Prkaa1
entrez
105787
canonical
uniprot
Q5EG47
canonical
ensembl
ENSMUSG00000050697
resolver
ensp
ENSMUSP00000063166
resolver
ensp
ENSMUSP00000154562
resolver
enst
ENSMUST00000051186
resolver
enst
ENSMUST00000228218
resolver
genesymbol
Prkaa1
resolver
uniprot
A0A2I3BRE2
resolver
uniprot
Q3TUQ7
resolver
uniprot
Q8BUX6
resolver
uniprot_entry
A0A2I3BRE2_MOUSE
resolver
uniprot_entry
AAPK1_MOUSE
resolver
uniprot_entry
Q3TUQ7_MOUSE
resolver
uniprot_entry
Q8BUX6_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Activated by phosphorylation on Thr-183 by STK11/LKB1 (PubMed:15980064, PubMed:16054095, PubMed:21459323, PubMed:39695235). Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or PRKAG3) results in allosteric activation, inducing phosphorylation on Thr-183 (PubMed:15980064, PubMed:16054095). AMP-binding to gamma subunit also sustains activity by preventing dephosphorylation of Thr-183 (PubMed:15980064, PubMed:16054095). ADP also stimulates Thr-183 phosphorylation, without stimulating already phosphorylated AMPK (PubMed:15980064, PubMed:16054095). ATP promotes dephosphorylation of Thr-183, rendering the enzyme inactive (PubMed:15980064, PubMed:16054095). Under physiological conditions AMPK mainly exists in its inactive form in complex with ATP, which is much more abundant than AMP (PubMed:15980064, PubMed:16054095). Inhibited by modified adenosine monophosphate (AMP) N(6)-methyl-AMP (m6AMP), N(6),N(6)-dimethyl-AMP (m6,6AMP) and N(6)-isopentenyl-AMP (i6AMP) (PubMed:40840445). Activated by lithocholic acid in response to calorie restriction: activation is mediated by the AXIN1-STK11/LKB1 axis, which promotes phosphorylation by STK11/LKB1, leading to mTORC1 inhibition (PubMed:25002183, PubMed:39695227, PubMed:39695235). 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 (By similarity). {ECO:0000250|UniProtKB:Q13131, ECO:0000269|PubMed:15980064, ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:21459323, ECO:0000269|PubMed:25002183, ECO:0000269|PubMed:39695227, ECO:0000269|PubMed:39695235, ECO:0000269|PubMed:40840445}.
uniprot
proteins
amino_acid_sequence
MRRLSSWRKMATAEKQKHDGRVKIGHYILGDTLGVGTFGKVKVGKHELTGHKVAVKILNRQKIRSLDVVGKIRREIQNLKLFRHPHIIKLYQVISTPSDIFMVMEYVSGGELFDYICKNGRLDEKESRRLFQQILSGVDYCHRHMVVHRDLKPENVLLDAHMNAKIADFGLSNMMSDGEFLRTSCGSPNYAAPEVISGRLYAGPEVDIWSSGVILYALLCGTLPFDDDHVPTLFKKICDGIFYTPQYLNPSVISLLKHMLQVDPMKRAAIKDIREHEWFKQDLPKYLFPEDPSYSSTMIDDEALKEVCEKFECSEEEVLSCLYNRNHQDPLAVAYHLIIDNRRIMNEAKDFYLATSPPDSFLDDHHLTRPHPERVPFLVAETPRARHTLDELNPQKSKHQGVRKAKWHLGIRSQSRPNDIMAEVCRAIKQLDYEWKVVNPYYLRVRRKNPVTSTFSKMSLQLYQVDSRTYLLDFRSIDDEITEAKSGTATPQRSGSISNYRSCQRSDSDAEAQGKPSDVSLTSSVTSLDSSPVDVAPRPGSHTIEFFEMCANLIKILAQ
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.11.26
uniprot
proteins
ec_number
2.7.11.31
uniprot
proteins
function
FUNCTION: Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism (By similarity). 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 (By similarity). AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators (By similarity). 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:15878856). 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). 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 (PubMed:16804075, PubMed:16804077). 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:16148943, PubMed:16308421, PubMed:20647423, PubMed:21459323). Acts as a key regulator of glucose homeostasis in liver by phosphorylating CRTC2/TORC2, leading to CRTC2/TORC2 sequestration in the cytoplasm (PubMed:16148943, PubMed:16308421). In response to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), leading to promote transcription (PubMed:20647423). 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:18439900, PubMed:21205641, PubMed:21258367, PubMed:24093678, PubMed:25002183, PubMed:32912901, PubMed:39695235). Also phosphorylates and inhibits GATOR2 subunit WDR24 in response to nutrient limitation, leading to suppress glucose-mediated mTORC1 activation (By similarity). 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 (By similarity). In response to nutrient limitation, promotes autophagy by phosphorylating and activating ATG1/ULK1 (PubMed:21205641, PubMed:21258367). In that process, it also activates WDR45/WIPI4 (By similarity). Phosphorylates CASP6, thereby preventing its autoprocessing and subsequent activation (By similarity). In response to nutrient limitation, phosphorylates transcription factor FOXO3 promoting FOXO3 mitochondrial import (PubMed:23283301). Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin (By similarity). AMPK also acts as a regulator of circadian rhythm by mediating phosphorylation of CRY1, leading to destabilize it (PubMed:19833968). May regulate the Wnt signaling pathway by phosphorylating CTNNB1, leading to stabilize it (PubMed:20361929). 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 (By similarity). Also phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1 (By similarity). Regulates hepatic lipogenesis. Activated via SIRT3, represses sterol regulatory element-binding protein (SREBP) transcriptional activities and ATP-consuming lipogenesis to restore cellular energy balance. Upon stress, regulates mitochondrial fragmentation through phosphorylation of MTFR1L (By similarity). Phosphorylates ALDH7A1 in response to cellular stress, such as hypoxia or ferroptotic stress, promoting ALDH7A1 recruitment to membranes (By similarity). {ECO:0000250|UniProtKB:P54645, ECO:0000250|UniProtKB:Q13131, ECO:0000269|PubMed:15878856, ECO:0000269|PubMed:16148943, ECO:0000269|PubMed:16308421, ECO:0000269|PubMed:16804075, ECO:0000269|PubMed:16804077, ECO:0000269|PubMed:18439900, ECO:0000269|PubMed:19833968, ECO:0000269|PubMed:20361929, ECO:0000269|PubMed:20647423, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:21258367, ECO:0000269|PubMed:21459323, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:24093678, ECO:0000269|PubMed:25002183, ECO:0000269|PubMed:32912901, ECO:0000269|PubMed:34077757, ECO:0000269|PubMed:36804859, ECO:0000269|PubMed:39695235}.
uniprot
proteins
mass_dalton
63929
uniprot
proteins
mutagenesis
MUTAGEN 168; /note="D->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:15878856, ECO:0000269|PubMed:21258367
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-183 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (PubMed:16054095, PubMed:21459323, PubMed:39695235). Also phosphorylated at Thr-183 by CAMKK2; triggered by a rise in intracellular calcium ions, without detectable changes in the AMP/ATP ratio (PubMed:15980064). CAMKK1 can also phosphorylate Thr-183, but at a much lower level (By similarity). Dephosphorylated by protein phosphatase 2A and 2C (PP2A and PP2C) (By similarity). 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 (By similarity). Dephosphorylated by PPM1A and PPM1B (By similarity). {ECO:0000250|UniProtKB:Q13131, ECO:0000269|PubMed:15980064, ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:21459323, ECO:0000269|PubMed:39695235}.; PTM: Ubiquitinated. {ECO:0000269|PubMed:18254724}.; PTM: Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity. {ECO:0000250|UniProtKB:Q13131}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SNF1 subfamily
uniprot
proteins
pubmed
15878856
uniprot
proteins
pubmed
15980064
uniprot
proteins
pubmed
16054095
uniprot
proteins
pubmed
16148943
uniprot
proteins
pubmed
16308421
uniprot
proteins
pubmed
16804075
uniprot
proteins
pubmed
16804077
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
18254724
uniprot
proteins
pubmed
18439900
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
19833968
uniprot
proteins
pubmed
20361929
uniprot
proteins
pubmed
20647423
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21205641
uniprot
proteins
pubmed
21258367
uniprot
proteins
pubmed
21459323
uniprot
proteins
pubmed
21460634
uniprot
proteins
pubmed
23283301
uniprot
proteins
pubmed
24093678
uniprot
proteins
pubmed
25002183
uniprot
proteins
pubmed
32912901
uniprot
proteins
pubmed
34077757
uniprot
proteins
pubmed
36804859
uniprot
proteins
pubmed
39695227
uniprot
proteins
pubmed
39695235
uniprot
proteins
pubmed
40840445
uniprot
proteins
sequence_length
559
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13131}. Nucleus {ECO:0000269|PubMed:19833968}. Late endosome {ECO:0000269|PubMed:25002183}. Note=In response to stress, recruited by p53/TP53 to specific promoters (By similarity). Translocates to late endosomes in response to calorie restriction (PubMed:25002183). {ECO:0000250|UniProtKB:Q13131, ECO:0000269|PubMed:25002183}.
uniprot
proteins