Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT085VVA)

DOT Name Telomerase reverse transcriptase (TERT)
Synonyms EC 2.7.7.49; HEST2; Telomerase catalytic subunit; Telomerase-associated protein 2; TP2
Gene Name TERT
Related Disease
Dyskeratosis congenita, autosomal dominant 2 ( )
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 ( )
Acute myelogenous leukaemia ( )
Dyskeratosis congenita ( )
Hoyeraal-Hreidarsson syndrome ( )
Melanoma, cutaneous malignant, susceptibility to, 9 ( )
UniProt ID
TERT_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2BCK; 4B18; 4MNQ; 5MEN; 5MEO; 5MEP; 5MEQ; 5MER; 5UGW; 7BG9; 7QXA; 7QXB; 7QXS; 7TRD; 7TRE; 7TRF; 7V99
EC Number
2.7.7.49
Pfam ID
PF00078 ; PF12009 ; PF21399
Sequence
MPRAPRCRAVRSLLRSHYREVLPLATFVRRLGPQGWRLVQRGDPAAFRALVAQCLVCVPW
DARPPPAAPSFRQVSCLKELVARVLQRLCERGAKNVLAFGFALLDGARGGPPEAFTTSVR
SYLPNTVTDALRGSGAWGLLLRRVGDDVLVHLLARCALFVLVAPSCAYQVCGPPLYQLGA
ATQARPPPHASGPRRRLGCERAWNHSVREAGVPLGLPAPGARRRGGSASRSLPLPKRPRR
GAAPEPERTPVGQGSWAHPGRTRGPSDRGFCVVSPARPAEEATSLEGALSGTRHSHPSVG
RQHHAGPPSTSRPPRPWDTPCPPVYAETKHFLYSSGDKEQLRPSFLLSSLRPSLTGARRL
VETIFLGSRPWMPGTPRRLPRLPQRYWQMRPLFLELLGNHAQCPYGVLLKTHCPLRAAVT
PAAGVCAREKPQGSVAAPEEEDTDPRRLVQLLRQHSSPWQVYGFVRACLRRLVPPGLWGS
RHNERRFLRNTKKFISLGKHAKLSLQELTWKMSVRDCAWLRRSPGVGCVPAAEHRLREEI
LAKFLHWLMSVYVVELLRSFFYVTETTFQKNRLFFYRKSVWSKLQSIGIRQHLKRVQLRE
LSEAEVRQHREARPALLTSRLRFIPKPDGLRPIVNMDYVVGARTFRREKRAERLTSRVKA
LFSVLNYERARRPGLLGASVLGLDDIHRAWRTFVLRVRAQDPPPELYFVKVDVTGAYDTI
PQDRLTEVIASIIKPQNTYCVRRYAVVQKAAHGHVRKAFKSHVSTLTDLQPYMRQFVAHL
QETSPLRDAVVIEQSSSLNEASSGLFDVFLRFMCHHAVRIRGKSYVQCQGIPQGSILSTL
LCSLCYGDMENKLFAGIRRDGLLLRLVDDFLLVTPHLTHAKTFLRTLVRGVPEYGCVVNL
RKTVVNFPVEDEALGGTAFVQMPAHGLFPWCGLLLDTRTLEVQSDYSSYARTSIRASLTF
NRGFKAGRNMRRKLFGVLRLKCHSLFLDLQVNSLQTVCTNIYKILLLQAYRFHACVLQLP
FHQQVWKNPTFFLRVISDTASLCYSILKAKNAGMSLGAKGAAGPLPSEAVQWLCHQAFLL
KLTRHRVTYVPLLGSLRTAQTQLSRKLPGTTLTALEAAANPALPSDFKTILD
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.
Tissue Specificity 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.
KEGG Pathway
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Pathways in cancer (hsa05200 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Reactome Pathway
Formation of the beta-catenin (R-HSA-201722 )
Telomere Extension By Telomerase (R-HSA-171319 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Dyskeratosis congenita, autosomal dominant 2 DISPG5HC Definitive Semidominant [1]
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1 DISXRXK7 Definitive Autosomal dominant [2]
Acute myelogenous leukaemia DISCSPTN Strong Autosomal dominant [3]
Dyskeratosis congenita DISSXV0K Supportive Autosomal dominant [4]
Hoyeraal-Hreidarsson syndrome DISAUR8F Supportive Autosomal dominant [5]
Melanoma, cutaneous malignant, susceptibility to, 9 DISJVXNY Limited Autosomal dominant [2]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Telomerase reverse transcriptase (TERT) decreases the response to substance of Temozolomide. [59]
DTI-015 DMXZRW0 Approved Telomerase reverse transcriptase (TERT) decreases the response to substance of DTI-015. [59]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Telomerase reverse transcriptase (TERT). [6]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the methylation of Telomerase reverse transcriptase (TERT). [40]
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61 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Telomerase reverse transcriptase (TERT). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Telomerase reverse transcriptase (TERT). [8]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Telomerase reverse transcriptase (TERT). [9]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Telomerase reverse transcriptase (TERT). [10]
Arsenic DMTL2Y1 Approved Arsenic increases the expression of Telomerase reverse transcriptase (TERT). [11]
Quercetin DM3NC4M Approved Quercetin increases the expression of Telomerase reverse transcriptase (TERT). [12]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Telomerase reverse transcriptase (TERT). [13]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide decreases the expression of Telomerase reverse transcriptase (TERT). [14]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Telomerase reverse transcriptase (TERT). [15]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Telomerase reverse transcriptase (TERT). [15]
Decitabine DMQL8XJ Approved Decitabine decreases the activity of Telomerase reverse transcriptase (TERT). [16]
Selenium DM25CGV Approved Selenium decreases the expression of Telomerase reverse transcriptase (TERT). [17]
Fulvestrant DM0YZC6 Approved Fulvestrant decreases the expression of Telomerase reverse transcriptase (TERT). [18]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Telomerase reverse transcriptase (TERT). [19]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Telomerase reverse transcriptase (TERT). [20]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Telomerase reverse transcriptase (TERT). [21]
Aspirin DM672AH Approved Aspirin increases the expression of Telomerase reverse transcriptase (TERT). [22]
Paclitaxel DMLB81S Approved Paclitaxel decreases the expression of Telomerase reverse transcriptase (TERT). [23]
Sodium lauryl sulfate DMLJ634 Approved Sodium lauryl sulfate decreases the expression of Telomerase reverse transcriptase (TERT). [24]
Mitomycin DMH0ZJE Approved Mitomycin decreases the expression of Telomerase reverse transcriptase (TERT). [25]
Azacitidine DMTA5OE Approved Azacitidine decreases the expression of Telomerase reverse transcriptase (TERT). [26]
Gemcitabine DMSE3I7 Approved Gemcitabine decreases the activity of Telomerase reverse transcriptase (TERT). [27]
Zidovudine DM4KI7O Approved Zidovudine decreases the activity of Telomerase reverse transcriptase (TERT). [28]
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Telomerase reverse transcriptase (TERT). [29]
Gefitinib DM15F0X Approved Gefitinib decreases the expression of Telomerase reverse transcriptase (TERT). [30]
Glutathione DMAHMT9 Approved Glutathione increases the expression of Telomerase reverse transcriptase (TERT). [31]
Abacavir DMMN36E Approved Abacavir decreases the activity of Telomerase reverse transcriptase (TERT). [32]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Telomerase reverse transcriptase (TERT). [33]
Berberine DMC5Q8X Phase 4 Berberine decreases the activity of Telomerase reverse transcriptase (TERT). [34]
Resveratrol DM3RWXL Phase 3 Resveratrol decreases the expression of Telomerase reverse transcriptase (TERT). [35]
Epigallocatechin gallate DMCGWBJ Phase 3 Epigallocatechin gallate decreases the expression of Telomerase reverse transcriptase (TERT). [36]
Curcumin DMQPH29 Phase 3 Curcumin decreases the activity of Telomerase reverse transcriptase (TERT). [37]
Camptothecin DM6CHNJ Phase 3 Camptothecin increases the expression of Telomerase reverse transcriptase (TERT). [31]
Buparlisib DM1WEHC Phase 3 Buparlisib decreases the expression of Telomerase reverse transcriptase (TERT). [38]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Telomerase reverse transcriptase (TERT). [35]
phorbol 12-myristate 13-acetate DMJWD62 Phase 2 phorbol 12-myristate 13-acetate decreases the expression of Telomerase reverse transcriptase (TERT). [39]
Puerarin DMJIMXH Phase 2 Puerarin decreases the expression of Telomerase reverse transcriptase (TERT). [35]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Telomerase reverse transcriptase (TERT). [41]
VS-5584 DMMO3G5 Phase 1 VS-5584 decreases the expression of Telomerase reverse transcriptase (TERT). [42]
Sphingosine DMO1FTI Phase 1 Sphingosine affects the activity of Telomerase reverse transcriptase (TERT). [43]
MANUMYCIN A DM1SWOY Terminated MANUMYCIN A decreases the expression of Telomerase reverse transcriptase (TERT). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Telomerase reverse transcriptase (TERT). [45]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Telomerase reverse transcriptase (TERT). [46]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Telomerase reverse transcriptase (TERT). [19]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Telomerase reverse transcriptase (TERT). [47]
Deguelin DMXT7WG Investigative Deguelin decreases the expression of Telomerase reverse transcriptase (TERT). [48]
D-glucose DMMG2TO Investigative D-glucose decreases the activity of Telomerase reverse transcriptase (TERT). [49]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Telomerase reverse transcriptase (TERT). [50]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the expression of Telomerase reverse transcriptase (TERT). [51]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug decreases the expression of Telomerase reverse transcriptase (TERT). [52]
ELLAGIC ACID DMX8BS5 Investigative ELLAGIC ACID increases the expression of Telomerase reverse transcriptase (TERT). [18]
(E)-4-(3,5-dimethoxystyryl)phenol DMYXI2V Investigative (E)-4-(3,5-dimethoxystyryl)phenol decreases the expression of Telomerase reverse transcriptase (TERT). [53]
Choline DM5D9YK Investigative Choline affects the expression of Telomerase reverse transcriptase (TERT). [54]
Staurosporine DM0E9BR Investigative Staurosporine decreases the activity of Telomerase reverse transcriptase (TERT). [43]
MANGIFERIN DMWAF5Z Investigative MANGIFERIN decreases the activity of Telomerase reverse transcriptase (TERT). [55]
HONOKIOL DMJWT3X Investigative HONOKIOL decreases the expression of Telomerase reverse transcriptase (TERT). [56]
Aniline DMLCAR9 Investigative Aniline decreases the expression of Telomerase reverse transcriptase (TERT). [57]
RO-316233 DMAGLPW Investigative RO-316233 decreases the activity of Telomerase reverse transcriptase (TERT). [43]
(S)-DHPA DMQSC21 Investigative (S)-DHPA increases the expression of Telomerase reverse transcriptase (TERT). [26]
5-(2-methylpiperazin-1-ylsulfonyl)isoquinoline DMV3KBE Investigative 5-(2-methylpiperazin-1-ylsulfonyl)isoquinoline decreases the activity of Telomerase reverse transcriptase (TERT). [43]
BOLDINE DMMVB5P Investigative BOLDINE decreases the activity of Telomerase reverse transcriptase (TERT). [58]
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⏷ Show the Full List of 61 Drug(s)

References

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