PRKAA2

Protein kinase, AMP-activated, alpha 2 catalytic subunit

PDB rendering based on 2h6d.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2H6D, 2LTU, 2YZA, 3AQV, 4CFE, 4CFF

Identifiers

Symbols

PRKAA2 ; AMPK; AMPK2; AMPKa2; PRKAA

External IDs

OMIM: 600497 MGI: 1336173 HomoloGene: 4551 IUPHAR: 1542 ChEMBL: 2116 GeneCards: PRKAA2 Gene

EC number

2.7.11.1, 2.7.11.27, 2.7.11.31

Gene ontology
Molecular function	• chromatin binding • protein kinase activity • protein serine/threonine kinase activity • AMP-activated protein kinase activity • protein serine/threonine/tyrosine kinase activity • protein binding • ATP binding • histone serine kinase activity • metal ion binding • [hydroxymethylglutaryl-CoA reductase (NADPH) kinase activity] • [acetyl-CoA carboxylase kinase activity]
Cellular component	• nucleoplasm • cytosol
Biological process	• energy reserve metabolic process • transcription, DNA-templated • regulation of transcription, DNA-templated • protein phosphorylation • fatty acid biosynthetic process • cholesterol biosynthetic process • carnitine shuttle • autophagy • response to stress • cell cycle arrest • signal transduction • insulin receptor signaling pathway • lipid biosynthetic process • positive regulation of autophagy • Wnt signaling pathway • cellular response to nutrient levels • negative regulation of TOR signaling • histone-serine phosphorylation • cellular response to glucose starvation • regulation of fatty acid biosynthetic process • glucose homeostasis • regulation of circadian rhythm • negative regulation of apoptotic process • cellular lipid metabolic process • small molecule metabolic process • positive regulation of glycolytic process • rhythmic process • fatty acid homeostasis • membrane organization • regulation of energy homeostasis
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
57.11 – 57.18 Mb

Chr 4:
105.03 – 105.11 Mb

PubMed search

5'-AMP-activated protein kinase catalytic subunit alpha-2 is an enzyme that in humans is encoded by the PRKAA2 gene.^[1]^[2]

Function

The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia.^[2]

References

↑ Aguan K, Scott J, See CG, Sarkar NH (Dec 1994). "Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals". Gene 149 (2): 345–50. doi:10.1016/0378-1119(94)90174-0. PMID 7959015.
↑ 2.0 2.1 "Entrez Gene: PRKAA2 protein kinase, AMP-activated, alpha 2 catalytic subunit".

Hardie DG, MacKintosh RW (1995). "AMP-activated protein kinase--an archetypal protein kinase cascade?". Bioessays 14 (10): 699–704. doi:10.1002/bies.950141011. PMID 1365882.
Hardie DG (1992). "Regulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase". Biochim. Biophys. Acta 1123 (3): 231–8. doi:10.1016/0005-2760(92)90001-c. PMID 1536860.
Carling D (2004). "The AMP-activated protein kinase cascade--a unifying system for energy control". Trends Biochem. Sci. 29 (1): 18–24. doi:10.1016/j.tibs.2003.11.005. PMID 14729328.
Beri RK, Marley AE, See CG, Sopwith WF, Aguan K, Carling D et al. (1995). "Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase". FEBS Lett. 356 (1): 117–21. doi:10.1016/0014-5793(94)01247-4. PMID 7988703.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Vavvas D, Apazidis A, Saha AK, Gamble J, Patel A, Kemp BE et al. (1997). "Contraction-induced changes in acetyl-CoA carboxylase and 5'-AMP-activated kinase in skeletal muscle". J. Biol. Chem. 272 (20): 13255–61. doi:10.1074/jbc.272.20.13255. PMID 9148944.
Stapleton D, Woollatt E, Mitchelhill KI, Nicholl JK, Fernandez CS, Michell BJ 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.
Stein SC, Woods A, Jones NA, Davison MD, Carling D (2000). "The regulation of AMP-activated protein kinase by phosphorylation". Biochem. J. 345 Pt 3 (3): 437–43. doi:10.1042/0264-6021:3450437. PMC 1220775. PMID 10642499.
da Silva Xavier G, Leclerc I, Salt IP, Doiron B, Hardie DG, Kahn A 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.
Mu J, Brozinick JT, Valladares O, Bucan M, Birnbaum MJ (2001). "A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle". Mol. Cell 7 (5): 1085–94. doi:10.1016/S1097-2765(01)00251-9. PMID 11389854.
Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Müller C, Carling D et al. (2002). "Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase". Nature 415 (6869): 339–43. doi:10.1038/415339a. PMID 11797013.
Dubbelhuis PF, Meijer AJ (2002). "Hepatic amino acid-dependent signaling is under the control of AMP-dependent protein kinase". FEBS Lett. 521 (1–3): 39–42. doi:10.1016/S0014-5793(02)02815-6. PMID 12067722.
Esumi H, Izuishi K, Kato K, Hashimoto K, Kurashima Y, Kishimoto A 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.
Nielsen JN, Mustard KJ, Graham DA, Yu H, MacDonald CS, Pilegaard H et al. (2003). "5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle". J. Appl. Physiol. 94 (2): 631–41. doi:10.1152/japplphysiol.00642.2002. PMID 12391032.
Wojtaszewski JF, Mourtzakis M, Hillig T, Saltin B, Pilegaard H (2002). "Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise". Biochem. Biophys. Res. Commun. 298 (3): 309–16. doi:10.1016/S0006-291X(02)02465-8. PMID 12413941.
Hallows KR, McCane JE, Kemp BE, Witters LA, Foskett JK (2003). "Regulation of channel gating by AMP-activated protein kinase modulates cystic fibrosis transmembrane conductance regulator activity in lung submucosal cells". J. Biol. Chem. 278 (2): 998–1004. doi:10.1074/jbc.M210621200. PMID 12427743.
Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ et al. (2003). "AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation". Proc. Natl. Acad. Sci. U.S.A. 99 (25): 15983–7. doi:10.1073/pnas.252625599. PMC 138551. PMID 12444247.

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

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

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

Biochemistry overview
Enzymes overview
By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
  - 2.7.10
  - 11-12
- 8
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
  - 22
  - 23
  - 24
- 5
- 6
- 7
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

PRKAA2

Function

References

Further reading