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 27-MAR-2024, entry version 212. 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 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 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. 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). Regulates CC hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory CC element-binding protein (SREBP) transcriptional activities and ATP- CC consuming lipogenesis to restore cellular energy balance. 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; 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 -!- PTM: Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated CC protein kinase (AMPK) activity. {ECO:0000250|UniProtKB:Q13131}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. SNF1 subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10116-ENSRNOP00000017626; -. DR Ensembl; ENSRNOT00000017626.6; ENSRNOP00000017626.3; ENSRNOG00000012799.6. DR Ensembl; ENSRNOT00055010340; ENSRNOP00055008022; ENSRNOG00055006356. DR Ensembl; ENSRNOT00060024468; ENSRNOP00060019521; ENSRNOG00060014285. DR Ensembl; ENSRNOT00065037009; ENSRNOP00065029820; ENSRNOG00065021742. DR GeneID; 65248; -. DR KEGG; rno:65248; -. DR AGR; RGD:3387; -. 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; 5475340at2759; -. 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 cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0030424; C:axon; IMP:ARUK-UCL. DR GO; GO:0000785; C:chromatin; ISO:RGD. 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; ISS:UniProtKB. 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: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; 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: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:1904262; P:negative regulation of TORC1 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:1904179; P:positive regulation of adipose tissue development; 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:0045893; P:positive regulation of DNA-templated transcription; ISO: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; NAS:UniProtKB. 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: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:0014823; P:response to activity; IDA:RGD. DR GO; GO:0031000; P:response to caffeine; IDA:RGD. DR GO; GO:0043627; P:response to estrogen; IEP: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; cd14079; STKc_AMPK_alpha; 1. DR CDD; cd14403; UBA_AID_AAPK1; 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; IPR039137; AMPKA1_C. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR049020; PRKAA1/2_AID. 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 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. DR Genevisible; P54645; RN. 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; Glycoprotein; Kinase; Lipid biosynthesis; KW Lipid metabolism; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; KW Sterol metabolism; Transcription; Transcription regulation; Transferase; KW Ubl conjugation; 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 //