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<StructureSection load='1tze' size='400' side='right' caption='Structure of human Grb2 SH2 domain (pink) complex with phosphotyrosyl heptapeptide (gold)  (PDB entry [[1tze]])' scene=''>
<StructureSection load='' size='350' side='right' caption='Structure of human Grb2 SH2 domain (green) complex with phosphotyrosyl polypeptide (magenta)  (PDB entry [[1bmb]])' scene='51/516448/Cv/1'>
== Function ==
'''Growth factor receptor-bound protein 2''' (GRB2) is an adaptor protein.  It links the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases.  GRB2 contains an SH2 domain which binds tyrosine phosphorylated sequences and 2 SH3 domains which direct complex formation of proline-rich sequences.  GRB2 is involved in signal transduction.
'''Growth factor receptor-bound proteins''' (GRB) are adaptor proteins.  GRBs contain SH2, Ras-associated (RA) and pleckstrin homology (PH) domains. <br />
* '''GRB2''' links the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases.  GRB2 contains an SH2 domain which binds tyrosine phosphorylated sequences and 2 SH3 domains which direct complex formation of proline-rich sequences.  GRB2 is involved in signal transduction<ref>PMID:1322798</ref>.<br />
*  '''GRB7''' interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway<ref>PMID:19717535</ref>.<br />
*  '''GRB10''' and '''GRB14''' interact with insulin receptor and insulin-like growth factor receptors<ref>PMID:12783867</ref>.  For additional details on GRB10 see [[Grb10 SH2 Domain]].<br />


==3D structures of Grb2==
== Structural highlights ==
Human GRB2 residue <scene name='51/516448/Cv/5'>Trp121 forces the phosphotyrosyl containing ligand</scene> into a turn conformation. Water molecules are shown as red spheres. <scene name='51/516448/Cv/6'>Phosphotyrosine binding</scene>  <ref>PMID:10090780</ref>.


[[1ghu]] – hGRB2 SH2 domain (mutant) – human<br />
==3D structures of growth factor receptor-bound proteins==
[[1fhs]], [[1jyu]], [[2aoa]], [[2h46]] - hGRB2 SH2 domain<br />
[[Growth factor receptor-bound proteins 3D structures]]
[[2vvk]], [[2vwf]], [[2w0z]] - hGRB2 SH3 domain<br />
[[1tze]], [[1bmb]], [[1bm2]], [[1zfp]], [[1qg1]], [[1jyq]], [[1jyr]], [[2aob]], [[2h5k]], [[2huw]], [[3c7i]], [[3imd]], [[3imj]], [[3in7]], [[3in8]], [[3kfj]], [[3n8m]], [[3n7y]], [[3n84]], [[3mxc]], [[3mxy]], [[3ov1]], [[3ove]], [[3s8n]], [[3s8o]] - hGRB2 SH2 domain + phosphotyrosyl peptide<br />
[[1x0n]] - hGRB2 SH2 domain + inhibitor - NMR<br />
[[1cj1]] - hGRB2 SH2 domain + phosphotyrosyl derivative<br />
[[1gbq]], [[2gbq]], [[3gbq]], [[4gbq]], [[1aze]] - GRB2 SH3 domain + SOS-1 peptide – NMR<br />
[[1io6]], [[1h3h]] - GRB2 SH3 domain + ligand peptide – NMR


</StructureSection>
== References ==
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Jaime Prilusky, Joel L. Sussman
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