Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0003637
UniProt IDP31751
Primary gene name(s)AKT2
Synonym gene name(s)unknown
Protein nameRAC-beta serine/threonine-protein kinase
Protein functionAKT2 is one of 3 closely related serine/threonine-protein kinases, AKT1, AKT2 and AKT3 called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5, apoptosis signal-related kinase. Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors, Forkhead family of transcription factors, leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1, cyclic AMP, cAMP-response element binding protein. The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase, ACLY, thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase, PDE3B via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase, PI(3K to mediate the effects of various growth factors such as platelet-derived growth factor, PDGF, epidermal growth factor, EGF, insulin and insulin-like growth factor I, IGF-I. AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development.; FUNCTION: One of the few specific substrates of AKT2 identified recently is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1. AKT2 seems also to be the principal isoform responsible of the regulation of glucose uptake. Phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. Phosphorylates CLK2 on 'Thr-343'.
Subcellular locationCytoplasm. Nucleus. Cell membrane;
Peripheral membrane protein. Early endosome {ECO:0000250|UniProtKB:Q60823}. Note=Localizes within both nucleus and cytoplasm of proliferative primary myoblasts and mostly within the nucleus of differentiated primary myoblasts. By virtue of the N-terminal PH domain, is recruited to sites of the plasma membrane containing increased PI(3,4,5P3 or PI(3,4P2, cell membrane targeting is also facilitared by interaction with CLIP3. Colocalizes with WDFY2 in early endosomes, By similarity. {ECO:0000250|UniProtKB:Q60823}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P31751
Gene Ontology
(Biological Process)
Complete annatation
activation of GTPase activity [GO:0090630];
apoptotic process [GO:0006915];
carbohydrate transport [GO:0008643];
cellular protein modification process [GO:0006464];
cellular response to insulin stimulus [GO:0032869];
fat cell differentiation [GO:0045444];
glucose metabolic process [GO:0006006];
glycogen biosynthetic process [GO:0005978];
insulin receptor signaling pathway [GO:0008286];
intracellular protein transmembrane transport [GO:0065002];
intracellular signal transduction [GO:0035556];
mammary gland epithelial cell differentiation [GO:0060644];
negative regulation of plasma membrane long-chain fatty acid transport [GO:0010748];
peptidyl-serine phosphorylation [GO:0018105];
peripheral nervous system myelin maintenance [GO:0032287];
positive regulation of cell migration [GO:0030335];
positive regulation of cell motility [GO:2000147];
positive regulation of fatty acid beta-oxidation [GO:0032000];
positive regulation of glucose import [GO:0046326];
positive regulation of glucose import in response to insulin stimulus [GO:2001275];
positive regulation of glucose metabolic process [GO:0010907];
positive regulation of glycogen biosynthetic process [GO:0045725];
positive regulation of protein phosphorylation [GO:0001934];
positive regulation of protein targeting to membrane [GO:0090314];
positive regulation of vesicle fusion [GO:0031340];
protein localization to plasma membrane [GO:0072659];
regulation of cell cycle arrest [GO:0071156];
regulation of cell migration [GO:0030334];
regulation of translation [GO:0006417];
signal transduction [GO:0007165]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cell cortex [GO:0005938];
cytosol [GO:0005829];
early endosome [GO:0005769];
insulin-responsive compartment [GO:0032593];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
ruffle membrane [GO:0032587]
Protein-protein interaction106711
Phylogenetic treeP31751
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. CD30.2445327924329030.4582725959747140.578822137478496
AZA vs. DISU0.1130990681080810.6546276827455870.960105617623075
AZA vs. IL7-0.07522694330824920.6953321929390180.999311006273513
AZA vs. SAHA0.05798884103792680.8120084955749240.952990973395859
DISU vs. CD3-0.1442545463995240.6941388858216670.785868193278672
DISU vs. IL7-0.1976527925280270.4326689656425750.786030929990578
DISU vs. SAHA-0.05282249959894140.8559522190268470.9615850182806
DMSO vs. AZA0.09104671646295690.5864280320467411
DMSO vs. CD3-0.1677454017401030.6028527331608780.698319921272813
DMSO vs. DISU-0.02466976939531520.9193760044540390.988899823982894
DMSO vs. IL7-0.1584790844646690.3777781870194330.832872524258073
DMSO vs. SAHA-0.0378576819724080.8722875570288990.968193093696104
HIV vs. Mock in Activation0.1782357792720340.7743378678822070.999983755607037
HIV vs. Mock in Latency0.02012325244408390.902785070387940.999834320637052
IL7 vs. CD3-0.3136913691937160.3323147896372420.470857381481683
SAHA vs. CD3-0.2100307016601930.5567508154844190.660024763164741
SAHA vs. IL70.1301910051858630.59276808541450.792389239006946
(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) unknown
(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
OK 0.0540065 0.766226
(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
1.032 1.202 1.179 1.247 1.166
(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
DB07812 N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide experimental unknown unknown
DB07859 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE experimental unknown unknown
DB07947 ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE experimental unknown unknown
DB08073 (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1GZK X-ray 2.3Å A=146-460.
1GZN X-ray 2.5Å A=146-480.
1GZO X-ray 2.7Å A=146-460.
1MRV X-ray 2.8Å A=143-481.
1MRY X-ray 2.8Å A=143-481.
1O6K X-ray 1.7Å A=146-481.
1O6L X-ray 1.6Å A=146-467.
1P6S NMR - A=1-111.
2JDO X-ray 1.8Å A=146-467.
2JDR X-ray 2.3Å A=146-467.
2UW9 X-ray 2.1Å A=146-467.
2X39 X-ray 1.9Å A=146-467.
2XH5 X-ray 2.7Å A=146-479.
3D0E X-ray 2.0Å A/B=146-480.
3E87 X-ray 2.3Å A/B=146-480.
3E88 X-ray 2.5Å A/B=146-480.
3E8D X-ray 2.7Å A/B=146-480.

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

HIV Partner Interaction Type PubMed
Nef induces phosphorylation of 18826950
20012528
Vpr decreases phosphorylation of 17349711
Nef interacts with 23746211
24658403
Vpr regulated by 24225433
Envelope surface glycoprotein gp120 decreases phosphorylation of 11208609
Tat activates 11156964
17157319
19479051
20019835
21029719
21483469
21765914
9394803
11156964
11994280
17157319
18187620
21763505
23811558
Envelope surface glycoprotein gp120 modulated by 16524887
Nef decreases phosphorylation of 21606541
Tat upregulates 11994280
Tat interacts with 23077641
24244375
matrix induces phosphorylation of 21423810
22904195
Vpr involves 26270987
26270987
Envelope surface glycoprotein gp120 inhibited by 10869418
16841089
20818790
Vpr inhibits 15616007
Tat induces phosphorylation of 20661303
21697490
23301033
Envelope surface glycoprotein gp120 activates 23251686
23742646
Envelope surface glycoprotein gp120 regulated by 15689238
2004121318300076
Tat downregulates 24469921
Nef activates 23604117
23604117
25104021
matrix activates 22904195
24623414

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04010 MAPK signaling pathway - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04014 Ras signaling pathway - Homo sapiens (human)
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04022 cGMP-PKG signaling pathway - Homo sapiens (human)
hsa04024 cAMP signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04072 Phospholipase D signaling pathway - 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)
hsa04210 Apoptosis - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04213 Longevity regulating pathway - multiple species - Homo sapiens (human)
hsa04261 Adrenergic signaling in cardiomyocytes - Homo sapiens (human)
hsa04370 VEGF signaling pathway - Homo sapiens (human)
hsa04380 Osteoclast differentiation - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04620 Toll-like receptor signaling pathway - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04664 Fc epsilon RI signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04668 TNF signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04725 Cholinergic synapse - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04914 Progesterone-mediated oocyte maturation - Homo sapiens (human)
hsa04915 Estrogen signaling pathway - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04923 Regulation of lipolysis in adipocytes - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa04973 Carbohydrate digestion and absorption - Homo sapiens (human)
hsa05142 Chagas disease (American trypanosomiasis) - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05152 Tuberculosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05211 Renal cell carcinoma - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05222 Small cell lung cancer - Homo sapiens (human)
hsa05223 Non-small cell lung cancer - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)
hsa05230 Central carbon metabolism in cancer - Homo sapiens (human)
hsa05231 Choline metabolism in cancer - Homo sapiens (human)
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