5'-AMP-activated protein kinase catalytic subunit alpha-1

Details

Name
5'-AMP-activated protein kinase catalytic subunit alpha-1
Synonyms
  • 2.7.11.1
  • ACACA kinase
  • Acetyl-CoA carboxylase kinase
  • AMPK subunit alpha-1
  • AMPK1
  • HMGCR kinase
  • Hydroxymethylglutaryl-CoA reductase kinase
  • Tau-protein kinase PRKAA1
Gene Name
PRKAA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037059|5'-AMP-activated protein kinase catalytic subunit alpha-1
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNR
QKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNG
RLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEF
LRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDG
IFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMID
DEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDS
FLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDI
MAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDE
ITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPG
SHTIEFFEMCANLIKILAQ
Number of residues
559
Molecular Weight
64008.64
Theoretical pI
7.64
GO Classification
Functions
[acetyl-CoA carboxylase] kinase activity / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / AMP-activated protein kinase activity / ATP binding / cAMP-dependent protein kinase activity / chromatin binding / histone serine kinase activity / metal ion binding / protein kinase activity / tau-protein kinase activity
Processes
activation of MAPK activity / cell cycle arrest / cellular response to ethanol / cellular response to glucose starvation / cellular response to hydrogen peroxide / cellular response to hypoxia / cellular response to nutrient levels / cellular response to prostaglandin E stimulus / cholesterol biosynthetic process / cold acclimation / fatty acid biosynthetic process / fatty acid homeostasis / fatty acid oxidation / gene expression / glucose homeostasis / glucose metabolic process / histone-serine phosphorylation / insulin receptor signaling pathway / intracellular signal transduction / lipid biosynthetic process / macroautophagy / negative regulation of apoptotic process / negative regulation of glucose import in response to insulin stimulus / negative regulation of glucosylceramide biosynthetic process / negative regulation of lipid catabolic process / negative regulation of TOR signaling / positive regulation of autophagy / positive regulation of cell proliferation / positive regulation of cholesterol biosynthetic process / positive regulation of gene expression / positive regulation of glycolytic process / positive regulation of skeletal muscle tissue development / protein heterooligomerization / protein phosphorylation / regulation of circadian rhythm / regulation of energy homeostasis / regulation of peptidyl-serine phosphorylation / regulation of transcription, DNA-templated / regulation of vesicle-mediated transport / response to activity / response to caffeine / response to camptothecin / response to gamma radiation / response to hypoxia / response to UV / rhythmic process / signal transduction / transcription initiation from RNA polymerase II promoter / Wnt signaling pathway
Components
apical plasma membrane / cytoplasm / cytosol / intracellular / nucleotide-activated protein kinase complex / nucleus
General Function
Tau-protein 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. 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 has tau-protein kinase activity: in response to amyloid beta A4 protein (APP) exposure, activated by CAMKK2, leading to phosphorylation of MAPT/TAU; however the relevance of such data remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010471|5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1)
ATGCGCAGACTCAGTTCCTGGAGAAAGATGGCGACAGCCGAGAAGCAGAAACACGACGGG
CGGGTGAAGATCGGCCACTACATTCTGGGTGACACGCTGGGGGTCGGCACCTTCGGCAAA
GTGAAGGTTGGCAAACATGAATTGACTGGGCATAAAGTAGCTGTGAAGATACTCAATCGA
CAGAAGATTCGGAGCCTTGATGTGGTAGGAAAAATCCGCAGAGAAATTCAGAACCTCAAG
CTTTTCAGGCATCCTCATATAATTAAACTGTACCAGGTCATCAGTACACCATCTGATATT
TTCATGGTGATGGAATATGTCTCAGGAGGAGAGCTATTTGATTATATCTGTAAGAATGGA
AGGCTGGATGAAAAAGAAAGTCGGCGTCTGTTCCAACAGATCCTTTCTGGTGTGGATTAT
TGTCACAGGCATATGGTGGTCCATAGAGATTTGAAACCTGAAAATGTCCTGCTTGATGCA
CACATGAATGCAAAGATAGCTGATTTTGGTCTTTCAAACATGATGTCAGATGGTGAATTT
TTAAGAACAAGTTGTGGCTCACCCAACTATGCTGCACCAGAAGTAATTTCAGGAAGATTG
TATGCAGGCCCAGAGGTAGATATATGGAGCAGTGGGGTTATTCTCTATGCTTTATTATGT
GGAACCCTTCCATTTGATGATGACCATGTGCCAACTCTTTTTAAGAAGATATGTGATGGG
ATCTTCTATACCCCTCAATATTTAAATCCTTCTGTGATTAGCCTTTTGAAACATATGCTG
CAGGTGGATCCCATGAAGAGGGCCACAATCAAAGATATCAGGGAACATGAATGGTTTAAA
CAGGACCTTCCAAAATATCTCTTTCCTGAGGATCCATCATATAGTTCAACCATGATTGAT
GATGAAGCCTTAAAAGAAGTATGTGAAAAGTTTGAGTGCTCAGAAGAGGAAGTTCTCAGC
TGTCTTTACAACAGAAATCACCAGGATCCTTTGGCAGTTGCCTACCATCTCATAATAGAT
AACAGGAGAATAATGAATGAAGCCAAAGATTTCTATTTGGCGACAAGCCCACCTGATTCT
TTTCTTGATGATCATCACCTGACTCGGCCCCATCCTGAAAGAGTACCATTCTTGGTTGCT
GAAACACCAAGGGCACGCCATACCCTTGATGAATTAAATCCACAGAAATCCAAACACCAA
GGTGTAAGGAAAGCAAAATGGCATTTAGGAATTAGAAGTCAAAGTCGACCAAATGATATT
ATGGCAGAAGTATGTAGAGCAATCAAACAATTGGATTATGAATGGAAGGTTGTAAACCCA
TATTATTTGCGTGTACGAAGGAAGAATCCTGTGACAAGCACTTACTCCAAAATGAGTCTA
CAGTTATACCAAGTGGATAGTAGAACTTATCTACTGGATTTCCGTAGTATTGATGATGAA
ATTACAGAAGCCAAATCAGGGACTGCTACTCCACAGAGATCGGGATCAGTTAGCAACTAT
CGATCTTGCCAAAGGAGTGATTCAGATGCTGAGGCTCAAGGAAAATCCTCAGAAGTTTCT
CTTACCTCATCTGTGACCTCACTTGACTCTTCTCCTGTTGACCTAACTCCAAGACCTGGA
AGTCACACAATAGAATTTTTTGAGATGTGTGCAAATCTAATTAAAATTCTTGCACAATAA
Chromosome Location
5
Locus
5p12
External Identifiers
ResourceLink
UniProtKB IDQ13131
UniProtKB Entry NameAAPK1_HUMAN
GenBank Protein ID4115829
GenBank Gene IDAB022017
GenAtlas IDPRKAA1
HGNC IDHGNC:9376
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00131Adenosine phosphateapproved, investigational, nutraceuticalunknownactivatorDetails
DB00171ATPinvestigational, nutraceuticalunknownDetails
DB00914Phenforminapproved, investigational, withdrawnyesactivatorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00945Acetylsalicylic acidapproved, vet_approvedunknownactivatorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails
DB00273TopiramateapprovedunknowninducerDetails