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O14746

- TERT_HUMAN

UniProt

O14746 - TERT_HUMAN

Protein

Telomerase reverse transcriptase

Gene

TERT

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    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

    1. metal ion binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: BHF-UCL
    4. telomerase activity Source: UniProtKB
    5. telomeric DNA binding Source: ProtInc
    6. telomeric RNA binding Source: BHF-UCL
    7. telomeric template RNA reverse transcriptase activity Source: UniProtKB

    GO - Biological processi

    1. DNA strand elongation Source: BHF-UCL
    2. negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
    3. replicative senescence Source: BHF-UCL
    4. telomere formation via telomerase Source: BHF-UCL
    5. telomere maintenance Source: UniProtKB
    6. telomere maintenance via telomerase Source: BHF-UCL

    Keywords - Molecular functioni

    Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase

    Keywords - Ligandi

    DNA-binding, Magnesium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_200753. formation of the beta-catenin:TCF transactivating complex.
    REACT_7974. Telomere Extension By Telomerase.

    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
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:11730. TERT.

    Subcellular locationi

    Nucleusnucleolus. 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

    1. chromosome, telomeric region Source: UniProtKB
    2. cytoplasm Source: UniProtKB-SubCell
    3. nuclear telomere cap complex Source: BHF-UCL
    4. nucleolus Source: UniProtKB-SubCell
    5. nucleoplasm Source: UniProtKB
    6. PML body Source: UniProtKB-SubCell
    7. telomerase holoenzyme complex Source: UniProtKB

    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) [MIM:609135]: A 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.4 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
    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
    VAR_062783
    Natural varianti682 – 6821G → D in AA susceptibility; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 1 Publication
    VAR_062537
    Natural varianti726 – 7261T → M in AA susceptibility; very severe; no effect on telomerase catalytic activity but shortened telomeres. 1 Publication
    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) [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.2 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti902 – 9021K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 1 Publication
    VAR_036869
    Natural varianti979 – 9791R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 1 Publication
    VAR_062542
    Natural varianti1127 – 11271F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 1 Publication
    VAR_062544
    Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 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.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti170 – 1701V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 Publication
    VAR_068792
    Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
    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
    VAR_036866
    Natural varianti716 – 7161A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 Publication
    VAR_068794
    Natural varianti772 – 7721Y → C in PFBMFT1; moderate. 1 Publication
    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
    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
    VAR_068797
    Natural varianti902 – 9021K → R in PFBMFT1. 1 Publication
    VAR_068798
    Natural varianti923 – 9231P → L in PFBMFT1. 1 Publication
    VAR_068799
    Natural varianti1025 – 10251V → F in PFBMFT1. 1 Publication
    VAR_068800
    Natural varianti1090 – 10901V → M in PFBMFT1; severe. 1 Publication
    VAR_036870
    Dyskeratosis congenita, autosomal recessive, 4 (DKCB4) [MIM:613989]: A 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.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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
    VAR_068793
    Natural varianti721 – 7211P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 1 Publication
    VAR_062538
    Natural varianti811 – 8111R → C in DKCB4; 50% reduction in telomerase activity. 1 Publication
    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
    VAR_062541
    Pulmonary fibrosis, idiopathic (IPF) [MIM:178500]: A 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.
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Melanoma, cutaneous malignant 9 (CMM9) [MIM:615134]: A 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.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

    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.
    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. 5 Publications
    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.

    Keywords - Diseasei

    Disease mutation, Dyskeratosis congenita

    Organism-specific databases

    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.

    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

    PaxDbiO14746.
    PRIDEiO14746.

    PTM databases

    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

    ArrayExpressiO14746.
    BgeeiO14746.
    CleanExiHS_TERT.
    GenevestigatoriO14746.

    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.By similarity

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi112874. 63 interactions.
    DIPiDIP-40646N.
    IntActiO14746. 11 interactions.
    MINTiMINT-133963.
    STRINGi9606.ENSP00000309572.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2BCKX-ray2.80C/F461-469[»]
    4B18X-ray2.52B222-240[»]
    4MNQX-ray2.74C540-548[»]
    ProteinModelPortaliO14746.
    SMRiO14746. Positions 344-593, 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

    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

    eggNOGiNOG276584.
    HOGENOMiHOG000148780.
    HOVERGENiHBG000460.
    InParanoidiO14746.
    KOiK11126.
    OMAiWLCYHAF.
    OrthoDBiEOG744TB3.
    PhylomeDBiO14746.
    TreeFamiTF329048.

    Family and domain databases

    InterProiIPR000477. RT_dom.
    IPR021891. Telomerase_RBD.
    IPR003545. Telomerase_RT.
    [Graphical view]
    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. Align

    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

    MPRAPRCRAV RSLLRSHYRE VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL     50
    VAQCLVCVPW DARPPPAAPS FRQVSCLKEL VARVLQRLCE RGAKNVLAFG 100
    FALLDGARGG PPEAFTTSVR SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV 150
    HLLARCALFV LVAPSCAYQV CGPPLYQLGA ATQARPPPHA SGPRRRLGCE 200
    RAWNHSVREA GVPLGLPAPG ARRRGGSASR SLPLPKRPRR GAAPEPERTP 250
    VGQGSWAHPG RTRGPSDRGF CVVSPARPAE EATSLEGALS GTRHSHPSVG 300
    RQHHAGPPST SRPPRPWDTP CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL 350
    RPSLTGARRL VETIFLGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH 400
    AQCPYGVLLK THCPLRAAVT PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ 450
    LLRQHSSPWQ VYGFVRACLR RLVPPGLWGS RHNERRFLRN TKKFISLGKH 500
    AKLSLQELTW KMSVRDCAWL RRSPGVGCVP AAEHRLREEI LAKFLHWLMS 550
    VYVVELLRSF FYVTETTFQK NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE 600
    LSEAEVRQHR EARPALLTSR LRFIPKPDGL RPIVNMDYVV GARTFRREKR 650
    AERLTSRVKA LFSVLNYERA RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ 700
    DPPPELYFVK VDVTGAYDTI PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA 750
    AHGHVRKAFK SHVSTLTDLQ PYMRQFVAHL QETSPLRDAV VIEQSSSLNE 800
    ASSGLFDVFL RFMCHHAVRI RGKSYVQCQG IPQGSILSTL LCSLCYGDME 850
    NKLFAGIRRD GLLLRLVDDF LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL 900
    RKTVVNFPVE DEALGGTAFV QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA 950
    RTSIRASLTF NRGFKAGRNM RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN 1000
    IYKILLLQAY RFHACVLQLP FHQQVWKNPT FFLRVISDTA SLCYSILKAK 1050
    NAGMSLGAKG AAGPLPSEAV QWLCHQAFLL KLTRHRVTYV PLLGSLRTAQ 1100
    TQLSRKLPGT TLTALEAAAN PALPSDFKTI LD 1132
    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
    VAR_062535
    Natural varianti65 – 651P → A Associated with acute myeloid leukemia. 2 Publications
    VAR_062780
    Natural varianti170 – 1701V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 Publication
    VAR_068792
    Natural varianti202 – 2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. 3 Publications
    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
    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
    VAR_062783
    Natural varianti682 – 6821G → D in AA susceptibility; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 1 Publication
    VAR_062537
    Natural varianti694 – 6941V → M in PFBMFT1; moderate. 2 Publications
    VAR_036866
    Natural varianti704 – 7041P → S in DKCB4; the mutant protein has 13% residual activity. 1 Publication
    VAR_068793
    Natural varianti716 – 7161A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 Publication
    VAR_068794
    Natural varianti721 – 7211P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 1 Publication
    VAR_062538
    Natural varianti726 – 7261T → M in AA susceptibility; very severe; no effect on telomerase catalytic activity but shortened telomeres. 1 Publication
    VAR_062539
    Natural varianti772 – 7721Y → C in PFBMFT1; moderate. 1 Publication
    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
    VAR_062540
    Natural varianti841 – 8411L → F in PFBMFT1. 1 Publication
    VAR_068796
    Natural varianti865 – 8651R → H in PFBMFT1. 1 Publication
    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
    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
    VAR_062541
    Natural varianti902 – 9021K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 1 Publication
    VAR_036869
    Natural varianti902 – 9021K → R in PFBMFT1. 1 Publication
    VAR_068798
    Natural varianti923 – 9231P → L in PFBMFT1. 1 Publication
    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. 1 Publication
    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
    VAR_036870
    Natural varianti1110 – 11101T → M in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 Publication
    VAR_062543
    Natural varianti1127 – 11271F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 1 Publication
    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:
    EMBL
    GenBank
    DDBJ
    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.
    UCSCiuc003jca.1. human. [O14746-1]
    uc003jcc.1. human. [O14746-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS3861.2. [O14746-1 ]
    CCDS54831.1. [O14746-3 ]
    PIRi T03844.
    RefSeqi NP_001180305.1. NM_001193376.1. [O14746-3 ]
    NP_937983.2. NM_198253.2. [O14746-1 ]
    UniGenei Hs.492203.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2BCK X-ray 2.80 C/F 461-469 [» ]
    4B18 X-ray 2.52 B 222-240 [» ]
    4MNQ X-ray 2.74 C 540-548 [» ]
    ProteinModelPortali O14746.
    SMRi O14746. Positions 344-593, 818-1019.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112874. 63 interactions.
    DIPi DIP-40646N.
    IntActi O14746. 11 interactions.
    MINTi MINT-133963.
    STRINGi 9606.ENSP00000309572.

    Chemistry

    BindingDBi O14746.
    ChEMBLi CHEMBL2916.

    PTM databases

    PhosphoSitei O14746.

    Proteomic databases

    PaxDbi O14746.
    PRIDEi O14746.

    Protocols and materials databases

    DNASUi 7015.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000310581 ; ENSP00000309572 ; ENSG00000164362 . [O14746-1 ]
    ENST00000334602 ; ENSP00000334346 ; ENSG00000164362 . [O14746-3 ]
    ENST00000460137 ; ENSP00000425003 ; ENSG00000164362 . [O14746-4 ]
    ENST00000508104 ; ENSP00000426042 ; ENSG00000164362 . [O14746-2 ]
    GeneIDi 7015.
    KEGGi hsa:7015.
    UCSCi uc003jca.1. human. [O14746-1 ]
    uc003jcc.1. human. [O14746-3 ]

    Organism-specific databases

    CTDi 7015.
    GeneCardsi GC05M001253.
    GeneReviewsi TERT.
    HGNCi HGNC:11730. TERT.
    MIMi 178500. phenotype.
    187270. gene+phenotype.
    609135. phenotype.
    613989. phenotype.
    614742. phenotype.
    615134. phenotype.
    neXtProti NX_O14746.
    Orphaneti 1775. Dyskeratosis congenita.
    618. Familial melanoma.
    3322. Hoyeraal-Hreidarsson syndrome.
    88. Idiopathic aplastic anemia.
    2032. Idiopathic pulmonary fibrosis.
    PharmGKBi PA36447.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG276584.
    HOGENOMi HOG000148780.
    HOVERGENi HBG000460.
    InParanoidi O14746.
    KOi K11126.
    OMAi WLCYHAF.
    OrthoDBi EOG744TB3.
    PhylomeDBi O14746.
    TreeFami TF329048.

    Enzyme and pathway databases

    Reactomei REACT_200753. formation of the beta-catenin:TCF transactivating complex.
    REACT_7974. Telomere Extension By Telomerase.

    Miscellaneous databases

    EvolutionaryTracei O14746.
    GeneWikii Telomerase_reverse_transcriptase.
    GenomeRNAii 7015.
    NextBioi 13641567.
    PROi O14746.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14746.
    Bgeei O14746.
    CleanExi HS_TERT.
    Genevestigatori O14746.

    Family and domain databases

    InterProi IPR000477. RT_dom.
    IPR021891. Telomerase_RBD.
    IPR003545. Telomerase_RT.
    [Graphical view ]
    Pfami PF00078. RVT_1. 1 hit.
    PF12009. Telomerase_RBD. 1 hit.
    [Graphical view ]
    PRINTSi PR01365. TELOMERASERT.
    SMARTi SM00975. Telomerase_RBD. 1 hit.
    [Graphical view ]
    PROSITEi PS50878. RT_POL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization."
      Meyerson M., Counter C.M., Eaton E.N., Ellisen L.W., Steiner P., Caddle S.D., Ziaugra L., Beijersbergen R.L., Davidoff M.J., Liu Q., Bacchetti S., Haber D.A., Weinberg R.A.
      Cell 90:785-795(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Embryonic kidney.
    3. "Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT)."
      Wick M., Zubov D., Hagen G.
      Gene 232:97-106(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    4. "Expression profile of a gamma-deletion variant of the human telomerase reverse transcriptase gene."
      Hisatomi H., Ohyashiki K., Ohyashiki J.H., Nagao K., Kanamaru T., Hirata H., Hibi N., Tsukada Y.
      Neoplasia 5:193-197(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    5. "Differential alternative splicing expressions of telomerase reverse transcriptase in gastrointestinal cell lines."
      Nagao K., Katsumata K., Aizawa Y., Saito N., Hirata H., Sasaki H., Yamamoto S., Hikiji K., Koiwa T., Hisatomi H.
      Oncol. Rep. 11:127-131(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
      Tissue: Stomach cancer.
    6. "Sequence of a BAC carrying the entire hTERT gene."
      Londono-Vallejo J.A.
      Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    7. NIEHS SNPs program
      Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-412 AND THR-1062.
    8. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "Regulated expression of telomerase activity in human T lymphocyte development and activation."
      Weng N.P., Levine B.L., June C.H., Hodes R.J.
      J. Exp. Med. 183:2471-2479(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, INDUCTION.
    11. "Human telomerase contains evolutionarily conserved catalytic and structural subunits."
      Harrington L., Zhou W., McPhail T., Oulton R., Yeung D.S., Mar V., Bass M.B., Robinson M.O.
      Genes Dev. 11:3109-3115(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN TELOMERASE ACTIVITY, TISSUE SPECIFICITY, ASSOCIATION WITH TEP1, MUTAGENESIS OF ASP-712; ASP-868 AND ASP-869.
    12. "Reconstitution of human telomerase activity in vitro."
      Beattie T.L., Zhou W., Robinson M.O., Harrington L.
      Curr. Biol. 8:177-180(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECONSTITUTION OF THE TELOMERASE COMPLEX, MUTAGENESIS OF ASP-712; ASP-868 AND ASP-869.
    13. "Polymerization defects within human telomerase are distinct from telomerase RNA and TEP1 binding."
      Beattie T.L., Zhou W., Robinson M.O., Harrington L.
      Mol. Biol. Cell 11:3329-3340(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: ASSOCIATION WITH TEP1.
    14. "Stable association of hsp90 and p23, but Not hsp70, with active human telomerase."
      Forsythe H.L., Jarvis J.L., Turner J.W., Elmore L.W., Holt S.E.
      J. Biol. Chem. 276:15571-15574(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HSPA1A; HSP90A AND PTGES3.
    15. "Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707."
      Haendeler J., Hoffmann J., Brandes R.P., Zeiher A.M., Dimmeler S.
      Mol. Cell. Biol. 23:4598-4610(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT TYR-707, SUBCELLULAR LOCATION, INTERACTION WITH RAN AND XP01, MUTAGENESIS OF TYR-707.
    16. "Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length."
      Song H., Li Y., Chen G., Xing Z., Zhao J., Yokoyama K.K., Li T., Zhao M.
      Biochem. Biophys. Res. Commun. 316:1116-1123(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MCRS1.
    17. "Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells."
      Haendeler J., Hoffmann J., Diehl J.F., Vasa M., Spyridopoulos I., Zeiher A.M., Dimmeler S.
      Circ. Res. 94:768-775(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION.
    18. "Immunohistochemical localization of hTERT protein in human tissues."
      Yan P., Benhattar J., Seelentag W., Stehle J.C., Bosman F.T.
      Histochem. Cell Biol. 121:391-397(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    19. Cited for: INTERACTION WITH NCL, SUBCELLULAR LOCATION.
    20. "Functional organization of repeat addition processivity and DNA synthesis determinants in the human telomerase multimer."
      Moriarty T.J., Marie-Egyptienne D.T., Autexier C.
      Mol. Cell. Biol. 24:3720-3733(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTIONAL DOMAINS, MUTAGENESIS OF TRP-547 AND ASP-868.
    21. "Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT."
      Kim J.H., Park S.-M., Kang M.R., Oh S.-Y., Lee T.H., Muller M.T., Chung I.K.
      Genes Dev. 19:776-781(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MKRN1, UBIQUITINATION.
    22. "An anchor site-type defect in human telomerase that disrupts telomere length maintenance and cellular immortalization."
      Moriarty T.J., Ward R.J., Taboski M.A., Autexier C.
      Mol. Biol. Cell 16:3152-3161(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASP-868.
    23. "Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth."
      Rahman R., Mo L., Cui W.
      Biochem. Biophys. Res. Commun. 350:796-802(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ARG-631; ASP-712 AND ASP-868.
    24. "The loss of telomerase activity in highly differentiated CD8+CD28-CD27- T cells is associated with decreased Akt (Ser473) phosphorylation."
      Plunkett F.J., Franzese O., Finney H.M., Fletcher J.M., Belaramani L.L., Salmon M., Dokal I., Webster D., Lawson A.D., Akbar A.N.
      J. Immunol. 178:7710-7719(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, FUNCTION.
    25. "Purification of human telomerase complexes identifies factors involved in telomerase biogenesis and telomere length regulation."
      Fu D., Collins K.
      Mol. Cell 28:773-785(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NAT10.
    26. "Characterization of physical and functional anchor site interactions in human telomerase."
      Wyatt H.D., Lobb D.A., Beattie T.L.
      Mol. Cell. Biol. 27:3226-3240(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING, MUTAGENESIS OF 137-TRP--LEU-141; ASP-712 AND 930-TRP--LEU-934.
    27. "The active site residue Valine 867 in human telomerase reverse transcriptase influences nucleotide incorporation and fidelity."
      Drosopoulos W.C., Prasad V.R.
      Nucleic Acids Res. 35:1155-1168(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF LEU-866 AND VAL-867.
    28. "Nuclear protein tyrosine phosphatase Shp-2 is one important negative regulator of nuclear export of telomerase reverse transcriptase."
      Jakob S., Schroeder P., Lukosz M., Buchner N., Spyridopoulos I., Altschmied J., Haendeler J.
      J. Biol. Chem. 283:33155-33161(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTPN11, PHOSPHORYLATION AT TYR-707, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-707.
    29. "Ionizing radiation up-regulates telomerase activity in cancer cell lines by post-translational mechanism via ras/phosphatidylinositol 3-kinase/Akt pathway."
      Ram R., Uziel O., Eldan O., Fenig E., Beery E., Lichtenberg S., Nordenberg Y., Lahav M.
      Clin. Cancer Res. 15:914-923(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, FUNCTION, SUBCELLULAR LOCATION.
    30. "PML-IV functions as a negative regulator of telomerase by interacting with TERT."
      Oh W., Ghim J., Lee E.W., Yang M.R., Kim E.T., Ahn J.H., Song J.
      J. Cell Sci. 122:2613-2622(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PML.
    31. Cited for: INTERACTION WITH SMARCA4, FUNCTION.
    32. "Human telomerase reverse transcriptase (hTERT) Q169 is essential for telomerase function in vitro and in vivo."
      Wyatt H.D., Tsang A.R., Lobb D.A., Beattie T.L.
      PLoS ONE 4:E7176-E7176(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DNA-BINDING, MUTAGENESIS OF GLN-169.
    33. "A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis."
      Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M., Veenstra T.D., Terns M.P., Artandi S.E.
      Science 323:644-648(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
    34. "Nuclear import of hTERT requires a bipartite nuclear localization signal and Akt-mediated phosphorylation."
      Chung J., Khadka P., Chung I.K.
      J. Cell Sci. 125:2684-2697(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-227, SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNAL.
    35. "Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation."
      Jung H.Y., Wang X., Jun S., Park J.I.
      J. Biol. Chem. 288:7252-7262(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-457, UBIQUITINATION, MUTAGENESIS OF SER-457.
    36. "HIV-1 Vpr protein inhibits telomerase activity via the EDD-DDB1-VPRBP E3 ligase complex."
      Wang X., Singh S., Jung H.Y., Yang G., Jun S., Sastry K.J., Park J.I.
      J. Biol. Chem. 288:15474-15480(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    37. Cited for: INVOLVEMENT IN CMM9.
    38. Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 461-469 IN COMPLEX WITH CLASS I MAJOR HISTOCOMPATIBILITY COMPLEX (MHC).
    39. "Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure."
      Vulliamy T.J., Walne A., Baskaradas A., Mason P.J., Marrone A., Dokal I.
      Blood Cells Mol. Dis. 34:257-263(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AA SUSCEPTIBILITY THR-202, VARIANTS DKCA2 TRP-979 AND LEU-1127, CHARACTERIZATION OF VARIANT AA SUSCEPTIBILTY THR-202, CHARACTERIZATION OF VARIANTS DKCA2 TRP-979 AND LEU-1127.
    40. "Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia."
      Yamaguchi H., Calado R.T., Ly H., Kajigaya S., Baerlocher G.M., Chanock S.J., Lansdorp P.M., Young N.S.
      N. Engl. J. Med. 352:1413-1424(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PFBMFT1 THR-202; TYR-412; MET-694; CYS-772 AND MET-1090, VARIANTS THR-279; GLU-441 DEL AND THR-1062.
    41. "Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita."
      Armanios M., Chen J.-L., Chang Y.-P.C., Brodsky R.A., Hawkins A., Griffin C.A., Eshleman J.R., Cohen A.R., Chakravarti A., Hamosh A., Greider C.W.
      Proc. Natl. Acad. Sci. U.S.A. 102:15960-15964(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT DKCA2 ASN-902, CHARACTERIZATION OF VARIANT DKCA2 ASN-902.
    42. Cited for: INVOLVEMENT IN CAD SUSCEPTIBILITY.
    43. "Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation."
      Vulliamy T.J., Marrone A., Knight S.W., Walne A., Mason P.J., Dokal I.
      Blood 107:2680-2685(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT DKCB4 ARG-721.
    44. "Mutations in telomerase catalytic protein in Japanese children with aplastic anemia."
      Liang J., Yagasaki H., Kamachi Y., Hama A., Matsumoto K., Kato K., Kudo K., Kojima S.
      Haematologica 91:656-658(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AA SUSCEPTIBILITY ASP-682 AND MET-726, CHARACTERIZATION OF MET-726.
    45. "Functional characterization of natural telomerase mutations found in patients with hematologic disorders."
      Xin Z.T., Beauchamp A.D., Calado R.T., Bradford J.W., Regal J.A., Shenoy A., Liang Y., Lansdorp P.M., Young N.S., Ly H.
      Blood 109:524-532(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AA SUSCEPTIBILITY ASN-570, CHARACTERIZATION OF VARIANTS ASN-570; ASP-682; ARG-721; MET-726; ASN-902; TRP-979 AND LEU-1127.
    46. "Telomerase reverse-transcriptase homozygous mutations in autosomal recessive dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome."
      Marrone A., Walne A., Tamary H., Masunari Y., Kirwan M., Beswick R., Vulliamy T., Dokal I.
      Blood 110:4198-4205(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS DKCB4 CYS-811 AND TRP-901, CHARACTERIZATION OF VARIANTS DKCB4 CYS-811 AND TRP-901.
    47. Cited for: VARIANTS IDIOPATHIC PULMONARY FIBROSIS SUSCEPTIBILITY GLN-55 AND MET-1110, CHARACTERIZATION OF VARIANTS GLN-55 AND MET-1110.
    48. Cited for: VARIANT PFBMFT1 HIS-865.
    49. "Complex inheritance pattern of dyskeratosis congenita in two families with 2 different mutations in the telomerase reverse transcriptase gene."
      Du H.Y., Pumbo E., Manley P., Field J.J., Bayliss S.J., Wilson D.B., Mason P.J., Bessler M.
      Blood 111:1128-1130(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS DKCB4 TYR-412 AND SER-704, CHARACTERIZATION OF VARIANTS DKCB4 TYR-412 AND SER-704.
    50. "Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia."
      Kirwan M., Vulliamy T., Marrone A., Walne A.J., Beswick R., Hillmen P., Kelly R., Stewart A., Bowen D., Schonland S.O., Whittle A.M., McVerry A., Gilleece M., Dokal I.
      Hum. Mutat. 30:1567-1573(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ALA-65; MET-299; LYS-522 AND THR-1062, VARIANTS AA SUSCEPTIBILITY THR-202; TYR-412; GLU-441 DEL; ASN-570; GLN-631; MET-694 AND LEU-785.
    51. Cited for: VARIANTS ALA-65; MET-299; TYR-412; GLU-441 DEL; LYS-522 AND THR-1062.
    52. "Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase."
      Parry E.M., Alder J.K., Qi X., Chen J.J., Armanios M.
      Blood 117:5607-5611(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PFBMFT1 MET-170; THR-716; PHE-841; ARG-902 AND PHE-1025, CHARACTERIZATION OF VARIANTS PFBMFT1 MET-170; THR-716; PHE-841 AND PHE-1025.
    53. "Ancestral mutation in telomerase causes defects in repeat addition processivity and manifests as familial pulmonary fibrosis."
      Alder J.K., Cogan J.D., Brown A.F., Anderson C.J., Lawson W.E., Lansdorp P.M., Phillips J.A. III, Loyd J.E., Chen J.J., Armanios M.
      PLoS Genet. 7:E1001352-E1001352(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PFBMFT1 ILE-791 AND MET-867, CHARACTERIZATION OF VARIANTS PFBMFT1 ILE-791 AND MET-867.
    54. "Pulmonary fibrosis, bone marrow failure, and telomerase mutation."
      Gansner J.M., Rosas I.O., Ebert B.L.
      N. Engl. J. Med. 366:1551-1553(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PFBMFT1 LEU-923.

    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: October 1, 2014
    This is version 142 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

    External Data

    Dasty 3