PRKAA2
5'-AMP-activated protein kinase catalytic subunit alpha-2
Also known as: AAPK2_HUMAN, AMPK, AMPKa2, PRKAA
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P54646
- Gene
- PRKAA2
- Ensembl
- ENSG00000162409
- Chromosome
- 1
- Canonical length
- 552 aa
- Protein class
- Enzymes, FDA approved drug targets, Predicted membrane proteins, Transporters
- Subcellular location
- Nucleoplasm,Nuclear speckles,Golgi apparatus,Basal body,Cytosol
OverviewNCBI Gene
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. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
552 residues, UniProt reviewed canonical sequence.
>P54646|PRKAA2
1 MAEKQKHDGR VKIGHYVLGD TLGVGTFGKV KIGEHQLTGH KVAVKILNRQ KIRSLDVVGK
61 IKREIQNLKL FRHPHIIKLY QVISTPTDFF MVMEYVSGGE LFDYICKHGR VEEMEARRLF
121 QQILSAVDYC HRHMVVHRDL KPENVLLDAH MNAKIADFGL SNMMSDGEFL RTSCGSPNYA
181 APEVISGRLY AGPEVDIWSC GVILYALLCG TLPFDDEHVP TLFKKIRGGV FYIPEYLNRS
241 VATLLMHMLQ VDPLKRATIK DIREHEWFKQ DLPSYLFPED PSYDANVIDD EAVKEVCEKF
301 ECTESEVMNS LYSGDPQDQL AVAYHLIIDN RRIMNQASEF YLASSPPSGS FMDDSAMHIP
361 PGLKPHPERM PPLIADSPKA RCPLDALNTT KPKSLAVKKA KWHLGIRSQS KPYDIMAEVY
421 RAMKQLDFEW KVVNAYHLRV RRKNPVTGNY VKMSLQLYLV DNRSYLLDFK SIDDEVVEQR
481 SGSSTPQRSC SAAGLHRPRS SFDSTTAESH SLSGSLTGSL TGSTLSSVSP RLGSHTMDFF
541 EMCASLITTL ARLocalizationUniProt · AlphaFold · HPA
Whether an antibody against PRKAA2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.36
- Highest tissue expression
- 38 nTPM
Expression across tissuesHPA
Tissue
- heart muscle: 38 nTPM
- skeletal muscle: 36 nTPM
- tongue: 34 nTPM
- kidney: 13 nTPM
- retina: 13 nTPM
- parathyroid gland: 7.8 nTPM
Single-cell type
- myonuclei: 482 nCPM
- cardiomyocytes: 390 nCPM
- renal collecting duct intercalated cells: 336 nCPM
- thymic myoid cells: 243 nCPM
- distal convoluted tubule cells: 222 nCPM
- rod photoreceptor cells: 214 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- choroid plexus: 15 nTPM
- cerebral cortex: 14 nTPM
- basal ganglia: 13 nTPM
- cerebellum: 12 nTPM
- hypothalamus: 10 nTPM
- white matter: 8.8 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.92
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.99
- DepMap mean gene effect
- -0.15
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- autophagy
- cellular response to calcium ion
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to nutrient levels
- cellular response to oxidative stress
- cellular response to prostaglandin E stimulus
- cellular response to xenobiotic stimulus
- cholesterol biosynthetic process
- energy homeostasis
- fatty acid biosynthetic process
- fatty acid homeostasis
- glucose homeostasis
- lipid biosynthetic process
- lipid droplet disassembly
- negative regulation of apoptotic process
- negative regulation of gene expression
- negative regulation of hepatocyte apoptotic process
- negative regulation of TOR signaling
- negative regulation of TORC1 signaling
- negative regulation of tubulin deacetylation
- positive regulation of autophagy
- positive regulation of glycolytic process
- positive regulation of macroautophagy
- positive regulation of protein localization
- protein localization to lipid droplet
- regulation of circadian rhythm
- regulation of macroautophagy
- regulation of microtubule cytoskeleton organization
- regulation of stress granule assembly
- response to muscle activity
- rhythmic process
- signal transduction
- Wnt signaling pathway
Molecular functions
- [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
- AMP-activated protein kinase activity
- ATP binding
- chromatin binding
- histone H2BS36 kinase activity
- metal ion binding
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- protein serine/threonine/tyrosine kinase activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Protein kinase, ATP binding site
- KA1 domain/Ssp2, C-terminal
- AMPK, C-terminal adenylate sensor domain
- PRKAA1/2, autoinhibitory domain
- Protein kinase domain
- Adenylate sensor of SNF1-like protein kinase
- AMP-activated protein kinase, alpha subunit, autoinhibitory domain
- PRKAA2, UBA-like autoinhibitory domain
- 5'-AMP-activated protein kinase catalytic subunit alpha-2, C-terminal
KeywordsUniProt
- ATP-binding
- Autophagy
- Biological rhythms
- Cholesterol biosynthesis
- Cholesterol metabolism
- Chromatin regulator
- Cytoplasm
- Fatty acid biosynthesis
- Fatty acid metabolism
- Kinase
- Lipid biosynthesis
- Lipid metabolism
- Magnesium
- Metal-binding
- Nucleotide-binding
- Nucleus
- Phosphoprotein
- Serine/threonine-protein kinase
- Steroid biosynthesis
- Steroid metabolism
- Sterol biosynthesis
- Sterol metabolism
- Transcription
- Transcription regulation
- Transferase
- Ubl conjugation
- Wnt signaling pathway
InteractionsUniProt · HPA
Protein binding partners of PRKAA2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads PRKAA2 as an antibody target. Whether an autoantibody or antibody against PRKAA2 could matter depends on whether native PRKAA2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
PRKAA2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label PRKAA2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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