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; AllianceGenome:HGNC:21163
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
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Genomic context

Location:: 6p21.33

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (30699807..30717281, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (30564011..30581484, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (30667584..30685058, 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?

Targeting MDC1 promotes apoptosis and sensitizes Imatinib resistance in CML cells by mainly disrupting non-homologous end-joining repair.
Title: Targeting MDC1 promotes apoptosis and sensitizes Imatinib resistance in CML cells by mainly disrupting non-homologous end-joining repair.
Loss of ID3 in pancreatic cancer cells increases DNA damage without impairing MDC1 recruitment to the nuclear foci.
Title: Loss of ID3 in pancreatic cancer cells increases DNA damage without impairing MDC1 recruitment to the nuclear foci.
Functional defects of cancer-associated MDC1 mutations in DNA damage repair.
Title: Functional defects of cancer-associated MDC1 mutations in DNA damage repair.
Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.
Title: Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Coregulator in Invasive Lobular Carcinoma of the Breast.
Impacts of lipid-related metabolites, adiposity, and genetic background on blood eosinophil counts: the Nagahama study.
Title: Impacts of lipid-related metabolites, adiposity, and genetic background on blood eosinophil counts: the Nagahama study.
MDC1 depletion promotes cisplatin induced cell death in cervical cancer cells.
Title: MDC1 depletion promotes cisplatin induced cell death in cervical cancer cells.
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.

Submit: New GeneRIF Correction See all GeneRIFs (98)

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

EBI GWAS Catalog

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

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: 381 organisms have orthologs with human gene MDC1
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables FHA domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in mitotic intra-S DNA damage checkpoint signaling	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of transcription initiation by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Component	Evidence Code	Pubs
located_in chromosome	ISS Inferred from Sequence or Structural Similarity more info
located_in focal adhesion	IDA Inferred from Direct Assay more info
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in 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, Q96QC2

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 Annotation Release 110 details...

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

30699807..30717281 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047419589.1 → XP_047275545.1 mediator of DNA damage checkpoint protein 1 isoform X11
XM_047419588.1 → XP_047275544.1 mediator of DNA damage checkpoint protein 1 isoform X10
XM_047419586.1 → XP_047275542.1 mediator of DNA damage checkpoint protein 1 isoform X7
XM_005249494.6 → 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, Q96QC2

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_047419582.1 → XP_047275538.1 mediator of DNA damage checkpoint protein 1 isoform X3

UniProtKB/Swiss-Prot

Q96QC2

UniProtKB/TrEMBL

A0A1U9XBC1
XM_047419584.1 → XP_047275540.1 mediator of DNA damage checkpoint protein 1 isoform X3

UniProtKB/Swiss-Prot

Q96QC2

UniProtKB/TrEMBL

A0A1U9XBC1
XM_017011522.3 → XP_016867011.1 mediator of DNA damage checkpoint protein 1 isoform X9
XM_047419585.1 → XP_047275541.1 mediator of DNA damage checkpoint protein 1 isoform X6
XM_047419581.1 → XP_047275537.1 mediator of DNA damage checkpoint protein 1 isoform X2
XM_047419587.1 → XP_047275543.1 mediator of DNA damage checkpoint protein 1 isoform X8
XM_047419580.1 → XP_047275536.1 mediator of DNA damage checkpoint protein 1 isoform X1
XM_047419583.1 → XP_047275539.1 mediator of DNA damage checkpoint protein 1 isoform X3

UniProtKB/Swiss-Prot

Q96QC2

UniProtKB/TrEMBL

A0A1U9XBC1
XM_011515003.4 → 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, Q96QC2

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_005249498.5 → 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_005249497.5 → XP_005249554.1 mediator of DNA damage checkpoint protein 1 isoform X5

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_005249492.3 → 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 (6) summary

PTZ00449
Location:964 → 1397

PTZ00449; 104 kDa microneme/rhoptry antigen; Provisional

PHA03247
Location:1248 → 1778

PHA03247; large tegument protein UL36; Provisional

cd00060
Location:54 → 144

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:843 → 983

SMC_prok_A; chromosome segregation protein SMC, primarily archaeal type

cd17744
Location:1914 → 1984

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

cd18441
Location:2016 → 2096

BRCT_MDC1_rpt2; second BRCT domain of mediator of DNA damage checkpoint protein 1 (MDC1) and similar proteins
XM_011515004.4 → XP_011513306.1 mediator of DNA damage checkpoint protein 1 isoform X4

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 ...