstract

SPRY and B30.2 are homologous domains which can be identified in 11 protein families encoded in the human genome. These include cell surface receptors of the immunoglobulin super-family (BTNs), negative regulators of the JAK/STAT pathway (SOCS-box SSB1-4) and proteins encoded by the numerous TRIM genes. Collectively, proteins containing SPRY and B30.2 domains cover a wide range of functions, including regulation of cytokine signalling (SOCS), RNA metabolism (DDX1, hnRNPs), intracellular calcium release (RyR receptors), immunity to retroviruses (TRIM5alpha) as well as regulatory and developmental processes (HERC1, Ash2L). In order to clarify the evolutionary relationship between the two domains, we compiled a curated database of SPRY and B30.2-domain sequences. We show that while SPRY domains are evolutionarily ancient, B30.2 domains, found in BTN and TRIM proteins, are a more recent evolutionary adaptation, comprising the combination of SPRY with an additional domain, PRY. The combination of SPRY and PRY to produce B30.2 domains may have been selected and maintained as a component of immune defence.

Figures

Figure 2
Figure 2
(a)Alignments of representative B30.2 domains used to seed the HMM analysis. These represent human BTN and TRIM B30.2 amino acid sequences and STNX, the only non-human sequence used. Three blocks of conserved residues are evident (underlined) giving the motifs used previously to characterize B30.2 domains. (b) Alignments of representative SPRY domains from human proteins. Two minimal motifs can be identified (underlined) which accounts for the amino acid similarity to B30.2 sequences detected by HMM analysis. (c) A comparison of conserved motifs in B30.2 and SPRY domains. The B30.2 domain is longer than SPRY and is composed of PRY and SPRY domain motifs combined. Amino acid identity between B30.2 and SPRY domains amounts to 9 conserved residues, comprising two minimal motifs, separated by up to 80 amino acids. B30.2 and SPRY are very distant homologues. Boxed residues in motif 2 highlight the block of three conserved aromatic residues.
Figure 1
Figure 1
Structure and function of SPRY and B30.2 protein families. Schematic representation of the domain architecture of 11 protein families with SPRY or B30.2 domains in the human genome. Representative amino acid sequences of human proteins were used and domain assignments predicted using BLASTp.

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