Description: Homo sapiens telomerase reverse transcriptase (TERT), transcript variant 1, mRNA. RefSeq Summary (NM_198253): Telomerase is a ribonucleoprotein polymerase that maintains telomere ends by addition of the telomere repeat TTAGGG. The enzyme consists of a protein component with reverse transcriptase activity, encoded by this gene, and an RNA component which serves as a template for the telomere repeat. Telomerase expression plays a role in cellular senescence, as it is normally repressed in postnatal somatic cells resulting in progressive shortening of telomeres. Deregulation of telomerase expression in somatic cells may be involved in oncogenesis. Studies in mouse suggest that telomerase also participates in chromosomal repair, since de novo synthesis of telomere repeats may occur at double-stranded breaks. Alternatively spliced variants encoding different isoforms of telomerase reverse transcriptase have been identified; the full-length sequence of some variants has not been determined. Alternative splicing at this locus is thought to be one mechanism of regulation of telomerase activity. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr5:1,253,287-1,295,162 Size: 41,876 Total Exon Count: 16 Strand: - Coding Region Position: hg19 chr5:1,253,843-1,295,104 Size: 41,262 Coding Exon Count: 16
ID:TERT_HUMAN DESCRIPTION: RecName: Full=Telomerase reverse transcriptase; EC=2.7.7.49; AltName: Full=HEST2; AltName: Full=Telomerase catalytic subunit; AltName: Full=Telomerase-associated protein 2; Short=TP2; FUNCTION: Telomerase 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. CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1). SUBUNIT: Homodimer; dimerization is required to produce a functional complex. Oligomer; can form oligomers in the absence of the telomerase RNA template component (TERC). Catalytic subunit of the telomerase holoenzyme complex composed minimally of TERT and TERC. The telomerase complex is composed of TERT, DKC1, WDR79/TCAB1, NOP10, NHP2, GAR1, TEP1, EST1A, POT1 and a telomerase RNA template component (TERC). The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase. Interacts directly with HSP90A and PTGES3. Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed. Interacts with RAN; the interaction promotes nuclear export of TERT. Interacts with XPO1. Interacts with PTPN11; the interaction retains TERT in the nucleus. Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT. Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling. Interacts with MCRS1 (isoform MCRS2); the interaction inhibits in vitro telomerase activity. Interacts with PIF1; the interaction has no effect on the elongation activity of TERT. Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity. Interacts with GNL3L (By similarity). INTERACTION: Q9Y265:RUVBL1; NbExp=11; IntAct=EBI-1772203, EBI-353675; SUBCELLULAR LOCATION: Nucleus, nucleolus. 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. TISSUE SPECIFICITY: Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T- lymphocytes. INDUCTION: Activated by cytotoxic events and down-regulated during aging. In peripheral T-lymphocytes, induced By CD3 and by PMA/ionomycin. Inhibited by herbimycin B. DOMAIN: The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers. DOMAIN: The RNA-interacting domain 1 (RD1)/N-terminal extension (NTE) is required for interaction with the pseudoknot-template domain of each of TERC dimers. It contains anchor sites that bind primer nucleotides upstream of the RNA-DNA hybrid and is thus an essential determinant of repeat addition processivity. DOMAIN: The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA sythesis. PTM: Ubiquitinated, leading to proteasomal degradation. PTM: Phosphorylation at Tyr-707 under oxidative stress leads to translocation of TERT to the cytoplasm and reduces its antiapoptotic activity. Dephosphorylated by SHP2/PTPN11 leading to nuclear retention. Phosphorylation by the AKT pathway promotes nuclear location. DISEASE: Note=Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis. DISEASE: Defects in TERT are associated with susceptibilty to aplastic anemia (AA) [MIM:609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis. DISEASE: Note=Genetic variations in TERT are associated with coronary artery disease (CAD). DISEASE: Defects in TERT are the cause of dyskeratosis congenita autosomal dominant type 2 (DKCA2) [MIM:613989]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DISEASE: Defects in TERT are the cause of pulmonary fibrosis, and/or bone marrow failure, telomere-related, type 1 (PFBMFT1) [MIM:614742]. A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. infections, fatal pulmonary complications, or malignancy. DISEASE: Defects in TERT are the cause of dyskeratosis congenita autosomal recessive type 4 (DKCB4) [MIM:613989]. A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DISEASE: Defects in TERT are a cause of susceptibility to pulmonary fibrosis idiopathic (IPF) [MIM:178500]. Pulmonary fibrosis is a lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. It results in acute lung injury with subsequent scarring and endstage lung disease. SIMILARITY: Belongs to the reverse transcriptase family. Telomerase subfamily. SIMILARITY: Contains 1 reverse transcriptase domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/tert/";
aplastic anaemia Vulliamy T et al. 2002, Association between aplastic anaemia and mutations in telomerase RNA., Lancet. 2002 Jun;359(9324):2168-70.
[PubMed 12090986]
Erythrocyte Count Yoichiro Kamatani et al. Nature genetics 2010, Genome-wide association study of hematological and biochemical traits in a Japanese population., Nature genetics.
[PubMed 20139978]
glioma Shete ,et al. 2009, Genome-wide association study identifies five susceptibility loci for glioma, Nature genetics 2009 41- 8 : 899-904.
[PubMed 19578367]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14746
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000723 telomere maintenance GO:0001172 transcription, RNA-templated GO:0006278 RNA-dependent DNA biosynthetic process GO:0007004 telomere maintenance via telomerase GO:0007005 mitochondrion organization GO:0010629 negative regulation of gene expression GO:0022616 DNA strand elongation GO:0030177 positive regulation of Wnt signaling pathway GO:0030422 production of siRNA involved in RNA interference GO:0031647 regulation of protein stability GO:0032092 positive regulation of protein binding GO:0032774 RNA biosynthetic process GO:0042635 positive regulation of hair cycle GO:0043066 negative regulation of apoptotic process GO:0043524 negative regulation of neuron apoptotic process GO:0045766 positive regulation of angiogenesis GO:0046326 positive regulation of glucose import GO:0046686 response to cadmium ion GO:0051000 positive regulation of nitric-oxide synthase activity GO:0060253 negative regulation of glial cell proliferation GO:0070200 establishment of protein localization to telomere GO:0071456 cellular response to hypoxia GO:0071897 DNA biosynthetic process GO:0090399 replicative senescence GO:1900087 positive regulation of G1/S transition of mitotic cell cycle GO:1902895 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1903620 positive regulation of transdifferentiation GO:1903704 negative regulation of production of siRNA involved in RNA interference GO:1904707 positive regulation of vascular smooth muscle cell proliferation GO:1904751 positive regulation of protein localization to nucleolus GO:1904754 positive regulation of vascular associated smooth muscle cell migration GO:1904837 beta-catenin-TCF complex assembly GO:2000352 negative regulation of endothelial cell apoptotic process GO:2000648 positive regulation of stem cell proliferation GO:2000773 negative regulation of cellular senescence GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
AX810038 - Sequence 3 from Patent EP1333094. AX810378 - Sequence 343 from Patent EP1333094. BC062321 - Homo sapiens telomerase reverse transcriptase, mRNA (cDNA clone IMAGE:5095305). AF015950 - Homo sapiens telomerase reverse transcriptase (hTRT) mRNA, complete cds. AX810036 - Sequence 1 from Patent EP1333094. DM139039 - Methods of enriching fetal cells. AF018167 - Homo sapiens telomerase catalytic subunit (hEST2) mRNA, complete cds. LF384934 - JP 2014500723-A/192437: Polycomb-Associated Non-Coding RNAs. JD158390 - Sequence 139414 from Patent EP1572962. JD460795 - Sequence 441819 from Patent EP1572962. JD470918 - Sequence 451942 from Patent EP1572962. JD440572 - Sequence 421596 from Patent EP1572962. JD440571 - Sequence 421595 from Patent EP1572962. JD374234 - Sequence 355258 from Patent EP1572962. JD366868 - Sequence 347892 from Patent EP1572962. JD389101 - Sequence 370125 from Patent EP1572962. JD450836 - Sequence 431860 from Patent EP1572962. JD421653 - Sequence 402677 from Patent EP1572962. JD139876 - Sequence 120900 from Patent EP1572962. JD058166 - Sequence 39190 from Patent EP1572962. JD459106 - Sequence 440130 from Patent EP1572962. JD334816 - Sequence 315840 from Patent EP1572962. JD103528 - Sequence 84552 from Patent EP1572962. BC156388 - Synthetic construct Homo sapiens clone IMAGE:100061944, MGC:190131 telomerase reverse transcriptase (TERT) mRNA, encodes complete protein. BC172541 - Synthetic construct Homo sapiens clone IMAGE:100069235, MGC:199246 telomerase reverse transcriptase (TERT) mRNA, encodes complete protein. AB085628 - Homo sapiens mRNA for telomerase reverse transcriptase, complete cds. AB086379 - Homo sapiens hTERT mRNA for beta and gamma deletion isoform of telomerase reverse transcriptase, complete cds. AB086950 - Homo sapiens TERT mRNA for ABG-deleted variant of telomerase reverse transcriptase, complete cds. LF331999 - JP 2014500723-A/139502: Polycomb-Associated Non-Coding RNAs. JF896284 - Homo sapiens telomerase reverse transcriptase isoform Delta2-13 (TERT) mRNA, partial sequence, alternatively spliced. JF896281 - Homo sapiens telomerase reverse transcriptase isoform Delta3p-12 (TERT) mRNA, partial sequence, alternatively spliced. JF896285 - Homo sapiens telomerase reverse transcriptase isoform Delta4-13 (TERT) mRNA, partial cds, alternatively spliced. JF896283 - Homo sapiens telomerase reverse transcriptase isoform Delta2-8 (TERT) mRNA, partial sequence, alternatively spliced. JF896280 - Homo sapiens telomerase reverse transcriptase isoform Delta2 (TERT) mRNA, partial sequence, alternatively spliced. AX810043 - Sequence 8 from Patent EP1333094. JF896282 - Homo sapiens telomerase reverse transcriptase isoform Delta4C (TERT) mRNA, partial cds, alternatively spliced. JF896286 - Homo sapiens telomerase reverse transcriptase isoform INTR1 (TERT) mRNA, partial sequence, alternatively spliced. MA620511 - JP 2018138019-A/192437: Polycomb-Associated Non-Coding RNAs. MA567576 - JP 2018138019-A/139502: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_achPathway - Role of nicotinic acetylcholine receptors in the regulation of apoptosis h_telPathway - Telomeres, Telomerase, Cellular Aging, and Immortality
Reactome (by CSHL, EBI, and GO)
Protein O14746 (Reactome details) participates in the following event(s):
R-HSA-164616 Biogenesis And Assembly Of The Telomerase RNP R-HSA-3322422 Beta-catenin recruits SMARCA4 R-HSA-163096 Recruitment of Telomerase RNP to the Telomeric Chromosome End R-HSA-163120 Disassociation of Telomerase RNP and the Chromosome End R-HSA-163099 Alignment Of The RNA Template On The Telomeric Chromosome End R-HSA-164617 Elongation of Extended Telomeric Chromosome End R-HSA-164620 Translocation Of Telomerase RNP And Alignment Of RNA Template (TERC) To Extended Single Stranded Telomeric Chromosome-End R-HSA-163090 Elongation Of The Telomeric Chromosome End R-HSA-171319 Telomere Extension By Telomerase R-HSA-201722 Formation of the beta-catenin:TCF transactivating complex R-HSA-180786 Extension of Telomeres R-HSA-201681 TCF dependent signaling in response to WNT R-HSA-157579 Telomere Maintenance R-HSA-195721 Signaling by WNT R-HSA-73886 Chromosome Maintenance R-HSA-162582 Signal Transduction R-HSA-1640170 Cell Cycle
GeneReviews article(s) related to gene TERT: dkc (Dyskeratosis Congenita and Related Telomere Biology Disorders) pf (Pulmonary Fibrosis Predisposition Overview)
Gene Model Information
category:
coding
nonsense-mediated-decay:
no
RNA accession:
NM_198253.2
exon count:
16
CDS single in 3' UTR:
no
RNA size:
4018
ORF size:
3399
CDS single in intron:
no
Alignment % ID:
100.00
txCdsPredict score:
6998.00
frame shift in genome:
no
% Coverage:
99.88
has start codon:
yes
stop codon in genome:
no
# of Alignments:
1
has end codon:
yes
retained intron:
no
# AT/AC introns
0
selenocysteine:
no
end bleed into intron:
0
# strange splices:
0
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Methods, Credits, and Use Restrictions
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US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
