View source for 1nf1

==THE GAP RELATED DOMAIN OF NEUROFIBROMIN==
<StructureSection load='1nf1' size='340' side='right' caption='[[1nf1]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1nf1]] 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=1NF1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NF1 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=1nf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nf1 OCA], [http://pdbe.org/1nf1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nf1 RCSB], [http://www.ebi.ac.uk/pdbsum/1nf1 PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Defects in NF1 are the cause of neurofibromatosis type 1 (NF1) [MIM:[http://omim.org/entry/162200 162200]]; also known as von Recklinghausen syndrome. A disease characterized by patches of skin pigmentation (cafe-au-lait spots), Lisch nodules of the iris, tumors in the peripheral nervous system and fibromatous skin tumors. Individuals with the disorder have increased susceptibility to the development of benign and malignant tumors.<ref>PMID:2114220</ref> <ref>PMID:1302608</ref> <ref>PMID:7981679</ref> <ref>PMID:8081387</ref> <ref>PMID:8544190</ref> <ref>PMID:8834249</ref> <ref>PMID:8807336</ref> <ref>PMID:9003501</ref> <ref>PMID:9150739</ref> <ref>PMID:9101300</ref> <ref>PMID:9298829</ref> <ref>PMID:9668168</ref> <ref>PMID:10336779</ref> <ref>PMID:11258625</ref> <ref>PMID:10220149</ref> <ref>PMID:10712197</ref> <ref>PMID:10607834</ref> <ref>PMID:10980545</ref> <ref>PMID:11735023</ref> <ref>PMID:11857752</ref> <ref>PMID:12522551</ref> <ref>PMID:12552569</ref> <ref>PMID:12746402</ref> <ref>PMID:15523642</ref> <ref>PMID:15146469</ref> <ref>PMID:15060124</ref> <ref>PMID:15520408</ref> <ref>PMID:15948193</ref> <ref>PMID:21838856</ref>   Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:[http://omim.org/entry/607785 607785]]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. Germline mutations of NF1 account for the association of JMML with type 1 neurofibromatosis (NF1).  Defects in NF1 are the cause of Watson syndrome (WS) [MIM:[http://omim.org/entry/193520 193520]]. WS is characterized by the presence of pulmonary stenosis, cafe-au-lait spots, and mental retardation. WS is considered as an atypical form of NF1.  Defects in NF1 are a cause of familial spinal neurofibromatosis (FSNF) [MIM:[http://omim.org/entry/162210 162210]]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.<ref>PMID:11704931</ref>   Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM:[http://omim.org/entry/601321 601321]]. NFNS is characterized by manifestations of both NF1 and Noonan syndrome (NS). NS is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis.<ref>PMID:12707950</ref> <ref>PMID:16380919</ref> <ref>PMID:19845691</ref>   Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:[http://omim.org/entry/114500 114500]]. 
== Function ==
[[http://www.uniprot.org/uniprot/NF1_HUMAN NF1_HUMAN]] Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity.<ref>PMID:2121371</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nf/1nf1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1nf1 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Neurofibromin is the product of the NF1 gene, whose alteration is responsible for the pathogenesis of neurofibromatosis type 1 (NF1), one of the most frequent genetic disorders in man. It acts as a GTPase activating protein (GAP) on Ras; based on homology to p120GAP, a segment spanning 250-400 aa and termed GAP-related domain (NF1GRD; 25-40 kDa) has been shown to be responsible for GAP activity and represents the only functionally defined segment of neurofibromin. Missense mutations found in NF1 patients map to NF1GRD, underscoring its importance for pathogenesis. X-ray crystallographic analysis of a proteolytically treated catalytic fragment of NF1GRD comprising residues 1198-1530 (NF1-333) of human neurofibromin reveals NF1GRD as a helical protein that resembles the corresponding fragment derived from p120GAP (GAP-334). A central domain (NF1c) containing all residues conserved among RasGAPs is coupled to an extra domain (NF1ex), which despite very limited sequence homology is surprisingly similar to the corresponding part of GAP-334. Numerous point mutations found in NF1 patients or derived from genetic screening protocols can be analysed on the basis of the three-dimensional structural model, which also allows identification of the site where structural changes in a differentially spliced isoform are to be expected. Based on the structure of the complex between Ras and GAP-334 described earlier, a model of the NF1GRD-Ras complex is proposed which is used to discuss the strikingly different properties of the Ras-p120GAP and Ras-neurofibromin interactions.

Structural analysis of the GAP-related domain from neurofibromin and its implications.,Scheffzek K, Ahmadian MR, Wiesmuller L, Kabsch W, Stege P, Schmitz F, Wittinghofer A EMBO J. 1998 Aug 3;17(15):4313-27. PMID:9687500<ref>PMID:9687500</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1nf1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Ahmadian, M R]]
[[Category: Kabsch, W]]
[[Category: Scheffzek, K]]
[[Category: Schmitz, F]]
[[Category: Stege, P]]
[[Category: Wiesmueller, L]]
[[Category: Wittinghofer, A]]
[[Category: Arginine finger]]
[[Category: Cancer]]
[[Category: Gap]]
[[Category: Growth regulation]]
[[Category: Gtp hydrolysis]]
[[Category: Neurofibromin]]
[[Category: Nf1]]
[[Category: Patient mutation]]
[[Category: Ra]]
[[Category: Signal transduction]]
[[Category: Signaling protein]]
[[Category: Type i neurofibromatosis]]