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1rpy

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Revision as of 13:44, 25 December 2014

CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS

Structural highlights

1rpy is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[SH2B2_RAT] Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis (By similarity). Involved in stimulation of glucose uptake by insulin. Involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Induces cytoskeletal reorganization and neurite outgrowth in cultured neurons.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The adaptor protein APS is a substrate of the insulin receptor and couples receptor activation with phosphorylation of Cbl to facilitate glucose uptake. The interaction with the activated insulin receptor is mediated by the Src homology 2 (SH2) domain of APS. Here, we present the crystal structure of the APS SH2 domain in complex with the phosphorylated tyrosine kinase domain of the insulin receptor. The structure reveals a novel dimeric configuration of the APS SH2 domain, wherein the C-terminal half of each protomer is structurally divergent from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine, pTyr-1162, coordinated by two lysine residues in beta strand D. This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor.

Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.,Hu J, Liu J, Ghirlando R, Saltiel AR, Hubbard SR Mol Cell. 2003 Dec;12(6):1379-89. PMID:14690593^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qian X, Riccio A, Zhang Y, Ginty DD. Identification and characterization of novel substrates of Trk receptors in developing neurons. Neuron. 1998 Nov;21(5):1017-29. PMID:9856458
↑ Ahmed Z, Smith BJ, Pillay TS. The APS adapter protein couples the insulin receptor to the phosphorylation of c-Cbl and facilitates ligand-stimulated ubiquitination of the insulin receptor. FEBS Lett. 2000 Jun 9;475(1):31-4. PMID:10854852
↑ Liu J, Kimura A, Baumann CA, Saltiel AR. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. Mol Cell Biol. 2002 Jun;22(11):3599-609. PMID:11997497
↑ Ahn MY, Katsanakis KD, Bheda F, Pillay TS. Primary and essential role of the adaptor protein APS for recruitment of both c-Cbl and its associated protein CAP in insulin signaling. J Biol Chem. 2004 May 14;279(20):21526-32. Epub 2004 Mar 18. PMID:15031295 doi:10.1074/jbc.M307740200
↑ Hu J, Liu J, Ghirlando R, Saltiel AR, Hubbard SR. Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor. Mol Cell. 2003 Dec;12(6):1379-89. PMID:14690593

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1rpy"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1rpy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RPY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1RPY FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rpy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rpy RCSB], [http://www.ebi.ac.uk/pdbsum/1rpy PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1rpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rpy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1rpy RCSB], [http://www.ebi.ac.uk/pdbsum/1rpy PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/SH2B2_RAT SH2B2_RAT]] Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis (By similarity). Involved in stimulation of glucose uptake by insulin. Involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Induces cytoskeletal reorganization and neurite outgrowth in cultured neurons.<ref>PMID:9856458</ref> <ref>PMID:10854852</ref> <ref>PMID:11997497</ref> <ref>PMID:15031295</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 32: @@
 </StructureSection>
 [[Category: Rattus norvegicus]]
-[[Category: Ghirlando, R.]]
+[[Category: Ghirlando, R]]
-[[Category: Hu, J.]]
+[[Category: Hu, J]]
-[[Category: Hubbard, S R.]]
+[[Category: Hubbard, S R]]
-[[Category: Liu, J.]]
+[[Category: Liu, J]]
-[[Category: Saltiel, A R.]]
+[[Category: Saltiel, A R]]
 [[Category: Adapter protein]]
 [[Category: Sh2 domain]]
 [[Category: Signaling protein]]

1rpy

From Proteopedia

Revision as of 13:44, 25 December 2014

CRYSTAL STRUCTURE OF THE DIMERIC SH2 DOMAIN OF APS

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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