SNF1_YEAST
ID SNF1_YEAST Reviewed; 633 AA.
AC P06782; D6VTA0;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 230.
DE RecName: Full=Carbon catabolite-derepressing protein kinase {ECO:0000303|PubMed:3526554};
DE EC=2.7.11.1 {ECO:0000269|PubMed:15719021, ECO:0000269|PubMed:2557546, ECO:0000269|PubMed:3526554};
DE AltName: Full=Sucrose nonfermentating protein 1 {ECO:0000303|PubMed:6366512};
GN Name=SNF1 {ECO:0000303|PubMed:6366512};
GN Synonyms=CAT1, CCR1 {ECO:0000303|PubMed:1944227}, GLC2, PAS14;
GN OrderedLocusNames=YDR477W; ORFNames=D8035.20;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=3526554; DOI=10.1126/science.3526554;
RA Celenza J.L., Carlson M.;
RT "A yeast gene that is essential for release from glucose repression encodes
RT a protein kinase.";
RL Science 233:1175-1180(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP PROTEIN SEQUENCE OF 274-284; 528-539 AND 622-630, AND PHOSPHORYLATION AT
RP THR-210.
RX PubMed=7905477; DOI=10.1016/s0021-9258(17)41951-x;
RA Mitchelhill K.I., Stapleton D., Gao G., House C., Michell B., Katsis F.,
RA Witters L.A., Kemp B.E.;
RT "Mammalian AMP-activated protein kinase shares structural and functional
RT homology with the catalytic domain of yeast Snf1 protein kinase.";
RL J. Biol. Chem. 269:2361-2364(1994).
RN [5]
RP IDENTIFICATION, AND FUNCTION.
RX PubMed=6366512; DOI=10.1128/mcb.4.1.49-53.1984;
RA Celenza J.L., Carlson M.;
RT "Cloning and genetic mapping of SNF1, a gene required for expression of
RT glucose-repressible genes in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 4:49-53(1984).
RN [6]
RP INDUCTION.
RX PubMed=6366513; DOI=10.1128/mcb.4.1.54-60.1984;
RA Celenza J.L., Carlson M.;
RT "Structure and expression of the SNF1 gene of Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 4:54-60(1984).
RN [7]
RP FUNCTION.
RX PubMed=3049551; DOI=10.1128/jb.170.10.4838-4845.1988;
RA Bisson L.F.;
RT "High-affinity glucose transport in Saccharomyces cerevisiae is under
RT general glucose repression control.";
RL J. Bacteriol. 170:4838-4845(1988).
RN [8]
RP MUTAGENESIS OF LYS-84, CATALYTIC ACTIVITY, INTERACTION WITH SNF4, AND
RP ACTIVITY REGULATION.
RX PubMed=2557546; DOI=10.1128/mcb.9.11.5034-5044.1989;
RA Celenza J.L., Carlson M.;
RT "Mutational analysis of the Saccharomyces cerevisiae SNF1 protein kinase
RT and evidence for functional interaction with the SNF4 protein.";
RL Mol. Cell. Biol. 9:5034-5044(1989).
RN [9]
RP INTERACTION WITH SNF4.
RX PubMed=2481228; DOI=10.1128/mcb.9.11.5045-5054.1989;
RA Celenza J.L., Eng F.J., Carlson M.;
RT "Molecular analysis of the SNF4 gene of Saccharomyces cerevisiae: evidence
RT for physical association of the SNF4 protein with the SNF1 protein
RT kinase.";
RL Mol. Cell. Biol. 9:5045-5054(1989).
RN [10]
RP FUNCTION.
RX PubMed=1944227; DOI=10.1007/bf00267461;
RA Denis C.L., Audino D.C.;
RT "The CCR1 (SNF1) and SCH9 protein kinases act independently of cAMP-
RT dependent protein kinase and the transcriptional activator ADR1 in
RT controlling yeast ADH2 expression.";
RL Mol. Gen. Genet. 229:395-399(1991).
RN [11]
RP FUNCTION.
RX PubMed=8289797; DOI=10.1128/mcb.14.2.1160-1170.1994;
RA Ulery T.L., Jang S.H., Jaehning J.A.;
RT "Glucose repression of yeast mitochondrial transcription: kinetics of
RT derepression and role of nuclear genes.";
RL Mol. Cell. Biol. 14:1160-1170(1994).
RN [12]
RP MUTAGENESIS OF GLY-53 AND THR-210.
RX PubMed=1468623; DOI=10.1093/genetics/132.3.639;
RA Estruch F., Treitel M.A., Yang X., Carlson M.;
RT "N-terminal mutations modulate yeast SNF1 protein kinase function.";
RL Genetics 132:639-650(1992).
RN [13]
RP INTERACTION WITH SIP1; SIP2 AND GAL83.
RX PubMed=7813428; DOI=10.1002/j.1460-2075.1994.tb06933.x;
RA Yang X., Jiang R., Carlson M.;
RT "A family of proteins containing a conserved domain that mediates
RT interaction with the yeast SNF1 protein kinase complex.";
RL EMBO J. 13:5878-5886(1994).
RN [14]
RP FUNCTION, AND INTERACTION WITH SIP4.
RX PubMed=8628258; DOI=10.1128/mcb.16.5.1921;
RA Lesage P., Yang X., Carlson M.;
RT "Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster
RT transcriptional activator: a new role for SNF1 in the glucose response.";
RL Mol. Cell. Biol. 16:1921-1928(1996).
RN [15]
RP INTERACTION WITH SNF4; SIP1; SIP2 AND GAL83.
RX PubMed=9121458; DOI=10.1128/mcb.17.4.2099;
RA Jiang R., Carlson M.;
RT "The Snf1 protein kinase and its activating subunit, Snf4, interact with
RT distinct domains of the Sip1/Sip2/Gal83 component in the kinase complex.";
RL Mol. Cell. Biol. 17:2099-2106(1997).
RN [16]
RP PHOSPHORYLATION AT THR-210, AND MUTAGENESIS OF LYS-84 AND THR-210.
RX PubMed=11486005; DOI=10.1074/jbc.m104418200;
RA McCartney R.R., Schmidt M.C.;
RT "Regulation of Snf1 kinase. Activation requires phosphorylation of
RT threonine 210 by an upstream kinase as well as a distinct step mediated by
RT the Snf4 subunit.";
RL J. Biol. Chem. 276:36460-36466(2001).
RN [17]
RP PHOSPHORYLATION AT THR-210, AND INTERACTION WITH SAK1.
RX PubMed=12748292; DOI=10.1128/mcb.23.11.3909-3917.2003;
RA Nath N., McCartney R.R., Schmidt M.C.;
RT "Yeast Pak1 kinase associates with and activates Snf1.";
RL Mol. Cell. Biol. 23:3909-3917(2003).
RN [18]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF CAT8.
RX PubMed=15121831; DOI=10.1128/mcb.24.10.4083-4091.2004;
RA Charbon G., Breunig K.D., Wattiez R., Vandenhaute J., Noel-Georis I.;
RT "Key role of Ser562/661 in Snf1-dependent regulation of Cat8p in
RT Saccharomyces cerevisiae and Kluyveromyces lactis.";
RL Mol. Cell. Biol. 24:4083-4091(2004).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3, AND IDENTIFICATION IN THE SNF1
RP KINASE COMPLEX.
RX PubMed=15719021; DOI=10.1038/sj.emboj.7600577;
RA Lo W.-S., Gamache E.R., Henry K.W., Yang D., Pillus L., Berger S.L.;
RT "Histone H3 phosphorylation can promote TBP recruitment through distinct
RT promoter-specific mechanisms.";
RL EMBO J. 24:997-1008(2005).
RN [21]
RP INTERACTION WITH CTK1.
RX PubMed=16182287; DOI=10.1016/j.febslet.2005.08.057;
RA Van Driessche B., Coddens S., Van Mullem V., Vandenhaute J.;
RT "Glucose deprivation mediates interaction between CTDK-I and Snf1 in
RT Saccharomyces cerevisiae.";
RL FEBS Lett. 579:5318-5324(2005).
RN [22]
RP PHOSPHORYLATION, AND INTERACTION WITH SAK1.
RX PubMed=16847059; DOI=10.1074/jbc.m603811200;
RA Elbing K., Rubenstein E.M., McCartney R.R., Schmidt M.C.;
RT "Subunits of the Snf1 kinase heterotrimer show interdependence for
RT association and activity.";
RL J. Biol. Chem. 281:26170-26180(2006).
RN [23]
RP SUBCELLULAR LOCATION.
RX PubMed=17237508; DOI=10.1534/genetics.106.068932;
RA Sarma N.J., Haley T.M., Barbara K.E., Buford T.D., Willis K.A.,
RA Santangelo G.M.;
RT "Glucose-responsive regulators of gene expression in Saccharomyces
RT cerevisiae function at the nuclear periphery via a reverse recruitment
RT mechanism.";
RL Genetics 175:1127-1135(2007).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-487, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413 AND SER-632, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [27]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-461, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
RN [28]
RP SUMOYLATION AT LYS-549 BY MMS21, AND MUTAGENESIS OF LYS-549.
RX PubMed=24108357; DOI=10.1073/pnas.1304839110;
RA Simpson-Lavy K.J., Johnston M.;
RT "Sumoylation regulates the SNF1 protein kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17432-17437(2013).
RN [29]
RP FUNCTION.
RX PubMed=25730376; DOI=10.1042/bj20140734;
RA Ferrer-Dalmau J., Randez-Gil F., Marquina M., Prieto J.A., Casamayor A.;
RT "Protein kinase Snf1 is involved in the proper regulation of the unfolded
RT protein response in Saccharomyces cerevisiae.";
RL Biochem. J. 468:33-47(2015).
RN [30]
RP DOMAIN, MUTAGENESIS OF GLY-357 AND LEU-367, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=25869125; DOI=10.1074/jbc.m115.647032;
RA Jiao R., Postnikoff S., Harkness T.A., Arnason T.G.;
RT "The SNF1 kinase ubiquitin-associated domain restrains its activation,
RT activity, and the yeast life span.";
RL J. Biol. Chem. 290:15393-15404(2015).
RN [31]
RP FUNCTION, AND INTERACTION WITH CYR1.
RX PubMed=26309257; DOI=10.1074/jbc.m115.658005;
RA Nicastro R., Tripodi F., Gaggini M., Castoldi A., Reghellin V., Nonnis S.,
RA Tedeschi G., Coccetti P.;
RT "Snf1 phosphorylates adenylate cyclase and negatively regulates protein
RT kinase A-dependent transcription in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 290:24715-24726(2015).
RN [32]
RP FUNCTION.
RX PubMed=25428989; DOI=10.1091/mbc.e14-06-1088;
RA DeMille D., Badal B.D., Evans J.B., Mathis A.D., Anderson J.F., Grose J.H.;
RT "PAS kinase is activated by direct SNF1-dependent phosphorylation and
RT mediates inhibition of TORC1 through the phosphorylation and activation of
RT Pbp1.";
RL Mol. Biol. Cell 26:569-582(2015).
RN [33]
RP FUNCTION.
RX PubMed=26667037; DOI=10.1128/mcb.00436-15;
RA Braun K.A., Dombek K.M., Young E.T.;
RT "Snf1-dependent transcription confers glucose-induced decay upon the mRNA
RT product.";
RL Mol. Cell. Biol. 36:628-644(2015).
RN [34]
RP FUNCTION, AND PHOSPHORYLATION AT THR-210.
RX PubMed=26394309; DOI=10.1371/journal.pgen.1005491;
RA Mizuno T., Masuda Y., Irie K.;
RT "The Saccharomyces cerevisiae AMPK, Snf1, negatively regulates the Hog1
RT MAPK pathway in ER stress response.";
RL PLoS Genet. 11:E1005491-E1005491(2015).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 41-315, AND DOMAIN.
RX PubMed=16236260; DOI=10.1016/j.bbrc.2005.09.181;
RA Rudolph M.J., Amodeo G.A., Bai Y., Tong L.;
RT "Crystal structure of the protein kinase domain of yeast AMP-activated
RT protein kinase Snf1.";
RL Biochem. Biophys. Res. Commun. 337:1224-1228(2005).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 46-319, AND DOMAIN.
RX PubMed=16531232; DOI=10.1016/j.str.2005.12.008;
RA Nayak V., Zhao K., Wyce A., Schwartz M.F., Lo W.S., Berger S.L.,
RA Marmorstein R.;
RT "Structure and dimerization of the kinase domain from yeast Snf1, a member
RT of the Snf1/AMPK protein family.";
RL Structure 14:477-485(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 460-630 IN COMPLEX WITH SNF4 AND
RP SIP2, DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=17851534; DOI=10.1038/nature06127;
RA Amodeo G.A., Rudolph M.J., Tong L.;
RT "Crystal structure of the heterotrimer core of Saccharomyces cerevisiae
RT AMPK homologue SNF1.";
RL Nature 449:492-495(2007).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 41-315, DOMAIN, AND
RP PHOSPHORYLATION AT THR-210.
RX PubMed=19474788; DOI=10.1038/nature08075;
RA Chen L., Jiao Z.H., Zheng L.S., Zhang Y.Y., Xie S.T., Wang Z.X., Wu J.W.;
RT "Structural insight into the autoinhibition mechanism of AMP-activated
RT protein kinase.";
RL Nature 459:1146-1149(2009).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 50-320, AND DOMAIN.
RX PubMed=20823513; DOI=10.1107/s1744309110028265;
RA Rudolph M.J., Amodeo G.A., Tong L.;
RT "An inhibited conformation for the protein kinase domain of the
RT Saccharomyces cerevisiae AMPK homolog Snf1.";
RL Acta Crystallogr. F 66:999-1002(2010).
RN [40]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 457-633, AND PHOSPHORYLATION AT
RP THR-210.
RX PubMed=22019086; DOI=10.1016/j.cmet.2011.09.009;
RA Mayer F.V., Heath R., Underwood E., Sanders M.J., Carmena D.,
RA McCartney R.R., Leiper F.C., Xiao B., Jing C., Walker P.A., Haire L.F.,
RA Ogrodowicz R., Martin S.R., Schmidt M.C., Gamblin S.J., Carling D.;
RT "ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated
RT protein kinase.";
RL Cell Metab. 14:707-714(2011).
CC -!- FUNCTION: Serine/threonine protein kinase essential for release from
CC glucose repression (PubMed:3526554, PubMed:6366512, PubMed:3049551,
CC PubMed:1944227, PubMed:8289797, PubMed:8628258, PubMed:25869125).
CC Catalytic subunit of the AMP-activated protein kinase complex also
CC known as the SNF1 kinase complex (Snf1c), a central regulator of
CC cellular energy homeostasis, which, in response to a fall in
CC intracellular ATP levels, activates energy-producing pathways and
CC inhibits energy-consuming processes (PubMed:8289797, PubMed:26667037).
CC The complex phosphorylates histone H3 to form H3S10ph, which promotes
CC H3K14ac formation, leading to transcriptional activation through TBP
CC recruitment to the promoters (PubMed:15719021). The complex also
CC negatively regulates the HOG1 MAPK pathway in ER stress response
CC including unfolded protein response (UPR) (PubMed:25730376,
CC PubMed:26394309). Under nutrient/energy depletion, the complex
CC phosphorylates and activates PAS kinase PSK1 which in turn activates
CC PBS1, leading to the inhibition of the TORC1 signaling pathway
CC (PubMed:25428989). SNF1 also interacts and phosphorylates adenylate
CC cyclase CYR1 and negatively regulates the protein kinase A signaling
CC pathway (PubMed:26309257). Also phosphorylates and regulates the
CC transcriptional activator CAT8 (PubMed:15121831).
CC {ECO:0000269|PubMed:15121831, ECO:0000269|PubMed:15719021,
CC ECO:0000269|PubMed:1944227, ECO:0000269|PubMed:25428989,
CC ECO:0000269|PubMed:25730376, ECO:0000269|PubMed:25869125,
CC ECO:0000269|PubMed:26309257, ECO:0000269|PubMed:26394309,
CC ECO:0000269|PubMed:26667037, ECO:0000269|PubMed:3049551,
CC ECO:0000269|PubMed:3526554, ECO:0000269|PubMed:6366512,
CC ECO:0000269|PubMed:8289797, ECO:0000269|PubMed:8628258}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:15719021, ECO:0000269|PubMed:2557546,
CC ECO:0000269|PubMed:3526554};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:15719021,
CC ECO:0000269|PubMed:2557546, ECO:0000269|PubMed:3526554};
CC -!- ACTIVITY REGULATION: The kinase activity is positively regulated by
CC SNF4 via sequestration of the SNF1 auto-inhibitory domain (AID)
CC (PubMed:2557546, PubMed:17851534). {ECO:0000269|PubMed:17851534,
CC ECO:0000269|PubMed:2557546}.
CC -!- SUBUNIT: Component of the AMP-activated protein kinase complex also
CC known as the SNF1 kinase complex (Snf1c), a heterotrimeric complex
CC composed of an alpha subunit (SNF1), a regulatory subunit beta (GAL83
CC and substoichiometric alternate beta subunits SIP1 and SIP2), and a
CC regulatory subunit gamma (SNF4) (PubMed:2557546, PubMed:2481228,
CC PubMed:7813428, PubMed:9121458, PubMed:15719021, PubMed:17851534).
CC Interacts with the transcriptional activator SIP4 (PubMed:8628258).
CC Interacts with SAK1 (PubMed:12748292, PubMed:16847059). Interacts with
CC CTK1 (PubMed:16182287): Interacts with adenylate cyclase CYR1
CC (PubMed:26309257). {ECO:0000269|PubMed:12748292,
CC ECO:0000269|PubMed:15719021, ECO:0000269|PubMed:16182287,
CC ECO:0000269|PubMed:16847059, ECO:0000269|PubMed:17851534,
CC ECO:0000269|PubMed:2481228, ECO:0000269|PubMed:2557546,
CC ECO:0000269|PubMed:26309257, ECO:0000269|PubMed:7813428,
CC ECO:0000269|PubMed:8628258, ECO:0000269|PubMed:9121458}.
CC -!- INTERACTION:
CC P06782; Q00684: CDC14; NbExp=2; IntAct=EBI-17516, EBI-4192;
CC P06782; Q04739: GAL83; NbExp=5; IntAct=EBI-17516, EBI-7244;
CC P06782; P22211: NPR1; NbExp=2; IntAct=EBI-17516, EBI-12207;
CC P06782; Q00816: REG1; NbExp=7; IntAct=EBI-17516, EBI-8270;
CC P06782; P38232: REG2; NbExp=3; IntAct=EBI-17516, EBI-14921;
CC P06782; P34164: SIP2; NbExp=11; IntAct=EBI-17516, EBI-17187;
CC P06782; P06782: SNF1; NbExp=6; IntAct=EBI-17516, EBI-17516;
CC P06782; P12904: SNF4; NbExp=22; IntAct=EBI-17516, EBI-17537;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:25869125}. Nucleus
CC {ECO:0000269|PubMed:25869125}. Nucleus membrane
CC {ECO:0000269|PubMed:17237508}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17237508}. Note=Nuclear translocation occurs under
CC nitrogen and glucose starvation conditions (PubMed:25869125).
CC {ECO:0000269|PubMed:25869125}.
CC -!- INDUCTION: Expression of the SNF1 gene itself is not glucose
CC repressible (PubMed:6366513). {ECO:0000269|PubMed:6366513}.
CC -!- DOMAIN: The regulatory domain (RS) also called auto-inhibitory domain
CC (AID) inhibits kinase activity of the protein kinase domain (KD)
CC (PubMed:19474788, PubMed:20823513). The AID is sequestered by SNF4
CC within the AMP-activated protein kinase complex which might correspond
CC to the activated SNF1 form (PubMed:17851534).
CC {ECO:0000269|PubMed:17851534, ECO:0000269|PubMed:19474788,
CC ECO:0000269|PubMed:20823513}.
CC -!- DOMAIN: The ubiquitin-associated domain (UBA) localized within the AID
CC dampens kinase activation, probably by restraining SNF1-SNF4
CC associations (PubMed:25869125). Moreover, the UBA domain influences
CC life span in a FKH1- and FKH2-dependent mechanism (PubMed:25869125).
CC {ECO:0000269|PubMed:25869125}.
CC -!- PTM: Phosphorylation at Thr-210 in response to glucose limitation leads
CC to activation of kinase activity (PubMed:11486005, PubMed:12748292).
CC ADP, but not AMP, protects the enzyme from dephosphorylation at Thr-210
CC by GLC7 (PubMed:22019086). {ECO:0000269|PubMed:12748292,
CC ECO:0000269|PubMed:22019086}.
CC -!- PTM: Sumoylation by the SUMO (E3) ligase MMS21 leads to inhibition by
CC interaction of SUMO attached to Lys-549 with a SUMO-interacting
CC sequence motif located near the active site of SNF1, and by targeting
CC SNF1 for glucose-induced destruction via the SLX5-SLX8 (SUMO-directed)
CC ubiquitin ligase (PubMed:24108357). {ECO:0000269|PubMed:24108357}.
CC -!- MISCELLANEOUS: Present with 589 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. SNF1 subfamily. {ECO:0000305}.
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DR EMBL; M13971; AAA35058.1; -; Genomic_DNA.
DR EMBL; U33050; AAB64904.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12310.1; -; Genomic_DNA.
DR PIR; A26030; A26030.
DR RefSeq; NP_010765.3; NM_001180785.3.
DR PDB; 2FH9; X-ray; 2.80 A; A=46-319.
DR PDB; 2QLV; X-ray; 2.60 A; A/D=460-630.
DR PDB; 3DAE; X-ray; 2.90 A; A/B=41-315.
DR PDB; 3HYH; X-ray; 2.20 A; A/B=41-315.
DR PDB; 3MN3; X-ray; 2.38 A; A=50-320.
DR PDB; 3T4N; X-ray; 2.30 A; A=457-633.
DR PDB; 3TDH; X-ray; 2.30 A; A=457-633.
DR PDB; 3TE5; X-ray; 2.50 A; A=457-633.
DR PDBsum; 2FH9; -.
DR PDBsum; 2QLV; -.
DR PDBsum; 3DAE; -.
DR PDBsum; 3HYH; -.
DR PDBsum; 3MN3; -.
DR PDBsum; 3T4N; -.
DR PDBsum; 3TDH; -.
DR PDBsum; 3TE5; -.
DR AlphaFoldDB; P06782; -.
DR SMR; P06782; -.
DR BioGRID; 32529; 853.
DR ComplexPortal; CPX-231; Snf1 protein kinase complex variant GAL83.
DR ComplexPortal; CPX-232; Snf1 protein kinase complex variant SIP1.
DR ComplexPortal; CPX-2800; Snf1 protein kinase complex variant SIP2.
DR DIP; DIP-18N; -.
DR IntAct; P06782; 55.
DR MINT; P06782; -.
DR STRING; 4932.YDR477W; -.
DR iPTMnet; P06782; -.
DR MaxQB; P06782; -.
DR PaxDb; P06782; -.
DR PRIDE; P06782; -.
DR EnsemblFungi; YDR477W_mRNA; YDR477W; YDR477W.
DR GeneID; 852088; -.
DR KEGG; sce:YDR477W; -.
DR SGD; S000002885; SNF1.
DR VEuPathDB; FungiDB:YDR477W; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000167424; -.
DR HOGENOM; CLU_000288_59_3_1; -.
DR InParanoid; P06782; -.
DR OMA; KALNYEW; -.
DR BioCyc; YEAST:G3O-30003-MON; -.
DR BRENDA; 2.7.11.1; 984.
DR Reactome; R-SCE-1632852; Macroautophagy.
DR Reactome; R-SCE-163680; AMPK inhibits chREBP transcriptional activation activity.
DR Reactome; R-SCE-176187; Activation of ATR in response to replication stress.
DR Reactome; R-SCE-200425; Carnitine metabolism.
DR Reactome; R-SCE-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-SCE-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-SCE-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR EvolutionaryTrace; P06782; -.
DR PRO; PR:P06782; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P06782; protein.
DR GO; GO:0000144; C:cellular bud neck septin ring; IDA:SGD.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:SGD.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0005774; C:vacuolar membrane; IDA:SGD.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IMP:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:SGD.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004672; F:protein kinase activity; HDA:SGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:SGD.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IMP:SGD.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IDA:SGD.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:SGD.
DR GO; GO:0030447; P:filamentous growth; IMP:ComplexPortal.
DR GO; GO:0071940; P:fungal-type cell wall assembly; IMP:SGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0001403; P:invasive growth in response to glucose limitation; IMP:SGD.
DR GO; GO:0017148; P:negative regulation of translation; IMP:SGD.
DR GO; GO:1900436; P:positive regulation of filamentous growth of a population of unicellular organisms in response to starvation; IMP:SGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:SGD.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IMP:SGD.
DR GO; GO:2000222; P:positive regulation of pseudohyphal growth; IMP:SGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:SGD.
DR GO; GO:1904547; P:regulation of cellular response to glucose starvation; EXP:ComplexPortal.
DR GO; GO:2000217; P:regulation of invasive growth in response to glucose limitation; IMP:ComplexPortal.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:SGD.
DR GO; GO:0006986; P:response to unfolded protein; IMP:SGD.
DR GO; GO:0090606; P:single-species surface biofilm formation; IMP:SGD.
DR CDD; cd14334; UBA_SNF1_fungi; 1.
DR DisProt; DP02769; -.
DR InterPro; IPR032270; AMPK_C.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR013896; SNF1_UBA.
DR Pfam; PF16579; AdenylateSensor; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF08587; UBA_2; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF103243; SSF103243; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Carbohydrate metabolism; Cytoplasm;
KW Direct protein sequencing; Isopeptide bond; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..633
FT /note="Carbon catabolite-derepressing protein kinase"
FT /id="PRO_0000086670"
FT DOMAIN 55..306
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:16236260, ECO:0000269|PubMed:16531232"
FT DOMAIN 348..389
FT /note="UBA"
FT /evidence="ECO:0000269|PubMed:25869125"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..392
FT /note="Auto-inhibitory domain (AID)"
FT /evidence="ECO:0000269|PubMed:17851534,
FT ECO:0000269|PubMed:19474788"
FT REGION 317..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 409..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 16..33
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 318..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..424
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 177
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 61..69
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 210
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11486005,
FT ECO:0000269|PubMed:12748292, ECO:0000269|PubMed:22019086,
FT ECO:0000269|PubMed:26394309, ECO:0000269|PubMed:7905477"
FT MOD_RES 413
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 487
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT CROSSLNK 461
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
FT CROSSLNK 549
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000269|PubMed:24108357"
FT MUTAGEN 53
FT /note="G->R: Exhibits greater activity than wild-type SNFl
FT in an immune complex assay where other associated molecules
FT are present, but exhibits the same activity in a protein
FT blot assay."
FT /evidence="ECO:0000269|PubMed:1468623"
FT MUTAGEN 84
FT /note="K->R: Inactivates the kinase activity without
FT affecting protein levels."
FT /evidence="ECO:0000269|PubMed:11486005,
FT ECO:0000269|PubMed:2557546"
FT MUTAGEN 210
FT /note="T->A: Inactivates the kinase activity without
FT affecting protein levels."
FT /evidence="ECO:0000269|PubMed:11486005,
FT ECO:0000269|PubMed:1468623"
FT MUTAGEN 357
FT /note="G->A: Alters kinase activation and biological
FT activity, including enhanced allosteric subunit
FT associations and increased oxidative stress resistance and
FT life span; when associated with I-367."
FT /evidence="ECO:0000269|PubMed:25869125"
FT MUTAGEN 367
FT /note="L->I: Alters kinase activation and biological
FT activity, including enhanced allosteric subunit
FT associations and increased oxidative stress resistance and
FT life span; when associated with A-357."
FT /evidence="ECO:0000269|PubMed:25869125"
FT MUTAGEN 549
FT /note="K->R: Decreases sumoylation of SNF1."
FT /evidence="ECO:0000269|PubMed:24108357"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:3MN3"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:3HYH"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 80..87
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:3DAE"
FT HELIX 97..109
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 118..123
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 139..145
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 151..170
FT /evidence="ECO:0007829|PDB:3HYH"
FT TURN 180..182
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3HYH"
FT TURN 207..209
FT /evidence="ECO:0007829|PDB:3MN3"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:3MN3"
FT HELIX 220..223
FT /evidence="ECO:0007829|PDB:3HYH"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 232..247
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 257..266
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 277..286
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 297..302
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 304..307
FT /evidence="ECO:0007829|PDB:3HYH"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3HYH"
FT TURN 317..319
FT /evidence="ECO:0007829|PDB:3MN3"
FT HELIX 471..473
FT /evidence="ECO:0007829|PDB:3T4N"
FT HELIX 475..485
FT /evidence="ECO:0007829|PDB:3T4N"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:3T4N"
FT STRAND 506..511
FT /evidence="ECO:0007829|PDB:3T4N"
FT HELIX 515..529
FT /evidence="ECO:0007829|PDB:3T4N"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:3T4N"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:3T4N"
FT STRAND 543..548
FT /evidence="ECO:0007829|PDB:3T4N"
FT STRAND 565..576
FT /evidence="ECO:0007829|PDB:3T4N"
FT STRAND 579..590
FT /evidence="ECO:0007829|PDB:3T4N"
FT HELIX 607..610
FT /evidence="ECO:0007829|PDB:2QLV"
FT HELIX 613..628
FT /evidence="ECO:0007829|PDB:3T4N"
SQ SEQUENCE 633 AA; 72045 MW; F5C63565C986C4E3 CRC64;
MSSNNNTNTA PANANSSHHH HHHHHHHHHH GHGGSNSTLN NPKSSLADGA HIGNYQIVKT
LGEGSFGKVK LAYHTTTGQK VALKIINKKV LAKSDMQGRI EREISYLRLL RHPHIIKLYD
VIKSKDEIIM VIEYAGNELF DYIVQRDKMS EQEARRFFQQ IISAVEYCHR HKIVHRDLKP
ENLLLDEHLN VKIADFGLSN IMTDGNFLKT SCGSPNYAAP EVISGKLYAG PEVDVWSCGV
ILYVMLCRRL PFDDESIPVL FKNISNGVYT LPKFLSPGAA GLIKRMLIVN PLNRISIHEI
MQDDWFKVDL PEYLLPPDLK PHPEEENENN DSKKDGSSPD NDEIDDNLVN ILSSTMGYEK
DEIYESLESS EDTPAFNEIR DAYMLIKENK SLIKDMKANK SVSDELDTFL SQSPPTFQQQ
SKSHQKSQVD HETAKQHARR MASAITQQRT YHQSPFMDQY KEEDSTVSIL PTSLPQIHRA
NMLAQGSPAA SKISPLVTKK SKTRWHFGIR SRSYPLDVMG EIYIALKNLG AEWAKPSEED
LWTIKLRWKY DIGNKTNTNE KIPDLMKMVI QLFQIETNNY LVDFKFDGWE SSYGDDTTVS
NISEDEMSTF SAYPFLHLTT KLIMELAVNS QSN
