Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0013353
UniProt IDO14746
Primary gene name(s)TERT
Synonym gene name(s)EST2, TCS1, TRT
Protein nameTelomerase reverse transcriptase
Protein functionTelomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis. {ECO:0000269|PubMed:14963003, ECO:0000269|PubMed:15082768, ECO:0000269|PubMed:15857955, ECO:0000269|PubMed:17026956, ECO:0000269|PubMed:17264120, ECO:0000269|PubMed:17296728, ECO:0000269|PubMed:17548608, ECO:0000269|PubMed:19188162, ECO:0000269|PubMed:19567472, ECO:0000269|PubMed:19571879, ECO:0000269|PubMed:19777057, ECO:0000269|PubMed:9389643}.
Subcellular locationNucleus, nucleolus {ECO:0000269|PubMed:22226966}. Nucleus, nucleoplasm. Nucleus. Chromosome, telomere. Cytoplasm. Nucleus, PML body. Note=Shuttling between nuclear and cytoplasm depends on cell cycle, phosphorylation states, transformation and DNA damage. Diffuse localization in the nucleoplasm. Enriched in nucleoli of certain cell types. Translocated to the cytoplasm via nuclear pores in a CRM1/RAN-dependent manner involving oxidative stress-mediated phosphorylation at Tyr-707. Dephosphorylation at this site by SHP2 retains TERT in the nucleus. Translocated to the nucleus by phosphorylation by AKT.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O14746
Gene Ontology
(Biological Process)
Complete annatation
beta-catenin-TCF complex assembly [GO:1904837];
cellular response to hypoxia [GO:0071456];
DNA biosynthetic process [GO:0071897];
DNA strand elongation [GO:0022616];
establishment of protein localization to telomere [GO:0070200];
mitochondrion organization [GO:0007005];
negative regulation of cellular senescence [GO:2000773];
negative regulation of endothelial cell apoptotic process [GO:2000352];
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand [GO:2001240];
negative regulation of gene expression [GO:0010629];
negative regulation of glial cell proliferation [GO:0060253];
negative regulation of neuron apoptotic process [GO:0043524];
negative regulation of production of siRNA involved in RNA interference [GO:1903704];
positive regulation of angiogenesis [GO:0045766];
positive regulation of G1/S transition of mitotic cell cycle [GO:1900087];
positive regulation of glucose import [GO:0046326];
positive regulation of hair cycle [GO:0042635];
positive regulation of nitric-oxide synthase activity [GO:0051000];
positive regulation of pri-miRNA transcription from RNA polymerase II promoter [GO:1902895];
positive regulation of protein binding [GO:0032092];
positive regulation of protein localization to nucleolus [GO:1904751];
positive regulation of stem cell proliferation [GO:2000648];
positive regulation of transdifferentiation [GO:1903620];
positive regulation of vascular associated smooth muscle cell migration [GO:1904754];
positive regulation of vascular smooth muscle cell proliferation [GO:1904707];
positive regulation of Wnt signaling pathway [GO:0030177];
production of siRNA involved in RNA interference [GO:0030422];
regulation of protein stability [GO:0031647];
replicative senescence [GO:0090399];
response to cadmium ion [GO:0046686];
RNA biosynthetic process [GO:0032774];
RNA-dependent DNA biosynthetic process [GO:0006278];
telomere maintenance [GO:0000723];
telomere maintenance via telomerase [GO:0007004];
transcription, RNA-templated [GO:0001172]
Gene Ontology
(Molecular Function)
Complete annatation
DNA binding [GO:0003677];
metal ion binding [GO:0046872];
nucleotidyltransferase activity [GO:0016779];
protein homodimerization activity [GO:0042803];
RNA binding [GO:0003723];
RNA-directed DNA polymerase activity [GO:0003964];
telomerase activity [GO:0003720];
telomerase RNA binding [GO:0070034];
telomerase RNA reverse transcriptase activity [GO:0003721];
telomeric DNA binding [GO:0042162];
transcription coactivator binding [GO:0001223];
tRNA binding [GO:0000049]
Gene Ontology
(Cellular Component)
Complete annatation
chromosome, telomeric region [GO:0000781];
mitochondrial nucleoid [GO:0042645];
nuclear chromosome, telomeric region [GO:0000784];
nuclear telomere cap complex [GO:0000783];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605];
RNA-directed RNA polymerase complex [GO:0031379];
telomerase catalytic core complex [GO:0000333];
telomerase holoenzyme complex [GO:0005697];
TERT-RMRP complex [GO:1990572]
Protein-protein interaction112874
Phylogenetic treeO14746
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. 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 Activation-1.229600518726190.1002600257589640.999983755607037
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) 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 0.369554 0.484426
(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
DB04937 GV1001 investigational unknown unknown
DB05036 Grn163l investigational unknown unknown
DB00495 Zidovudine approved unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2BCK X-ray 2.8Å C/F=461-469.
4B18 X-ray 2.5Å B=222-240.
4MNQ X-ray 2.7Å C=540-548.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 9662195
Tat inhibits 23287597
Vpr downregulates 23612978
Tat inhibited by 20139322
Tat downregulates 15017382

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05166 HTLV-I infection - Homo sapiens (human)