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
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.
BLASTN |
BLASTP |
Design Primers |
Restriction Fragment Map |
Restriction Fragment Sizes |
Six-Frame Translation
BLASTN vs. fungi |
BLASTP at NCBI |
BLASTP vs. fungi
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.
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
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
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View computational annotations
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 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 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
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.
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.
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
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.
\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 / YLR318W Overview
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