The AVIT protein family. Secreted cysteine-rich vertebrate proteins with diverse functions

Abstract

Homologues of a protein originally isolated from snake venom and frog skin secretions are present in many vertebrate species. They contain 80-90 amino acids, 10 of which are cysteines with identical spacing. Various names have been given to these proteins, such as mamba intestinal protein 1 (MIT1), Bv8 (Bombina variegata molecular mass approximately 8 kDa), prokineticins and endocrine-gland vascular endothelial growth factor (EG-VEGF). Their amino-terminal sequences are identical, and so we propose that the sequence of their first four residues, AVIT, is used as a name for this family. From a comparison of the sequences, two types of AVIT proteins can be discerned. These proteins seem to be distributed widely in mammalian tissues and are known to bind to G-protein-coupled receptors. Members of this family have been shown to stimulate contraction of the guinea pig ileum, to cause hyperalgesia after injection into rats and to be active as specific growth factors. Moreover, the messenger RNA level of one of these AVIT proteins changes rhythmically in the region of the brain known as the suprachiasmatic nucleus. This shows that members of this new family of small proteins are involved in diverse biological processes.

Figure 1

Amino-acid sequences of mature AVIT proteins from different species. All mammalian and fish sequences are deduced from cloned complementary DNAs. Numbers refer to type 1 and type 2 proteins. B, bull; Bom, Bombina; F, fugu; H, human; M, mouse; Mam, black mamba; R, rat. The mamba sequence is from Joubert & Strydom (1980) and Schweitz et al. (1999); the Bombina cDNA sequence is from Mollay et al. (1999); human and mouse sequences are from Wechselberger et al. (1999), Li et al. (2001) and LeCouter et al. (2001); rat sequences are from Masuda et al. (2002); the bovine sequence has been deposited in GenBank (M.W. et al., personal communication; accession number ); the fugu sequences have been kindly communicated by H. Tian.

Figure 2

Phylogenetic tree constructed with CLUSTAL W (version 1.82) software using the amino-acid sequences of the mature proteins. (Abbreviations are as in Fig. 1.)

Figure 3

Comparison of signal peptides of type 1 and type 2 AVIT proteins. Signs used are as defined in CLUSTAL W (an asterisk denotes identity in all sequences of the alignment; colons denote conserved substitutions; full stops denote semi-conserved substitutions).

Figure 4

Amino-acid sequences of the basic insert encoded by exon 3 of mammalian type 2 AVIT genes. (Symbols are as in Fig. 3.)