{PDOC50115}
{PS50115; ARFGAP}
{BEGIN}
*************************************************
* ARF GTPase-activating proteins domain profile *
*************************************************

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 beta has
been  solved  [3].  It consists of a three-stranded beta-sheet surrounded by 5
alpha  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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2002 / First entry.

[ 1] Ireland L.S., Johnston G.C., Drebot M.A., Dhillon N., DeMaggio A.J.,
     Hoekstra M.F., Singer R.A.
     "A member of a novel family of yeast 'zn-finger' proteins mediates the
     transition from stationary phase to cell proliferation."
     EMBO J. 13:3812-3821(1994).
     PubMed=8070409
[ 2] Vitale N., Moss J., Vaughan M.
     "Molecular characterization of the GTPase-activating domain of
     ADP-ribosylation factor domain protein 1 (ARD1)."
     J. Biol. Chem. 273:2553-2560(1998).
     PubMed=9446556
[ 3] Mandiyan V., Andreev J., Schlessinger J., Hubbard S.R.
     "Crystal structure of the ARF-GAP domain and ankyrin repeats of
     PYK2-associated protein beta."
     EMBO J. 18:6890-6898(1999).
     PubMed=10601011; DOI=10.1093/emboj/18.24.6890
[ 4] Goldberg J.
     "Structural and functional analysis of the ARF1-ARFGAP complex reveals
     a role for coatomer in GTP hydrolysis."
     Cell 96:893-902(1999).
     PubMed=10102276

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}