Reviewed,
UniProtKB/Swiss-Prot P54645 (AAPK1_RAT)
Last modified
February 9, 2010.
Version 94.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
Third-party data |
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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 | ||||
| Gene names |
| ||||
| Organism | Rattus norvegicus (Rat) | ||||
| Taxonomic identifier | 10116 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › 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 | 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. Ref.4 Ref.6 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. |
| Enzyme regulation | Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-183 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. Ref.4 Ref.6 |
| Subunit structure | Heterotrimer of an alpha catalytic subunit, a beta and a gamma non-catalytic subunits. Interacts with FNIP1 and FNIP2 By similarity. Ref.3 |
| 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. |
Ontologies
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 | ||||||||||||||||||||||||
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 STK11 Ref.4 | ||||||||||||||||||||||||
| Modified residue | 184 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 187 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 269 | 1 | Phosphothreonine Ref.5 | ||||||||||||||||||||||||
| Modified residue | 355 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||
| Modified residue | 356 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 382 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||
| Modified residue | 397 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 441 | 1 | Phosphotyrosine By similarity | ||||||||||||||||||||||||
| Modified residue | 442 | 1 | Phosphotyrosine By similarity | ||||||||||||||||||||||||
| Modified residue | 467 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 476 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 486 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 488 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||
| Modified residue | 490 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||
| Modified residue | 496 | 1 | Phosphoserine Ref.5 | ||||||||||||||||||||||||
| Modified residue | 502 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 506 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 508 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 520 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 522 | 1 | Phosphothreonine By similarity | ||||||||||||||||||||||||
| Modified residue | 523 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 524 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
| Modified residue | 527 | 1 | Phosphoserine By similarity | ||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||
| Mutagenesis | 183 | 1 | T → E: Hinders activation. Ref.5 | ||||||||||||||||||||||||
| Mutagenesis | 269 | 1 | T → A: Hinders activation. Ref.5 | ||||||||||||||||||||||||
| Mutagenesis | 269 | 1 | T → D: Retains activation ability. Ref.5 | ||||||||||||||||||||||||
| Mutagenesis | 496 | 1 | S → A: Hinders activation. Ref.5 | ||||||||||||||||||||||||
| Mutagenesis | 496 | 1 | S → D: Retains activation ability. Ref.5 | ||||||||||||||||||||||||
| Sequence conflict | 13 – 14 | 2 | Missing in AAC52355. Ref.2 | ||||||||||||||||||||||||
| Sequence conflict | 473 | 1 | D → L AA sequence Ref.2 | ||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||
| 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
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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: 8557660] [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] | "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. |
| [4] | "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-183. |
| [5] | "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-269 AND SER-496, MUTAGENESIS OF THR-183; THR-269 AND SER-496, MASS SPECTROMETRY. |
| [6] | "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. |
| [7] | "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: 17851531] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 405-557. |
| + | 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. | ||||||||||||||||||||||||
| UniGene | Rn.87789 | ||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ModBase | Search... | ||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||
| STRING | P54645. | ||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||
| PhosphoSite | P54645. | ||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||
| PRIDE | P54645. | ||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||
| Ensembl | ENSRNOT00000017626; ENSRNOP00000017626; ENSRNOG00000012799; Rattus norvegicus. [Genome view] | ||||||||||||||||||||||||
| GeneID | 65248. | ||||||||||||||||||||||||
| KEGG | rno:65248. | ||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||
| CTD | 65248. | ||||||||||||||||||||||||
| RGD | 3387. Prkaa1. | ||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||
| eggNOG | roNOG12508. | ||||||||||||||||||||||||
| HOVERGEN | P54645. | ||||||||||||||||||||||||
| InParanoid | P54645. | ||||||||||||||||||||||||
| PhylomeDB | P54645. | ||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||
| BRENDA | 2.7.11.1. 248. | ||||||||||||||||||||||||
Gene expression databases | |||||||||||||||||||||||||
| ArrayExpress | P54645. | ||||||||||||||||||||||||
| Genevestigator | P54645. | ||||||||||||||||||||||||
| GermOnline | ENSRNOG00000012799. Rattus norvegicus. | ||||||||||||||||||||||||
Family and domain databases | |||||||||||||||||||||||||
| InterPro | IPR020636. Ca/CaM-dep_prot_kinase-like. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR015741. Prot_kinase_Snf1-like_AMPK. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_prot_kinase-like_dom. IPR008271. Ser/Thr_prot_kinase_AS. IPR002290. Ser/Thr_prot_kinase_dom. [Graphical view] | ||||||||||||||||||||||||
| PANTHER | PTHR22982:SF61. AMPK. 1 hit. PTHR22982. Ca/CaM-dep_prot_kinase-like. 1 hit. | ||||||||||||||||||||||||
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| SMART | SM00220. S_TKc. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| PROSITE | PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view] | ||||||||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||||||||
Other Resources | |||||||||||||||||||||||||
| NextBio | 614203. | ||||||||||||||||||||||||
Entry information
| Entry name | AAPK1_RAT | ||||||||
| Accession | Primary (citable) accession number: P54645 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


