AAPK1_RAT
ID AAPK1_RAT Reviewed; 559 AA.
AC P54645;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-1;
DE Short=AMPK subunit alpha-1;
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 EC=2.7.11.27 {ECO:0000269|PubMed:9029219};
DE AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase;
DE Short=HMGCR kinase;
DE EC=2.7.11.31 {ECO:0000269|PubMed:2369897};
DE AltName: Full=Tau-protein kinase PRKAA1;
DE EC=2.7.11.26 {ECO:0000305|PubMed:21204788};
GN Name=Prkaa1; Synonyms=Ampk1;
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 [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-559, AND PROTEIN SEQUENCE OF 24-40;
RP 90-115; 129-140; 150-160; 166-182; 236-257; 272-276; 286-305; 326-341;
RP 350-367; 375-384; 409-426; 437-446; 458-475 AND 507-517.
RC STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Liver;
RX PubMed=8557660; DOI=10.1074/jbc.271.2.611;
RA Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T.,
RA House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.;
RT "Mammalian AMP-activated protein kinase subfamily.";
RL J. Biol. Chem. 271:611-614(1996).
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 IDENTIFICATION IN THE AMPK COMPLEX.
RC STRAIN=Sprague-Dawley; TISSUE=Hypothalamus, and Liver;
RX PubMed=7961907; DOI=10.1016/s0021-9258(18)43879-3;
RA Stapleton D., Gao G., Michell B.J., Widmer J., Mitchelhill K.I., Teh T.,
RA House C.M., Witters L.A., Kemp B.E.;
RT "Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are
RT homologs of proteins that interact with yeast Snf1 protein kinase.";
RL J. Biol. Chem. 269:29343-29346(1994).
RN [5]
RP PHOSPHORYLATION AT THR-183, 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 [6]
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 [7]
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
RP PHOSPHORYLATION AT THR-183, 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 [13]
RP FUNCTION, ACTIVITY REGULATION, AND PHOSPHORYLATION AT THR-183.
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 [14]
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 [15]
RP PHOSPHORYLATION AT THR-269 AND SER-496, MUTAGENESIS OF THR-183; THR-269 AND
RP SER-496, AND IDENTIFICATION BY MASS 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 [16]
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 [17]
RP PHOSPHORYLATION AT THR-183, 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 [18]
RP PHOSPHORYLATION AT THR-183, 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 [19]
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 [20]
RP PHOSPHORYLATION BY ULK1 AND ULK, AND PHOSPHORYLATION AT SER-360; THR-368;
RP SER-397; SER-486 AND THR-488.
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 [21]
RP FUNCTION IN PHOSPHORYLATION OF MAPT.
RX PubMed=21204788; DOI=10.1042/bj20101485;
RA Thornton C., Bright N.J., Sastre M., Muckett P.J., Carling D.;
RT "AMP-activated protein kinase (AMPK) is a tau kinase, activated in response
RT to amyloid beta-peptide exposure.";
RL Biochem. J. 434:503-512(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486; THR-490 AND SER-496, AND
RP IDENTIFICATION BY 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 [23]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 405-557 IN COMPLEX WITH PRKAB2 AND
RP PRKAG1.
RX PubMed=17851531; DOI=10.1038/nature06161;
RA Xiao B., Heath R., Saiu P., Leiper F.C., Leone P., Jing C., Walker P.A.,
RA Haire L., Eccleston J.F., Davis C.T., Martin S.R., Carling D.,
RA Gamblin S.J.;
RT "Structural basis for AMP binding to mammalian AMP-activated protein
RT kinase.";
RL Nature 449:496-500(2007).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 13-559 IN COMPLEX WITH PRKAB2 AND
RP PRKAG1, AND MUTAGENESIS OF 386-ARG--GLU-391.
RX PubMed=21399626; DOI=10.1038/nature09932;
RA Xiao B., Sanders M.J., Underwood E., Heath R., Mayer F.V., Carmena D.,
RA Jing C., Walker P.A., Eccleston J.F., Haire L.F., Saiu P., Howell S.A.,
RA Aasland R., Martin S.R., Carling D., Gamblin S.J.;
RT "Structure of mammalian AMPK and its regulation by ADP.";
RL Nature 472:230-233(2011).
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:11598104,
CC PubMed:11069105, PubMed:12065600). 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:12740371, PubMed:11724780). 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 TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation,
CC negatively regulates the mTORC1 complex by phosphorylating RPTOR
CC component of the mTORC1 complex and by phosphorylating and activating
CC TSC2 (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. Phosphorylates CASP6,
CC thereby preventing its autoprocessing and subsequent activation (By
CC similarity). In response to nutrient limitation, phosphorylates
CC transcription factor FOXO3 promoting FOXO3 mitochondrial import (By
CC similarity). Also acts as a regulator of cellular polarity by
CC remodeling the actin cytoskeleton; probably by indirectly activating
CC myosin (By similarity). AMPK also acts as a regulator of circadian
CC rhythm by mediating phosphorylation of CRY1, leading to destabilize it
CC (By similarity). May regulate the Wnt signaling pathway by
CC phosphorylating CTNNB1, leading to stabilize it (By similarity). Also
CC has tau-protein kinase activity: in response to amyloid beta A4 protein
CC (APP) exposure, activated by CAMKK2, leading to phosphorylation of
CC MAPT/TAU; however the relevance of such data remains unclear in vivo
CC (PubMed:21204788). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and
CC SLC12A1 (PubMed:10025949, PubMed:17341212, PubMed:14709557).
CC {ECO:0000250|UniProtKB:Q13131, ECO:0000250|UniProtKB:Q5EG47,
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:21204788,
CC ECO:0000269|PubMed:2369897, 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; EC=2.7.11.27;
CC 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 -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC Evidence={ECO:0000305|PubMed:21204788};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26; Evidence={ECO:0000305|PubMed:21204788};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on Thr-183. Binding
CC of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3)
CC results in allosteric activation, inducing phosphorylation on Thr-183.
CC AMP-binding to gamma subunit also sustains activity by preventing
CC dephosphorylation of Thr-183. ADP also stimulates Thr-183
CC phosphorylation, without stimulating already phosphorylated AMPK. ATP
CC promotes dephosphorylation of Thr-183, 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. {ECO:0000269|PubMed:14511394, ECO:0000269|PubMed:14614828,
CC ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:16054096,
CC ECO:0000269|PubMed:8910387}.
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) (PubMed:17851531, PubMed:21399626,
CC PubMed:7961907). Interacts with FNIP1 and FNIP2 (By similarity).
CC {ECO:0000250|UniProtKB:Q13131, ECO:0000269|PubMed:17851531,
CC ECO:0000269|PubMed:21399626, ECO:0000269|PubMed:7961907}.
CC -!- INTERACTION:
CC P54645; Q76JQ2: Flcn; NbExp=2; IntAct=EBI-7596967, EBI-7596839;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13131}. Nucleus
CC {ECO:0000250|UniProtKB:Q13131}. Note=In response to stress, recruited
CC by p53/TP53 to specific promoters. {ECO:0000250|UniProtKB:Q13131}.
CC -!- TISSUE SPECIFICITY: Low expression in kidney, liver, lung, heart and
CC brain.
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|UniProtKB:Q5EG47}.
CC -!- PTM: Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-
CC related adapter-alpha (STRADA) pseudo kinase and CAB39. Also
CC phosphorylated at Thr-183 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-183, but at a much lower
CC level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and
CC PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate
CC AMPK activity and suggesting the existence of a regulatory feedback
CC loop between ULK1, ULK2 and AMPK. There is some ambiguity for some
CC phosphosites: Ser-360/Thr-368 and Ser-486/Thr-488. Dephosphorylated by
CC PPM1A and PPM1B (By similarity). {ECO:0000250|UniProtKB:Q13131}.
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; CH474048; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U40819; AAC52355.1; -; mRNA.
DR RefSeq; NP_062015.2; NM_019142.2.
DR PDB; 2V8Q; X-ray; 2.10 A; A=407-559.
DR PDB; 2V92; X-ray; 2.40 A; A=407-559.
DR PDB; 2V9J; X-ray; 2.53 A; A=407-559.
DR PDB; 2Y8L; X-ray; 2.50 A; A=407-555.
DR PDB; 2Y8Q; X-ray; 2.80 A; A=407-555.
DR PDB; 2YA3; X-ray; 2.51 A; A=407-555.
DR PDB; 4CFH; X-ray; 3.24 A; A=13-481, C=535-559.
DR PDB; 4EAI; X-ray; 2.28 A; A=405-479, A=540-559.
DR PDB; 4EAJ; X-ray; 2.61 A; A=405-479, A=540-559.
DR PDB; 4EAK; X-ray; 2.50 A; A=405-479, A=540-559.
DR PDB; 4EAL; X-ray; 2.51 A; A=405-479, A=540-559.
DR PDB; 4F2L; X-ray; 1.50 A; A=295-347.
DR PDB; 4QFG; X-ray; 3.46 A; A=11-480, A=536-559.
DR PDB; 4QFR; X-ray; 3.34 A; A=11-480, A=536-559.
DR PDB; 4QFS; X-ray; 3.55 A; A=11-479, A=536-559.
DR PDB; 5KQ5; X-ray; 3.41 A; A=11-480, A=536-559.
DR PDB; 5T5T; X-ray; 3.46 A; A=11-480, A=536-559.
DR PDB; 5UFU; X-ray; 3.45 A; A=269-559.
DR PDB; 6E4T; X-ray; 3.40 A; A=11-480, A=536-559.
DR PDB; 6E4U; X-ray; 3.27 A; A=11-480, A=536-559.
DR PDB; 6E4W; X-ray; 3.35 A; A=11-480, A=536-559.
DR PDBsum; 2V8Q; -.
DR PDBsum; 2V92; -.
DR PDBsum; 2V9J; -.
DR PDBsum; 2Y8L; -.
DR PDBsum; 2Y8Q; -.
DR PDBsum; 2YA3; -.
DR PDBsum; 4CFH; -.
DR PDBsum; 4EAI; -.
DR PDBsum; 4EAJ; -.
DR PDBsum; 4EAK; -.
DR PDBsum; 4EAL; -.
DR PDBsum; 4F2L; -.
DR PDBsum; 4QFG; -.
DR PDBsum; 4QFR; -.
DR PDBsum; 4QFS; -.
DR PDBsum; 5KQ5; -.
DR PDBsum; 5T5T; -.
DR PDBsum; 5UFU; -.
DR PDBsum; 6E4T; -.
DR PDBsum; 6E4U; -.
DR PDBsum; 6E4W; -.
DR AlphaFoldDB; P54645; -.
DR SMR; P54645; -.
DR BioGRID; 249325; 368.
DR CORUM; P54645; -.
DR DIP; DIP-57168N; -.
DR IntAct; P54645; 317.
DR MINT; P54645; -.
DR STRING; 10116.ENSRNOP00000017626; -.
DR BindingDB; P54645; -.
DR ChEMBL; CHEMBL4533; -.
DR iPTMnet; P54645; -.
DR PhosphoSitePlus; P54645; -.
DR jPOST; P54645; -.
DR PaxDb; P54645; -.
DR PRIDE; P54645; -.
DR Ensembl; ENSRNOT00000017626; ENSRNOP00000017626; ENSRNOG00000012799.
DR GeneID; 65248; -.
DR KEGG; rno:65248; -.
DR CTD; 5562; -.
DR RGD; 3387; Prkaa1.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00940000158865; -.
DR HOGENOM; CLU_000288_59_3_1; -.
DR InParanoid; P54645; -.
DR OMA; HHFTRPH; -.
DR OrthoDB; 1127668at2759; -.
DR PhylomeDB; P54645; -.
DR TreeFam; TF314032; -.
DR BRENDA; 2.7.11.1; 5301.
DR BRENDA; 2.7.11.31; 5301.
DR Reactome; R-RNO-1632852; Macroautophagy.
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 SABIO-RK; P54645; -.
DR EvolutionaryTrace; P54645; -.
DR PRO; PR:P54645; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Proteomes; UP000234681; Chromosome 2.
DR Bgee; ENSRNOG00000012799; Expressed in ileum and 20 other tissues.
DR Genevisible; P54645; RN.
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:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IMP:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IMP:ARUK-UCL.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0031588; C:nucleotide-activated protein kinase complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA: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:0042557; F:eukaryotic elongation factor-2 kinase activator activity; NAS:UniProtKB.
DR GO; GO:0035174; F:histone serine kinase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO: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:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015721; P:bile acid and bile salt transport; IEP:RGD.
DR GO; GO:0038183; P:bile acid signaling pathway; IEP:RGD.
DR GO; GO:0061762; P:CAMKK-AMPK signaling cascade; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; IMP:ARUK-UCL.
DR GO; GO:0071361; P:cellular response to ethanol; IEP:RGD.
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:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
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; IEP:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0009631; P:cold acclimation; IDA:RGD.
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:0019395; P:fatty acid oxidation; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; ISO:RGD.
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:0061744; P:motor behavior; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:RGD.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0017148; P:negative regulation of translation; NAS:UniProtKB.
DR GO; GO:1904428; P:negative regulation of tubulin deacetylation; ISO:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISO:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; NAS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; NAS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; NAS:UniProtKB.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IDA:UniProtKB.
DR GO; GO:1903109; P:positive regulation of mitochondrial transcription; ISO:RGD.
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:1903955; P:positive regulation of protein targeting to mitochondrion; ISO:RGD.
DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; ISO:RGD.
DR GO; GO:1990044; P:protein localization to lipid droplet; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0120188; P:regulation of bile acid secretion; IEP:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IEP:RGD.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0062028; P:regulation of stress granule assembly; ISO:RGD.
DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IMP:RGD.
DR GO; GO:1904486; P:response to 17alpha-ethynylestradiol; IEP:RGD.
DR GO; GO:0014823; P:response to activity; IDA:RGD.
DR GO; GO:0031000; P:response to caffeine; IDA:RGD.
DR GO; GO:1901563; P:response to camptothecin; ISO:RGD.
DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0009411; P:response to UV; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd12199; AMPKA1_C; 1.
DR CDD; cd14403; UBA_AID_AAPK1; 1.
DR InterPro; IPR032270; AMPK_C.
DR InterPro; IPR039137; AMPKA1_C.
DR InterPro; IPR028375; KA1/Ssp2_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028797; PRKAA1_UBA.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF16579; AdenylateSensor; 1.
DR Pfam; PF00069; Pkinase; 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; 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..559
FT /note="5'-AMP-activated protein kinase catalytic subunit
FT alpha-1"
FT /id="PRO_0000085593"
FT DOMAIN 27..279
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 302..381
FT /note="AIS"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT REGION 484..536
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..531
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 33..41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 32
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 183
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 269
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:12764152"
FT MOD_RES 355
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 356
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 360
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000305|PubMed:21460634"
FT MOD_RES 368
FT /note="Phosphothreonine; by ULK1"
FT /evidence="ECO:0000305|PubMed:21460634"
FT MOD_RES 382
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 397
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000269|PubMed:21460634"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 486
FT /note="Phosphoserine; by ULK1"
FT /evidence="ECO:0000305|PubMed:21460634,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 488
FT /note="Phosphothreonine; by ULK1"
FT /evidence="ECO:0000305|PubMed:21460634"
FT MOD_RES 490
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12764152,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 524
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13131"
FT MUTAGEN 183
FT /note="T->E: Hinders activation."
FT /evidence="ECO:0000269|PubMed:12764152"
FT MUTAGEN 269
FT /note="T->A: Hinders activation."
FT /evidence="ECO:0000269|PubMed:12764152"
FT MUTAGEN 269
FT /note="T->D: Retains activation ability."
FT /evidence="ECO:0000269|PubMed:12764152"
FT MUTAGEN 386..391
FT /note="RHTLDE->AHALAA: Allosterically activated by AMP but
FT is not protected against dephosphorylation by AMP or ADP."
FT /evidence="ECO:0000269|PubMed:21399626"
FT MUTAGEN 496
FT /note="S->A: Hinders activation."
FT /evidence="ECO:0000269|PubMed:12764152"
FT MUTAGEN 496
FT /note="S->D: Retains activation ability."
FT /evidence="ECO:0000269|PubMed:12764152"
FT CONFLICT 13..14
FT /note="Missing (in Ref. 2; AAC52355)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="D -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 27..34
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 41..46
FT /evidence="ECO:0007829|PDB:4CFH"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 52..59
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:4CFH"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:5UFU"
FT TURN 112..117
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 124..143
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:4QFG"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:6E4U"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 193..196
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 204..220
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 230..238
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 250..259
FT /evidence="ECO:0007829|PDB:4CFH"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 270..274
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:4F2L"
FT HELIX 315..323
FT /evidence="ECO:0007829|PDB:4F2L"
FT HELIX 330..347
FT /evidence="ECO:0007829|PDB:4F2L"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:4CFH"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:4CFH"
FT STRAND 407..413
FT /evidence="ECO:0007829|PDB:2V8Q"
FT HELIX 417..430
FT /evidence="ECO:0007829|PDB:2V8Q"
FT STRAND 434..439
FT /evidence="ECO:0007829|PDB:2V8Q"
FT STRAND 442..448
FT /evidence="ECO:0007829|PDB:2V8Q"
FT TURN 450..452
FT /evidence="ECO:0007829|PDB:2V8Q"
FT STRAND 455..464
FT /evidence="ECO:0007829|PDB:2V8Q"
FT STRAND 466..468
FT /evidence="ECO:0007829|PDB:2V8Q"
FT STRAND 470..477
FT /evidence="ECO:0007829|PDB:2V8Q"
FT HELIX 542..555
FT /evidence="ECO:0007829|PDB:2V8Q"
SQ SEQUENCE 559 AA; 63973 MW; A869C340A85785ED CRC64;
MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR
QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG
RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF
LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG
IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID
DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS
FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI
MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTFSKMSL QLYQVDSRTY LLDFRSIDDE
ITEAKSGTAT PQRSGSISNY RSCQRSDSDA EAQGKPSEVS LTSSVTSLDS SPVDVAPRPG
SHTIEFFEMC ANLIKILAQ
