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UniProtKB - O14746 (TERT_HUMAN)

Protein

Telomerase reverse transcriptase

Gene

TERT

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

Functioni

Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis.12 Publications

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei169Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template1
Metal bindingi712Magnesium; catalyticPROSITE-ProRule annotation1
Sitei867Required for nucleotide incorporation and primer extension rate1
Metal bindingi868Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi869Magnesium; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDNA-binding, Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase
LigandMagnesium, Metal-binding

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Telomerase reverse transcriptase (EC:2.7.7.492 Publications)
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164362.18
HGNCiHGNC:11730 TERT
MIMi187270 gene+phenotype
neXtProtiNX_O14746

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

Pathology & Biotechi

Involvement in diseasei

Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis.
Aplastic anemia (AA)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
See also OMIM:609135
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036865441Missing in AA; associated with susceptibility to acute myeloid leukemia. 3 Publications1
Natural variantiVAR_062536570K → N in AA; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications1
Natural variantiVAR_062783631R → Q in AA. 1 PublicationCorresponds to variant dbSNP:rs199422294EnsemblClinVar.1
Natural variantiVAR_062537682G → D in AA; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs199422295EnsemblClinVar.1
Natural variantiVAR_062539726T → M in AA; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 PublicationsCorresponds to variant dbSNP:rs149566858EnsemblClinVar.1
Natural variantiVAR_062784785P → L in AA. 1 Publication1
Genetic variations in TERT are associated with coronary artery disease (CAD).
Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
See also OMIM:613989
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036869902K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs121918665EnsemblClinVar.1
Natural variantiVAR_062542979R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 3 PublicationsCorresponds to variant dbSNP:rs199422305EnsemblClinVar.1
Natural variantiVAR_0625441127F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications1
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length.
See also OMIM:614742
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068792170V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907248EnsemblClinVar.1
Natural variantiVAR_025149412H → Y in PFBMFT1, AA and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. 5 PublicationsCorresponds to variant dbSNP:rs34094720EnsemblClinVar.1
Natural variantiVAR_068794716A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907249EnsemblClinVar.1
Natural variantiVAR_036867772Y → C in PFBMFT1; moderate. 1 PublicationCorresponds to variant dbSNP:rs121918663EnsemblClinVar.1
Natural variantiVAR_068795791V → 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 PublicationCorresponds to variant dbSNP:rs141425941EnsemblClinVar.1
Natural variantiVAR_068796841L → F in PFBMFT1. 1 Publication1
Natural variantiVAR_036868865R → H in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs121918666EnsemblClinVar.1
Natural variantiVAR_068797867V → 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 PublicationCorresponds to variant dbSNP:rs201159197EnsemblClinVar.1
Natural variantiVAR_068798902K → R in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907250EnsemblClinVar.1
Natural variantiVAR_068799923P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251EnsemblClinVar.1
Natural variantiVAR_0688001025V → F in PFBMFT1. 1 Publication1
Natural variantiVAR_0368701090V → M in PFBMFT1; severe. 1 PublicationCorresponds to variant dbSNP:rs121918664EnsemblClinVar.1
Dyskeratosis congenita, autosomal recessive, 4 (DKCB4)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
See also OMIM:613989
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068793704P → S in DKCB4; the mutant protein has 13% residual activity. 2 PublicationsCorresponds to variant dbSNP:rs199422297EnsemblClinVar.1
Natural variantiVAR_062538721P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs199422299EnsemblClinVar.1
Natural variantiVAR_062540811R → C in DKCB4; 50% reduction in telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422301EnsemblClinVar.1
Natural variantiVAR_062541901R → W in DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422304EnsemblClinVar.1
Pulmonary fibrosis, idiopathic (IPF)
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. In some cases, the disorder can be rapidly progressive and characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease.
See also OMIM:178500
Melanoma, cutaneous malignant 9 (CMM9)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.
See also OMIM:615134

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi137 – 141WGLLL → AAAAA: Reduced catalytic activity and repeat addition processivity. Complete loss of catalytic activity but no loss of binding to telomeric primers; when associated with 930-A--A-934. 1 Publication5
Mutagenesisi169Q → 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 Publication1
Mutagenesisi169Q → 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 Publication1
Mutagenesisi169Q → 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 Publication1
Mutagenesisi457S → A: Abolishes phosphorylation by DYRK2. 1 Publication1
Mutagenesisi547W → A: Defective in high-affinity TERC interactions. 1 Publication1
Mutagenesisi631R → A: Abolishes telomerase catalytic activity. 1 Publication1
Mutagenesisi707Y → 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 Publications1
Mutagenesisi712D → A: Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers. 4 Publications1
Mutagenesisi866L → 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 Publication1
Mutagenesisi867V → A: About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity. 1 Publication1
Mutagenesisi867V → 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 Publication1
Mutagenesisi867V → 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 Publication1
Mutagenesisi868 – 869DD → AA: Loss of telomerase activity. 2
Mutagenesisi868D → A: Loss of telomerase activity. 5 Publications1
Mutagenesisi869D → A: Loss of telomerase activity. 2 Publications1
Mutagenesisi930 – 934WCGLL → AAAAA: Completely abolishes telomerase-mediated primer extension and reduced binding to short telomeric primers. Complete loss of catalytic activity but no further loss of binding to telomeric primers; when associated with 137-A--A-141. 1 Publication5

Keywords - Diseasei

Disease mutation, Dyskeratosis congenita

Organism-specific databases

DisGeNETi7015
GeneReviewsiTERT
MalaCardsiTERT
MIMi178500 phenotype
187270 gene+phenotype
609135 phenotype
613989 phenotype
614742 phenotype
615134 phenotype
OpenTargetsiENSG00000164362
Orphaneti1775 Dyskeratosis congenita
618 Familial melanoma
3322 Hoyeraal-Hreidarsson syndrome
88 Idiopathic aplastic anemia
2032 Idiopathic pulmonary fibrosis
PharmGKBiPA36447

Chemistry databases

ChEMBLiCHEMBL2916
DrugBankiDB05036 Grn163l
DB04937 GV1001
DB00495 Zidovudine

Polymorphism and mutation databases

BioMutaiTERT

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000549251 – 1132Telomerase reverse transcriptaseAdd BLAST1132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei227Phosphoserine; by PKB/AKT11 Publication1
Modified residuei457Phosphoserine; by DYRK21 Publication1
Modified residuei707Phosphotyrosine; by SRC-type Tyr-kinases2 Publications1

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.1 Publication
(Microbial infection) In case of infection by HIV-1, the EDVP complex is hijacked by HIV-1 via interaction between HIV-1 Vpr and DCAF1/VPRBP, leading to ubiquitination and degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO14746
PaxDbiO14746
PeptideAtlasiO14746
PRIDEiO14746
ProteomicsDBi48203
48204 [O14746-2]
48205 [O14746-3]

PTM databases

iPTMnetiO14746
PhosphoSitePlusiO14746

Expressioni

Tissue specificityi

Expressed at a high level in thymocyte subpopulations, at an intermediate level in tonsil T-lymphocytes, and at a low to undetectable level in peripheral blood T-lymphocytes.2 Publications

Inductioni

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

Gene expression databases

BgeeiENSG00000164362 Expressed in 146 organ(s), highest expression level in uterus
CleanExiHS_TERT
GenevisibleiO14746 HS

Organism-specific databases

HPAiHPA054641
HPA065897

Interactioni

Subunit structurei

Catalytic component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC) (PubMed:19179534, PubMed:20351177, PubMed:29695869). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1 (PubMed:19179534). The molecular chaperone HSP90/P23 complex is required for correct assembly and stabilization of the active telomerase (PubMed:11274138). Interacts directly with HSP90A and PTGES3 (PubMed:11274138). Interacts with HSPA1A; the interaction occurs in the absence of TERC and dissociates once the complex has formed (PubMed:11274138). Interacts with RAN; the interaction promotes nuclear export of TERT (PubMed:12808100). Interacts with XPO1 (PubMed:12808100). Interacts with PTPN11; the interaction retains TERT in the nucleus (PubMed:18829466). Interacts with NCL (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains); the interaction is important for nucleolar localization of TERT (PubMed:15371412). Interacts with SMARCA4 (via the bromodomain); the interaction regulates Wnt-mediated signaling (By similarity). Interacts with MCRS1 (isoform MCRS2); the interaction inhibits in vitro telomerase activity (PubMed:15044100). Interacts with PIF1; the interaction has no effect on the elongation activity of TERT (By similarity). Interacts with PML; the interaction recruits TERT to PML bodies and inhibits telomerase activity (PubMed:19567472). Interacts with GNL3L (By similarity). Interacts with isoform 1 and isoform 2 of NVL (PubMed:22226966). Interacts with DHX36 (PubMed:21846770).By similarity11 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112874, 67 interactors
ComplexPortaliCPX-17 Telomerase catalytic core complex
CPX-20 TERT-RMRP complex
CPX-265 Telomerase holoenzyme complex
CORUMiO14746
DIPiDIP-40646N
ELMiO14746
IntActiO14746, 23 interactors
MINTiO14746
STRINGi9606.ENSP00000309572

Chemistry databases

BindingDBiO14746

Structurei

Secondary structure

11132
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14746
SMRiO14746
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14746

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini605 – 935Reverse transcriptasePROSITE-ProRule annotationAdd BLAST331

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 230RNA-interacting domain 1Add BLAST230
Regioni58 – 197GQ motifAdd BLAST140
Regioni137 – 141Required for regulating specificity for telomeric DNA and for processivity for primer elongation5
Regioni231 – 324LinkerAdd BLAST94
Regioni301 – 538Required for oligomerizationAdd BLAST238
Regioni325 – 550RNA-interacting domain 2Add BLAST226
Regioni376 – 521QFP motifAdd BLAST146
Regioni397 – 417CP motifAdd BLAST21
Regioni914 – 928Required for oligomerizationAdd BLAST15
Regioni930 – 934Primer grip sequence5
Regioni936 – 1132CTEAdd BLAST197

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi222 – 240Bipartite nuclear localization signalAdd BLAST19
Motifi328 – 333TFLY; involved in RNA bindingBy similarity6

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

Belongs to the reverse transcriptase family. Telomerase subfamily.Curated

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR000477 RT_dom
IPR021891 Telomerase_RBD
IPR003545 Telomerase_RT
PANTHERiPTHR12066 PTHR12066, 1 hit
PfamiView protein in Pfam
PF00078 RVT_1, 1 hit
PF12009 Telomerase_RBD, 1 hit
PRINTSiPR01365 TELOMERASERT
SMARTiView protein in SMART
SM00975 Telomerase_RBD, 1 hit
PROSITEiView protein in PROSITE
PS50878 RT_POL, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O14746-1) [UniParc]FASTAAdd to basket

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

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

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

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

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

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

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

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti516D → G in AAC51724 (PubMed:9288757).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06253555L → Q in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907247EnsemblClinVar.1
Natural variantiVAR_06278065P → A Associated with acute myeloid leukemia. 2 PublicationsCorresponds to variant dbSNP:rs544215765EnsemblClinVar.1
Natural variantiVAR_068792170V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907248EnsemblClinVar.1
Natural variantiVAR_036863202A → T in PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres. 3 PublicationsCorresponds to variant dbSNP:rs121918661EnsemblClinVar.1
Natural variantiVAR_036864279A → T1 PublicationCorresponds to variant dbSNP:rs61748181EnsemblClinVar.1
Natural variantiVAR_062781299V → M Associated with acute myeloid leukemia. 2 PublicationsCorresponds to variant dbSNP:rs756624928Ensembl.1
Natural variantiVAR_025149412H → Y in PFBMFT1, AA and DKCB4; severe and moderate; associated with susceptibility to acute myelogenous leukemia; the mutant protein has 36% residual activity. 5 PublicationsCorresponds to variant dbSNP:rs34094720EnsemblClinVar.1
Natural variantiVAR_036865441Missing in AA; associated with susceptibility to acute myeloid leukemia. 3 Publications1
Natural variantiVAR_062782522R → K Associated with acute myeloid leukemia. 2 Publications1
Natural variantiVAR_062536570K → N in AA; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications1
Natural variantiVAR_062783631R → Q in AA. 1 PublicationCorresponds to variant dbSNP:rs199422294EnsemblClinVar.1
Natural variantiVAR_062537682G → D in AA; non-severe; abolishes telomerase catalytic activity but little effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs199422295EnsemblClinVar.1
Natural variantiVAR_036866694V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar.1
Natural variantiVAR_068793704P → S in DKCB4; the mutant protein has 13% residual activity. 2 PublicationsCorresponds to variant dbSNP:rs199422297EnsemblClinVar.1
Natural variantiVAR_068794716A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907249EnsemblClinVar.1
Natural variantiVAR_062538721P → R in DKCB4; no effect on telomerase catalytic activity and little effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs199422299EnsemblClinVar.1
Natural variantiVAR_062539726T → M in AA; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 PublicationsCorresponds to variant dbSNP:rs149566858EnsemblClinVar.1
Natural variantiVAR_036867772Y → C in PFBMFT1; moderate. 1 PublicationCorresponds to variant dbSNP:rs121918663EnsemblClinVar.1
Natural variantiVAR_062784785P → L in AA. 1 Publication1
Natural variantiVAR_068795791V → 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 PublicationCorresponds to variant dbSNP:rs141425941EnsemblClinVar.1
Natural variantiVAR_062540811R → C in DKCB4; 50% reduction in telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422301EnsemblClinVar.1
Natural variantiVAR_068796841L → F in PFBMFT1. 1 Publication1
Natural variantiVAR_036868865R → H in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs121918666EnsemblClinVar.1
Natural variantiVAR_068797867V → 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 PublicationCorresponds to variant dbSNP:rs201159197EnsemblClinVar.1
Natural variantiVAR_062541901R → W in DKCB4; severe phenotype overlapping with Hoyeraal-Hreidarsson syndrome; very short telomeres and greatly reduced telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422304EnsemblClinVar.1
Natural variantiVAR_036869902K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs121918665EnsemblClinVar.1
Natural variantiVAR_068798902K → R in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907250EnsemblClinVar.1
Natural variantiVAR_068799923P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251EnsemblClinVar.1
Natural variantiVAR_053726948S → R. Corresponds to variant dbSNP:rs34062885Ensembl.1
Natural variantiVAR_062542979R → W in DKCA2; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 3 PublicationsCorresponds to variant dbSNP:rs199422305EnsemblClinVar.1
Natural variantiVAR_0688001025V → F in PFBMFT1. 1 Publication1
Natural variantiVAR_0251501062A → T Increased incidence in sporadic acute myeloid leukemia. 4 PublicationsCorresponds to variant dbSNP:rs35719940EnsemblClinVar.1
Natural variantiVAR_0368701090V → M in PFBMFT1; severe. 1 PublicationCorresponds to variant dbSNP:rs121918664EnsemblClinVar.1
Natural variantiVAR_0625431110T → M in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422306EnsemblClinVar.1
Natural variantiVAR_0625441127F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_053369711 – 722Missing in isoform 4. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_019587764 – 807STLTD…SGLFD → LRPVPGDPAGLHPLHAALQP VLRRHGEQAVCGDSAGRAAP AFGG in isoform 2 and isoform 4. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_019588808 – 1132Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST325
Alternative sequenceiVSP_021727885 – 947Missing in isoform 3. 1 PublicationAdd BLAST63

Sequence databases

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

Genome annotation databases

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

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BCKX-ray2.80C/F461-469[»]
4B18X-ray2.52B222-240[»]
4MNQX-ray2.74C540-548[»]
5MENX-ray2.81C540-548[»]
5MEOX-ray1.77C540-548[»]
5MEPX-ray2.71C/F540-548[»]
5MEQX-ray2.27C540-546[»]
5MERX-ray1.88C/F540-546[»]
5UGWX-ray2.31A961-1132[»]
ProteinModelPortaliO14746
SMRiO14746
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112874, 67 interactors
ComplexPortaliCPX-17 Telomerase catalytic core complex
CPX-20 TERT-RMRP complex
CPX-265 Telomerase holoenzyme complex
CORUMiO14746
DIPiDIP-40646N
ELMiO14746
IntActiO14746, 23 interactors
MINTiO14746
STRINGi9606.ENSP00000309572

Chemistry databases

BindingDBiO14746
ChEMBLiCHEMBL2916
DrugBankiDB05036 Grn163l
DB04937 GV1001
DB00495 Zidovudine

PTM databases

iPTMnetiO14746
PhosphoSitePlusiO14746

Polymorphism and mutation databases

BioMutaiTERT

Proteomic databases

EPDiO14746
PaxDbiO14746
PeptideAtlasiO14746
PRIDEiO14746
ProteomicsDBi48203
48204 [O14746-2]
48205 [O14746-3]

Protocols and materials databases

DNASUi7015
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7015
DisGeNETi7015
EuPathDBiHostDB:ENSG00000164362.18
GeneCardsiTERT
GeneReviewsiTERT
HGNCiHGNC:11730 TERT
HPAiHPA054641
HPA065897
MalaCardsiTERT
MIMi178500 phenotype
187270 gene+phenotype
609135 phenotype
613989 phenotype
614742 phenotype
615134 phenotype
neXtProtiNX_O14746
OpenTargetsiENSG00000164362
Orphaneti1775 Dyskeratosis congenita
618 Familial melanoma
3322 Hoyeraal-Hreidarsson syndrome
88 Idiopathic aplastic anemia
2032 Idiopathic pulmonary fibrosis
PharmGKBiPA36447
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiTERT human
EvolutionaryTraceiO14746
GeneWikiiTelomerase_reverse_transcriptase
GenomeRNAii7015
PROiPR:O14746
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164362 Expressed in 146 organ(s), highest expression level in uterus
CleanExiHS_TERT
GenevisibleiO14746 HS

Family and domain databases

InterProiView protein in InterPro
IPR000477 RT_dom
IPR021891 Telomerase_RBD
IPR003545 Telomerase_RT
PANTHERiPTHR12066 PTHR12066, 1 hit
PfamiView protein in Pfam
PF00078 RVT_1, 1 hit
PF12009 Telomerase_RBD, 1 hit
PRINTSiPR01365 TELOMERASERT
SMARTiView protein in SMART
SM00975 Telomerase_RBD, 1 hit
PROSITEiView protein in PROSITE
PS50878 RT_POL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTERT_HUMAN
AccessioniPrimary (citable) accession number: O14746
Secondary accession number(s): O14783
, Q2XS35, Q8N6C3, Q8NG38, Q8NG46
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: October 10, 2018
This is version 177 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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