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P54645 (AAPK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length559 AA.
Sequence statusComplete.
Protein existenceEvidence 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/ULK1: 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 ATG1/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 shows 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. Dephosphorylated by PPM1A and PPM1B By similarity. 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 processAutophagy
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 componentCytoplasm
Nucleus
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionChromatin regulator
Kinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

activation of MAPK activity

Inferred from electronic annotation. Source: InterPro

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 nutrient levels

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to organonitrogen compound

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: Ensembl

glucose homeostasis

Inferred from sequence or structural similarity. Source: UniProtKB

glucose metabolic process

Inferred from electronic annotation. Source: Ensembl

lipid biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of TOR signaling

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 gene expression

Inferred from electronic annotation. Source: Ensembl

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

protein phosphorylation

Non-traceable author statement PubMed 9845345. Source: UniProtKB

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-templated

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

response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

rhythmic process

Inferred from electronic annotation. Source: UniProtKB-KW

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentAMP-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

protein complex

Inferred from direct assay Ref.13. Source: RGD

   Molecular_functionAMP-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: UniProtKB-EC

[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity

Inferred from electronic annotation. Source: UniProtKB-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

kinase binding

Inferred from physical interaction PubMed 16026327. Source: RGD

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein C-terminus binding

Inferred from physical interaction PubMed 15695819. Source: RGD

protein serine/threonine kinase activity

Inferred from direct assay PubMed 8955377. Source: RGD

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FlcnQ76JQ22EBI-7596967,EBI-7596839

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5595595'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085593

Regions

Domain27 – 279253Protein kinase
Nucleotide binding33 – 419ATP By similarity
Region302 – 38180AIS By similarity

Sites

Active site1501Proton acceptor By similarity
Binding site561ATP By similarity

Amino acid modifications

Modified residue321Phosphothreonine By similarity
Modified residue1831Phosphothreonine; by LKB1 and CaMKK2 Ref.5 Ref.12 Ref.13 Ref.17 Ref.18
Modified residue2691Phosphothreonine Ref.15
Modified residue3561Phosphoserine By similarity
Modified residue3601Phosphoserine; by ULK1 Probable
Modified residue3681Phosphothreonine; by ULK1 Probable
Modified residue3821Phosphothreonine By similarity
Modified residue3971Phosphoserine; by ULK1 Ref.20
Modified residue4671Phosphoserine By similarity
Modified residue4861Phosphoserine; by ULK1 Probable
Modified residue4881Phosphothreonine; by ULK1 Probable
Modified residue4901Phosphothreonine By similarity
Modified residue4961Phosphoserine Ref.15

Experimental info

Mutagenesis1831T → E: Hinders activation. Ref.15
Mutagenesis2691T → A: Hinders activation. Ref.15
Mutagenesis2691T → D: Retains activation ability. Ref.15
Mutagenesis386 – 3916RHTLDE → AHALAA: Allosterically activated by AMP but is not protected against dephosphorylation by AMP or ADP. Ref.23
Mutagenesis4961S → A: Hinders activation. Ref.15
Mutagenesis4961S → D: Retains activation ability. Ref.15
Sequence conflict13 – 142Missing in AAC52355. Ref.2
Sequence conflict4731D → L AA sequence Ref.2

Secondary structure

........................................................................... 559
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P54645 [UniParc].

Last modified July 28, 2009. Version 2.
Checksum: A869C340A85785ED

FASTA55963,973
        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 

« Hide

References

« Hide '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, IDENTIFICATION BY 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.
RefSeqNP_062015.2. NM_019142.2.
UniGeneRn.87789.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2V8QX-ray2.10A407-559[»]
2V92X-ray2.40A407-559[»]
2V9JX-ray2.53A407-559[»]
2Y8LX-ray2.50A407-555[»]
2Y8QX-ray2.80A407-555[»]
2YA3X-ray2.51A407-555[»]
4CFHX-ray3.24A13-481[»]
C535-559[»]
4EAIX-ray2.28A405-559[»]
4EAJX-ray2.61A405-559[»]
4EAKX-ray2.50A405-559[»]
4EALX-ray2.51A405-559[»]
4F2LX-ray1.50A295-347[»]
ProteinModelPortalP54645.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249325. 1 interaction.
DIPDIP-57168N.
IntActP54645. 1 interaction.
MINTMINT-4566241.
STRING10116.ENSRNOP00000017626.

Chemistry

BindingDBP54645.
ChEMBLCHEMBL4533.

PTM databases

PhosphoSiteP54645.

Proteomic databases

PRIDEP54645.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000017626; ENSRNOP00000017626; ENSRNOG00000012799.
GeneID65248.
KEGGrno:65248.

Organism-specific databases

CTD5562.
RGD3387. Prkaa1.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00740000115114.
HOGENOMHOG000233016.
HOVERGENHBG050432.
InParanoidP54645.
KOK07198.
OMAMKRATIR.
OrthoDBEOG7RRF6K.
PhylomeDBP54645.
TreeFamTF314032.

Enzyme and pathway databases

BRENDA2.7.11.1. 5301.

Gene expression databases

GenevestigatorP54645.

Family and domain databases

InterProIPR028375. KA1/Ssp2_C.
IPR011009. Kinase-like_dom.
IPR028797. PRKAA1.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR24343:SF81. PTHR24343:SF81. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF103243. SSF103243. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP54645.
NextBio614203.
PROP54645.

Entry information

Entry nameAAPK1_RAT
AccessionPrimary (citable) accession number: P54645
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 28, 2009
Last modified: April 16, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references