ARFGAP1 explained

ADP-ribosylation factor GTPase-activating protein 1 is an enzyme that in humans is encoded by the ARFGAP1 gene.^{[1] [2]} Two transcript variants encoding different isoforms have been found for this gene.

Function

The protein encoded by this gene is a GTPase-activating protein (GAP) which associates with the Golgi apparatus and which interacts with ADP-ribosylation factor 1 (ARF1). The encoded protein promotes hydrolysis of ARF1-bound GTP and is required for the dissociation of coat proteins from Golgi-derived membranes and vesicles. Dissociation of the coat proteins is required for the fusion of these vesicles with target compartments. The activity of this protein is stimulated by phosphoinositides and inhibited by phosphatidylcholine.^[2]

The protein has two amphipathic lipid packing sensor motifs (ALPS), that let the protein sense the curvature of the membrane (<30 nm) or lipid packing defects, and in this way evaluate if the vesicle is mature and ready for coat disassembly.^{[3] [4]}

Interactions

ARFGAP1 has been shown to interact with KDELR1 and LRRK2.^{[5] [6] [7]}

References

Further reading

• Rothman JE . Mechanisms of intracellular protein transport . Nature . 372 . 6501 . 55–63 . November 1994 . 7969419 . 10.1038/372055a0 . 1994Natur.372...55R . 4238576 .
• Bernards A, Settleman J . GAP control: regulating the regulators of small GTPases . Trends in Cell Biology . 14 . 7 . 377–85 . July 2004 . 15246431 . 10.1016/j.tcb.2004.05.003 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Cukierman E, Huber I, Rotman M, Cassel D . The ARF1 GTPase-activating protein: zinc finger motif and Golgi complex localization . Science . 270 . 5244 . 1999–2002 . December 1995 . 8533093 . 10.1126/science.270.5244.1999 . 1995Sci...270.1999C . 37708069 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Aoe T, Cukierman E, Lee A, Cassel D, Peters PJ, Hsu VW . The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1 . The EMBO Journal . 16 . 24 . 7305–16 . December 1997 . 9405360 . 1170331 . 10.1093/emboj/16.24.7305 .
• Mossessova E, Gulbis JM, Goldberg J . Structure of the guanine nucleotide exchange factor Sec7 domain of human arno and analysis of the interaction with ARF GTPase . Cell . 92 . 3 . 415–23 . February 1998 . 9476900 . 10.1016/S0092-8674(00)80933-2 . 8093935 . free .
• Huber I, Cukierman E, Rotman M, Aoe T, Hsu VW, Cassel D . Requirement for both the amino-terminal catalytic domain and a noncatalytic domain for in vivo activity of ADP-ribosylation factor GTPase-activating protein . The Journal of Biological Chemistry . 273 . 38 . 24786–91 . September 1998 . 9733781 . 10.1074/jbc.273.38.24786 . free .
• Zhang C, Yu Y, Zhang S, Liu M, Xing G, Wei H, Bi J, Liu X, Zhou G, Dong C, Hu Z, Zhang Y, Luo L, Wu C, Zhao S, He F . Characterization, chromosomal assignment, and tissue expression of a novel human gene belonging to the ARF GAP family . Genomics . 63 . 3 . 400–8 . February 2000 . 10704287 . 10.1006/geno.1999.6095 .
• Majoul I, Straub M, Hell SW, Duden R, Söling HD . KDEL-cargo regulates interactions between proteins involved in COPI vesicle traffic: measurements in living cells using FRET . Developmental Cell . 1 . 1 . 139–53 . July 2001 . 11703931 . 10.1016/S1534-5807(01)00004-1 . free .
• Yu S, Roth MG . Casein kinase I regulates membrane binding by ARF GAP1 . Molecular Biology of the Cell . 13 . 8 . 2559–70 . August 2002 . 12181329 . 117925 . 10.1091/mbc.E02-04-0189 .
• Yang JS, Lee SY, Gao M, Bourgoin S, Randazzo PA, Premont RT, Hsu VW . ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat . The Journal of Cell Biology . 159 . 1 . 69–78 . October 2002 . 12379802 . 2173491 . 10.1083/jcb.200206015 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .

Notes and References

1. Book: Huber I, Rotman M, Pick E, Makler V, Rothem L, Cukierman E, Cassel D . Expression, purification, and properties of ADP-ribosylation factor (ARF) GTPase activating protein-1 . Regulators and Effectors of Small GTPases Part E: GTPases Involved in Visicular Traffic . Methods in Enzymology . 329 . 307–16 . February 2001 . 11210549 . 10.1016/S0076-6879(01)29092-2 . 9780121822309 .
2. Web site: Entrez Gene: ARFGAP1 ADP-ribosylation factor GTPase activating protein 1.
3. Mesmin B, Drin G, Levi S, Rawet M, Cassel D, Bigay J, Antonny B . Two lipid-packing sensor motifs contribute to the sensitivity of ArfGAP1 to membrane curvature . Biochemistry . 46 . 7 . 1779–90 . February 2007 . 17253781 . 10.1021/bi062288w .
4. Antonny B . Mechanisms of membrane curvature sensing . Annual Review of Biochemistry . 80 . 101–23 . June 2011 . 21438688 . 10.1146/annurev-biochem-052809-155121 .
5. Aoe T, Cukierman E, Lee A, Cassel D, Peters PJ, Hsu VW . The KDEL receptor, ERD2, regulates intracellular traffic by recruiting a GTPase-activating protein for ARF1 . The EMBO Journal . 16 . 24 . 7305–16 . December 1997 . 9405360 . 1170331 . 10.1093/emboj/16.24.7305 .
6. Majoul I, Straub M, Hell SW, Duden R, Söling HD . KDEL-cargo regulates interactions between proteins involved in COPI vesicle traffic: measurements in living cells using FRET . Developmental Cell . 1 . 1 . 139–53 . July 2001 . 11703931 . 10.1016/S1534-5807(01)00004-1 . free .
7. Stafa K, Trancikova A, Webber PJ, Glauser L, West AB, Moore DJ . GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1 . PLOS Genetics . 8 . 2 . e1002526 . February 2012 . 22363216 . 3280333 . 10.1371/journal.pgen.1002526 . free .