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    RAD9A RAD9 checkpoint clamp component A [ Homo sapiens (human) ]

    Gene ID: 5883, updated on 16-Apr-2024

    Summary

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    Official Symbol
    RAD9Aprovided by HGNC
    Official Full Name
    RAD9 checkpoint clamp component Aprovided by HGNC
    Primary source
    HGNC:HGNC:9827
    See related
    Ensembl:ENSG00000172613 MIM:603761; AllianceGenome:HGNC:9827
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    RAD9
    Summary
    This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair. This protein possesses 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. It forms a checkpoint protein complex with RAD1 and HUS1. This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in spleen (RPKM 9.1), skin (RPKM 8.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11q13.2
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (67391986..67398412)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (67386101..67392527)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (67159457..67165883)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100130987 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5088 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5089 Neighboring gene RN7SK pseudogene 239 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67134979-67135478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3626 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3627 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3628 Neighboring gene cardiotrophin like cytokine factor 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67146845-67147566 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5090 Neighboring gene hESC enhancers GRCh37_chr11:67158624-67159539 and GRCh37_chr11:67159574-67160078 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67164978-67165559 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:67165560-67166140 Neighboring gene RNA, U6 small nuclear 1238, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3630 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5091 Neighboring gene protein phosphatase 1 catalytic subunit alpha Neighboring gene TBC1 domain family member 10C Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5092 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67179513-67180014 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67180015-67180514 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:67183887-67184722 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3631 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3632 Neighboring gene carnosine synthase 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9. Chen KY, et al. PLoS One, 2019. PMID 31310624, Free PMC Article
    2. The checkpoint clamp protein Rad9 facilitates DNA-end resection and prevents alternative non-homologous end joining. Tsai FL, et al. Cell Cycle, 2014. PMID 25485590, Free PMC Article
    3. Checkpoint protein Rad9 plays an important role in nucleotide excision repair. Li T, et al. DNA Repair (Amst), 2013 Apr 1. PMID 23433811
    4. Reduced mRNA and protein expression of the genomic caretaker RAD9A in primary fibroblasts of individuals with childhood and independent second cancer. Weis E, et al. PLoS One, 2011. PMID 21991345, Free PMC Article
    5. Cell cycle-dependent processing of DNA lesions controls localization of Rad9 to sites of genotoxic stress. Warmerdam DO, et al. Cell Cycle, 2009 Jun 1. PMID 19411845

    See all (137) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis for intra- and intermolecular interactions on RAD9 subunit of 9-1-1 checkpoint clamp implies functional 9-1-1 regulation by RHINO.
      Title: Structural basis for intra- and intermolecular interactions on RAD9 subunit of 9-1-1 checkpoint clamp implies functional 9-1-1 regulation by RHINO.
    2. DNMT1 and DNMT3B regulate tumorigenicity of human prostate cancer cells by controlling RAD9 expression through targeted methylation.
      Title: DNMT1 and DNMT3B regulate tumorigenicity of human prostate cancer cells by controlling RAD9 expression through targeted methylation.
    3. Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases.
      Title: Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases.
    4. breast and lung tumor suppressive activities of resveratrol are, at least in part, mediated by the upregulation of Rad9 in a DNA damage response pathway involving reactive oxygen species
      Title: Resveratrol induced premature senescence and inhibited epithelial-mesenchymal transition of cancer cells via induction of tumor suppressor Rad9.
    5. RAD9A drives metastasis by controlling AGR2 abundance.
      Title: RAD9A promotes metastatic phenotypes through transcriptional regulation of anterior gradient 2 (AGR2).
    6. The authors show that human Cyclin-Dependent-Kinases (CDKs) target the RAD9 subunit of the 9-1-1 checkpoint clamp on Thr292, to modulate DNA damage checkpoint activation. Thr292 phosphorylation on RAD9 creates a binding site for Polo-Like-Kinase1 (PLK1), which phosphorylates RAD9 on Thr313.
      Title: The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress.
    7. TLK1B mediated phosphorylation of Rad9 regulates its nuclear/cytoplasmic localization and cell cycle checkpoint
      Title: TLK1B mediated phosphorylation of Rad9 regulates its nuclear/cytoplasmic localization and cell cycle checkpoint.
    8. RAD9 has a prominent role in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.
      Title: Regulation of ATRIP protein abundance by RAD9 in the DNA damage repair pathway.
    9. these results demonstrate a positive feedback loop involving Rad9A-dependend activation of Chk1.
      Title: Chk1 Activation Protects Rad9A from Degradation as Part of a Positive Feedback Loop during Checkpoint Signalling.
    10. Intramolecular binding of the rad9 C-terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding.
      Title: Intramolecular Binding of the Rad9 C Terminus in the Checkpoint Clamp Rad9-Hus1-Rad1 Is Closely Linked with Its DNA Binding.
    Submit: New GeneRIF Correction See all GeneRIFs (66)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3'-5' exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables SH3 domain binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables double-stranded DNA 3'-5' DNA exonuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables histone deacetylase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage checkpoint signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in DNA replication checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to ionizing radiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to ionizing radiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in intrinsic apoptotic signaling pathway in response to DNA damage IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in mitotic intra-S DNA damage checkpoint signaling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of checkpoint clamp complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of checkpoint clamp complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cell cycle checkpoint control protein RAD9A
    Names
    DNA repair exonuclease rad9 homolog A
    RAD9 homolog A
    hRAD9
    NP_001230153.1
    NP_004575.1
    XP_006718715.1
    XP_016873587.1
    XP_047283337.1
    XP_047283338.1
    XP_047283339.1
    XP_054225560.1
    XP_054225561.1
    XP_054225562.1
    XP_054225563.1
    XP_054225564.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001243224.1 → NP_001230153.1  cell cycle checkpoint control protein RAD9A isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate 5' terminal exon (with an in-frame AUG) compared to variant 1. This results in a a shorter isoform (2) with a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AA708970, CB164642, CN402466, U53174
      UniProtKB/Swiss-Prot
      Q99638
      Conserved Domains (1) summary
      cl24017
      Location:1 → 191
      PCNA; Proliferating Cell Nuclear Antigen (PCNA) domain found in eukaryotes and archaea. These polymerase processivity factors play a role in DNA replication and repair. PCNA encircles duplex DNA in its central cavity, providing a DNA-bound platform for the ...

    2. NM_004584.3 → NP_004575.1  cell cycle checkpoint control protein RAD9A isoform 1

      See identical proteins and their annotated locations for NP_004575.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes the longer isoform (1).
      Source sequence(s)
      AA708970, BC014848, U53174
      Consensus CDS
      CCDS8159.1
      UniProtKB/Swiss-Prot
      B2RCZ8, Q6FI29, Q96C41, Q99638
      Related
      ENSP00000311360.2, ENST00000307980.7
      Conserved Domains (1) summary
      pfam04139
      Location:13 → 265
      Rad9; Rad9

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      67391986..67398412
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047427382.1 → XP_047283338.1  cell cycle checkpoint control protein RAD9A isoform X3

    2. XM_047427383.1 → XP_047283339.1  cell cycle checkpoint control protein RAD9A isoform X4

    3. XM_047427381.1 → XP_047283337.1  cell cycle checkpoint control protein RAD9A isoform X2

    4. XM_006718652.4 → XP_006718715.1  cell cycle checkpoint control protein RAD9A isoform X1

      Conserved Domains (2) summary
      cd00577
      Location:47 → 278
      PCNA; Proliferating Cell Nuclear Antigen (PCNA) domain found in eukaryotes and archaea. These polymerase processivity factors play a role in DNA replication and repair. PCNA encircles duplex DNA in its central cavity, providing a DNA-bound platform for the ...
      pfam04139
      Location:46 → 276
      Rad9; Rad9

    5. XM_017018098.2 → XP_016873587.1  cell cycle checkpoint control protein RAD9A isoform X5

      Related
      ENST00000535644.1
      Conserved Domains (1) summary
      cl24017
      Location:1 → 75
      PCNA; Proliferating Cell Nuclear Antigen (PCNA) domain found in eukaryotes and archaea. These polymerase processivity factors play a role in DNA replication and repair. PCNA encircles duplex DNA in its central cavity, providing a DNA-bound platform for the ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      67386101..67392527
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369587.1 → XP_054225562.1  cell cycle checkpoint control protein RAD9A isoform X3

    2. XM_054369588.1 → XP_054225563.1  cell cycle checkpoint control protein RAD9A isoform X4

    3. XM_054369586.1 → XP_054225561.1  cell cycle checkpoint control protein RAD9A isoform X2

    4. XM_054369585.1 → XP_054225560.1  cell cycle checkpoint control protein RAD9A isoform X1

    5. XM_054369589.1 → XP_054225564.1  cell cycle checkpoint control protein RAD9A isoform X5

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q99638.1 GenPept UniProtKB/Swiss-Prot:Q99638

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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