Gene/Proteome Database (LMPD)

LMPD ID
LMP012732
Gene ID
65248
Species
Rattus norvegicus (Rat)
Gene Name
protein kinase, AMP-activated, alpha 1 catalytic subunit
Gene Symbol
Prkaa1
Synonyms
AMPKalpha1;
Alternate Names
5'-AMP-activated protein kinase catalytic subunit alpha-1; ACACA kinase; HMGCR kinase; AMPK alpha-1 chain; tau-protein kinase PRKAA1; acetyl-CoA carboxylase kinase; hydroxymethylglutaryl-CoA reductase kinase;
Chromosome
2
Map Location
2q16
EC Number
2.7.11.1
Summary
catalytic subunit of AMP-activated protein kinase; phosphorylates hepatic acetyl-CoA carboxylase and adipose hormone-sensitive lipase [RGD, Feb 2006]
Orthologs
View orthologs and multiple alignments for Prkaa1

Proteins

5'-AMP-activated protein kinase catalytic subunit alpha-1
Refseq ID NP_062015
Protein GI 478247105
UniProt ID P54645
mRNA ID NM_019142
Length 559
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRATIKDIREHEWFKQDLPKYLFPEDPSYSSTMIDDEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDSFLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDEITEAKSGTATPQRSGSISNYRSCQRSDSDAEAQGKPSEVSLTSSVTSLDSSPVDVAPRPGSHTIEFFEMCANLIKILAQ

Gene Information

Entrez Gene ID
65248
Gene Name
protein kinase, AMP-activated, alpha 1 catalytic subunit
Gene Symbol
Prkaa1
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0031588 IDA:UniProtKB C AMP-activated protein kinase complex
GO:0016324 IDA:UniProtKB C apical plasma membrane
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005634 ISS:UniProtKB C nucleus
GO:0043234 IDA:RGD C protein complex
GO:0004679 IDA:UniProtKB F AMP-activated protein kinase activity
GO:0005524 IDA:RGD 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:0003682 ISS:UniProtKB F chromatin binding
GO:0042557 NAS:UniProtKB F eukaryotic elongation factor-2 kinase activator activity
GO:0035174 ISS:UniProtKB F histone serine kinase activity
GO:0019900 IPI:RGD F kinase binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0008022 IPI:RGD F protein C-terminus binding
GO:0004674 IDA:RGD F protein serine/threonine kinase activity
GO:0050321 IEA:UniProtKB-EC F tau-protein kinase activity
GO:0016055 IEA:UniProtKB-KW P Wnt signaling pathway
GO:0000187 IEA:InterPro P activation of MAPK activity
GO:0006914 IEA:UniProtKB-KW P autophagy
GO:0071361 IEP:RGD P cellular response to ethanol
GO:0042149 ISS:UniProtKB P cellular response to glucose starvation
GO:0070301 IEP:RGD P cellular response to hydrogen peroxide
GO:0071456 IEP:RGD P cellular response to hypoxia
GO:0031669 ISS:UniProtKB P cellular response to nutrient levels
GO:0071417 IEP:RGD P cellular response to organonitrogen compound
GO:0006695 IEA:UniProtKB-KW P cholesterol biosynthetic process
GO:0009631 IDA:RGD P cold acclimation
GO:0006633 IEA:UniProtKB-KW P fatty acid biosynthetic process
GO:0055089 IDA: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: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 IMP:RGD P negative regulation of glucose import in response to insulin stimulus
GO:0050995 ISS:UniProtKB P negative regulation of lipid catabolic process
GO:0017148 NAS:UniProtKB P negative regulation of translation
GO:0010508 ISS:UniProtKB P positive regulation of autophagy
GO:0008284 IDA:RGD P positive regulation of cell proliferation
GO:0046321 NAS:UniProtKB P positive regulation of fatty acid oxidation
GO:0010628 IEA:Ensembl P positive regulation of gene expression
GO:0045722 NAS:UniProtKB P positive regulation of gluconeogenesis
GO:0046326 NAS:UniProtKB P positive regulation of glucose import
GO:0045821 IDA:UniProtKB P positive regulation of glycolytic process
GO:0051291 IDA:RGD P protein heterooligomerization
GO:0006468 NAS:UniProtKB P protein phosphorylation
GO:0042752 ISS:UniProtKB P regulation of circadian rhythm
GO:2000505 IDA:UniProtKB P regulation of energy homeostasis
GO:0006355 IEA:UniProtKB-KW P regulation of transcription, DNA-templated
GO:0060627 IMP:RGD P regulation of vesicle-mediated transport
GO:0009411 IEA:Ensembl P response to UV
GO:0014823 IDA:RGD P response to activity
GO:0031000 IDA:RGD P response to caffeine
GO:1901563 IEA:Ensembl P response to camptothecin
GO:0010332 ISS:UniProtKB P response to gamma radiation
GO:0048511 IEA:UniProtKB-KW P rhythmic process
GO:0006351 IEA:UniProtKB-KW P transcription, DNA-templated

KEGG Pathway Links

KEGG Pathway ID Description
ko04152 AMPK signaling pathway
rno04152 AMPK signaling pathway
ko04920 Adipocytokine signaling pathway
rno04920 Adipocytokine signaling pathway
ko04710 Circadian rhythm
rno04710 Circadian rhythm
rno04068 FoxO signaling pathway
ko05410 Hypertrophic cardiomyopathy (HCM)
rno05410 Hypertrophic cardiomyopathy (HCM)
ko04910 Insulin signaling pathway
rno04910 Insulin signaling pathway
ko04932 Non-alcoholic fatty liver disease (NAFLD)
rno04932 Non-alcoholic fatty liver disease (NAFLD)
ko04921 Oxytocin signaling pathway
rno04921 Oxytocin signaling pathway
ko04151 PI3K-Akt signaling pathway
rno04151 PI3K-Akt signaling pathway
ko04140 Regulation of autophagy
rno04140 Regulation of autophagy
ko04150 mTOR signaling pathway
rno04150 mTOR signaling pathway

REACTOME Pathway Links

REACTOME Pathway ID Description
5954019 Energy dependent regulation of mTOR by LKB1-AMPK
5953430 IGF1R signaling cascade
5953428 IRS-mediated signalling
5953425 IRS-related events
5953429 IRS-related events triggered by IGF1R
5953422 Insulin receptor signalling cascade
5953432 PI3K Cascade
5953733 PKB-mediated events
5954018 Regulation of AMPK activity via LKB1
5954161 Regulation of Rheb GTPase activity by AMPK
5953381 Signal Transduction
5953423 Signaling by Insulin receptor
5953431 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
5953766 mTOR signalling

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_RAT
UniProt ID
P54645
Species
Rat

Comments

Comment Type Description
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:CHEBI:18420; Evidence= ;
Domain The AIS (autoinhibitory sequence) region shows some sequence similarity with the ubiquitin-associated domains and represses kinase activity
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. 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:0000269|PubMed:14511394, ECO:0000269|PubMed:14614828, ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:16054096, ECO:0000269|PubMed:8910387}.
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:0000269|PubMed:10025949, ECO:0000269|PubMed:11069105, ECO:0000269|PubMed:11598104, ECO:0000269|PubMed:11724780, ECO:0000269|PubMed:12065600, ECO:0000269|PubMed:12740371, ECO:0000269|PubMed:14511394, ECO:0000269|PubMed:14709557, ECO:0000269|PubMed:17341212, ECO:0000269|PubMed:21204788, ECO:0000269|PubMed:2369897, ECO:0000269|PubMed:9029219}.
Interaction Q76JQ2:Flcn; NbExp=2; IntAct=EBI-7596967, EBI-7596839;
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. There is some ambiguity for some phosphosites: Ser-360/Thr-368 and Ser- 486/Thr-488. Dephosphorylated by PPM1A and PPM1B (By similarity)
Ptm Ubiquitinated
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:0000269|PubMed:17851531, ECO:0000269|PubMed:21399626, ECO:0000269|PubMed:7961907}.
Tissue Specificity Low expression in kidney, liver, lung, heart and brain.

Identical and Related Proteins

Unique RefSeq proteins for LMP012732 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
478247105 RefSeq NP_062015 559 5'-AMP-activated protein kinase catalytic subunit alpha-1

Identical Sequences to LMP012732 proteins

Reference Database Accession Length Protein Name
GI:478247105 SwissProt P54645.2 559 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 [Rattus norvegicus]

Related Sequences to LMP012732 proteins

Reference Database Accession Length Protein Name
GI:478247105 RefSeq NP_001013385.3 559 5'-AMP-activated protein kinase catalytic subunit alpha-1 [Mus musculus]
GI:478247105 SwissProt Q5EG47.2 559 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 [Mus musculus]
GI:478247105 SwissProt P54645.2 559 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 [Rattus norvegicus]