ID AAPK2_RAT Reviewed; 552 AA.
AC Q09137;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 27-MAR-2024, entry version 189.
DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-2;
DE Short=AMPK subunit alpha-2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:2369897, ECO:0000269|PubMed:9029219};
DE AltName: Full=Acetyl-CoA carboxylase kinase;
DE Short=ACACA kinase;
DE AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase;
DE Short=HMGCR kinase;
DE EC=2.7.11.31 {ECO:0000269|PubMed:2369897};
GN Name=Prkaa2; Synonyms=Ampk, Ampk2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), AND PARTIAL PROTEIN
RP SEQUENCE.
RC TISSUE=Liver;
RX PubMed=7908907; DOI=10.1016/s0021-9258(19)78143-5;
RA Carling D., Aguan K., Woods A., Verhoeven A.J.M., Beri R.K., Brennan C.H.,
RA Sidebottom C., Davison M.D., Scott J.;
RT "Mammalian AMP-activated protein kinase is homologous to yeast and plant
RT protein kinases involved in the regulation of carbon metabolism.";
RL J. Biol. Chem. 269:11442-11448(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=7718624; DOI=10.1016/0167-4889(94)00222-z;
RA Gao G., Widmer J., Stapleton D., Teh T., Cox T., Kemp B.E., Witters L.A.;
RT "Catalytic subunits of the porcine and rat 5'-AMP-activated protein kinase
RT are members of the SNF1 protein kinase family.";
RL Biochim. Biophys. Acta 1266:73-82(1995).
RN [3]
RP CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF HMGCR.
RX PubMed=2369897; DOI=10.1002/j.1460-2075.1990.tb07420.x;
RA Clarke P.R., Hardie D.G.;
RT "Regulation of HMG-CoA reductase: identification of the site phosphorylated
RT by the AMP-activated protein kinase in vitro and in intact rat liver.";
RL EMBO J. 9:2439-2446(1990).
RN [4]
RP PHOSPHORYLATION AT THR-172, AND ACTIVITY REGULATION.
RX PubMed=8910387; DOI=10.1074/jbc.271.44.27879;
RA Hawley S.A., Davison M., Woods A., Davies S.P., Beri R.K., Carling D.,
RA Hardie D.G.;
RT "Characterization of the AMP-activated protein kinase kinase from rat liver
RT and identification of threonine 172 as the major site at which it
RT phosphorylates AMP-activated protein kinase.";
RL J. Biol. Chem. 271:27879-27887(1996).
RN [5]
RP CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF ACACA AND ACACB.
RX PubMed=9029219; DOI=10.1152/jappl.1997.82.1.219;
RA Winder W.W., Wilson H.A., Hardie D.G., Rasmussen B.B., Hutber C.A.,
RA Call G.B., Clayton R.D., Conley L.M., Yoon S., Zhou B.;
RT "Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated
RT protein kinase and protein kinase A.";
RL J. Appl. Physiol. 82:219-225(1997).
RN [6]
RP FUNCTION IN PHOSPHORYLATION OF NOS3.
RX PubMed=10025949; DOI=10.1016/s0014-5793(98)01705-0;
RA Chen Z.P., Mitchelhill K.I., Michell B.J., Stapleton D.,
RA Rodriguez-Crespo I., Witters L.A., Power D.A., Ortiz de Montellano P.R.,
RA Kemp B.E.;
RT "AMP-activated protein kinase phosphorylation of endothelial NO synthase.";
RL FEBS Lett. 443:285-289(1999).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF PFKFB2.
RX PubMed=11069105; DOI=10.1016/s0960-9822(00)00742-9;
RA Marsin A.S., Bertrand L., Rider M.H., Deprez J., Beauloye C., Vincent M.F.,
RA Van den Berghe G., Carling D., Hue L.;
RT "Phosphorylation and activation of heart PFK-2 by AMPK has a role in the
RT stimulation of glycolysis during ischaemia.";
RL Curr. Biol. 10:1247-1255(2000).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF IRS1.
RX PubMed=11598104; DOI=10.1074/jbc.c100483200;
RA Jakobsen S.N., Hardie D.G., Morrice N., Tornqvist H.E.;
RT "5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse
RT C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside.";
RL J. Biol. Chem. 276:46912-46916(2001).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF MLXIPL.
RX PubMed=11724780; DOI=10.1074/jbc.m107895200;
RA Kawaguchi T., Osatomi K., Yamashita H., Kabashima T., Uyeda K.;
RT "Mechanism for fatty acid 'sparing' effect on glucose-induced
RT transcription: regulation of carbohydrate-responsive element-binding
RT protein by AMP-activated protein kinase.";
RL J. Biol. Chem. 277:3829-3835(2002).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF PFKFB3.
RX PubMed=12065600; DOI=10.1074/jbc.m205213200;
RA Marsin A.S., Bouzin C., Bertrand L., Hue L.;
RT "The stimulation of glycolysis by hypoxia in activated monocytes is
RT mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-
RT kinase.";
RL J. Biol. Chem. 277:30778-30783(2002).
RN [11]
RP PHOSPHORYLATION AT THR-172, AND ACTIVITY REGULATION.
RX PubMed=14614828; DOI=10.1016/j.cub.2003.10.031;
RA Woods A., Johnstone S.R., Dickerson K., Leiper F.C., Fryer L.G.,
RA Neumann D., Schlattner U., Wallimann T., Carlson M., Carling D.;
RT "LKB1 is the upstream kinase in the AMP-activated protein kinase cascade.";
RL Curr. Biol. 13:2004-2008(2003).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-172.
RX PubMed=14511394; DOI=10.1186/1475-4924-2-28;
RA Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P.,
RA Alessi D.R., Hardie D.G.;
RT "Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25
RT alpha/beta are upstream kinases in the AMP-activated protein kinase
RT cascade.";
RL J. Biol. 2:28.1-28.16(2003).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF HNF4A.
RX PubMed=12740371; DOI=10.1074/jbc.m304112200;
RA Hong Y.H., Varanasi U.S., Yang W., Leff T.;
RT "AMP-activated protein kinase regulates HNF4alpha transcriptional activity
RT by inhibiting dimer formation and decreasing protein stability.";
RL J. Biol. Chem. 278:27495-27501(2003).
RN [14]
RP PHOSPHORYLATION AT THR-258 AND SER-491, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=12764152; DOI=10.1074/jbc.m303946200;
RA Woods A., Vertommen D., Neumann D., Turk R., Bayliss J., Schlattner U.,
RA Wallimann T., Carling D., Rider M.H.;
RT "Identification of phosphorylation sites in AMP-activated protein kinase
RT (AMPK) for upstream AMPK kinases and study of their roles by site-directed
RT mutagenesis.";
RL J. Biol. Chem. 278:28434-28442(2003).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF EEF2K.
RX PubMed=14709557; DOI=10.1074/jbc.m309773200;
RA Browne G.J., Finn S.G., Proud C.G.;
RT "Stimulation of the AMP-activated protein kinase leads to activation of
RT eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel
RT site, serine 398.";
RL J. Biol. Chem. 279:12220-12231(2004).
RN [16]
RP PHOSPHORYLATION AT THR-172, AND ACTIVITY REGULATION.
RX PubMed=16054095; DOI=10.1016/j.cmet.2005.05.009;
RA Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M.,
RA Frenguelli B.G., Hardie D.G.;
RT "Calmodulin-dependent protein kinase kinase-beta is an alternative upstream
RT kinase for AMP-activated protein kinase.";
RL Cell Metab. 2:9-19(2005).
RN [17]
RP PHOSPHORYLATION AT THR-172, AND ACTIVITY REGULATION.
RX PubMed=16054096; DOI=10.1016/j.cmet.2005.06.005;
RA Woods A., Dickerson K., Heath R., Hong S.-P., Momcilovic M.,
RA Johnstone S.R., Carlson M., Carling D.;
RT "Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-
RT activated protein kinase in mammalian cells.";
RL Cell Metab. 2:21-33(2005).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF SLC12A1.
RX PubMed=17341212; DOI=10.1042/bj20061850;
RA Fraser S.A., Gimenez I., Cook N., Jennings I., Katerelos M., Katsis F.,
RA Levidiotis V., Kemp B.E., Power D.A.;
RT "Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-
RT activated protein kinase (AMPK).";
RL Biochem. J. 405:85-93(2007).
RN [19]
RP PHOSPHORYLATION BY ULK1.
RX PubMed=21460634; DOI=10.4161/auto.7.7.15451;
RA Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M.,
RA Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.;
RT "Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory
RT feedback loop.";
RL Autophagy 7:696-706(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [21]
RP SUBUNIT.
RX PubMed=25687571; DOI=10.1074/mcp.m114.047159;
RA Boutchueng-Djidjou M., Collard-Simard G., Fortier S., Hebert S.S.,
RA Kelly I., Landry C.R., Faure R.L.;
RT "The last enzyme of the de novo purine synthesis pathway 5-aminoimidazole-
RT 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC)
RT plays a central role in insulin signaling and the Golgi/endosomes protein
RT network.";
RL Mol. Cell. Proteomics 14:1079-1092(2015).
CC -!- FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an
CC energy sensor protein kinase that plays a key role in regulating
CC cellular energy metabolism (PubMed:14511394). In response to reduction
CC of intracellular ATP levels, AMPK activates energy-producing pathways
CC and inhibits energy-consuming processes: inhibits protein, carbohydrate
CC and lipid biosynthesis, as well as cell growth and proliferation (By
CC similarity). AMPK acts via direct phosphorylation of metabolic enzymes,
CC and by longer-term effects via phosphorylation of transcription
CC regulators (By similarity). Regulates lipid synthesis by
CC phosphorylating and inactivating lipid metabolic enzymes such as ACACA,
CC ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol
CC synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB)
CC and hormone-sensitive lipase (LIPE) enzymes, respectively
CC (PubMed:2369897, PubMed:9029219). Promotes lipolysis of lipid droplets
CC by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (By
CC similarity). Regulates insulin-signaling and glycolysis by
CC phosphorylating IRS1, PFKFB2 and PFKFB3 (PubMed:11069105,
CC PubMed:11598104, PubMed:12065600). Involved in insulin receptor/INSR
CC internalization (By similarity). AMPK stimulates glucose uptake in
CC muscle by increasing the translocation of the glucose transporter
CC SLC2A4/GLUT4 to the plasma membrane, possibly by mediating
CC phosphorylation of TBC1D4/AS160 (By similarity). Regulates
CC transcription and chromatin structure by phosphorylating transcription
CC regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3,
CC histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53,
CC SREBF1, SREBF2 and PPARGC1A (PubMed:11724780, PubMed:12740371). Acts as
CC a key regulator of glucose homeostasis in liver by phosphorylating
CC CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By
CC similarity). In response to stress, phosphorylates 'Ser-36' of histone
CC H2B (H2BS36ph), leading to promote transcription (By similarity). Acts
CC as a key regulator of cell growth and proliferation by phosphorylating
CC FNIP1, TSC2, RPTOR, WDR24 and ATG1/ULK1: in response to nutrient
CC limitation, negatively regulates the mTORC1 complex by phosphorylating
CC RPTOR component of the mTORC1 complex and by phosphorylating and
CC activating TSC2 (By similarity). Also phosphorylates and inhibits
CC GATOR2 subunit WDR24 in response to nutrient limitation, leading to
CC suppress glucose-mediated mTORC1 activation (By similarity). In
CC response to energetic stress, phosphorylates FNIP1, inactivating the
CC non-canonical mTORC1 signaling, thereby promoting nuclear translocation
CC of TFEB and TFE3, and inducing transcription of lysosomal or autophagy
CC genes (By similarity). In response to nutrient limitation, promotes
CC autophagy by phosphorylating and activating ATG1/ULK1 (By similarity).
CC In that process also activates WDR45/WIPI4 (By similarity).
CC Phosphorylates CASP6, thereby preventing its autoprocessing and
CC subsequent activation (By similarity). AMPK also acts as a regulator of
CC circadian rhythm by mediating phosphorylation of CRY1, leading to
CC destabilize it (By similarity). May regulate the Wnt signaling pathway
CC by phosphorylating CTNNB1, leading to stabilize it (By similarity).
CC Also acts as a regulator of cellular polarity by remodeling the actin
CC cytoskeleton; probably by indirectly activating myosin (By similarity).
CC Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1
CC (PubMed:10025949, PubMed:14709557, PubMed:17341212). Plays an important
CC role in the differential regulation of pro-autophagy (composed of
CC PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed
CC of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose
CC starvation (By similarity). Can inhibit the non-autophagy complex by
CC phosphorylating PIK3C3 and can activate the pro-autophagy complex by
CC phosphorylating BECN1 (By similarity). Upon glucose starvation,
CC promotes ARF6 activation in a kinase-independent manner leading to cell
CC migration (By similarity). Upon glucose deprivation mediates the
CC phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear
CC localization signal of ACSS2, required for its interaction with KPNA1
CC and nuclear translocation (By similarity).
CC {ECO:0000250|UniProtKB:P54646, ECO:0000250|UniProtKB:Q8BRK8,
CC ECO:0000269|PubMed:10025949, ECO:0000269|PubMed:11069105,
CC ECO:0000269|PubMed:11598104, ECO:0000269|PubMed:11724780,
CC ECO:0000269|PubMed:12065600, ECO:0000269|PubMed:12740371,
CC ECO:0000269|PubMed:14511394, ECO:0000269|PubMed:14709557,
CC ECO:0000269|PubMed:17341212, ECO:0000269|PubMed:2369897,
CC ECO:0000269|PubMed:9029219}.
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:2369897, ECO:0000269|PubMed:9029219};
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:2369897,
CC ECO:0000269|PubMed:9029219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[acetyl-CoA carboxylase] = ADP + H(+) + O-
CC phospho-L-seryl-[acetyl-CoA carboxylase]; Xref=Rhea:RHEA:20333,
CC Rhea:RHEA-COMP:13722, Rhea:RHEA-COMP:13723, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:9029219};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A
CC reductase] = ADP + H(+) + O-phospho-L-seryl-[3-hydroxy-3-
CC methylglutaryl-coenzyme A reductase]; Xref=Rhea:RHEA:23172,
CC Rhea:RHEA-COMP:13692, Rhea:RHEA-COMP:13693, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421,
CC ChEBI:CHEBI:456216; EC=2.7.11.31;
CC Evidence={ECO:0000269|PubMed:2369897};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-172. Binding
CC of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3)
CC results in allosteric activation, inducing phosphorylation on Thr-172.
CC AMP-binding to gamma subunit also sustains activity by preventing
CC dephosphorylation of Thr-172. ADP also stimulates Thr-172
CC phosphorylation, without stimulating already phosphorylated AMPK. ATP
CC promotes dephosphorylation of Thr-172, rendering the enzyme inactive.
CC Under physiological conditions AMPK mainly exists in its inactive form
CC in complex with ATP, which is much more abundant than AMP. Selectively
CC inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-
CC pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a
CC natural polyphenol present in red wine, and S17834, a synthetic
CC polyphenol. Salicylate/aspirin directly activates kinase activity,
CC primarily by inhibiting Thr-172 dephosphorylation (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1
CC or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic
CC subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.
CC Associates with internalized INSR complexes on Golgi/endosomal
CC membranes; PRKAA2/AMPK2 together with ATIC and HACD3/PTPLAD1 is
CC proposed to be part of a signaling network regulating INSR
CC autophosphorylation and endocytosis (PubMed:25687571). Interacts with
CC DUSP29 (By similarity). Interacts with ARF6 (By similarity). The
CC phosphorylated form at Thr-172 mediated by CamKK2 interacts with ACSS2
CC (By similarity). {ECO:0000250|UniProtKB:P54646,
CC ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:25687571}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8BRK8}. Nucleus
CC {ECO:0000250|UniProtKB:P54646}. Note=In response to stress, recruited
CC by p53/TP53 to specific promoters. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=Q09137-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q09137-2; Sequence=VSP_004949, VSP_004950;
CC -!- TISSUE SPECIFICITY: Skeletal muscle, lower levels in liver, heart and
CC kidney.
CC -!- INDUCTION: By AMP.
CC -!- DOMAIN: The AIS (autoinhibitory sequence) region shows some sequence
CC similarity with the ubiquitin-associated domains and represses kinase
CC activity. {ECO:0000250|UniProtKB:Q13131}.
CC -!- PTM: Ubiquitinated. {ECO:0000250}.
CC -!- PTM: Phosphorylated at Thr-172 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Also
CC phosphorylated at Thr-172 by CAMKK2; triggered by a rise in
CC intracellular calcium ions, without detectable changes in the AMP/ATP
CC ratio. CAMKK1 can also phosphorylate Thr-172, but at much lower level.
CC Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C).
CC Phosphorylated by ULK1; leading to negatively regulate AMPK activity
CC and suggesting the existence of a regulatory feedback loop between ULK1
CC and AMPK. Dephosphorylated by PPM1A and PPM1B at Thr-172 (mediated by
CC STK11/LKB1) (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform Short]: Lacks the sequence parts essential for
CC kinase activity and is therefore inactive. {ECO:0000305}.
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; Z29486; CAA82620.1; -; mRNA.
DR EMBL; U12149; AAA85033.1; -; mRNA.
DR PIR; A53621; A53621.
DR RefSeq; NP_076481.1; NM_023991.1. [Q09137-1]
DR AlphaFoldDB; Q09137; -.
DR BMRB; Q09137; -.
DR SMR; Q09137; -.
DR BioGRID; 249382; 8.
DR CORUM; Q09137; -.
DR IntAct; Q09137; 1.
DR STRING; 10116.ENSRNOP00000010680; -.
DR BindingDB; Q09137; -.
DR ChEMBL; CHEMBL4637; -.
DR iPTMnet; Q09137; -.
DR PhosphoSitePlus; Q09137; -.
DR jPOST; Q09137; -.
DR PaxDb; 10116-ENSRNOP00000010680; -.
DR GeneID; 78975; -.
DR KEGG; rno:78975; -.
DR UCSC; RGD:620893; rat. [Q09137-1]
DR AGR; RGD:620893; -.
DR CTD; 5563; -.
DR RGD; 620893; Prkaa2.
DR eggNOG; KOG0583; Eukaryota.
DR InParanoid; Q09137; -.
DR OrthoDB; 5475340at2759; -.
DR PhylomeDB; Q09137; -.
DR BRENDA; 2.7.11.1; 5301.
DR BRENDA; 2.7.11.31; 5301.
DR Reactome; R-RNO-1632852; Macroautophagy.
DR Reactome; R-RNO-163680; AMPK inhibits chREBP transcriptional activation activity.
DR Reactome; R-RNO-200425; Carnitine metabolism.
DR Reactome; R-RNO-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-RNO-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-RNO-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-RNO-9759194; Nuclear events mediated by NFE2L2.
DR SABIO-RK; Q09137; -.
DR PRO; PR:Q09137; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0030424; C:axon; IMP:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IMP:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IMP:ARUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0050405; F:[acetyl-CoA carboxylase] kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0047322; F:[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004679; F:AMP-activated protein kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0140823; F:histone H2BS36 kinase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:RGD.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:RGD.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:ARUK-UCL.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:ARUK-UCL.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR GO; GO:0071417; P:cellular response to organonitrogen compound; IEP:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISO:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0097009; P:energy homeostasis; IDA:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0055089; P:fatty acid homeostasis; IDA:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:1905691; P:lipid droplet disassembly; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:1903944; P:negative regulation of hepatocyte apoptotic process; ISO:RGD.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:1904262; P:negative regulation of TORC1 signaling; ISS:UniProtKB.
DR GO; GO:1904428; P:negative regulation of tubulin deacetylation; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IDA:UniProtKB.
DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; ISO:RGD.
DR GO; GO:1903829; P:positive regulation of protein localization; ISO:RGD.
DR GO; GO:1990044; P:protein localization to lipid droplet; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IDA:RGD.
DR GO; GO:0016241; P:regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0062028; P:regulation of stress granule assembly; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IDA:RGD.
DR GO; GO:0031000; P:response to caffeine; IDA:RGD.
DR GO; GO:0014850; P:response to muscle activity; ISO:RGD.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd12200; AMPKA2_C; 1.
DR CDD; cd14079; STKc_AMPK_alpha; 1.
DR CDD; cd14404; UBA_AID_AAPK2; 1.
DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR Gene3D; 3.30.310.80; Kinase associated domain 1, KA1; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR032270; AMPK_C.
DR InterPro; IPR039148; AMPKA2_C.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR049020; PRKAA1/2_AID.
DR InterPro; IPR028783; PRKAA2.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1.
DR PANTHER; PTHR24346:SF82; SERINE_THREONINE-PROTEIN KINASE MARK-A-RELATED; 1.
DR Pfam; PF16579; AdenylateSensor; 1.
DR Pfam; PF21147; AMPK_alpha_AID; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF103243; KA1-like; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 Alternative splicing; ATP-binding; Autophagy; Biological rhythms;
KW Cholesterol biosynthesis; Cholesterol metabolism; Chromatin regulator;
KW Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis;
KW Fatty acid metabolism; Kinase; Lipid biosynthesis; Lipid metabolism;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation;
KW Wnt signaling pathway.
FT CHAIN 1..552
FT /note="5'-AMP-activated protein kinase catalytic subunit
FT alpha-2"
FT /id="PRO_0000085597"
FT DOMAIN 16..268
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 291..376
FT /note="AIS"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT REGION 478..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..520
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 139
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 22..30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 45
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 172
FT /note="Phosphothreonine; by LKB1 and CaMKK2"
FT /evidence="ECO:0000269|PubMed:14511394,
FT ECO:0000269|PubMed:14614828, ECO:0000269|PubMed:16054095,
FT ECO:0000269|PubMed:16054096, ECO:0000269|PubMed:8910387"
FT MOD_RES 258
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12764152"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12764152"
FT VAR_SEQ 32..388
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7908907"
FT /id="VSP_004949"
FT VAR_SEQ 392..552
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:7908907"
FT /id="VSP_004950"
FT CONFLICT 355
FT /note="M -> S (in Ref. 2; AAA85033)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="N -> D (in Ref. 2; AAA85033)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 552 AA; 62258 MW; 2829E07F674D89B1 CRC64;
MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ KIRSLDVVGK
IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE LFDYICKHGR VEEVEARRLF
QQILSAVDYC HRHMVVHRDL KPENVLLDAQ MNAKIADFGL SNMMSDGEFL RTSCGSPNYA
APEVISGRLY AGPEVDIWSC GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPEYLNRS
IATLLMHMLQ VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF
ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPTGS FMDDMAMHIP
PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA KWHLGIRSQS KPYDIMAEVY
RAMKQLDFEW KVVNAYHLRV RRKNPVTGNY VKMSLQLYLV DNRSYLLDFK SIDDEVVEQR
SGSSTPQRSC SAAGLHRPRS SVDSSTAENH SLSGSLTGSL TGSTLSSASP RLGSHTMDFF
EMCASLITAL AR
//
