SH2 domain
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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.
Binding and phosphorylation
SH2 domains typically bind a phosphorylated tyrosine residue in the context of a longer peptide motif within a target proteins, and SH2 domains represent the largest class of known pTyr-recognition domains[1].
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. The intimate relationship between tyrosine kinases and SH2 domains is supported by their coordinate emergence during eukaryotic evolution.
Diversity
SH2 domains are not present in yeast and appear at the boundary between protozoa and animalia in organisms such as the social amoeba Dictyostelium discoideum[2].
A detailed bioinformatic examination of SH2 domains of human and mouse reveals 120 SH2 domains contained within 110 proteins encoded by the human genome[3], representing a rapid rate of evolutionary expansion among the SH2 domains.
A large number of SH2 domain structures have been solved and many SH2 proteins have been knocked out in mouse.[4]
Proteins with SH2 domains include:
Functions
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.
References
- ↑ Pawson, T., Gish, G., Nash, P. (2001). SH2 domains, interaction modules and cellular wiring. Trends in Cell Biology 11(12): 504-511.
- ↑ Eichinger, L. et al. (2005). The genome of the social amoeba Dictyostelium discoideum. Nature 435, 43-57.
- ↑ Liu et al. (2006), The Human and Mouse Complement of SH2 Domain Proteins – establishing the boundaries of phosphotyrosine signaling. Molecular Cell 22: 851-868.
- ↑ http://sh2.uchicago.edu/
External links
- Entry for the SH2 domain in the SMART database
- Nash Lab: SH2 domain
- Pawson Lab: SH2 domain
- List of SH2 domain proteins in SCOP database
Protein tertiary structure | |
|---|---|
| General | Structural domain | Protein folding | Structure determination methods |
| All-α folds: | Helix bundle | Globin fold | Homeodomain fold | Alpha solenoid |
| All-β folds: | Immunoglobulin fold | Beta barrel | Beta-propeller |
| α/β folds: | TIM barrel | Leucine-rich repeat | Flavodoxin fold | Rossmann fold | Thioredoxin fold | Trefoil knot fold |
| α+β folds: | DNA clamp | Ferredoxin fold | Ribonuclease A | SH2-like fold |
| Irregular folds: | Conotoxin |
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Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
