UniProt Accession

 MDC1_HUMAN; Q14676; A2AB04; A2BF04; A2RRA8; A7YY86; B0S8A2; Q0EFC2; Q2L6H7; Q2TAZ4; Q5JP55; Q5JP56; Q5ST83; Q68CQ3; Q86Z06; Q96QC2 

Genbank Protein ID

 D79992; CR749828; BA000025; AB088099; AB202097; AB103605; AL662848; AL662797; AL845353; AL845353; AL662848; AL662797; BX248307; BX248307; BX927283; BX927283; CR936878; CR936878; CR788240; CR788240; CR759873; CR759873; CH471081; BC110645; BC152556 

Genbank Nucleotide ID

 BAA11487.2; CAH18685.1; BAB63322.1; BAC54931.1; BAE78617.1; BAF31266.1; CAI17440.1; CAI18195.1; CAI41890.2; CAI41891.1; CAM24847.1; CAM25512.1; CAM25928.1; CAM25929.1; CAQ06769.1; CAQ06770.1; CAQ06813.1; CAQ06814.1; CAQ07571.1; CAQ07572.1; CAQ08690.1; CAQ08691.1; EAX03321.1; AAI10646.1; AAI52557.1 

Protein Name

 Mediator of DNA damage checkpoint protein 1 

Protein Synonyms/Alias

 Nuclear factor with BRCT domains 1 

Gene Name

 MDC1 

Gene Synonyms/Alias

 KIAA0170; NFBD1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
45	SGAHGPEKDFPLHLG	ubiquitination	[1, 2]
487	LVRAHSEKDQPPFGD	acetylation	[3]
812	RGRQTVDKVMGIPKE	acetylation	[3, 4, 5, 6]
1402	RKNRSSGKTPETLVP	acetylation	[4, 5, 6]
1740	LAAPIDHKPCSAPLE	acetylation	[6]
1812	PKASQSRKRSLATMD	acetylation	[7]
1840	SQKTVIIKEEEEDTA	sumoylation	[8]
1852	DTAEKPGKEEDVVTP	acetylation	[7]
1885	SRSLRRTKLNQESTA	ubiquitination	[9]
2075	GVLKQEAKPEAFVLS	ubiquitination	[10]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [4] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [5] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [8] Sumoylation of MDC1 is important for proper DNA damage response.
 Luo K, Zhang H, Wang L, Yuan J, Lou Z.
 EMBO J. 2012 Jun 29;31(13):3008-19. [PMID: 22635276]
 [9] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [10] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 54 105 FHA.
 DOMAIN 1892 1970 BRCT 1.
 DOMAIN 1991 2082 BRCT 2.
 REGION 1 150 Interaction with CHEK2.
 REGION 2 220 Interaction with the MRN complex.
 REGION 145 568 Required for nuclear localization (NLS1).
 REGION 1148 1610 Interaction with the PRKDC complex.
 REGION 1698 2089 Required for nuclear localization (NLS2).
 MOD_RES 4 4 Phosphothreonine; by ATM.
 MOD_RES 108 108 Phosphoserine.
 MOD_RES 168 168 Phosphoserine.
 MOD_RES 299 299 Phosphoserine.
 MOD_RES 301 301 Phosphothreonine.
 MOD_RES 329 329 Phosphoserine.
 MOD_RES 331 331 Phosphothreonine.
 MOD_RES 372 372 Phosphoserine.
 MOD_RES 376 376 Phosphoserine.
 MOD_RES 378 378 Phosphothreonine.
 MOD_RES 394 394 Phosphoserine.
 MOD_RES 397 397 Phosphoserine.
 MOD_RES 402 402 Phosphoserine.
 MOD_RES 404 404 Phosphothreonine.
 MOD_RES 411 411 Phosphoserine.
 MOD_RES 449 449 Phosphothreonine.
 MOD_RES 453 453 Phosphoserine.
 MOD_RES 455 455 Phosphothreonine.
 MOD_RES 485 485 Phosphoserine.
 MOD_RES 495 495 Phosphoserine.
 MOD_RES 498 498 Phosphoserine.
 MOD_RES 513 513 Phosphoserine.
 MOD_RES 523 523 Phosphothreonine.
 MOD_RES 780 780 Phosphoserine.
 MOD_RES 793 793 Phosphoserine.
 MOD_RES 812 812 N6-acetyllysine.
 MOD_RES 955 955 Phosphoserine.
 MOD_RES 988 988 Phosphoserine (By similarity).
 MOD_RES 1033 1033 Phosphoserine.
 MOD_RES 1068 1068 Phosphoserine.
 MOD_RES 1157 1157 Phosphothreonine.
 MOD_RES 1198 1198 Phosphothreonine.
 MOD_RES 1399 1399 Phosphoserine.
 MOD_RES 1400 1400 Phosphoserine.
 MOD_RES 1402 1402 N6-acetyllysine.
 MOD_RES 1403 1403 Phosphothreonine.
 MOD_RES 1425 1425 Phosphothreonine.
 MOD_RES 1466 1466 Phosphothreonine.
 MOD_RES 1548 1548 Phosphothreonine.
 MOD_RES 1567 1567 Phosphothreonine.
 MOD_RES 1589 1589 Phosphothreonine.
 MOD_RES 1604 1604 Phosphoserine.
 MOD_RES 1630 1630 Phosphothreonine.
 MOD_RES 1664 1664 Phosphothreonine.
 MOD_RES 1671 1671 Phosphothreonine.
 MOD_RES 1681 1681 Phosphoserine.
 MOD_RES 1697 1697 Phosphothreonine.
 MOD_RES 1702 1702 Phosphoserine.
 MOD_RES 1711 1711 Phosphoserine.
 MOD_RES 1775 1775 Phosphoserine.
 MOD_RES 1800 1800 Phosphothreonine.
 MOD_RES 1820 1820 Phosphoserine.
 MOD_RES 1858 1858 Phosphothreonine.
 CROSSLNK 1840 1840 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Cell cycle; Chromosome; Complete proteome; DNA damage; DNA repair; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 2089 AA 

Protein Sequence

Gene Ontology

 GO:0005694; C:chromosome; ISS:UniProtKB.
 GO:0005925; C:focal adhesion; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome.
 GO:0031573; P:intra-S DNA damage checkpoint; TAS:UniProtKB. 

Interpro

 IPR001357; BRCT_dom.
 IPR000253; FHA_dom.
 IPR008984; SMAD_FHA_domain. 

Pfam

 PF00498; FHA 

SMART

 SM00292; BRCT
 SM00240; FHA 

PROSITE

 PS50172; BRCT
 PS50006; FHA_DOMAIN 

PRINTS