InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKAA1

Summary

InnateDB Protein

IDBP-18228.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKAA1

Protein Name

protein kinase, AMP-activated, alpha 1 catalytic subunit

Synonyms

AMPK; AMPKa1;

Species

Homo sapiens

Ensembl Protein

ENSP00000346148

InnateDB Gene

IDBG-18226 (PRKAA1)

Protein Structure

UniProt Annotation

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:0000269PubMed:11518699, ECO:0000269PubMed:11554766, ECO:0000269PubMed:12519745, ECO:0000269PubMed:14651849, ECO:0000269PubMed:15866171, ECO:0000269PubMed:17486097, ECO:0000269PubMed:17711846, ECO:0000269PubMed:18184930, ECO:0000269PubMed:18439900, ECO:0000269PubMed:20074060, ECO:0000269PubMed:20160076, ECO:0000269PubMed:21205641}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:15866171}. Nucleus {ECO:0000269PubMed:15866171}. Note=In response to stress, recruited by p53/TP53 to specific promoters.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 144 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	144 [view]
Protein-Protein	141 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003682	chromatin binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004679	AMP-activated protein kinase activity
GO:0004691	cAMP-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019900	kinase binding
GO:0035174	histone serine kinase activity
GO:0046872	metal ion binding
GO:0047322	[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity
GO:0050321	tau-protein kinase activity
GO:0050405	[acetyl-CoA carboxylase] kinase activity

Biological Process

GO:0000187	activation of MAPK activity
GO:0001666	response to hypoxia
GO:0006006	glucose metabolic process
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006633	fatty acid biosynthetic process
GO:0006695	cholesterol biosynthetic process
GO:0006914	autophagy
GO:0007050	cell cycle arrest
GO:0007165	signal transduction
GO:0008284	positive regulation of cell proliferation
GO:0008286	insulin receptor signaling pathway
GO:0008610	lipid biosynthetic process
GO:0009411	response to UV
GO:0009631	cold acclimation
GO:0010332	response to gamma radiation
GO:0010508	positive regulation of autophagy
GO:0010628	positive regulation of gene expression
GO:0014823	response to activity
GO:0016055	Wnt signaling pathway
GO:0019395	fatty acid oxidation
GO:0031000	response to caffeine
GO:0031669	cellular response to nutrient levels
GO:0032007	negative regulation of TOR signaling
GO:0035404	histone-serine phosphorylation
GO:0042149	cellular response to glucose starvation
GO:0042542	response to hydrogen peroxide
GO:0042593	glucose homeostasis
GO:0042752	regulation of circadian rhythm
GO:0043066	negative regulation of apoptotic process
GO:0045542	positive regulation of cholesterol biosynthetic process
GO:0045821	positive regulation of glycolytic process
GO:0046318	negative regulation of glucosylceramide biosynthetic process
GO:0048511	rhythmic process
GO:0050995	negative regulation of lipid catabolic process
GO:0051291	protein heterooligomerization
GO:0055089	fatty acid homeostasis
GO:0060627	regulation of vesicle-mediated transport
GO:0070301	cellular response to hydrogen peroxide
GO:0071361	cellular response to ethanol
GO:0071417	cellular response to organonitrogen compound
GO:0071456	cellular response to hypoxia
GO:1901563	response to camptothecin
GO:2000505	regulation of energy homeostasis
GO:2001274	negative regulation of glucose import in response to insulin stimulus

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016324	apical plasma membrane
GO:0031588	AMP-activated protein kinase complex
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR028375 KA1 domain/Ssp2 C-terminal domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt