MDC1
entrez
9656
canonical
uniprot
Q14676
canonical
ensembl
ENSG00000137337
resolver
ensembl
ENSG00000206481
resolver
ensembl
ENSG00000224587
resolver
ensembl
ENSG00000225589
resolver
ensembl
ENSG00000228575
resolver
ensembl
ENSG00000231135
resolver
ensembl
ENSG00000234012
resolver
ensembl
ENSG00000237095
resolver
ensp
ENSP00000365588
resolver
ensp
ENSP00000373060
resolver
ensp
ENSP00000404318
resolver
ensp
ENSP00000530577
resolver
ensp
ENSP00000609713
resolver
ensp
ENSP00000609715
resolver
enst
ENST00000383566
resolver
enst
ENST00000435664
resolver
genesymbol
MDC1
resolver
genesymbol_syn
KIAA0170
resolver
genesymbol_syn
NFBD1
resolver
hgnc
HGNC:21163
resolver
uniprot
A1Z5I9
resolver
uniprot
A2AB04
resolver
uniprot
A2BF04
resolver
uniprot
A2RRA8
resolver
uniprot
A7YY86
resolver
uniprot
B0S8A2
resolver
uniprot
Q0EFC2
resolver
uniprot
Q2L6H7
resolver
uniprot
Q2TAZ4
resolver
uniprot
Q5JP55
resolver
uniprot
Q5JP56
resolver
uniprot
Q5ST83
resolver
uniprot
Q68CQ3
resolver
uniprot
Q86Z06
resolver
uniprot
Q96QC2
resolver
uniprot_entry
A1Z5I9_HUMAN
resolver
uniprot_entry
MDC1_HUMAN
resolver
uniprot_sec
A2AB04
resolver
uniprot_sec
A2BF04
resolver
uniprot_sec
A2RRA8
resolver
uniprot_sec
A7YY86
resolver
uniprot_sec
B0S8A2
resolver
uniprot_sec
Q0EFC2
resolver
uniprot_sec
Q2L6H7
resolver
uniprot_sec
Q2TAZ4
resolver
uniprot_sec
Q5JP55
resolver
uniprot_sec
Q5JP56
resolver
uniprot_sec
Q5ST83
resolver
uniprot_sec
Q68CQ3
resolver
uniprot_sec
Q86Z06
resolver
uniprot_sec
Q96QC2
resolver
amino_acid_sequence
MEDTQAIDWDVEEEEETEQSSESLRCNVEPVGRLHIFSGAHGPEKDFPLHLGKNVVGRMPDCSVALPFPSISKQHAEIEILAWDKAPILRDCGSLNGTQILRPPKVLSPGVSHRLRDQELILFADLLCQYHRLDVSLPFVSRGPLTVEETPRVQGETQPQRLLLAEDSEEEVDFLSERRMVKKSRTTSSSVIVPESDEEGHSPVLGGLGPPFAFNLNSDTDVEEGQQPATEEASSAARRGATVEAKQSEAEVVTEIQLEKDQPLVKERDNDTKVKRGAGNGVVPAGVILERSQPPGEDSDTDVDDDSRPPGRPAEVHLERAQPFGFIDSDTDAEEERIPATPVVIPMKKRKIFHGVGTRGPGAPGLAHLQESQAGSDTDVEEGKAPQAVPLEKSQASMVINSDTDDEEEVSAALTLAHLKESQPAIWNRDAEEDMPQRVVLLQRSQTTTERDSDTDVEEEELPVENREAVLKDHTKIRALVRAHSEKDQPPFGDSDDSVEADKSSPGIHLERSQASTTVDINTQVEKEVPPGSAIIHIKKHQVSVEGTNQTDVKAVGGPAKLLVVSLEEAWPLHGDCETDAEEGTSLTASVVADVRKSQLPAEGDAGAEWAAAVLKQERAHEVGAQGGPPVAQVEQDLPISRENLTDLVVDTDTLGESTQPQREGAQVPTGREREQHVGGTKDSEDNYGDSEDLDLQATQCFLENQGLEAVQSMEDEPTQAFMLTPPQELGPSHCSFQTTGTLDEPWEVLATQPFCLRESEDSETQPFDTHLEAYGPCLSPPRAIPGDQHPESPVHTEPMGIQGRGRQTVDKVMGIPKETAERVGPERGPLERETEKLLPERQTDVTGEEELTKGKQDREQKQLLARDTQRQESDKNGESASPERDRESLKVEIETSEEIQEKQVQKQTLPSKAFEREVERPVANRECDPAELEEKVPKVILERDTQRGEPEGGSQDQKGQASSPTPEPGVGAGDLPGPTSAPVPSGSQSGGRGSPVSPRRHQKGLLNCKMPPAEKASRIRAAEKVSRGDQESPDACLPPTVPEAPAPPQKPLNSQSQKHLAPPPLLSPLLPSIKPTVRKTRQDGSQEAPEAPLSSELEPFHPKPKIRTRKSSRMTPFPATSAAPEPHPSTSTAQPVTPKPTSQATRSRTNRSSVKTPEPVVPTAPELQPSTSTDQPVTSEPTSQVTRGRKSRSSVKTPETVVPTALELQPSTSTDRPVTSEPTSQATRGRKNRSSVKTPEPVVPTAPELQPSTSTDQPVTSEPTYQATRGRKNRSSVKTPEPVVPTAPELRPSTSTDRPVTPKPTSRTTRSRTNMSSVKTPETVVPTAPELQISTSTDQPVTPKPTSRTTRSRTNMSSVKNPESTVPIAPELPPSTSTEQPVTPEPTSRATRGRKNRSSGKTPETLVPTAPKLEPSTSTDQPVTPEPTSQATRGRTNRSSVKTPETVVPTAPELQPSTSTDQPVTPEPTSQATRGRTDRSSVKTPETVVPTAPELQASASTDQPVTSEPTSRTTRGRKNRSSVKTPETVVPAAPELQPSTSTDQPVTPEPTSRATRGRTNRSSVKTPESIVPIAPELQPSTSRNQLVTPEPTSRATRCRTNRSSVKTPEPVVPTAPEPHPTTSTDQPVTPKLTSRATRRKTNRSSVKTPKPVEPAASDLEPFTPTDQSVTPEAIAQGGQSKTLRSSTVRAMPVPTTPEFQSPVTTDQPISPEPITQPSCIKRQRAAGNPGSLAAPIDHKPCSAPLEPKSQASRNQRWGAVRAAESLTAIPEPASPQLLETPIHASQIQKVEPAGRSRFTPELQPKASQSRKRSLATMDSPPHQKQPQRGEVSQKTVIIKEEEEDTAEKPGKEEDVVTPKPGKRKRDQAEEEPNRIPSRSLRRTKLNQESTAPKVLFTGVVDARGERAVLALGGSLAGSAAEASHLVTDRIRRTVKFLCALGRGIPILSLDWLHQSRKAGFFLPPDEYVVTDPEQEKNFGFSLQDALSRARERRLLEGYEIYVTPGVQPPPPQMGEIISCCGGTYLPSMPRSYKPQRVVITCPQDFPHCSIPLRVGLPLLSPEFLLTGVLKQEAKPEAFVLSPLEMSST
uniprot
proteins
function
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). {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:30898438}.
uniprot
proteins
mass_dalton
226666
uniprot
proteins
mutagenesis
MUTAGEN 45; /note="K->A: Constitutively enhanced interaction with RNF8."; /evidence="ECO:0000269|PubMed:24240613"; MUTAGEN 58; /note="R->A: Abrogates binding to the MRE11 complex and to CHEK2."; /evidence="ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004"; MUTAGEN 72; /note="S->A: Abrogates binding to CHEK2."; /evidence="ECO:0000269|PubMed:12607004"; MUTAGEN 96; /note="N->A: Abrogates binding to CHEK2; when associated with A-97 and A-98."; /evidence="ECO:0000269|PubMed:12607004"; MUTAGEN 97; /note="G->A: Abrogates binding to CHEK2; when associated with A-96 and A-98."; /evidence="ECO:0000269|PubMed:12607004"; MUTAGEN 98; /note="T->A: Abrogates binding to CHEK2; when associated with A-96 and A-97."; /evidence="ECO:0000269|PubMed:12607004"; MUTAGEN 168; /note="S->A: Decreased phosphorylation by CK2, leading to impaired interaction with TOPBP1; when associated with A-196."; /evidence="ECO:0000269|PubMed:30898438"; MUTAGEN 196; /note="S->A: Decreased phosphorylation by CK2, leading to impaired interaction with TOPBP1; when associated with A-168."; /evidence="ECO:0000269|PubMed:30898438"; MUTAGEN 299..301; /note="SDT->ADA: Decreased phosphorylation by CK2, leading to impaired interaction with NBN."; /evidence="ECO:0000269|PubMed:18411307"; MUTAGEN 453..455; /note="SDT->ADA: Decreased phosphorylation by CK2, leading to impaired interaction with NBN."; /evidence="ECO:0000269|PubMed:18411307"; MUTAGEN 1840; /note="K->R: Suppresses RNF4-mediated ubiquitination, accumulates at sites of DNA damage, defective homologous recombination."; /evidence="ECO:0000269|PubMed:22635276
uniprot
proteins
post_translational_modification
PTM: Phosphorylated upon exposure to ionizing radiation (IR), ultraviolet radiation (UV), and hydroxyurea (HU) (PubMed:12607003, PubMed:12607004, PubMed:12607005). Phosphorylation in response to IR requires ATM, NBN, and possibly CHEK2 (PubMed:12607003, PubMed:12607004, PubMed:12607005). Also phosphorylated during the G2/M phase of the cell cycle and during activation of the mitotic spindle checkpoint (PubMed:12607003, PubMed:12607004, PubMed:12607005). Phosphorylation at Thr-4 by ATM stabilizes and enhances homodimerization via the FHA domain (PubMed:22234877). Phosphorylated at Ser-168 and Ser-196 by CK2 in response to DNA damage during mitosis, promoting interaction with TOPBP1 (PubMed:30898438). Phosphorylated by CK2 in response to DNA damage, promoting interaction with NBN and recruitment of the MRN complex to DNA damage sites (PubMed:18411307, PubMed:18583988, PubMed:18678890). {ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:22234877, ECO:0000269|PubMed:30898438}.; PTM: Sumoylation at Lys-1840 by PIAS4 following DNA damage promotes ubiquitin-mediated degradation. {ECO:0000269|PubMed:22635276}.; PTM: Ubiquitinated by RNF4, leading to proteasomal degradation; undergoes 'Lys-48'-linked polyubiquitination. {ECO:0000269|PubMed:22635276}.; PTM: Methylated at Lys-45. Demethylation at Lys-45 by JMJD1C after exposure to IR promotes MDC1-RNF8 interaction, RNF8-dependent MDC1 ubiquitination and recruitment of RAP80-BRCA1 to polyubiquitylated MDC1. {ECO:0000269|PubMed:24240613}.
uniprot
proteins
pubmed
12475977
uniprot
proteins
pubmed
12499369
uniprot
proteins
pubmed
12551934
uniprot
proteins
pubmed
12607003
uniprot
proteins
pubmed
12607004
uniprot
proteins
pubmed
12607005
uniprot
proteins
pubmed
12611903
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14695167
uniprot
proteins
pubmed
15201865
uniprot
proteins
pubmed
15279781
uniprot
proteins
pubmed
15377652
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16049003
uniprot
proteins
pubmed
16377563
uniprot
proteins
pubmed
16702430
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17693683
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18006705
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18283122
uniprot
proteins
pubmed
18411307
uniprot
proteins
pubmed
18582474
uniprot
proteins
pubmed
18583988
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18678890
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20008512
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20159462
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21482717
uniprot
proteins
pubmed
22139841
uniprot
proteins
pubmed
22234877
uniprot
proteins
pubmed
22635276
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23891287
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24240613
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25114211
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
30898438
uniprot
proteins
pubmed
35842428
uniprot
proteins
pubmed
8724849
uniprot
proteins
sequence_length
2089
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12475977, ECO:0000269|PubMed:12499369, ECO:0000269|PubMed:12551934, ECO:0000269|PubMed:12607003, ECO:0000269|PubMed:12607004, ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:12611903, ECO:0000269|PubMed:14695167, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:15377652, ECO:0000269|PubMed:20008512}. Chromosome {ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:18411307, ECO:0000269|PubMed:18582474, ECO:0000269|PubMed:18583988, ECO:0000269|PubMed:18678890, ECO:0000269|PubMed:20008512, ECO:0000269|PubMed:21482717, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35842428}. Note=Associated with chromatin (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563). Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AX (PubMed:12607005, PubMed:15201865, PubMed:16049003, PubMed:16377563, PubMed:30898438, PubMed:35842428). Colocalizes with APTX at sites of DNA double-strand breaks (PubMed:20008512). {ECO:0000269|PubMed:12607005, ECO:0000269|PubMed:15201865, ECO:0000269|PubMed:16049003, ECO:0000269|PubMed:16377563, ECO:0000269|PubMed:20008512, ECO:0000269|PubMed:30898438, ECO:0000269|PubMed:35842428}.
uniprot
proteins