Protein kinase, AMP-activated, alpha 1

Protein-coding gene in the species Homo sapiens
PRKAA1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

4RED, 4RER, 4REW, 5EZV

Identifiers
AliasesPRKAA1, AMPK, AMPKa1, Protein kinase, AMP-activated, alpha 1, protein kinase AMP-activated catalytic subunit alpha 1
External IDsOMIM: 602739; MGI: 2145955; HomoloGene: 49590; GeneCards: PRKAA1; OMA:PRKAA1 - orthologs
EC number2.7.11.26
Gene location (Human)
Chromosome 5 (human)
Chr.Chromosome 5 (human)[1]
Chromosome 5 (human)
Genomic location for PRKAA1
Genomic location for PRKAA1
Bandn/aStart40,759,379 bp[1]
End40,798,374 bp[1]
Gene location (Mouse)
Chromosome 15 (mouse)
Chr.Chromosome 15 (mouse)[2]
Chromosome 15 (mouse)
Genomic location for PRKAA1
Genomic location for PRKAA1
Band15|15 A1Start5,173,343 bp[2]
End5,211,380 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • Achilles tendon

  • sperm

  • rectum

  • gallbladder

  • gastric mucosa

  • stromal cell of endometrium

  • epithelium of colon

  • tibial arteries

  • body of pancreas

  • Descending thoracic aorta
Top expressed in
  • granulocyte

  • islet of Langerhans

  • epithelium of small intestine

  • mammillary body

  • white adipose tissue

  • hand

  • ventromedial nucleus

  • medial vestibular nucleus

  • lateral hypothalamus

  • ventral tegmental area
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • transferase activity
  • nucleotide binding
  • protein kinase activity
  • cAMP-dependent protein kinase activity
  • [acetyl-CoA carboxylase kinase activity]
  • AMP-activated protein kinase activity
  • histone serine kinase activity
  • chromatin binding
  • metal ion binding
  • kinase activity
  • protein serine/threonine kinase activity
  • tau-protein kinase activity
  • protein C-terminus binding
  • protein binding
  • [hydroxymethylglutaryl-CoA reductase (NADPH) kinase activity]
  • ATP binding
  • tau protein binding
Cellular component
  • nucleotide-activated protein kinase complex
  • apical plasma membrane
  • nucleoplasm
  • nucleus
  • cytoplasm
  • cytosol
  • nuclear speck
  • intracellular anatomical structure
  • axon
  • dendrite
  • protein-containing complex
  • neuronal cell body
Biological process
  • cellular response to organonitrogen compound
  • steroid metabolic process
  • cellular response to glucose starvation
  • sterol biosynthetic process
  • lipid biosynthetic process
  • regulation of transcription, DNA-templated
  • response to hypoxia
  • cellular response to ethanol
  • glucose homeostasis
  • positive regulation of skeletal muscle tissue development
  • protein heterooligomerization
  • rhythmic process
  • phosphorylation
  • lipid metabolism
  • regulation of vesicle-mediated transport
  • negative regulation of apoptotic process
  • cholesterol metabolic process
  • Wnt signaling pathway
  • response to activity
  • fatty acid metabolic process
  • transcription, DNA-templated
  • cellular response to prostaglandin E stimulus
  • autophagy
  • protein phosphorylation
  • negative regulation of TOR signaling
  • cold acclimation
  • positive regulation of gene expression
  • response to camptothecin
  • fatty acid biosynthetic process
  • fatty acid homeostasis
  • regulation of circadian rhythm
  • fatty acid oxidation
  • regulation of peptidyl-serine phosphorylation
  • cellular response to nutrient levels
  • positive regulation of cell population proliferation
  • negative regulation of glucosylceramide biosynthetic process
  • glucose metabolic process
  • positive regulation of cholesterol biosynthetic process
  • response to caffeine
  • cholesterol biosynthetic process
  • negative regulation of lipid catabolic process
  • response to gamma radiation
  • macroautophagy
  • response to UV
  • positive regulation of glycolytic process
  • response to hydrogen peroxide
  • cellular response to hypoxia
  • signal transduction
  • cellular response to hydrogen peroxide
  • steroid biosynthetic process
  • regulation of signal transduction by p53 class mediator
  • positive regulation of autophagy
  • CAMKK-AMPK signaling cascade
  • regulation of macroautophagy
  • chromatin organization
  • positive regulation of mitochondrial transcription
  • positive regulation of protein targeting to mitochondrion
  • negative regulation of gene expression
  • cellular response to oxidative stress
  • intracellular signal transduction
  • negative regulation of insulin receptor signaling pathway
  • motor behavior
  • regulation of stress granule assembly
  • neuron cellular homeostasis
  • regulation of microtubule cytoskeleton organization
  • cellular response to calcium ion
  • cellular response to glucose stimulus
  • energy homeostasis
  • positive regulation of protein localization
  • negative regulation of tubulin deacetylation
  • positive regulation of peptidyl-lysine acetylation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

5562

105787

Ensembl

ENSG00000132356

ENSMUSG00000050697

UniProt

Q13131

Q5EG47

RefSeq (mRNA)

NM_006251
NM_206907

NM_001013367
NM_001355640

RefSeq (protein)
NP_006242
NP_996790
NP_001341957
NP_001341958
NP_001341963

NP_001341964
NP_001341965
NP_001341966

NP_001013385
NP_001342569

Location (UCSC)Chr 5: 40.76 – 40.8 MbChr 15: 5.17 – 5.21 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.[5][6]

The protein encoded by this gene belongs to the serine/threonine protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed.[6]

Interactions

Protein kinase, AMP-activated, alpha 1 has been shown to interact with TSC2.[7][8]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000132356 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000050697 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Stapleton D, Mitchelhill KI, Gao G, Widmer J, Michell BJ, Teh T, House CM, Fernandez CS, Cox T, Witters LA, Kemp BE (Feb 1996). "Mammalian AMP-activated protein kinase subfamily". J Biol Chem. 271 (2): 611–4. doi:10.1074/jbc.271.2.611. PMID 8557660.
  6. ^ a b "Entrez Gene: PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit".
  7. ^ Inoki, Ken; Zhu Tianqing; Guan Kun-Liang (Nov 2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell. 115 (5). United States: 577–90. doi:10.1016/S0092-8674(03)00929-2. ISSN 0092-8674. PMID 14651849. S2CID 18173817.
  8. ^ Shaw, Reuben J; Bardeesy Nabeel; Manning Brendan D; Lopez Lyle; Kosmatka Monica; DePinho Ronald A; Cantley Lewis C (Jul 2004). "The LKB1 tumor suppressor negatively regulates mTOR signaling". Cancer Cell. 6 (1). United States: 91–9. doi:10.1016/j.ccr.2004.06.007. ISSN 1535-6108. PMID 15261145.

Further reading

  • Munday MR, Campbell DG, Carling D, Hardie DG (1988). "Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase". Eur. J. Biochem. 175 (2): 331–8. doi:10.1111/j.1432-1033.1988.tb14201.x. PMID 2900138.
  • Woods A, Cheung PC, Smith FC, et al. (1996). "Characterization of AMP-activated protein kinase beta and gamma subunits. Assembly of the heterotrimeric complex in vitro". J. Biol. Chem. 271 (17): 10282–90. doi:10.1074/jbc.271.48.30517. PMID 8626596.
  • Hawley SA, Davison M, Woods A, et al. (1996). "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". J. Biol. Chem. 271 (44): 27879–87. doi:10.1074/jbc.271.44.27879. PMID 8910387.
  • Stapleton D, Woollatt E, Mitchelhill KI, et al. (1997). "AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location". FEBS Lett. 409 (3): 452–6. doi:10.1016/S0014-5793(97)00569-3. PMID 9224708. S2CID 39329574.
  • Velasco G, Gómez del Pulgar T, Carling D, Guzmán M (1998). "Evidence that the AMP-activated protein kinase stimulates rat liver carnitine palmitoyltransferase I by phosphorylating cytoskeletal components". FEBS Lett. 439 (3): 317–20. doi:10.1016/S0014-5793(98)01400-8. PMID 9845345. S2CID 29493620.
  • Crute BE, Seefeld K, Gamble J, et al. (1999). "Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase". J. Biol. Chem. 273 (52): 35347–54. doi:10.1074/jbc.273.52.35347. PMID 9857077.
  • da Silva Xavier G, Leclerc I, Salt IP, et al. (2000). "Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4023–8. Bibcode:2000PNAS...97.4023D. doi:10.1073/pnas.97.8.4023. PMC 18135. PMID 10760274.
  • Hallows KR, Raghuram V, Kemp BE, et al. (2000). "Inhibition of cystic fibrosis transmembrane conductance regulator by novel interaction with the metabolic sensor AMP-activated protein kinase". J. Clin. Invest. 105 (12): 1711–21. doi:10.1172/JCI9622. PMC 378514. PMID 10862786.
  • Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
  • Chen ZP, McConell GK, Michell BJ, et al. (2000). "AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation". Am. J. Physiol. Endocrinol. Metab. 279 (5): E1202–6. doi:10.1152/ajpendo.2000.279.5.E1202. PMID 11052978. S2CID 13387968.
  • Blázquez C, Geelen MJ, Velasco G, Guzmán M (2001). "The AMP-activated protein kinase prevents ceramide synthesis de novo and apoptosis in astrocytes". FEBS Lett. 489 (2–3): 149–53. doi:10.1016/S0014-5793(01)02089-0. PMID 11165240. S2CID 35584617.
  • Diggle TA, Subkhankulova T, Lilley KS, et al. (2001). "Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity". Biochem. J. 353 (Pt 3): 621–6. doi:10.1042/0264-6021:3530621. PMC 1221608. PMID 11171059.
  • Wang X, Li W, Williams M, et al. (2001). "Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase". EMBO J. 20 (16): 4370–9. doi:10.1093/emboj/20.16.4370. PMC 125559. PMID 11500364.
  • Xi X, Han J, Zhang JZ (2001). "Stimulation of glucose transport by AMP-activated protein kinase via activation of p38 mitogen-activated protein kinase". J. Biol. Chem. 276 (44): 41029–34. doi:10.1074/jbc.M102824200. PMID 11546797.
  • Fryer LG, Foufelle F, Barnes K, et al. (2002). "Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells". Biochem. J. 363 (Pt 1): 167–74. doi:10.1042/0264-6021:3630167. PMC 1222463. PMID 11903059.
  • Yang CS, Weiner H (2002). "Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol". Arch. Biochem. Biophys. 400 (1): 105–10. doi:10.1006/abbi.2002.2778. PMID 11913976.
  • Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002). "AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling". J. Biol. Chem. 277 (27): 23977–80. doi:10.1074/jbc.C200171200. PMID 11997383.
  • Esumi H, Izuishi K, Kato K, et al. (2002). "Hypoxia and nitric oxide treatment confer tolerance to glucose starvation in a 5'-AMP-activated protein kinase-dependent manner". J. Biol. Chem. 277 (36): 32791–8. doi:10.1074/jbc.M112270200. PMID 12091379.
  • Horman S, Browne G, Krause U, et al. (2003). "Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis". Curr. Biol. 12 (16): 1419–23. doi:10.1016/S0960-9822(02)01077-1. PMID 12194824. S2CID 9865400.

External links

  • PDBe-KB provides an overview of all the structure information available in the PDB for Human 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)
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  • 2h6d: Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)
    2h6d: Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)
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Non-specific serine/threonine protein kinases (EC 2.7.11.1)
Pyruvate dehydrogenase kinase (EC 2.7.11.2)
Dephospho-(reductase kinase) kinase (EC 2.7.11.3)
3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4)
(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)
(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)
Myosin-heavy-chain kinase (EC 2.7.11.7)
Fas-activated serine/threonine kinase (EC 2.7.11.8)
Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)
  • -
IκB kinase (EC 2.7.11.10)
cAMP-dependent protein kinase (EC 2.7.11.11)
cGMP-dependent protein kinase (EC 2.7.11.12)
Protein kinase C (EC 2.7.11.13)
Rhodopsin kinase (EC 2.7.11.14)
Beta adrenergic receptor kinase (EC 2.7.11.15)
G-protein coupled receptor kinases (EC 2.7.11.16)
Ca2+/calmodulin-dependent (EC 2.7.11.17)
Myosin light-chain kinase (EC 2.7.11.18)
Phosphorylase kinase (EC 2.7.11.19)
Elongation factor 2 kinase (EC 2.7.11.20)
Polo kinase (EC 2.7.11.21)
Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)
Polo kinase (EC 2.7.11.21)
Cyclin-dependent kinase (EC 2.7.11.22)
(RNA-polymerase)-subunit kinase (EC 2.7.11.23)
Mitogen-activated protein kinase (EC 2.7.11.24)
MAP3K (EC 2.7.11.25)
Tau-protein kinase (EC 2.7.11.26)
(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)
  • -
Tropomyosin kinase (EC 2.7.11.28)
  • -
Low-density-lipoprotein receptor kinase (EC 2.7.11.29)
  • -
Receptor protein serine/threonine kinase (EC 2.7.11.30)
MAP2K
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