Protein:TERT |
Protein Summary |
 Gene summary |
| Gene name: TERT | ASpdb.0 ID: 7015 | Gene | Gene symbol | TERT | Gene ID | 7015 |
| Gene name | telomerase reverse transcriptase |
| Synonyms | CMM9|DKCA2|DKCB4|EST2|PFBMFT1|TCS1|TP2|TRT|hEST2|hTRT |
| Cytomap | 5p15.33 |
| Type of gene | protein-coding |
| Description | telomerase reverse transcriptasetelomerase catalytic subunittelomerase-associated protein 2 |
| Modification date | 20240416 |
| UniProtAcc | O14746 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | TERT | GO:0000049 | tRNA binding | 21937513 |
| Gene | TERT | GO:0000333 | telomerase catalytic core complex | 9398860|9443919|16507993|17940095|18082603 |
| Gene | TERT | GO:0000781 | chromosome, telomeric region | 25589350 |
| Gene | TERT | GO:0001172 | RNA-templated transcription | 19701182 |
| Gene | TERT | GO:0003677 | DNA binding | 21937513 |
| Gene | TERT | GO:0003720 | telomerase activity | 9398860|9443919|12135483|16043710|16507993|17940095|18082603|21531765|29695869 |
| Gene | TERT | GO:0003721 | telomerase RNA reverse transcriptase activity | 9398860|15632080|17940095|19701182 |
| Gene | TERT | GO:0003964 | RNA-directed DNA polymerase activity | 21937513 |
| Gene | TERT | GO:0003968 | RNA-dependent RNA polymerase activity | 19701182 |
| Gene | TERT | GO:0005634 | nucleus | 21829167|24415760 |
| Gene | TERT | GO:0005654 | nucleoplasm | 19567472 |
| Gene | TERT | GO:0005697 | telomerase holoenzyme complex | 12135483|18082603|29695869 |
| Gene | TERT | GO:0005730 | nucleolus | 22226966 |
| Gene | TERT | GO:0005829 | cytosol | - |
| Gene | TERT | GO:0006278 | RNA-templated DNA biosynthetic process | 9398860 |
| Gene | TERT | GO:0007004 | telomere maintenance via telomerase | 9443919|16043710|17940095|19701182|21531765|29695869 |
| Gene | TERT | GO:0007005 | mitochondrion organization | 21937513 |
| Gene | TERT | GO:0010629 | negative regulation of gene expression | 11927518 |
| Gene | TERT | GO:0016605 | PML body | 19567472 |
| Gene | TERT | GO:0016607 | nuclear speck | - |
| Gene | TERT | GO:0022616 | DNA strand elongation | 16043710 |
| Gene | TERT | GO:0030422 | siRNA processing | 19701182 |
| Gene | TERT | GO:0031647 | regulation of protein stability | 24415760|26194824 |
| Gene | TERT | GO:0032092 | positive regulation of protein binding | 24415760 |
| Gene | TERT | GO:0042645 | mitochondrial nucleoid | 21937513 |
| Gene | TERT | GO:0042803 | protein homodimerization activity | 11432839 |
| Gene | TERT | GO:0051000 | positive regulation of nitric-oxide synthase activity | 11927518 |
| Gene | TERT | GO:0070034 | telomerase RNA binding | 11432839 |
| Gene | TERT | GO:0070200 | establishment of protein localization to telomere | 25589350 |
| Gene | TERT | GO:0071897 | DNA biosynthetic process | 9398860 |
| Gene | TERT | GO:0098680 | template-free RNA nucleotidyltransferase | 19701182 |
| Gene | TERT | GO:0140745 | siRNA transcription | 19701182 |
| Gene | TERT | GO:1904751 | positive regulation of protein localization to nucleolus | 24415760 |
| Gene | TERT | GO:1990572 | TERT-RMRP complex | 19701182 |
| Gene | TERT | GO:2000773 | negative regulation of cellular senescence | 11927518 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| O14746-1 | O14746-1_5ugw_A.pdb | 5UGW | X-ray | 2.31 | A | 965 | 1122 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| O14746 | TERT | O14746-1 | O14746-2 | 1132 | 807 | 764 | 807 | Substitution | STLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFD | LRPVPGDPAGLHPLHAALQPVLRRHGEQAVCGDSAGRAAPAFGG | 764 | 807 |
| O14746 | TERT | O14746-1 | O14746-2 | 1132 | 807 | 808 | 1132 | Deletion | none | none | 807 | 807 |
| O14746 | TERT | O14746-1 | O14746-3 | 1132 | 1069 | 885 | 947 | Deletion | none | none | 884 | 884 |
| O14746 | TERT | O14746-1 | O14746-4 | 1132 | 795 | 711 | 722 | Deletion | none | none | 710 | 710 |
| O14746 | TERT | O14746-1 | O14746-4 | 1132 | 795 | 764 | 807 | Substitution | STLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFD | LRPVPGDPAGLHPLHAALQPVLRRHGEQAVCGDSAGRAAPAFGG | 752 | 795 |
| O14746 | TERT | O14746-1 | O14746-4 | 1132 | 795 | 808 | 1132 | Deletion | none | none | 795 | 795 |
| Multiple sequence alignment of our canonical and alternatively spliced TERT |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of TERT |
| UniProt-id | ENSG | ENST | ENSP |
| O14746-1 | ENSG00000164362.21 | ENST00000310581.10 | ENSP00000309572.5 |
| O14746-3 | ENSG00000164362.21 | ENST00000334602.10 | ENSP00000334346.6 |
| O14746-4 | ENSG00000164362.21 | ENST00000460137.6 | ENSP00000425003.1 |
| UniProt-id | NM ID | NP ID |
| O14746-1 | NM_198253.2 | NP_937983.2 |
| O14746-3 | NM_001193376.1 | NP_001180305.1 |
| Amino acid sequences of our canonical and alternatively spliced TERT |
| accession_id | Protein sequence |
| O14746-1 | MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCE RGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGF CVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQ LLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGL RPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFDVFL RFMCHHAVRIRGKSYVQCQGIPQGSILSTLLCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNL RKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTFNRGFKAGRNMRRKLFGVLRLKCHSLFLDLQ VNSLQTVCTNIYKILLLQAYRFHACVLQLPFHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLL |
| O14746-2 | MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCE RGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGF CVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQ LLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGL RPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI |
| O14746-3 | MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCE RGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGF CVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQ LLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGL RPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHLQETSPLRDAVVIEQSSSLNEASSGLFDVFL RFMCHHAVRIRGKSYVQCQGIPQGSILSTLLCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLSYARTSIRASLTFNRG FKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLPFHQQVWKNPTFFLRVISDTASLCYSILKAKNAG |
| O14746-4 | MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPWDARPPPAAPSFRQVSCLKELVARVLQRLCE RGAKNVLAFGFALLDGARGGPPEAFTTSVRSYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRRGAAPEPERTPVGQGSWAHPGRTRGPSDRGF CVVSPARPAEEATSLEGALSGTRHSHPSVGRQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVTPAAGVCAREKPQGSVAAPEEEDTDPRRLVQ LLRQHSSPWQVYGFVRACLRRLVPPGLWGSRHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRELSEAEVRQHREARPALLTSRLRFIPKPDGL RPIVNMDYVVGARTFRREKRAERLTSRVKALFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKDRLTEVIASI |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| TERT (go to UniProt):O14746 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Substitution;Start=764;End=807 |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Deletion;Start=808;End=1132 |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Deletion;Start=885;End=947 |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Deletion;Start=711;End=722 |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Substitution;Start=764;End=807 |
| O14746 | Domain | 605 | 935 | Note=Reverse transcriptase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00405 | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 914 | 928 | Note=Required for oligomerization | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 914 | 928 | Note=Required for oligomerization | Type=Deletion;Start=885;End=947 |
| O14746 | Region | 914 | 928 | Note=Required for oligomerization | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 930 | 934 | Note=Primer grip sequence | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 930 | 934 | Note=Primer grip sequence | Type=Deletion;Start=885;End=947 |
| O14746 | Region | 930 | 934 | Note=Primer grip sequence | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 936 | 1132 | Note=CTE | Type=Deletion;Start=808;End=1132 |
| O14746 | Region | 936 | 1132 | Note=CTE | Type=Deletion;Start=885;End=947 |
| O14746 | Region | 936 | 1132 | Note=CTE | Type=Deletion;Start=808;End=1132 |
Gene Isoform Structures and Expression Levels for TERT |
| Gene structures of our canonical and alternative spliced genes of TERT * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of O14746-1 |
| 3D view using mol* of O14746-2 |
| 3D view using mol* of O14746-3 |
| 3D view using mol* of O14746-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of O14746-1 |
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| pLDDT distribution across the protein length of O14746-2 |
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| pLDDT distribution across the protein length of O14746-3 |
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| pLDDT distribution across the protein length of O14746-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of O14746-1 |
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| Ramachandran plot of O14746-3 |
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| Ramachandran plot of O14746-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| O14746-1 | 1.007 | 180 | 1.002 | 531.307 | 0.521 | 0.709 | 0.921 | 0.625 | 1.115 | 0.561 | 0.622 | 105,106,108,123,606,610,611,612,613,614,615,616,61 7,618,619,636,639,640,645,646,647,649,650,651,653, 654,656,657,660,741,743,795,796,797,800,819,822,82 3,824 |
| O14746-2 | 1.061 | 565 | 1.097 | 1389.493 | 0.51 | 0.747 | 0.923 | 0.747 | 0.892 | 0.838 | 0.727 | 9,10,13,14,78,82,96,99,100,114,115,123,124,125,126 ,127,129,130,132,159,165,166,167,168,169,174,175,1 76,637,648,651,652,655,656,659,660,662,663,666,667 ,670,671,739,740,741,742,743,744,745,746,747,748,7 49,756,758,759,760,761,762,763,764,765,766,767,770 ,771,772,773,774,775,777,780,781,783,784,785,787,7 88,789,791,792 |
| O14746-3 | 1.066 | 90 | 0.958 | 152.292 | 0.357 | 0.852 | 1.178 | 1.254 | 1.365 | 0.919 | 0.567 | 606,610,611,612,613,615,616,618,639,640,647,650,65 1,654,817,819,822,824 |
| O14746-4 | 1.093 | 108 | 1.15 | 331.681 | 0.502 | 0.748 | 0.968 | 1.402 | 0.731 | 1.918 | 0.553 | 46,49,50,53,127,129,130,131,133,134,135,136,137,16 0,162,168,170,759,760,761,762,764,765,766,769 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of O14746-1_O14746-1_5ugw_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O14746-1_5ugw_A_O14746-2.pdb |
| 3D view using mol* of O14746-1_5ugw_A_O14746-3.pdb |
| 3D view using mol* of O14746-1_5ugw_A_O14746-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of O14746-1_O14746-2.pdb |
| 3D view using mol* of O14746-1_O14746-3.pdb |
| 3D view using mol* of O14746-1_O14746-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/O14746-1_vs_O14746-2.png |
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| ./stats/secondary_structure/figure/O14746-1_vs_O14746-3.png |
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| ./stats/secondary_structure/figure/O14746-1_vs_O14746-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/O14746-1_vs_O14746-2.png |
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| ./stats/relative_asa/O14746-1_vs_O14746-3.png |
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| ./stats/relative_asa/O14746-1_vs_O14746-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to TERT |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| O14746 | TERT | DB00495 | Zidovudine | approved | inhibitor |
| O14746 | TERT | DB12747 | Tertomotide | investigational | |
| O14746 | TERT | DB05036 | Grn163l | investigational |
Related Diseases to TERT |
| Previous studies relating to the alternative splicing of TERT and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| TERT | 12598334 | Full-length telomerase reverse transcriptase messenger RNA is an independent prognostic factor in neuroblastoma. | Telomerase activity (TA) is the most recently recognized prognostic factor in neuroblastoma, and its outstanding predictive power was documented by several studies. However, TA measurements require fresh tumor tissue that is not always available in daily clinical practice. We previously described a reverse transcriptase-polymerase chain reaction assay that we used to investigate the possible prognostic relevance of the telomerase catalytic subunit, hTERT, at the mRNA level. Because hTERT mRNA undergoes alternative splicing as a regulatory mechanism of TA, we discriminated between truncated and full-length hTERT transcripts. In a retrospective study on 124 neuroblastomas, 56 (45.2%) tumors showed spliced hTERT transcripts, whereas 30 (24.2%) contained full-length hTERT transcripts. The presence of both spliced and full-length hTERT transcripts was significantly associated with MYCN amplification. hTERT in general showed no correlation to other prognostic factors, ie, International Neuroblastoma Staging System stage, International Neuroblastoma Pathology classification grade, or age at diagnosis, whereas the presence of full-length transcripts was significantly associated with higher stages. The presence of any hTERT transcripts carried no significant prognostic information, yet full-length hTERT transcripts were highly predictive of poor outcome (P < 0.0001). In a multivariate analysis, full-length hTERT transcripts and International Neuroblastoma Pathology classification grade emerged as the sole independent predictors of event-free survival, with relative risks of 10.0 and 3.9, respectively. The strong statistical correlation of full-length hTERT transcripts with clinical outcome in neuroblastoma suggests that the reverse transcriptase-polymerase chain reaction analysis of hTERT transcripts may be equatable to TA measurements. Because this assay is well suited for archival material, it could become a useful adjunct in evaluating the prognosis of individual neuroblastoma cases. | D001932 | Brain Neoplasms |
| TERT | 12598334 | Full-length telomerase reverse transcriptase messenger RNA is an independent prognostic factor in neuroblastoma. | Telomerase activity (TA) is the most recently recognized prognostic factor in neuroblastoma, and its outstanding predictive power was documented by several studies. However, TA measurements require fresh tumor tissue that is not always available in daily clinical practice. We previously described a reverse transcriptase-polymerase chain reaction assay that we used to investigate the possible prognostic relevance of the telomerase catalytic subunit, hTERT, at the mRNA level. Because hTERT mRNA undergoes alternative splicing as a regulatory mechanism of TA, we discriminated between truncated and full-length hTERT transcripts. In a retrospective study on 124 neuroblastomas, 56 (45.2%) tumors showed spliced hTERT transcripts, whereas 30 (24.2%) contained full-length hTERT transcripts. The presence of both spliced and full-length hTERT transcripts was significantly associated with MYCN amplification. hTERT in general showed no correlation to other prognostic factors, ie, International Neuroblastoma Staging System stage, International Neuroblastoma Pathology classification grade, or age at diagnosis, whereas the presence of full-length transcripts was significantly associated with higher stages. The presence of any hTERT transcripts carried no significant prognostic information, yet full-length hTERT transcripts were highly predictive of poor outcome (P < 0.0001). In a multivariate analysis, full-length hTERT transcripts and International Neuroblastoma Pathology classification grade emerged as the sole independent predictors of event-free survival, with relative risks of 10.0 and 3.9, respectively. The strong statistical correlation of full-length hTERT transcripts with clinical outcome in neuroblastoma suggests that the reverse transcriptase-polymerase chain reaction analysis of hTERT transcripts may be equatable to TA measurements. Because this assay is well suited for archival material, it could become a useful adjunct in evaluating the prognosis of individual neuroblastoma cases. | D009447 | Neuroblastoma |
| TERT | 14654914 | Differential alternative splicing expressions of telomerase reverse transcriptase in gastrointestinal cell lines. | Telomerase is a cellular RNA-dependent DNA polymerase that serves to maintain the tandem arrays of telomeric TTAGGG repeats at eukaryotic chromosome ends. One of the human telomerase components is hTERT, which has three alternative spliced sites that introduce eight isoforms of hTERT mRNA. The expression of these isoforms in gastrointestinal cell lines is unknown. We developed a PCR-based assay for detecting these splicing variants. In gastric and hepatocellular carcinoma cell lines, the gamma deletion variant and its combination variants, alpha- and gamma-, beta- and gamma-, and alpha-, beta- and gamma-deletion variants were frequently detected, while they were not detected in colorectal carcinoma cell lines. Our results provide important information of use for more detailed studies on the regulation of telomerase activity. | D005770 | Gastrointestinal Neoplasms |
| TERT | 16170363 | Hypoxic regulation of telomerase gene expression by transcriptional and post-transcriptional mechanisms. | Basal telomerase activity is dependent on expression of the hTERT and hTR genes and upregulation of telomerase gene expression is associated with tumour development. It is therefore possible that signal transduction pathways involved in tumour development and features of the tumour environment itself may influence telomerase gene regulation. The majority of solid tumours contain regions of hypoxia and it has recently been demonstrated that hypoxia can increase telomerase activity by mechanisms that are still poorly defined. Here, we show that hypoxia induces the transcriptional activity of both hTR and hTERT gene promoters. While endogenous hTR expression is regulated at the transcriptional level, hTERT is subject to regulation by alternative splicing under hypoxic conditions, which involves a switch in the splice pattern in favour of the active variant. Furthermore, analysis of the chromatin landscape of the telomerase promoters reveals dynamic recruitment of a transcriptional complex involving the hypoxia-inducible factor-1 transcription factor, p300, RNA polymerase II and TFIIB, to both promoters during hypoxia, which traffics along and remains associated with the hTERT gene as transcription proceeds. These studies show that hTERT and hTR are subject to similar controls under hypoxia and highlight the rapid and dynamic regulation of the telomerase genes in vivo. | D000860 | Hypoxia |
| TERT | 16939641 | Characterization of novel alternative splicing sites in human telomerase reverse transcriptase (hTERT): analysis of expression and mutual correlation in mRNA isoforms from normal and tumour tissues. | Human telomerase reverse transcriptase (hTERT) is a key component for synthesis and maintenance of telomeres on chromosome ends and is required for the continued proliferation of cells. Estimation of hTERT expression therefore has broad relevance in oncology and stem cell research. Several splicing variants of hTERT have been described whose regulated expression contributes to the control of telomerase activity. Knowledge of the different hTERT mRNA isoforms and the ability to distinguish between them is an important issue when evaluating telomerase expression. | D003110 | Colonic Neoplasms |
| TERT | 16939641 | Characterization of novel alternative splicing sites in human telomerase reverse transcriptase (hTERT): analysis of expression and mutual correlation in mRNA isoforms from normal and tumour tissues. | Human telomerase reverse transcriptase (hTERT) is a key component for synthesis and maintenance of telomeres on chromosome ends and is required for the continued proliferation of cells. Estimation of hTERT expression therefore has broad relevance in oncology and stem cell research. Several splicing variants of hTERT have been described whose regulated expression contributes to the control of telomerase activity. Knowledge of the different hTERT mRNA isoforms and the ability to distinguish between them is an important issue when evaluating telomerase expression. | D008175 | Lung Neoplasms |
| TERT | 19079992 | [Changes of alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis]. | The expression of human telomerase reverse transcriptase (hTERT) is positively correlated to the activity of telomerase. Alternative splicing exists in the transcription of hTERT and special splicing patterns may change during tumor progression. This study was to reveal the changes of hTERT alterative splicing pattern in gastric carcinogenesis. | D005757 | Gastritis, Atrophic |
| TERT | 19079992 | [Changes of alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis]. | The expression of human telomerase reverse transcriptase (hTERT) is positively correlated to the activity of telomerase. Alternative splicing exists in the transcription of hTERT and special splicing patterns may change during tumor progression. This study was to reveal the changes of hTERT alterative splicing pattern in gastric carcinogenesis. | D011230 | Precancerous Conditions |
| TERT | 19079992 | [Changes of alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis]. | The expression of human telomerase reverse transcriptase (hTERT) is positively correlated to the activity of telomerase. Alternative splicing exists in the transcription of hTERT and special splicing patterns may change during tumor progression. This study was to reveal the changes of hTERT alterative splicing pattern in gastric carcinogenesis. | D013274 | Stomach Neoplasms |
| TERT | 19188747 | Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis. | We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. | D000230 | Adenocarcinoma |
| TERT | 19188747 | Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis. | We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. | D005757 | Gastritis, Atrophic |
| TERT | 19188747 | Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis. | We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. | D008679 | Metaplasia |
| TERT | 19188747 | Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis. | We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. | D011230 | Precancerous Conditions |
| TERT | 19188747 | Changes of the alternative splicing variants of human telomerase reverse transcriptase during gastric carcinogenesis. | We attempted to reveal the changes of the human telomerase reverse transcriptase (hTERT) alternative splicing pattern in gastric carcinogenesis. | D013274 | Stomach Neoplasms |
| TERT | 20225759 | Changes of telomerase activity by alternative splicing of full-length and beta variants of hTERT in breast cancer patients. | Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. Although the positions of the spliced sites suggest that many of the variants do not code for functional reverse transcriptase, the functions of the spliced variants of hTERT are unknown. We analyzed hTERT splicing patterns with respect to telomerase activity in breast cancer. We examined telomerase activity by telomeric repeat amplification protocol (TRAP) assay and detected spliced variants of hTERT by reverse transcription-polymerase chain reaction (RT-PCR). Of 45 breast cancer patients, 38 (84%) were found to express telomerase activity and 41 (91%) expressed hTERT. In patients with telomerase activity, 14 (37%) expressed all four types of variants (full length, alpha, beta, and alpha/beta). Eleven patients (29%) expressed both the full-length and beta variant. Eight patients (22%) expressed the beta variant only and 3 (8%) expressed the full-length type only. When comparing telomerase activity to the expression of splicing variants, a tendency was found for lower telomerase activity in patients expressing the beta variant only (45 +/- 11) versus those expressing all four types (64 +/- 32) and those coexpressing the full-length type with the beta variant (61 +/- 22) (p = 0.06, respectively). In patients with both full-length and beta variants coexpression, increment of beta variant showed a decreased telomerase activity regardless of the full-length variant expression (p = 0.027). Telomerase activity changed with alternative splicing of the full-length and beta variants expression of hTERT in breast cancer. | D001943 | Breast Neoplasms |
| TERT | 20225759 | Changes of telomerase activity by alternative splicing of full-length and beta variants of hTERT in breast cancer patients. | Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. Although the positions of the spliced sites suggest that many of the variants do not code for functional reverse transcriptase, the functions of the spliced variants of hTERT are unknown. We analyzed hTERT splicing patterns with respect to telomerase activity in breast cancer. We examined telomerase activity by telomeric repeat amplification protocol (TRAP) assay and detected spliced variants of hTERT by reverse transcription-polymerase chain reaction (RT-PCR). Of 45 breast cancer patients, 38 (84%) were found to express telomerase activity and 41 (91%) expressed hTERT. In patients with telomerase activity, 14 (37%) expressed all four types of variants (full length, alpha, beta, and alpha/beta). Eleven patients (29%) expressed both the full-length and beta variant. Eight patients (22%) expressed the beta variant only and 3 (8%) expressed the full-length type only. When comparing telomerase activity to the expression of splicing variants, a tendency was found for lower telomerase activity in patients expressing the beta variant only (45 +/- 11) versus those expressing all four types (64 +/- 32) and those coexpressing the full-length type with the beta variant (61 +/- 22) (p = 0.06, respectively). In patients with both full-length and beta variants coexpression, increment of beta variant showed a decreased telomerase activity regardless of the full-length variant expression (p = 0.027). Telomerase activity changed with alternative splicing of the full-length and beta variants expression of hTERT in breast cancer. | D018270 | Carcinoma, Ductal, Breast |
| TERT | 20225759 | Changes of telomerase activity by alternative splicing of full-length and beta variants of hTERT in breast cancer patients. | Human telomerase reverse transcriptase (hTERT) expression level may not always correlate with telomerase activity. Although the positions of the spliced sites suggest that many of the variants do not code for functional reverse transcriptase, the functions of the spliced variants of hTERT are unknown. We analyzed hTERT splicing patterns with respect to telomerase activity in breast cancer. We examined telomerase activity by telomeric repeat amplification protocol (TRAP) assay and detected spliced variants of hTERT by reverse transcription-polymerase chain reaction (RT-PCR). Of 45 breast cancer patients, 38 (84%) were found to express telomerase activity and 41 (91%) expressed hTERT. In patients with telomerase activity, 14 (37%) expressed all four types of variants (full length, alpha, beta, and alpha/beta). Eleven patients (29%) expressed both the full-length and beta variant. Eight patients (22%) expressed the beta variant only and 3 (8%) expressed the full-length type only. When comparing telomerase activity to the expression of splicing variants, a tendency was found for lower telomerase activity in patients expressing the beta variant only (45 +/- 11) versus those expressing all four types (64 +/- 32) and those coexpressing the full-length type with the beta variant (61 +/- 22) (p = 0.06, respectively). In patients with both full-length and beta variants coexpression, increment of beta variant showed a decreased telomerase activity regardless of the full-length variant expression (p = 0.027). Telomerase activity changed with alternative splicing of the full-length and beta variants expression of hTERT in breast cancer. | D018275 | Carcinoma, Lobular |
| TERT | 22723897 | Quantification of alternative splicing variants of human telomerase reverse transcriptase and correlations with telomerase activity in lung cancer. | Telomerase plays important roles in the development and progression of malignant tumors, and its activity is primarily determined by transcriptional regulation of human telomerase reverse transcriptase (hTERT). Several mRNA alternative splicing variants (ASVs) for hTERT have been identified, but it remains unclear whether telomerase activity is directly associated with hTERT splicing transcripts. In this study, we developed novel real-time PCR protocols using molecular beacons and applied to lung carcinoma cell lines and cancerous tissues for quantification of telomerase activity and three essential hTERT deletion transcripts respectively. The results showed that lung carcinoma cell lines consistently demonstrated telomerase activity (14.22-31.43 TPG units per 100 cells) and various hTERT alternative splicing transcripts. For 165 lung cancer cases, telomerase activity showed significant correlation with tumor differentiation (poorly->moderately->well-differentiated, P<0.01) and with histotypes (combined small cell and squamous cell carcinoma>squamous cell carcinoma>adenosquamous carcinoma>adenocarcinoma, P<0.05). Although the overall hTERT transcripts were detected in all the samples, they were not associated with telomerase activity (r = 0.092, P = 0.24). Telomerase activity was significantly correlated with the transcriptional constituent ratio of α-deletion (r = -0.267, P = 0.026), β-deletion (r = -0.693, P = 0.0001) and γ-deletion (r = -0.614, P = 0.001). The positive rate and average constituent ratio of β-deletion transcripts (92.12%, 0.23) were higher than those of α-deletion (41.82%, 0.12) or γ-deletion (16.36%, 0.18) transcripts. The combined small-cell and squamous cell carcinomas expressed less deletion transcripts, especially β-deletion, than other histotypes, which might explain their higher telomerase activity. In conclusion, the molecular beacon-based real-time PCR protocols are rapid, sensitive and specific methods to quantify telomerase activity and hTERT ASVs. Telomerase activity may serve as a reliable and effective molecular marker to assist the evaluation of histological subtype and differentiation of lung carcinomas. Further studies on hTERT deletion splicing transcripts, rather than the overall hTERT transcripts, may improve our understanding of telomerase regulation. | D008175 | Lung Neoplasms |
| TERT | 23610451 | The major reverse transcriptase-incompetent splice variant of the human telomerase protein inhibits telomerase activity but protects from apoptosis. | Human telomerase reverse transcriptase (hTERT; the catalytic protein subunit of telomerase) is subjected to numerous alternative splicing events, but the regulation and function of these splice variants is obscure. Full-length hTERT includes conserved domains that encode reverse transcriptase activity, RNA binding, and other functions. The major splice variant termed α+β- or β-deletion is highly expressed in stem and cancer cells, where it codes for a truncated protein lacking most of the reverse transcriptase domain but retaining the known RNA-binding motifs. In a breast cancer cell panel, we found that β-deletion was the hTERT transcript that was most highly expressed. Splicing of this transcript was controlled by the splice regulators SRSF11, HNRNPH2, and HNRNPL, and the β-deletion transcript variant was associated with polyribosomes in cells. When ectopically overexpressed, β-deletion protein competed for binding to telomerase RNA (hTR/TERC), thereby inhibiting endogenous telomerase activity. Overexpressed β-deletion protein localized to the nucleus and mitochondria and protected breast cancer cells from cisplatin-induced apoptosis. Our results reveal that a major hTERT splice variant can confer a growth advantage to cancer cells independent of telomere maintenance, suggesting that hTERT makes multiple contributions to cancer pathophysiology. | D001943 | Breast Neoplasms |
| TERT | 23933091 | Physiological and pathological significance of human telomerase reverse transcriptase splice variants. | Human telomerase reverse transcriptase (hTERT) is tightly regulated at various transcriptional and post-transcriptional levels. Alternative splicing of hTERT has been shown in many human tissues and cell lines regardless of telomerase status and may play a role in regulation of telomerase activity and other cellular functions. Catalytically inactive splice variants make up a substantial proportion of total hTERT mRNA and are at least partly translated into protein. Shifts in splicing patterns occur in development, tumorigenesis and in response to exogenous stimuli in a tissue- and cell type-specific manner. This review focuses on prevalence, patterns and regulation of hTERT alternative splicing, describes associations with telomerase activity and telomere length, and discusses the potential significance of hTERT alternative splice variants in cancer as well as possible telomere-independent functions. | D063646 | Carcinogenesis |
| TERT | 23933091 | Physiological and pathological significance of human telomerase reverse transcriptase splice variants. | Human telomerase reverse transcriptase (hTERT) is tightly regulated at various transcriptional and post-transcriptional levels. Alternative splicing of hTERT has been shown in many human tissues and cell lines regardless of telomerase status and may play a role in regulation of telomerase activity and other cellular functions. Catalytically inactive splice variants make up a substantial proportion of total hTERT mRNA and are at least partly translated into protein. Shifts in splicing patterns occur in development, tumorigenesis and in response to exogenous stimuli in a tissue- and cell type-specific manner. This review focuses on prevalence, patterns and regulation of hTERT alternative splicing, describes associations with telomerase activity and telomere length, and discusses the potential significance of hTERT alternative splice variants in cancer as well as possible telomere-independent functions. | D009369 | Neoplasms |
Clinically important variants in TERT |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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