Description: Homo sapiens RAS p21 protein activator (GTPase activating protein) 1 (RASA1), transcript variant 1, mRNA. RefSeq Summary (NM_002890): The protein encoded by this gene is located in the cytoplasm and is part of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Mutations leading to changes in the binding sites of either protein are associated with basal cell carcinomas. Mutations also have been associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM) and Parkes Weber syndrome. Alternative splicing results in two isoforms where the shorter isoform, lacking the N-terminal hydrophobic region but retaining the same activity, appears to be abundantly expressed in placental but not adult tissues. [provided by RefSeq, May 2012]. Transcript (Including UTRs) Position: hg19 chr5:86,564,070-86,687,743 Size: 123,674 Total Exon Count: 25 Strand: + Coding Region Position: hg19 chr5:86,564,269-86,686,700 Size: 122,432 Coding Exon Count: 25
ID:RASA1_HUMAN DESCRIPTION: RecName: Full=Ras GTPase-activating protein 1; Short=GAP; Short=GTPase-activating protein; Short=RasGAP; AltName: Full=Ras p21 protein activator; AltName: Full=p120GAP; FUNCTION: Inhibitory regulator of the Ras-cyclic AMP pathway. Stimulates the GTPase of normal but not oncogenic Ras p21; this stimulation may be further increased in the presence of NCK1. SUBUNIT: Interacts with SQTSM1. Interacts with SPSB1; the interaction does not promote degradation. Interacts with CAV2 (tyrosine phosphorylated form). Directly interacts with NCK1. Interacts with PDGFRB (tyrosine phosphorylated). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1. INTERACTION: P16333:NCK1; NbExp=6; IntAct=EBI-1026476, EBI-389883; SUBCELLULAR LOCATION: Cytoplasm. TISSUE SPECIFICITY: In placental villi, detected only in the trophoblast layer (cytotrophoblast and syncytiotrophoblast). Not detected in stromal, endothelial or Hofbauer cells (at protein level). PTM: The N-terminus is blocked. PTM: Phosphorylated by SRC and LCK. The phosphorylation SRC inhibits its ability to stimulate the Ras-GTPase activity, whereas phosphorylation by LCK does not display any effect on stimulation activity. DISEASE: Note=Mutations in the SH2 domain of RASA seem to be oncogenic and cause basal cell carcinomas. DISEASE: Defects in RASA1 are the cause of capillary malformation- arteriovenous malformation (CMAVM) [MIM:608354]. CMAVM is a disorder characterized by atypical capillary malformations that are multiple, small, round to oval in shape and pinkish red in color. These capillary malformations are associated with either arteriovenous malformation, arteriovenous fistula, or Parkes Weber syndrome. DISEASE: Defects in RASA1 are a cause of Parkes Weber syndrome (PKWS) [MIM:608355]. PKWS is a disorder characterized by a cutaneous flush with underlying multiple micro-arteriovenous fistulas, in association with soft tissue and skeletal hypertrophy of the affected limb. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 Ras-GAP domain. SIMILARITY: Contains 2 SH2 domains. SIMILARITY: Contains 1 SH3 domain. WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/RASA1";
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): RASA1 CDC HuGE Published Literature: RASA1 Positive Disease Associations: Leukemia, Myeloid, Acute Related Studies:
Leukemia, Myeloid, Acute Fernando P G Silva , et al. Haematologica 2009 94(11):1546-54, Genome wide molecular analysis of minimally differentiated acute myeloid leukemia., Haematologica 2009 94(11):1546-54.
[PubMed 19773259]
Our results suggest that in patients without RUNX1 mutation, several other molecular aberrations, separately or in combination, contribute to a common minimally differentiated phenotype.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P20936
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.