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Overview

Uniprot IDQ14676
Protein NameMediator of DNA damage checkpoint protein 1
Gene NameMDC1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1004 VSPRRHQKGLLNCKM
1010 QKGLLNCKMPPAEKA
1016 CKMPPAEKASRIRAA
1106 EPFHPKPKIRTRKSS
1632 TDQPVTPKLTSRATR
1648 KTNRSSVKTPKPVEP
1722 ITQPSCIKRQRAAGN
1790 IHASQIQKVEPAGRS
1806 FTPELQPKASQSRKR
1835 QRGEVSQKTVIIKEE
1885 SRSLRRTKLNQESTA
351 VIPMKKRKIFHGVGT
472 ENREAVLKDHTKIRA
476 AVLKDHTKIRALVRA
540 SAIIHIKKHQVSVEG
554 GTNQTDVKAVGGPAK
597 SVVADVRKSQLPAEG
812 RGRQTVDKVMGIPKE

Function

Histone reader protein 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 (PubMed:12475977, PubMed:12499369, PubMed:12551934, PubMed:12607003, PubMed:12607004, PubMed:12607005, PubMed:12611903, PubMed:14695167, PubMed:15201865, PubMed:15377652, PubMed:16049003, PubMed:16377563, PubMed:30898438). Specifically recognizes and binds histone H2AX phosphorylated at 'Ser-139', a marker of DNA damage, serving as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage sites (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438). Also required for downstream events subsequent to the recruitment of these proteins (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:18582474). These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53/p53 and apoptosis (PubMed:12499369, PubMed:12551934, PubMed:12607004). ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (PubMed:12499369, PubMed:12551934, PubMed:12607004). Required for chromosomal stability during mitosis by promoting recruitment of TOPBP1 to DNA double strand breaks (DSBs): TOPBP1 forms filamentous assemblies that bridge MDC1 and tether broken chromosomes during mitosis (PubMed:30898438). Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs (PubMed:18411307, PubMed:18582474, PubMed:18583988, PubMed:18678890)

Protein Sequence

10 MEDTQAIDWD 20 VEEEEETEQS 30 SESLRCNVEP 40 VGRLHIFSGA 50 HGPEKDFPLH 60 LGKNVVGRMP 70 DCSVALPFPS 80 ISKQHAEIEI 90 LAWDKAPILR 100 DCGSLNGTQI 110 LRPPKVLSPG 120 VSHRLRDQEL 130 ILFADLLCQY 140 HRLDVSLPFV 150 SRGPLTVEET 160 PRVQGETQPQ 170 RLLLAEDSEE 180 EVDFLSERRM 190 VKKSRTTSSS 200 VIVPESDEEG 210 HSPVLGGLGP 220 PFAFNLNSDT 230 DVEEGQQPAT 240 EEASSAARRG 250 ATVEAKQSEA 260 EVVTEIQLEK 270 DQPLVKERDN 280 DTKVKRGAGN 290 GVVPAGVILE 300 RSQPPGEDSD 310 TDVDDDSRPP 320 GRPAEVHLER 330 AQPFGFIDSD 340 TDAEEERIPA 350 TPVVIPMKKR 360 KIFHGVGTRG 370 PGAPGLAHLQ 380 ESQAGSDTDV 390 EEGKAPQAVP 400 LEKSQASMVI 410 NSDTDDEEEV 420 SAALTLAHLK 430 ESQPAIWNRD 440 AEEDMPQRVV 450 LLQRSQTTTE 460 RDSDTDVEEE 470 ELPVENREAV 480 LKDHTKIRAL 490 VRAHSEKDQP 500 PFGDSDDSVE 510 ADKSSPGIHL 520 ERSQASTTVD 530 INTQVEKEVP 540 PGSAIIHIKK 550 HQVSVEGTNQ 560 TDVKAVGGPA 570 KLLVVSLEEA 580 WPLHGDCETD 590 AEEGTSLTAS 600 VVADVRKSQL 610 PAEGDAGAEW 620 AAAVLKQERA 630 HEVGAQGGPP 640 VAQVEQDLPI 650 SRENLTDLVV 660 DTDTLGESTQ 670 PQREGAQVPT 680 GREREQHVGG 690 TKDSEDNYGD 700 SEDLDLQATQ 710 CFLENQGLEA 720 VQSMEDEPTQ 730 AFMLTPPQEL 740 GPSHCSFQTT 750 GTLDEPWEVL 760 ATQPFCLRES 770 EDSETQPFDT 780 HLEAYGPCLS 790 PPRAIPGDQH 800 PESPVHTEPM 810 GIQGRGRQTV 820 DKVMGIPKET 830 AERVGPERGP 840 LERETEKLLP 850 ERQTDVTGEE 860 ELTKGKQDRE 870 QKQLLARDTQ 880 RQESDKNGES 890 ASPERDRESL 900 KVEIETSEEI 910 QEKQVQKQTL 920 PSKAFEREVE 930 RPVANRECDP 940 AELEEKVPKV 950 ILERDTQRGE 960 PEGGSQDQKG 970 QASSPTPEPG 980 VGAGDLPGPT 990 SAPVPSGSQS 1000 GGRGSPVSPR 1010 RHQKGLLNCK 1020 MPPAEKASRI 1030 RAAEKVSRGD 1040 QESPDACLPP 1050 TVPEAPAPPQ 1060 KPLNSQSQKH 1070 LAPPPLLSPL 1080 LPSIKPTVRK 1090 TRQDGSQEAP 1100 EAPLSSELEP 1110 FHPKPKIRTR 1120 KSSRMTPFPA 1130 TSAAPEPHPS 1140 TSTAQPVTPK 1150 PTSQATRSRT 1160 NRSSVKTPEP 1170 VVPTAPELQP 1180 STSTDQPVTS 1190 EPTSQVTRGR 1200 KSRSSVKTPE 1210 TVVPTALELQ 1220 PSTSTDRPVT 1230 SEPTSQATRG 1240 RKNRSSVKTP 1250 EPVVPTAPEL 1260 QPSTSTDQPV 1270 TSEPTYQATR 1280 GRKNRSSVKT 1290 PEPVVPTAPE 1300 LRPSTSTDRP 1310 VTPKPTSRTT 1320 RSRTNMSSVK 1330 TPETVVPTAP 1340 ELQISTSTDQ 1350 PVTPKPTSRT 1360 TRSRTNMSSV 1370 KNPESTVPIA 1380 PELPPSTSTE 1390 QPVTPEPTSR 1400 ATRGRKNRSS 1410 GKTPETLVPT 1420 APKLEPSTST 1430 DQPVTPEPTS 1440 QATRGRTNRS 1450 SVKTPETVVP 1460 TAPELQPSTS 1470 TDQPVTPEPT 1480 SQATRGRTDR 1490 SSVKTPETVV 1500 PTAPELQASA 1510 STDQPVTSEP 1520 TSRTTRGRKN 1530 RSSVKTPETV 1540 VPAAPELQPS 1550 TSTDQPVTPE 1560 PTSRATRGRT 1570 NRSSVKTPES 1580 IVPIAPELQP 1590 STSRNQLVTP 1600 EPTSRATRCR 1610 TNRSSVKTPE 1620 PVVPTAPEPH 1630 PTTSTDQPVT 1640 PKLTSRATRR 1650 KTNRSSVKTP 1660 KPVEPAASDL 1670 EPFTPTDQSV 1680 TPEAIAQGGQ 1690 SKTLRSSTVR 1700 AMPVPTTPEF 1710 QSPVTTDQPI 1720 SPEPITQPSC 1730 IKRQRAAGNP 1740 GSLAAPIDHK 1750 PCSAPLEPKS 1760 QASRNQRWGA 1770 VRAAESLTAI 1780 PEPASPQLLE 1790 TPIHASQIQK 1800 VEPAGRSRFT 1810 PELQPKASQS 1820 RKRSLATMDS 1830 PPHQKQPQRG 1840 EVSQKTVIIK 1850 EEEEDTAEKP 1860 GKEEDVVTPK 1870 PGKRKRDQAE 1880 EEPNRIPSRS 1890 LRRTKLNQES 1900 TAPKVLFTGV 1910 VDARGERAVL 1920 ALGGSLAGSA 1930 AEASHLVTDR 1940 IRRTVKFLCA 1950 LGRGIPILSL 1960 DWLHQSRKAG 1970 FFLPPDEYVV 1980 TDPEQEKNFG 1990 FSLQDALSRA 2000 RERRLLEGYE 2010 IYVTPGVQPP 2020 PPQMGEIISC 2030 CGGTYLPSMP 2040 RSYKPQRVVI 2050 TCPQDFPHCS 2060 IPLRVGLPLL 2070 SPEFLLTGVL 2080 KQEAKPEAFV LSPLEMSST

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005694 chromosome
Cellular Component GO:0016604 nuclear body
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0035861 site of double-strand break
Molecular Function GO:0140463 chromatin-protein adaptor activity
Molecular Function GO:0140566 histone reader activity
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006281 DNA repair
Biological Process GO:0000076 DNA replication checkpoint signaling
Biological Process GO:0031573 mitotic intra-S DNA damage checkpoint signaling
Biological Process GO:1990166 protein localization to site of double-strand break

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[5] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.