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

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
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: mouse all

Genomic context

Location:: 6p21.33

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MDC1 plays a role in tumorigenesis of oral squamous cell carcinoma
Title: Effect of silencing of mediator of DNA damage checkpoint protein 1 on the growth of oral squamous cell carcinoma in vitro and in vivo.
The PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin.
Title: MDC1 PST-repeat region promotes histone H2AX-independent chromatin association and DNA damage tolerance.
we find that TOPBP1 forms filamentous structures capable of bridging MDC1 foci in mitosis, indicating that MDC1-TOPBP1 complexes tether DSBs until repair is reactivated in the following G1 phase. Thus, we reveal an important, hitherto-unnoticed cooperation between MDC1 and TOPBP1 in maintaining genome stability during cell division
Title: MDC1 Interacts with TOPBP1 to Maintain Chromosomal Stability during Mitosis.
CTD Tyr1-phosphorylated RNAPII (CTD Y1P) synthetizes strand-specific, damage-responsive transcripts (DARTs), which trigger formation of double-stranded (ds)RNA intermediates via DNA-RNA hybrid intermediates to promote recruitment of p53-binding protein 1 (53BP1) and Mediator of DNA damage checkpoint 1 (MDC1) to endogenous DSBs.
Title: Tyrosine kinase c-Abl couples RNA polymerase II transcription to DNA double-strand breaks.
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.
LRH1 activates MDC1 expression to promote chemotherapy resistance involved in DNA damage in breast cancer.LRH1 binds to MDC1 promoter and activates MDC1 transcription.
Title: LRH1 enhances cell resistance to chemotherapy by transcriptionally activating MDC1 expression and attenuating DNA damage in human breast cancer.
Our data highlight that NFBD1 participates in the regulation of proliferation and apoptosis in laryngeal squamous cell carcinoma
Title: NFBD1/MDC1 participates in the regulation of proliferation and apoptosis in human laryngeal squamous cell carcinoma.
These findings indicate that the c-Fos/miR-22/MDC1 axis plays a relevant role in DNA repair in terminally differentiated cells, which may facilitate our understanding of molecular mechanism underlying the downregulating DNA repair in differentiated cells.
Title: c-Fos-dependent miR-22 targets MDC1 and regulates DNA repair in terminally differentiated cells.
key component of the DNA damage response and interacts with several factors such as gamma-H2AX
Title: ID3 regulates the MDC1-mediated DNA damage response in order to maintain genome stability.
prognostic marker in predicting relapse-free survival in oral squamous cell carcinoma
Title: Mediator of DNA damage checkpoint protein 1 (MDC1) as a prognostic marker for patients with oral squamous cell carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (92)

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

Associated conditions

Description	Tests
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH36324 (e-PCR)
- UniSTS:31510

RH25387 (e-PCR)
- UniSTS:12643

SHGC-170044 (e-PCR)
- UniSTS:173709

WI-15445 (e-PCR)
- UniSTS:81329

Homology

Homologs of the MDC1 gene: The MDC1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 252 organisms have orthologs with human gene MDC1
Orthologs

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

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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)

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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_014641.3 → NP_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, ENST00000376406.8

Conserved Domains (5) summary

pfam00498
Location:55 → 110

FHA; FHA domain

cl00038
Location:1882 → 1968

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:822 → 962

SMC_N; RecF/RecN/SMC N terminal domain

cl25751
Location:943 → 1376

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:1227 → 1757

Atrophin-1; Atrophin-1 family

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p13 Primary Assembly

Range

30699807..30717988 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005249494.5 → XP_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:55 → 110

FHA; FHA domain

cl00038
Location:1882 → 1968

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:822 → 962

SMC_N; RecF/RecN/SMC N terminal domain

cl25751
Location:943 → 1376

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:1227 → 1757

Atrophin-1; Atrophin-1 family
XM_017011520.2 → XP_016867009.1 mediator of DNA damage checkpoint protein 1 isoform X4

Conserved Domains (2) summary

cd00027
Location:1905 → 1957

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:55 → 123

FHA; FHA domain
XM_017011521.2 → XP_016867010.1 mediator of DNA damage checkpoint protein 1 isoform X7

Conserved Domains (2) summary

cd00027
Location:1716 → 1768

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:55 → 123

FHA; FHA domain
XM_011515001.3 → XP_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:55 → 110

FHA; FHA domain

cl00038
Location:1882 → 1968

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:822 → 962

SMC_N; RecF/RecN/SMC N terminal domain

cl25751
Location:943 → 1376

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:1227 → 1757

Atrophin-1; Atrophin-1 family
XM_011515004.3 → XP_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:1778 → 1830

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 ...
XM_017011522.2 → XP_016867011.1 mediator of DNA damage checkpoint protein 1 isoform X9
XM_005249493.4 → XP_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:1926 → 1978

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:76 → 144

FHA; FHA domain
XM_005249498.4 → XP_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:1663 → 1715

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:76 → 144

FHA; FHA domain
XM_005249497.4 → XP_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:1737 → 1789

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:76 → 144

FHA; FHA domain
XM_005249492.2 → XP_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:1927 → 1979

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:76 → 144

FHA; FHA domain
XM_011515003.3 → XP_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:55 → 110

FHA; FHA domain

cl00038
Location:1882 → 1968

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:822 → 962

SMC_N; RecF/RecN/SMC N terminal domain

cl25751
Location:943 → 1376

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:1227 → 1757

Atrophin-1; Atrophin-1 family
XM_017011519.2 → XP_016867008.1 mediator of DNA damage checkpoint protein 1 isoform X3

UniProtKB/Swiss-Prot

Q14676

UniProtKB/TrEMBL

A0A1U9XBC1

Conserved Domains (5) summary

pfam00498
Location:55 → 110

FHA; FHA domain

cl00038
Location:1882 → 1968

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:822 → 962

SMC_N; RecF/RecN/SMC N terminal domain

cl25751
Location:943 → 1376

DUF4045; Domain of unknown function (DUF4045)

cl26464
Location:1227 → 1757

Atrophin-1; Atrophin-1 family