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Reviewed, UniProtKB/Swiss-Prot P54645 (AAPK1_RAT)

Last modified November 25, 2008. Version 80. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    5'-AMP-activated protein kinase catalytic subunit alpha-1
      Short name=AMPK alpha-1 chain
    EC=2.7.11.1
Gene names
Name: Prkaa1
Synonyms: Ampk1
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length548 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Responsible for the regulation of fatty acid synthesis by phosphorylation of acetyl-CoA carboxylase. It also regulates cholesterol synthesis via phosphorylation and inactivation of hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Appears to act as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-AMP rises in response to fuel limitation and/or hypoxia. This is a catalytic subunit.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-172 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Also activated by phosphorylation by CAMKK2 triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio.

Subunit structure

Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 By similarity.

Tissue specificity

Low expression in kidney, liver, lung, heart and brain.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 5485485'-AMP-activated protein kinase catalytic subunit alpha-1
PRO_0000085593

Regions

Domain16 – 268253Protein kinase
Nucleotide binding22 – 309ATP By similarity

Sites

Active site1391Proton acceptor By similarity
Binding site451ATP By similarity

Amino acid modifications

Modified residue1721Phosphothreonine; by STK11
Modified residue1731Phosphoserine By similarity
Modified residue2581Phosphothreonine
Modified residue3451Phosphoserine By similarity
Modified residue3711Phosphothreonine By similarity
Modified residue4311Phosphotyrosine By similarity
Modified residue4751Phosphoserine By similarity
Modified residue4791Phosphothreonine By similarity
Modified residue4851Phosphoserine
Modified residue4971Phosphoserine By similarity

Experimental info

Mutagenesis1721T → E: Hinders activation
Mutagenesis2581T → A: Hinders activation
Mutagenesis2581T → D: Retains activation ability
Mutagenesis4851S → A: Hinders activation
Mutagenesis4851S → D: Retains activation ability
Sequence conflict4621D → L protein sequence Ref.1

Secondary structure

................... 548
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P54645-1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 5CCA3281C195F867

FASTA54862,600
        10         20         30         40         50         60 
MAEKQKHDGR VKIGHYILGD TLGVGTFGKV KVGKHELTGH KVAVKILNRQ KIRSLDVVGK 

        70         80         90        100        110        120 
IRREIQNLKL FRHPHIIKLY QVISTPSDIF MVMEYVSGGE LFDYICKNGR LDEKESRRLF 

       130        140        150        160        170        180 
QQILSGVDYC HRHMVVHRDL KPENVLLDAH MNAKIADFGL SNMMSDGEFL RTSCGSPNYA 

       190        200        210        220        230        240 
APEVISGRLY AGPEVDIWSS GVILYALLCG TLPFDDDHVP TLFKKICDGI FYTPQYLNPS 

       250        260        270        280        290        300 
VISLLKHMLQ VDPMKRATIK DIREHEWFKQ DLPKYLFPED PSYSSTMIDD EALKEVCEKF 

       310        320        330        340        350        360 
ECSEEEVLSC LYNRNHQDPL AVAYHLIIDN RRIMNEAKDF YLATSPPDSF LDDHHLTRPH 

       370        380        390        400        410        420 
PERVPFLVAE TPRARHTLDE LNPQKSKHQG VRKAKWHLGI RSQSRPNDIM AEVCRAIKQL 

       430        440        450        460        470        480 
DYEWKVVNPY YLRVRRKNPV TSTFSKMSLQ LYQVDSRTYL LDFRSIDDEI TEAKSGTATP 

       490        500        510        520        530        540 
QRSGSISNYR SCQRSDSDAE AQGKPSEVSL TSSVTSLDSS PVDVAPRPGS HTIEFFEMCA 


NLIKILAQ 

« Hide

References

[1]"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: 8557660] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 13-29; 79-104; 118-129; 139-149; 155-171; 225-246; 261-265; 275-294; 315-330; 339-356; 364-373; 396-415; 426-435; 447-464 AND 496-506.
Strain: Sprague-Dawley.
Tissue: Hypothalamus and Liver.
[2]"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: 7961907] [Abstract]
Cited for: INTERACTION WITH SUBUNITS BETA AND GAMMA.
Strain: Sprague-Dawley.
Tissue: Hypothalamus and Liver.
[3]"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: 14511394] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-172.
[4]"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: 12764152] [Abstract]
Cited for: PHOSPHORYLATION AT THR-258 AND SER-485, MUTAGENESIS OF THR-172; THR-258 AND SER-485, MASS SPECTROMETRY.
[5]"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: 16054095] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

U40819 mRNA. Translation: AAC52355.1.
RefSeqNP_062015.1.
UniGeneRn.87789

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2V8QX-ray2.10A396-548[»]
2V92X-ray2.40A396-548[»]
2V9JX-ray2.53A396-548[»]
SMRP54645. Positions 10-278.
ModBaseSearch...

PTM databases

PhosphoSiteP54645.

Genome annotation databases

EnsemblENSRNOG00000012799. Rattus norvegicus. [Contig view]
GeneID65248.
KEGGrno:65248.

Organism-specific databases

RGD3387. Prkaa1.

Phylogenomic databases

HOVERGENP54645.

Gene expression databases

ArrayExpressP54645.
GermOnlineENSRNOG00000012799. Rattus norvegicus.

Family and domain databases

InterProIPR015741. AMPK.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PANTHERPTHR22982:SF61. AMPK. 1 hit.
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio614203.

Entry information

Entry nameAAPK1_RAT
AccessionPrimary (citable) accession number: P54645
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 25, 2008
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents