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UniProtKB - O14746 (TERT_HUMAN)

Entry version 196 (02 Jun 2021)
Sequence version 1 (01 Jan 1998)
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Protein

Telomerase reverse transcriptase

Gene

TERT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei169Required for optimal binding of telomeric ssDNA and incorporation of nucleotides at the second position of the template1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi712Magnesium; catalyticPROSITE-ProRule annotation1
Sitei867Required for nucleotide incorporation and primer extension rate1
Metal bindingi868Magnesium; catalyticPROSITE-ProRule annotation1
Metal bindingi869Magnesium; catalyticPROSITE-ProRule annotation1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

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

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O14746

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-171319, Telomere Extension By Telomerase
R-HSA-201722, Formation of the beta-catenin:TCF transactivating complex

SIGNOR Signaling Network Open Resource

More...SIGNORi		O14746

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TERT
Synonyms:EST2, TCS1, TRT
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 5

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:11730, TERT

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		187270, gene+phenotype

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O14746

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000164362.18

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus, Telomere

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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 variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>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_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_036866694V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs483352771Ensembl.1
Genetic variations in TERT are associated with coronary artery disease (CAD).
Dyskeratosis congenita, autosomal dominant, 2 (DKCA2)3 Publications
The disease is caused by variants 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.
Related information in OMIM
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 PublicationsCorresponds to variant dbSNP:rs1176273130Ensembl.1
Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1)5 Publications
The disease is caused by variants 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.
Related information in OMIM
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_036863202A → T in PFBMFT1 and AA; severe and moderate; associated with disease susceptibility; shorter telomeres. 3 PublicationsCorresponds to variant dbSNP:rs121918661EnsemblClinVar.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_036866694V → M in PFBMFT1 and AA; moderate. 2 PublicationsCorresponds to variant dbSNP:rs121918662EnsemblClinVar.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:rs387907250Ensembl.1
Natural variantiVAR_068799923P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251Ensembl.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 variants 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
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_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 variants 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.
Related information in OMIM
Melanoma, cutaneous malignant 9 (CMM9)1 Publication
Disease susceptibility is associated with variants 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.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>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 variant, Dyskeratosis congenita

Organism-specific databases

DisGeNET

More...DisGeNETi		7015

GeneReviews a resource of expert-authored, peer-reviewed disease descriptions.

More...GeneReviewsi		TERT

MalaCards human disease database

More...MalaCardsi		TERT
MIMi178500, phenotype
187270, gene+phenotype
609135, phenotype
613989, phenotype
614742, phenotype
615134, phenotype

Open Targets

More...OpenTargetsi		ENSG00000164362

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...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

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA36447

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O14746, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2916

Drug and drug target database

More...DrugBanki		DB05036, Grn163l
DB12747, Tertomotide
DB00495, Zidovudine

DrugCentral

More...DrugCentrali		O14746

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TERT

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000549251 – 1132Telomerase reverse transcriptaseAdd BLAST1132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei227Phosphoserine; by PKB/AKT11 Publication1
Modified residuei457Phosphoserine; by DYRK21 Publication1
Modified residuei707Phosphotyrosine; by SRC-type Tyr-kinases2 Publications1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...EPDi		O14746

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O14746

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O14746

PeptideAtlas

More...PeptideAtlasi		O14746

PRoteomics IDEntifications database

More...PRIDEi		O14746

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		48203 [O14746-1]
48204 [O14746-2]
48205 [O14746-3]
73418

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O14746

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O14746

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000164362, Expressed in stromal cell of endometrium and 153 other tissues

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O14746, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000164362, Group enriched (bone marrow, lymphoid tissue, testis)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		112874, 98 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...ComplexPortali		CPX-17, Telomerase catalytic core complex
CPX-20, TERT-RMRP complex
CPX-265, Telomerase holoenzyme complex

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O14746

Database of interacting proteins

More...DIPi		DIP-40646N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		O14746

Protein interaction database and analysis system

More...IntActi		O14746, 24 interactors

Molecular INTeraction database

More...MINTi		O14746

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000309572

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O14746

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O14746, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

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

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O14746

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O14746

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini605 – 935Reverse transcriptasePROSITE-ProRule annotationAdd BLAST331

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 230RNA-interacting domain 1Add BLAST230
Regioni58 – 197GQ motifAdd BLAST140
Regioni137 – 141Required for regulating specificity for telomeric DNA and for processivity for primer elongation5
Regioni210 – 320DisorderedSequence analysisAdd BLAST111
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
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi222 – 240Bipartite nuclear localization signalAdd BLAST19
Motifi328 – 333TFLY; involved in RNA bindingBy similarity6

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>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.

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the reverse transcriptase family. Telomerase subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1005, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000018531

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_001996_2_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O14746

Identification of Orthologs from Complete Genome Data

More...OMAi		HCAPHRV

Database of Orthologous Groups

More...OrthoDBi		1297956at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O14746

TreeFam database of animal gene trees

More...TreeFami		TF329048

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR043502, DNA/RNA_pol_sf
IPR000477, RT_dom
IPR021891, Telomerase_RBD
IPR003545, Telomerase_RT

The PANTHER Classification System

More...PANTHERi		PTHR12066, PTHR12066, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00078, RVT_1, 1 hit
PF12009, Telomerase_RBD, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR01365, TELOMERASERT

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00975, Telomerase_RBD, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56672, SSF56672, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50878, RT_POL, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (4+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 4 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> 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.Curated
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

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A590UK92A0A590UK92_HUMAN
Telomerase reverse transcriptase
TERT hCG_1990943
574Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>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:rs756624928EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs483352771Ensembl.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_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:rs387907250Ensembl.1
Natural variantiVAR_068799923P → L in PFBMFT1. 1 PublicationCorresponds to variant dbSNP:rs387907251Ensembl.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 PublicationsCorresponds to variant dbSNP:rs1176273130Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>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:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

The Consensus CDS (CCDS) project

More...CCDSi		CCDS3861.2 [O14746-1]
CCDS54831.1 [O14746-3]

Protein sequence database of the Protein Information Resource

More...PIRi		T03844

NCBI Reference Sequences

More...RefSeqi		NP_001180305.1, NM_001193376.1 [O14746-3]
NP_937983.2, NM_198253.2 [O14746-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000310581; ENSP00000309572; ENSG00000164362 [O14746-1]
ENST00000334602; ENSP00000334346; ENSG00000164362 [O14746-3]
ENST00000460137; ENSP00000425003; ENSG00000164362 [O14746-4]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		7015

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:7015

UCSC genome browser

More...UCSCi		uc003jcb.2, human [O14746-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>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]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...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[»]
SMRiO14746
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi112874, 98 interactors
ComplexPortaliCPX-17, Telomerase catalytic core complex
CPX-20, TERT-RMRP complex
CPX-265, Telomerase holoenzyme complex
CORUMiO14746
DIPiDIP-40646N
ELMiO14746
IntActiO14746, 24 interactors
MINTiO14746
STRINGi9606.ENSP00000309572

Chemistry databases

BindingDBiO14746
ChEMBLiCHEMBL2916
DrugBankiDB05036, Grn163l
DB12747, Tertomotide
DB00495, Zidovudine
DrugCentraliO14746

PTM databases

iPTMnetiO14746
PhosphoSitePlusiO14746

Genetic variation databases

BioMutaiTERT

Proteomic databases

EPDiO14746
MassIVEiO14746
PaxDbiO14746
PeptideAtlasiO14746
PRIDEiO14746
ProteomicsDBi48203 [O14746-1]
48204 [O14746-2]
48205 [O14746-3]
73418

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		O14746, 9 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		8998, 983 antibodies

The DNASU plasmid repository

More...DNASUi		7015

Genome annotation databases

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

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		7015
DisGeNETi7015

GeneCards: human genes, protein and diseases

More...GeneCardsi		TERT
GeneReviewsiTERT
HGNCiHGNC:11730, TERT
HPAiENSG00000164362, Group enriched (bone marrow, lymphoid tissue, testis)
MalaCardsiTERT
MIMi178500, phenotype
187270, gene+phenotype
609135, phenotype
613989, phenotype
614742, phenotype
615134, phenotype
neXtProtiNX_O14746
OpenTargetsiENSG00000164362
Orphaneti457246, 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
PharmGKBiPA36447
VEuPathDBiHostDB:ENSG00000164362.18

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1005, Eukaryota
GeneTreeiENSGT00390000018531
HOGENOMiCLU_001996_2_0_1
InParanoidiO14746
OMAiHCAPHRV
OrthoDBi1297956at2759
PhylomeDBiO14746
TreeFamiTF329048

Enzyme and pathway databases

PathwayCommonsiO14746
ReactomeiR-HSA-171319, Telomere Extension By Telomerase
R-HSA-201722, Formation of the beta-catenin:TCF transactivating complex
SIGNORiO14746

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		7015, 18 hits in 1001 CRISPR screens
EvolutionaryTraceiO14746

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Telomerase_reverse_transcriptase

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		7015
PharosiO14746, Tchem

Protein Ontology

More...PROi		PR:O14746
RNActiO14746, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000164362, Expressed in stromal cell of endometrium and 153 other tissues
GenevisibleiO14746, HS

Family and domain databases

InterProiView protein in InterPro
IPR043502, DNA/RNA_pol_sf
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
SUPFAMiSSF56672, SSF56672, 1 hit
PROSITEiView protein in PROSITE
PS50878, RT_POL, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTERT_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O14746
Secondary accession number(s): O14783
, Q2XS35, Q8N6C3, Q8NG38, Q8NG46
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: June 2, 2021
This is version 196 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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