1wer

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(Difference between revisions)

Revision as of 13:44, 6 January 2015

RAS-GTPASE-ACTIVATING DOMAIN OF HUMAN P120GAP

Structural highlights

1wer is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	GENE FRAGMENT OF P120GAP (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[RASA1_HUMAN] Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas. Defects in RASA1 are the cause of capillary malformation-arteriovenous malformation (CMAVM) [MIM:608354]. CMAVM is a disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome.^[1] Defects in RASA1 are a cause of Parkes Weber syndrome (PKWS) [MIM:608355]. PKWS is a disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb.

Function

[RASA1_HUMAN] Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1.^[2] ^[3]

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

Ras-related GTP-binding proteins function as molecular switches which cycle between GTP-bound 'on'- and GDP-bound 'off'-states. GTP hydrolysis is the common timing mechanism that mediates the return from the 'on' to the 'off'-state. It is usually slow but can be accelerated by orders of magnitude upon interaction with GTPase-activating proteins (GAPs). In the case of Ras, a major regulator of cellular growth, point mutations are found in approximately 30% of human tumours which render the protein unable to hydrolyse GTP, even in the presence of Ras-GAPs. The first structure determination of a GTPase-activating protein reveals the catalytically active fragment of the Ras-specific p120GAP (ref. 2), GAP-334, as an elongated, exclusively helical protein which appears to represent a novel protein fold. The molecule consists of two domains, one of which contains all the residues conserved among different GAPs for Ras. From the location of conserved residues around a shallow groove in the central domain we can identify the site of interaction with Ras x GTP. This leads to a model for the interaction between Ras and GAP that satisfies numerous biochemical and genetic data on this important regulatory process.

Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras.,Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A Nature. 1996 Dec 12;384(6609):591-6. PMID:8955277^[4]

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

References

↑ Eerola I, Boon LM, Mulliken JB, Burrows PE, Dompmartin A, Watanabe S, Vanwijck R, Vikkula M. Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet. 2003 Dec;73(6):1240-9. Epub 2003 Nov 24. PMID:14639529 doi:S0002-9297(07)63977-9
↑ Zhang Y, Zhang G, Mollat P, Carles C, Riva M, Frobert Y, Malassine A, Rostene W, Thang DC, Beltchev B, et al.. Purification, characterization, and cellular localization of the 100-kDa human placental GTPase-activating protein. J Biol Chem. 1993 Sep 5;268(25):18875-81. PMID:8360177
↑ Giglione C, Gonfloni S, Parmeggiani A. Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm. Eur J Biochem. 2001 Jun;268(11):3275-83. PMID:11389730
↑ Scheffzek K, Lautwein A, Kabsch W, Ahmadian MR, Wittinghofer A. Crystal structure of the GTPase-activating domain of human p120GAP and implications for the interaction with Ras. Nature. 1996 Dec 12;384(6609):591-6. PMID:8955277 doi:10.1038/384591a0

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1wer]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WER OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WER FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GENE FRAGMENT OF P120GAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GENE FRAGMENT OF P120GAP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1wer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wer OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wer RCSB], [http://www.ebi.ac.uk/pdbsum/1wer 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=1wer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wer OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wer RCSB], [http://www.ebi.ac.uk/pdbsum/1wer PDBsum]</span></td></tr>
-<table>
+</table>
 == Disease ==
 [[http://www.uniprot.org/uniprot/RASA1_HUMAN RASA1_HUMAN]] Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas.  Defects in RASA1 are the cause of capillary malformation-arteriovenous malformation (CMAVM) [MIM:[http://omim.org/entry/608354 608354]]. CMAVM is a disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome.<ref>PMID:14639529</ref>   Defects in RASA1 are a cause of Parkes Weber syndrome (PKWS) [MIM:[http://omim.org/entry/608355 608355]]. PKWS is a disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb.
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ahmadian, M R.]]
+[[Category: Ahmadian, M R]]
-[[Category: Kabsch, W.]]
+[[Category: Kabsch, W]]
-[[Category: Lautwein, A.]]
+[[Category: Lautwein, A]]
-[[Category: Scheffzek, K.]]
+[[Category: Scheffzek, K]]
-[[Category: Wittinghofer, A.]]
+[[Category: Wittinghofer, A]]
 [[Category: Cancer]]
 [[Category: Gap]]

1wer

From Proteopedia

Revision as of 13:44, 6 January 2015

RAS-GTPASE-ACTIVATING DOMAIN OF HUMAN P120GAP

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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