InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TERT

Summary

InnateDB Protein

IDBP-11004.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TERT

Protein Name

telomerase reverse transcriptase

Synonyms

CMM9; DKCA2; DKCB4; EST2; hEST2; hTRT; PFBMFT1; TCS1; TP2; TRT;

Species

Homo sapiens

Ensembl Protein

ENSP00000334346

InnateDB Gene

IDBG-10998 (TERT)

Protein Structure

UniProt Annotation

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:0000269PubMed:14963003, ECO:0000269PubMed:15082768, ECO:0000269PubMed:15857955, ECO:0000269PubMed:17026956, ECO:0000269PubMed:17264120, ECO:0000269PubMed:17296728, ECO:0000269PubMed:17548608, ECO:0000269PubMed:19188162, ECO:0000269PubMed:19567472, ECO:0000269PubMed:19571879, ECO:0000269PubMed:19777057, ECO:0000269PubMed:9389643}.

Subcellular Localization

Nucleus, nucleolus. 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.

Disease Associations

Note=Activation of telomerase has been implicated in cell immortalization and cancer cell pathogenesis.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:0000269PubMed:15885610, ECO:0000269PubMed:16627250, ECO:0000269PubMed:16990594, ECO:0000269PubMed:19760749}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Note=Genetic variations in TERT are associated with coronary artery disease (CAD).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:0000269PubMed:15885610, ECO:0000269PubMed:16247010}. Note=The disease is caused by mutations affecting the gene represented in this entry.Pulmonary fibrosis, and/or bone marrow failure, telomere- related, 1 (PFBMFT1) [MIM:614742]: A 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:0000269PubMed:15814878, ECO:0000269PubMed:17460043, ECO:0000269PubMed:21436073, ECO:0000269PubMed:21483807, ECO:0000269PubMed:22512499}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:16332973, ECO:0000269PubMed:17785587, ECO:0000269PubMed:18042801}. Note=The disease is caused by mutations affecting the gene represented in this entry.Pulmonary fibrosis, idiopathic (IPF) [MIM:178500]: A lung disease characterized by shortness of breath, radiographically evident diffuse pulmonary infiltrates, and varying degrees of inflammation and fibrosis on biopsy. In some cases, the disorder can be rapidly progressive and characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.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 also may involve other sites. {ECO:0000269PubMed:23348503}. Note=Disease susceptibility is associated with variations 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. {ECO:0000269PubMed:8676067, ECO:0000269PubMed:9389643}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 97 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	97 [view]
Protein-Protein	96 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003720	telomerase activity
GO:0003721	telomeric template RNA reverse transcriptase activity
GO:0003964	RNA-directed DNA polymerase activity
GO:0005515	protein binding
GO:0042162	telomeric DNA binding
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding
GO:0070034	telomeric RNA binding

Biological Process

GO:0000723	telomere maintenance
GO:0007004	telomere maintenance via telomerase
GO:0022616	DNA strand elongation
GO:0032203	telomere formation via telomerase
GO:0090399	replicative senescence
GO:2001240	negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Cellular Component

GO:0000781	chromosome, telomeric region
GO:0000783	nuclear telomere cap complex
GO:0005654	nucleoplasm
GO:0005697	telomerase holoenzyme complex
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0016605	PML body