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{PDOC00017}
{PS00017; ATP_GTP_A}
{BEGIN}
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* ATP/GTP-binding site motif A (P-loop) *
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From sequence comparisons and crystallographic data analysis it has been shown
[1,2,3,4,5,6] that an appreciable proportion of proteins that  bind ATP or GTP
share a number of more or less conserved sequence motifs.   The best conserved
of these  motifs  is  a  glycine-rich region, which typically forms a flexible
loop between a beta-strand and an alpha-helix. This loop interacts with one of
the phosphate  groups  of  the  nucleotide.   This sequence motif is generally
referred to as the 'A' consensus sequence [1] or the 'P-loop' [5].

There are numerous ATP- or GTP-binding proteins  in which the P-loop is found.
We list below  a number of protein  families  for  which  the relevance of the
presence of such motif has been noted:

 - ATP synthase alpha and beta subunits (see <PDOC00137>).
 - Myosin heavy chains.
 - Kinesin heavy chains and kinesin-like proteins (see <PDOC00343>).
 - Dynamins and dynamin-like proteins (see <PDOC00362>).
 - Guanylate kinase (see <PDOC00670>).
 - Thymidine kinase (see <PDOC00524>).
 - Thymidylate kinase (see <PDOC01034>).
 - Shikimate kinase (see <PDOC00868>).
 - Nitrogenase iron protein family (nifH/chlL) (see <PDOC00580>).
 - ATP-binding proteins involved  in 'active transport' (ABC transporters) [7]
   (see <PDOC00185>).
 - DNA and RNA helicases [8,9,10].
 - GTP-binding elongation factors (EF-Tu, EF-1alpha, EF-G, EF-2, etc.).
 - Ras family of GTP-binding proteins (Ras, Rho, Rab, Ral, Ypt1, SEC4, etc.).
 - Nuclear protein ran (see <PDOC00859>).
 - ADP-ribosylation factors family (see <PDOC00781>).
 - Bacterial dnaA protein (see <PDOC00771>).
 - Bacterial recA protein (see <PDOC00131>).
 - Bacterial recF protein (see <PDOC00539>).
 - Guanine nucleotide-binding proteins alpha subunits (Gi, Gs, Gt, G0, etc.).
 - DNA mismatch repair proteins mutS family (See <PDOC00388>).
 - Bacterial type II secretion system protein E (see <PDOC00567>).

Not all ATP- or GTP-binding proteins are picked-up by this motif.  A number of
proteins escape detection because the structure   of their ATP-binding site is
completely different from that of the P-loop.  Examples  of  such proteins are
the E1-E2 ATPases or  the  glycolytic kinases.   In  other ATP- or GTP-binding
proteins the flexible loop exists  in a  slightly different form; this is  the
case for tubulins or protein kinases.  A special mention must  be reserved for
adenylate  kinase,  in  which  there  is a  single  deviation  from the P-loop
pattern: in the last position Gly is found instead of Ser or Thr.

-Consensus pattern: [AG]-x(4)-G-K-[ST]
-Sequences known to belong to this class detected by the pattern: a majority.
-Other sequence(s) detected in Swiss-Prot: in addition to the proteins  listed
 above,  the 'A' motif is also  found in a number  of other proteins.  Most of
 these proteins  probably  bind  a nucleotide, but others are definitively not
 ATP- or GTP-binding (as for example  chymotrypsin,  or  human  ferritin light
 chain).

-Expert(s) to contact by email:
           Koonin E.V.; 
koonin@ncbi.nlm.nih.gov -Last update: July 1999 / Text revised. [ 1] Walker J.E., Saraste M., Runswick M.J., Gay N.J. "Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold." EMBO J. 1:945-951(1982). PubMed=6329717 [ 2] Moller W., Amons R. "Phosphate-binding sequences in nucleotide-binding proteins." FEBS Lett. 186:1-7(1985). PubMed=2989003 [ 3] Fry D.C., Kuby S.A., Mildvan A.S. "ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins." Proc. Natl. Acad. Sci. U.S.A. 83:907-911(1986). PubMed=2869483 [ 4] Dever T.E., Glynias M.J., Merrick W.C. "GTP-binding domain: three consensus sequence elements with distinct spacing." Proc. Natl. Acad. Sci. U.S.A. 84:1814-1818(1987). PubMed=3104905 [ 5] Saraste M., Sibbald P.R., Wittinghofer A. "The P-loop -- a common motif in ATP- and GTP-binding proteins." Trends Biochem. Sci. 15:430-434(1990). PubMed=2126155 [ 6] Koonin E.V. "A superfamily of ATPases with diverse functions containing either classical or deviant ATP-binding motif." J. Mol. Biol. 229:1165-1174(1993). PubMed=8445645 [ 7] Higgins C.F., Hyde S.C., Mimmack M.M., Gileadi U., Gill D.R., Gallagher M.P. "Binding protein-dependent transport systems." J. Bioenerg. Biomembr. 22:571-592(1990). PubMed=2229036 [ 8] Hodgman T.C. "A new superfamily of replicative proteins." Nature 333:22-23(1988) and Nature 333:578-578(1988) (Errata). PubMed=3362205; DOI=10.1038/333022b0 [ 9] Linder P., Lasko P.F., Ashburner M., Leroy P., Nielsen P.J., Nishi K., Schnier J., Slonimski P.P. "Birth of the D-E-A-D box." Nature 337:121-122(1989). PubMed=2563148; DOI=10.1038/337121a0 [10] Gorbalenya A.E., Koonin E.V., Donchenko A.P., Blinov V.M. Nucleic Acids Res. 17:4713-4730(1989). -------------------------------------------------------------------------------- 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}