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Protein

Mediator of DNA damage checkpoint protein 1

Gene

Mdc1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Enzyme and pathway databases

ReactomeiR-RNO-3108214. SUMOylation of DNA damage response and repair proteins.
R-RNO-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-RNO-5693571. Nonhomologous End-Joining (NHEJ).
R-RNO-5693607. Processing of DNA double-strand break ends.
R-RNO-69473. G2/M DNA damage checkpoint.

Names & Taxonomyi

Protein namesi
Recommended name:
Mediator of DNA damage checkpoint protein 1
Gene namesi
Name:Mdc1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi1559468. Mdc1.

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity

  • Note: Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires phosphorylation of H2AFX. Colocalizes with APTX at sites of DNA double-strand breaks (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12791279Mediator of DNA damage checkpoint protein 1PRO_0000096321Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei4 – 41PhosphothreonineBy similarity
Modified residuei146 – 1461PhosphothreonineBy similarity
Modified residuei168 – 1681PhosphoserineCombined sources
Modified residuei176 – 1761PhosphoserineCombined sources
Modified residuei298 – 2981PhosphoserineCombined sources
Modified residuei300 – 3001PhosphothreonineBy similarity
Modified residuei314 – 3141PhosphoserineBy similarity
Modified residuei316 – 3161PhosphothreonineBy similarity
Modified residuei350 – 3501PhosphoserineCombined sources
Modified residuei354 – 3541PhosphoserineCombined sources
Modified residuei356 – 3561PhosphothreonineCombined sources
Modified residuei372 – 3721PhosphoserineBy similarity
Modified residuei380 – 3801PhosphoserineCombined sources
Modified residuei382 – 3821PhosphothreonineCombined sources
Modified residuei394 – 3941PhosphoserineBy similarity
Modified residuei411 – 4111PhosphoserineCombined sources
Modified residuei421 – 4211PhosphoserineCombined sources
Modified residuei434 – 4341PhosphoserineBy similarity
Modified residuei438 – 4381PhosphoserineCombined sources
Modified residuei440 – 4401PhosphothreonineCombined sources
Modified residuei457 – 4571PhosphoserineBy similarity
Modified residuei466 – 4661PhosphothreonineBy similarity
Modified residuei488 – 4881PhosphoserineBy similarity
Modified residuei489 – 4891PhosphoserineBy similarity
Modified residuei550 – 5501PhosphoserineCombined sources
Modified residuei587 – 5871PhosphoserineCombined sources
Modified residuei589 – 5891PhosphoserineCombined sources
Modified residuei730 – 7301PhosphoserineBy similarity
Modified residuei745 – 7451PhosphoserineBy similarity
Modified residuei764 – 7641N6-acetyllysineBy similarity
Modified residuei793 – 7931PhosphoserineCombined sources
Modified residuei801 – 8011PhosphoserineCombined sources
Modified residuei824 – 8241PhosphoserineBy similarity
Modified residuei889 – 8891PhosphothreonineBy similarity
Modified residuei951 – 9511PhosphothreonineBy similarity
Modified residuei1008 – 10081PhosphoserineBy similarity
Modified residuei1009 – 10091PhosphoserineBy similarity
Modified residuei1012 – 10121PhosphoserineBy similarity
Modified residuei1016 – 10161PhosphoserineBy similarity
Cross-linki1034 – 1034Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki1034 – 1034Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1054 – 10541PhosphothreonineBy similarity

Post-translational modificationi

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 (By similarity).By similarity
Sumoylation at Lys-1034 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation.By similarity
Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ5U2M8.
PRIDEiQ5U2M8.

PTM databases

iPTMnetiQ5U2M8.
PhosphoSiteiQ5U2M8.

Expressioni

Gene expression databases

BgeeiENSRNOG00000032813.
ExpressionAtlasiQ5U2M8. baseline and differential.
GenevisibleiQ5U2M8. RN.

Interactioni

Subunit structurei

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. Interacts with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN. This interaction is independent of DNA and does not appear to be regulated by phosphorylation of MDC1. Interacts with CHEK2, which is also independent of DNA and requires ATM-mediated phosphorylation 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) (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000049009.

Structurei

3D structure databases

ProteinModelPortaliQ5U2M8.
SMRiQ5U2M8. Positions 1085-1278.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 10552FHAPROSITE-ProRule annotationAdd
BLAST
Domaini1085 – 116379BRCT 1PROSITE-ProRule annotationAdd
BLAST
Domaini1184 – 127592BRCT 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 150150Interaction with CHEK2By similarityAdd
BLAST
Regioni2 – 222221Interaction with the MRN complexBy similarityAdd
BLAST

Domaini

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 (By similarity).By similarity

Sequence similaritiesi

Contains 2 BRCT domains.PROSITE-ProRule annotation
Contains 1 FHA domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG4111RPS. LUCA.
GeneTreeiENSGT00600000084454.
HOGENOMiHOG000113506.
HOVERGENiHBG080567.
InParanoidiQ5U2M8.
OMAiFADFPCQ.
OrthoDBiEOG091G0V3Z.
PhylomeDBiQ5U2M8.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
3.40.50.10190. 1 hit.
InterProiIPR001357. BRCT_dom.
IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamiPF00498. FHA. 1 hit.
PF16770. RTT107_BRCT_5. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 2 hits.
SM00240. FHA. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF52113. SSF52113. 2 hits.
PROSITEiPS50172. BRCT. 2 hits.
PS50006. FHA_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5U2M8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MENTQVIDWD AEEEEETEIS SGSLGYSVEP IGRLRFFSGT HGPERDFPLY
60 70 80 90 100
LGKNVVGRSP DCSVALPFPS ISKQHAVIEI SAWNKAPILQ DCGSLNGTQI
110 120 130 140 150
VKPPRVLAPG VSHRLRDQEL ILFADFPCQY HRLNVPPPLV PRSLLTIEKT
160 170 180 190 200
PRIRGRSQNS RVLLAEDSEE EGDFPSGRSV ANGSRNTASP SATVVPESDE
210 220 230 240 250
EGSSPGPSVP GPSSPFGLGS DTDESQGQQP GVEESSLADN SGAAGEPEQP
260 270 280 290 300
EVNGVTTGTL AQPTKDKFKD TKMKEEAGSA GVPVGSVVEG SPTLGEDSDT
310 320 330 340 350
EADEERQPSG SGDSDTDVEE ERVPVKKNQV LLGVGIGGPG ARGVAHLQDS
360 370 380 390 400
PTGSDTDVEE DKTALAAPPE RSHTAMVINS DTDEEERGEE EEVSAALTLA
410 420 430 440 450
RLKERGIALW SGEPGTEEVK SQPQVLVERS QSASGRDSDT DVEEGSSGGK
460 470 480 490 500
REIVPDSPMD VDETLTVTQP ESQPPCRPND VDEDVDMSSP GSHLEGKKAS
510 520 530 540 550
SALVDKNRAQ VEEEVPGPSV TLGEKHQVPL EGAQPPEEAR ETAVQEGSSS
560 570 580 590 600
PVADIRMSQQ PVAEDAGTEC AAAVSEQKSA LEVGAQSRSP AAPVEQVVVR
610 620 630 640 650
TDTSGDPTLP QREGAQTPTG REREAHVGGT KHAKECCDEP EDLCLSATQC
660 670 680 690 700
FVEGESQHPG AVQSLEDEPT QVFPCLPQEP GPSHLSLPTP GADTLDVPWE
710 720 730 740 750
VLATQPFCLR EQTETSEPID THEAHGSQPS LPGEPPGHQH PVPTSLDHTE
760 770 780 790 800
LLRIDDREMQ TVEKAMGHLS CQMMPDGKAS GDDPEPSDHR LFSPVPEASA
810 820 830 840 850
SPQSLLTSQS QKQSTPQPMF PTSSSELALP ETLHTKPNVR PRRSSRMTPS
860 870 880 890 900
PHSSAALKPY TTCPTNQPAA SRPTSRPTRG RANRSSTRTP ELIVPTGPEL
910 920 930 940 950
QPSTSTEQPG IPNLTSQVTE GRAHSTSVNM PEPVLTGPEA QPLTSAEQSV
960 970 980 990 1000
TSNLNPRAQP LTLEPVPQTS HQRRRRATGK QGSRTAPVGP KSYSTPAEPE
1010 1020 1030 1040 1050
PQSSASQSSG ASEADSPHQK RPRRQVTQKT VVVKEEDPGE IQVKEEPQET
1060 1070 1080 1090 1100
AIPTPGKRKR DPAEGETQGN PTRSRRTKPN QEAAAPKVLF TGVVDSRGER
1110 1120 1130 1140 1150
AVLALGGSLA SSVNEASHLV TDRIRRTVKF LCAVGKGIPI LSLNWLYQSR
1160 1170 1180 1190 1200
KAGCFLPPDD YLVTDPEQEK NFSFSLRDSL SRARERRLLE DYEIHVTPGV
1210 1220 1230 1240 1250
QPPPPQMGEI ISCCGGTVLP SMPHSYKLHR VVITCTEDLP RCAIASRLGL
1260 1270
PLLSPEFLLT GVLKQEATPE AFVLSNLEM
Length:1,279
Mass (Da):136,948
Last modified:July 5, 2005 - v2
Checksum:iC89F981C5B08DCAA
GO

Sequence cautioni

The sequence AAH85955 differs from that shown. Reason: Erroneous initiation. Curated
The sequence CAE84032 differs from that shown. Reason: Erroneous gene model prediction. Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX883048 Genomic DNA. Translation: CAE84032.1. Sequence problems.
BC085955 mRNA. Translation: AAH85955.1. Different initiation.
RefSeqiNP_001159747.1. NM_001166275.1.
UniGeneiRn.106312.

Genome annotation databases

EnsembliENSRNOT00000046798; ENSRNOP00000049009; ENSRNOG00000032813.
GeneIDi309595.
KEGGirno:309595.
UCSCiRGD:1559468. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX883048 Genomic DNA. Translation: CAE84032.1. Sequence problems.
BC085955 mRNA. Translation: AAH85955.1. Different initiation.
RefSeqiNP_001159747.1. NM_001166275.1.
UniGeneiRn.106312.

3D structure databases

ProteinModelPortaliQ5U2M8.
SMRiQ5U2M8. Positions 1085-1278.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000049009.

PTM databases

iPTMnetiQ5U2M8.
PhosphoSiteiQ5U2M8.

Proteomic databases

PaxDbiQ5U2M8.
PRIDEiQ5U2M8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000046798; ENSRNOP00000049009; ENSRNOG00000032813.
GeneIDi309595.
KEGGirno:309595.
UCSCiRGD:1559468. rat.

Organism-specific databases

CTDi9656.
RGDi1559468. Mdc1.

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG4111RPS. LUCA.
GeneTreeiENSGT00600000084454.
HOGENOMiHOG000113506.
HOVERGENiHBG080567.
InParanoidiQ5U2M8.
OMAiFADFPCQ.
OrthoDBiEOG091G0V3Z.
PhylomeDBiQ5U2M8.

Enzyme and pathway databases

ReactomeiR-RNO-3108214. SUMOylation of DNA damage response and repair proteins.
R-RNO-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-RNO-5693571. Nonhomologous End-Joining (NHEJ).
R-RNO-5693607. Processing of DNA double-strand break ends.
R-RNO-69473. G2/M DNA damage checkpoint.

Miscellaneous databases

PROiQ5U2M8.

Gene expression databases

BgeeiENSRNOG00000032813.
ExpressionAtlasiQ5U2M8. baseline and differential.
GenevisibleiQ5U2M8. RN.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
3.40.50.10190. 1 hit.
InterProiIPR001357. BRCT_dom.
IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamiPF00498. FHA. 1 hit.
PF16770. RTT107_BRCT_5. 1 hit.
[Graphical view]
SMARTiSM00292. BRCT. 2 hits.
SM00240. FHA. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
SSF52113. SSF52113. 2 hits.
PROSITEiPS50172. BRCT. 2 hits.
PS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDC1_RAT
AccessioniPrimary (citable) accession number: Q5U2M8
Secondary accession number(s): Q6MG15
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: September 7, 2016
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.