SH2 domain

Encyclopedia : S : SH : SH2 : SH2 domain

"SH2" redirects here. For the microprocessor, see SuperH.

Ribbon diagram of the SH2 domain of human P56-Lck tyrosine kinase (PDB accession code 1LKK, chain A), colored from blue (N-terminus) to red (C-terminus).

The Src homology 2 domain (or SH2 domain) is a protein domain of about 100 amino acid residues first identified as a conserved sequence region among the oncoproteins Src and Fps. Similar sequences were later found in many other intracellular proteins involved in signal transduction, such as Abl, ZAP70, STAT proteins,Grb2, and RasGAP.

The SH2 domain predominantly binds a phosphorylated tyrosine residue in a target proteins, although non-phosphorylated tyrosine motifs have been identified as binding targets. Phosphorylation of tyrosine residues in a protein occurs during signal transduction and is carried out by tyrosine kinases. In this way, phosphorylation of a substrate by tyrosine kinases acts as a switch to trigger binding to an SH2 domain-containing protein.

Many biological signaling proteins use this mode of regulated protein-protein interactions as a means to localize proteins to various sub-cellular compartments, control enzymatic activities of proteins as well as nucleate multiprotein complexes, to name a few. The SH2 domain has thus become a prototype for a large number of modular interaction domains that have been since identified. The discovery of the SH2 domain and its many roles in signal transduction introduced the critical concept of how biology has exploited the use of modular interaction domains to create complex signaling networks.

Examples

Proteins with SH2 domains include:

Abl
GRB2
RasGAP
STAT proteins
ZAP70
SHP2
PI3K
CRK
SOCS
Src

For a complete list of SH2 domain proteins in human and mouse, see the SH2 Domain site at The University of Chicago (link below)

External links

Protein domains:
BZIP \| DED \| Kringle \| PH \| SH2 \| SH3 \| Zinc finger

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