TERT
entrez
7015
canonical
uniprot
O14746
canonical
ensembl
ENSG00000164362
resolver
ensp
ENSP00000309572
resolver
ensp
ENSP00000334346
resolver
genesymbol
TERT
resolver
genesymbol_syn
EST2
resolver
genesymbol_syn
TCS1
resolver
genesymbol_syn
TRT
resolver
hgnc
HGNC:11730
resolver
uniprot
O14783
resolver
uniprot
Q2XS35
resolver
uniprot
Q8N6C3
resolver
uniprot
Q8NG38
resolver
uniprot
Q8NG46
resolver
uniprot_entry
TERT_HUMAN
resolver
uniprot_sec
O14783
resolver
uniprot_sec
Q2XS35
resolver
uniprot_sec
Q8N6C3
resolver
uniprot_sec
Q8NG38
resolver
uniprot_sec
Q8NG46
resolver
amino_acid_sequence
MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGAATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRLVETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEILAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTIPQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTLLCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNLRKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTFNRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLPFHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLLKLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAANPALPSDFKTILD
uniprot
proteins
disease_involvement
DISEASE: Note=Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis.; DISEASE: Aplastic anemia (AA) [MIM:609135]: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia. {ECO:0000269|PubMed:15885610, ECO:0000269|PubMed:16627250, ECO:0000269|PubMed:16990594, ECO:0000269|PubMed:19760749}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: Note=Genetic variations in TERT are associated with coronary artery disease (CAD).; DISEASE: Dyskeratosis congenita, autosomal dominant, 2 (DKCA2) [MIM:613989]: A rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:15885610, ECO:0000269|PubMed:16247010, ECO:0000269|PubMed:21602826}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 1 (PFBMFT1) [MIM:614742]: An autosomal dominant 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. {ECO:0000269|PubMed:15814878, ECO:0000269|PubMed:17392301, ECO:0000269|PubMed:17460043, ECO:0000269|PubMed:21436073, ECO:0000269|PubMed:21483807, ECO:0000269|PubMed:22512499}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Dyskeratosis congenita, autosomal recessive, 4 (DKCB4) [MIM:613989]: A severe form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. {ECO:0000269|PubMed:16332973, ECO:0000269|PubMed:17785587, ECO:0000269|PubMed:18042801, ECO:0000269|PubMed:21602826}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Melanoma, cutaneous malignant 9 (CMM9) [MIM:615134]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. {ECO:0000269|PubMed:23348503}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.7.49
uniprot
proteins
function
FUNCTION: Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. Active in progenitor and cancer cells. Inactive, or very low activity, in normal somatic cells. Catalytic component of the teleromerase holoenzyme complex whose main activity is the elongation of telomeres by acting as a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme. Catalyzes the RNA-dependent extension of 3'-chromosomal termini with the 6-nucleotide telomeric repeat unit, 5'-TTAGGG-3'. The catalytic cycle involves primer binding, primer extension and release of product once the template boundary has been reached or nascent product translocation followed by further extension. More active on substrates containing 2 or 3 telomeric repeats. Telomerase activity is regulated by a number of factors including telomerase complex-associated proteins, chaperones and polypeptide modifiers. Modulates Wnt signaling. Plays important roles in aging and antiapoptosis. {ECO:0000269|PubMed:14963003, ECO:0000269|PubMed:15082768, ECO:0000269|PubMed:15857955, ECO:0000269|PubMed:17026956, ECO:0000269|PubMed:17264120, ECO:0000269|PubMed:17296728, ECO:0000269|PubMed:17548608, ECO:0000269|PubMed:19188162, ECO:0000269|PubMed:19567472, ECO:0000269|PubMed:19571879, ECO:0000269|PubMed:19777057, ECO:0000269|PubMed:9389643}.
uniprot
proteins
mass_dalton
126997
uniprot
proteins
mutagenesis
MUTAGEN 137..141; /note="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."; /evidence="ECO:0000269|PubMed:17296728"; MUTAGEN 169; /note="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."; /evidence="ECO:0000269|PubMed:19777057"; MUTAGEN 169; /note="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."; /evidence="ECO:0000269|PubMed:19777057"; MUTAGEN 169; /note="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."; /evidence="ECO:0000269|PubMed:19777057"; MUTAGEN 457; /note="S->A: Abolishes phosphorylation by DYRK2."; /evidence="ECO:0000269|PubMed:23362280"; MUTAGEN 547; /note="W->A: Defective in high-affinity TERC interactions."; /evidence="ECO:0000269|PubMed:15082768"; MUTAGEN 631; /note="R->A: Abolishes telomerase catalytic activity."; /evidence="ECO:0000269|PubMed:17026956"; MUTAGEN 707; /note="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."; /evidence="ECO:0000269|PubMed:12808100, ECO:0000269|PubMed:18829466"; MUTAGEN 712; /note="D->A: Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers."; /evidence="ECO:0000269|PubMed:17026956, ECO:0000269|PubMed:17296728, ECO:0000269|PubMed:9389643, ECO:0000269|PubMed:9443919"; MUTAGEN 866; /note="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."; /evidence="ECO:0000269|PubMed:17264120"; MUTAGEN 867; /note="V->A: About 75% reduction in telomerase activity, about 80% reduction in repeat reduction rate and 3.9-fold increase in nucleotide incorporation fidelity."; /evidence="ECO:0000269|PubMed:17264120"; MUTAGEN 867; /note="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."; /evidence="ECO:0000269|PubMed:17264120"; MUTAGEN 867; /note="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."; /evidence="ECO:0000269|PubMed:17264120"; MUTAGEN 868..869; /note="DD->AA: Loss of telomerase activity."; MUTAGEN 868; /note="D->A: Loss of telomerase activity."; /evidence="ECO:0000269|PubMed:15082768, ECO:0000269|PubMed:15857955, ECO:0000269|PubMed:17026956, ECO:0000269|PubMed:9389643, ECO:0000269|PubMed:9443919"; MUTAGEN 869; /note="D->A: Loss of telomerase activity."; /evidence="ECO:0000269|PubMed:9389643, ECO:0000269|PubMed:9443919"; MUTAGEN 930..934; /note="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."; /evidence="ECO:0000269|PubMed:17296728
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:12808100, ECO:0000269|PubMed:18829466, ECO:0000269|PubMed:22366458, ECO:0000269|PubMed:23362280}.; PTM: Ubiquitinated by the EDVP complex, a E3 ligase complex following phosphorylation at Ser-457 by DYRK2. Ubiquitinated leads to proteasomal degradation. {ECO:0000269|PubMed:23362280}.; PTM: (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. {ECO:0000269|PubMed:23362280}.
uniprot
proteins
protein_family
Reverse transcriptase family
uniprot
proteins
protein_family
Telomerase subfamily
uniprot
proteins
pubmed
10333526
uniprot
proteins
pubmed
11029039
uniprot
proteins
pubmed
11274138
uniprot
proteins
pubmed
12808100
uniprot
proteins
pubmed
12869302
uniprot
proteins
pubmed
14654914
uniprot
proteins
pubmed
14963003
uniprot
proteins
pubmed
15044100
uniprot
proteins
pubmed
15082768
uniprot
proteins
pubmed
15138842
uniprot
proteins
pubmed
15371412
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15805468
uniprot
proteins
pubmed
15814878
uniprot
proteins
pubmed
15857955
uniprot
proteins
pubmed
15885610
uniprot
proteins
pubmed
16247010
uniprot
proteins
pubmed
16323248
uniprot
proteins
pubmed
16332973
uniprot
proteins
pubmed
16627250
uniprot
proteins
pubmed
16890917
uniprot
proteins
pubmed
16990594
uniprot
proteins
pubmed
17026956
uniprot
proteins
pubmed
17264120
uniprot
proteins
pubmed
17296728
uniprot
proteins
pubmed
17392301
uniprot
proteins
pubmed
17460043
uniprot
proteins
pubmed
17548608
uniprot
proteins
pubmed
17785587
uniprot
proteins
pubmed
18042801
uniprot
proteins
pubmed
18082603
uniprot
proteins
pubmed
18829466
uniprot
proteins
pubmed
19147845
uniprot
proteins
pubmed
19179534
uniprot
proteins
pubmed
19188162
uniprot
proteins
pubmed
19567472
uniprot
proteins
pubmed
19571879
uniprot
proteins
pubmed
19760749
uniprot
proteins
pubmed
19777057
uniprot
proteins
pubmed
20351177
uniprot
proteins
pubmed
21436073
uniprot
proteins
pubmed
21483807
uniprot
proteins
pubmed
21602826
uniprot
proteins
pubmed
21846770
uniprot
proteins
pubmed
22226966
uniprot
proteins
pubmed
22366458
uniprot
proteins
pubmed
22512499
uniprot
proteins
pubmed
23348503
uniprot
proteins
pubmed
23362280
uniprot
proteins
pubmed
23612978
uniprot
proteins
pubmed
29490055
uniprot
proteins
pubmed
29695869
uniprot
proteins
pubmed
31355908
uniprot
proteins
pubmed
8676067
uniprot
proteins
pubmed
9252327
uniprot
proteins
pubmed
9288757
uniprot
proteins
pubmed
9389643
uniprot
proteins
pubmed
9443919
uniprot
proteins
sequence_length
1132
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:22226966}. Nucleus, nucleoplasm. Nucleus. Chromosome, telomere. Cytoplasm. Nucleus, PML body. Note=Shuttling between nuclear and cytoplasm depends on cell cycle, phosphorylation states, transformation and DNA damage. Diffuse localization in the nucleoplasm. Enriched in nucleoli of certain cell types. Translocated to the cytoplasm via nuclear pores in a CRM1/RAN-dependent manner involving oxidative stress-mediated phosphorylation at Tyr-707. Dephosphorylation at this site by SHP2 retains TERT in the nucleus. Translocated to the nucleus by phosphorylation by AKT.
uniprot
proteins