MDC1_PIG
ID MDC1_PIG Reviewed; 2042 AA.
AC Q767L8; Q767K4;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 101.
DE RecName: Full=Mediator of DNA damage checkpoint protein 1;
GN Name=MDC1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Large white;
RX PubMed=14673549; DOI=10.1007/s00251-003-0627-0;
RA Shigenari A., Ando A., Renard C., Chardon P., Shiina T., Kulski J.K.,
RA Yasue H., Inoko H.;
RT "Nucleotide sequencing analysis of the swine 433-kb genomic segment located
RT between the non-classical and classical SLA class I gene clusters.";
RL Immunogenetics 55:695-705(2004).
CC -!- FUNCTION: Required for checkpoint mediated cell cycle arrest in
CC response to DNA damage within both the S phase and G2/M phases of the
CC cell cycle. May serve as a scaffold for the recruitment of DNA repair
CC and signal transduction proteins to discrete foci of DNA damage marked
CC by 'Ser-139' phosphorylation of histone H2AX. Also required for
CC downstream events subsequent to the recruitment of these proteins.
CC These include phosphorylation and activation of the ATM, CHEK1 and
CC CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2
CC may also be activated independently by a parallel pathway mediated by
CC TP53BP1 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with several proteins involved in the DNA
CC damage response, although not all these interactions may be direct.
CC Interacts with H2AX, which requires phosphorylation of H2AX. Interacts
CC with the MRN complex, composed of MRE11, RAD50, and NBN. Interacts with
CC CHEK2, which requires ATM-mediated phosphorylation within the FHA
CC domain of CHEK2. Interacts constitutively with the BRCA1-BARD1 complex,
CC SMC1A and TP53BP1. Interacts with ATM and FANCD2, and these
CC interactions are reduced upon DNA damage. Also interacts with the PRKDC
CC complex, composed of XRCC6/KU70, XRCC5/KU80 and PRKDC/XRCC7. This
CC interaction may be required for PRKDC autophosphorylation, which is
CC essential for DNA double strand break (DSB) repair. When phosphorylated
CC by ATM, interacts with RNF8 (via FHA domain). Interacts with CEP164.
CC When phosphorylated, interacts with APTX (via FHA-like domain) (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Chromosome {ECO:0000250}.
CC Note=Associated with chromatin. Relocalizes to discrete nuclear foci
CC following DNA damage, this requires phosphorylation of H2AX.
CC Colocalizes with APTX at sites of DNA double-strand breaks (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: Tandemly repeated BRCT domains are characteristic of proteins
CC involved in DNA damage signaling. In MDC1, these repeats are required
CC for localization to chromatin which flanks sites of DNA damage marked
CC by 'Ser-139' phosphorylation of H2AX (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated upon exposure to ionizing radiation (IR),
CC ultraviolet radiation (UV), and hydroxyurea (HU). Phosphorylation in
CC response to IR requires ATM, NBN, and possibly CHEK2. Also
CC phosphorylated during the G2/M phase of the cell cycle and during
CC activation of the mitotic spindle checkpoint. Phosphorylation at Thr-4
CC by ATM stabilizes and enhances homodimerization via the FHA domain (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Sumoylation by PIAS4 following DNA damage promotes ubiquitin-
CC mediated degradation. {ECO:0000250}.
CC -!- PTM: Ubiquitinated by RNF4, leading to proteasomal degradation;
CC undergoes 'Lys-48'-linked polyubiquitination. {ECO:0000250}.
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DR EMBL; AB113356; BAD08434.1; -; Genomic_DNA.
DR EMBL; AB113357; BAD08445.1; -; Genomic_DNA.
DR RefSeq; NP_001116610.1; NM_001123138.1.
DR AlphaFoldDB; Q767L8; -.
DR SMR; Q767L8; -.
DR STRING; 9823.ENSSSCP00000001438; -.
DR PaxDb; Q767L8; -.
DR PeptideAtlas; Q767L8; -.
DR GeneID; 100144453; -.
DR KEGG; ssc:100144453; -.
DR CTD; 9656; -.
DR eggNOG; KOG2043; Eukaryota.
DR InParanoid; Q767L8; -.
DR OrthoDB; 670424at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF16770; RTT107_BRCT_5; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
PE 3: Inferred from homology;
KW Acetylation; Cell cycle; Chromosome; DNA damage; DNA repair;
KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..2042
FT /note="Mediator of DNA damage checkpoint protein 1"
FT /id="PRO_0000096320"
FT DOMAIN 54..105
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DOMAIN 1845..1923
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1944..2035
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 1..150
FT /note="Interaction with CHEK2"
FT /evidence="ECO:0000250"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..219
FT /note="Interaction with the MRN complex"
FT REGION 139..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..557
FT /note="Required for nuclear localization (NLS1)"
FT /evidence="ECO:0000250"
FT REGION 185..387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 419..585
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 642..727
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 747..1843
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1137..1580
FT /note="Interaction with the PRKDC complex"
FT /evidence="ECO:0000250"
FT REGION 1661..2042
FT /note="Required for nuclear localization (NLS2)"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..20
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 253..268
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..497
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 658..686
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 711..727
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 815..856
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 857..879
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 885..923
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1030..1115
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1152..1167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1234..1248
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1317..1331
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1354..1371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1385..1412
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1422..1436
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1437..1453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1463..1479
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1480..1496
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1504..1520
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1551..1565
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1579..1616
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1659..1681
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1710..1728
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1789..1832
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 4
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 146
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2M8"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 293
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 323
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 370
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 449
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 502
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 512
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5U2M8"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 802
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 945
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 989
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1027
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1080
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1146
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1187
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1228
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1269
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1381
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1384
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1385
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1399
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1440
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1507
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5PSV9"
FT MOD_RES 1522
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1538
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1541
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1563
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1575
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1579
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1593
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1634
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1754
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1774
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT MOD_RES 1896
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
FT CROSSLNK 1744
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q14676"
SQ SEQUENCE 2042 AA; 217917 MW; 897310CC1674C549 CRC64;
MEDTQVINWE AEEEEVEEGP SEPLGCNLQP VGQLRIFSSS YGPEKDFPLY LGKNVVGRMP
ECSVALPFSS ISKQHAVIEI LAWNKAPVLR DCGSLNGTQI LRPPKVLGPG VSHRLRNREL
ILFADLPCQY HRLDVPPPLV SRGPLTVEET PRGQGGTQPH RLLLAEDSEE EVDSLSERCV
VKGPKTSLTT VIPESDEEGP SPAPDGPGPP FAFNLNSDTD EEESQQPGAG EAPSAAETEQ
PKPVTTEIQL IKDQCPVKEK HKDARVKRAA SNGVVPVGAI LERSQPAGED SDTDVDEGSG
LPRRPAGAHS ERAQPCGFID SDTDAEEEGI PATPAVVPVK KRQIFHEVGT ESPQAPGVAH
AQESPAGSDT DIEEGEAPRT VPLDSSRASM MIDSNMDDEE EVSAALTLAR LRESQAVPWN
RDAGAGDHRA QPVALLDQSQ ASAGRDSDTD MEEEGLPLEK RGSLPKGPAD KAHPEKSQPP
LRGSDVKVEE DERSPGVHPG RSQASATVDA ITQVEEKAPP RPAVTLSEQH QVPVAWTPQT
DVEAEGDPAK LPVVHPAEAR PPPAGGHEPD VEKNTSLAAS AGADVRKSQL LAEGDAGTEW
AVAILAQDRA LGAGAQSVSA RAQVGQDLPL VSREHLADVA VDTGAPGEAT QTQREGTQAL
TERERELNVD RTIDSGDNRD DSEDLDLQAT QCFVEGENQS PEAVPSMEDE PTQAFPSTLP
QEPGPSCCSF QASGTLDEPW ELLATQPFCP RESEASEIQP VDTHLEARGL CPSPPRAALP
EQHPESPEPL GSQGGGRQTV EKATGTPRET AEGPTPERGP LERATKEPPS EGERGGMGEE
GLPRGTQDRE EKQVLAGVTQ RQESDRTVKS TSTDGGLESL QVEIETPKEM QENEIEKQTL
ARDMLEREAE KPVAERESEA GGPEVKVPEA VQDRGPLRAE AEGTSQDQKG QASNLTPEPG
AGVGYLQGLA SAPAAPRSQA GGGGEAPVSP RRQQRGDLNC KMPPAEKSGV RAAFSPSLPS
PHGDQESPEA CLPPEPPEAS APLQNPLPSQ SPKHPAPQSR LSPPPPPLEQ STPRTRPPQS
QESPEPPFSS ELDPPNPEPK VRPQGSPPLS PIPLEAHPTS PTDQAGSPEP TSRAARGGTH
RSFEVTPMSV VPTALELQSS TSADQPVVPK PTLRAPWGRT HRSSVKTPEP NIPTAPELQP
STPTDQPVAP EPLSRATRGR TPRASVKTSE PVVPAAPEPQ PSTPTDQPVV PKPTLRAPRG
RTHRSSVKTP EPNIPTAPEL RPSTPTDQPV APEPLSRATR GRTPRASVKS PEQNVPTAPE
HPQPSTPTDQ PVTPKPTSRA TRGRAHRSSV KTPAASEPLP SASTDQPITP KPTSRGRAHR
SSAKTPELQP PTSTGQPVTP RPTSQATRGR THRSSIKTPE PVVPTDPEPQ PSTPTDQPIT
PELTSAATRG RTRRSSVKTP EPVVPTDPEP QPSTPTDQPI TPKPTSWATR GQAHRSSVKT
PEPHVPTDPE PQPSTPTDQP VTPKPTSRAT RGRARKSSVK TPEPAVPTAA EPQPSASTDQ
PITPKPTSRG RAHRSSAKTP ELQPPTSTGQ PFTPRPTSGA TQGRTHRSSA KTSQAVEPTA
PDLEPPSPIG QPVTPKVIAE GGQNRILRSS RVGAVPGPTP PELQCPVPTE QPVPPEPIPR
ASCSRRPRAT RKRESLTAHV GPDPCSAPPE PNSRSSRTQS LSTTPEPTLP QLPEAPAHAP
QIPKVEAAGR PGFTLEPQPK ATQKRKRPLA PADSPPLPKR LQRGEVPPKT VILEEEENPT
ARPGREEDAV IPEPGKRKRD QTEEEPRGVP SRSLRRTKPA QESTAPRVLF TGVVDARGER
AVLALGGSLA SSVAEASHLV TDRIRRTVKF LCALGRGIPI LSLDWLHQSR KAGCFLPPDE
YVVTDPEQEK NFGFSLREAL SRARERKLLE GYEIHVTPGV QPPPPQMGEI ISCCGGTVLP
SMPRSYKPQR VVITCSQDFP RCSVPFRLGL PVLSPEFLLT GVLKQEAKPE AFVLSTLEMA
SA
