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ENSG00000237095 Gene

protein-coding   GIFtS: 18
GCID: GC06Mm30746          (predicted)

ENSG00000237095


  Search for ENSG00000237095
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
KIAA01703
NFBD13
Nuclear Factor With BRCT Domains 13

External Ids:    Ensembl: ENSG000002370957   UniProtKB: Q146763   

Export aliases for ENSG00000237095 gene to outside databases


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for ENSG00000237095 Gene:
ENSG00000237095 is a protein-coding gene.

UniProtKB/Swiss-Prot: MDC1_HUMAN, Q14676
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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for ENSG00000237095
         Other transcription factors

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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ENSG00000237095


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_MCFp21.33   

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06Mm30746:       (about GC identifiers)

Start:
30,746,071 bp from start of contig ALT_REF_LOCI_5      End:
30,764,152 bp from start of contig ALT_REF_LOCI_5
Size:
18,082 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: MDC1_HUMAN, Q14676 (See protein sequence)
Recommended Name: Mediator of DNA damage checkpoint protein 1  
Size: 2089 amino acids; 226666 Da
Subunit: 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 MRE11A/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)
Sequence caution: Sequence=BAA11487.2; Type=Erroneous initiation; Sequence=CAH18685.1; Type=Erroneous termination;
Positions=1804; Note=Translated as Gln;
Selected PDB 3D structures from and Proteopedia for ENSG00000237095 (see all 10):
2ADO (3D)        2AZM (3D)        2ETX (3D)        3K05 (3D)        3UEO (3D)        3UMZ (3D)    
Secondary accessions: A2AB04 A2BF04 A2RRA8 A7YY86 B0S8A2 Q0EFC2 Q2L6H7 Q2TAZ4 Q5JP55 Q5JP56
Q5ST83 Q68CQ3 Q86Z06 Q96QC2
Alternative splicing: 4 isoforms:  Q14676-1   Q14676-2   Q14676-3   Q14676-4   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ENSG00000237095: NX_Q14676

Explore proteomics data for ENSG00000237095 at MOPED

Post-translational modifications: 

  • 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 domain1
  • Sumoylation at Lys-1840 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation1
  • Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ENSG00000237095 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB


    ENSEMBL proteins: 
     ENSP00000409167   ENSP00000397021   ENSP00000407703   ENSP00000404954   ENSP00000391230  
     ENSP00000447787   ENSP00000448679   ENSP00000449586   ENSP00000447883  
    Reactome Protein details: Q14676

    ENSG00000237095 Human Recombinant Protein Products:

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    ENSG00000237095 Assay Products:

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    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    3 InterPro protein domains:
     IPR008984 SMAD_FHA_domain
     IPR000253 FHA_dom
     IPR001357 BRCT_dom

    Graphical View of Domain Structure for InterPro Entry Q14676

    ProtoNet protein and cluster: Q14676

    2 Blocks protein domains:
    IPB000253 Forkhead-associated (FHA)
    IPB001357 BRCT domain


    UniProtKB/Swiss-Prot: MDC1_HUMAN, Q14676
    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
    Similarity: Contains 2 BRCT domains
    Similarity: Contains 1 FHA domain


    Find genes that share domains with ENSG00000237095           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MDC1_HUMAN, Q14676
    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

         Gene Ontology (GO): 3 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
    GO:0008022protein C-terminus binding ----
    GO:0070975FHA domain binding ----
         
    Find genes that share ontologies with ENSG00000237095           About GenesLikeMe


    Animal Models:
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MDC1_HUMAN, Q14676: Nucleus. Chromosome (By similarity). 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

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ----
    GO:0005654nucleoplasm ----
    GO:0005694chromosome ----
    GO:0005925focal adhesion ----

    Find genes that share ontologies with ENSG00000237095           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Find genes that share SuperPaths with ENSG00000237095           About GenesLikeMe

    Pathways by sourceSee SuperPaths
    Show all pathways


    2 Reactome Pathways for ENSG00000237095
        Recruitment of repair and signaling proteins to double-strand breaks
    ATM mediated phosphorylation of repair proteins


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ENSG00000237095
    Interactions:

        Search GeneGlobe Interaction Network for ENSG00000237095

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ENSG00000237095 (Q146761, 2, 3 ENSP000004091674) via UniProtKB, MINT, STRING, and/or I2D (see all 103)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MRE11AP499592, 3, ENSP000003258634MINT-6805435 MINT-6805527 MINT-6805327 MINT-6805250 MINT-6805281 MINT-6805549 MINT-6805304 MINT-6805376 I2D: score=3 STRING: ENSP00000325863
    NBNO609341, 2, 3, ENSP000002654334EBI-495644,EBI-494844 MINT-6805462 MINT-7891588 MINT-6805527 MINT-6805435 MINT-7891606 MINT-7891437 MINT-6805493 MINT-6805327 MINT-7891485 MINT-6805569 MINT-6805250 MINT-6805281 MINT-7891501 MINT-6805304 MINT-7891455 MINT-6805376 MINT-7891515 MINT-6805510 MINT-7891469 I2D: score=5 STRING: ENSP00000265433
    RAD50Q928782, 3, ENSP000002653354MINT-6805549 MINT-6805304 MINT-6805435 MINT-6805527 MINT-6805376 MINT-6805327 MINT-6805250 MINT-6805281 I2D: score=3 STRING: ENSP00000265335
    H2AFXP161041, 2, 3, ENSP000003643104EBI-495644,EBI-494830 MINT-6805304 I2D: score=4 STRING: ENSP00000364310
    RNF8O760641, 3, ENSP000003625784EBI-495644,EBI-373337 I2D: score=3 STRING: ENSP00000362578
    About this table

    Gene Ontology (GO): 4 biological process terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000724double-strand break repair via homologous recombination ----
    GO:0006281DNA repair ----
    GO:0006302double-strand break repair ----
    GO:0031573intra-S DNA damage checkpoint ----

    Find genes that share ontologies with ENSG00000237095           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Tocris compounds for ENSG00000237095 (MDC1)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    12 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000449153(uc011hmw.2 uc011hmx.2) ENST00000481417 ENST00000425790
    ENST00000476411 ENST00000494715 ENST00000422195 ENST00000455729 ENST00000423726
    ENST00000553048 ENST00000546487 ENST00000553196 ENST00000547353
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    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --

    ENSG00000237095 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ENSG00000237095 Protein Expression

    UniProtKB/Swiss-Prot: MDC1_HUMAN, Q14676
    Tissue specificity: Highly expressed in testis

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    ENSEMBL Gene Tree for ENSG00000237095 (if available)
    TreeFam Gene Tree for ENSG00000237095 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing ENSG00000237095
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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      --

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ENSG00000237095 gene, integrated from 10 sources (see all 35):
    (articles sorted by number of sources associating them with ENSG00000237095)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Sumoylation of MDC1 is important for proper DNA damage response. (PubMed id 22635276)2 Luo K.... Lou Z. (EMBO J. 2012)
    2. Molecular basis for the association of microcephalin (MCPH1) protein with the cell division cycle protein 27 (Cdc27) subunit of the anaphase-promoting complex. (PubMed id 22139841)2 Singh N.... Couch F.J. (J. Biol. Chem. 2012)
    3. Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkhead-associated domain. (PubMed id 22234877)2 Liu J.... Ye K. (Nucleic Acids Res. 2012)
    4. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. (PubMed id 21406692)2 Rigbolt K.T....Blagoev B. (Sci. Signal. 2011)
    5. CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response. (PubMed id 20008512)2 Becherel O.J.... Lavin M.F. (Nucleic Acids Res. 2010)
    6. Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. (PubMed id 20068231)2 Olsen J.V....Mann M. (Sci. Signal. 2010)
    7. Comparison of the structures and peptide binding specificities of the BRCT domains of MDC1 and BRCA1. (PubMed id 20159462)2 Campbell S.J.... Glover J.N. (Structure 2010)
    8. Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. (PubMed id 19690332)2 Mayya V.... Han D.K. (Sci. Signal. 2009)
    9. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. (PubMed id 19413330)2 Gauci S....Mohammed S. (Anal. Chem. 2009)
    10. Lysine acetylation targets protein complexes and co-regulates major cellular functions. (PubMed id 19608861)2 Choudhary C.... Mann M. (Science 2009)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Ensembl:ENSG00000237095

    (According to HUGE)
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    HUGE: KIAA0170

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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      --

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ENSG00000237095 gene:
    Search GeneIP for patents involving ENSG00000237095

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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    GeneCards Homepage - Last full update: 7 May 2014 - Incrementals: 9 May 2014 , 2 Jun 2014 , 26 Jun 2014 , 30 Jun 2014 , 21 Aug 2014 , 8 Sep 2014

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