PROSITE documentation PDOC50001
Src homology 2 (SH2) domain profile


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>).
  • Mammalian phosphatidyl inositol 3-kinase regulatory p85 subunit.
  • 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.

Expert(s) to contact by email:

Zvelebil M.

Last update:

November 1995 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

SH2, PS50001; Src homology 2 (SH2) domain profile  (MATRIX)


1AuthorsSadowski I. Stone J.C. Pawson T.
TitleA noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps.
SourceMol. Cell. Biol. 6:4396-4408(1986).
PubMed ID3025655

2AuthorsRussel R.B. Breed J. Barton G.J.
SourceFEBS Lett. 304:15-20(1992).

3AuthorsMarangere L.E.M. Pawson T.
SourceJ. Cell Sci. Suppl. 18:97-104(1994).

4AuthorsPawson T. Schlessingert J.
TitleSH2 and SH3 domains.
SourceCurr. Biol. 3:434-442(1993).
PubMed ID15335710

5AuthorsMayer B.J. Baltimore D.
TitleSignalling through SH2 and SH3 domains.
SourceTrends Cell Biol. 3:8-13(1993).
PubMed ID14731533

6AuthorsPawson T.
TitleProtein modules and signalling networks.
SourceNature 373:573-580(1995).
PubMed ID7531822

7AuthorsKuriyan J. Cowburn D.
SourceCurr. Opin. Struct. Biol. 3:828-837(1993).

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