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| | ==GTPase like domain of Centaurin Gamma 1 (Human)== | | ==GTPase like domain of Centaurin Gamma 1 (Human)== |
| - | <StructureSection load='2bmj' size='340' side='right' caption='[[2bmj]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='2bmj' size='340' side='right'caption='[[2bmj]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bmj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BMJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BMJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bmj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BMJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BMJ FirstGlance]. <br> |
| - | </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=2bmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bmj OCA], [http://pdbe.org/2bmj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bmj RCSB], [http://www.ebi.ac.uk/pdbsum/2bmj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bmj ProSAT]</span></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]] 2.1Å</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=2bmj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bmj OCA], [https://pdbe.org/2bmj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bmj RCSB], [https://www.ebi.ac.uk/pdbsum/2bmj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bmj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AGAP2_HUMAN AGAP2_HUMAN]] GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.<ref>PMID:12640130</ref> <ref>PMID:14761976</ref> <ref>PMID:15118108</ref> <ref>PMID:16079295</ref> | + | [https://www.uniprot.org/uniprot/AGAP2_HUMAN AGAP2_HUMAN] GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.<ref>PMID:12640130</ref> <ref>PMID:14761976</ref> <ref>PMID:15118108</ref> <ref>PMID:16079295</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Doyle, D A]] | + | [[Category: Arrowsmith C]] |
| - | [[Category: Edwards, A]] | + | [[Category: Doyle DA]] |
| - | [[Category: Elkins, J M]] | + | [[Category: Edwards A]] |
| - | [[Category: Structural genomic]] | + | [[Category: Elkins JM]] |
| - | [[Category: Soundararajan, M]] | + | [[Category: Soundararajan M]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Yang, X]] | + | [[Category: Yang X]] |
| - | [[Category: Centaurin ank repeat]]
| + | |
| - | [[Category: Gtp-binding]]
| + | |
| - | [[Category: Gtpase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Sgc]]
| + | |
| Structural highlights
Function
AGAP2_HUMAN GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.[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
Centaurins are a family of proteins that contain GTPase-activating protein domains, with the gamma family members containing in addition a GTPase-like domain. Centaurins reside mainly in the nucleus and are known to activate phosphoinositide 3-kinase, a key regulator of cell proliferation, motility and vesicular trafficking. In the present study, using X-ray structural analysis, enzymatic assays and nucleotide-binding studies, we show that, for CENTG1 (centaurin gamma-1) the GTPase-like domain has broader trinucleotide specificity. Alterations within the G4 motif of CENTG1 from the highly conserved NKXD found in typical GTPases to TQDR result in the loss of specificity, a lower affinity for the nucleotides and higher turnover rates. These results indicate that the centaurins could be more accurately classified as NTPases and point to alternative mechanisms of cell signalling control.
The centaurin gamma-1 GTPase-like domain functions as an NTPase.,Soundararajan M, Yang X, Elkins JM, Sobott F, Doyle DA Biochem J. 2007 Feb 1;401(3):679-88. PMID:17037982[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Xia C, Ma W, Stafford LJ, Liu C, Gong L, Martin JF, Liu M. GGAPs, a new family of bifunctional GTP-binding and GTPase-activating proteins. Mol Cell Biol. 2003 Apr;23(7):2476-88. PMID:12640130
- ↑ Ahn JY, Rong R, Kroll TG, Van Meir EG, Snyder SH, Ye K. PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt activity and mediates cellular invasion. J Biol Chem. 2004 Apr 16;279(16):16441-51. Epub 2004 Feb 3. PMID:14761976 doi:http://dx.doi.org/10.1074/jbc.M312175200
- ↑ Ahn JY, Hu Y, Kroll TG, Allard P, Ye K. PIKE-A is amplified in human cancers and prevents apoptosis by up-regulating Akt. Proc Natl Acad Sci U S A. 2004 May 4;101(18):6993-8. Epub 2004 Apr 26. PMID:15118108 doi:http://dx.doi.org/10.1073/pnas.0400921101
- ↑ Nie Z, Fei J, Premont RT, Randazzo PA. The Arf GAPs AGAP1 and AGAP2 distinguish between the adaptor protein complexes AP-1 and AP-3. J Cell Sci. 2005 Aug 1;118(Pt 15):3555-66. PMID:16079295 doi:http://dx.doi.org/10.1242/jcs.02486
- ↑ Soundararajan M, Yang X, Elkins JM, Sobott F, Doyle DA. The centaurin gamma-1 GTPase-like domain functions as an NTPase. Biochem J. 2007 Feb 1;401(3):679-88. PMID:17037982 doi:10.1042/BJ20060555
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