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3pg7, resolution 2.19Å ()
Ligands: ,
Gene: NF1 (Homo sapiens)

Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Crystal structure of the H. sapiens NF1 SEC-PH domain (del1750 mutant)

Publication Abstract from PubMed

Neurofibromatosis type 1 (NF1) is a common genetic disorder caused by alterations in the tumor suppressor gene NF1. Clinical manifestations include various neural crest derived tumors, pigmentation anomalies, bone deformations and learning disabilities. NF1 encodes the Ras specific GTPase activating protein (RasGAP) neurofibromin, of which the central RasGAP related domain as well as a Sec14-like (residues 1560-1699) and a tightly interacting pleckstrin homology (PH)-like (1713-1818) domain are currently well defined. However, patient-derived non-truncating mutations have been reported along the whole NF1 gene, suggesting further essential protein functions. Focusing on the Sec14-PH module, we have engineered such non-truncating mutations and analyzed their implications on protein function and structure using lipid binding assays, CD spectroscopy and X-ray crystallography. While lipid binding appears to be preserved among most non-truncating mutants, we see major structural changes for two of the alterations. Judging from these changes and our biochemical data, we suggest the presence of an additional intermolecular contact surface in the lid-lock region of the protein. (c) 2010 Wiley-Liss, Inc.

Structural and biochemical consequences of NF1 associated non-truncating mutations in the Sec14-PH module of neurofibromin., Welti S, Kuhn S, D'Angelo I, Bruugger B, Kaufmann D, Scheffzek K, Hum Mutat. 2010 Nov 18. PMID:21089070

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


[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].


[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]

About this Structure

3pg7 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.


  • Welti S, Kuhn S, D'Angelo I, Bruugger B, Kaufmann D, Scheffzek K. Structural and biochemical consequences of NF1 associated non-truncating mutations in the Sec14-PH module of neurofibromin. Hum Mutat. 2010 Nov 18. PMID:21089070 doi:10.1002/humu.21405
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  16. Fahsold R, Hoffmeyer S, Mischung C, Gille C, Ehlers C, Kucukceylan N, Abdel-Nour M, Gewies A, Peters H, Kaufmann D, Buske A, Tinschert S, Nurnberg P. Minor lesion mutational spectrum of the entire NF1 gene does not explain its high mutability but points to a functional domain upstream of the GAP-related domain. Am J Hum Genet. 2000 Mar;66(3):790-818. PMID:10712197 doi:10.1086/302809
  17. Ars E, Serra E, Garcia J, Kruyer H, Gaona A, Lazaro C, Estivill X. Mutations affecting mRNA splicing are the most common molecular defects in patients with neurofibromatosis type 1. Hum Mol Genet. 2000 Jan 22;9(2):237-47. PMID:10607834
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  25. De Luca A, Schirinzi A, Buccino A, Bottillo I, Sinibaldi L, Torrente I, Ciavarella A, Dottorini T, Porciello R, Giustini S, Calvieri S, Dallapiccola B. Novel and recurrent mutations in the NF1 gene in Italian patients with neurofibromatosis type 1. Hum Mutat. 2004 Jun;23(6):629. PMID:15146469 doi:10.1002/humu.9245
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  27. 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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  29. 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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  31. Baralle D, Mattocks C, Kalidas K, Elmslie F, Whittaker J, Lees M, Ragge N, Patton MA, Winter RM, ffrench-Constant C. Different mutations in the NF1 gene are associated with Neurofibromatosis-Noonan syndrome (NFNS). Am J Med Genet A. 2003 May 15;119A(1):1-8. PMID:12707950 doi:10.1002/ajmg.a.20023
  32. De Luca A, Bottillo I, Sarkozy A, Carta C, Neri C, Bellacchio E, Schirinzi A, Conti E, Zampino G, Battaglia A, Majore S, Rinaldi MM, Carella M, Marino B, Pizzuti A, Digilio MC, Tartaglia M, Dallapiccola B. NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome. Am J Hum Genet. 2005 Dec;77(6):1092-101. Epub 2005 Oct 26. PMID:16380919 doi:S0002-9297(07)63392-8
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