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 H... See more...

Aliases for MDC1 Gene

Aliases for MDC1 Gene

  • Mediator Of DNA Damage Checkpoint 1 2 3 5
  • Mediator Of DNA Damage Checkpoint Protein 1 3 4
  • Nuclear Factor With BRCT Domains 1 3 4
  • NFBD1 3 4
  • Homologue To Drosophila Photoreceptor Protein Calphotin 3
  • Mediator Of DNA-Damage Checkpoint 1 2
  • KIAA0170 4

External Ids for MDC1 Gene

Previous GeneCards Identifiers for MDC1 Gene

  • GC06M030438
  • GC06M030773
  • GC06M030775
  • GC06M030667
  • GC06M030701
  • GC06M030702
  • GC06M030713
  • GC06M030714
  • GC06M030712
  • GC06M030703
  • GC06M030705
  • GC06M030706
  • GC06M030707
  • GC06M030708
  • GC06M030709
  • GC06M030710

Summaries for MDC1 Gene

Entrez Gene Summary for MDC1 Gene

  • 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]

GeneCards Summary for MDC1 Gene

MDC1 (Mediator Of DNA Damage Checkpoint 1) is a Protein Coding gene. Diseases associated with MDC1 include Nijmegen Breakage Syndrome and Riddle Syndrome. Among its related pathways are Metabolism of proteins and DNA Double-Strand Break Repair. Gene Ontology (GO) annotations related to this gene include protein C-terminus binding and FHA domain binding. An important paralog of this gene is PAXIP1.

UniProtKB/Swiss-Prot Summary for MDC1 Gene

  • Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AFX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.

Gene Wiki entry for MDC1 Gene

Additional gene information for MDC1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MDC1 Gene

Genomics for MDC1 Gene

GeneHancer (GH) Regulatory Elements for MDC1 Gene

Promoters and enhancers for MDC1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MDC1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MDC1

Top Transcription factor binding sites by QIAGEN in the MDC1 gene promoter:
  • GR-alpha
  • IRF-1
  • p53
  • STAT1
  • STAT3

Genomic Locations for MDC1 Gene

Genomic Locations for MDC1 Gene
chr6:30,699,807-30,717,966
(GRCh38/hg38)
Size:
18,160 bases
Orientation:
Minus strand
chr6:30,667,584-30,685,666
(GRCh37/hg19)
Size:
18,083 bases
Orientation:
Minus strand

Genomic View for MDC1 Gene

Genes around MDC1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MDC1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MDC1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

Proteins for MDC1 Gene

  • Protein details for MDC1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14676-MDC1_HUMAN
    Recommended name:
    Mediator of DNA damage checkpoint protein 1
    Protein Accession:
    Q14676
    Secondary Accessions:
    • A2AB04
    • A2BF04
    • A2RRA8
    • A7YY86
    • B0S8A2
    • Q0EFC2
    • Q2L6H7
    • Q2TAZ4
    • Q5JP55
    • Q5JP56
    • Q5ST83
    • Q68CQ3
    • Q86Z06
    • Q96QC2

    Protein attributes for MDC1 Gene

    Size:
    2089 amino acids
    Molecular mass:
    226666 Da
    Quaternary structure:
    • Homodimer. Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with H2AFX, which requires phosphorylation of H2AFX on 'Ser-139'. Interacts with the MRN complex, composed of MRE11, RAD50, and NBN. Interacts with CHEK2, which requires ATM-mediated phosphorylation of 'Thr-68' within the FHA domain of CHEK2. Interacts constitutively with the BRCA1-BARD1 complex, SMC1A and TP53BP1. Interacts with ATM and FANCD2, and these interactions are reduced upon DNA damage. Also interacts with the PRKDC complex, composed of XRCC6/KU70, XRCC5/KU80 and PRKDC/XRCC7. This interaction may be required for PRKDC autophosphorylation, which is essential for DNA double strand break (DSB) repair. When phosphorylated by ATM, interacts with RNF8 (via FHA domain). Interacts with CEP164. When phosphorylated, interacts with APTX (via FHA-like domain).
    SequenceCaution:
    • Sequence=BAA11487.2; Type=Erroneous initiation; Evidence={ECO:0000305}; Sequence=CAH18685.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for MDC1 Gene

    Alternative splice isoforms for MDC1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MDC1 Gene

Post-translational modifications for MDC1 Gene

  • Phosphorylated upon exposure to ionizing radiation (IR), ultraviolet radiation (UV), and hydroxyurea (HU). Phosphorylation in response to IR requires ATM, NBN, and possibly CHEK2. Also phosphorylated during the G2/M phase of the cell cycle and during activation of the mitotic spindle checkpoint. Phosphorylation at Thr-4 by ATM stabilizes and enhances homodimerization via the FHA domain.
  • Sumoylation at Lys-1840 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation.
  • Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination.
  • Ubiquitination at Lys45
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for MDC1 Gene

Domains & Families for MDC1 Gene

Gene Families for MDC1 Gene

Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Protein Domains for MDC1 Gene

Blocks:
  • Forkhead-associated (FHA)
  • BRCT domain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MDC1 Gene

GenScript: Design optimal peptide antigens:
  • Mediator of DNA damage checkpoint 1 variant 2 (A1Z5I6_HUMAN)
  • Mediator of DNA damage checkpoint 1 variant 4 (A1Z5I8_HUMAN)
  • Mediator of DNA damage checkpoint 1 variant 1 (A1Z5I9_HUMAN)
  • Mediator of DNA damage checkpoint 1 (B7ZCV9_HUMAN)
  • Nuclear factor with BRCT domains 1 (MDC1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q14676

UniProtKB/Swiss-Prot:

MDC1_HUMAN :
  • Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AFX.
Domain:
  • Tandemly repeated BRCT domains are characteristic of proteins involved in DNA damage signaling. In MDC1, these repeats are required for localization to chromatin which flanks sites of DNA damage marked by 'Ser-139' phosphorylation of H2AFX.
genes like me logo Genes that share domains with MDC1: view

Function for MDC1 Gene

Molecular function for MDC1 Gene

UniProtKB/Swiss-Prot Function:
Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AFX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.

Phenotypes From GWAS Catalog for MDC1 Gene

Gene Ontology (GO) - Molecular Function for MDC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12607005
GO:0008022 protein C-terminus binding IPI 17577209
GO:0042802 identical protein binding IPI 21293379
GO:0070975 FHA domain binding IPI 20008512
genes like me logo Genes that share ontologies with MDC1: view
genes like me logo Genes that share phenotypes with MDC1: view

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for MDC1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MDC1 Gene

Localization for MDC1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MDC1 Gene

Nucleus. Chromosome. Note=Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AFX. Colocalizes with APTX at sites of DNA double-strand breaks.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MDC1 gene
Compartment Confidence
nucleus 5
cytosol 3
cytoskeleton 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MDC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 15604234
GO:0005654 nucleoplasm TAS --
GO:0005694 chromosome ISS --
GO:0005925 focal adhesion IDA --
GO:0016604 nuclear body IDA --
genes like me logo Genes that share ontologies with MDC1: view

Pathways & Interactions for MDC1 Gene

genes like me logo Genes that share pathways with MDC1: view

Pathways by source for MDC1 Gene

3 GeneGo (Thomson Reuters) pathways for MDC1 Gene
  • DNA damage_ATM/ATR regulation of G1/S checkpoint
  • DNA damage_DNA-damage-induced responses
  • DNA damage_Role of Brca1 and Brca2 in DNA repair
1 Qiagen pathway for MDC1 Gene
  • ATM Pathway

SIGNOR curated interactions for MDC1 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MDC1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006281 DNA repair IEA --
GO:0006303 double-strand break repair via nonhomologous end joining TAS --
GO:0006974 cellular response to DNA damage stimulus IEA --
GO:0007049 cell cycle IEA --
GO:0031573 intra-S DNA damage checkpoint TAS 17577209
genes like me logo Genes that share ontologies with MDC1: view

Drugs & Compounds for MDC1 Gene

(1) Drugs for MDC1 Gene - From: ApexBio

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Temozolomide Approved, Investigational Pharma Alkylating Agents 859

(1) ApexBio Compounds for MDC1 Gene

Compound Action Cas Number
Temozolomide 85622-93-1
genes like me logo Genes that share compounds with MDC1: view

Drug Products

Transcripts for MDC1 Gene

mRNA/cDNA for MDC1 Gene

1 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
9 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for MDC1

Alternative Splicing Database (ASD) splice patterns (SP) for MDC1 Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c ^ 3 ^ 4a · 4b · 4c · 4d ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13 ^ 14 ^ 15a · 15b ^ 16 ^ 17 ^
SP1: - -
SP2:
SP3: - - -
SP4: -
SP5:
SP6:
SP7:
SP8:
SP9: - - -
SP10:
SP11:

ExUns: 18
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for MDC1 Gene

GeneLoc Exon Structure for
MDC1

Expression for MDC1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MDC1 Gene

Protein differential expression in normal tissues from HIPED for MDC1 Gene

This gene is overexpressed in Testis (32.4), Peripheral blood mononuclear cells (10.1), and Retina (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MDC1 Gene



Protein tissue co-expression partners for MDC1 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MDC1

SOURCE GeneReport for Unigene cluster for MDC1 Gene:

Hs.653495

mRNA Expression by UniProt/SwissProt for MDC1 Gene:

Q14676-MDC1_HUMAN
Tissue specificity: Highly expressed in testis.

Evidence on tissue expression from TISSUES for MDC1 Gene

  • Blood(4.6)
  • Liver(4.2)
  • Pancreas(4.2)
  • Nervous system(2.7)
  • Spleen(2.6)
genes like me logo Genes that share expression patterns with MDC1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MDC1 Gene

Orthologs for MDC1 Gene

This gene was present in the common ancestor of animals.

Orthologs for MDC1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MDC1 31 30
  • 96.06 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MDC1 31 30
  • 77.23 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MDC1 31 30
  • 74.35 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mdc1 30
  • 72.92 (n)
mouse
(Mus musculus)
Mammalia Mdc1 17 31 30
  • 70.86 (n)
oppossum
(Monodelphis domestica)
Mammalia MDC1 31
  • 37 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MDC1 31
  • 26 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MDC1 31
  • 19 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii MDC1 31
  • 16 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta ptip 31
  • 8 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea pis-1 31
  • 12 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5902 31
  • 23 (a)
OneToOne
Species where no ortholog for MDC1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for MDC1 Gene

ENSEMBL:
Gene Tree for MDC1 (if available)
TreeFam:
Gene Tree for MDC1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MDC1: view image

Paralogs for MDC1 Gene

Paralogs for MDC1 Gene

genes like me logo Genes that share paralogs with MDC1: view

Variants for MDC1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MDC1 Gene

SNP ID Clinical significance and condition Chr 06 pos Variation AA Info Type
716887 Benign: not provided 30,712,186(-) A/C MISSENSE_VARIANT
716888 Benign: not provided 30,712,862(-) A/G NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
716889 Benign: not provided 30,713,191(-) C/T MISSENSE_VARIANT
725735 Benign: not provided 30,703,429(-) T/C MISSENSE_VARIANT
747196 Likely Benign: not provided 30,704,104(-) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for MDC1 Gene

Structural Variations from Database of Genomic Variants (DGV) for MDC1 Gene

Variant ID Type Subtype PubMed ID
esv2670269 CNV deletion 23128226
esv2731791 CNV deletion 23290073
esv2731796 CNV deletion 23290073
esv2731797 CNV deletion 23290073
esv2731798 CNV deletion 23290073
esv2759413 CNV loss 17122850
esv3411275 CNV duplication 20981092
nsv1074389 CNV deletion 25765185
nsv1122126 CNV deletion 24896259
nsv1144137 CNV deletion 24896259
nsv601264 CNV loss 21841781
nsv601481 CNV loss 21841781
nsv830626 CNV loss 17160897

Variation tolerance for MDC1 Gene

Residual Variation Intolerance Score: 99.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 10.93; 91.92% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MDC1 Gene

Human Gene Mutation Database (HGMD)
MDC1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MDC1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MDC1 Gene

Disorders for MDC1 Gene

MalaCards: The human disease database

(9) MalaCards diseases for MDC1 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards
Search MDC1 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MDC1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MDC1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MDC1 Gene

Publications for MDC1 Gene

  1. MDC1 is a mediator of the mammalian DNA damage checkpoint. (PMID: 12607005) Stewart GS … Elledge SJ (Nature 2003) 2 3 4 23 54
  2. CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response. (PMID: 20008512) Becherel OJ … Lavin MF (Nucleic acids research 2010) 3 4 23 54
  3. Sequence variant discovery in DNA repair genes from radiosensitive and radiotolerant prostate brachytherapy patients. (PMID: 19638463) Pugh TJ … Moore RA (Clinical cancer research : an official journal of the American Association for Cancer Research 2009) 3 23 41 54
  4. Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. (PMID: 12611903) Lou Z … Chen J (The Journal of biological chemistry 2003)