PROSITE documentation PDOC50115 [for PROSITE entry PS50115]

ARF GTPase-activating proteins domain profile





Description

The ARFGAP domain was first identified in the cell cycle control GTPase activating protein (GAP) GCS1 [1]. GCS1 is important for the inactivation of the ADP ribosylation factor ARF a member of the Ras superfamily of GTP-binding proteins. GTP-bound form of ARF is essential for the maintenance of normal Golgi morphology, it participates in recruitment of coat proteins which are required for budding and fission of membranes. Before the fusion with an acceptor compartment the membrane must be uncoated. This step required the hydrolysis of GTP associated to ARF, a process dependent on the ARFGAP domain of GCS1 [1].

The ARFGAP domain contains a characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-Cys-x2-Cys) which displays some similarity to the C4-type GATA zinc finger. The ARFGAP domain display no obvious similarity to other GAP proteins. However a C4-type zinc finger is also found in the ARD1 GAP domain [2].

The 3D structure of the ARFGAP domain of the PYK2-associated protein β has been solved [3]. It consists of a three-stranded β-sheet surrounded by 5 α helices. The domain is organized around a central zinc atom which is coordinated by 4 cysteines (see <PDB:1DCQ>). The ARFGAP domain is clearly unrelated to the other GAP proteins structures which are exclusively helical. Classical GAP proteins accelerate GTPase activity by supplying an arginin finger to the active site. Crystal structure of ARFGAP bound to ARF [4] revealed that the ARFGAP domain does not supply an arginine to the active site which suggest a more indirect role of the ARFGAP domain in the GTPase hydrolysis.

We have developed a profile that covers the entire ARFGAP domain.

Last update:

May 2002 / First entry.

Technical section

PROSITE method (with tools and information) covered by this documentation:

ARFGAP, PS50115; ARF GTPase-activating proteins domain profile  (MATRIX)


References

1AuthorsIreland L.S., Johnston G.C., Drebot M.A., Dhillon N., DeMaggio A.J., Hoekstra M.F., Singer R.A.
TitleA member of a novel family of yeast 'zn-finger' proteins mediates the transition from stationary phase to cell proliferation.
SourceEMBO J. 13:3812-3821(1994).
PubMed ID8070409

2AuthorsVitale N., Moss J., Vaughan M.
TitleMolecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1).
SourceJ. Biol. Chem. 273:2553-2560(1998).
PubMed ID9446556

3AuthorsMandiyan V., Andreev J., Schlessinger J., Hubbard S.R.
TitleCrystal structure of the ARF-GAP domain and ankyrin repeats of PYK2-associated protein beta.
SourceEMBO J. 18:6890-6898(1999).
PubMed ID10601011
DOI10.1093/emboj/18.24.6890

4AuthorsGoldberg J.
TitleStructural and functional analysis of the ARF1-ARFGAP complex reveals a role for coatomer in GTP hydrolysis.
SourceCell 96:893-902(1999).
PubMed ID10102276



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