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In yeast, five gene products are required for telomerase activity in vivo: Est2p (the catalytic reverse transcriptase subunit), TLC1 (the template RNA), Est1p, Est3p and Cdc13p. Mutations in any of these five genes lead to progressive telomere shortening, the so-called ever shorter telomeres (EST) phenotype, followed by cell death. CDC13 is the only essential gene among the EST genes. Est2p and TLC1 form the catalytic core of telomerase, while Est1p, Est3p and Cdc13p which are dispensable for in vitro telomerase catalytic activity, play regulatory roles (6, 7, 11, 14, 16 and references therein). Cdc13p, a single stranded DNA binding protein required for telomere maintenance and elongation, binds to Est1p and this interaction is necessary for recruiting telomerase to the chromosomal ends. Est1p, Est2p and Est3p all bind to the TLC1 RNA template and Est1p also binds to 3' ends of single stranded DNA. Est1p forms a stable complex with TLC1 in the absence of Est2p or Est3p while association of Est3p with the enzyme requires an intact catalytic core. Est1p and Est3p are stable components of the telomerase holoenzyme (14).Although Est2p is associated with telomeres during late G1 and early S phase and telomerase activity can be detected throughout the cell cycle, telomere elongation is restricted to late S phase (8), suggesting that telomerase activity is regulated by the cell-cycle machinery. It has been proposed that Est1p, whose abundance is cell-cycle regulated, plays a role in activating Est2p during late S phase. In this model, Est1p binds to the TLC1 RNA of the Est2p-TLC1 core complex and then interacts with Cdc13p to convert the inactive telomere-bound Est2p to an active form (9, 12, 8, 9, 14). The telomerase recruitment step is regulated by the yeast ku heterodimer (Yku70p-Yku80p), and Stn1p which impart positive and negative control on the Cdc13p-Est1p interaction (16, 17). The telomere elongation activity is regulated, to avoid unlimited elongation of the telomere ends by a negative feedback mechanism that inhibits telomerase activity when shortened telomeres return to their equilibrium length. This negative feedback is mediated by a protein counting mechanism that can count the precise number of Rap1p molecules bound to a telomere (18, 19).Est2p is a homolog of p123, a telomerase protein, from the ciliated protozoan Euplotes aediculatus, which contains reverse transcriptase (RT) motifs. EST2 and p123 represent a new class of reverse transcriptase related to group II introns and non Long-terminal-repeat retrotransposons, and not related to RTs from retroviruses. Single amino acid substitutions within the reverse transcriptase motifs of Est2 protein lead to telomere shortening and senescence in yeast, indicating that these motifs are important for catalysis (7, 10, 13). Homologues of Est2p have been identified in human and S. pombe (11).In humans, telomere length is linked to aging and cancer: in human germline cells telomeres are long, whereas in cells of somatic tissues, telomerase activity is absent and the telomeres are short. Upon sufficient shortening, the somatic cells stop dividing and become senescent. Inappropriate telomerase activity is detected in most malignant tumors, and the genes required for telomerase activity are potential targets for cancer therapy (5, 7).

Human orthologs for four of the telomerase subunits are known. Est2p, the telomerase reverse transcriptase catalytic enzyme, is similar to TERT (OMIM), TLC1, the template RNA is similar to TERC/hTR (OMIM), while Cdc13p shares sequence similarity with human POT1 (OMIM) (4, 11). There are three Est1p like proteins in humans, although only hEST1A and hEST1B have been shown to be associated with the telomerase (15). A human ortholog for EST3 hasn't been identified. Mutations in TERT (OMIM) and TERC/hTR (OMIM) cause short telomeres and congenital aplastic anemia (OMIM, 4).", "date_edited": "2007-06-07"}, "literature_overview": {"primary_count": 121, "additional_count": 116, "review_count": 78, "go_count": 6, "phenotype_count": 6, "disease_count": 0, "interaction_count": 79, "regulation_count": 2, "ptm_count": 4, "funComplement_count": 0, "htp_count": 22, "total_count": 365}, "disease_overview": {"manual_disease_terms": [], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": null}, "ecnumbers": [{"display_name": "2.7.7.49", "link": "/ecnumber/EC:2.7.7.49"}], "URS_ID": null, "main_strain": "S288C", "regulation_overview": {"regulator_count": 2, "target_count": 0}, "reference_mapping": {"636339": 1, "605791": 2, "561950": 3, "532875": 4, "610800": 5, "583609": 6, "632043": 7, "610756": 8, "560382": 9, "646017": 10, "540136": 11, "645483": 12, "620087": 13, "551046": 14, "545077": 15, "548617": 16, "592067": 17, "639391": 18, "641496": 19}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: EST2", "date_created": "2000-05-19", "references": [{"id": 636339, "display_name": "Lendvay TS, et al. (1996)", "citation": "Lendvay TS, et al. (1996) Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144(4):1399-412", "pubmed_id": 8978029, "link": "/reference/S000043619", "year": 1996, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1093/genetics/144.4.1399"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1207693/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/8978029"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: TERT", "date_created": "2010-02-16", "references": []}, {"category": "Nomenclature conflict", "history_type": "LSP", "note": "Nomenclature conflict: The name EST2 has been used to describe both EST2/YLR318W, the catalytic subunit of telomerase, and IAH1/YOR126C, an isoamyl acetate-hydrolyzing esterase.", "date_created": "2003-12-09", "references": []}, {"category": "Nomenclature history", "history_type": "LSP", "note": "Nomenclature history: The name EST2 was once used by Fukuda, K, et al. (1998) for the gene now referred to as IAH1/YOR126C, an isoamyl acetate-hydrolyzing esterase. The EST2 name is generally used for the gene EST2/YLR318W, encoding the catalytic subunit of telomerase.", "date_created": "2003-02-12", "references": [{"id": 592432, "display_name": "Fukuda K, et al. (1998)", "citation": "Fukuda K, et al. (1998) Brewing properties of sake yeast whose EST2 gene encoding isoamyl acetate-hydrolyzing esterase was disrupted J Ferment Bioeng 85(1):101-106", "pubmed_id": null, "link": "/reference/S000058506", "year": 1998, "urls": []}]}, {"category": "Mapping", "history_type": "SEQUENCE", "note": "Mapping: Edition 13: The gene name EST2 has also been used to refer to the IAH1 isoamyl acetate hydrolytic enzyme gene located on chromosome XV", "date_created": "1996-09-21", "references": [{"id": 542519, "display_name": "Cherry JM, et al. (1996)", "citation": "Cherry JM, et al. (1996) \"Genetic and Physical Maps of Saccharomyces cerevisiae (Edition 13)\". Pp. 361-364 in 1996 Yeast Genetics and Molecular Biology Meeting Program and Abstracts. Bethesda, MD: The Genetics Society of America", "pubmed_id": null, "link": "/reference/S000076283", "year": 1996, "urls": []}]}, {"category": "Sequence change", "history_type": "SEQUENCE", "note": "Sequence change: Nucleotide change(s) in the coding region of EST2/YLR318W resulted in an altered protein sequence. The start, stop, and reading frame remain the same, but protein residue 162 is now Alanine rather than Valine.

\r\nNew    766978   AAATCGTGGGTAACAGATGTAACGAACCTCATCTGCCGCCCAAATGGGCTCAACGATCATCCTCATCATC  767047\r\n                ||||||||||||||||||||||||||||||||||||||||||||||||  ||||||||||||||||||||\r\nOld    766978   AAATCGTGGGTAACAGATGTAACGAACCTCATCTGCCGCCCAAATGGGTCCAACGATCATCCTCATCATC  767047", "date_created": "2011-02-03", "references": [{"id": 374815, "display_name": "Engel SR, et al. (2014)", "citation": "Engel SR, et al. (2014) The reference genome sequence of Saccharomyces cerevisiae: then and now. G3 (Bethesda) 4(3):389-98", "pubmed_id": 24374639, "link": "/reference/S000156273", "year": 2014, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1534/g3.113.008995"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962479/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/24374639"}]}]}], "complexes": [{"format_name": "CPX-3298", "display_name": "Telomerase holoenzyme complex"}]},
        tabs: {"id": 1286555, "protein_tab": true, "interaction_tab": true, "summary_tab": true, "go_tab": true, "sequence_section": true, "expression_tab": true, "phenotype_tab": true, "literature_tab": true, "wiki_tab": false, "regulation_tab": true, "sequence_tab": true, "history_tab": true, "homology_tab": true, "disease_tab": false}
    };


	
	
	
    
    
	
    EST2 | SGD
    
	
	
	









	
	

EST2 / YLR318W Overview


Standard Name
EST2 1
Systematic Name
YLR318W
SGD ID
SGD:S000004310
Aliases
TERT
Feature Type
ORF , Verified
Description
Reverse transcriptase subunit of the telomerase holoenzyme; essential for telomerase core catalytic activity, involved in other aspects of telomerase assembly and function; mutations in human homolog are associated with aplastic anemia 2 3 4
Name Description
Ever Shorter Telomeres 1
Comparative Info
Sequence Details

Sequence

The S. cerevisiae Reference Genome sequence is derived from laboratory strain S288C. Download DNA or protein sequence, view genomic context and coordinates. Click "Sequence Details" to view all sequence information for this locus, including that for other strains.


Protein Details

Protein

Basic sequence-derived (length, molecular weight, isoelectric point) and experimentally-determined (median abundance, median absolute deviation) protein information. Click "Protein Details" for further information about the protein such as half-life, abundance, domains, domains shared with other proteins, protein sequence retrieval for various strains, physico-chemical properties, protein modification sites, and external identifiers for the protein.


Length (a.a.)
884
Mol. Weight (Da)
102668.5
Isoelectric Point
9.68
Median Abundance (molecules/cell)
1154

Alleles

Curated mutant alleles for the specified gene, listed alphabetically. Click on the allele name to open the allele page. Click "SGD search" to view all alleles in search results.


View all EST2 alleles in SGD search

Gene Ontology Details

Gene Ontology

GO Annotations consist of four mandatory components: a gene product, a term from one of the three Gene Ontology (GO) controlled vocabularies (Molecular Function, Biological Process, and Cellular Component), a reference, and an evidence code. SGD has manually curated and high-throughput GO Annotations, both derived from the literature, as well as computational, or predicted, annotations. Click "Gene Ontology Details" to view all GO information and evidence for this locus as well as biological processes it shares with other genes.


Summary
Reverse transcriptase subunit of the telomerase holoenzyme involved in telomerase-dependent telomere maintenance; localizes to nucleolus

View computational annotations

Molecular Function

Manually Curated

Biological Process

Manually Curated

Cellular Component

Manually Curated

Complex

Macromolecular complex annotations are imported from the Complex Portal. These annotations have been derived from physical molecular interaction evidence extracted from the literature and cross-referenced in the entry, or by curator inference from information on homologs in closely related species or by inference from scientific background.


Phenotype Details

Phenotype

Phenotype annotations for a gene are curated single mutant phenotypes that require an observable (e.g., "cell shape"), a qualifier (e.g., "abnormal"), a mutant type (e.g., null), strain background, and a reference. In addition, annotations are classified as classical genetics or high-throughput (e.g., large scale survey, systematic mutation set). Whenever possible, allele information and additional details are provided. Click "Phenotype Details" to view all phenotype annotations and evidence for this locus as well as phenotypes it shares with other genes.


Interaction Details

Interaction

Interaction annotations are curated by BioGRID and include physical or genetic interactions observed between at least two genes. An interaction annotation is composed of the interaction type, name of the interactor, assay type (e.g., Two-Hybrid), annotation type (e.g., manual or high-throughput), and a reference, as well as other experimental details. Click "Interaction Details" to view all interaction annotations and evidence for this locus, including an interaction visualization.


186 total interactions for 99 unique genes

Physical Interactions

  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 12
  • Affinity Capture-Western: 21
  • Co-localization: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 1

Genetic Interactions

  • Dosage Growth Defect: 2
  • Dosage Rescue: 8
  • Negative Genetic: 3
  • Phenotypic Enhancement: 49
  • Phenotypic Suppression: 34
  • Positive Genetic: 3
  • Synthetic Growth Defect: 24
  • Synthetic Lethality: 12
  • Synthetic Rescue: 14
Regulation Details

Regulation

The number of putative Regulators (genes that regulate it) and Targets (genes it regulates) for the given locus, based on experimental evidence. This evidence includes data generated through high-throughput techniques. Click "Regulation Details" to view all regulation annotations, shared GO enrichment among regulation Targets, and a regulator/target diagram for the locus.


Regulators
2
Targets
0
Expression Details

Expression

Expression data are derived from records contained in the Gene Expression Omnibus (GEO), and are first log2 transformed and normalized. Referenced datasets may contain one or more condition(s), and as a result there may be a greater number of conditions than datasets represented in a single clickable histogram bar. The histogram division at 0.0 separates the down-regulated (green) conditions and datasets from those that are up-regulated (red). Click "Expression Details" to view all expression annotations and details for this locus, including a visualization of genes that share a similar expression pattern.


Summary Paragraph

A summary of the locus, written by SGD Biocurators following a thorough review of the literature. Links to gene names and curated GO terms are included within the Summary Paragraphs.


Last Updated: 2007-06-07

Literature Details

Literature

All manually curated literature for the specified gene, organized into topics according to their relevance to the gene (Primary Literature, Additional Literature, or Review). Click "Literature Details" to view all literature information for this locus, including shared literature between genes.


Primary
121
Additional
116
Reviews
78

Resources


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