PRKAA2 protein kinase AMP-activated catalytic subunit alpha 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRKAA2provided by HGNC
Official Full Name: protein kinase AMP-activated catalytic subunit alpha 2provided by HGNC
Primary source: HGNC:HGNC:9377
See related: Ensembl:ENSG00000162409 MIM:600497; AllianceGenome:HGNC:9377
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AMPK; AMPK2; PRKAA; AMPKa2
Summary: 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]
Expression: Biased expression in heart (RPKM 14.0), kidney (RPKM 6.8) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p32.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (56645314..56715335)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (56524182..56594202)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (57110987..57181008)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.
Title: SIRT5-mediated PRKAA2 succinylation ameliorates apoptosis of human placental trophoblasts in hypertensive disorder complicating pregnancy.
The BHLHE40-PPM1F-AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer.
Title: The BHLHE40‒PPM1F‒AMPK pathway regulates energy metabolism and is associated with the aggressiveness of endometrial cancer.
AMPKalpha2 promotes tumor immune escape by inducing CD8+ T-cell exhaustion and CD4+ Treg cell formation in liver hepatocellular carcinoma.
Title: AMPKα2 promotes tumor immune escape by inducing CD8+ T-cell exhaustion and CD4+ Treg cell formation in liver hepatocellular carcinoma.
Frequent loss-of-function mutations in the AMPK-alpha2 catalytic subunit suggest a tumour suppressor role in human skin cancers.
Title: Frequent loss-of-function mutations in the AMPK-α2 catalytic subunit suggest a tumour suppressor role in human skin cancers.
Assessing the gene expression of the adenosine 5'-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients.
Title: Assessing the gene expression of the adenosine 5'-monophosphate-activated protein kinase (AMPK) and its relation with the IL-6 and IL-10 plasma levels in COVID-19 patients.
AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via Bad[Ser136] phosphorylation.
Title: AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via Bad(Ser136) phosphorylation.
Changes in AMPK activity induces cellular senescence in human dental follicle cells.
Title: Changes in AMPK activity induces cellular senescence in human dental follicle cells.
Impact of AMPK on cervical carcinoma progression and metastasis.
Title: Impact of AMPK on cervical carcinoma progression and metastasis.
CircCDC6 restrains tumor growth and glycolysis energy metabolism in colorectal cancer via regulating miR-3187-3p and downstream PRKAA2.
Title: CircCDC6 restrains tumor growth and glycolysis energy metabolism in colorectal cancer via regulating miR-3187-3p and downstream PRKAA2.
The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma.
Title: The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma.

Submit: New GeneRIF Correction See all GeneRIFs (110)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat-induced LTR transactivation is reversed by tanshinone II A through the AMPK-Nampt pathway	PubMed
	tat	Knockdown of SIRT1 by its inhibitor or siRNA results in Tat-mediated reduction of phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC)	PubMed
Vif	vif	Protein kinase A (PKA) binds and phosphorylates A3G at Thr32 in vitro and in vivo. This phosphorylation event reduces the binding of A3G to Vif and its subsequent ubiquitination and degradation	PubMed
Vpr	vpr	HIV-1 Vpr directly interacts with PKA and is phosphorylated at position Ser79 by PKA. PKA activity is necessary for virion-delivered Vpr cell cycle arrest	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D1S2690 (e-PCR), detects polymorphism
- UniSTS:14341

PRKAA2 (e-PCR)
- UniSTS:479768

SHGC-74882 (e-PCR)
- UniSTS:41280

SHGC-68634 (e-PCR)
- UniSTS:95555

D1S2084 (e-PCR)
- UniSTS:49232

GDB:573976 (e-PCR)
- UniSTS:157783

SHGC-35382 (e-PCR)
- UniSTS:68708

PRKAA2_1075 (e-PCR)
- UniSTS:277615

SHGC-141488 (e-PCR)
- UniSTS:181951

SHGC-74886 (e-PCR)
- UniSTS:53448

D1S2056E (e-PCR)
- UniSTS:16629

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables AMP-activated protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables AMP-activated protein kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity	IEA Inferred from Electronic Annotation more info
enables chromatin binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H2BS36 kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables protein serine/threonine/tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in autophagy	IEA Inferred from Electronic Annotation more info
involved_in cellular response to calcium ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to glucose starvation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to glucose starvation	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to glucose stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to nutrient levels	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to nutrient levels	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to nutrient levels	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to prostaglandin E stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in cholesterol biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in fatty acid biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in fatty acid homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in lipid biosynthetic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_positive_effect lipid droplet disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TOR signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of TOR signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of TORC1 signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of hepatocyte apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of tubulin deacetylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of autophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of glycolytic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of macroautophagy	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of peptidyl-lysine acetylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein localization	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to lipid droplet	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of macroautophagy	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of microtubule cytoskeleton organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of stress granule assembly	IEA Inferred from Electronic Annotation more info
involved_in response to muscle activity	IEA Inferred from Electronic Annotation more info
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic stress granule	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
part_of nucleotide-activated protein kinase complex	IBA Inferred from Biological aspect of Ancestor more info
part_of nucleotide-activated protein kinase complex	IPI Inferred from Physical Interaction more info	PubMed
part_of nucleotide-activated protein kinase complex	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: 5'-AMP-activated protein kinase catalytic subunit alpha-2

Names: 5'-AMP-activated protein kinase, catalytic alpha-2 chain; ACACA kinase; AMPK alpha 2; AMPK subunit alpha-2; AMPK-alpha-2 chain; HMGCR kinase; acetyl-CoA carboxylase kinase; hydroxymethylglutaryl-CoA reductase kinase; protein kinase, AMP-activated, alpha 2 catalytic subunit

NP_006243.2

EC 2.7.11.1

EC 2.7.11.31

XP_016857182.1

EC 2.7.11.1

EC 2.7.11.31

XP_054193514.1

EC 2.7.11.1

EC 2.7.11.31

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_006252.4 → NP_006243.2 5'-AMP-activated protein kinase catalytic subunit alpha-2

See identical proteins and their annotated locations for NP_006243.2

Status: VALIDATED

Source sequence(s)

AC099789, AL035705, BC069740, BM979925, DA710012

Consensus CDS

CCDS605.1

UniProtKB/Swiss-Prot

P54646, Q9H1E8, Q9UD43

UniProtKB/TrEMBL

A0MZF5, B2RA25

Related

ENSP00000360290.4, ENST00000371244.9

Conserved Domains (3) summary

cd12200
Location:395 → 550

AMPKA2_C; C-terminal regulatory domain of 5'-AMP-activated serine/threonine kinase, subunit alpha

cd14404
Location:285 → 349

UBA_AID_AAPK2; UBA-like autoinhibitory domain (AID) found in vertebrate 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPKalpha-2)

cd14079
Location:13 → 268

STKc_AMPK_alpha; Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

56645314..56715335

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017001693.2 → XP_016857182.1 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1

UniProtKB/TrEMBL

A0MZF5

Conserved Domains (3) summary

cd12200
Location:305 → 460

AMPKA2_C; C-terminal regulatory domain of 5'-AMP-activated serine/threonine kinase, subunit alpha

cd14404
Location:195 → 259

UBA_AID_AAPK2; UBA-like autoinhibitory domain (AID) found in vertebrate 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPKalpha-2)

cl21453
Location:1 → 178

PKc_like; Protein Kinases, catalytic domain