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    MDC1 mediator of DNA-damage checkpoint 1 [ Homo sapiens ]

    Gene ID: 9656, updated on 11-May-2012
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    Summary

    Official Symbol
    MDC1provided by HGNC
    Official Full Name
    mediator of DNA-damage checkpoint 1provided by HGNC
    Primary source
    HGNC:21163
    Locus tag
    DAAP-285E11.7
    See related
    Ensembl:ENSG00000137337; HPRD:16252; MIM:607593; Vega:OTTHUMG00000031075
    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
    NFBD1; KIAA0170; MGC166888; DKFZp781A0122
    Summary
    The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    6p21.3
    Sequence :
    Chromosome: 6; NC_000006.11 (30667584..30685458, complement)
    See MDC1 in Epigenomics, MapViewer

    Chromosome 6 - NC_000006.11Genomic Context describing neighboring genes Neighboring gene nurim (nuclear envelope membrane protein) Neighboring gene ribosomal protein L7 pseudogene 4 Neighboring gene tubulin, beta class I Neighboring gene flotillin 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Dimerization, but not phosphothreonine binding, is conserved between the forkhead-associated domains of Drosophila MU2 and human MDC1. Luo S, et al. FEBS Lett, 2012 Feb 17. PMID 22273583.
    2. Structural delineation of MDC1-FHA domain binding with CHK2-pThr68. Wu HH, et al. Biochemistry, 2012 Jan 17. PMID 22211259.
    3. Identification of ubiquitinated proteins from human multiple myeloma U266 cells by proteomics. Jia H, et al. Biomed Environ Sci, 2011 Aug. PMID 22108332.
    4. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    5. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.

    See all (86) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. As compared to the MDC1 forkhead-associated FHA) domain, the MU2 FHA domain dimerizes using a different and more stable interface and contains a degenerate phosphothreonine-binding pocket.
      Title: Dimerization, but not phosphothreonine binding, is conserved between the forkhead-associated domains of Drosophila MU2 and human MDC1.
    2. MDC1 is required for the recruitment of RAP80 to DNA double-strand breaks.
      Title: Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80.
    3. structural insight into MDC1-CHK2 interaction
      Title: Structural delineation of MDC1-FHA domain binding with CHK2-pThr68.
    4. This study provides the first evidence that interactions involving MDC1 can be regulated by ubiquitylation
      Title: MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner.
    5. most NFBD1 regulated genes are regulated in both the absence and presence of IR, thus pointing toward a novel function for NFBD1 outside of the DNA damage response
      Title: NFBD1/MDC1 regulates Cav1 and Cav2 independently of DNA damage and p53.
    6. this study reveals that human NIPBL is a novel protein recruited to DSB sites, and the recruitment is controlled by MDC1, RNF168 and HP1gamma.
      Title: Recruitment of the cohesin loading factor NIPBL to DNA double-strand breaks depends on MDC1, RNF168 and HP1γ in human cells.
    7. The specific TopBP1-MDC1 interaction was mediated by the fifth BRCT domain of TopBP1 and the Ser-Asp-Thr repeats of MDC1. TopBP1 accumulation at stalled replication forks was promoted by the H2AX/MDC1 signaling cascade.
      Title: MDC1 collaborates with TopBP1 in DNA replication checkpoint control.
    8. Mediator of DNA damage checkpoint protein 1 (MDC1) has a role in nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy
      Title: Mediator of DNA damage checkpoint protein 1 (MDC1) expression as a prognostic marker for nodal recurrence in early-stage breast cancer patients treated with breast-conserving surgery and radiation therapy.
    9. Results implicate MDC1 in the cellular apoptotic response.
      Title: MDC1 cleavage by caspase-3: a novel mechanism for inactivating the DNA damage response during apoptosis.
    10. High NFBD1 is associated with esophageal cancer.
      Title: Growth inhibition, morphology change, and cell cycle alterations in NFBD1-depleted human esophageal cancer cells.
    Submit: New GeneRIF Correction See all (54)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Q14676 Q13315 ATM    HPRD  PubMed  
    Q14676 Q99728 BARD1    HPRD  PubMed  
    Q14676 P38398 BRCA1    HPRD  PubMed  
    Q14676 O96017 CHEK2    HPRD  PubMed  
    Q14676 Q92793 CREBBP    HPRD  PubMed  
    Q14676 Q09472 EP300    HPRD  PubMed  
    Q14676 P16104 H2AFX    HPRD  PubMed  
    Q14676 Q14676 MDC1    HPRD  PubMed  
    Q14676 O60934 NBN    HPRD  PubMed  
    Q14676 Q14683 SMC1A    HPRD  PubMed  
    Q14676 P04637 TP53    HPRD  PubMed  
    Q14676 Q12888 TP53BP1    HPRD  PubMed  
    Q14676 Q96RU2 USP28    HPRD  PubMed  
    BioGRID:115014 BioGRID:122229 ANAPC1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115014 BioGRID:119537 ANAPC5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115014 BioGRID:106962 ATM    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:115014 BioGRID:114342 BANF1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115014 BioGRID:106829 BIRC5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:107140 BRCA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:114400 CDC16    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:115014 BioGRID:107431 CDC27    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:107489 CENPC1    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:116369 CHEK2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:108347 EP300    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115014 BioGRID:108896 GATA4    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:109268 H2AFX    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:123818 HDAC10    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:120968 HDAC8    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:114438 HERC2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:122776 MCPH1    BioGRID  PubMed Co-localization 
    BioGRID:115014 BioGRID:110358 MDM2    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:110501 MRE11A    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:110763 NBN    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:111426 POLR2A    BioGRID  PubMed Protein-peptide 
    BioGRID:115014 BioGRID:115417 RAD50    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:111825 RAD51    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:114492 RNF8    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:115014 BioGRID:112497 SUMO2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:115014 BioGRID:116256 TOPBP1    BioGRID  PubMed Affinity Capture-Western; Co-purification; Reconstituted Complex 
    BioGRID:115014 BioGRID:113010 TP53    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:113011 TP53BP1    BioGRID  PubMed Affinity Capture-Western; Co-localization; Reconstituted Complex 
    BioGRID:115014 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:115014 BioGRID:119697 UIMC1    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; Co-localization; Reconstituted Complex 
    BioGRID:115014 BioGRID:121683 USP28    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:115014 BioGRID:113323 WRN    BioGRID  PubMed Protein-peptide 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    FHA domain binding IPI
    Inferred from Physical Interaction
    more info
    		  
    protein C-terminus binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    DNA repair TAS
    Traceable Author Statement
    more info
    		  
    cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    double-strand break repair TAS
    Traceable Author Statement
    more info
    		  
    double-strand break repair via homologous recombination TAS
    Traceable Author Statement
    more info
    		  
    intra-S DNA damage checkpoint TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    focal adhesion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    mediator of DNA damage checkpoint protein 1
    Names
    mediator of DNA damage checkpoint protein 1
    nuclear factor with BRCT domains 1
    mediator of DNA damage checkpoint 1
    homologue to Drosophila photoreceptor protein calphotin
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    NCBI Reference Sequences (RefSeq)

    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_014641.2 → NP_055456.2  mediator of DNA damage checkpoint protein 1

      Status: REVIEWED

      Source sequence(s)
      AL662797, BU621433, D79992, EF177823
      Consensus CDS
      CCDS34384.1
      UniProtKB/TrEMBL
      A1Z5I9
      UniProtKB/Swiss-Prot
      Q14676
      Related
      ENSP00000365588, OTTHUMP00000029090, ENST00000376406, OTTHUMT00000076103
      Conserved Domains (3) summary
      cd00060
      Location:33 – 131
      Blast Score: 137
      FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
      TIGR02169
      Location:822 – 962
      Blast Score: 95
      SMC_prok_A; chromosome segregation protein SMC, primarily archaeal type
      PHA03247
      Location:1362 – 1810
      Blast Score: 142
      PHA03247; large tegument protein UL36; Provisional

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000006.11 Reference GRCh37.p5 Primary Assembly

      Range
      30667584..30685458, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_1

    Genomic

    1. NT_167244.1 Reference GRCh37.p5 ALT_REF_LOCI_1

      Range
      1979228..1997101, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.2 Reference GRCh37.p5 ALT_REF_LOCI_2

      Range
      2179653..2197527, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.1 Reference GRCh37.p5 ALT_REF_LOCI_3

      Range
      1961244..1979117, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.1 Reference GRCh37.p5 ALT_REF_LOCI_4

      Range
      2015679..2033552, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.1 Reference GRCh37.p5 ALT_REF_LOCI_5

      Range
      2049468..2067341, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.1 Reference GRCh37.p5 ALT_REF_LOCI_6

      Range
      1960516..1978389, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.1 Reference GRCh37.p5 ALT_REF_LOCI_7

      Range
      1999891..2017765, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000138.1 Alternate HuRef

      Range
      30467532..30485406, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AB088099.1 BAC54931.1
    genomic AB202097.1 BAE78617.1
    genomic AL662797.7 (22890..40764) None
    genomic AL662848.6 (7986..25860) None
    genomic AL845353.7 CAI41891.1
    genomic BA000025.2 BAB63322.1
    genomic BX248307.7 (2066..19940) None
    genomic BX927283.4 CAQ06770.1
    genomic CH471081.1 EAX03321.1
    genomic CR759873.4 CAQ08691.1
    genomic CR788240.3 CAQ07572.1
    genomic CR936878.10 CAQ06814.1
    mRNA AK298749.1 BAG60892.1
    mRNA AK302434.1 BAG63736.1
    mRNA BC110645.1 AAI10646.1
    mRNA BC131491.1 None
    mRNA BC152556.1 AAI52557.1
    mRNA BU621433.1 None
    mRNA CR749828.1 CAH18685.1
    mRNA D79992.1 BAA11487.2
    mRNA EF177820.1 ABM47418.1
    mRNA EF177821.1 ABM47419.1
    mRNA EF177822.1 ABM47420.1
    mRNA EF177823.1 ABM47421.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14676.3 GenPept UniProtKB/Swiss-Prot:Q14676
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    Additional Links

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Molecular Biology Databases
    Research Materials
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