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O14746 (TERT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Telomerase reverse transcriptase

EC=2.7.7.49
Alternative name(s):
HEST2
Telomerase catalytic subunit
Telomerase-associated protein 2
Short name=TP2
Gene names
Name:TERT
Synonyms:EST2, TCS1, TRT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1132 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis. Ref.11 Ref.17 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27 Ref.29 Ref.30 Ref.31 Ref.32

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Subunit structure

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. Ref.14 Ref.15 Ref.16 Ref.19 Ref.21 Ref.25 Ref.28 Ref.30 Ref.31 Ref.33

Subcellular location

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. Ref.15 Ref.17 Ref.18 Ref.19 Ref.28 Ref.29 Ref.30 Ref.34

Tissue specificity

Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes. Ref.10 Ref.11

Induction

Activated by cytotoxic events and down-regulated during aging. In peripheral T-lymphocytes, induced By CD3 and by PMA/ionomycin. Inhibited by herbimycin B. Ref.10

Domain

The primer grip sequence in the RT domain is required for telomerase activity and for stable association with short telomeric primers. Ref.20

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. Ref.20

The RNA-interacting domain 2 (RD2) is essential for both interaction with the CR4-CR5 domain of TERC and for DNA synthesis. Ref.20

Post-translational modification

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. Ref.15 Ref.24 Ref.28 Ref.29 Ref.34 Ref.35

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. Ref.21 Ref.35 Ref.36

Involvement in disease

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.39 Ref.44 Ref.45 Ref.50

Genetic variations in TERT are associated with coronary artery disease (CAD). Ref.42

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.39 Ref.41

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.40 Ref.48 Ref.52 Ref.53 Ref.54

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.43 Ref.46 Ref.49

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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.37

Sequence similarities

Belongs to the reverse transcriptase family. Telomerase subfamily.

Contains 1 reverse transcriptase domain.

Ontologies

Keywords
   Cellular componentChromosome
Cytoplasm
Nucleus
Telomere
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Dyskeratosis congenita
   LigandDNA-binding
Magnesium
Metal-binding
   Molecular functionNucleotidyltransferase
Ribonucleoprotein
RNA-directed DNA polymerase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA strand elongation

Inferred from direct assay PubMed 16043710. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from mutant phenotype PubMed 10449030. Source: BHF-UCL

replicative senescence

Inferred from mutant phenotype PubMed 9454332. Source: BHF-UCL

telomere formation via telomerase

Inferred from direct assay PubMed 16043710. Source: BHF-UCL

telomere maintenance

Traceable author statement PubMed 12135483. Source: UniProtKB

telomere maintenance via telomerase

Inferred from mutant phenotype PubMed 9454332. Source: BHF-UCL

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

chromosome, telomeric region

Inferred by curator PubMed 12135483. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear telomere cap complex

Inferred by curator PubMed 15632080. Source: BHF-UCL

nucleolus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleoplasm

Inferred from direct assay Ref.30. Source: UniProtKB

telomerase holoenzyme complex

Inferred from direct assay PubMed 12135483. Source: UniProtKB

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 15381700Ref.33Ref.30. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 11432839. Source: BHF-UCL

telomerase activity

Inferred from direct assay PubMed 12135483. Source: UniProtKB

telomeric DNA binding

Traceable author statement Ref.1. Source: ProtInc

telomeric RNA binding

Inferred from direct assay PubMed 11432839. Source: BHF-UCL

telomeric template RNA reverse transcriptase activity

Traceable author statement PubMed 14991929. Source: UniProtKB

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O14746-1)

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.
Isoform 2 (identifier: O14746-2)

The sequence of this isoform differs from the canonical sequence as follows:
     764-807: STLTDLQPYM...LNEASSGLFD → LRPVPGDPAG...AGRAAPAFGG
     808-1132: Missing.
Isoform 3 (identifier: O14746-3)

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.
Isoform 4 (identifier: O14746-4)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11321132Telomerase reverse transcriptase
PRO_0000054925

Regions

Domain605 – 935331Reverse transcriptase
Region1 – 230230RNA-interacting domain 1
Region58 – 197140GQ motif
Region137 – 1415Required for regulating specificity for telomeric DNA and for processivity for primer elongation
Region231 – 32494Linker
Region301 – 538238Required for oligomerization
Region325 – 550226RNA-interacting domain 2
Region376 – 521146QFP motif
Region397 – 41721CP motif
Region914 – 92815Required for oligomerization
Region930 – 9345Primer grip sequence
Region936 – 1132197CTE
Motif222 – 24019Bipartite nuclear localization signal

Sites

Metal binding7121Magnesium; catalytic By similarity
Metal binding8681Magnesium; catalytic By similarity
Metal binding8691Magnesium; catalytic By similarity
Site1691Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template
Site8671Required for nucleotide incorporation and primer extension rate

Amino acid modifications

Modified residue2271Phosphoserine; by PKB/AKT1 Ref.34
Modified residue4571Phosphoserine; by DYRK2 Ref.35
Modified residue7071Phosphotyrosine; by SRC-type Tyr-kinases Ref.15 Ref.28

Natural variations

Alternative sequence711 – 72212Missing in isoform 4.
VSP_053369
Alternative sequence764 – 80744STLTD…SGLFD → LRPVPGDPAGLHPLHAALQP VLRRHGEQAVCGDSAGRAAP AFGG in isoform 2 and isoform 4.
VSP_019587
Alternative sequence808 – 1132325Missing in isoform 2 and isoform 4.
VSP_019588
Alternative sequence885 – 94763Missing in isoform 3.
VSP_021727
Natural variant551L → Q in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. Ref.47
VAR_062535
Natural variant651P → A Associated with acute myeloid leukemia. Ref.50 Ref.51
VAR_062780
Natural variant1701V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. Ref.52
VAR_068792
Natural variant2021A → T in PFBMFT1 and AA susceptibilty; severe and moderate; shorter telomeres. Ref.39 Ref.40 Ref.50
VAR_036863
Natural variant2791A → T. Ref.40
Corresponds to variant rs61748181 [ dbSNP | Ensembl ].
VAR_036864
Natural variant2991V → M Associated with acute myeloid leukemia. Ref.50 Ref.51
VAR_062781
Natural variant4121H → Y in PFBMFT1 and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. Ref.7 Ref.40 Ref.49 Ref.50 Ref.51
Corresponds to variant rs34094720 [ dbSNP | Ensembl ].
VAR_025149
Natural variant4411Missing in AA susceptibility; associated with susceptibility to acute myeloid leukemia. Ref.40 Ref.50 Ref.51
VAR_036865
Natural variant5221R → K Associated with acute myeloid leukemia. Ref.50 Ref.51
VAR_062782
Natural variant5701K → N in AA susceptibility; abolishes telomerase catalytic activity but no effect on binding to TERC. Ref.45 Ref.50
VAR_062536
Natural variant6311R → Q in AA susceptibility. Ref.50
VAR_062783
Natural variant6821G → D in AA susceptibility; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. Ref.44 Ref.45
VAR_062537
Natural variant6941V → M in PFBMFT1; moderate. Ref.40 Ref.50
VAR_036866
Natural variant7041P → S in DKCB4; the mutant protein has 13% residual activity. Ref.49
VAR_068793
Natural variant7161A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. Ref.52
VAR_068794
Natural variant7211P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. Ref.43 Ref.45
VAR_062538
Natural variant7261T → M in AA susceptibility; very severe; no effect on telomerase catalytic activity but shortened telomeres. Ref.44 Ref.45
VAR_062539
Natural variant7721Y → C in PFBMFT1; moderate. Ref.40
VAR_036867
Natural variant7851P → L in AA susceptibility. Ref.50
VAR_062784
Natural variant7911V → I in PFBMFT1; associated with Met-867 in cis on the same allele; the double mutant shows severe defects in telomere repeat addition processivity. Ref.53
Corresponds to variant rs141425941 [ dbSNP | Ensembl ].
VAR_068795
Natural variant8111R → C in DKCB4; 50% reduction in telomerase activity. Ref.46
VAR_062540
Natural variant8411L → F in PFBMFT1. Ref.52
VAR_068796
Natural variant8651R → H in PFBMFT1. Ref.48
VAR_036868
Natural variant8671V → 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. Ref.53
VAR_068797
Natural variant9011R → W in DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity. Ref.46
VAR_062541
Natural variant9021K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. Ref.41 Ref.45
VAR_036869
Natural variant9021K → R in PFBMFT1. Ref.52
VAR_068798
Natural variant9231P → L in PFBMFT1. Ref.54
VAR_068799
Natural variant9481S → R.
Corresponds to variant rs34062885 [ dbSNP | Ensembl ].
VAR_053726
Natural variant9791R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. Ref.39 Ref.45
VAR_062542
Natural variant10251V → F in PFBMFT1. Ref.52
VAR_068800
Natural variant10621A → T Increased incidence in sporadic acute myeloid leukemia. Ref.7 Ref.40 Ref.50 Ref.51
Corresponds to variant rs35719940 [ dbSNP | Ensembl ].
VAR_025150
Natural variant10901V → M in PFBMFT1; severe. Ref.40
VAR_036870
Natural variant11101T → M in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. Ref.47
VAR_062543
Natural variant11271F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. Ref.39 Ref.45
VAR_062544

Experimental info

Mutagenesis137 – 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. Ref.26
Mutagenesis1691Q → 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. Ref.32
Mutagenesis1691Q → 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. Ref.32
Mutagenesis1691Q → 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. Ref.32
Mutagenesis4571S → A: Abolishes phosphorylation by DYRK2. Ref.35
Mutagenesis5471W → A: Defective in high-affinity TERC interactions. Ref.20
Mutagenesis6311R → A: Abolishes telomerase catalytic activity. Ref.23
Mutagenesis7071Y → 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. Ref.15 Ref.28
Mutagenesis7121D → A: Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers. Ref.11 Ref.12 Ref.23 Ref.26
Mutagenesis8661L → 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. Ref.27
Mutagenesis8671V → A: About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity. Ref.27
Mutagenesis8671V → 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. Ref.27
Mutagenesis8671V → 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. Ref.27
Mutagenesis868 – 8692DD → AA: Loss of telomerase activity. Ref.11 Ref.12 Ref.20 Ref.22 Ref.23
Mutagenesis8681D → A: Loss of telomerase activity. Ref.11 Ref.12 Ref.20 Ref.22 Ref.23
Mutagenesis8691D → A: Loss of telomerase activity. Ref.11 Ref.12
Mutagenesis930 – 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. Ref.26
Sequence conflict5161D → G in AAC51724. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 94E35469C4CA33A0

FASTA1,132126,997
        10         20         30         40         50         60 
MPRAPRCRAV RSLLRSHYRE VLPLATFVRR LGPQGWRLVQ RGDPAAFRAL VAQCLVCVPW 

        70         80         90        100        110        120 
DARPPPAAPS FRQVSCLKEL VARVLQRLCE RGAKNVLAFG FALLDGARGG PPEAFTTSVR 

       130        140        150        160        170        180 
SYLPNTVTDA LRGSGAWGLL LRRVGDDVLV HLLARCALFV LVAPSCAYQV CGPPLYQLGA 

       190        200        210        220        230        240 
ATQARPPPHA SGPRRRLGCE RAWNHSVREA GVPLGLPAPG ARRRGGSASR SLPLPKRPRR 

       250        260        270        280        290        300 
GAAPEPERTP VGQGSWAHPG RTRGPSDRGF CVVSPARPAE EATSLEGALS GTRHSHPSVG 

       310        320        330        340        350        360 
RQHHAGPPST SRPPRPWDTP CPPVYAETKH FLYSSGDKEQ LRPSFLLSSL RPSLTGARRL 

       370        380        390        400        410        420 
VETIFLGSRP WMPGTPRRLP RLPQRYWQMR PLFLELLGNH AQCPYGVLLK THCPLRAAVT 

       430        440        450        460        470        480 
PAAGVCAREK PQGSVAAPEE EDTDPRRLVQ LLRQHSSPWQ VYGFVRACLR RLVPPGLWGS 

       490        500        510        520        530        540 
RHNERRFLRN TKKFISLGKH AKLSLQELTW KMSVRDCAWL RRSPGVGCVP AAEHRLREEI 

       550        560        570        580        590        600 
LAKFLHWLMS VYVVELLRSF FYVTETTFQK NRLFFYRKSV WSKLQSIGIR QHLKRVQLRE 

       610        620        630        640        650        660 
LSEAEVRQHR EARPALLTSR LRFIPKPDGL RPIVNMDYVV GARTFRREKR AERLTSRVKA 

       670        680        690        700        710        720 
LFSVLNYERA RRPGLLGASV LGLDDIHRAW RTFVLRVRAQ DPPPELYFVK VDVTGAYDTI 

       730        740        750        760        770        780 
PQDRLTEVIA SIIKPQNTYC VRRYAVVQKA AHGHVRKAFK SHVSTLTDLQ PYMRQFVAHL 

       790        800        810        820        830        840 
QETSPLRDAV VIEQSSSLNE ASSGLFDVFL RFMCHHAVRI RGKSYVQCQG IPQGSILSTL 

       850        860        870        880        890        900 
LCSLCYGDME NKLFAGIRRD GLLLRLVDDF LLVTPHLTHA KTFLRTLVRG VPEYGCVVNL 

       910        920        930        940        950        960 
RKTVVNFPVE DEALGGTAFV QMPAHGLFPW CGLLLDTRTL EVQSDYSSYA RTSIRASLTF 

       970        980        990       1000       1010       1020 
NRGFKAGRNM RRKLFGVLRL KCHSLFLDLQ VNSLQTVCTN IYKILLLQAY RFHACVLQLP 

      1030       1040       1050       1060       1070       1080 
FHQQVWKNPT FFLRVISDTA SLCYSILKAK NAGMSLGAKG AAGPLPSEAV QWLCHQAFLL 

      1090       1100       1110       1120       1130 
KLTRHRVTYV PLLGSLRTAQ TQLSRKLPGT TLTALEAAAN PALPSDFKTI LD 

« Hide

Isoform 2 [UniParc].

Checksum: 199664460CE6D763
Show »

FASTA80790,226
Isoform 3 [UniParc].

Checksum: BE1E77A653B1C666
Show »

FASTA1,069120,048
Isoform 4 [UniParc].

Checksum: 6BEAC8A6D1A2E8CB
Show »

FASTA79588,965

References

« Hide 'large scale' references
[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]"Telomerase catalytic subunit homologs from fission yeast and human."
Nakamura T.M., Morin G.B., Chapman K.B., Weinrich S.L., Andrews W.H., Lingner J., Harley C.B., Cech T.R.
Science 277:955-959(1997) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Nucleolin interacts with telomerase."
Khurts S., Masutomi K., Delgermaa L., Arai K., Oishi N., Mizuno H., Hayashi N., Hahn W.C., Murakami S.
J. Biol. Chem. 279:51508-51515(2004) [PubMed] [Europe PMC] [Abstract]
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]"Telomerase modulates Wnt signalling by association with target gene chromatin."
Park J.I., Venteicher A.S., Hong J.Y., Choi J., Jun S., Shkreli M., Chang W., Meng Z., Cheung P., Ji H., McLaughlin M., Veenstra T.D., Nusse R., McCrea P.D., Artandi S.E.
Nature 460:66-72(2009) [PubMed] [Europe PMC] [Abstract]
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]"TERT promoter mutations in familial and sporadic melanoma."
Horn S., Figl A., Rachakonda P.S., Fischer C., Sucker A., Gast A., Kadel S., Moll I., Nagore E., Hemminki K., Schadendorf D., Kumar R.
Science 339:959-961(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CMM9.
[38]"Crystal structure of HLA-A*2402 complexed with a telomerase peptide."
Cole D.K., Rizkallah P.J., Gao F., Watson N.I., Boulter J.M., Bell J.I., Sami M., Gao G.F., Jakobsen B.K.
Eur. J. Immunol. 36:170-179(2006) [PubMed] [Europe PMC] [Abstract]
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]"Coronary artery disease and a functional polymorphism of hTERT."
Matsubara Y., Murata M., Watanabe K., Saito I., Miyaki K., Omae K., Ishikawa M., Matsushita K., Iwanaga S., Ogawa S., Ikeda Y.
Biochem. Biophys. Res. Commun. 348:669-672(2006) [PubMed] [Europe PMC] [Abstract]
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]"Telomerase mutations in families with idiopathic pulmonary fibrosis."
Armanios M.Y., Chen J.J., Cogan J.D., Alder J.K., Ingersoll R.G., Markin C., Lawson W.E., Xie M., Vulto I., Phillips J.A., Lansdorp P.M., Greider C.W., Loyd J.E.
N. Engl. J. Med. 356:1317-1326(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS IDIOPATHIC PULMONARY FIBROSIS SUSCEPTIBILITY GLN-55 AND MET-1110, CHARACTERIZATION OF VARIANTS GLN-55 AND MET-1110.
[48]"Adult-onset pulmonary fibrosis caused by mutations in telomerase."
Tsakiri K.D., Cronkhite J.T., Kuan P.J., Xing C., Raghu G., Weissler J.C., Rosenblatt R.L., Shay J.W., Garcia C.K.
Proc. Natl. Acad. Sci. U.S.A. 104:7552-7557(2007) [PubMed] [Europe PMC] [Abstract]
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]"Constitutional hypomorphic telomerase mutations in patients with acute myeloid leukemia."
Calado R.T., Regal J.A., Hills M., Yewdell W.T., Dalmazzo L.F., Zago M.A., Lansdorp P.M., Hogge D., Chanock S.J., Estey E.H., Falcao R.P., Young N.S.
Proc. Natl. Acad. Sci. U.S.A. 106:1187-1192(2009) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3861.2. [O14746-1]
CCDS54831.1. [O14746-3]
PIRT03844.
RefSeqNP_001180305.1. NM_001193376.1. [O14746-3]
NP_937983.2. NM_198253.2. [O14746-1]
UniGeneHs.492203.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BCKX-ray2.80C/F461-469[»]
4B18X-ray2.52B222-240[»]
4MNQX-ray2.74C540-548[»]
ProteinModelPortalO14746.
SMRO14746. Positions 344-593, 818-1019.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112874. 63 interactions.
DIPDIP-40646N.
IntActO14746. 11 interactions.
MINTMINT-133963.
STRING9606.ENSP00000309572.

Chemistry

BindingDBO14746.
ChEMBLCHEMBL2916.

PTM databases

PhosphoSiteO14746.

Proteomic databases

PaxDbO14746.
PRIDEO14746.

Protocols and materials databases

DNASU7015.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296820; ENSP00000296820; ENSG00000164362. [O14746-2]
ENST00000310581; ENSP00000309572; ENSG00000164362. [O14746-1]
ENST00000334602; ENSP00000334346; ENSG00000164362. [O14746-3]
ENST00000460137; ENSP00000425003; ENSG00000164362. [O14746-4]
ENST00000508104; ENSP00000426042; ENSG00000164362. [O14746-2]
GeneID7015.
KEGGhsa:7015.
UCSCuc003jca.1. human. [O14746-1]
uc003jcc.1. human. [O14746-3]

Organism-specific databases

CTD7015.
GeneCardsGC05M001253.
GeneReviewsTERT.
HGNCHGNC:11730. TERT.
MIM178500. phenotype.
187270. gene+phenotype.
609135. phenotype.
613989. phenotype.
614742. phenotype.
615134. phenotype.
neXtProtNX_O14746.
Orphanet1775. Dyskeratosis congenita.
618. Familial melanoma.
3322. Hoyeraal-Hreidarsson syndrome.
88. Idiopathic aplastic anemia.
2032. Idiopathic pulmonary fibrosis.
PharmGKBPA36447.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG276584.
HOGENOMHOG000148780.
HOVERGENHBG000460.
InParanoidO14746.
KOK11126.
OMAWLCYHAF.
OrthoDBEOG744TB3.
PhylomeDBO14746.
TreeFamTF329048.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressO14746.
BgeeO14746.
CleanExHS_TERT.
GenevestigatorO14746.

Family and domain databases

InterProIPR000477. RT_dom.
IPR021891. Telomerase_RBD.
IPR003545. Telomerase_RT.
[Graphical view]
PfamPF00078. RVT_1. 1 hit.
PF12009. Telomerase_RBD. 1 hit.
[Graphical view]
PRINTSPR01365. TELOMERASERT.
SMARTSM00975. Telomerase_RBD. 1 hit.
[Graphical view]
PROSITEPS50878. RT_POL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO14746.
GeneWikiTelomerase_reverse_transcriptase.
GenomeRNAi7015.
NextBio13641567.
PROO14746.
SOURCESearch...

Entry information

Entry nameTERT_HUMAN
AccessionPrimary (citable) accession number: O14746
Secondary accession number(s): O14783 expand/collapse secondary AC list , Q2XS35, Q8N6C3, Q8NG38, Q8NG46
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: July 9, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM