Gene/Proteome Database (LMPD)

LMPD ID
LMP001886
Gene ID
5562
Species
Homo sapiens (Human)
Gene Name
protein kinase, AMP-activated, alpha 1 catalytic subunit
Gene Symbol
PRKAA1
Synonyms
AMPK; AMPKa1
Alternate Names
5'-AMP-activated protein kinase catalytic subunit alpha-1;,ACACA kinase; AMPK alpha 1; HMGCR kinase; AMPK subunit alpha-1; tau-protein kinase PRKAA1; acetyl-CoA carboxylase kinase; AMP -activate kinase alpha 1 subunit; hydroxymethylglutaryl-CoA reductase kinase; AMP-activated protein kinase, catalytic, alpha-1', "5'-AMP-activated protein kinase, catalytic alpha-1 chain
Chromosome
5
Map Location
5p12
EC Number
2.7.11.1
Summary
The protein encoded by this gene belongs to the ser/thr protein kinase family. It is the catalytic subunit of the 5'-prime-AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor conserved in all eukaryotic cells. The kinase activity of AMPK is activated by the stimuli that increase the cellular AMP/ATP ratio. AMPK regulates the activities of a number of key metabolic enzymes through phosphorylation. It protects cells from stresses that cause ATP depletion by switching off ATP-consuming biosynthetic pathways. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PRKAA1

Proteins

5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1
Refseq ID NP_006242
Protein GI 94557301
UniProt ID Q13131
mRNA ID NM_006251
Length 559
RefSeq Status REVIEWED
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMIDDEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDSFLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDEITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPGSHTIEFFEMCANLIKILAQ
5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 2
Refseq ID NP_996790
Protein GI 94557299
UniProt ID Q13131
mRNA ID NM_206907
Length 574
RefSeq Status REVIEWED
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRKSDVPGVVKTGSTKELDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMIDDEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDSFLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTYSKMSLQLYQVDSRTYLLDFRSIDDEITEAKSGTATPQRSGSVSNYRSCQRSDSDAEAQGKSSEVSLTSSVTSLDSSPVDLTPRPGSHTIEFFEMCANLIKILAQ

Gene Information

Entrez Gene ID
5562
Gene Name
protein kinase, AMP-activated, alpha 1 catalytic subunit
Gene Symbol
PRKAA1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0031588 ISS:UniProtKB C AMP-activated protein kinase complex
GO:0016324 IEA:Ensembl C apical plasma membrane
GO:0005737 IDA:HPA C cytoplasm
GO:0005829 TAS:Reactome C cytosol
GO:0005622 IC:UniProtKB C intracellular
GO:0005634 ISS:UniProtKB C nucleus
GO:0004679 IDA:UniProtKB F AMP-activated protein kinase activity
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0050405 IEA:UniProtKB-EC F [acetyl-CoA carboxylase] kinase activity
GO:0047322 IEA:UniProtKB-EC F [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
GO:0004691 NAS:UniProtKB F cAMP-dependent protein kinase activity
GO:0003682 ISS:UniProtKB F chromatin binding
GO:0035174 ISS:UniProtKB F histone serine kinase activity
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0004672 IDA:UniProtKB F protein kinase activity
GO:0050321 IEA:UniProtKB-EC F tau-protein kinase activity
GO:0016055 IEA:UniProtKB-KW P Wnt signaling pathway
GO:0000187 NAS:UniProtKB P activation of MAPK activity
GO:0006914 IEA:UniProtKB-KW P autophagy
GO:0007050 TAS:Reactome P cell cycle arrest
GO:0071361 IEA:Ensembl P cellular response to ethanol
GO:0042149 ISS:UniProtKB P cellular response to glucose starvation
GO:0070301 IEA:Ensembl P cellular response to hydrogen peroxide
GO:0071456 IEA:Ensembl P cellular response to hypoxia
GO:0031669 ISS:UniProtKB P cellular response to nutrient levels
GO:0006695 IEA:UniProtKB-KW P cholesterol biosynthetic process
GO:0009631 IEA:Ensembl P cold acclimation
GO:0006633 IEA:UniProtKB-KW P fatty acid biosynthetic process
GO:0055089 ISS:UniProtKB P fatty acid homeostasis
GO:0019395 IEA:Ensembl P fatty acid oxidation
GO:0042593 ISS:UniProtKB P glucose homeostasis
GO:0006006 IEA:Ensembl P glucose metabolic process
GO:0008286 TAS:Reactome P insulin receptor signaling pathway
GO:0008610 ISS:UniProtKB P lipid biosynthetic process
GO:0032007 ISS:UniProtKB P negative regulation of TOR signaling
GO:0043066 ISS:UniProtKB P negative regulation of apoptotic process
GO:2001274 IEA:Ensembl P negative regulation of glucose import in response to insulin stimulus
GO:0046318 NAS:UniProtKB P negative regulation of glucosylceramide biosynthetic process
GO:0050995 ISS:UniProtKB P negative regulation of lipid catabolic process
GO:0010508 ISS:UniProtKB P positive regulation of autophagy
GO:0008284 IEA:Ensembl P positive regulation of cell proliferation
GO:0045542 NAS:UniProtKB P positive regulation of cholesterol biosynthetic process
GO:0010628 IDA:UniProtKB P positive regulation of gene expression
GO:0045821 ISS:UniProtKB P positive regulation of glycolytic process
GO:0051291 IEA:Ensembl P protein heterooligomerization
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0042752 ISS:UniProtKB P regulation of circadian rhythm
GO:2000505 ISS:UniProtKB P regulation of energy homeostasis
GO:0006355 IEA:UniProtKB-KW P regulation of transcription, DNA-templated
GO:0060627 IEA:Ensembl P regulation of vesicle-mediated transport
GO:0009411 IEA:Ensembl P response to UV
GO:0014823 IEA:Ensembl P response to activity
GO:0031000 IEA:Ensembl P response to caffeine
GO:1901563 IEA:Ensembl P response to camptothecin
GO:0010332 ISS:UniProtKB P response to gamma radiation
GO:0001666 NAS:UniProtKB P response to hypoxia
GO:0048511 IEA:UniProtKB-KW P rhythmic process
GO:0007165 TAS:ProtInc P signal transduction
GO:0006351 IEA:UniProtKB-KW P transcription, DNA-templated

KEGG Pathway Links

KEGG Pathway ID Description
hsa04152 AMPK signaling pathway
hsa04068 FoxO signaling pathway
hsa04932 Non-alcoholic fatty liver disease (NAFLD)
hsa04921 Oxytocin signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR028797 5'-AMP-activated protein kinase catalytic subunit alpha-1
IPR028375 KA1 domain/Ssp2 C-terminal domain
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR011009 Protein kinase-like domain
IPR008271 Serine/threonine-protein kinase, active site
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain

UniProt Annotations

Entry Information

Gene Name
protein kinase, AMP-activated, alpha 1 catalytic subunit
Protein Entry
AAPK1_HUMAN
UniProt ID
Q13131
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q13131-1; Sequence=Displayed; Name=2; IsoId=Q13131-2; Sequence=VSP_035431;
Catalytic Activity ATP + [acetyl-CoA carboxylase] = ADP + [acetyl-CoA carboxylase] phosphate.
Catalytic Activity ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate.
Catalytic Activity ATP + [tau protein] = ADP + [tau protein] phosphate.
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Cofactor Name=Mg(2+); Xref=ChEBI
Domain The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity. {ECO
Enzyme Regulation Activated by phosphorylation on Thr-183. Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183. AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183. ADP also stimulates Thr- 183 phosphorylation, without stimulating already phosphorylated AMPK. ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive. Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP. AMPK is activated by antihyperglycemic drug metformin, a drug prescribed to patients with type 2 diabetes: in vivo, metformin seems to mainly inhibit liver gluconeogenesis. However, metformin can be used to activate AMPK in muscle and other cells in culture or ex vivo (PubMed:11602624). Selectively inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]- 3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by resveratrol, a natural polyphenol present in red wine, and S17834, a synthetic polyphenol. {ECO
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. {ECO
Interaction P08238:HSP90AB1; NbExp=2; IntAct=EBI-1181405, EBI-352572; Q9Y478:PRKAB1; NbExp=5; IntAct=EBI-1181405, EBI-719769; O43741:PRKAB2; NbExp=6; IntAct=EBI-1181405, EBI-1053424;
Ptm Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a much lower level. Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK. Dephosphorylated by PPM1A and PPM1B. {ECO
Ptm Ubiquitinated.
Sequence Caution Sequence=AAA64850.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAD43027.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=AAH37303.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=BAA36547.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ; Sequence=BAG35788.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Similarity Contains 1 protein kinase domain.
Subcellular Location Cytoplasm . Nucleus . Note=In response to stress, recruited by p53/TP53 to specific promoters.
Subunit AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non- catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2. {ECO

Identical and Related Proteins

Unique RefSeq proteins for LMP001886 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
94557301 RefSeq NP_006242 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1
94557299 RefSeq NP_996790 574 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 2

Identical Sequences to LMP001886 proteins

Reference Database Accession Length Protein Name
GI:94557301 GenBank EAW56000.1 559 protein kinase, AMP-activated, alpha 1 catalytic subunit, isoform CRA_a [Homo sapiens]
GI:94557301 GenBank JAA13923.1 559 protein kinase, AMP-activated, alpha 1 catalytic subunit [Pan troglodytes]
GI:94557301 GenBank JAA13924.1 559 protein kinase, AMP-activated, alpha 1 catalytic subunit [Pan troglodytes]
GI:94557299 GenBank JAA13925.1 574 protein kinase, AMP-activated, alpha 1 catalytic subunit [Pan troglodytes]
GI:94557301 RefSeq XP_003274422.1 559 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Nomascus leucogenys]
GI:94557301 RefSeq XP_003811017.1 559 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X2 [Pan paniscus]
GI:94557299 RefSeq XP_003811018.1 574 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [Pan paniscus]
GI:94557299 RefSeq XP_009238944.1 574 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [Pongo abelii]
GI:94557299 RefSeq XP_009447514.1 574 PREDICTED: LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase catalytic subunit alpha-1 [Pan troglodytes]
GI:94557301 SwissProt Q13131.4 559 RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-1; Short=AMPK subunit alpha-1; AltName: Full=Acetyl-CoA carboxylase kinase; Short=ACACA kinase; AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase; Short=HMGCR kinase; AltName: Full=Tau-protein kinase PRKAA1 [Homo sapiens]

Related Sequences to LMP001886 proteins

Reference Database Accession Length Protein Name
GI:94557299 GenBank AAH48980.1 574 Protein kinase, AMP-activated, alpha 1 catalytic subunit [Homo sapiens]
GI:94557301 GenBank JAB11230.1 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Callithrix jacchus]
GI:94557299 GenBank JAB11231.1 574 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 2 [Callithrix jacchus]
GI:94557301 GenBank JAB16357.1 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Callithrix jacchus]
GI:94557301 GenBank JAB16358.1 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Callithrix jacchus]
GI:94557301 GenBank JAB31828.1 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Callithrix jacchus]
GI:94557299 GenBank AIC54945.1 574 PRKAA1, partial [synthetic construct]
GI:94557301 RefSeq XP_004058959.1 559 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [Gorilla gorilla gorilla]
GI:94557299 RefSeq XP_004058960.1 574 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 2 [Gorilla gorilla gorilla]
GI:94557299 RefSeq XP_003274423.2 645 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 2 [Nomascus leucogenys]
GI:94557299 RefSeq XP_006733395.1 574 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [Leptonychotes weddellii]
GI:94557301 RefSeq XP_003899658.2 559 PREDICTED: 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [Papio anubis]