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RAS p21 protein activator 1

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Title: RAS p21 protein activator 1  
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Subject: Neurofibromatosis type I, SH2 domain, Huntingtin, Insulin-like growth factor 1 receptor
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RAS p21 protein activator 1

RAS p21 protein activator (GTPase activating protein) 1
PDB rendering based on 1wer.
Available structures
PDB Ortholog search: RCSB
RASA1 Gene
RNA expression pattern

RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-kDa cytosolic human protein that provides two principal activities:

  • Inactivation of Ras from its active GTP-bound form to its inactive GDP-bound form by enhancing the endogenous GTPase activity of Ras, via its C-terminal GAP domain
  • Mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains

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. 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.[1]


RasGAP contains one SH3 domain and two SH2 domains, a PH domain, and a GAP domain.


RAS p21 protein activator 1 has been shown to interact with SOCS3,[2] ANXA6,[3] Huntingtin,[4] KHDRBS1,[5][6][7] Src,[8][9] EPHB3,[10] EPH receptor B2,[11][12] Insulin-like growth factor 1 receptor,[13] PTK2B,[14][15] DOK1,[16][17][18] PDGFRB,[19][20] HCK,[21] Caveolin 2,[22] DNAJA3,[23] HRAS,[9][24][25] GNB2L1 [26] and NCK1.[27] The mRNA can interact with Mir-132 microRNA; this process is linked to angiogenesis.[28]

Disease Database

RASA1 gene variant database


External links

  • GeneReviews/NCBI/NIH/UW entry on Capillary Malformation-Arteriovenous Malformation Syndrome and RASA1-Related Parkes Weber Syndrome
  • OMIM entries in RASA1 related disorders

Further reading

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