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MDC1 mediator of DNA damage checkpoint 1 [ Homo sapiens (human) ]

Gene ID: 9656, updated on 12-Aug-2018

Summary

Official Symbol
MDC1provided by HGNC
Official Full Name
mediator of DNA damage checkpoint 1provided by HGNC
Primary source
HGNC:HGNC:21163
See related
Ensembl:ENSG00000137337 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
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]
Expression
Broad expression in testis (RPKM 20.6), thyroid (RPKM 7.4) and 25 other tissues See more
Orthologs

Genomic context

See MDC1 in Genome Data Viewer
Location:
6p21.33
Exon count:
18
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 6 NC_000006.12 (30699807..30717988, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (30667584..30685458, complement)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene nurim Neighboring gene ribosomal protein L7 pseudogene 4 Neighboring gene MDC1 antisense RNA 1 Neighboring gene tubulin beta class I Neighboring gene flotillin 1

Genomic regions, transcripts, and products

Expression

  • 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
NHGRI GWA Catalog

Pathways from BioSystems

  • ATM Signaling Network in Development and Disease, organism-specific biosystem (from WikiPathways)
    ATM Signaling Network in Development and Disease, organism-specific biosystemThis pathway is modeled after Figure 4 in the article "The ATM signaling network in development and disease" (See Bibliography). When DNA is damaged, DDR begins to work on recuperating the damage th...
  • ATM Signaling Pathway, organism-specific biosystem (from WikiPathways)
    ATM Signaling Pathway, organism-specific biosystemAtaxia-telangiectasia (A-T) is a highly pleiotropic, autosomal recessive disease that leads to multisystem defects and has an intricate cellular phenotype, all linked to the functional inactivation o...
  • Cell Cycle, organism-specific biosystem (from REACTOME)
    Cell Cycle, organism-specific biosystem
    Cell Cycle
  • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
    Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
  • DNA Double Strand Break Response, organism-specific biosystem (from REACTOME)
    DNA Double Strand Break Response, organism-specific biosystemDNA double strand break (DSB) response involves sensing of DNA DSBs by the MRN complex which triggers ATM activation. ATM phosphorylates a number of proteins involved in DNA damage checkpoint signali...
  • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
    DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
    G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
  • G2/M DNA damage checkpoint, organism-specific biosystem (from REACTOME)
    G2/M DNA damage checkpoint, organism-specific biosystemThroughout the cell cycle, the genome is constantly monitored for damage, resulting either from errors of replication, by-products of metabolism or through extrinsic sources such as ultra-violet or i...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
    HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
  • Homology Directed Repair, organism-specific biosystem (from REACTOME)
    Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Nonhomologous End-Joining (NHEJ), organism-specific biosystem (from REACTOME)
    Nonhomologous End-Joining (NHEJ), organism-specific biosystemThe nonhomologous end joining (NHEJ) pathway is initiated in response to the formation of DNA double-strand breaks (DSBs) induced by DNA-damaging agents, such as ionizing radiation. DNA DSBs are reco...
  • Post-translational protein modification, organism-specific biosystem (from REACTOME)
    Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
  • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
    Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...
  • Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystem (from REACTOME)
    Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystemActivated ATM phosphorylates a number of proteins involved in the DNA damage checkpoint and DNA repair (Thompson and Schild 2002, Ciccia and Elledge 2010), thereby triggering and coordinating accumul...
  • SUMO E3 ligases SUMOylate target proteins, organism-specific biosystem (from REACTOME)
    SUMO E3 ligases SUMOylate target proteins, organism-specific biosystemSUMO proteins are conjugated to lysine residues of target proteins via an isopeptide bond with the C-terminal glycine of SUMO (reviewed in Zhao 2007, Gareau and Lima 2010, Hannoun et al. 2010, Citro ...
  • SUMOylation, organism-specific biosystem (from REACTOME)
    SUMOylation, organism-specific biosystemSmall Ubiquitin-like MOdifiers (SUMOs) are a family of 3 proteins (SUMO1,2,3) that are reversibly conjugated to lysine residues of target proteins via a glycine-lysine isopeptide bond (reviewed in Ha...
  • SUMOylation of DNA damage response and repair proteins, organism-specific biosystem (from REACTOME)
    SUMOylation of DNA damage response and repair proteins, organism-specific biosystemSeveral factors that participate in DNA damage response and repair are SUMOylated (reviewed in Dou et al. 2011, Bekker-Jensen and Mailand 2011, Ulrich 2012, Psakhye and Jentsch 2012, Bologna and Ferr...
  • TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystemSeveral DNA repair genes contain p53 response elements and their transcription is positively regulated by TP53 (p53). TP53-mediated regulation probably ensures increased protein level of DNA repair g...
  • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
    Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • KIAA0170, MGC166888, DKFZp781A0122

Gene Ontology Provided by GOA

Function Evidence Code Pubs
FHA domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
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
double-strand break repair via nonhomologous end joining TAS
Traceable Author Statement
more info
 
intra-S DNA damage checkpoint TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
chromosome ISS
Inferred from Sequence or Structural Similarity
more info
 
focal adhesion IDA
Inferred from Direct Assay
more info
 
nuclear body IDA
Inferred from Direct Assay
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
mediator of DNA damage checkpoint protein 1
Names
homologue to Drosophila photoreceptor protein calphotin
nuclear factor with BRCT domains 1

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

    See identical proteins and their annotated locations for NP_055456.2

    Status: REVIEWED

    Source sequence(s)
    AL662797, BU621433, D79992, EF177823
    Consensus CDS
    CCDS34384.1
    UniProtKB/Swiss-Prot
    Q14676
    UniProtKB/TrEMBL
    A0A1U9XBC1, A1Z5I9
    Related
    ENSP00000365588.3, OTTHUMP00000029090, ENST00000376406.7, OTTHUMT00000076103
    Conserved Domains (5) summary
    pfam00498
    Location:55110
    FHA; FHA domain
    cl00038
    Location:18821968
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    cl25732
    Location:822962
    SMC_N; RecF/RecN/SMC N terminal domain
    cl25751
    Location:9431376
    DUF4045; Domain of unknown function (DUF4045)
    cl26464
    Location:12271757
    Atrophin-1; Atrophin-1 family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p12 Primary Assembly

    Range
    30699807..30717988 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005249494.5XP_005249551.1  mediator of DNA damage checkpoint protein 1 isoform X3

    See identical proteins and their annotated locations for XP_005249551.1

    UniProtKB/Swiss-Prot
    Q14676
    UniProtKB/TrEMBL
    A0A1U9XBC1
    Conserved Domains (5) summary
    pfam00498
    Location:55110
    FHA; FHA domain
    cl00038
    Location:18821968
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    cl25732
    Location:822962
    SMC_N; RecF/RecN/SMC N terminal domain
    cl25751
    Location:9431376
    DUF4045; Domain of unknown function (DUF4045)
    cl26464
    Location:12271757
    Atrophin-1; Atrophin-1 family
  2. XM_017011520.2XP_016867009.1  mediator of DNA damage checkpoint protein 1 isoform X4

    Conserved Domains (2) summary
    cd00027
    Location:19051957
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:55123
    FHA; FHA domain
  3. XM_017011521.2XP_016867010.1  mediator of DNA damage checkpoint protein 1 isoform X7

    Conserved Domains (2) summary
    cd00027
    Location:17161768
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:55123
    FHA; FHA domain
  4. XM_011515001.3XP_011513303.1  mediator of DNA damage checkpoint protein 1 isoform X3

    See identical proteins and their annotated locations for XP_011513303.1

    UniProtKB/Swiss-Prot
    Q14676
    UniProtKB/TrEMBL
    A0A1U9XBC1
    Conserved Domains (5) summary
    pfam00498
    Location:55110
    FHA; FHA domain
    cl00038
    Location:18821968
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    cl25732
    Location:822962
    SMC_N; RecF/RecN/SMC N terminal domain
    cl25751
    Location:9431376
    DUF4045; Domain of unknown function (DUF4045)
    cl26464
    Location:12271757
    Atrophin-1; Atrophin-1 family
  5. XM_011515004.3XP_011513306.1  mediator of DNA damage checkpoint protein 1 isoform X5

    See identical proteins and their annotated locations for XP_011513306.1

    Conserved Domains (1) summary
    cd00027
    Location:17781830
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
  6. XM_017011522.2XP_016867011.1  mediator of DNA damage checkpoint protein 1 isoform X9

  7. XM_005249493.4XP_005249550.1  mediator of DNA damage checkpoint protein 1 isoform X2

    See identical proteins and their annotated locations for XP_005249550.1

    Conserved Domains (2) summary
    cd00027
    Location:19261978
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:76144
    FHA; FHA domain
  8. XM_005249498.4XP_005249555.1  mediator of DNA damage checkpoint protein 1 isoform X8

    See identical proteins and their annotated locations for XP_005249555.1

    Conserved Domains (2) summary
    cd00027
    Location:16631715
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:76144
    FHA; FHA domain
  9. XM_005249497.4XP_005249554.1  mediator of DNA damage checkpoint protein 1 isoform X6

    See identical proteins and their annotated locations for XP_005249554.1

    Conserved Domains (2) summary
    cd00027
    Location:17371789
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:76144
    FHA; FHA domain
  10. XM_005249492.2XP_005249549.1  mediator of DNA damage checkpoint protein 1 isoform X1

    See identical proteins and their annotated locations for XP_005249549.1

    Conserved Domains (2) summary
    cd00027
    Location:19271979
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    pfam00498
    Location:76144
    FHA; FHA domain
  11. XM_011515003.3XP_011513305.1  mediator of DNA damage checkpoint protein 1 isoform X3

    See identical proteins and their annotated locations for XP_011513305.1

    UniProtKB/Swiss-Prot
    Q14676
    UniProtKB/TrEMBL
    A0A1U9XBC1
    Conserved Domains (5) summary
    pfam00498
    Location:55110
    FHA; FHA domain
    cl00038
    Location:18821968
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    cl25732
    Location:822962
    SMC_N; RecF/RecN/SMC N terminal domain
    cl25751
    Location:9431376
    DUF4045; Domain of unknown function (DUF4045)
    cl26464
    Location:12271757
    Atrophin-1; Atrophin-1 family
  12. XM_017011519.2XP_016867008.1  mediator of DNA damage checkpoint protein 1 isoform X3

    UniProtKB/Swiss-Prot
    Q14676
    UniProtKB/TrEMBL
    A0A1U9XBC1
    Conserved Domains (5) summary
    pfam00498
    Location:55110
    FHA; FHA domain
    cl00038
    Location:18821968
    BRCT; Breast Cancer Suppressor Protein (BRCA1), carboxy-terminal domain. The BRCT domain is found within many DNA damage repair and cell cycle checkpoint proteins. The unique diversity of this domain superfamily allows BRCT modules to interact forming homo ...
    cl25732
    Location:822962
    SMC_N; RecF/RecN/SMC N terminal domain
    cl25751
    Location:9431376
    DUF4045; Domain of unknown function (DUF4045)
    cl26464
    Location:12271757
    Atrophin-1; Atrophin-1 family

Reference GRCh38.p12 ALT_REF_LOCI_1

Genomic

  1. NT_167244.2 Reference GRCh38.p12 ALT_REF_LOCI_1

    Range
    2029312..2047185 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p12 ALT_REF_LOCI_2

    Range
    2179547..2197421 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p12 ALT_REF_LOCI_3

    Range
    1955659..1973532 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p12 ALT_REF_LOCI_4

    Range
    2010059..2027932 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p12 ALT_REF_LOCI_5

    Range
    2043883..2061756 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p12 ALT_REF_LOCI_6

    Range
    1954920..1972793 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p12 ALT_REF_LOCI_7

    Range
    2000593..2018467 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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