UniProtKB - O14746 (TERT_HUMAN)
Telomerase reverse transcriptase
TERT
Functioni
Catalytic activityi
- EC:2.7.7.492 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 169 | Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template | 1 | |
Metal bindingi | 712 | Magnesium; catalyticPROSITE-ProRule annotation | 1 | |
Sitei | 867 | Required for nucleotide incorporation and primer extension rate | 1 | |
Metal bindingi | 868 | Magnesium; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 869 | Magnesium; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- chaperone binding Source: BHF-UCL
- DNA binding Source: BHF-UCL
- identical protein binding Source: IntAct
- metal ion binding Source: UniProtKB-KW
- protein C-terminus binding Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- protein N-terminus binding Source: BHF-UCL
- RNA binding Source: BHF-UCL
- RNA-directed 5'-3' RNA polymerase activity Source: BHF-UCL
- RNA-directed DNA polymerase activity Source: BHF-UCL
- telomerase activity Source: UniProtKB
- telomerase RNA binding Source: BHF-UCL
- telomerase RNA reverse transcriptase activity Source: BHF-UCL
- telomeric DNA binding Source: GO_Central
- template-free RNA nucleotidyltransferase Source: BHF-UCL
- transcription coactivator binding Source: BHF-UCL
- tRNA binding Source: BHF-UCL
GO - Biological processi
- beta-catenin-TCF complex assembly Source: Reactome
- cellular response to hypoxia Source: BHF-UCL
- DNA biosynthetic process Source: BHF-UCL
- DNA strand elongation Source: BHF-UCL
- double-stranded RNA biosynthetic process Source: ARUK-UCL
- establishment of protein localization to telomere Source: BHF-UCL
- mitochondrion organization Source: BHF-UCL
- negative regulation of cellular senescence Source: BHF-UCL
- negative regulation of endothelial cell apoptotic process Source: Ensembl
- negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
- negative regulation of gene expression Source: BHF-UCL
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of production of miRNAs involved in gene silencing by miRNA Source: ARUK-UCL
- negative regulation of production of siRNA involved in RNA interference Source: BHF-UCL
- positive regulation of angiogenesis Source: Ensembl
- positive regulation of G1/S transition of mitotic cell cycle Source: Ensembl
- positive regulation of glucose import Source: Ensembl
- positive regulation of hair cycle Source: BHF-UCL
- positive regulation of nitric-oxide synthase activity Source: BHF-UCL
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of protein binding Source: BHF-UCL
- positive regulation of protein localization to nucleolus Source: BHF-UCL
- positive regulation of stem cell proliferation Source: BHF-UCL
- positive regulation of transdifferentiation Source: Ensembl
- positive regulation of vascular associated smooth muscle cell migration Source: Ensembl
- positive regulation of vascular associated smooth muscle cell proliferation Source: Ensembl
- positive regulation of Wnt signaling pathway Source: BHF-UCL
- production of siRNA involved in RNA interference Source: BHF-UCL
- regulation of protein stability Source: BHF-UCL
- replicative senescence Source: BHF-UCL
- response to cadmium ion Source: Ensembl
- RNA-dependent DNA biosynthetic process Source: BHF-UCL
- telomere maintenance Source: UniProtKB
- telomere maintenance via telomerase Source: UniProtKB
- transcription, RNA-templated Source: BHF-UCL
Keywordsi
Molecular function | DNA-binding, Nucleotidyltransferase, Ribonucleoprotein, RNA-directed DNA polymerase, Transferase |
Ligand | Magnesium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | O14746 |
Reactomei | R-HSA-171319, Telomere Extension By Telomerase R-HSA-201722, Formation of the beta-catenin:TCF transactivating complex |
SIGNORi | O14746 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000164362.18 |
HGNCi | HGNC:11730, TERT |
MIMi | 187270, gene+phenotype |
neXtProti | NX_O14746 |
Subcellular locationi
Nucleus
- nucleolus 1 Publication
- nucleoplasm
- Nucleus
- PML body
Other locations
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.
Cytosol
- cytosol Source: HPA
Mitochondrion
- mitochondrial nucleoid Source: BHF-UCL
Nucleus
- nuclear chromosome, telomeric region Source: BHF-UCL
- nuclear speck Source: HPA
- nuclear telomere cap complex Source: BHF-UCL
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: BHF-UCL
- PML body Source: UniProtKB-SubCell
- telomerase catalytic core complex Source: BHF-UCL
- telomerase holoenzyme complex Source: UniProtKB
Plasma Membrane
- plasma membrane Source: Ensembl
Other locations
- chromosome, telomeric region Source: UniProtKB
- RNA-directed RNA polymerase complex Source: BHF-UCL
- TERT-RMRP complex Source: BHF-UCL
Keywords - Cellular componenti
Chromosome, Cytoplasm, Nucleus, TelomerePathology & Biotechi
Involvement in diseasei
Aplastic anemia (AA)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036863 | 202 | A → T in PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres. 3 PublicationsCorresponds to variant dbSNP:rs121918661EnsemblClinVar. | 1 | |
Natural variantiVAR_036865 | 441 | Missing in AA; associated with susceptibility to acute myeloid leukemia. 3 Publications | 1 | |
Natural variantiVAR_062536 | 570 | K → N in AA; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications | 1 | |
Natural variantiVAR_062783 | 631 | R → Q in AA. 1 PublicationCorresponds to variant dbSNP:rs199422294EnsemblClinVar. | 1 | |
Natural variantiVAR_062537 | 682 | G → 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_036866 | 694 | V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar. | 1 | |
Natural variantiVAR_062539 | 726 | T → M in AA; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 PublicationsCorresponds to variant dbSNP:rs149566858EnsemblClinVar. | 1 | |
Natural variantiVAR_062784 | 785 | P → L in AA. 1 PublicationCorresponds to variant dbSNP:rs483352771Ensembl. | 1 |
Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)3 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_036869 | 902 | K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs121918665EnsemblClinVar. | 1 | |
Natural variantiVAR_062542 | 979 | R → 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_062544 | 1127 | F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs1176273130Ensembl. | 1 |
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1)5 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_068792 | 170 | V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907248EnsemblClinVar. | 1 | |
Natural variantiVAR_036863 | 202 | A → T in PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres. 3 PublicationsCorresponds to variant dbSNP:rs121918661EnsemblClinVar. | 1 | |
Natural variantiVAR_025149 | 412 | H → 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_036866 | 694 | V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar. | 1 | |
Natural variantiVAR_068794 | 716 | A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907249EnsemblClinVar. | 1 | |
Natural variantiVAR_036867 | 772 | Y → C in PFBMFT1; moderate. 1 PublicationCorresponds to variant dbSNP:rs121918663EnsemblClinVar. | 1 | |
Natural variantiVAR_068795 | 791 | V → 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_068796 | 841 | L → F in PFBMFT1. 1 Publication | 1 | |
Natural variantiVAR_036868 | 865 | R → H in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs121918666EnsemblClinVar. | 1 | |
Natural variantiVAR_068797 | 867 | V → 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_068798 | 902 | K → R in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907250Ensembl. | 1 | |
Natural variantiVAR_068799 | 923 | P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251EnsemblClinVar. | 1 | |
Natural variantiVAR_068800 | 1025 | V → F in PFBMFT1. 1 Publication | 1 | |
Natural variantiVAR_036870 | 1090 | V → M in PFBMFT1; severe. 1 PublicationCorresponds to variant dbSNP:rs121918664EnsemblClinVar. | 1 |
Dyskeratosis congenita, autosomal recessive, 4 (DKCB4)4 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_025149 | 412 | H → 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_068793 | 704 | P → S in DKCB4; the mutant protein has 13% residual activity. 2 PublicationsCorresponds to variant dbSNP:rs199422297EnsemblClinVar. | 1 | |
Natural variantiVAR_062538 | 721 | P → 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_062540 | 811 | R → C in DKCB4; 50% reduction in telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422301EnsemblClinVar. | 1 | |
Natural variantiVAR_062541 | 901 | R → 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)
Melanoma, cutaneous malignant 9 (CMM9)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 137 – 141 | WGLLL → AAAAA: Reduced catalytic activity and repeat addition processivity. Complete loss of catalytic activity but no loss of binding to telomeric primers; when associated with 930-A--A-934. 1 Publication | 5 | |
Mutagenesisi | 169 | Q → 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 | 1 | |
Mutagenesisi | 169 | Q → 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 | 1 | |
Mutagenesisi | 169 | Q → 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 | 1 | |
Mutagenesisi | 457 | S → A: Abolishes phosphorylation by DYRK2. 1 Publication | 1 | |
Mutagenesisi | 547 | W → A: Defective in high-affinity TERC interactions. 1 Publication | 1 | |
Mutagenesisi | 631 | R → A: Abolishes telomerase catalytic activity. 1 Publication | 1 | |
Mutagenesisi | 707 | Y → 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 | 1 | |
Mutagenesisi | 712 | D → A: Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers. 4 Publications | 1 | |
Mutagenesisi | 866 | L → 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 | 1 | |
Mutagenesisi | 867 | V → 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 | 1 | |
Mutagenesisi | 867 | V → 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 | 1 | |
Mutagenesisi | 867 | V → 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 | 1 | |
Mutagenesisi | 868 – 869 | DD → AA: Loss of telomerase activity. | 2 | |
Mutagenesisi | 868 | D → A: Loss of telomerase activity. 5 Publications | 1 | |
Mutagenesisi | 869 | D → A: Loss of telomerase activity. 2 Publications | 1 | |
Mutagenesisi | 930 – 934 | WCGLL → AAAAA: Completely abolishes telomerase-mediated primer extension and reduced binding to short telomeric primers. Complete loss of catalytic activity but no further loss of binding to telomeric primers; when associated with 137-A--A-141. 1 Publication | 5 |
Keywords - Diseasei
Disease mutation, Dyskeratosis congenitaOrganism-specific databases
DisGeNETi | 7015 |
GeneReviewsi | TERT |
MalaCardsi | TERT |
MIMi | 178500, phenotype 187270, gene+phenotype 609135, phenotype 613989, phenotype 614742, phenotype 615134, phenotype |
OpenTargetsi | ENSG00000164362 |
Orphaneti | 457246, Clear cell sarcoma of kidney 146, Differentiated thyroid carcinoma 1775, Dyskeratosis congenita 618, Familial melanoma 3322, Hoyeraal-Hreidarsson syndrome 88, Idiopathic aplastic anemia 2032, Idiopathic pulmonary fibrosis 2495, Meningioma |
PharmGKBi | PA36447 |
Miscellaneous databases
Pharosi | O14746, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2916 |
DrugBanki | DB05036, Grn163l DB12747, Tertomotide DB00495, Zidovudine |
DrugCentrali | O14746 |
Polymorphism and mutation databases
BioMutai | TERT |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000054925 | 1 – 1132 | Telomerase reverse transcriptaseAdd BLAST | 1132 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 227 | Phosphoserine; by PKB/AKT11 Publication | 1 | |
Modified residuei | 457 | Phosphoserine; by DYRK21 Publication | 1 | |
Modified residuei | 707 | Phosphotyrosine; by SRC-type Tyr-kinases2 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O14746 |
MassIVEi | O14746 |
PaxDbi | O14746 |
PeptideAtlasi | O14746 |
PRIDEi | O14746 |
ProteomicsDBi | 48203 [O14746-1] 48204 [O14746-2] 48205 [O14746-3] 73418 |
PTM databases
iPTMneti | O14746 |
PhosphoSitePlusi | O14746 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000164362, Expressed in stromal cell of endometrium and 152 other tissues |
Genevisiblei | O14746, HS |
Organism-specific databases
HPAi | ENSG00000164362, Group enriched (bone marrow, lymphoid tissue, testis) |
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).
Interacts with ATF7 (PubMed:29490055).
By similarity12 PublicationsBinary interactionsi
Hide detailsO14746
GO - Molecular functioni
- chaperone binding Source: BHF-UCL
- identical protein binding Source: IntAct
- protein C-terminus binding Source: BHF-UCL
- protein homodimerization activity Source: BHF-UCL
- protein N-terminus binding Source: BHF-UCL
- transcription coactivator binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 112874, 98 interactors |
ComplexPortali | CPX-17, Telomerase catalytic core complex CPX-20, TERT-RMRP complex CPX-265, Telomerase holoenzyme complex |
CORUMi | O14746 |
DIPi | DIP-40646N |
ELMi | O14746 |
IntActi | O14746, 24 interactors |
MINTi | O14746 |
STRINGi | 9606.ENSP00000309572 |
Chemistry databases
BindingDBi | O14746 |
Miscellaneous databases
RNActi | O14746, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O14746 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O14746 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 605 – 935 | Reverse transcriptasePROSITE-ProRule annotationAdd BLAST | 331 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 230 | RNA-interacting domain 1Add BLAST | 230 | |
Regioni | 58 – 197 | GQ motifAdd BLAST | 140 | |
Regioni | 137 – 141 | Required for regulating specificity for telomeric DNA and for processivity for primer elongation | 5 | |
Regioni | 231 – 324 | LinkerAdd BLAST | 94 | |
Regioni | 301 – 538 | Required for oligomerizationAdd BLAST | 238 | |
Regioni | 325 – 550 | RNA-interacting domain 2Add BLAST | 226 | |
Regioni | 376 – 521 | QFP motifAdd BLAST | 146 | |
Regioni | 397 – 417 | CP motifAdd BLAST | 21 | |
Regioni | 914 – 928 | Required for oligomerizationAdd BLAST | 15 | |
Regioni | 930 – 934 | Primer grip sequence | 5 | |
Regioni | 936 – 1132 | CTEAdd BLAST | 197 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 222 – 240 | Bipartite nuclear localization signalAdd BLAST | 19 | |
Motifi | 328 – 333 | TFLY; involved in RNA bindingBy similarity | 6 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1005, Eukaryota |
GeneTreei | ENSGT00390000018531 |
HOGENOMi | CLU_001996_2_0_1 |
InParanoidi | O14746 |
OMAi | HCAPHRV |
OrthoDBi | 1297956at2759 |
PhylomeDBi | O14746 |
TreeFami | TF329048 |
Family and domain databases
InterProi | View protein in InterPro IPR043502, DNA/RNA_pol_sf IPR000477, RT_dom IPR021891, Telomerase_RBD IPR003545, Telomerase_RT |
PANTHERi | PTHR12066, PTHR12066, 1 hit |
Pfami | View protein in Pfam PF00078, RVT_1, 1 hit PF12009, Telomerase_RBD, 1 hit |
PRINTSi | PR01365, TELOMERASERT |
SMARTi | View protein in SMART SM00975, Telomerase_RBD, 1 hit |
SUPFAMi | SSF56672, SSF56672, 1 hit |
PROSITEi | View protein in PROSITE PS50878, RT_POL, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A590UK92 | A0A590UK92_HUMAN | Telomerase reverse transcriptase | TERT hCG_1990943 | 574 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 516 | D → G in AAC51724 (PubMed:9288757).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_062535 | 55 | L → Q in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907247EnsemblClinVar. | 1 | |
Natural variantiVAR_062780 | 65 | P → A Associated with acute myeloid leukemia. 2 PublicationsCorresponds to variant dbSNP:rs544215765EnsemblClinVar. | 1 | |
Natural variantiVAR_068792 | 170 | V → M in PFBMFT1; the mutant protein is demonstrated to cause decreased telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907248EnsemblClinVar. | 1 | |
Natural variantiVAR_036863 | 202 | A → T in PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres. 3 PublicationsCorresponds to variant dbSNP:rs121918661EnsemblClinVar. | 1 | |
Natural variantiVAR_036864 | 279 | A → T1 PublicationCorresponds to variant dbSNP:rs61748181EnsemblClinVar. | 1 | |
Natural variantiVAR_062781 | 299 | V → M Associated with acute myeloid leukemia. 2 PublicationsCorresponds to variant dbSNP:rs756624928EnsemblClinVar. | 1 | |
Natural variantiVAR_025149 | 412 | H → 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_036865 | 441 | Missing in AA; associated with susceptibility to acute myeloid leukemia. 3 Publications | 1 | |
Natural variantiVAR_062782 | 522 | R → K Associated with acute myeloid leukemia. 2 Publications | 1 | |
Natural variantiVAR_062536 | 570 | K → N in AA; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 Publications | 1 | |
Natural variantiVAR_062783 | 631 | R → Q in AA. 1 PublicationCorresponds to variant dbSNP:rs199422294EnsemblClinVar. | 1 | |
Natural variantiVAR_062537 | 682 | G → 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_036866 | 694 | V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar. | 1 | |
Natural variantiVAR_068793 | 704 | P → S in DKCB4; the mutant protein has 13% residual activity. 2 PublicationsCorresponds to variant dbSNP:rs199422297EnsemblClinVar. | 1 | |
Natural variantiVAR_068794 | 716 | A → T in PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs387907249EnsemblClinVar. | 1 | |
Natural variantiVAR_062538 | 721 | P → 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_062539 | 726 | T → M in AA; very severe; no effect on telomerase catalytic activity but shortened telomeres. 2 PublicationsCorresponds to variant dbSNP:rs149566858EnsemblClinVar. | 1 | |
Natural variantiVAR_036867 | 772 | Y → C in PFBMFT1; moderate. 1 PublicationCorresponds to variant dbSNP:rs121918663EnsemblClinVar. | 1 | |
Natural variantiVAR_062784 | 785 | P → L in AA. 1 PublicationCorresponds to variant dbSNP:rs483352771Ensembl. | 1 | |
Natural variantiVAR_068795 | 791 | V → 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_062540 | 811 | R → C in DKCB4; 50% reduction in telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422301EnsemblClinVar. | 1 | |
Natural variantiVAR_068796 | 841 | L → F in PFBMFT1. 1 Publication | 1 | |
Natural variantiVAR_036868 | 865 | R → H in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs121918666EnsemblClinVar. | 1 | |
Natural variantiVAR_068797 | 867 | V → 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_062541 | 901 | R → 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_036869 | 902 | K → N in DKCA2; abolishes telomerase catalytic activity but no effect on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs121918665EnsemblClinVar. | 1 | |
Natural variantiVAR_068798 | 902 | K → R in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907250Ensembl. | 1 | |
Natural variantiVAR_068799 | 923 | P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251EnsemblClinVar. | 1 | |
Natural variantiVAR_053726 | 948 | S → R. Corresponds to variant dbSNP:rs34062885Ensembl. | 1 | |
Natural variantiVAR_062542 | 979 | R → 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_068800 | 1025 | V → F in PFBMFT1. 1 Publication | 1 | |
Natural variantiVAR_025150 | 1062 | A → T Increased incidence in sporadic acute myeloid leukemia. 4 PublicationsCorresponds to variant dbSNP:rs35719940EnsemblClinVar. | 1 | |
Natural variantiVAR_036870 | 1090 | V → M in PFBMFT1; severe. 1 PublicationCorresponds to variant dbSNP:rs121918664EnsemblClinVar. | 1 | |
Natural variantiVAR_062543 | 1110 | T → M in idiopathic pulmonary fibrosis susceptibility; impaired telomerase activity. 1 PublicationCorresponds to variant dbSNP:rs199422306EnsemblClinVar. | 1 | |
Natural variantiVAR_062544 | 1127 | F → L in DKCA2; severe; shortened telomeres but no effect on telomerase catalytic activity nor on binding to TERC. 2 PublicationsCorresponds to variant dbSNP:rs1176273130Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053369 | 711 – 722 | Missing in isoform 4. 1 PublicationAdd BLAST | 12 | |
Alternative sequenceiVSP_019587 | 764 – 807 | STLTD…SGLFD → LRPVPGDPAGLHPLHAALQP VLRRHGEQAVCGDSAGRAAP AFGG in isoform 2 and isoform 4. 2 PublicationsAdd BLAST | 44 | |
Alternative sequenceiVSP_019588 | 808 – 1132 | Missing in isoform 2 and isoform 4. 2 PublicationsAdd BLAST | 325 | |
Alternative sequenceiVSP_021727 | 885 – 947 | Missing in isoform 3. 1 PublicationAdd BLAST | 63 |
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 |
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] |
Genome annotation databases
Ensembli | ENST00000310581; ENSP00000309572; ENSG00000164362 [O14746-1] ENST00000334602; ENSP00000334346; ENSG00000164362 [O14746-3] ENST00000460137; ENSP00000425003; ENSG00000164362 [O14746-4] |
GeneIDi | 7015 |
KEGGi | hsa:7015 |
UCSCi | uc003jcb.2, human [O14746-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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 |
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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
5MEN | X-ray | 2.81 | C | 540-548 | [»] | |
5MEO | X-ray | 1.77 | C | 540-548 | [»] | |
5MEP | X-ray | 2.71 | C/F | 540-548 | [»] | |
5MEQ | X-ray | 2.27 | C | 540-546 | [»] | |
5MER | X-ray | 1.88 | C/F | 540-546 | [»] | |
5UGW | X-ray | 2.31 | A | 961-1132 | [»] | |
SMRi | O14746 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112874, 98 interactors |
ComplexPortali | CPX-17, Telomerase catalytic core complex CPX-20, TERT-RMRP complex CPX-265, Telomerase holoenzyme complex |
CORUMi | O14746 |
DIPi | DIP-40646N |
ELMi | O14746 |
IntActi | O14746, 24 interactors |
MINTi | O14746 |
STRINGi | 9606.ENSP00000309572 |
Chemistry databases
BindingDBi | O14746 |
ChEMBLi | CHEMBL2916 |
DrugBanki | DB05036, Grn163l DB12747, Tertomotide DB00495, Zidovudine |
DrugCentrali | O14746 |
PTM databases
iPTMneti | O14746 |
PhosphoSitePlusi | O14746 |
Polymorphism and mutation databases
BioMutai | TERT |
Proteomic databases
EPDi | O14746 |
MassIVEi | O14746 |
PaxDbi | O14746 |
PeptideAtlasi | O14746 |
PRIDEi | O14746 |
ProteomicsDBi | 48203 [O14746-1] 48204 [O14746-2] 48205 [O14746-3] 73418 |
Protocols and materials databases
ABCDi | O14746, 9 sequenced antibodies |
Antibodypediai | 8998, 949 antibodies |
DNASUi | 7015 |
Genome annotation databases
Ensembli | ENST00000310581; ENSP00000309572; ENSG00000164362 [O14746-1] ENST00000334602; ENSP00000334346; ENSG00000164362 [O14746-3] ENST00000460137; ENSP00000425003; ENSG00000164362 [O14746-4] |
GeneIDi | 7015 |
KEGGi | hsa:7015 |
UCSCi | uc003jcb.2, human [O14746-1] |
Organism-specific databases
CTDi | 7015 |
DisGeNETi | 7015 |
EuPathDBi | HostDB:ENSG00000164362.18 |
GeneCardsi | TERT |
GeneReviewsi | TERT |
HGNCi | HGNC:11730, TERT |
HPAi | ENSG00000164362, Group enriched (bone marrow, lymphoid tissue, testis) |
MalaCardsi | TERT |
MIMi | 178500, phenotype 187270, gene+phenotype 609135, phenotype 613989, phenotype 614742, phenotype 615134, phenotype |
neXtProti | NX_O14746 |
OpenTargetsi | ENSG00000164362 |
Orphaneti | 457246, Clear cell sarcoma of kidney 146, Differentiated thyroid carcinoma 1775, Dyskeratosis congenita 618, Familial melanoma 3322, Hoyeraal-Hreidarsson syndrome 88, Idiopathic aplastic anemia 2032, Idiopathic pulmonary fibrosis 2495, Meningioma |
PharmGKBi | PA36447 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1005, Eukaryota |
GeneTreei | ENSGT00390000018531 |
HOGENOMi | CLU_001996_2_0_1 |
InParanoidi | O14746 |
OMAi | HCAPHRV |
OrthoDBi | 1297956at2759 |
PhylomeDBi | O14746 |
TreeFami | TF329048 |
Enzyme and pathway databases
PathwayCommonsi | O14746 |
Reactomei | R-HSA-171319, Telomere Extension By Telomerase R-HSA-201722, Formation of the beta-catenin:TCF transactivating complex |
SIGNORi | O14746 |
Miscellaneous databases
BioGRID-ORCSi | 7015, 16 hits in 850 CRISPR screens |
EvolutionaryTracei | O14746 |
GeneWikii | Telomerase_reverse_transcriptase |
GenomeRNAii | 7015 |
Pharosi | O14746, Tchem |
PROi | PR:O14746 |
RNActi | O14746, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164362, Expressed in stromal cell of endometrium and 152 other tissues |
Genevisiblei | O14746, HS |
Family and domain databases
InterProi | View protein in InterPro IPR043502, DNA/RNA_pol_sf IPR000477, RT_dom IPR021891, Telomerase_RBD IPR003545, Telomerase_RT |
PANTHERi | PTHR12066, PTHR12066, 1 hit |
Pfami | View protein in Pfam PF00078, RVT_1, 1 hit PF12009, Telomerase_RBD, 1 hit |
PRINTSi | PR01365, TELOMERASERT |
SMARTi | View protein in SMART SM00975, Telomerase_RBD, 1 hit |
SUPFAMi | SSF56672, SSF56672, 1 hit |
PROSITEi | View protein in PROSITE PS50878, RT_POL, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TERT_HUMAN | |
Accessioni | O14746Primary (citable) accession number: O14746 Secondary accession number(s): O14783 Q8NG46 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 30, 2000 |
Last sequence update: | January 1, 1998 | |
Last modified: | December 2, 2020 | |
This is version 193 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations