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Protein

Telomerase reverse transcriptase

Gene

TERT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.12 Publications

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei169 – 1691Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template
Metal bindingi712 – 7121Magnesium; catalyticPROSITE-ProRule annotation
Sitei867 – 8671Required for nucleotide incorporation and primer extension rate
Metal bindingi868 – 8681Magnesium; catalyticPROSITE-ProRule annotation
Metal bindingi869 – 8691Magnesium; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  • DNA binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • nucleotidyltransferase activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • RNA binding Source: BHF-UCL
  • RNA-directed DNA polymerase activity Source: BHF-UCL
  • telomerase activity Source: UniProtKB
  • telomerase RNA binding Source: BHF-UCL
  • telomerase RNA reverse transcriptase activity Source: UniProtKB
  • telomeric DNA binding Source: ProtInc
  • transcription coactivator binding Source: BHF-UCL
  • tRNA binding Source: BHF-UCL

GO - Biological processi

  • beta-catenin-TCF complex assembly Source: Reactome
  • cellular response to hypoxia Source: BHF-UCL
  • DNA biosynthetic process Source: BHF-UCL
  • DNA strand elongation Source: BHF-UCL
  • establishment of protein localization to telomere Source: BHF-UCL
  • mitochondrion organization Source: BHF-UCL
  • negative regulation of cellular senescence Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of production of siRNA involved in RNA interference Source: BHF-UCL
  • positive regulation of hair cycle Source: Ensembl
  • positive regulation of nitric-oxide synthase activity Source: BHF-UCL
  • positive regulation of pri-miRNA transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of protein binding Source: BHF-UCL
  • positive regulation of protein localization to nucleolus Source: BHF-UCL
  • positive regulation of stem cell proliferation Source: Ensembl
  • positive regulation of Wnt signaling pathway Source: BHF-UCL
  • production of siRNA involved in RNA interference Source: BHF-UCL
  • regulation of protein stability Source: BHF-UCL
  • replicative senescence Source: BHF-UCL
  • RNA biosynthetic process Source: BHF-UCL
  • RNA-dependent DNA biosynthetic process Source: BHF-UCL
  • telomere maintenance Source: UniProtKB
  • telomere maintenance via telomerase Source: BHF-UCL
  • transcription, RNA-templated Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-171319. Telomere Extension By Telomerase.
R-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
SIGNORiO14746.

Names & Taxonomyi

Protein namesi
Recommended name:
Telomerase reverse transcriptase (EC:2.7.7.49)
Alternative name(s):
HEST2
Telomerase catalytic subunit
Telomerase-associated protein 2
Short name:
TP2
Gene namesi
Name:TERT
Synonyms:EST2, TCS1, TRT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:11730. TERT.

Subcellular locationi

  • Nucleusnucleolus 1 Publication
  • Nucleusnucleoplasm
  • Nucleus
  • Chromosometelomere
  • Cytoplasm
  • NucleusPML 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.

GO - Cellular componenti

  • chromosome, telomeric region Source: UniProtKB
  • mitochondrial nucleoid Source: BHF-UCL
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nuclear telomere cap complex Source: BHF-UCL
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: UniProtKB
  • nucleus Source: BHF-UCL
  • PML body Source: UniProtKB-SubCell
  • RNA-directed RNA polymerase complex Source: BHF-UCL
  • telomerase catalytic core complex Source: BHF-UCL
  • telomerase holoenzyme complex Source: UniProtKB
  • TERT-RMRP complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

Pathology & Biotechi

Involvement in diseasei

Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis.

Aplastic anemia (AA)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
See also OMIM:609135
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
Corresponds to variant rs121918661 [ dbSNP | Ensembl ].
VAR_036863
Natural varianti441 – 4411Missing in AA susceptibility; associated with susceptibility to acute myeloid leukemia. 3 Publications
VAR_036865
Natural varianti570 – 5701K → N in AA susceptibility; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications
VAR_062536
Natural varianti631 – 6311R → Q in AA susceptibility. 1 Publication
Corresponds to variant rs199422294 [ dbSNP | Ensembl ].
VAR_062783
Natural varianti682 – 6821G → D in AA susceptibility; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 2 Publications
Corresponds to variant rs199422295 [ dbSNP | Ensembl ].
VAR_062537
Natural varianti726 – 7261T → M in AA susceptibility; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 Publications
Corresponds to variant rs149566858 [ dbSNP | Ensembl ].
VAR_062539
Natural varianti785 – 7851P → L in AA susceptibility. 1 Publication
VAR_062784

Genetic variations in TERT are associated with coronary artery disease (CAD).

Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613989
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti902 – 9021K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications
Corresponds to variant rs121918665 [ dbSNP | Ensembl ].
VAR_036869
Natural varianti979 – 9791R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications
Corresponds to variant rs199422305 [ dbSNP | Ensembl ].
VAR_062542
Natural varianti1127 – 11271F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications
VAR_062544
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614742
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti170 – 1701V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 Publication
Corresponds to variant rs387907248 [ dbSNP | Ensembl ].
VAR_068792
Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
Corresponds to variant rs121918661 [ dbSNP | Ensembl ].
VAR_036863
Natural varianti412 – 4121H → Y in PFBMFT1 and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. 5 Publications
Corresponds to variant rs34094720 [ dbSNP | Ensembl ].
VAR_025149
Natural varianti694 – 6941V → M in PFBMFT1; moderate. 2 Publications
Corresponds to variant rs121918662 [ dbSNP | Ensembl ].
VAR_036866
Natural varianti716 – 7161A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 Publication
Corresponds to variant rs387907249 [ dbSNP | Ensembl ].
VAR_068794
Natural varianti772 – 7721Y → C in PFBMFT1; moderate. 1 Publication
Corresponds to variant rs121918663 [ dbSNP | Ensembl ].
VAR_036867
Natural varianti791 – 7911V → I in PFBMFT1; associated with Met-867 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity. 1 Publication
Corresponds to variant rs141425941 [ dbSNP | Ensembl ].
VAR_068795
Natural varianti841 – 8411L → F in PFBMFT1. 1 Publication
VAR_068796
Natural varianti865 – 8651R → H in PFBMFT1. 1 Publication
Corresponds to variant rs121918666 [ dbSNP | Ensembl ].
VAR_036868
Natural varianti867 – 8671V → M in PFBMFT1; associated with Ile-791 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity; this mutation causes most if not all of the functional defects. 1 Publication
Corresponds to variant rs201159197 [ dbSNP | Ensembl ].
VAR_068797
Natural varianti902 – 9021K → R in PFBMFT1. 1 Publication
Corresponds to variant rs387907250 [ dbSNP | Ensembl ].
VAR_068798
Natural varianti923 – 9231P → L in PFBMFT1. 1 Publication
Corresponds to variant rs387907251 [ dbSNP | Ensembl ].
VAR_068799
Natural varianti1025 – 10251V → F in PFBMFT1. 1 Publication
VAR_068800
Natural varianti1090 – 10901V → M in PFBMFT1; severe. 1 Publication
Corresponds to variant rs121918664 [ dbSNP | Ensembl ].
VAR_036870
Dyskeratosis congenita, autosomal recessive, 4 (DKCB4)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe form of dyskeratosis congenita, 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.
See also OMIM:613989
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti412 – 4121H → Y in PFBMFT1 and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. 5 Publications
Corresponds to variant rs34094720 [ dbSNP | Ensembl ].
VAR_025149
Natural varianti704 – 7041P → S in DKCB4; the mutant protein has 13% residual activity. 1 Publication
Corresponds to variant rs199422297 [ dbSNP | Ensembl ].
VAR_068793
Natural varianti721 – 7211P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 2 Publications
Corresponds to variant rs199422299 [ dbSNP | Ensembl ].
VAR_062538
Natural varianti811 – 8111R → C in DKCB4; 50% reduction in telomerase activity. 1 Publication
Corresponds to variant rs199422301 [ dbSNP | Ensembl ].
VAR_062540
Natural varianti901 – 9011R → W in DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity. 1 Publication
Corresponds to variant rs199422304 [ dbSNP | Ensembl ].
VAR_062541
Pulmonary fibrosis, idiopathic (IPF)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. In some cases, the disorder can be rapidly progressive and characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease.
See also OMIM:178500
Melanoma, cutaneous malignant 9 (CMM9)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
See also OMIM:615134

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi137 – 1415WGLLL → AAAAA: Reduced catalytic activity and repeat addition processivity. Complete loss of catalytic activity but no loss of binding to telomeric primers; when associated with 930-A--A-934. 1 Publication
Mutagenesisi169 – 1691Q → A: About 80% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. Little effect on repeat addition processivity, nor on TR interaction nor on protein levels. 1 Publication
Mutagenesisi169 – 1691Q → N: About 85% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction. 1 Publication
Mutagenesisi169 – 1691Q → T: About 90% loss of enzymatic activity. Greatly reduced incorporation of second nucleotide. Altered strength of binding to ssDNA. No effect on protein levels nor on TR interaction. 1 Publication
Mutagenesisi457 – 4571S → A: Abolishes phosphorylation by DYRK2. 1 Publication
Mutagenesisi547 – 5471W → A: Defective in high-affinity TERC interactions. 1 Publication
Mutagenesisi631 – 6311R → A: Abolishes telomerase catalytic activity. 1 Publication
Mutagenesisi707 – 7071Y → F: Abolishes oxidative stress-induced phosphorylation and RAN binding. Impaired nuclear export and enhanced antiapoptotic activity against ROS-dependent apoptosis induction. Impaired interaction with PTPN11. No dephosphorylation by PTPN11. 2 Publications
Mutagenesisi712 – 7121D → A: Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers. 4 Publications
Mutagenesisi866 – 8661L → Y: Moderate reduction in telomerase activity, no change in repeat extension rate nor on nucleotide incorporation fidelity. Little further reduction in activity but 13.5-fold increase in nucleotide incorporation fidelity; when associated with M-867. 1 Publication
Mutagenesisi867 – 8671V → A: About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity. 1 Publication
Mutagenesisi867 – 8671V → M: About 75% reduction in telomerase activity, about 50% reduction in repeat extension rate and 5.2-fold increase in nucleotide incorporation fidelity. Little further reduction in activity and 13.5-fold increase in nucleotide incorporation fidelity; when associated with Y-866. 1 Publication
Mutagenesisi867 – 8671V → T: Severe reduction in telomerase activity, about 50% reduction in repeat extension rate and 2.2-fold increase in nucleotide incorporation fidelity. No further reduction in activity but 2.8-fold increase in nucleotide incorporation fidelity; when associated with Y-866. 1 Publication
Mutagenesisi868 – 8692DD → AA: Loss of telomerase activity.
Mutagenesisi868 – 8681D → A: Loss of telomerase activity. 5 Publications
Mutagenesisi869 – 8691D → A: Loss of telomerase activity. 2 Publications
Mutagenesisi930 – 9345WCGLL → AAAAA: Completely abolishes telomerase-mediated primer extension and reduced binding to short telomeric primers. Complete loss of catalytic activity but no further loss of binding to telomeric primers; when associated with 137-A--A-141. 1 Publication

Keywords - Diseasei

Disease mutation, Dyskeratosis congenita

Organism-specific databases

MalaCardsiTERT.
MIMi178500. phenotype.
187270. gene+phenotype.
609135. phenotype.
613989. phenotype.
614742. phenotype.
615134. phenotype.
Orphaneti1775. Dyskeratosis congenita.
618. Familial melanoma.
3322. Hoyeraal-Hreidarsson syndrome.
88. Idiopathic aplastic anemia.
2032. Idiopathic pulmonary fibrosis.
PharmGKBiPA36447.

Chemistry

ChEMBLiCHEMBL2916.
DrugBankiDB00495. Zidovudine.

Polymorphism and mutation databases

BioMutaiTERT.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11321132Telomerase reverse transcriptasePRO_0000054925Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei227 – 2271Phosphoserine; by PKB/AKT11 Publication
Modified residuei457 – 4571Phosphoserine; by DYRK21 Publication
Modified residuei707 – 7071Phosphotyrosine; by SRC-type Tyr-kinases2 Publications

Post-translational modificationi

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 at Ser-227 by the AKT pathway promotes nuclear location. Phosphorylation at the G2/M phase at Ser-457 by DYRK2 promotes ubiquitination by the EDVP complex and degradation.4 Publications
Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-457 by DYRK2. Ubiquitinated leads to proteasomal degradation. In case of infection by HIV-1, the EDVP complex is hijacked by HIV-1 via interaction between HIV-1 Vpr and DCAF1/VPRBP, leading to ubiquitination and degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO14746.
PaxDbiO14746.
PeptideAtlasiO14746.
PRIDEiO14746.

PTM databases

iPTMnetiO14746.
PhosphoSiteiO14746.

Expressioni

Tissue specificityi

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.2 Publications

Inductioni

Activated by cytotoxic events and down-regulated during aging. In peripheral T-lymphocytes, induced By CD3 and by PMA/ionomycin. Inhibited by herbimycin B.1 Publication

Gene expression databases

BgeeiENSG00000164362.
CleanExiHS_TERT.
GenevisibleiO14746. HS.

Organism-specific databases

HPAiCAB025088.

Interactioni

Subunit structurei

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). Interacts with isoform 1 and isoform 2 of NVL (PubMed:22226966).By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GNL3Q9BVP23EBI-1772203,EBI-641642
PMLP29590-57EBI-1772203,EBI-304008
RUVBL1Q9Y26511EBI-1772203,EBI-353675
UPF1Q929003EBI-1772203,EBI-373471

GO - Molecular functioni

  • protein homodimerization activity Source: BHF-UCL
  • transcription coactivator binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112874. 66 interactions.
DIPiDIP-40646N.
IntActiO14746. 16 interactions.
MINTiMINT-133963.
STRINGi9606.ENSP00000309572.

Chemistry

BindingDBiO14746.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BCKX-ray2.80C/F461-469[»]
4B18X-ray2.52B222-240[»]
4MNQX-ray2.74C540-548[»]
ProteinModelPortaliO14746.
SMRiO14746. Positions 344-595, 818-1019.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14746.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini605 – 935331Reverse transcriptasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 230230RNA-interacting domain 1Add
BLAST
Regioni58 – 197140GQ motifAdd
BLAST
Regioni137 – 1415Required for regulating specificity for telomeric DNA and for processivity for primer elongation
Regioni231 – 32494LinkerAdd
BLAST
Regioni301 – 538238Required for oligomerizationAdd
BLAST
Regioni325 – 550226RNA-interacting domain 2Add
BLAST
Regioni376 – 521146QFP motifAdd
BLAST
Regioni397 – 41721CP motifAdd
BLAST
Regioni914 – 92815Required for oligomerizationAdd
BLAST
Regioni930 – 9345Primer grip sequence
Regioni936 – 1132197CTEAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi222 – 24019Bipartite nuclear localization signalAdd
BLAST
Motifi328 – 3336TFLY; involved in RNA bindingBy similarity

Domaini

The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers.
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.
The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis.

Sequence similaritiesi

Contains 1 reverse transcriptase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1005. Eukaryota.
ENOG410XQJH. LUCA.
GeneTreeiENSGT00390000018531.
HOGENOMiHOG000148780.
HOVERGENiHBG000460.
InParanoidiO14746.
KOiK11126.
OMAiWLCYHAF.
OrthoDBiEOG091G04DO.
PhylomeDBiO14746.
TreeFamiTF329048.

Family and domain databases

InterProiIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PANTHERiPTHR12066:SF0. PTHR12066:SF0. 1 hit.
PfamiPF00078. RVT_1. 1 hit.
PF12009. Telomerase_RBD. 1 hit.
[Graphical view]
PRINTSiPR01365. TELOMERASERT.
SMARTiSM00975. Telomerase_RBD. 1 hit.
[Graphical view]
PROSITEiPS50878. RT_POL. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14746-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRAPRCRAV RSLLRSHYRE VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL
60 70 80 90 100
VAQCLVCVPW DARPPPAAPS FRQVSCLKEL VARVLQRLCE RGAKNVLAFG
110 120 130 140 150
FALLDGARGG PPEAFTTSVR SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV
160 170 180 190 200
HLLARCALFV LVAPSCAYQV CGPPLYQLGA ATQARPPPHA SGPRRRLGCE
210 220 230 240 250
RAWNHSVREA GVPLGLPAPG ARRRGGSASR SLPLPKRPRR GAAPEPERTP
260 270 280 290 300
VGQGSWAHPG RTRGPSDRGF CVVSPARPAE EATSLEGALS GTRHSHPSVG
310 320 330 340 350
RQHHAGPPST SRPPRPWDTP CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL
360 370 380 390 400
RPSLTGARRL VETIFLGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH
410 420 430 440 450
AQCPYGVLLK THCPLRAAVT PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ
460 470 480 490 500
LLRQHSSPWQ VYGFVRACLR RLVPPGLWGS RHNERRFLRN TKKFISLGKH
510 520 530 540 550
AKLSLQELTW KMSVRDCAWL RRSPGVGCVP AAEHRLREEI LAKFLHWLMS
560 570 580 590 600
VYVVELLRSF FYVTETTFQK NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE
610 620 630 640 650
LSEAEVRQHR EARPALLTSR LRFIPKPDGL RPIVNMDYVV GARTFRREKR
660 670 680 690 700
AERLTSRVKA LFSVLNYERA RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ
710 720 730 740 750
DPPPELYFVK VDVTGAYDTI PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA
760 770 780 790 800
AHGHVRKAFK SHVSTLTDLQ PYMRQFVAHL QETSPLRDAV VIEQSSSLNE
810 820 830 840 850
ASSGLFDVFL RFMCHHAVRI RGKSYVQCQG IPQGSILSTL LCSLCYGDME
860 870 880 890 900
NKLFAGIRRD GLLLRLVDDF LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL
910 920 930 940 950
RKTVVNFPVE DEALGGTAFV QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA
960 970 980 990 1000
RTSIRASLTF NRGFKAGRNM RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN
1010 1020 1030 1040 1050
IYKILLLQAY RFHACVLQLP FHQQVWKNPT FFLRVISDTA SLCYSILKAK
1060 1070 1080 1090 1100
NAGMSLGAKG AAGPLPSEAV QWLCHQAFLL KLTRHRVTYV PLLGSLRTAQ
1110 1120 1130
TQLSRKLPGT TLTALEAAAN PALPSDFKTI LD
Length:1,132
Mass (Da):126,997
Last modified:January 1, 1998 - v1
Checksum:i94E35469C4CA33A0
GO
Isoform 2 (identifier: O14746-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     764-807: STLTDLQPYM...LNEASSGLFD → LRPVPGDPAG...AGRAAPAFGG
     808-1132: Missing.

Show »
Length:807
Mass (Da):90,226
Checksum:i199664460CE6D763
GO
Isoform 3 (identifier: O14746-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     885-947: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Show »
Length:1,069
Mass (Da):120,048
Checksum:iBE1E77A653B1C666
GO
Isoform 4 (identifier: O14746-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     711-722: Missing.
     764-807: STLTDLQPYM...LNEASSGLFD → LRPVPGDPAG...AGRAAPAFGG
     808-1132: Missing.

Show »
Length:795
Mass (Da):88,965
Checksum:i6BEAC8A6D1A2E8CB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti516 – 5161D → G in AAC51724 (PubMed:9288757).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti55 – 551L → Q in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 Publication
Corresponds to variant rs387907247 [ dbSNP | Ensembl ].
VAR_062535
Natural varianti65 – 651P → A Associated with acute myeloid leukemia. 2 Publications
Corresponds to variant rs544215765 [ dbSNP | Ensembl ].
VAR_062780
Natural varianti170 – 1701V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 Publication
Corresponds to variant rs387907248 [ dbSNP | Ensembl ].
VAR_068792
Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
Corresponds to variant rs121918661 [ dbSNP | Ensembl ].
VAR_036863
Natural varianti279 – 2791A → T.1 Publication
Corresponds to variant rs61748181 [ dbSNP | Ensembl ].
VAR_036864
Natural varianti299 – 2991V → M Associated with acute myeloid leukemia. 2 Publications
Corresponds to variant rs756624928 [ dbSNP | Ensembl ].
VAR_062781
Natural varianti412 – 4121H → Y in PFBMFT1 and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. 5 Publications
Corresponds to variant rs34094720 [ dbSNP | Ensembl ].
VAR_025149
Natural varianti441 – 4411Missing in AA susceptibility; associated with susceptibility to acute myeloid leukemia. 3 Publications
VAR_036865
Natural varianti522 – 5221R → K Associated with acute myeloid leukemia. 2 Publications
VAR_062782
Natural varianti570 – 5701K → N in AA susceptibility; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications
VAR_062536
Natural varianti631 – 6311R → Q in AA susceptibility. 1 Publication
Corresponds to variant rs199422294 [ dbSNP | Ensembl ].
VAR_062783
Natural varianti682 – 6821G → D in AA susceptibility; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 2 Publications
Corresponds to variant rs199422295 [ dbSNP | Ensembl ].
VAR_062537
Natural varianti694 – 6941V → M in PFBMFT1; moderate. 2 Publications
Corresponds to variant rs121918662 [ dbSNP | Ensembl ].
VAR_036866
Natural varianti704 – 7041P → S in DKCB4; the mutant protein has 13% residual activity. 1 Publication
Corresponds to variant rs199422297 [ dbSNP | Ensembl ].
VAR_068793
Natural varianti716 – 7161A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 Publication
Corresponds to variant rs387907249 [ dbSNP | Ensembl ].
VAR_068794
Natural varianti721 – 7211P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 2 Publications
Corresponds to variant rs199422299 [ dbSNP | Ensembl ].
VAR_062538
Natural varianti726 – 7261T → M in AA susceptibility; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 Publications
Corresponds to variant rs149566858 [ dbSNP | Ensembl ].
VAR_062539
Natural varianti772 – 7721Y → C in PFBMFT1; moderate. 1 Publication
Corresponds to variant rs121918663 [ dbSNP | Ensembl ].
VAR_036867
Natural varianti785 – 7851P → L in AA susceptibility. 1 Publication
VAR_062784
Natural varianti791 – 7911V → I in PFBMFT1; associated with Met-867 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity. 1 Publication
Corresponds to variant rs141425941 [ dbSNP | Ensembl ].
VAR_068795
Natural varianti811 – 8111R → C in DKCB4; 50% reduction in telomerase activity. 1 Publication
Corresponds to variant rs199422301 [ dbSNP | Ensembl ].
VAR_062540
Natural varianti841 – 8411L → F in PFBMFT1. 1 Publication
VAR_068796
Natural varianti865 – 8651R → H in PFBMFT1. 1 Publication
Corresponds to variant rs121918666 [ dbSNP | Ensembl ].
VAR_036868
Natural varianti867 – 8671V → M in PFBMFT1; associated with Ile-791 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity; this mutation causes most if not all of the functional defects. 1 Publication
Corresponds to variant rs201159197 [ dbSNP | Ensembl ].
VAR_068797
Natural varianti901 – 9011R → W in DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity. 1 Publication
Corresponds to variant rs199422304 [ dbSNP | Ensembl ].
VAR_062541
Natural varianti902 – 9021K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications
Corresponds to variant rs121918665 [ dbSNP | Ensembl ].
VAR_036869
Natural varianti902 – 9021K → R in PFBMFT1. 1 Publication
Corresponds to variant rs387907250 [ dbSNP | Ensembl ].
VAR_068798
Natural varianti923 – 9231P → L in PFBMFT1. 1 Publication
Corresponds to variant rs387907251 [ dbSNP | Ensembl ].
VAR_068799
Natural varianti948 – 9481S → R.
Corresponds to variant rs34062885 [ dbSNP | Ensembl ].
VAR_053726
Natural varianti979 – 9791R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications
Corresponds to variant rs199422305 [ dbSNP | Ensembl ].
VAR_062542
Natural varianti1025 – 10251V → F in PFBMFT1. 1 Publication
VAR_068800
Natural varianti1062 – 10621A → T Increased incidence in sporadic acute myeloid leukemia. 4 Publications
Corresponds to variant rs35719940 [ dbSNP | Ensembl ].
VAR_025150
Natural varianti1090 – 10901V → M in PFBMFT1; severe. 1 Publication
Corresponds to variant rs121918664 [ dbSNP | Ensembl ].
VAR_036870
Natural varianti1110 – 11101T → M in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 Publication
Corresponds to variant rs199422306 [ dbSNP | Ensembl ].
VAR_062543
Natural varianti1127 – 11271F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications
VAR_062544

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei711 – 72212Missing in isoform 4. 1 PublicationVSP_053369Add
BLAST
Alternative sequencei764 – 80744STLTD…SGLFD → LRPVPGDPAGLHPLHAALQP VLRRHGEQAVCGDSAGRAAP AFGG in isoform 2 and isoform 4. 2 PublicationsVSP_019587Add
BLAST
Alternative sequencei808 – 1132325Missing in isoform 2 and isoform 4. 2 PublicationsVSP_019588Add
BLAST
Alternative sequencei885 – 94763Missing in isoform 3. 1 PublicationVSP_021727Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018167 mRNA. Translation: AAC51724.1.
AF015950 mRNA. Translation: AAC51672.1.
AF128894, AF128893 Genomic DNA. Translation: AAD30037.1.
AB085628 mRNA. Translation: BAC11010.1.
AB086379 mRNA. Translation: BAC11014.1.
AB086950 mRNA. Translation: BAC11015.1.
AY007685 Genomic DNA. Translation: AAG23289.1.
DQ264729 Genomic DNA. Translation: ABB72674.1.
AC114291 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08167.1.
CCDSiCCDS3861.2. [O14746-1]
CCDS54831.1. [O14746-3]
PIRiT03844.
RefSeqiNP_001180305.1. NM_001193376.1. [O14746-3]
NP_937983.2. NM_198253.2. [O14746-1]
UniGeneiHs.492203.

Genome annotation databases

EnsembliENST00000310581; ENSP00000309572; ENSG00000164362. [O14746-1]
ENST00000334602; ENSP00000334346; ENSG00000164362. [O14746-3]
ENST00000460137; ENSP00000425003; ENSG00000164362. [O14746-4]
ENST00000508104; ENSP00000426042; ENSG00000164362. [O14746-2]
GeneIDi7015.
KEGGihsa:7015.
UCSCiuc003jcb.2. human. [O14746-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF018167 mRNA. Translation: AAC51724.1.
AF015950 mRNA. Translation: AAC51672.1.
AF128894, AF128893 Genomic DNA. Translation: AAD30037.1.
AB085628 mRNA. Translation: BAC11010.1.
AB086379 mRNA. Translation: BAC11014.1.
AB086950 mRNA. Translation: BAC11015.1.
AY007685 Genomic DNA. Translation: AAG23289.1.
DQ264729 Genomic DNA. Translation: ABB72674.1.
AC114291 Genomic DNA. No translation available.
CH471102 Genomic DNA. Translation: EAX08167.1.
CCDSiCCDS3861.2. [O14746-1]
CCDS54831.1. [O14746-3]
PIRiT03844.
RefSeqiNP_001180305.1. NM_001193376.1. [O14746-3]
NP_937983.2. NM_198253.2. [O14746-1]
UniGeneiHs.492203.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BCKX-ray2.80C/F461-469[»]
4B18X-ray2.52B222-240[»]
4MNQX-ray2.74C540-548[»]
ProteinModelPortaliO14746.
SMRiO14746. Positions 344-595, 818-1019.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112874. 66 interactions.
DIPiDIP-40646N.
IntActiO14746. 16 interactions.
MINTiMINT-133963.
STRINGi9606.ENSP00000309572.

Chemistry

BindingDBiO14746.
ChEMBLiCHEMBL2916.
DrugBankiDB00495. Zidovudine.

PTM databases

iPTMnetiO14746.
PhosphoSiteiO14746.

Polymorphism and mutation databases

BioMutaiTERT.

Proteomic databases

EPDiO14746.
PaxDbiO14746.
PeptideAtlasiO14746.
PRIDEiO14746.

Protocols and materials databases

DNASUi7015.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000310581; ENSP00000309572; ENSG00000164362. [O14746-1]
ENST00000334602; ENSP00000334346; ENSG00000164362. [O14746-3]
ENST00000460137; ENSP00000425003; ENSG00000164362. [O14746-4]
ENST00000508104; ENSP00000426042; ENSG00000164362. [O14746-2]
GeneIDi7015.
KEGGihsa:7015.
UCSCiuc003jcb.2. human. [O14746-1]

Organism-specific databases

CTDi7015.
GeneCardsiTERT.
GeneReviewsiTERT.
HGNCiHGNC:11730. TERT.
HPAiCAB025088.
MalaCardsiTERT.
MIMi178500. phenotype.
187270. gene+phenotype.
609135. phenotype.
613989. phenotype.
614742. phenotype.
615134. phenotype.
neXtProtiNX_O14746.
Orphaneti1775. Dyskeratosis congenita.
618. Familial melanoma.
3322. Hoyeraal-Hreidarsson syndrome.
88. Idiopathic aplastic anemia.
2032. Idiopathic pulmonary fibrosis.
PharmGKBiPA36447.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1005. Eukaryota.
ENOG410XQJH. LUCA.
GeneTreeiENSGT00390000018531.
HOGENOMiHOG000148780.
HOVERGENiHBG000460.
InParanoidiO14746.
KOiK11126.
OMAiWLCYHAF.
OrthoDBiEOG091G04DO.
PhylomeDBiO14746.
TreeFamiTF329048.

Enzyme and pathway databases

ReactomeiR-HSA-171319. Telomere Extension By Telomerase.
R-HSA-201722. Formation of the beta-catenin:TCF transactivating complex.
SIGNORiO14746.

Miscellaneous databases

EvolutionaryTraceiO14746.
GeneWikiiTelomerase_reverse_transcriptase.
GenomeRNAii7015.
PROiO14746.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164362.
CleanExiHS_TERT.
GenevisibleiO14746. HS.

Family and domain databases

InterProiIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PANTHERiPTHR12066:SF0. PTHR12066:SF0. 1 hit.
PfamiPF00078. RVT_1. 1 hit.
PF12009. Telomerase_RBD. 1 hit.
[Graphical view]
PRINTSiPR01365. TELOMERASERT.
SMARTiSM00975. Telomerase_RBD. 1 hit.
[Graphical view]
PROSITEiPS50878. RT_POL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTERT_HUMAN
AccessioniPrimary (citable) accession number: O14746
Secondary accession number(s): O14783
, Q2XS35, Q8N6C3, Q8NG38, Q8NG46
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: September 7, 2016
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.