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Some of the identified targets of Rad53p are the transcriptional regulator Swi6p and the kinases Dun1p and Dbf4p. Activation of these particular targets by Rad53p leads to G1 cyclin induction, ribonucleotide reductase activation, and inhibition of late firing of DNA replication origins, respectively (20, 26, 27, 28).Rad53p activation occurs both through autophosphorylation and direct phosphorylation by Mec1p (12, 13). Rad53p autophosphorylation is dependent on the presence of Mec1p, and Mec1p-mediated direct phosphorylation appears to depend on the presence of Rad9p (13, 15). Rad9p binds to two Rad53p forkhead-associated (FHA) domains, modular domains that facilitate protein-protein interactions, making Rad53p a suitable substrate for Mec1p (15, 18). The Rad53p N-terminal FHA domain is the interaction site for the type 2C phosphatases Ptc2p and Ptc3p, implicated inhibitors of Rad53p function (19). RAD53 expression has also been shown to depend on the presence of Rad9p (21).

Loss of Rad53p leads to multiple defects, including impaired checkpoint activation, inability to recover from replication blocks, X-ray sensitivity, and excess histone accumulation resulting in slow growth and chromosome loss (14, 22, 25, 24). RAD53 is the homolog of S. pombe CDS1 and human CHK2 (OMIM; 29, 30). Mutations in the human tumor suppressor CHK2 have been associated with sporadic cancer as well as familial breast cancer and Li-Fraumeni syndrome (OMIM; 31, 8).", "date_edited": "2006-03-24"}, "literature_overview": {"primary_count": 350, "additional_count": 430, "review_count": 206, "go_count": 9, "phenotype_count": 14, "disease_count": 3, "interaction_count": 291, "regulation_count": 17, "ptm_count": 13, "funComplement_count": 5, "htp_count": 20, "total_count": 1096}, "disease_overview": {"manual_disease_terms": [{"annotation_type": "manually curated", "qualifiers": [null], "term": {"link": "/disease/DOID:1612", "display_name": "breast cancer"}, "evidence_codes": [{"display_name": "ISS", "link": "http://wiki.geneontology.org/index.php/Inferred_from_Sequence_or_structural_Similarity_(ISS)"}, {"display_name": "IGI", "link": "http://wiki.geneontology.org/index.php/Inferred_from_Genetic_Interaction_(IGI)"}, {"display_name": "IMP", "link": "http://wiki.geneontology.org/index.php/Inferred_from_Mutant_Phenotype_(IMP)"}]}], "htp_disease_terms": [], "computational_annotation_count": 0, "date_last_reviewed": "2022-04-12", "paragraph": "Yeast RAD53 is homologous to human CHEK2, and has been used to study breast cancer"}, "ecnumbers": [{"display_name": "2.7.12.1", "link": "/ecnumber/EC:2.7.12.1"}], "URS_ID": null, "main_strain": "S288C", "genetic_position": -109.0, "regulation_overview": {"regulator_count": 10, "target_count": 77}, "reference_mapping": {"596211": 1, "561422": 2, "553600": 3, "517231": 4, "397497": 5, "374708": 6, "383850": 7, "535105": 8, "312334": 9, "410701": 10, "604767": 11, "525783": 12, "645474": 13, "613620": 14, "529531": 15, "592929": 16, "563830": 17, "618652": 18, "552176": 19, "605955": 20, "607940": 21, "553074": 22, "593909": 23, "547520": 24, "576085": 25, "537485": 26, "554479": 27, "647160": 28, "575938": 29, "615748": 30, "575932": 31, "641019": 32}, "history": [{"category": "Name", "history_type": "LSP", "note": "Name: LSD1", "date_created": "2010-02-16", "references": []}, {"category": "Name", "history_type": "LSP", "note": "Name: MEC2", "date_created": "2010-02-16", "references": [{"id": 604767, "display_name": "Weinert TA, et al. (1994)", "citation": "Weinert TA, et al. (1994) Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 8(6):652-65", "pubmed_id": 7926756, "link": "/reference/S000054274", "year": 1994, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1101/gad.8.6.652"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/7926756"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: RAD53", "date_created": "2000-05-19", "references": [{"id": 596211, "display_name": "Game JC and Mortimer RK (1974)", "citation": "Game JC and Mortimer RK (1974) A genetic study of x-ray sensitive mutants in yeast. Mutat Res 24(3):281-92", "pubmed_id": 4606119, "link": "/reference/S000057188", "year": 1974, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1016/0027-5107(74)90176-6"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/4606119"}]}]}, {"category": "Name", "history_type": "LSP", "note": "Name: SPK1", "date_created": "2010-02-16", "references": [{"id": 641019, "display_name": "Stern DF, et al. (1991)", "citation": "Stern DF, et al. (1991) Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine. Mol Cell Biol 11(2):987-1001", "pubmed_id": 1899289, "link": "/reference/S000042043", "year": 1991, "urls": [{"display_name": "DOI full text", "link": "http://dx.doi.org/10.1128/mcb.11.2.987-1001.1991"}, {"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC359764/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/1899289"}]}]}, {"category": "Nomenclature conflict", "history_type": "LSP", "note": "Nomenclature conflict: SAD1 has been used to refer to both RAD53/YPL153C, a checkpoint protein involved in DNA repair, and SAD1/YFR005C, a protein involved in mRNA splicing.", "date_created": "2003-12-09", "references": []}, {"category": "Mapping", "history_type": "SEQUENCE", "note": "Mapping: Edition 13: RAD53 has also been referred to as SAD1, but should not be confused with the SAD1 gene on chromosome III that appears to be involved in SnRNP assembly.", "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": "Mapping", "history_type": "SEQUENCE", "note": "Mapping: Edition 14: Although RAD53 has also been called SPK1, it is unrelated to the S. pombe SPK1 gene", "date_created": "1997-10-20", "references": [{"id": 587084, "display_name": "Cherry JM, et al. (1997)", "citation": "Cherry JM, et al. (1997) Genetic and physical maps of Saccharomyces cerevisiae. Nature 387(6632 Suppl):67-73", "pubmed_id": 9169866, "link": "/reference/S000060841", "year": 1997, "urls": [{"display_name": "PMC full text", "link": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057085/"}, {"display_name": "PubMed", "link": "http://www.ncbi.nlm.nih.gov/pubmed/9169866"}]}]}], "complexes": [{"format_name": "CPX-1322", "display_name": "RAD53-ASF1 complex"}]}, tabs: {"id": 1282958, "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": true} }; RAD53 | SGD

RAD53 / YPL153C Overview


Standard Name
RAD53 1
Systematic Name
YPL153C
SGD ID
SGD:S000006074
Aliases
LSD1 , MEC2 11 , SPK1 32
Feature Type
ORF , Verified
Description
DNA damage response kinase; signal transduction pathway component required for DNA damage and replication checkpoints, promoting cell cycle arrest and DNA repair; role in initiation of DNA replication; inhibits gene gating through NPC protein phosphorylation, to promote fork stability; activates downstream kinase Dun1p; senses mtDNA depletion and mitochondrial ROS; relocalizes to cytosol under hypoxia; contains two FHA domains; human homolog CHEK2 implicated in breast cancer complements the null 2 3 4 5 6 7 8 9 10
Name Description
RADiation sensitive 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.)
821
Mol. Weight (Da)
91965.5
Isoelectric Point
7.94
Median Abundance (molecules/cell)
1533 +/- 520
Half-life (hr)
7.8

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 RAD53 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
Protein serine/threonine/tyrosine kinase that binds DNA replication origins; involved in the DNA damage checkpoint, DNA replication initiation, and the biosynthesis of deoxyribonucleoside triphosphates; localizes to the nucleus and the cytosol

View computational annotations

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.


Summary
Gene variously classified as essential and as non-essential; null and point mutants display sensitivity to DNA-damaging agents, including MMS, HU, UV light, and X-rays, and an abnormal mitotic cell cycle; apoptotic DNA degradation is more rapid in rad53-21 mutant than in wild type; in large-scale studies, replicative lifespan of the null mutant is shortened, while overexpression impedes growth
Disease Details

Disease

Disease Annotations consist of three mandatory components: a gene product, a term from the Disease Ontology (DO) controlled vocabulary and an evidence code. SGD provides manually curated DO Annotations derived from the literature. Click "Disease Details" to view all Disease information and evidence for this locus as well as diseases it shares with other genes.


Summary
Yeast RAD53 is homologous to human CHEK2, and has been used to study breast cancer

Manually Curated

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.


1364 total interactions for 780 unique genes

Physical Interactions

  • Affinity Capture-MS: 83
  • Affinity Capture-RNA: 5
  • Affinity Capture-Western: 73
  • Biochemical Activity: 101
  • Co-crystal Structure: 3
  • Co-localization: 2
  • Co-purification: 1
  • PCA: 1
  • Protein-peptide: 10
  • Proximity Label-MS: 206
  • Reconstituted Complex: 15
  • Two-hybrid: 33

Genetic Interactions

  • Dosage Growth Defect: 17
  • Dosage Lethality: 5
  • Dosage Rescue: 35
  • Negative Genetic: 280
  • Phenotypic Enhancement: 38
  • Phenotypic Suppression: 77
  • Positive Genetic: 35
  • Synthetic Growth Defect: 143
  • Synthetic Lethality: 71
  • Synthetic Rescue: 130
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
10
Targets
77
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: 2006-03-24

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
350
Additional
430
Reviews
206

Resources