Mdc1 mediator of DNA damage checkpoint 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mdc1provided by MGI
Official Full Name: mediator of DNA damage checkpoint 1provided by MGI
Primary source: MGI:MGI:3525201
See related: Ensembl:ENSMUSG00000061607 AllianceGenome:MGI:3525201
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Nfbd1; mKIAA0170; 6820401C03
Summary: The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 7 divergent copies 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. Mice with mutations in this gene exhibit growth retardation, male infertility, immune defects, chromosome instability, DNA repair defects, and radiation sensitivity. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis adult (RPKM 20.0), CNS E11.5 (RPKM 9.8) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 B1; 17 18.7 cM

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (36152390..36170562)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (35841495..35859670)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.
Title: Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.
Mdc1 was dispensable for the synapsis of the autosomes and played only a minor role in X-Y synapsis, compared with the action of H2afx.
Title: H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells.
Low MDC1 expression promotes invasion and metastasis of pancreatic ductal adenocarcinoma.
Title: SOX9 activity is induced by oncogenic Kras to affect MDC1 and MCMs expression in pancreatic cancer.
MDC1 plays a fundamentally significant role in maintenance of genomic stability through a DNA damage response-independent pathway.
Title: DNA Damage Response-Independent Role for MDC1 in Maintaining Genomic Stability.
MDC1 silencing enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in xenograft tumor growth inhibition.
Title: Silencing NFBD1/MDC1 enhances the radiosensitivity of human nasopharyngeal cancer CNE1 cells and results in tumor growth inhibition.
oligomerization of MDC1 plays an important role in DDR and help understand the formation of proteins complexes at the sites of DNA damage.
Title: Oligomerization of MDC1 protein is important for proper DNA damage response.
structural insight into MDC1-CHK2 interaction
Title: Structural delineation of MDC1-FHA domain binding with CHK2-pThr68.
the DNA damage response pathway centered on MDC1 triggers epigenetic silencing of sex chromosomes in germ cells
Title: MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells.
Data show that loss of Mof leads to reduction of histone H4 K16 acetylation, cell cycle arrest, chromosome aberration, defects in DNA damage repair, and complete loss of Mdc1 response to DNA damage.
Title: MOF and H4 K16 acetylation play important roles in DNA damage repair by modulating recruitment of DNA damage repair protein Mdc1.
Data show that ATM-dependent resection at a subset of DSBs leads to ATR-dependent Chk1 activation, and that 53BP1(-/-) and MDC1(-/-) cells manifest a checkpoint defect at high radiation doses.
Title: Role of ATM and the damage response mediator proteins 53BP1 and MDC1 in the maintenance of G(2)/M checkpoint arrest.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Gene trapped (1) 1 citation
Transposon induced (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables chromatin-protein adaptor activity	ISO Inferred from Sequence Orthology more info
enables chromatin-protein adaptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables histone reader activity	ISO Inferred from Sequence Orthology more info
enables histone reader activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in DNA damage response	ISO Inferred from Sequence Orthology more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA replication checkpoint signaling	ISO Inferred from Sequence Orthology more info
involved_in DNA replication checkpoint signaling	ISS Inferred from Sequence or Structural Similarity more info
involved_in chromatin organization	IEA Inferred from Electronic Annotation more info
involved_in protein localization to site of double-strand break	ISO Inferred from Sequence Orthology more info
involved_in protein localization to site of double-strand break	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in chromosome	IDA Inferred from Direct Assay more info	PubMed
located_in focal adhesion	ISO Inferred from Sequence Orthology more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISO Inferred from Sequence Orthology more info	PubMed
is_active_in site of double-strand break	ISO Inferred from Sequence Orthology more info
is_active_in site of double-strand break	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: mediator of DNA damage checkpoint protein 1

Names: mediation of DNA damage checkpoint 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)

NM_001010833.2 → NP_001010833.2 mediator of DNA damage checkpoint protein 1 isoform a

See identical proteins and their annotated locations for NP_001010833.2

Status: REVIEWED

Source sequence(s)

AK033009, BC085140, BC094363, BY022698, CR974451

Consensus CDS

CCDS37604.1

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7

UniProtKB/TrEMBL

E9QK89

Related

ENSMUSP00000080949.7, ENSMUST00000082337.13

Conserved Domains (4) summary

PHA03247
Location:952 → 1429

PHA03247; large tegument protein UL36; Provisional

cd17744
Location:1512 → 1582

BRCT_MDC1_rpt1; first BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins

cd18441
Location:1614 → 1693

BRCT_MDC1_rpt2; second BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins

pfam00498
Location:55 → 110

FHA; FHA domain
NM_001405521.1 → NP_001392450.1 mediator of DNA damage checkpoint protein 1 isoform a

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7

UniProtKB/TrEMBL

E9QK89
NM_001405522.1 → NP_001392451.1 mediator of DNA damage checkpoint protein 1 isoform a

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7

UniProtKB/TrEMBL

E9QK89
NM_001405523.1 → NP_001392452.1 mediator of DNA damage checkpoint protein 1 isoform b

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405524.1 → NP_001392453.1 mediator of DNA damage checkpoint protein 1 isoform b

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405525.1 → NP_001392454.1 mediator of DNA damage checkpoint protein 1 isoform b

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405526.1 → NP_001392455.1 mediator of DNA damage checkpoint protein 1 isoform c

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405527.1 → NP_001392456.1 mediator of DNA damage checkpoint protein 1 isoform d

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405528.1 → NP_001392457.1 mediator of DNA damage checkpoint protein 1 isoform d

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7
NM_001405529.1 → NP_001392458.1 mediator of DNA damage checkpoint protein 1 isoform d

Status: REVIEWED

Source sequence(s)

CR974451

UniProtKB/Swiss-Prot

Q52KG1, Q5PSV9, Q5U4D3, Q6ZQH7