SH2 domain

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SH2 domain of human P56-Lck tyrosine kinase
Identifiers
Symbol SH2
Pfam PF00017
InterPro IPR000980
SMART SH2
PROSITE PDOC50001
SCOP 1sha
OPM protein 1xa6
Available PDB structures:

1k9aB:82-156 1jwoA:122-196 1a81G:168-244 1cszA:168-244 1csyA:168-244 1m61A:163-239 1nrvB:493-574 1mw4A:431-512 2augA:439-520 2shpA:112-197 1x6cA:110-194 2b3oA:110-194 1aycA:6-81 1ayaB:6-81 1aybA:6-81 1ayd :6-81 1ju5A:13-104 1spsA:148-230 1sprC:148-230 1bkl :148-230 1bkm :148-230 1kc2A:148-230 1is0A:148-230 1nzvA:148-230 1nzlA:148-230 1skj :148-230 1shbA:148-230 1shaA:148-230 1p13B:148-230 2ptkA:148-230 1f1wA:148-230 1f2fA:148-230 1o4kA:151-233 1o4iA:151-233 1o4hA:151-233 1a09B:151-233 1o46A:151-233 1o43A:151-233 1o4dA:151-233 1o4bA:151-233 1kswA:151-233 1a1bB:151-233 1a1eB:151-233 1o4jA:151-233 1o4mA:151-233 1o4cA:151-233 1a08A:151-233 1a07B:151-233 1o49A:151-233 1fmk :151-233 1o4nA:151-233 1hcsB:151-233 2src :151-233 1a1aB:151-233 1a1cA:151-233 1o4fA:151-233 1o4eA:151-233 1o4qA:151-233 1o4rA:151-233 1o48A:151-233 1shdA:151-233 1y57A:151-233 1hctB:151-233 1o45A:151-233 1o4gA:151-233 1o4oA:151-233 1o47A:151-233 1o42A:151-233 1o44A:151-233 1o4aA:151-233 1o41A:151-233 1o4pA:151-233 1o4lA:151-233 1g83A:149-231 1aotF:149-231 1aouF:149-231 1lkkA:127-209 1ijrA:127-209 1fbzB:127-209 1cweA:127-209 1lcjA:127-209 1cwdL:127-209 1lckA:127-209 1bhfA:127-209 1lklA:127-209 1qcfA:144-226 1ad5A:144-226 2hckB:144-226 3hck :144-226 1blj :118-199 1blk :118-199 1picA:624-698 1h9oA:624-698 1bfj :624-698 1bfi :624-698 1qadA:624-698 1z3kA:285-359 1fhs :60-135 1cj1A:60-135 1fyrA:60-135 2aobC:60-135 1bm2A:60-135 1bmbA:60-135 1griA:60-135 1x0nA:60-135 1jyuA:60-135 1qg1E:60-135 2aoaB:60-135 1jyqB:60-135 1zfpE:60-135 1jyrA:60-135 1ghu :60-135 1r1qB:58-132 1r1sA:58-132 1r1pD:58-132 1wcpA:488-559 1mil :488-559 1opkA:127-202 2abl :127-202 1oplA:127-202 1ab2 :127-202 1ka6A:7-87 1d4wA:7-87 1d1zA:7-87 1m27A:7-87 1d4tA:7-87 1ka7A:7-87 1i3zA:5-86 2cs0A:34-109 2fciA:668-741 2pleA:668-741 2pldA:668-741 1wquA:460-530 1rqqC:409-486 1rpyA:409-486 2crhA:671-745 1xa6A:59-130 2pna :333-408 2pnb :333-408 1oo4A:333-408 1oo3A:333-408 1fu5A:333-408 1fu6A:333-408 1luiA:245-328 1lukA:245-328 1lumA:245-328 1lunA:245-328 1yvlA:573-668 1bf5A:573-668 1bg1A:584-674 1y1uA:589-670 1uurA:587-658 1uusA:587-658

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.

Contents

[edit] Binding and phosphorylation

SH2 domains typically bind a phosphorylated tyrosine residue in the context of a longer peptide motif within a target protein, 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.

[edit] 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 mice.[4]

Proteins with SH2 domains include:

[edit] 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.

[edit] Human proteins containing this domain

ABL1; ABL2; BCAR3; BLK; BLNK; BMX; BTK; CHN1; CHN2; CISH; CRK; CRKL; CSK; DAPP1; FER; FES; FGR; FRK; FYN; GRAP; GRAP2; GRB10; GRB14; GRB2; GRB7; GRID; HCK; HSH2D; INPP5D; INPPL1; ITK; JAK2; LCK; LCP2; LYN; MATK; NCK1; NCK2; PIK3R1; PIK3R2; PIK3R3; PLCG1; PLCG2; PTK6; PTPN11; PTPN6; RASA1; SH2B; SH2B1; SH2B2; SH2B3; SH2D1A; SH2D1B; SH2D2A; SH2D3A; SH2D3C; SH2D4A; SH2D4B; SH2D5; SH2D6; SH3BP2; SHB; SHC1; SHC3; SHC4; SHD; SHE; SLA; SLA2; SOCS1; SOCS2; SOCS3; SOCS4; SOCS5; SOCS6; SOCS7; SRC; SRMS; STAT1; STAT2; STAT3; STAT4; STAT5A; STAT5B; STAT6; SUPT6H; SYK; TEC; TENC1; TNS; TNS1; TNS3; TNS4; TXK; VAV1; VAV2; VAV3; YES1; ZAP70;

[edit] References

  1. ^ Pawson, T., Gish, G., Nash, P. (2001). SH2 domains, interaction modules and cellular wiring. Trends in Cell Biology 11(12): 504-511.
  2. ^ Eichinger, L. et al. (2005). The genome of the social amoeba Dictyostelium discoideum. Nature 435, 43-57.
  3. ^ Liu et al. (2006), The Human and Mouse Complement of SH2 Domain Proteins – establishing the boundaries of phosphotyrosine signaling. Molecular Cell 22: 851-868.
  4. ^ the SH2 domain

5. Huang H, Li L et al. (2008) Defining the Specificity Space of the Human Src Homology 2 Domain. Mol Cell Proteomics. 7:768-84.

[edit] External links

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Protein tertiary structure
General
All-α folds:
All-β folds:
α/β folds:
α+β folds:
Irregular folds:
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