{PDOC50877}
{PS50877; GOLOCO}
{BEGIN}
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* GoLoco/GPR motif profile *
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In  heterotrimeric  G-protein  signalling,  cell surface receptors (GPCRs) are
coupled  to  membrane-associated  heterotrimers  comprising  a GTP-hydrolyzing
subunit  G-alpha  and  a  G-beta/G-gamma dimer. The inactive form contains the
alpha subunit bound to GDP and complexes with the beta and gamma subunit. When
the  ligand  is  associated to the receptor, GDP is displaced from G-alpha and
GTP  is  bound. GTP/G-alpha complex dissociates from the trimer and associates
to  an  effector  until  the  intrinsic GTPase activity of G-alpha returns the
protein   to   GDP  bound  form.  Reassociation  of  GDP  bound  G-alpha  with
G-beta/G-gamma  dimer  terminates  the signal. Several mechanisms regulate the
signal  output  at  different  stage  of the G-protein cascade. Two classes of
intracellular  proteins  act  as  inhibitors  of  G protein activation: GTPase
activating  proteins  (GAPs),  which enhance GTP hydrolysis (see <PDOC50132>),
and  guanine  dissociation  inhibitors (GDIs), which inhibit GDP dissociation.
The  GoLoco  or  G-protein  regulatory  (GPR) motif found in various G-protein
regulators [1,2] acts as a GDI on G-alpha(i) [3,4,5].

The  crystal structure of the GoLoco motif in complex with G-alpha(i) has been
solved  (see  <PDB:1KJY>)  [6].  It consists of three small alpha helices. The
highly  conserved  Asp-Gln-Arg  triad  within  the  GoLoco  motif participates
directly  in  GDP  binding  by  extending  the  arginine  side  chain into the
nucleotide binding pocket, highly reminiscent of the catalytic arginine finger
employed  in  GTPase-activating protein (see <PDOC50238>). This addition of an
arginine in the binding pocket affects the interaction of GDP with G-alpha and
therefore is certainly important for the GoLoco GDI activity [6,7].

Some proteins known to contain a GoLoco motif are listed below:

 - Mammalian  regulators  of  G-protein signaling 12 and 14 (RGS12 and RGS14),
   multifaceted signal transduction regulators.
 - Loco, the drosophila RGS12 homologue.
 - Mammalian  Purkinje-cell  protein-2  (Pcp2). It may function as a cell-type
   specific  modulator  for  G protein-mediated cell signaling. It is uniquely
   expressed in cerebellar Purkinje cells and in retinal bipolar neurons.
 - Eukaryotic   Rap1GAP.  A  GTPase  activator  for  the  nuclear  ras-related
   regulatory protein RAP-1A.
 - Drosophila  protein  Rapsynoid (also known as Partner of Inscuteable, Pins)
   and  its mammalian homologues AGS3 and LGN. They form a G-protein regulator
   family that also contains TPR repeats.

The profile we developed covers the whole conserved region.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: April 2003 / First entry.

[ 1] Siderovski D.P., Diverse-Pierluissi M., De Vries L.
     "The GoLoco motif: a Galphai/o binding motif and potential
     guanine-nucleotide exchange factor."
     Trends Biochem. Sci. 24:340-341(1999).
     PubMed=10470031
[ 2] Ponting C.P.
     "Raf-like Ras/Rap-binding domains in RGS12- and still-life-like
     signalling proteins."
     J. Mol. Med. 77:695-698(1999).
     PubMed=10606204
[ 3] De Vries L., Fischer T., Tronchere H., Brothers G.M., Strockbine B.,
     Siderovski D.P., Farquhar M.G.
     Proc. Natl. Acad. Sci. U.S.A. 97:14364-14369(2000).
[ 4] Natochin M., Lester B., Peterson Y.K., Bernard M.L., Lanier S.M.,
     Artemyev N.O.
     "AGS3 inhibits GDP dissociation from galpha subunits of the Gi family
     and rhodopsin-dependent activation of transducin."
     J. Biol. Chem. 275:40981-40985(2000).
     PubMed=11024022; DOI=10.1074/jbc.M006478200
[ 5] Kimple R.J., De Vries L., Tronchere H., Behe C.I., Morris R.A.,
     Gist Farquhar M., Siderovski D.P.
     "RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with
     guanine nucleotide dissociation inhibitor Activity."
     J. Biol. Chem. 276:29275-29281(2001).
     PubMed=11387333; DOI=10.1074/jbc.M103208200
[ 6] Kimple R.J., Kimple M.E., Betts L., Sondek J., Siderovski D.P.
     "Structural determinants for GoLoco-induced inhibition of nucleotide
     release by Galpha subunits."
     Nature 416:878-881(2002).
     PubMed=11976690; DOI=10.1038/416878a
[ 7] Peterson Y.K., Hazard S. III, Graber S.G., Lanier S.M.
     "Identification of structural features in the G-protein regulatory
     motif required for regulation of heterotrimeric G-proteins."
     J. Biol. Chem. 277:6767-6770(2002).
     PubMed=11756403; DOI=10.1074/jbc.C100699200

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