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	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.

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

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

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 448
  • detected by PS50001: 425 (true positives)
  • undetected by PS50001: 23 (23 false negatives and 0 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50001:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50001
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50001
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50001
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50001
• View ligand binding statistics of PS50001
• Matching PDB structures: 1A07 1A08 1A09 1A1A ... [ALL]

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.
	Source	Mol. Cell. Biol. 6:4396-4408(1986).
	PubMed ID	3025655

2	Authors	Russel R.B., Breed J., Barton G.J.
	Source	FEBS Lett. 304:15-20(1992).

3	Authors	Marangere L.E.M., Pawson T.
	Source	J. Cell Sci. Suppl. 18:97-104(1994).

4	Authors	Pawson T., Schlessingert J.
	Title	SH2 and SH3 domains.
	Source	Curr. Biol. 3:434-442(1993).
	PubMed ID	15335710

5	Authors	Mayer B.J., Baltimore D.
	Title	Signalling through SH2 and SH3 domains.
	Source	Trends Cell Biol. 3:8-13(1993).
	PubMed ID	14731533

6	Authors	Pawson T.
	Title	Protein modules and signalling networks.
	Source	Nature 373:573-580(1995).
	PubMed ID	7531822
	DOI	10.1038/373573a0

7	Authors	Kuriyan J., Cowburn D.
	Source	Curr. Opin. Struct. Biol. 3:828-837(1993).

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