ARHGAP26
Encyclopedia
Rho GTPase activating protein 26 (ARHGAP26) also known as GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) is a protein
which in humans is encoded by the ARHGAP26 gene
.
/GEEC endocytic pathway, the most prevalent clathrin
-independent endocytic pathway discovered to date. By virtue of an N-terminal BAR domain
, GRAF1 sculpts the endocytic membranes of this pathway into 40 nm diameter tubules and vesicles that allow uptake of extracellular fluid, GPI-linked proteins and certain bacterial exotoxins into cells. The role of dynamin
in the CLIC/GEEC pathway is controversial, but GRAF1 interacts strongly with this protein and acute inhibition of dynamin
action abrogates CLIC/GEEC endocytosis
. There are several members of the GRAF family of proteins, including GRAF2, GRAF3 and oligophrenin, all of which likely play similar roles during clathrin-independent endocytic events. Mutations of both GRAF1 and oligophrenin are strongly implicated in causing human disease (leukaemia and mental retardation
respectively).
with PKN3
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the ARHGAP26 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
GRAF is a multidomain protein that is necessary for the CLICClathrin-independent carrier
Clathrin-independent carriers are prevalent tubulovesicular membranes responsible for non-clathrin mediated endocytic events. They appear to endocytose material into GEECs. Collectively, CLICs and GEECs comprise the CLIC/GEEC endocytic pathway, which is regulated by GRAF1....
/GEEC endocytic pathway, the most prevalent clathrin
Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
-independent endocytic pathway discovered to date. By virtue of an N-terminal BAR domain
BAR domain
BAR domains are highly conserved protein dimerisation domains that occur in many proteins involved in membrane dynamics in a cell. The BAR domain is banana shaped and binds to membrane via its concave face. It is capable of sensing membrane curvature by binding preferentially to curved membranes...
, GRAF1 sculpts the endocytic membranes of this pathway into 40 nm diameter tubules and vesicles that allow uptake of extracellular fluid, GPI-linked proteins and certain bacterial exotoxins into cells. The role of dynamin
Dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface as well as at the...
in the CLIC/GEEC pathway is controversial, but GRAF1 interacts strongly with this protein and acute inhibition of dynamin
Dynamin
Dynamin is a GTPase responsible for endocytosis in the eukaryotic cell. Dynamins are principally involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface as well as at the...
action abrogates CLIC/GEEC endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. There are several members of the GRAF family of proteins, including GRAF2, GRAF3 and oligophrenin, all of which likely play similar roles during clathrin-independent endocytic events. Mutations of both GRAF1 and oligophrenin are strongly implicated in causing human disease (leukaemia and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
respectively).
Interactions
ARHGAP26 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with PKN3
PKN3 (gene)
PKN3 is a protein kinase C-related molecule and thought to be an effector mediating malignant cell growth downstream of activated phosphoinositide 3-kinase...
.
External links
- ARHGAP26 Info with links in the Cell Migration Gateway