SH3 (src Homology-3) domains are small protein modules containing approximately 50 amino acid residues [ (PUBMED:15335710) (PUBMED:11256992) ]. They are found in a great variety of intracellular or membrane-associated proteins [ (PUBMED:1639195) (PUBMED:14731533) (PUBMED:7531822) ] for example, in a variety of proteins with enzymatic activity, in adaptor proteins, such as fodrin and yeast actin binding protein ABP-1.
The SH3 domain has a characteristic fold which consists of five or six beta-strands arranged as two tightly packed anti-parallel beta sheets. The linker regions may contain short helices. The surface of the SH3-domain bears a flat, hydrophobic ligand-binding pocket which consists of three shallow grooves defined by conservative aromatic residues in which the ligand adopts an extended left-handed helical arrangement. The ligand binds with low affinity but this may be enhanced by multiple interactions. The region bound by the SH3 domain is in all cases proline-rich and contains PXXP as a core-conserved binding motif. The function of the SH3 domain is not well understood but they may mediate many diverse processes such as increasing local concentration of proteins, altering their subcellular location and mediating the assembly of large multiprotein complexes [ (PUBMED:7953536) ].
SH3 domains are widespread among metazoan intracellular signalling proteins and typically bind proline-rich polypeptides. This SH3 domain is a prokaryotic homologue. It might have two possible functions: (1) promoting survival of a pathogen within the invaded cell by modulating pathways controlled by SH3 domains; or (2) promoting invasion by binding to receptors on eukaryotic cells [ (PUBMED:10322416) (PUBMED:10369758) ].
Family alignment:
There are 47276 SH3b domains in 28882 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing SH3b domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with SH3b domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing SH3b domain in the selected taxonomic class.
Eukaryotic signalling domain homologues in archaea and bacteria. Ancient ancestry and horizontal gene transfer.
J Mol Biol. 1999; 289: 729-45
Display abstract
Phyletic distributions of eukaryotic signalling domains were studied using recently developed sensitive methods for protein sequence analysis, with an emphasis on the detection and accurate enumeration of homologues in bacteria and archaea. A major difference was found between the distributions of enzyme families that are typically found in all three divisions of cellular life and non-enzymatic domain families that are usually eukaryote-specific. Previously undetected bacterial homologues were identified for# plant pathogenesis-related proteins, Pad1, von Willebrand factor type A, src homology 3 and YWTD repeat-containing domains. Comparisons of the domain distributions in eukaryotes and prokaryotes enabled distinctions to be made between the domains originating prior to the last common ancestor of all known life forms and those apparently originating as consequences of horizontal gene transfer events. A number of transfers of signalling domains from eukaryotes to bacteria were confidently identified, in contrast to only a single case of apparent transfer from eukaryotes to archaea.
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 SH3b domain which could be assigned to a KEGG orthologous group, and not all proteins containing SH3b domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.