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Protein

Mediator of DNA damage checkpoint protein 1

Gene

Mdc1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 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 - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Names & Taxonomyi

Protein namesi
Recommended name:
Mediator of DNA damage checkpoint protein 1
Gene namesi
Name:Mdc1
Synonyms:Kiaa0170
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:3525201. Mdc1.

Subcellular locationi

  • Nucleus
  • Chromosome

  • 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

  • chromosome Source: UniProtKB
  • focal adhesion Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 17071707Mediator of DNA damage checkpoint protein 1PRO_0000096318Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei4 – 41PhosphothreonineBy similarity
Modified residuei146 – 1461PhosphothreonineBy similarity
Modified residuei168 – 1681PhosphoserineCombined sources
Modified residuei176 – 1761PhosphoserineBy similarity
Modified residuei298 – 2981PhosphoserineBy similarity
Modified residuei300 – 3001PhosphothreonineBy similarity
Modified residuei313 – 3131PhosphoserineBy similarity
Modified residuei315 – 3151PhosphothreonineBy similarity
Modified residuei360 – 3601PhosphoserineBy similarity
Modified residuei362 – 3621PhosphothreonineBy similarity
Modified residuei385 – 3851PhosphoserineBy similarity
Modified residuei387 – 3871PhosphothreonineBy similarity
Modified residuei398 – 3981PhosphoserineBy similarity
Modified residuei415 – 4151PhosphoserineBy similarity
Modified residuei425 – 4251PhosphoserineBy similarity
Modified residuei438 – 4381PhosphoserineCombined sources
Modified residuei442 – 4421PhosphoserineCombined sources
Modified residuei444 – 4441PhosphothreonineCombined sources
Modified residuei461 – 4611PhosphoserineCombined sources
Modified residuei470 – 4701PhosphothreonineCombined sources
Modified residuei492 – 4921PhosphoserineCombined sources
Modified residuei493 – 4931PhosphoserineCombined sources
Modified residuei591 – 5911PhosphoserineCombined sources
Modified residuei593 – 5931PhosphoserineCombined sources
Modified residuei595 – 5951PhosphoserineCombined sources
Modified residuei735 – 7351PhosphoserineBy similarity
Modified residuei750 – 7501PhosphoserineBy similarity
Modified residuei769 – 7691N6-acetyllysineBy similarity
Modified residuei885 – 8851PhosphoserineBy similarity
Modified residuei929 – 9291PhosphoserineBy similarity
Modified residuei962 – 9621PhosphoserineBy similarity
Modified residuei991 – 9911PhosphoserineBy similarity
Modified residuei1056 – 10561PhosphothreonineCombined sources
Modified residuei1104 – 11041PhosphoserineCombined sources
Modified residuei1126 – 11261PhosphoserineCombined sources
Modified residuei1128 – 11281PhosphoserineCombined sources
Modified residuei1132 – 11321PhosphothreonineCombined sources
Modified residuei1173 – 11731PhosphothreonineBy similarity
Modified residuei1234 – 12341PhosphothreonineBy similarity
Modified residuei1297 – 12971PhosphothreonineCombined sources
Modified residuei1298 – 12981PhosphothreonineCombined sources
Modified residuei1327 – 13271PhosphoserineBy similarity
Modified residuei1352 – 13521PhosphothreonineBy similarity
Modified residuei1359 – 13591PhosphoserineBy similarity
Modified residuei1375 – 13751PhosphothreonineBy similarity
Modified residuei1435 – 14351PhosphoserineCombined sources
Modified residuei1436 – 14361PhosphoserineCombined sources
Modified residuei1439 – 14391PhosphoserineCombined sources
Modified residuei1443 – 14431PhosphoserineCombined sources
Cross-linki1461 – 1461Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)By similarity
Cross-linki1461 – 1461Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei1480 – 14801PhosphothreonineCombined sources
Modified residuei1496 – 14961N6-acetyllysineCombined sources

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-1461 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

EPDiQ5PSV9.
MaxQBiQ5PSV9.
PaxDbiQ5PSV9.
PeptideAtlasiQ5PSV9.
PRIDEiQ5PSV9.

PTM databases

iPTMnetiQ5PSV9.
PhosphoSiteiQ5PSV9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000061607.
CleanExiMM_MDC1.

Interactioni

Subunit structurei

Homodimer. Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with CHEK2, which 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). Interacts with H2AFX, which requires phosphorylation of H2AFX. Interacts with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi232163. 6 interactions.
STRINGi10090.ENSMUSP00000080949.

Structurei

Secondary structure

1
1707
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi31 – 366Combined sources
Beta strandi45 – 495Combined sources
Beta strandi51 – 599Combined sources
Beta strandi62 – 654Combined sources
Beta strandi76 – 805Combined sources
Beta strandi88 – 914Combined sources
Beta strandi98 – 1003Combined sources
Turni101 – 1044Combined sources
Beta strandi105 – 1073Combined sources
Beta strandi120 – 1234Combined sources
Beta strandi126 – 1327Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3VA1X-ray1.74A/B29-139[»]
3VA4X-ray1.54A/B29-139[»]
ProteinModelPortaliQ5PSV9.
SMRiQ5PSV9. Positions 29-135, 1509-1703.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini54 – 10552FHAPROSITE-ProRule annotationAdd
BLAST
Domaini1510 – 158879BRCT 1PROSITE-ProRule annotationAdd
BLAST
Domaini1609 – 170092BRCT 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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi995 – 1394400Pro-richAdd
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

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG4111RPS. LUCA.
HOGENOMiHOG000113506.
HOVERGENiHBG080567.
InParanoidiQ5PSV9.
PhylomeDBiQ5PSV9.

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. 1 hit.
PROSITEiPS50172. BRCT. 1 hit.
PS50006. FHA_DOMAIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5PSV9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MESTQVIDWD AEEEEETELS SGSLGYSVEP IGQLRLFSGT HGPERDFPLY
60 70 80 90 100
LGKNVVGRSP DCSVALPFPS ISKQHAVIEI SAWNKAPILQ DCGSLNGTQI
110 120 130 140 150
VKPPRVLPPG VSHRLRDQEL ILFADFPCQY HRLDVPPPLV PRSLLTIEKT
160 170 180 190 200
PRIRIESQNS RVLLAADSEE EGDFPSGRCV ANGQRNTASP SATVVPESDE
210 220 230 240 250
EVSSPAPSVP GPSSPFGLGS DTDEEQGQQP GVEESSLADS SGAAGEAEQP
260 270 280 290 300
EANGTTAGIQ AQPTEHKLKD TKVKKEAGRA GVSDGSVLER SPTLGEDSDT
310 320 330 340 350
EVDEDHKPGF ADSETDVEEE RIPVTPPVAP VKKNQVLLAV GIGDPEAPGV
360 370 380 390 400
AHLQDCLAGS GTDVEDKTAL DVPLERNHTP MVINSDTDEE EEEEEEVSAA
410 420 430 440 450
LTLAHLKERG IGLWSRDPGA EEVKSQPQVL VEQSQSASGR DSDTDVEEES
460 470 480 490 500
SGRKREIIPD SPMDVDEALT VTQPESQPPR RPNDADEYMD MSSPGSHLVV
510 520 530 540 550
NQASFAVVGK TRAQVEEEVP GPSVILGEKH QVPLEGAQPP EEAWETAVQE
560 570 580 590 600
GSSSPEAAAS VRPSQQPVAE DAGTECATAV SEQESTLEVR SQSGSPAAPV
610 620 630 640 650
EQVVIHTDTS GDPTLPQREG AQTPTGRERE AHVGRTKSAK ECCDAEPEDL
660 670 680 690 700
CLPATQCFVE GESQHPEAVQ SLENEPTQLF PCTLPQEPGP SHLSLQTPGA
710 720 730 740 750
DTLDVPWEVL ATQPFCLREQ SETSELHEAH GSQPSLPREP PGHQHLVHTS
760 770 780 790 800
PVHTELLRIE GREIQTVEKA MGIPKEMADR MTPEREPLER EIRGRTENSE
810 820 830 840 850
RDVIGEELIQ GTKDREPKKV LARDSQRKEA DKDLEGNRES LEVEIEMSKD
860 870 880 890 900
SQKRERKVEK PEPKREWEPA DLEVTPDRGV TEEGSHDQKG QIASLTLKPG
910 920 930 940 950
VGVKDLEGLA SAPIITGSQA DGGKGDPLSP GRQQRGRLSC QTTPAGKASR
960 970 980 990 1000
GDPEPPDHCL FSSVPEASTQ SLLTSQSQKQ STPQPLFSTS SSEIPLPESL
1010 1020 1030 1040 1050
HTKPNVRPRR SSRMTPSPHS SAALKPNTTC PTNQPAASRP TSRPTRGRAN
1060 1070 1080 1090 1100
RSSTRTPELI VPVDPELQPS TSTEQPVIPK LTSQVTEGRV QMPEPLLTGP
1110 1120 1130 1140 1150
EIQSPTSTEQ SVTPDRKPRA TRGRPSKSPN KTPEPLISTG PELQPPTSIE
1160 1170 1180 1190 1200
QPVIPKPTSR VTRGRPRKSS VRTPESVVST GPELQPLTSI EQPVIPEPRA
1210 1220 1230 1240 1250
TRGRPSKSSI KTPESVVPTG PELQPLTSAK QPVTPNLTSR ASRGRSSKSI
1260 1270 1280 1290 1300
RTPEPVVQTG PEFHPSTSTE QPDTREPSSQ ARTRRSAVKT PEASVPTTPE
1310 1320 1330 1340 1350
LQPFTSKKQP APKPTALVTQ GRTYKPSTED CESVGPVAPD FEPSTSTDHL
1360 1370 1380 1390 1400
VTPKVTDQSL TLQSSPLSAS PVSSTPDLKP PVPIAQPVTP EPIPQANHQR
1410 1420 1430 1440 1450
KRRAAGKQGS RTVPLGHKSY SALSEPEPQS SASQSSGASE ADSPRQKRPR
1460 1470 1480 1490 1500
RQASQKTVVI KEEPVETEVK EEPQETAIPT PEKRKRDHAE EVTQGKPTRS
1510 1520 1530 1540 1550
RRTKPNQETA PKVLFTGVMD SRGERAVLAL GGSLASSVNE ASHLVTDRIR
1560 1570 1580 1590 1600
RTVKFLCALG KGIPILSLNW LYQSRKAGCF LPPDDYLVTD PEQEKNFSFS
1610 1620 1630 1640 1650
LRDSLCRARE RRLLEDYEIH VTPGVQPPPP QMGEIISCCG GTFLPSMPHS
1660 1670 1680 1690 1700
YKLHRVIITC TEDLPRCAIP SRLGLPLLSP EFLLTGVLKQ EATPEAFVLS

NLEMSST
Length:1,707
Mass (Da):184,670
Last modified:January 4, 2005 - v1
Checksum:iF6ECCD30BBED265D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti396 – 3961E → EE in AAH94363 (PubMed:15489334).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY826432 Genomic DNA. Translation: AAV85449.1.
BC085140 mRNA. Translation: AAH85140.1.
BC094363 mRNA. Translation: AAH94363.1.
AK129074 mRNA. Translation: BAC97884.1.
RefSeqiNP_001010833.2. NM_001010833.2.
UniGeneiMm.218511.

Genome annotation databases

GeneIDi240087.
KEGGimmu:240087.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY826432 Genomic DNA. Translation: AAV85449.1.
BC085140 mRNA. Translation: AAH85140.1.
BC094363 mRNA. Translation: AAH94363.1.
AK129074 mRNA. Translation: BAC97884.1.
RefSeqiNP_001010833.2. NM_001010833.2.
UniGeneiMm.218511.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3VA1X-ray1.74A/B29-139[»]
3VA4X-ray1.54A/B29-139[»]
ProteinModelPortaliQ5PSV9.
SMRiQ5PSV9. Positions 29-135, 1509-1703.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi232163. 6 interactions.
STRINGi10090.ENSMUSP00000080949.

PTM databases

iPTMnetiQ5PSV9.
PhosphoSiteiQ5PSV9.

Proteomic databases

EPDiQ5PSV9.
MaxQBiQ5PSV9.
PaxDbiQ5PSV9.
PeptideAtlasiQ5PSV9.
PRIDEiQ5PSV9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi240087.
KEGGimmu:240087.

Organism-specific databases

CTDi9656.
MGIiMGI:3525201. Mdc1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG2043. Eukaryota.
ENOG4111RPS. LUCA.
HOGENOMiHOG000113506.
HOVERGENiHBG080567.
InParanoidiQ5PSV9.
PhylomeDBiQ5PSV9.

Miscellaneous databases

ChiTaRSiMdc1. mouse.
PROiQ5PSV9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000061607.
CleanExiMM_MDC1.

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. 1 hit.
PROSITEiPS50172. BRCT. 1 hit.
PS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDC1_MOUSE
AccessioniPrimary (citable) accession number: Q5PSV9
Secondary accession number(s): Q52KG1, Q5U4D3, Q6ZQH7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: January 4, 2005
Last modified: September 7, 2016
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.