Recombinant Human Telomerase reverse transcriptase (TERT), partial

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

Subcellular Location

Nucleus, nucleolus; Nucleus, nucleoplasm; Nucleus; Chromosome, telomere; Cytoplasm; Nucleus, PML body

Disease Association

[Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis] | Aplastic anemia (AA) : 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. [Disease susceptibility is associated with variants affecting the gene represented in this entry] | [Genetic variations in TERT are associated with coronary artery disease (CAD)] | Dyskeratosis congenita, autosomal dominant, 2 (DKCA2) : 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. [The disease is caused by variants affecting the gene represented in this entry] | Pulmonary fibrosis, and/or bone marrow failure syndrome, telomere-related, 1 (PFBMFT1) : 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. [The disease is caused by variants affecting the gene represented in this entry] | Dyskeratosis congenita, autosomal recessive, 4 (DKCB4) : 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. [The disease is caused by variants affecting the gene represented in this entry] | Melanoma, cutaneous malignant 9 (CMM9) : 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. [Disease susceptibility is associated with variants affecting the gene represented in this entry]

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

Subunit

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)

• Meyerson M. et al. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. — Cell (1997)
• Nakamura T.M. et al. Telomerase catalytic subunit homologs from fission yeast and human. — Science (1997)
• Wick M. et al. Genomic organization and promoter characterization of the gene encoding the human telomerase reverse transcriptase (hTERT). — Gene (1999)
• Hisatomi H. et al. Expression profile of a gamma-deletion variant of the human telomerase reverse transcriptase gene. — Neoplasia (2003)
• Nagao K. et al. Differential alternative splicing expressions of telomerase reverse transcriptase in gastrointestinal cell lines. — Oncol. Rep. (2004)
• Londono-Vallejo J.A. et al. Sequence of a BAC carrying the entire hTERT gene. (OCT-)
• PubMed: CI-7CALKN8DBM7GF (OCT-)
• Schmutz J. et al. The DNA sequence and comparative analysis of human chromosome 5. — Nature (2004)