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FLASH GENE
Symbol TERT contributors: mct/ - updated : 11-09-2015
HGNC name telomerase reverse transcriptase
HGNC id 11730
Corresponding disease
DKC3 dyskeratosis congenita 3
Location 5p15.33      Physical location : 1.253.286 - 1.295.162
Synonym name
  • telomerase-associated protein 2
  • telomerase catalytic subunit 1
  • Synonym symbol(s) hEST2, TCS1, TP2, EST2, TRT, hTERT
    EC.number 2.7.7.49
    DNA
    TYPE virus associated
    STRUCTURE 41.88 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    cytosine-phosphate-guanine/HTF
    Binding site   transcription factor
    motif repetitive sequence   other
    text structure
  • consensus binding sites and CMYc binding site
  • a VNTR in intron 6
  • E box in the promoter
  • promoter region between -1623 and -1047 was responsible of its transcriptional suppression )
  • TERT promoter has been shown to promote TERT gene expression selectively in tumor cells but not in normal cells
  • promoter contains potential responsible elements for several direct and indirect negative transcriptional regulators, including Sp1/Sp3, AP1, WT1, MZF-2, CTCF, Mad1, Menin
  • MCRS1 binds to the TERT proximal promoter
  • promoter is regulated by multiple transcription factors (TFs) and its activity is dependent on the chromatin environment
  • KLF2 represses TERT transcription by binding to the putative promoter element
  • MAPPING cloned Y linked N status confirmed
    Map pter - [WI-9907 - D5S678 - D5S417 ] - cen
    Text [TERT ]
    Physical map
    KIAA1909 5p15.33 KIAA1909 protein LOC389257 5 similar to Hypothetical protein KIAA0014 LOC133957 5p15.33 similar to RIKEN cDNA 0610011N22 SDHA 5p15 succinate dehydrogenase complex, subunit A, flavoprotein (Fp) PDCD6 5pter programmed cell death 6 LOC389258 5 similar to protein phosphatase 4, regulatory subunit 2 LOC391733 5 similar to Microneme antigen AHRR 5p15.3 aryl-hydrocarbon receptor repressor SEC6 SLC9A3 5p15.3 solute carrier family 9 (sodium/hydrogen exchanger), isoform 3 LOC389259 5 LOC389259 FLJ20413 5p15.33 hypothetical protein FLJ20413 FLJ10565 5p15.33 hypothetical protein FLJ10565 p25 5p15.3 brain-specific protein p25 alpha LOC389260 5 similar to zinc finger, DHHC domain containing 11 LOC389261 5 similar to hypothetical protein ZDHHC11 5p15.2 zinc finger, DHHC domain containing 11 FLJ13441 TRIP13 5p15.2 thyroid hormone receptor interactor 13 LOC389262 5 LOC389262 NKD2 5p15.3 naked cuticle homolog 2 (Drosophila) SLC12A7 5p15.3 solute carrier family 12 (potassium/chloride transporters), member 7 LOC389263 5 hypothetical gene supported by AK096096 LOC340024 5p15.33 hypothetical protein LOC340024 FLJ31236 5p15.33 hypothetical protein FLJ31236 TERT 5p15.33 telomerase reverse transcriptase CRR9 5pter-p15.3 cisplatin resistance related protein CRR9p SLC6A3 5p15.3 solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 FLJ12443 5p15.33 hypothetical protein FLJ12443 LOC389264 5 LOC389264 LOC340026 5p15.33 similar to succinate dehydrogenase flavoprotein subunit LOC389265 5 hypothetical gene supported by NM_174907 LOC389266 5 LOC389266 MRPL36 5p15.3 mitochondrial ribosomal protein L36 NDUFS6 5pter-p15.33 NADH dehydrogenase (ubiquinone) Fe-S protein 6, 13kDa (NADH-coenzyme Q reductase) LOC389267 5 similar to antifreeze glycoprotein precursor - black rockcod IRX4 5p15.3 iroquois homeobox protein 4
    RNA
    TRANSCRIPTS type messenger
    text alternatively spliced variants resulting in exon(s) deletion, insertion, unspliced intron insertion or both (PMID: 9328464)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 4018 126 1132 - 2013 23933091
  • isoform 1
  • 16 splicing 3982 125 1120 - 2013 23933091
  • isoform 2
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     stomach    
    Lymphoid/Immunelymph node   highly
     thymus   moderately
    Reproductivefemale systemovary   
    Respiratorylung   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell null (stem cell)
    cell lineage
    cell lines epithelial cancer cell lines, many immortal cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal domain (TEN) that is important for activity and processivity, involved in conformational changes required to position the 3prime-end of the primer in the active site during nucleotide addition, a function which is distinct from the role of the TEN domain in providing DNA binding affinity
  • a reverse transcriptase domain (RT)
  • AAs 965-981 constitute an active nucleolar-targeting signal (NTS) essential for mediating TERT nucleolar localization
  • conjugated RiboP
    HOMOLOGY
    interspecies homolog to rattus Tert (64.42 pc)
    homolog to murine Tert (64.32 pc)
    Homologene
    FAMILY
  • reverse transcriptase family
  • telomerase subfamily
  • CATEGORY enzyme , DNA associated , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,telomere
    intracellular,nucleus,nucleolus
    text
  • restricted to the nucleus, had an antiapoptotic effect
  • mitochondrial, induces apoptosis after oxidative stress
  • nucleolar localization is unrelated to telomerase function in cells
  • in primary cells, is released into the nucleoplasm during the late S/G2 stage of the cell cycle, coincident with the replication of telomeres
  • NVL interacts and co-localizes with TERT in the nucleolus, and TERT was predominantly co-localized with NVL2 in the nucleolus
  • TERT shuttles from the nucleus into mitochondria upon oxidative stress in cancer cells
  • basic FUNCTION
  • playing a crucial role in the immortality of tumor cells
  • involved in telomere maintenance and participating in the regulation of cell proliferation and replicative lifespan
  • putative upregulated c-Myc target gene
  • critical determinant in the mobilization of epidermal stem cells
  • essential component of telomerase production and of carcinogenesis
  • promotes cellular and organismal survival independently of telomerase activity
  • FEN1 and TERT complex could be participating in crucial events at telomeres, and understanding the role of this complex can pave way for telomerase based cancer therapeutics
  • essential role of TERT, and TERC in the hematopoietic system sugesting that telomerase levels in hematopoietic cells, while limiting and unable to prevent overall telomere shortening, are nevertheless crucial to maintain telomere homeostasis with age
  • activation of TERT is required for the maintenance of telomere length in cancer cells
  • TERT and TERC exert both reverse transcriptase-related (canonical) and noncanonical functions to affect tumor genome evolution through suppression or induction of polyploidization
  • telomere-independent role for telomerase as a transcriptional modulator of the NFKB signaling pathway and a possible contributor to cancer development and progression
  • TERT, a catalytic component of telomerase, plays dual roles in the TERF1 steady state pathway
  • novel function of TERT in telomere length regulation
  • its expression would function in counteracting against the stress because over-expression of TERT diminished ER stress-induced cell death
  • TPP1 and the TEN domain of the telomerase catalytic subunit TERT regulate telomerase recruitment
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    nucleotide, replication
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the telomerase complex, associating with NOLA1, NOLA2, NOLA3, NOLA4
  • forming with RMRP a ribonucleoprotein complex that has RNA-dependent RNA polymerase activity and produces double-strand RNAs
  • FEN1 forms a complex with telomerase in a cell cycle dependent manner
  • INTERACTION
    DNA
    RNA interacting with RMRP
    small molecule
    protein
  • binding to TERC
  • association with PINX1 within nucleoli might be through an indirect interaction and is mediated by a novel domain within the central region of PINX (interaction between PINX1 and TERT within the nucleolus might constitute a rapid responsive mechanism on telomerase functional modulation, important for cellular homeostasis)
  • interacting with SMYD3 (direct target of SMYD3 contributing to a SMYD3-mediated cellular transformation)
  • binding to SMAD3
  • interacting with SMARCA4 and activating Wnt/beta catenin signalling pathway
  • one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential
  • interacting with a putative gene on human chromosome 5 contributes to its transcriptional silencing
  • RUVBL2 is a transcriptional regulator of TERT
  • FEN1 and telomerase association occurs throughout the S phase, with the maximum association in the mid S phase (
  • DKC1 promotes TERT stability, endorsing the development of TERT supplementation strategies for the treatment of DKC1
  • NVL2 associates with catalytically competent telomerase through an interaction with TERT, and this association could be specific
  • TCF4 may bind to TERT promoter and activate TERT gene transcription upon forming a transcriptional complex with CTNNB1
  • during the cell cycle, DYRK2 interacts with TERT at the G2/M phase and induces degradation
  • DYRK2-associated DDB1-UBR5-VPRBP E3 ligase inhibits telomerase by TERT degradation
  • is a direct target of the HH signaling pathway, and HH signaling regulates telomerase reverse transcriptase in cancer cells
  • MCRS1 is a negative regulator of TERT expression and telomerase activity
  • DEK emerges as an TERT repressor shared by various leukemia subtypes and seems involved in the deregulation of numerous genes associated with leukemogenesis
  • PINX1 may maintain telomere integrity by regulating TERF1 stability and TERT may act as both a positive and a negative regulator of TERF1 homeostasis in a PINX1-dependent manner
  • interaction between TERT and PTTG1 by association of XRCC6 might be important for the enhancement of the limited self-renewal activity of MSCs and for understanding the regulatory mechanisms of self-renewal
  • FOXO3 functions downstream of SIRT1 and prevents the induction of cellular senescence by enhancing TERT gene expression
  • MYC functioned in maintaining chromatin-dependent repression of the TERT gene in addition to activating its promoter
  • stability of PINX1 is maintained in nucleolus in the presence of TERT, suggesting a role of TERT in the regulation of PINX1 steady-state levels
  • cell & other
    REGULATION
    induced by MYC
    inhibited by MAD1L1
    repressed by MEN1
    SIP1
    PRKCD, which function in telomerase reverse transcriptase (TERT) gene repression
    Other regulated by DNA methylation of the promoter region
    regulated by FRK
    regulated by truncated USF2 during lymphocyte activation
    condensed chromatin environment plays a role in silencing TERT during cell differentiation
    strongly repressed during differentiation of cells
    ASSOCIATED DISORDERS
    corresponding disease(s) DKC3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in cancer
    tumoral     --over  
    with BIRC5 in soft tissue sarcoma with very poor outlook
    constitutional somatic mutation      
    impair telomerase activity by haploinsufficiency and may be risk factors for marrow failure
    constitutional     --over  
    increases stem-like properties and decreases spontaneous differentiation in human mesenchymal stem cell lines
    tumoral somatic mutation      
    in 71p 100 of melanomas (pMID: 23348506)
    tumoral germinal mutation      
    mutations creating Ets/TCF binding motifs in the TERT promoter in familial melanoma
    Susceptibility
  • susceptibility to idiopathic pulmonary fibrosis
  • to lung adenocarcinoma
  • to squamous cell carcinoma of the head and neck
  • to haematological malignancies, including myelodysplastic syndrome and acute myeloid leukaemia as well as chronic lymphocytic leukaemia
  • to age-related disease idiopathic pulmonary fibrosis with telomere shortening
  • to testicular germ cell tumor (TGCT)
  • to variation of telomere length
  • Variant & Polymorphism SNP
  • significant association of an SNP in intron 2 of the TERT gene (rs2736100), which encodes a reverse transcriptase that is a component of a telomerase, to idiopathic pulmonary fibrosis
  • variants in TERT can impede telomere elongation causing stem cells to enter premature replicative senescence and/or apoptosis as telomeres become critically short
  • SNPs of TERT-rs2736098 (C > T) and CLPTM1L-rs401681(C > T), may be associated with a reduced risk of squamous cell carcinoma of the head and neck, particularly for their combined effect
  • rs2736100 associated with risk of lung adenocarcinoma
  • association between genetic marker rs2735940 and TGCT risk
  • variants associated with increased risk of haematological malignancies, including myelodysplastic syndrome and acute myeloid leukaemia as well as chronic lymphocytic leukaemia
  • two non-synonymous substitutions in the catalytic domain of the telomerase reverse transcriptase gene TERT: V791I and V867M increasing the risk of age-related disease idiopathic pulmonary fibrosis with telomere shortening
  • Candidate gene
    Marker
    Therapy target
  • TERT gene-based drug design may be useful in the treatment of leukemic myelopoiesis
  • ANIMAL & CELL MODELS
  • mouse lacking telomerase activity display decrease proliferation in testis and increased apoptosis