1nf1 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[NF1_HUMAN] Defects in NF1 are the cause of neurofibromatosis type 1 (NF1) [MIM: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.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Defects in NF1 are a cause of juvenile myelomonocytic leukemia (JMML) [MIM: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: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:162210]. Familial spinal NF is considered to be an alternative form of neurofibromatosis, showing multiple spinal tumors.[30] Defects in NF1 are a cause of neurofibromatosis-Noonan syndrome (NFNS) [MIM: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.[31][32][33] Defects in NF1 may be a cause of colorectal cancer (CRC) [MIM:114500].
Function
[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.[34]
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
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[35]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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↑De Luca A, Buccino A, Gianni D, Mangino M, Giustini S, Richetta A, Divona L, Calvieri S, Mingarelli R, Dallapiccola B. NF1 gene analysis based on DHPLC. Hum Mutat. 2003 Feb;21(2):171-2. PMID:12552569 doi:10.1002/humu.9111
↑Kluwe L, Tatagiba M, Funsterer C, Mautner VF. NF1 mutations and clinical spectrum in patients with spinal neurofibromas. J Med Genet. 2003 May;40(5):368-71. PMID:12746402
↑Zatkova A, Messiaen L, Vandenbroucke I, Wieser R, Fonatsch C, Krainer AR, Wimmer K. Disruption of exonic splicing enhancer elements is the principal cause of exon skipping associated with seven nonsense or missense alleles of NF1. Hum Mutat. 2004 Dec;24(6):491-501. PMID:15523642 doi:10.1002/humu.20103
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↑Mattocks C, Baralle D, Tarpey P, ffrench-Constant C, Bobrow M, Whittaker J. Automated comparative sequence analysis identifies mutations in 89% of NF1 patients and confirms a mutation cluster in exons 11-17 distinct from the GAP related domain. J Med Genet. 2004 Apr;41(4):e48. PMID:15060124
↑Ferner RE, Hughes RA, Hall SM, Upadhyaya M, Johnson MR. Neurofibromatous neuropathy in neurofibromatosis 1 (NF1). J Med Genet. 2004 Nov;41(11):837-41. PMID:15520408 doi:10.1136/jmg.2004.021683
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↑Ponti G, Losi L, Martorana D, Priola M, Boni E, Pollio A, Neri TM, Seidenari S. Clinico-pathological and biomolecular findings in Italian patients with multiple cutaneous neurofibromas. Hered Cancer Clin Pract. 2011 Aug 12;9:6. doi: 10.1186/1897-4287-9-6. PMID:21838856 doi:10.1186/1897-4287-9-6
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↑Scheffzek K, Ahmadian MR, Wiesmuller L, Kabsch W, Stege P, Schmitz F, Wittinghofer A. Structural analysis of the GAP-related domain from neurofibromin and its implications. EMBO J. 1998 Aug 3;17(15):4313-27. PMID:9687500 doi:10.1093/emboj/17.15.4313
