Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005106
UniProt IDP49841
Primary gene name(s)GSK3B
Synonym gene name(s)unknown
Protein nameGlycogen synthase kinase-3 beta
Protein functionConstitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase, GYS1 or GYS2, EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B, EIF2BE/EIF2B5 in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B, NFKB1 at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha, TNF/TNFA. Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation, PubMed:24391509. {ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.
Subcellular locationCytoplasm. Nucleus. Cell membrane. Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P49841
Gene Ontology
(Biological Process)
Complete annatation
animal organ morphogenesis [GO:0009887];
axonogenesis [GO:0007409];
beta-catenin destruction complex assembly [GO:1904885];
beta-catenin destruction complex disassembly [GO:1904886];
canonical Wnt signaling pathway [GO:0060070];
canonical Wnt signaling pathway involved in positive regulation of apoptotic process [GO:0044337];
cell migration [GO:0016477];
cellular response to hepatocyte growth factor stimulus [GO:0035729];
cellular response to interleukin-3 [GO:0036016];
chemical synaptic transmission, postsynaptic [GO:0099565];
circadian rhythm [GO:0007623];
dopamine receptor signaling pathway [GO:0007212];
epithelial to mesenchymal transition [GO:0001837];
ER overload response [GO:0006983];
extrinsic apoptotic signaling pathway in absence of ligand [GO:0097192];
fat cell differentiation [GO:0045444];
glycogen metabolic process [GO:0005977];
hippocampus development [GO:0021766];
hypermethylation of CpG island [GO:0044027];
intracellular signal transduction [GO:0035556];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
myoblast fusion [GO:0007520];
negative regulation of apoptotic process [GO:0043066];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of cardiac muscle hypertrophy [GO:0010614];
negative regulation of dopaminergic neuron differentiation [GO:1904339];
negative regulation of glycogen, starch synthase activity [GO:2000466];
negative regulation of glycogen biosynthetic process [GO:0045719];
negative regulation of neuron maturation [GO:0014043];
negative regulation of neuron projection development [GO:0010977];
negative regulation of NFAT protein import into nucleus [GO:0051534];
negative regulation of protein binding [GO:0032091];
negative regulation of protein complex assembly [GO:0031333];
negative regulation of protein localization to nucleus [GO:1900181];
negative regulation of type B pancreatic cell development [GO:2000077];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
positive regulation of axon extension [GO:0045773];
positive regulation of cardiac muscle cell differentiation [GO:2000727];
positive regulation of cell-matrix adhesion [GO:0001954];
positive regulation of GTPase activity [GO:0043547];
positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway [GO:1901030];
positive regulation of mitochondrion organization [GO:0010822];
positive regulation of neuron death [GO:1901216];
positive regulation of peptidyl-serine phosphorylation [GO:0033138];
positive regulation of peptidyl-threonine phosphorylation [GO:0010800];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein binding [GO:0032092];
positive regulation of protein catabolic process [GO:0045732];
positive regulation of protein complex assembly [GO:0031334];
positive regulation of protein export from nucleus [GO:0046827];
positive regulation of stem cell differentiation [GO:2000738];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein autophosphorylation [GO:0046777];
protein export from nucleus [GO:0006611];
protein localization to microtubule [GO:0035372];
protein phosphorylation [GO:0006468];
re-entry into mitotic cell cycle [GO:0000320];
regulation of cellular response to heat [GO:1900034];
regulation of gene expression by genetic imprinting [GO:0006349];
regulation of microtubule-based process [GO:0032886];
superior temporal gyrus development [GO:0071109];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
beta-catenin binding [GO:0008013];
kinase activity [GO:0016301];
NF-kappaB binding [GO:0051059];
p53 binding [GO:0002039];
protein kinase A catalytic subunit binding [GO:0034236];
protein kinase activity [GO:0004672];
protein kinase binding [GO:0019901];
protein serine/threonine kinase activity [GO:0004674];
RNA polymerase II transcription factor binding [GO:0001085];
tau-protein kinase activity [GO:0050321];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
axon [GO:0030424];
beta-catenin destruction complex [GO:0030877];
centrosome [GO:0005813];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendritic shaft [GO:0043198];
dendritic spine [GO:0043197];
growth cone [GO:0030426];
intracellular ribonucleoprotein complex [GO:0030529];
membrane raft [GO:0045121];
mitochondrion [GO:0005739];
neuronal cell body [GO:0043025];
neuronal postsynaptic density [GO:0097481];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
Wnt signalosome [GO:1990909]
Protein-protein interaction109187
Phylogenetic treeP49841
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
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. CD3-0.5091991887643730.1215531450174820.205663336518128
AZA vs. DISU0.04717337388762020.8521627985641280.989489441774853
AZA vs. IL70.08407474227545970.6623581219221080.999311006273513
AZA vs. SAHA0.02817525111199580.908084429307980.979987448982567
DISU vs. CD30.5433169973842580.1348083579715390.235797306574956
DISU vs. IL70.02783312623418050.9120072530095370.982368063898651
DISU vs. SAHA-0.01745343203316580.9522757708704290.989441867353937
DMSO vs. AZA-0.003816335255108210.9818629734346111
DMSO vs. CD30.4940243235066070.1239051977369460.20302717031837
DMSO vs. DISU-0.05281836559931280.8287349936063450.980781994971427
DMSO vs. IL70.09509183415391810.5974831376814610.911970258876874
DMSO vs. SAHA0.02542983321177070.9141231317167970.979403400357616
HIV vs. Mock in Activation0.1183385455346720.849520213835770.999983755607037
HIV vs. Mock in Latency-0.0133992612148480.9353738374677450.999834320637052
IL7 vs. CD30.6007171570168460.06244509372559630.131328993682979
SAHA vs. CD30.512532428865460.1489353621662010.239663351577296
SAHA vs. IL7-0.05939663779780710.8074864526704650.916747555731927
(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 -0.562672 0.000305467
(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
1.045 1.092 1.243 1.302 1.292
(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
DB01356 Lithium approved unknown inhibitor
DB01772 3-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-Dione experimental unknown unknown
DB01793 I-5 experimental unknown unknown
DB01950 N-(4-Methoxybenzyl)-N&,39;-(5-Nitro-1,3-Thiazol-2-Yl)Urea experimental unknown unknown
DB02010 Staurosporine experimental unknown unknown
DB02052 Indirubin-3&,39;-Monoxime experimental unknown unknown
DB04014 Alsterpaullone experimental unknown unknown
DB04395 Phosphoaminophosphonic Acid-Adenylate Ester experimental unknown unknown
DB07014 2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole experimental unknown unknown
DB07058 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thione experimental unknown unknown
DB07149 (7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one experimental unknown unknown
DB03444 (3e)-6&,39;-Bromo-2,3&,39;-Biindole-2&,39;,3(1h,1&,39;h)-Dione 3-Oxime experimental unknown unknown
DB07584 N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine experimental unknown unknown
DB07585 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine experimental unknown unknown
DB07676 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2&,39;H-2,3&,39;-biindol-2&,39;-one experimental unknown unknown
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
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
1GNG X-ray 2.6Å A/B=27-393.
1H8F X-ray 2.8Å A/B=35-386.
1I09 X-ray 2.7Å A/B=1-420.
1J1B X-ray 1.8Å A/B=1-420.
1J1C X-ray 2.1Å A/B=1-420.
1O6K X-ray 1.7Å C=3-12.
1O6L X-ray 1.6Å C=3-12.
1O9U X-ray 2.4Å A=35-384.
1PYX X-ray 2.4Å A/B=1-420.
1Q3D X-ray 2.2Å A/B=2-420.
1Q3W X-ray 2.3Å A/B=2-420.
1Q41 X-ray 2.1Å A/B=2-420.
1Q4L X-ray 2.7Å A/B=2-420.
1Q5K X-ray 1.9Å A/B=7-420.
1R0E X-ray 2.2Å A/B=35-420.
1UV5 X-ray 2.8Å A=35-384.
2JDO X-ray 1.8Å C=3-12.
2JDR X-ray 2.3Å C=3-12.
2JLD X-ray 2.3Å A/B=1-420.
2O5K X-ray 3.2Å A=29-393.
2OW3 X-ray 2.8Å A/B=35-386.
2UW9 X-ray 2.1Å C=3-12.
2X39 X-ray 1.9Å C=3-12.
2XH5 X-ray 2.7Å C=3-12.
3CQU X-ray 2.2Å C=3-12.
3CQW X-ray 2.0Å C=3-12.
3DU8 X-ray 2.2Å A/B=1-420.
3E87 X-ray 2.3Å C/D=3-12.
3E88 X-ray 2.5Å C/D=3-12.
3E8D X-ray 2.7Å C/D=3-12.
3F7Z X-ray 2.4Å A/B=35-383.
3F88 X-ray 2.6Å A/B=35-383.
3GB2 X-ray 2.4Å A=34-383.
3I4B X-ray 2.3Å A/B=7-420.
3L1S X-ray 2.9Å A/B=7-420.
3M1S X-ray 3.1Å A/B=1-420.
3MV5 X-ray 2.4Å C=3-12.
3OW4 X-ray 2.6Å C/D=3-12.
3PUP X-ray 2.9Å A/B=1-420.
3Q3B X-ray 2.7Å A/B=2-420.
3QKK X-ray 2.3Å C=3-12.
3SAY X-ray 2.2Å A/B=1-420.
3SD0 X-ray 2.7Å A/B=35-384.
3ZDI X-ray 2.6Å A=35-384.
3ZRK X-ray 2.3Å A/B=23-393.
3ZRL X-ray 2.4Å A/B=23-393.
3ZRM X-ray 2.4Å A/B=23-393.
4ACC X-ray 2.2Å A/B=1-420.
4ACD X-ray 2.6Å A/B=1-420.
4ACG X-ray 2.6Å A/B=1-420.
4ACH X-ray 2.6Å A/B=1-420.
4AFJ X-ray 1.9Å A/B=27-393.
4B7T X-ray 2.7Å A=35-384.
4DIT X-ray 2.6Å A=27-393.
4EKK X-ray 2.8Å C/D=3-12.
4IQ6 X-ray 3.1Å A/B=1-420.
4J1R X-ray 2.7Å A/B/C/D=1-420.
4J71 X-ray 2.3Å A/B=1-420.
4NM0 X-ray 2.5Å A=1-383.
4NM3 X-ray 2.1Å A=1-383.
4NM5 X-ray 2.3Å A=13-383.
4NM7 X-ray 2.3Å A=13-383.
4PTC X-ray 2.7Å A/B=1-420.
4PTE X-ray 2.0Å A/B=1-420.
4PTG X-ray 2.3Å A/B=1-420.
5F94 X-ray 2.5Å A/B=36-385.
5F95 X-ray 2.5Å A/B=36-385.
5HLN X-ray 3.1Å A/B=1-420.
5HLP X-ray 2.4Å A/B=1-420.
5K5N X-ray 2.2Å A/B=28-384.

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

HIV Partner Interaction Type PubMed
Nef induces phosphorylation of 18826950
Vpu binds 23047923
Envelope surface glycoprotein gp120 interacts with 18973553
Vpr downregulates 23912036
Tat activates 10428053
Envelope surface glycoprotein gp120 inhibited by 20818790
Tat induces phosphorylation of 23301033
Tat interacts with 21514616

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa04012 ErbB signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04150 mTOR signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04310 Wnt signaling pathway - Homo sapiens (human)
hsa04340 Hedgehog signaling pathway - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04510 Focal adhesion - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04657 IL-17 signaling pathway - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04662 B cell receptor signaling pathway - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04728 Dopaminergic synapse - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04916 Melanogenesis - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04932 Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
hsa05010 Alzheimer's disease - Homo sapiens (human)
hsa05160 Hepatitis C - 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)
hsa05210 Colorectal cancer - Homo sapiens (human)
hsa05213 Endometrial cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05217 Basal cell carcinoma - Homo sapiens (human)
hsa05224 Breast cancer - Homo sapiens (human)