The Src homology 2 (SH2) domain is a protein domain of about 100 amino-acid
residues first identified as a conserved sequence region between the
oncoproteins Src and Fps [1]. Similar sequences were later found in many other
intracellular signal-transducing proteins [2]. SH2 domains function as
regulatory modules of intracellular signalling cascades by interacting with
high affinity to phosphotyrosine-containing target peptides in a sequence-specific and strictly phosphorylation-dependent manner [3,4,5,6].
The SH2 domain has a conserved 3D structure consisting of two α helices
and six to seven β-strands. The core of the domain is formed by a
continuous β-meander composed of two connected β-sheets [7].
So far, SH2 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. Two
copies of the SH2 domain are found in those proteins in between the
catalytic 'X-' and 'Y-boxes' (see <PDOC50007>).
Some vertebrate and invertebrate protein-tyrosine phosphatases.
Mammalian Ras GTPase-activating protein (GAP).
Adaptor proteins mediating binding of guanine nucleotide exchange factors
to growth factor receptors: vertebrate GRB2, Caenorhabditis elegans sem-5
and Drosophila DRK.
Mammalian Vav oncoprotein, a guanine-nucleotide exchange factor of the
CDC24 family.
Miscellanous proteins interacting with vertebrate receptor protein
tyrosine kinases: oncoprotein Crk, mammalian cytoplasmic proteins Nck, Shc.
STAT proteins (signal transducers and activators of transcription).
Chicken tensin.
Yeast transcriptional control protein SPT6.
The profile developed to detect SH2 domains is based on a structural alignment
consisting of 8 gap-free blocks and 7 linker regions totaling 92 match
positions.
PROSITE method (with tools and information) covered by this documentation:
References
1
Authors
Sadowski I. Stone J.C. Pawson T.
Title
A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps.
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