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
UniProtKB Entry
P54646Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
histone H2BS36 kinase activity / protein serine kinase activity
Processes
autophagy / cellular response to calcium ion / cellular response to glucose stimulus / cellular response to oxidative stress / cellular response to xenobiotic stimulus / energy homeostasis / lipid droplet disassembly / negative regulation of gene expression / negative regulation of hepatocyte apoptotic process / negative regulation of TORC1 signaling / negative regulation of tubulin deacetylation / positive regulation of peptidyl-lysine acetylation / positive regulation of protein localization / protein localization to lipid droplet / regulation of microtubule cytoskeleton organization / regulation of stress granule assembly
Components
axon / cytoplasmic stress granule / dendrite / Golgi apparatus / neuronal cell body / nuclear speck / nucleus
General Function
Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (PubMed:17307971, PubMed:17712357). 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 (PubMed:17307971, PubMed:17712357). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (PubMed:17307971, PubMed:17712357). 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 (PubMed:7959015). Promotes lipolysis of lipid droplets by mediating phosphorylation of isoform 1 of CHKA (CHKalpha2) (PubMed:34077757). Regulates insulin-signaling and glycolysis by phosphorylating IRS1, PFKFB2 and PFKFB3 (By similarity). 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 (By similarity). 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 (PubMed:11518699, PubMed:11554766, PubMed:15866171, PubMed:17711846, PubMed:18184930). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (By similarity). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (By similarity). Acts as a key regulator of cell growth and proliferation by phosphorylating FNIP1, TSC2, RPTOR, WDR24 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 (PubMed:14651849, PubMed:20160076, PubMed:21205641). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (PubMed:36732624). In response to energetic stress, phosphorylates FNIP1, inactivating the non-canonical mTORC1 signaling, thereby promoting nuclear translocation of TFEB and TFE3, and inducing transcription of lysosomal or autophagy genes (PubMed:37079666). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641). In that process also activates WDR45/WIPI4 (PubMed:28561066). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (PubMed:32029622). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (By similarity). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (By similarity). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (PubMed:17486097). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (PubMed:12519745, PubMed:20074060). 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 (By similarity). Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1 (By similarity). Upon glucose starvation, promotes ARF6 activation in a kinase-independent manner leading to cell migration (PubMed:36017701). Upon glucose deprivation mediates the phosphorylation of ACSS2 at 'Ser-659', which exposes the nuclear localization signal of ACSS2, required for its interaction with KPNA1 and nuclear translocation (PubMed:28552616). Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (PubMed:36367943)
Specific Function
[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
Pfam Domain Function
Signal Regions
Not Available
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
1p32.2
External Identifiers
ResourceLink
UniProtKB IDP54646
UniProtKB Entry NameAAPK2_HUMAN
GeneCard IDPRKAA2
HGNC IDHGNC:9377
PDB ID(s)2H6D, 2LTU, 2YZA, 3AQV, 4CFE, 4CFF, 4ZHX, 5EZV, 5ISO, 6B1U, 6B2E, 6BX6, 7MYJ
KEGG IDhsa:5563
NCBI Gene ID5563
General References
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Associated Data

Bio-Entities
Bio-EntityType
5'-AMP-activated protein kinase catalytic subunit alpha-2 (Humans)protein
primary
5'-AMP-activated protein kinase (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Acetylsalicylic acidapproved, vet_approvedunknowntargetactivatorDetails
Fostamatinibapproved, investigationalunknowntargetinhibitorDetails
TopiramateapprovedunknowntransporterinducerDetails
Adenosine phosphateapproved, investigational, nutraceutical, withdrawnyestargetactivatorDetails