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The Src homology 3 (SH3) domain is a small protein domain of about 60 amino-acid residues first identified as a conserved sequence in the non-catalytic
part of several cytoplasmic protein tyrosine kinases (e.g. Src, Abl, Lck) .
Since then, it has been found in a great variety of other intracellular or
membrane-associated proteins [2,3,4,5].
The SH3 domain has a characteristic fold which consists of five or six β-strands arranged as two tightly packed anti-parallel β sheets. The linker
regions may contain short helices .
The function of the SH3 domain is not well understood. The current opinion is
that they mediate assembly of specific protein complexes via binding to
proline-rich peptides .
In general SH3 domains are found as single copies in a given protein, but
there is a significant number of protein with two SH3 domains and a few with
3 or 4 copies.
So far, SH3 domains have been identified in the following proteins:
Many vertebrate, invertebrate and retroviral cytoplasmic (non-receptor)
protein tyrosine kinases. In particular in the Src, Abl, Bkt, Csk and ZAP70
families of kinases.
Mammalian phosphatidylinositol-specific phospholipase C-γ-1 and -2.
Adaptor proteins mediating binding of guanine nucleotide exchange factors
to growth factor receptors: vertebrate GRB2, Caenorhabditis elegans sem-5
and Drosophila DRK. All of which have two SH3 domains.
Mammalian Vav oncoprotein, a guanine nucleotide exchange factor of the
Some guanine-nucleotide releasing factors of the CDC25 family: yeast CDC25,
yeast SCD25, fission yeast ste6.
MAGUK proteins. These proteins consist of at least three types of domains:
one or more copies of the DHR domain, a SH3 domain and a C-terminal
guanylate kinase domain (see <PDOC00670>). Members of this family are:
Drosophila lethal(1)discs large-1 tumor suppressor protein (gene Dlg1),
mammalian tight junction protein ZO-1, vertebrate erythrocyte membrane
protein p55, Caenorhabditis elegans protein lin-2, rat protein CASK and
mammalian synaptic proteins SAP90/PSD-95, CHAPSYN-110/PSD-93, SAP97/DLG1
Plakin family of proteins, important actors in cross-linking force-bearing
structures in the cell, contain a curious SH3 domain insertion in their
chain of spectrin repeats .
Miscellanous proteins interacting with vertebrate receptor protein
tyrosine kinases: mammalian cytoplasmic protein Nck (3 copies), oncoprotein
Crk (2 copies).
Chicken Src substrate p80/85 protein (cortactin) and the similar human
hemopoietic lineage cell specific protein Hs1.
Mammalian dihydrouridine-sensitive L-type calcium channel β (regulatory)
subunit including the related human myasthenic syndrome antigen B (MSYB).
Mammalian neutrophil cytosolic activators of NADPH oxidase: p47 (NCF-1),
p67 (NCF-2), and a potential homolog from Caenorhabditis elegans (B0303.7).
NCF-1 and -2 have two copies of the SH3 domain, while B0303.7 has four.
Some myosin heavy chains from amoebas, slime molds and yeast (gene MYO3).
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