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Protein

Mediator of DNA damage checkpoint protein 1

Gene

Mdc1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Keywordsi

Biological processCell 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-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi1559468 Mdc1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000963211 – 1279Mediator of DNA damage checkpoint protein 1Add BLAST1279

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4PhosphothreonineBy similarity1
Modified residuei146PhosphothreonineBy similarity1
Modified residuei168PhosphoserineCombined sources1
Modified residuei176PhosphoserineCombined sources1
Modified residuei298PhosphoserineCombined sources1
Modified residuei300PhosphothreonineBy similarity1
Modified residuei314PhosphoserineBy similarity1
Modified residuei316PhosphothreonineBy similarity1
Modified residuei350PhosphoserineCombined sources1
Modified residuei354PhosphoserineCombined sources1
Modified residuei356PhosphothreonineCombined sources1
Modified residuei372PhosphoserineBy similarity1
Modified residuei380PhosphoserineCombined sources1
Modified residuei382PhosphothreonineCombined sources1
Modified residuei394PhosphoserineBy similarity1
Modified residuei411PhosphoserineCombined sources1
Modified residuei421PhosphoserineCombined sources1
Modified residuei434PhosphoserineBy similarity1
Modified residuei438PhosphoserineCombined sources1
Modified residuei440PhosphothreonineCombined sources1
Modified residuei457PhosphoserineBy similarity1
Modified residuei466PhosphothreonineBy similarity1
Modified residuei488PhosphoserineBy similarity1
Modified residuei489PhosphoserineBy similarity1
Modified residuei550PhosphoserineCombined sources1
Modified residuei587PhosphoserineCombined sources1
Modified residuei589PhosphoserineCombined sources1
Modified residuei730PhosphoserineBy similarity1
Modified residuei745PhosphoserineBy similarity1
Modified residuei764N6-acetyllysineBy similarity1
Modified residuei793PhosphoserineCombined sources1
Modified residuei801PhosphoserineCombined sources1
Modified residuei824PhosphoserineBy similarity1
Modified residuei889PhosphothreonineBy similarity1
Modified residuei951PhosphothreonineBy similarity1
Cross-linki991Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1008PhosphoserineBy similarity1
Modified residuei1009PhosphoserineBy similarity1
Modified residuei1012PhosphoserineBy similarity1
Modified residuei1016PhosphoserineBy similarity1
Cross-linki1034Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateBy similarity
Cross-linki1034Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei1054PhosphothreonineBy similarity1

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
PhosphoSitePlusiQ5U2M8

Expressioni

Gene expression databases

BgeeiENSRNOG00000032813
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 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
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 105FHAPROSITE-ProRule annotationAdd BLAST52
Domaini1085 – 1163BRCT 1PROSITE-ProRule annotationAdd BLAST79
Domaini1184 – 1275BRCT 2PROSITE-ProRule annotationAdd BLAST92

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 150Interaction with CHEK2By similarityAdd BLAST150
Regioni2 – 222Interaction with the MRN complexBy similarityAdd BLAST221

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2043 Eukaryota
ENOG4111RPS LUCA
GeneTreeiENSGT00600000084454
HOGENOMiHOG000113506
HOVERGENiHBG080567
InParanoidiQ5U2M8
KOiK20780
OMAiFPLYLGK
OrthoDBiEOG091G0V3Z
PhylomeDBiQ5U2M8

Family and domain databases

CDDicd00027 BRCT, 1 hit
cd00060 FHA, 1 hit
Gene3Di3.40.50.10190, 2 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
IPR000253 FHA_dom
IPR008984 SMAD_FHA_dom_sf
PfamiView protein in Pfam
PF00498 FHA, 1 hit
PF16770 RTT107_BRCT_5, 1 hit
SMARTiView protein in SMART
SM00292 BRCT, 2 hits
SM00240 FHA, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF52113 SSF52113, 2 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 2 hits
PS50006 FHA_DOMAIN, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiMDC1_RAT
AccessioniPrimary (citable) accession number: Q5U2M8
Secondary accession number(s): Q6MG15
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: July 5, 2005
Last modified: May 23, 2018
This is version 118 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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