Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002315
UniProt IDP54646
Primary gene name(s)PRKAA2
Synonym gene name(s)AMPK, AMPK2
Protein name5'-AMP-activated protein kinase catalytic subunit alpha-2
Protein functionCatalytic 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. Involved in insulin receptor/INSR internalization, PubMed:25687571. 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 phosphorylates CFTR, EEF2K, KLC1, NOS3 and SLC12A1. Plays an important role in the differential regulation of pro-autophagy, composed of PIK3C3, BECN1, PIK3R4 and UVRAG or ATG14 and non-autophagy, composed of PIK3C3, BECN1 and PIK3R4 complexes, in response to glucose starvation. Can inhibit the non-autophagy complex by phosphorylating PIK3C3 and can activate the pro-autophagy complex by phosphorylating BECN1, By similarity. {ECO:0000250|UniProtKB:Q8BRK8, ECO:0000269|PubMed:11518699, ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, ECO:0000269|PubMed:21205641, ECO:0000269|PubMed:25687571, ECO:0000269|PubMed:7959015}.
Subcellular locationCytoplasm {ECO:0000250}. Nucleus {ECO:0000269|PubMed:15866171}. Note=In response to stress, recruited by p53/TP53 to specific promoters.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P54646
Gene Ontology
(Biological Process)
Complete annatation
carnitine shuttle [GO:0006853];
cell cycle arrest [GO:0007050];
cellular response to drug [GO:0035690];
cellular response to glucose starvation [GO:0042149];
cellular response to nutrient levels [GO:0031669];
cellular response to prostaglandin E stimulus [GO:0071380];
cholesterol biosynthetic process [GO:0006695];
fatty acid biosynthetic process [GO:0006633];
fatty acid homeostasis [GO:0055089];
glucose homeostasis [GO:0042593];
histone-serine phosphorylation [GO:0035404];
intracellular signal transduction [GO:0035556];
lipid biosynthetic process [GO:0008610];
macroautophagy [GO:0016236];
negative regulation of apoptotic process [GO:0043066];
negative regulation of TOR signaling [GO:0032007];
positive regulation of autophagy [GO:0010508];
positive regulation of glycolytic process [GO:0045821];
positive regulation of macroautophagy [GO:0016239];
protein phosphorylation [GO:0006468];
regulation of circadian rhythm [GO:0042752];
regulation of energy homeostasis [GO:2000505];
regulation of fatty acid biosynthetic process [GO:0042304];
regulation of macroautophagy [GO:0016241];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription, DNA-templated [GO:0006355];
response to muscle activity [GO:0014850];
response to stress [GO:0006950];
rhythmic process [GO:0048511];
signal transduction [GO:0007165];
transcription, DNA-templated [GO:0006351];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
[acetyl-CoA carboxylase] kinase activity [GO:0050405];
[hydroxymethylglutaryl-CoA reductase, NADPH] kinase activity [GO:0047322];
AMP-activated protein kinase activity [GO:0004679];
ATP binding [GO:0005524];
chromatin binding [GO:0003682];
histone serine kinase activity [GO:0035174];
metal ion binding [GO:0046872];
protein kinase activity [GO:0004672];
protein serine/threonine/tyrosine kinase activity [GO:0004712];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
nucleoplasm [GO:0005654];
nucleotide-activated protein kinase complex [GO:0031588];
nucleus [GO:0005634]
Protein-protein interaction111550
Phylogenetic treeP54646
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3unknownunknownunknown
AZA vs. DISUunknownunknownunknown
AZA vs. IL7unknownunknownunknown
AZA vs. SAHAunknownunknownunknown
DISU vs. CD3unknownunknownunknown
DISU vs. IL7unknownunknownunknown
DISU vs. SAHAunknownunknownunknown
DMSO vs. AZAunknownunknownunknown
DMSO vs. CD3unknownunknownunknown
DMSO vs. DISUunknownunknownunknown
DMSO vs. IL7unknownunknownunknown
DMSO vs. SAHAunknownunknownunknown
HIV vs. Mock in Activationunknownunknownunknown
HIV vs. Mock in Latencyunknownunknownunknown
IL7 vs. CD3unknownunknownunknown
SAHA vs. CD3unknownunknownunknown
SAHA vs. IL7unknownunknownunknown
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
NOTEST -2.64547 1
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00945 Acetylsalicylic acid approved, vet_approved unknown activator

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2H6D X-ray 1.8Å A=6-279.
2LTU NMR - A=282-339.
2YZA X-ray 3.0Å A=6-279.
3AQV X-ray 2.0Å A=6-279.
4CFE X-ray 3.0Å A/C=1-552.
4CFF X-ray 3.9Å A/C=1-552.
4ZHX X-ray 2.9Å A/C=2-552.
5EZV X-ray 2.9Å A/C=2-347# A/C=397-552.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Tat induces phosphorylation of 19720090
21344388
Vif inhibited by 18836454
Vpr phosphorylated by 20392842
21651489
Tat interacts with 24414799

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04140 Autophagy - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04213 Longevity regulating pathway - multiple species - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04710 Circadian rhythm - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04921 Oxytocin signaling pathway - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05410 Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
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