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| | <StructureSection load='1uti' size='340' side='right'caption='[[1uti]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='1uti' size='340' side='right'caption='[[1uti]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1uti]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UTI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1uti]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UTI FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1h3h|1h3h]], [[1oeb|1oeb]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1 2.7.11.1, 2.7.11.8, 2.7.11.9, 2.7.11.10, 2.7.11.11, 2.7.11.12, 2.7.11.13, 2.7.11.21, 2.7.11.22, 2.7.11.24, 2.7.11.25, 2.7.11.30 and 2.7.12.1] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uti OCA], [https://pdbe.org/1uti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uti RCSB], [https://www.ebi.ac.uk/pdbsum/1uti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uti ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uti OCA], [https://pdbe.org/1uti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uti RCSB], [https://www.ebi.ac.uk/pdbsum/1uti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uti ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GRP2_MOUSE GRP2_MOUSE]] Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway.<ref>PMID:9789079</ref> <ref>PMID:10777492</ref> <ref>PMID:10913189</ref> <ref>PMID:11432821</ref> <ref>PMID:11278453</ref> <ref>PMID:12239348</ref> <ref>PMID:15334074</ref> <ref>PMID:16357324</ref> <ref>PMID:17492052</ref> [[https://www.uniprot.org/uniprot/M4K1_MOUSE M4K1_MOUSE]] May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation.<ref>PMID:9003777</ref>
| + | [https://www.uniprot.org/uniprot/GRAP2_MOUSE GRAP2_MOUSE] Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Transferase]]
| + | [[Category: Domart MC]] |
| - | [[Category: Domart, M C]] | + | [[Category: Feller SM]] |
| - | [[Category: Feller, S M]] | + | [[Category: Harkiolaki M]] |
| - | [[Category: Harkiolaki, M]] | + | [[Category: Lewitzky M]] |
| - | [[Category: Lewitzky, M]] | + | |
| - | [[Category: Ppii helix]]
| + | |
| - | [[Category: Sh3 domain]]
| + | |
| - | [[Category: Sh3 domain-complex]]
| + | |
| - | [[Category: Signaling protein regulator]]
| + | |
| Structural highlights
Function
GRAP2_MOUSE Interacts with SLP-76 to regulate NF-AT activation. Binds to tyrosine-phosphorylated shc.
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
Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream of the T cell receptor. Its non-catalytic, C-terminal half contains several prolinerich motifs, which have been shown to interact with different SH3 domain-containing adaptor proteins in vitro. One of these, Mona/Gads, was also shown to bind HPK1 in mouse T cells in vivo. The region of HPK1 that binds to the Mona/Gads C-terminal SH3 domain has been mapped and shows only very limited similarity to a recently identified high affinity binding motif in SLP-76, another T-cell adaptor. Using isothermal titration calorimetry and x-ray crystallography, the binding of the HPK1 motif to Mona/Gads SH3C has now been characterized in molecular detail. The results indicate that although charge interactions through an RXXK motif are essential for complex formation, a PXXP motif in HPK1 strongly complements binding. This unexpected binding mode therefore differs considerably from the previously described interaction of Mona/Gads SH3C with SLP-76. The crystal structure of the complex highlights the great versatility of SH3 domains, which allows interactions with very different proteins. This currently limits our ability to categorize SH3 binding properties by simple rules.
Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix.,Lewitzky M, Harkiolaki M, Domart MC, Jones EY, Feller SM J Biol Chem. 2004 Jul 2;279(27):28724-32. Epub 2004 Apr 20. PMID:15100220[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lewitzky M, Harkiolaki M, Domart MC, Jones EY, Feller SM. Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix. J Biol Chem. 2004 Jul 2;279(27):28724-32. Epub 2004 Apr 20. PMID:15100220 doi:10.1074/jbc.M402745200
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