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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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| - | </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/ | + | </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=1bkd ConSurf]. |
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Revision as of 23:30, 7 February 2016
COMPLEX OF HUMAN H-RAS WITH HUMAN SOS-1
Structural highlights
Disease[RASH_HUMAN] Defects in HRAS are the cause of faciocutaneoskeletal syndrome (FCSS) [MIM:218040]. A rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities.[1] [2] [3] [4] [5] [6] [7] Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome.[8] Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms. Note=Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors. Defects in HRAS are a cause of susceptibility to bladder cancer (BLC) [MIM:109800]. A malignancy originating in tissues of the urinary bladder. It often presents with multiple tumors appearing at different times and at different sites in the bladder. Most bladder cancers are transitional cell carcinomas. They begin in cells that normally make up the inner lining of the bladder. Other types of bladder cancer include squamous cell carcinoma (cancer that begins in thin, flat cells) and adenocarcinoma (cancer that begins in cells that make and release mucus and other fluids). Bladder cancer is a complex disorder with both genetic and environmental influences. Note=Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC).[9] Defects in HRAS are the cause of Schimmelpenning-Feuerstein-Mims syndrome (SFM) [MIM:163200]. A disease characterized by sebaceous nevi, often on the face, associated with variable ipsilateral abnormalities of the central nervous system, ocular anomalies, and skeletal defects. Many oral manifestations have been reported, not only including hypoplastic and malformed teeth, and mucosal papillomatosis, but also ankyloglossia, hemihyperplastic tongue, intraoral nevus, giant cell granuloma, ameloblastoma, bone cysts, follicular cysts, oligodontia, and odontodysplasia. Sebaceous nevi follow the lines of Blaschko and these can continue as linear intraoral lesions, as in mucosal papillomatosis.[10] [SOS1_HUMAN] Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:135300]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.[11] Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.[12] [13] [14] [15] [16] [17] [18] [19] Function[RASH_HUMAN] Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.[20] [21] [22] [SOS1_HUMAN] Promotes the exchange of Ras-bound GDP by GTP. 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 PubMedThe crystal structure of human H-Ras complexed with the Ras guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 A resolution. The normally tight interaction of nucleotides with Ras is disrupted by Sos in two ways. First, the insertion into Ras of an alpha-helix from Sos results in the displacement of the Switch 1 region of Ras, opening up the nucleotide-binding site. Second, side chains presented by this helix and by a distorted conformation of the Switch 2 region of Ras alter the chemical environment of the binding site for the phosphate groups of the nucleotide and the associated magnesium ion, so that their binding is no longer favoured. Sos does not impede the binding sites for the base and the ribose of GTP or GDP, so the Ras-Sos complex adopts a structure that allows nucleotide release and rebinding. The structural basis of the activation of Ras by Sos.,Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J Nature. 1998 Jul 23;394(6691):337-43. PMID:9690470[23] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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