P54645 (AAPK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
5'-AMP-activated protein kinase catalytic subunit alpha-1
Short name=AMPK subunit alpha-1
EC=2.7.11.1

Alternative name(s):
Acetyl-CoA carboxylase kinase
Short name=ACACA kinase
EC=2.7.11.27
Hydroxymethylglutaryl-CoA reductase kinase
Short name=HMGCR kinase
EC=2.7.11.31
Tau-protein kinase PRKAA1
EC=2.7.11.26

Gene names

Name:	Prkaa1
Synonyms:	Ampk1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.16 Ref.19 Ref.21
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.3 Ref.6 ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.3 Ref.6 ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate. Ref.3 Ref.6 ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate. Ref.3 Ref.6
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Ref.5 Ref.12 Ref.13 Ref.17 Ref.18
Subunit structure	AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2. Ref.4
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. Note: In response to stress, recruited by p53/TP53 to specific promoters By similarity.
Tissue specificity	Low expression in kidney, liver, lung, heart and brain.
Domain	The AIS (autoinhibitory sequence) region some sequence similarity with the ubiquitin-associated domains and represses kinase activity By similarity.
Post-translational modification	Ubiquitinated By similarity. Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. There is some ambiguity for some phosphosites: Ser-360/Thr-368 and Ser-486/Thr-488. Ref.5 Ref.12 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Autophagy Biological rhythms Cholesterol biosynthesis Cholesterol metabolism Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism Transcription Transcription regulation Wnt signaling pathway
Cellular component	Cytoplasm Nucleus
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Chromatin regulator Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW autophagy Inferred from electronic annotation. Source: UniProtKB-KW cellular response to ethanol Inferred from expression pattern PubMed 20164678. Source: RGD cellular response to glucose starvation Inferred from sequence or structural similarity. Source: UniProtKB cellular response to hydrogen peroxide Inferred from expression pattern PubMed 18081811. Source: RGD cellular response to hypoxia Inferred from expression pattern PubMed 17720864. Source: RGD cellular response to organic nitrogen Inferred from expression pattern PubMed 19236843. Source: RGD cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW cold acclimation Inferred from direct assay PubMed 21945600. Source: RGD fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW fatty acid homeostasis Inferred from direct assay Ref.10. Source: UniProtKB fatty acid oxidation Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB glucose metabolic process Inferred from electronic annotation. Source: Compara lipid biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of TOR signaling cascade Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of glucose import in response to insulin stimulus Inferred from mutant phenotype PubMed 20501641. Source: RGD negative regulation of lipid catabolic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of translation Non-traceable author statement PubMed 12194824. Source: UniProtKB positive regulation of autophagy Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell proliferation Inferred from direct assay PubMed 17720864. Source: RGD positive regulation of fatty acid oxidation Non-traceable author statement PubMed 11997383. Source: UniProtKB positive regulation of gluconeogenesis Non-traceable author statement PubMed 11903059. Source: UniProtKB positive regulation of glucose import Non-traceable author statement PubMed 11903059. Source: UniProtKB positive regulation of glycolysis Inferred from direct assay Ref.8. Source: UniProtKB protein heterooligomerization Inferred from direct assay Ref.13. Source: RGD regulation of circadian rhythm Inferred from sequence or structural similarity. Source: UniProtKB regulation of energy homeostasis Inferred from direct assay Ref.10. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW regulation of vesicle-mediated transport Inferred from mutant phenotype PubMed 19139597. Source: RGD response to activity Inferred from direct assay PubMed 17253964. Source: RGD response to caffeine Inferred from direct assay PubMed 19608206. Source: RGD rhythmic process Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	AMP-activated protein kinase complex Inferred from direct assay Ref.22Ref.23. Source: UniProtKB apical plasma membrane Inferred from direct assay PubMed 18256313. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 18256313. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	AMP-activated protein kinase activity Inferred from direct assay Ref.8Ref.10Ref.23. Source: UniProtKB ATP binding Inferred from direct assay PubMed 16648175. Source: RGD [acetyl-CoA carboxylase] kinase activity Inferred from electronic annotation. Source: EC [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity Inferred from electronic annotation. Source: EC chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB eukaryotic elongation factor-2 kinase activator activity Non-traceable author statement PubMed 12194824. Source: UniProtKB histone serine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tau-protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 559

559

5'-AMP-activated protein kinase catalytic subunit alpha-1

PRO_0000085593

Regions

Domain

27 – 279

253

Protein kinase

Nucleotide binding

33 – 41

9

ATP By similarity

Region

302 – 381

80

AIS By similarity

Sites

Active site

150

1

Proton acceptor By similarity

Binding site

56

1

ATP By similarity

Amino acid modifications

Modified residue

32

1

Phosphothreonine By similarity

Modified residue

183

1

Phosphothreonine; by LKB1 and CaMKK2 Ref.5 Ref.12 Ref.13 Ref.17 Ref.18

Modified residue

184

1

Phosphoserine By similarity

Modified residue

269

1

Phosphothreonine Ref.15

Modified residue

356

1

Phosphoserine By similarity

Modified residue

360

1

Phosphoserine; by ULK1 Probable

Modified residue

368

1

Phosphothreonine; by ULK1 Probable

Modified residue

382

1

Phosphothreonine By similarity

Modified residue

397

1

Phosphoserine; by ULK1 Ref.20

Modified residue

467

1

Phosphoserine By similarity

Modified residue

486

1

Phosphoserine; by ULK1 Probable

Modified residue

488

1

Phosphothreonine; by ULK1 Probable

Modified residue

490

1

Phosphothreonine By similarity

Modified residue

496

1

Phosphoserine Ref.15

Modified residue

508

1

Phosphoserine By similarity

Experimental info

Mutagenesis

183

1

T → E: Hinders activation. Ref.15

Mutagenesis

269

1

T → A: Hinders activation. Ref.15

Mutagenesis

269

1

T → D: Retains activation ability. Ref.15

Mutagenesis

386 – 391

6

RHTLDE → AHALAA: Allosterically activated by AMP but is not protected against dephosphorylation by AMP or ADP. Ref.23

Mutagenesis

496

1

S → A: Hinders activation. Ref.15

Mutagenesis

496

1

S → D: Retains activation ability. Ref.15

Sequence conflict

13 – 14

2

Missing in AAC52355. Ref.2

Sequence conflict

473

1

D → L AA sequence Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

559

Helix Strand Turn

Details...

Beta strand

407 – 413

7

Helix

417 – 430

14

Beta strand

434 – 439

6

Beta strand

442 – 448

7

Turn

450 – 452

3

Beta strand

455 – 464

10

Beta strand

466 – 468

3

Beta strand

470 – 477

8

Helix

542 – 555

14

Sequences

	Sequence		Length	Mass (Da)
	P54645 [UniParc]. Last modified July 28, 2009. Version 2. Checksum: A869C340A85785ED	FASTA	559	63,973
	10 20 30 40 50 60 MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR 70 80 90 100 110 120 QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG 130 140 150 160 170 180 RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF 190 200 210 220 230 240 LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG 250 260 270 280 290 300 IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID 310 320 330 340 350 360 DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS 370 380 390 400 410 420 FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI 430 440 450 460 470 480 MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTFSKMSL QLYQVDSRTY LLDFRSIDDE 490 500 510 520 530 540 ITEAKSGTAT PQRSGSISNY RSCQRSDSDA EAQGKPSEVS LTSSVTSLDS SPVDVAPRPG 550 SHTIEFFEMC ANLIKILAQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"Mammalian AMP-activated protein kinase subfamily." Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E. J. Biol. Chem. 271:611-614(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 10-559, PROTEIN SEQUENCE OF 24-40; 90-115; 129-140; 150-160; 166-182; 236-257; 272-276; 286-305; 326-341; 350-367; 375-384; 409-426; 437-446; 458-475 AND 507-517. Strain: Sprague-Dawley. Tissue: Hypothalamus and Liver.
[3]	"Regulation of HMG-CoA reductase: identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver." Clarke P.R., Hardie D.G. EMBO J. 9:2439-2446(1990) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF HMGCR.
[4]	"Mammalian 5'-AMP-activated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase." Stapleton D., Gao G., Michell B.J., Widmer J., Mitchelhill K.I., Teh T., House C.M., Witters L.A., Kemp B.E. J. Biol. Chem. 269:29343-29346(1994) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE AMPK COMPLEX. Strain: Sprague-Dawley. Tissue: Hypothalamus and Liver.
[5]	"Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase." Hawley S.A., Davison M., Woods A., Davies S.P., Beri R.K., Carling D., Hardie D.G. J. Biol. Chem. 271:27879-27887(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[6]	"Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A." Winder W.W., Wilson H.A., Hardie D.G., Rasmussen B.B., Hutber C.A., Call G.B., Clayton R.D., Conley L.M., Yoon S., Zhou B. J. Appl. Physiol. 82:219-225(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION IN PHOSPHORYLATION OF ACACA AND ACACB.
[7]	"AMP-activated protein kinase phosphorylation of endothelial NO synthase." Chen Z.P., Mitchelhill K.I., Michell B.J., Stapleton D., Rodriguez-Crespo I., Witters L.A., Power D.A., Ortiz de Montellano P.R., Kemp B.E. FEBS Lett. 443:285-289(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF NOS3.
[8]	"Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia." Marsin A.S., Bertrand L., Rider M.H., Deprez J., Beauloye C., Vincent M.F., Van den Berghe G., Carling D., Hue L. Curr. Biol. 10:1247-1255(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PFKFB2.
[9]	"5'-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside." Jakobsen S.N., Hardie D.G., Morrice N., Tornqvist H.E. J. Biol. Chem. 276:46912-46916(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF IRS1.
[10]	"Mechanism for fatty acid 'sparing' effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase." Kawaguchi T., Osatomi K., Yamashita H., Kabashima T., Uyeda K. J. Biol. Chem. 277:3829-3835(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MLXIPL.
[11]	"The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase." Marsin A.S., Bouzin C., Bertrand L., Hue L. J. Biol. Chem. 277:30778-30783(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PFKFB3.
[12]	"LKB1 is the upstream kinase in the AMP-activated protein kinase cascade." Woods A., Johnstone S.R., Dickerson K., Leiper F.C., Fryer L.G., Neumann D., Schlattner U., Wallimann T., Carlson M., Carling D. Curr. Biol. 13:2004-2008(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[13]	"Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade." Hawley S.A., Boudeau J., Reid J.L., Mustard K.J., Udd L., Makela T.P., Alessi D.R., Hardie D.G. J. Biol. 2:28.1-28.16(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-183.
[14]	"AMP-activated protein kinase regulates HNF4alpha transcriptional activity by inhibiting dimer formation and decreasing protein stability." Hong Y.H., Varanasi U.S., Yang W., Leff T. J. Biol. Chem. 278:27495-27501(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF HNF4A.
[15]	"Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis." Woods A., Vertommen D., Neumann D., Turk R., Bayliss J., Schlattner U., Wallimann T., Carling D., Rider M.H. J. Biol. Chem. 278:28434-28442(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-269 AND SER-496, MUTAGENESIS OF THR-183; THR-269 AND SER-496, MASS SPECTROMETRY.
[16]	"Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398." Browne G.J., Finn S.G., Proud C.G. J. Biol. Chem. 279:12220-12231(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF EEF2K.
[17]	"Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase." Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., Hardie D.G. Cell Metab. 2:9-19(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[18]	"Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells." Woods A., Dickerson K., Heath R., Hong S.-P., Momcilovic M., Johnstone S.R., Carlson M., Carling D. Cell Metab. 2:21-33(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-183, ENZYME REGULATION.
[19]	"Regulation of the renal-specific Na+-K+-2Cl- co-transporter NKCC2 by AMP-activated protein kinase (AMPK)." Fraser S.A., Gimenez I., Cook N., Jennings I., Katerelos M., Katsis F., Levidiotis V., Kemp B.E., Power D.A. Biochem. J. 405:85-93(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF SLC12A1.
[20]	"Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop." Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B. Autophagy 7:696-706(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY ULK1 AND ULK, PHOSPHORYLATION AT SER-360; THR-368; SER-397; SER-486 AND THR-488.
[21]	"AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid beta-peptide exposure." Thornton C., Bright N.J., Sastre M., Muckett P.J., Carling D. Biochem. J. 434:503-512(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MAPT.
[22]	"Structural basis for AMP binding to mammalian AMP-activated protein kinase." Xiao B., Heath R., Saiu P., Leiper F.C., Leone P., Jing C., Walker P.A., Haire L., Eccleston J.F., Davis C.T., Martin S.R., Carling D., Gamblin S.J. Nature 449:496-500(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 405-557 IN COMPLEX WITH PRKAB2 AND PRKAG1.
[23]	"Structure of mammalian AMPK and its regulation by ADP." Xiao B., Sanders M.J., Underwood E., Heath R., Mayer F.V., Carmena D., Jing C., Walker P.A., Eccleston J.F., Haire L.F., Saiu P., Howell S.A., Aasland R., Martin S.R., Carling D., Gamblin S.J. Nature 472:230-233(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 13-559 IN COMPLEX WITH PRKAB2 AND PRKAG1, MUTAGENESIS OF 386-ARG--GLU-391.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

CH474048 Genomic DNA. No translation available.
U40819 mRNA. Translation: AAC52355.1.

IPI

IPI00215402.

RefSeq

NP_062015.1. NM_019142.1.

UniGene

Rn.87789.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V8Q	X-ray	2.10	A	407-559	[»]
2V92	X-ray	2.40	A	407-559	[»]
2V9J	X-ray	2.53	A	407-559	[»]
2Y8L	X-ray	2.50	A	407-555	[»]
2Y8Q	X-ray	2.80	A	407-555	[»]
2Y94	X-ray	3.24	A	13-481	[»]
			C	535-559	[»]
2YA3	X-ray	2.51	A	407-555	[»]
4EAI	X-ray	2.28	A	405-559	[»]
4EAJ	X-ray	2.61	A	405-559	[»]
4EAK	X-ray	2.50	A	405-559	[»]
4EAL	X-ray	2.51	A	405-559	[»]

ProteinModelPortal

P54645.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-57168N.

MINT

MINT-4566241.

STRING

10116.ENSRNOP00000017626.

PTM databases

PhosphoSite

P54645.

Proteomic databases

PRIDE

P54645.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000017626; ENSRNOP00000017626; ENSRNOG00000012799.

GeneID

65248.

KEGG

rno:65248.

Organism-specific databases

CTD

5562.

RGD

3387. Prkaa1.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00700000104077.

HOGENOM

HOG000233016.

HOVERGEN

HBG050432.

InParanoid

P54645.

KO

K07198.

OrthoDB

EOG4BK53H.

Enzyme and pathway databases

BRENDA

2.7.11.1. 5301.

Gene expression databases

Genevestigator

P54645.

GermOnline

ENSRNOG00000012799. Rattus norvegicus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

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Other

BindingDB

P54645.

ChEMBL

CHEMBL4533.

EvolutionaryTrace

P54645.

NextBio

614203.

Entry information

Entry name

AAPK1_RAT

Accession

Primary (citable) accession number: P54645

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	July 28, 2009
Last modified:	April 3, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program