5'-AMP-activated protein kinase catalytic subunit alpha-2

Details

Name
5'-AMP-activated protein kinase catalytic subunit alpha-2
Synonyms
  • 2.7.11.1
  • ACACA kinase
  • Acetyl-CoA carboxylase kinase
  • AMPK
  • AMPK subunit alpha-2
  • AMPK2
  • HMGCR kinase
  • Hydroxymethylglutaryl-CoA reductase kinase
Gene Name
PRKAA2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0013353|5'-AMP-activated protein kinase catalytic subunit alpha-2
MAEKQKHDGRVKIGHYVLGDTLGVGTFGKVKIGEHQLTGHKVAVKILNRQKIRSLDVVGK
IKREIQNLKLFRHPHIIKLYQVISTPTDFFMVMEYVSGGELFDYICKHGRVEEMEARRLF
QQILSAVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYA
APEVISGRLYAGPEVDIWSCGVILYALLCGTLPFDDEHVPTLFKKIRGGVFYIPEYLNRS
VATLLMHMLQVDPLKRATIKDIREHEWFKQDLPSYLFPEDPSYDANVIDDEAVKEVCEKF
ECTESEVMNSLYSGDPQDQLAVAYHLIIDNRRIMNQASEFYLASSPPSGSFMDDSAMHIP
PGLKPHPERMPPLIADSPKARCPLDALNTTKPKSLAVKKAKWHLGIRSQSKPYDIMAEVY
RAMKQLDFEWKVVNAYHLRVRRKNPVTGNYVKMSLQLYLVDNRSYLLDFKSIDDEVVEQR
SGSSTPQRSCSAAGLHRPRSSFDSTTAESHSLSGSLTGSLTGSTLSSVSPRLGSHTMDFF
EMCASLITTLAR
Number of residues
552
Molecular Weight
62319.055
Theoretical pI
Not Available
GO Classification
Functions
[acetyl-CoA carboxylase] kinase activity / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / AMP-activated protein kinase activity / ATP binding / chromatin binding / histone serine kinase activity / metal ion binding / protein kinase activity / protein serine/threonine kinase activity / protein serine/threonine/tyrosine kinase activity
Processes
carnitine shuttle / cell cycle arrest / cellular lipid metabolic process / cellular response to drug / cellular response to glucose starvation / cellular response to nutrient levels / cellular response to prostaglandin E stimulus / cholesterol biosynthetic process / energy reserve metabolic process / fatty acid biosynthetic process / fatty acid homeostasis / gene expression / glucose homeostasis / histone-serine phosphorylation / insulin receptor signaling pathway / intracellular signal transduction / lipid biosynthetic process / macroautophagy / membrane organization / mitochondrion organization / negative regulation of apoptotic process / negative regulation of TOR signaling / organelle organization / positive regulation of autophagy / positive regulation of glycolytic process / positive regulation of macroautophagy / protein phosphorylation / regulation of circadian rhythm / regulation of energy homeostasis / regulation of fatty acid biosynthetic process / regulation of macroautophagy / regulation of transcription, DNA-templated / response to muscle activity / response to stress / rhythmic process / signal transduction / small molecule metabolic process / transcription initiation from RNA polymerase II promoter / Wnt signaling pathway
Components
cytoplasm / cytosol / nucleoplasm / nucleotide-activated protein kinase complex
General Function
Protein serine/threonine/tyrosine kinase activity
Specific Function
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Regulates lipid synthesis by phosphorylating and inactivating lipid metabolic enzymes such as ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and cholesterol synthesis by phosphorylating acetyl-CoA carboxylase (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, respectively. Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3. Involved in insulin receptor/INSR internalization (PubMed:25687571). AMPK stimulates glucose uptake in muscle by increasing the translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane, possibly by mediating phosphorylation of TBC1D4/AS160. Regulates transcription and chromatin structure by phosphorylating transcription regulators involved in energy metabolism such as CRTC2/TORC2, FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm. In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription. Acts as a key regulator of cell growth and proliferation by phosphorylating TSC2, RPTOR and ATG1/ULK1: in response to nutrient limitation, negatively regulates the mTORC1 complex by phosphorylating RPTOR component of the mTORC1 complex and by phosphorylating and activating TSC2. In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1. AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it. May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy (composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14) and non-autophagy (composed of PIK3C3, BECN1 and PIK3R4) complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0013354|5'-AMP-activated protein kinase catalytic subunit alpha-2 (PRKAA2)
ATGGCTGAGAAGCAGAAGCACGACGGGCGGGTGAAGATCGGACACTACGTGCTGGGCGAC
ACGCTGGGCGTCGGCACCTTCGGCAAAGTGAAGATTGGAGAACATCAATTAACAGGCCAT
AAAGTGGCAGTTAAAATCTTAAATAGACAGAAGATTCGCAGTTTAGATGTTGTTGGAAAA
ATAAAACGAGAAATTCAAAATCTAAAACTCTTTCGTCATCCTCATATTATCAAACTATAC
CAGGTGATCAGCACTCCAACAGATTTTTTTATGGTAATGGAATATGTGTCTGGAGGTGAA
TTATTTGACTACATCTGTAAGCATGGACGGGTTGAAGAGATGGAAGCCAGGCGGCTCTTT
CAGCAGATTCTGTCTGCTGTGGATTACTGTCATAGGCATATGGTTGTTCATCGAGACCTG
AAACCAGAGAATGTCCTGTTGGATGCACACATGAATGCCAAGATAGCCGATTTCGGATTA
TCTAATATGATGTCAGATGGTGAATTTCTGAGAACTAGTTGCGGATCTCCAAATTATGCA
GCACCTGAAGTCATCTCAGGCAGATTGTATGCAGGTCCTGAAGTTGATATCTGGAGCTGT
GGTGTTATCTTGTATGCTCTTCTTTGTGGCACCCTCCCATTTGATGATGAGCATGTACCT
ACGTTATTTAAGAAGATCCGAGGGGGTGTCTTTTATATCCCAGAATATCTCAATCGTTCT
GTCGCCACTCTCCTGATGCATATGCTGCAGGTTGACCCACTGAAACGAGCAACTATCAAA
GACATAAGAGAGCATGAATGGTTTAAACAAGATTTGCCCAGTTACTTATTTCCTGAAGAC
CCTTCCTATGATGCTAACGTCATTGATGATGAGGCTGTGAAAGAAGTGTGTGAAAAATTT
GAATGTACAGAATCAGAAGTAATGAACAGTTTATATAGTGGTGACCCTCAAGACCAGCTT
GCAGTGGCTTATCATCTTATCATTGACAATCGGAGAATAATGAACCAAGCCAGTGAGTTC
TACCTCGCCTCTAGTCCTCCATCTGGTTCTTTTATGGATGATAGTGCCATGCATATTCCC
CCAGGCCTGAAACCTCATCCAGAAAGGATGCCACCTCTTATAGCAGACAGCCCCAAAGCA
AGATGTCCATTGGATGCACTGAATACGACTAAGCCCAAATCTTTAGCTGTGAAAAAAGCC
AAGTGGCATCTTGGAATCCGAAGTCAGAGCAAACCGTATGACATTATGGCTGAAGTTTAC
CGAGCTATGAAGCAGCTGGATTTTGAATGGAAGGTAGTGAATGCATACCATCTTCGTGTA
AGAAGAAAAAATCCAGTGACTGGCAATTACGTGAAAATGAGCTTACAACTTTACCTGGTT
GATAACAGGAGCTATCTTTTGGACTTTAAAAGCATTGATGATGAAGTAGTGGAGCAGAGA
TCTGGTTCCTCAACACCTCAGCGTTCCTGTTCTGCTGCTGGCTTACACAGACCAAGATCA
AGTTTTGATTCCACAACTGCAGAGAGCCATTCACTTTCTGGCTCTCTCACTGGCTCTTTG
ACCGGAAGCACATTGTCTTCAGTTTCACCTCGCCTGGGCAGTCACACCATGGATTTTTTT
GAAATGTGTGCCAGTCTGATTACTACTTTAGCCCGTTGA
Chromosome Location
1
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP54646
UniProtKB Entry NameAAPK2_HUMAN
HGNC IDHGNC:9377
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownactivatorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00273TopiramateapprovedunknowninducerDetails
DB00131Adenosine phosphateapproved, investigational, nutraceutical, withdrawnyesactivatorDetails