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Protein Page:
AMPKA2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
AMPKA2 a catalytic subunit of AMP-activated protein kinase (AMPK). Acts as an energy sensor, playing a key role in regulating cellular energy metabolism. A protein kinase of the CAMKL family whose activation is regulated by the balance between ADP/AMP/ATP, and intracellular Ca(2+) levels. Acts as a metabolic stress-sensing protein kinase switching off biosynthetic pathways when cellular ATP levels are depleted and when 5'-ADP and -AMP rise in response to fuel limitation and/or hypoxia. Activates energy-producing pathways and inhibits energy-consuming processes. Restores ATP levels in cells by switching off anabolic and switching on catabolic pathways. Activated primarily by rising ADP levels and not, as previously thought, solely by AMP. AMPK resembles an adenylate charge regulatory system in which anabolic and catabolic pathways are regulated by adenine nucleotide ratios. Acts via direct phosphorylation of metabolic enzymes and transcription regulators. Regulates fatty acid synthesis by phosphorylating acetyl-CoA carboxylase. Regulates cholesterol synthesis by phosphorylating and inactivating hormone-sensitive lipase and hydroxymethylglutaryl-CoA reductase. Activated by at least two distinct upstream kinases: the tumor suppressor LKB1 and CaMKK2. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton, probably by indirectly activating myosin. AMPK is a heterotrimer of an alpha catalytic subunit (AMPKA1 or -2), a beta (AMPKB1 or -2) and a gamma non-catalytic subunit (AMPKG1, -2 or -3). Different possible combinations of subunits give rise to 12 different holoenzymes. Binding of ADP or AMP to non-catalytic gamma subunit (PRKAG1, -2 or -3) results in allosteric activation. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo. Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. Salicylate/aspirin directly activates kinase activity. Studies in the mouse suggest that AMPK2 may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. Note: This description may include information from UniProtKB.
Protein type: Kinase, protein; EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); Protein kinase, CAMK; Autophagy; CAMK group; CAMKL family; AMPK subfamily
Cellular Component: nucleoplasm; cytosol
Molecular Function: AMP-activated protein kinase activity; protein serine/threonine kinase activity; protein binding; metal ion binding; protein serine/threonine/tyrosine kinase activity; [acetyl-CoA carboxylase] kinase activity; histone serine kinase activity; chromatin binding; ATP binding; protein kinase activity; [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
Biological Process: lipid biosynthetic process; rhythmic process; cellular lipid metabolic process; carnitine shuttle; glucose homeostasis; signal transduction; protein amino acid phosphorylation; cellular response to glucose starvation; cellular response to nutrient levels; regulation of fatty acid biosynthetic process; regulation of transcription, DNA-dependent; response to stress; cell cycle arrest; fatty acid biosynthetic process; positive regulation of autophagy; negative regulation of TOR signaling pathway; Wnt receptor signaling pathway; transcription, DNA-dependent; regulation of circadian rhythm; cholesterol biosynthetic process; fatty acid homeostasis; positive regulation of glycolysis; energy reserve metabolic process; insulin receptor signaling pathway; autophagy; negative regulation of apoptosis
Reference #:  P54646 (UniProtKB)
Alt. Names/Synonyms: 5'-AMP-activated protein kinase catalytic subunit alpha-2; 5'-AMP-activated protein kinase, catalytic alpha-2 chain; AAPK2; AMPK; AMPK subunit alpha-2; AMPK-alpha-2 chain; AMPK2; PRKAA; PRKAA2; protein kinase, AMP-activated, alpha 2 catalytic subunit
Gene Symbols: PRKAA2
Molecular weight: 62,320 Da
Basal Isoelectric point: 7.65  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Autophagy Signaling  |  Insulin Receptor Signaling  |  mTOR Signaling  |  Translation: eIF4E and p70S6K  |  Warburg Effect
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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AMPKA2

Protein Structure Not Found.

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Sites Implicated In
enzymatic activity, induced: T172‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 K60 RSLDVVGKIKREIQN
0 2 K69-ac KREIQNLkLFRHPHI
0 2 S165-p FGLSNMMsDGEFLRt
58 38 T172-p sDGEFLRtsCGsPNY
1 18 S173-p DGEFLRtsCGsPNYA
0 14 S176-p FLRtsCGsPNYAAPE
0 2 Y232-p KIRGGVFyIPEYLNR
0 1 Y236 GVFyIPEYLNRSVAT
1 1 T258 VDPLKRATIKDIREH
0 1 S310 TESEVMNSLYSGDPQ
0 1 Y324-p QDQLAVAyHLIIDNR
0 12 S377-p MPPLIADsPKARCPL
0 1 K379 PLIADsPKARCPLDA
0 2 K470 RSYLLDFKSIDDEVV
0 5 S481-p DEVVEQRsGsStPQR
0 1 S483-p VVEQRsGsStPQRSC
0 1 S484 VEQRsGsStPQRSCs
0 2 T485-p EQRsGsStPQRSCsA
3 5 S491-p StPQRSCsAAGLHRP
0 3 S500-p AGLHRPRssFDSTTA
0 2 S501-p GLHRPRssFDSTTAE
0 1 S509-p FDSTTAEsHsLSGSL
0 1 S511-p STTAEsHsLSGSLTG
0 1 T521-p GSLTGSLtGStLSsV
0 1 T524-p TGSLtGStLSsVSPR
0 1 S527-p LtGStLSsVSPRLGs
0 1 S534-p sVSPRLGsHTMDFFE
2531 : Phospho-AMPKalpha (Thr172) Antibody
2535 : Phospho-AMPK-alpha (Thr172) (40H9) Rabbit mAb
5256 : Phospho-AMPK alpha (Thr172) (40H9) Rabbit mAb (Biotinylated)
4185 : Phospho-AMPKalpha1 (Ser485)/AMPKalpha2 (Ser491) Antibody
  mouse

 
K60-ub RSLDVVGkIKREIQN
K69-ac KREIQNLkLFRHPHI
S165-p FGLSNMMsDGEFLRt
T172-p sDGEFLRtsCGsPNY
S173-p DGEFLRtsCGsPNYA
S176-p FLRtsCGsPNYAAPE
Y232-p KIRGGVFyIPDyLNR
Y236-p GVFyIPDyLNRSVAT
T258 VDPLKRATIKDIREH
S310-p TESEVMNsLYSGDPQ
Y324 QDQLAVAYHLIIDNR
S377-p MPPLIADsPkARCPL
K379-ub PLIADsPkARCPLDA
K470-ub RSYLLDFkSIDDEVV
S481-p DEVVEQRsGSstPQR
S483 VVEQRsGSstPQRSC
S484-p VEQRsGSstPQRSCs
T485-p EQRsGSstPQRSCsA
S491-p stPQRSCsAAGLHRA
S500-p AGLHRARssFDSSTA
S501-p GLHRARssFDSSTAE
N509 FDSSTAENHSLSGSL
S511 SSTAENHSLSGSLTG
T521-p GSLTGSLtGStLSSA
T524-p TGSLtGStLSSASPR
S527 LtGStLSSASPRLGS
S534 SASPRLGSHTMDFFE
2531 : Phospho-AMPKalpha (Thr172) Antibody
2535 : Phospho-AMPK-alpha (Thr172) (40H9) Rabbit mAb
5256 : Phospho-AMPK alpha (Thr172) (40H9) Rabbit mAb (Biotinylated)
  rat

 
K60 RSLDVVGKIKREIQN
K69 KREIQNLKLFRHPHI
S165 FGLSNMMSDGEFLRt
T172-p SDGEFLRtsCGSPNY
S173-p DGEFLRtsCGSPNYA
S176 FLRtsCGSPNYAAPE
Y232 KIRGGVFYIPEYLNR
Y236 GVFYIPEYLNRSIAT
T258-p VDPLKRAtIKDIREH
S310 TESEVMNSLYSGDPQ
Y324 QDQLAVAYHLIIDNR
S377-p MPPLIADsPKARCPL
K379 PLIADsPKARCPLDA
K470 RSYLLDFKSIDDEVV
S481 DEVVEQRSGSSTPQR
S483 VVEQRSGSSTPQRSC
S484 VEQRSGSSTPQRSCs
T485 EQRSGSSTPQRSCsA
S491-p STPQRSCsAAGLHRP
S500 AGLHRPRSSVDSSTA
S501 GLHRPRSSVDSSTAE
N509 VDSSTAENHSLSGSL
S511 SSTAENHSLSGSLTG
T521 GSLTGSLTGSTLSSA
T524 TGSLTGSTLSSASPR
S527 LTGSTLSSASPRLGS
S534 SASPRLGSHTMDFFE
2531 : Phospho-AMPKalpha (Thr172) Antibody
2535 : Phospho-AMPK-alpha (Thr172) (40H9) Rabbit mAb
5256 : Phospho-AMPK alpha (Thr172) (40H9) Rabbit mAb (Biotinylated)
4185 : Phospho-AMPKalpha1 (Ser485)/AMPKalpha2 (Ser491) Antibody
  pig

 
K60 RSLDVVGKIKREIQN
K69 KREIQNLKLFRHPHI
S165 FGLSNMMSDGEFLRt
T172-p SDGEFLRtSCGSPNY
S173 DGEFLRtSCGSPNYA
S176 FLRtSCGSPNYAAPE
Y232 KIRGGVFYIPEYLNR
Y236 GVFYIPEYLNRSVAT
T258 VDPLKRATIKDIREH
S310 TESEVMNSLYSGDPQ
Y324 QDQLAVAYHLVIDNR
S377 MPPLIADSPKARCPL
K379 PLIADSPKARCPLDA
K470 RSYLLDFKSIDDEVL
S481 DEVLEQRSGSSTPQR
S483 VLEQRSGSSTPQRSC
S484 LEQRSGSSTPQRSCS
T485 EQRSGSSTPQRSCSA
S491 STPQRSCSAAGLHRP
S500 AGLHRPRSSLDSVTA
S501 GLHRPRSSLDSVTAE
S509 LDSVTAESHSLSGSL
S511 SVTAESHSLSGSLSG
T521 GSLSGSLTGSMLPSV
M524 SGSLTGSMLPSVPPR
S527 LTGSMLPSVPPRLGS
S534 SVPPRLGSHTMDFFE
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