RAS p21 protein activator 1 or RasGAP (Ras GTPase activating protein), also known as RASA1, is a 120-
kDa
The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at re ...
cytosolic human protein that provides two principal activities:
* Inactivation of
Ras from its active
GTP-bound form to its inactive
GDP
Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is of ...
-bound form by enhancing the endogenous
GTPase
GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...
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.
Domains
RasGAP contains one
SH3 domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phosp ...
and two
SH2 domain
The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many other intracellular signal-transducing proteins. SH2 domains allow proteins containing those domains to dock to phosph ...
s, a
PH domain
In chemistry, pH (), historically denoting "potential of hydrogen" (or "power of hydrogen"), is a scale used to specify the acidity or basicity of an aqueous solution. Acidic solutions (solutions with higher concentrations of ions) are ...
, a C2 domain, and a
GAP domain.
Interactions
RAS p21 protein activator 1 has been shown to
interact
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with:
*
ANXA6,
*
CAV2,
*
DNAJA3
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the ''DNAJA3'' gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known ...
,
*
DOK1
Docking protein 1 is a protein that in humans is encoded by the ''DOK1'' gene.
Function
Docking protein 1 is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the c ...
,
*
EPHB2
Ephrin type-B receptor 2 is a protein that in humans is encoded by the ''EPHB2'' gene.
Function
Ephrin receptors and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system. Based on their stru ...
,
*
EPHB3,
*
GNB2L1
Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene.
Function
RACK1 was originally isolated and identified ...
*
HCK,
*
HRAS
GTPase HRas, from "Harvey Rat sarcoma virus", also known as transforming protein p21 is an enzyme that in humans is encoded by the gene. The ''HRAS'' gene is located on the short (p) arm of chromosome 11 at position 15.5, from base pair 522,241 ...
,
IGF1R
The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2 ...
,KHDRBS1
KH domain-containing, RNA-binding, signal transduction-associated protein 1 is a protein that in humans is encoded by the ''KHDRBS1'' gene.
This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associate ...
,NCK1
Cytoplasmic protein NCK1 is a protein that in humans is encoded by the ''NCK1'' gene.
Gene
The Nck (non-catalytic region of tyrosine kinase adaptor protein 1) belongs to the adaptor family of proteins. The nck gene was initially isolated from ...
,PDGFRB
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the ''PDGFRB'' gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.
Gene
The ''PDGFRB'' gene is located on h ...
,PTK2B
Protein tyrosine kinase 2 beta is an enzyme that in humans is encoded by the ''PTK2B'' gene.
Function
This gene encodes a cytoplasmic protein tyrosine kinase that is involved in calcium-induced regulation of ion channels and activation of the ...
,SOCS3
Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the ''SOCS3'' gene.
This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling ( SOCS), family ...
,
Disease databaseRASA1 gene variant database
References
Further reading
*
*
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
{{GTP-binding protein regulators
Proteins