{PDOC00017} {PS00017; ATP_GTP_A} {BEGIN} ***************************************** * ATP/GTP-binding site motif A (P-loop) * ***************************************** 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 ). - Myosin heavy chains. - Kinesin heavy chains and kinesin-like proteins (see ). - Dynamins and dynamin-like proteins (see ). - Guanylate kinase (see ). - Thymidine kinase (see ). - Thymidylate kinase (see ). - Shikimate kinase (see ). - Nitrogenase iron protein family (nifH/chlL) (see ). - ATP-binding proteins involved in 'active transport' (ABC transporters) [7] (see ). - 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 ). - ADP-ribosylation factors family (see ). - Bacterial dnaA protein (see ). - Bacterial recA protein (see ). - Bacterial recF protein (see ). - Guanine nucleotide-binding proteins alpha subunits (Gi, Gs, Gt, G0, etc.). - DNA mismatch repair proteins mutS family (See ). - Bacterial type II secretion system protein E (see ). 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}