Protein kinase, AMP-activated, alpha 1

Protein kinase, AMP-activated, alpha 1 catalytic subunit

PDB rendering based on 2h6d.

Available structures
PDB	2h6d

Identifiers

Symbols

PRKAA1; AMPK; AMPKa1; MGC33776; MGC57364

External IDs

OMIM: 602739 MGI: 2145955 HomoloGene: 49590 GeneCards: PRKAA1 Gene

EC number

2.7.11.1

Gene Ontology
Molecular function	• nucleotide binding • protein kinase activity • protein serine/threonine kinase activity • cAMP-dependent protein kinase activity • protein binding • ATP binding • metal ion binding
Cellular component	• intracellular • cytosol • cytosol
Biological process	• activation of MAPK activity • response to hypoxia • protein phosphorylation • fatty acid biosynthetic process • cell cycle arrest • signal transduction • insulin receptor signaling pathway • positive regulation of cholesterol biosynthetic process • positive regulation of anti-apoptosis • negative regulation of glucosylceramide biosynthetic process • regulation of fatty acid oxidation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
40.76 – 40.8 Mb

Chr 15:
5.09 – 5.13 Mb

PubMed search

[1]

[2]

5'-AMP-activated protein kinase catalytic subunit alpha-1 is an enzyme that in humans is encoded by the PRKAA1 gene.^[1]^[2]

The protein encoded by this gene belongs to the ser/thr 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.^[2]

Interactions

Protein kinase, AMP-activated, alpha 1 has been shown to interact with TSC2.^[3]^[4]

References

^ 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.
^ ^a ^b "Entrez Gene: PRKAA1 protein kinase, AMP-activated, alpha 1 catalytic subunit". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5562.
^ Inoki, Ken; Zhu Tianqing, Guan Kun-Liang (Nov. 2003). "TSC2 mediates cellular energy response to control cell growth and survival". Cell (United States) 115 (5): 577–90. doi:10.1016/S0092-8674(03)00929-2. ISSN 0092-8674. PMID 14651849.
^ 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 (United States) 6 (1): 91–9. doi:10.1016/j.ccr.2004.06.007. ISSN 1535-6108. PMID 15261145.

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.
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.
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. doi:10.1073/pnas.97.8.4023. PMC 18135. PMID 10760274. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18135.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=378514.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310934.
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. PMID 11052978.
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.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1221608.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=125559.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222463.
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.

PDB gallery

2h6d: Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1, LATS2, MAST1, MAST2, STK38, STK38L, CIT, ROCK1, SGK, SGK2, SGK3, Protein kinase B (AKT1, AKT2, AKT3), Ataxia telangiectasia mutated, Mammalian target of rapamycin, EIF-2 kinases (PKR, HRI, EIF2AK3, EIF2AK4), Wee1 (WEE1)

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1, PDK2, PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α (PRKAA1, PRKAA2) · β (PRKAB1, PRKAB2) · γ (PRKAG1, PRKAG2, PRKAG3)

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK, BCKDHA, BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2, IDH3A, IDH3B, IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase (Aurora A kinase, Aurora B kinase)

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK, STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK, IKK2, TBK1, IKBKE, IKBKG, IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A, PRKACG, PRKACB, PRKACA, PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G, PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C, Protein kinase Cζ, PKC alpha, PRKCB1, PRKCD, PRKCE, PRKCH, PRKCG, PRKCI, PRKCQ, Protein kinase N1, PKN2, PKN3,

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase, Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4, GRK5, GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2, CAMK1, CAMK2A, CAMK2B, CAMK2D, CAMK2G, CAMK4, MLCK, CASK, CHEK1, CHEK2, DAPK1, DAPK2, DAPK3, STK11, MAPKAPK2, MAPKAPK3, MAPKAPK5, MARK1, MARK2, MARK3, MARK4, MELK, MKNK1, MKNK2, NUAK1, NUAK2, OBSCN, PASK, PHKG1, PHKG2, PIM1, PIM2, PKD1, PRKD2, PRKD3, PSKH1, SNF1LK2, KIAA0999, STK40, SNF1LK, SNRK, SPEG, TSSK2, Kalirin, TRIB1, TRIB2, TRIB3, TRIO, Titin, DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK, MYLK2, MYLK3, MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1, PHKA2, PHKB, PHKG1, PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K, STK19

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1, PLK2, PLK3, PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1, CDK2, CDKL2, CDK3, CDK4, CDK5, CDKL5, CDK6, CDK7, CDK8, CDK9, CDK10, CDC2L5, CRKRS, PCTK1, PCTK2, PCTK3, PFTK1, CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5, RPS6KA4, P70S6 kinase, P70-S6 Kinase 1, RPS6KB2, RPS6KA2, RPS6KA3, RPS6KA1, RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated (MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK12, MAPK15), C-Jun N-terminal (MAPK8, MAPK9, MAPK10), P38 mitogen-activated protein (MAPK11, MAPK13, MAPK14)

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases (MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP3K6, MAP3K7, MAP3K8) RAFs (ARAF, BRAF, KSR1, KSR2), MLKs (MAP3K12, MAP3K13, MAP3K9, MAP3K10, MAP3K11, MAP3K7, ZAK), CDC7, MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1, TTK, GSK-3

(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)	Bone morphogenetic protein receptors (BMPR1, BMPR1A, BMPR1B, BMPR2), ACVR1, ACVR1B, ACVR1C, ACVR2A, ACVR2B, ACVRL1, Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAP2K6, MAP2K7

B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6

Protein kinase, AMP-activated, alpha 1

Interactions

References

Further reading