ARHGAP26
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.[1][2][3]
Function
GRAF is a multidomain protein that is necessary for the CLIC/GEEC endocytic pathway,[4] 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).
Interactions
ARHGAP26 has been shown to interact with PKN3.[5]
References
- ^ "Entrez Gene: ARHGAP26 Rho GTPase activating protein 26". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23092.
- ^ Hildebrand JD, Taylor JM, Parsons JT (June 1996). "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Mol. Cell. Biol. 16 (6): 3169–78. PMC 231310. PMID 8649427. http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=8649427.
- ^ Taylor JM, Macklem MM, Parsons JT (January 1999). "Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho". J. Cell. Sci. 112 ( Pt 2): 231–42. PMID 9858476. http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=9858476.
- ^ Lundmark R, Doherty GJ, Howes MT, Cortese K, Vallis Y, Parton RG, McMahon HT (November 2008). "The GTPase-Activating Protein GRAF1 Regulates the CLIC/GEEC Endocytic Pathway". Curr. Biol. 18 (22): 1802–8. doi:10.1016/j.cub.2008.10.044. PMC 2726289. PMID 19036340. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2726289.
- ^ Shibata, H; Oishi K, Yamagiwa A, Matsumoto M, Mukai H, Ono Y (Jul. 2001). "PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family". J. Biochem. (Japan) 130 (1): 23–31. ISSN 0021-924X. PMID 11432776.
Further reading
- Ramakers GJ (2002). "Rho proteins, mental retardation and the cellular basis of cognition". Trends Neurosci. 25 (4): 191–9. doi:10.1016/S0166-2236(00)02118-4. PMID 11998687.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Shibata H, Oishi K, Yamagiwa A, et al. (2001). "PKNbeta interacts with the SH3 domains of Graf and a novel Graf related protein, Graf2, which are GTPase activating proteins for Rho family". J. Biochem. 130 (1): 23–31. PMID 11432776.
- Borkhardt A, Bojesen S, Haas OA, et al. (2000). "The human GRAF gene is fused to MLL in a unique t(5;11)(q31;q23) and both alleles are disrupted in three cases of myelodysplastic syndrome/acute myeloid leukemia with a deletion 5q". Proc. Natl. Acad. Sci. U.S.A. 97 (16): 9168–73. doi:10.1073/pnas.150079597. PMC 16840. PMID 10908648. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16840.
- Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16267.
- Taylor JM, Macklem MM, Parsons JT (1999). "Cytoskeletal changes induced by GRAF, the GTPase regulator associated with focal adhesion kinase, are mediated by Rho". J. Cell. Sci. 112 ( Pt 2): 231–42. PMID 9858476.
- Ishikawa K, Nagase T, Suyama M, et al. (1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID 9734811.
- Billuart P, Bienvenu T, Ronce N, et al. (1998). "Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation". Nature 392 (6679): 923–6. doi:10.1038/31940. PMID 9582072.
- Taylor JM, Hildebrand JD, Mack CP, et al. (1998). "Characterization of graf, the GTPase-activating protein for rho associated with focal adhesion kinase. Phosphorylation and possible regulation by mitogen-activated protein kinase". J. Biol. Chem. 273 (14): 8063–70. doi:10.1074/jbc.273.14.8063. PMID 9525907.
- Hildebrand JD, Taylor JM, Parsons JT (1996). "An SH3 domain-containing GTPase-activating protein for Rho and Cdc42 associates with focal adhesion kinase". Mol. Cell. Biol. 16 (6): 3169–78. PMC 231310. PMID 8649427. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231310.
- Pillay TS, Sasaoka T, Olefsky JM (1995). "Insulin stimulates the tyrosine dephosphorylation of pp125 focal adhesion kinase". J. Biol. Chem. 270 (3): 991–4. doi:10.1074/jbc.270.3.991. PMID 7836419.
External links
|
PDB gallery
|
|
|
|
1f7c: CRYSTAL STRUCTURE OF THE BH DOMAIN FROM GRAF, THE GTPASE REGULATOR ASSOCIATED WITH FOCAL ADHESION KINASE
|
|
|
1ugv: Solution structure of the SH3 domain of human olygophrein-1 like protein (KIAA0621)
|
|
|
|