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Gene. 2004 Nov 24;342(2):251-61.

Src proteins/src genes: from sponges to mammals.

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Department of Molecular Biology, Rudjer Boskovic Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia.


The genome of marine sponge Suberites domuncula, a member of the most ancient and most simple metazoan phylum Porifera, encodes at least five genes for Src-type proteins, more than, i.e., Caenorhabditis elegans or Drosophila melanogaster (two in each). Three proteins, SRC1SD, SRC2SD and SRC3SD, were fully characterized. The overall homology (identity+similarity) among the three S. domuncula Srcs (68-71%) is much lower than the sequence conservation between orthologous Src proteins from freshwater sponges (82-85%). It is therefore very likely that several src genes/proteins were already present in the genome of Urmetazoa, the hypothetical metazoan ancestor. We have identified in the S. domuncula expressed sequence tags (ESTs) database further Src homology 2 (SH2) and 3 (SH3) domains that are unrelated to protein tyrosine kinases (PTKs). Src-related SH2 and SH3 domains from different species are much more conserved than SH2 and SH3 domains from different proteins in the same organism (S. domuncula), supporting the view that the common, ancestral src gene was already a multidomain protein composed of SH3, SH2 and tyrosine kinase (TK) domains. Two S. domuncula src genes were fully sequenced: src1SD gene has six and src2SD gene only one intron in front of SH2 domain, located at the same position in both genes. All vertebrate src genes, from fish to human, originated from the same ancestral gene, because they all have 10 introns at conserved positions. However, src genes in invertebrates have fewer introns that are located at different positions. Only the intron in front of the SH2 domain is present at the absolutely conserved position (and phase) in all known src genes, indicating that at least this intron was already present in the ancestral gene, common to all Metazoa. Our results also suggest that TK domain in this ancestral src was encoded on a single exon.

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