Reviewed,
UniProtKB/Swiss-Prot Q13131 (AAPK1_HUMAN)
Last modified
November 25, 2008.
Version 93.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
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 alpha-1 chain EC=2.7.11.1 | ||||
| Gene names |
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| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 550 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| 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. |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Magnesium. |
| Enzyme regulation | Binding of AMP results in allosteric activation, inducing phosphorylation on Thr-174 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. |
| Sequence similarities | Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily. Contains 1 protein kinase domain. |
| Sequence caution | The sequence AAH48980.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| Ppard | P35396 | 1 | EBI-1181405,EBI-1809541 | From a different organism. |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q13131-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q13131-2) The sequence of this isoform differs from the canonical sequence as follows: 112-112: R → RKSDVPGVVKTGSTKE |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 550 | 550 | 5'-AMP-activated protein kinase catalytic subunit alpha-1 | PRO_0000085589 | |||||
Regions | |||||||||
| Domain | 18 – 270 | 253 | Protein kinase | ||||||
| Nucleotide binding | 24 – 32 | 9 | ATP By similarity | ||||||
Sites | |||||||||
| Active site | 141 | 1 | Proton acceptor By similarity | ||||||
| Binding site | 47 | 1 | ATP By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 174 | 1 | Phosphothreonine; by STK11 By similarity | ||||||
| Modified residue | 175 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 260 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 347 | 1 | Phosphoserine | ||||||
| Modified residue | 373 | 1 | Phosphothreonine | ||||||
| Modified residue | 433 | 1 | Phosphotyrosine | ||||||
| Modified residue | 477 | 1 | Phosphoserine | ||||||
| Modified residue | 481 | 1 | Phosphothreonine | ||||||
| Modified residue | 487 | 1 | Phosphoserine | ||||||
| Modified residue | 499 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 112 | 1 | R → RKSDVPGVVKTGSTKE in isoform 2. | VSP_035431 | |||||
| Natural variant | 7 | 1 | Q → R in a breast cancer sample; somatic mutation. | VAR_035622 | |||||
Experimental info | |||||||||
| Sequence conflict | 1 | 1 | M → L in AAH48980. Ref.3 | ||||||
| Sequence conflict | 28 | 1 | T → A in AAA64850. Ref.4 | ||||||
| Sequence conflict | 193 | 1 | A → V in AAA64850. Ref.4 | ||||||
| Sequence conflict | 199 | 1 | I → L in AAA64850. Ref.4 | ||||||
| Sequence conflict | 260 | 1 | T → S in BAA36547. Ref.1 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Nucleotide sequence of cDNA for human AMP-activated protein kinase alpha-1." Yano K. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Mammary gland. |
| [2] | "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. Chen Z.Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood. |
| [3] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Testis. |
| [4] | Taboada E.N., Hickey D.A. Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-200. Tissue: Intestine. |
| [5] | "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 294-550. Tissue: Liver. |
| [6] | "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed: 14976552] [Abstract] Cited for: FUNCTION, ENZYME REGULATION. |
| [7] | "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. |
| [8] | "Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, MASS SPECTROMETRY. |
| [9] | "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J.Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-433, MASS SPECTROMETRY. |
| [10] | "Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-487, MASS SPECTROMETRY. Tissue: Platelet. |
| [11] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-373, MASS SPECTROMETRY. |
| [12] | "Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling." Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., Linehan W.M., Schmidt L.S., Zbar B. Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006) [PubMed: 17028174] [Abstract] Cited for: INTERACTION WITH FNIP1. |
| [13] | "Identification and characterization of a novel folliculin-interacting protein FNIP2." Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., Valera V.A., Linehan W.M., Schmidt L.S. Gene 415:60-67(2008) [PubMed: 18403135] [Abstract] Cited for: INTERACTION WITH FNIP2. |
| [14] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347; THR-373; SER-477; THR-481 AND SER-487, MASS SPECTROMETRY. |
| [15] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-7. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AB022017 mRNA. Translation: BAA36547.1. AF100763 mRNA. Translation: AAD43027.1. BC037303 mRNA. Translation: AAH37303.1. BC048980 mRNA. Translation: AAH48980.1. U22456 mRNA. Translation: AAA64850.1. Y12856 mRNA. Translation: CAA73361.1. | |
| PIR | G01743. |
| RefSeq | NP_006242.5. NP_996790.3. |
| UniGene | Hs.43322 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1A06 based on UniProtKB Q63450. |
| SMR | Q13131. Positions 12-280. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q13131. |
PTM databases | |
| PhosphoSite | Q13131. |
Genome annotation databases | |
| Ensembl | ENSG00000132356. Homo sapiens. [Contig view] |
| GeneID | 5562. |
| KEGG | hsa:5562. |
Organism-specific databases | |
| H-InvDB | HIX0004832. |
| HGNC | HGNC:9376. PRKAA1. |
| HPA | CAB005050. |
| MIM | 602739. gene. |
| PharmGKB | PA33744. |
| GenAtlas | Search... |
| GeneCards | Search... |
Phylogenomic databases | |
| HOVERGEN | Q13131. |
Gene expression databases | |
| ArrayExpress | Q13131. |
| CleanEx | HS_PRKAA1. |
| GermOnline | ENSG00000132356. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR015741. 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] |
| PANTHER | PTHR22982:SF61. AMPK. 1 hit. |
| Pfam | PF00069. Pkinase. 1 hit. [Graphical view] |
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] |
| 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 | |
| DrugBank | DB00131. Adenosine monophosphate. DB00171. Adenosine triphosphate. DB00914. Phenformin. |
| SOURCE | Search... |
Entry information
| Entry name | AAPK1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13131 Secondary accession number(s): O00286 Q9UNQ4 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


