2d4q | pdb_00002d4q

Crystal structure of the Sec-PH domain of the human neurofibromatosis type 1 protein

spinqualitylabelsall models 2d4q, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2d4q is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: OXN, POP Gene: neurofibromin (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [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. 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. 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. 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. 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 Neurofibromatosis type 1 (NF1) is a common tumour predisposition syndrome associated with numerous clinical complications. Mutations in the tumour suppressor gene NF1 are responsible for disease pathogenesis. This gene encodes the 320 kDa protein neurofibromin, the only clearly defined function of which is to act as a Ras-specific GTPase-activating protein (RasGAP). Here we report the structural discovery of a novel module in neurofibromin, composed of a Sec14p homologous segment and a previously undetected pleckstrin homology (PH)-like domain of potentially novel function. We show phospholipid binding by this bipartite module and identify residues that are involved in this activity; we also show that the PH-like domain is not sufficient for lipid binding. The unique architecture of the domain interface points to a model of how the PH-like domain may regulate binding of a ligand by the Sec14 module. A novel bipartite phospholipid-binding module in the neurofibromatosis type 1 protein.,D'Angelo I, Welti S, Bonneau F, Scheffzek K EMBO Rep. 2006 Feb;7(2):174-9. PMID:16397625 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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