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Mdc1

Protein FULL name:

mediator of DNA damage checkpoint protein 1 [Mus musculus].


Mdc1 (Mus musculus) is product of expression of Mdc1 gene.






FUNCTION: 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/CHK1 and CHEK2/CHK2/CDS1 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1 (By similarity).

SUBUNIT: Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with CHEK2/CHK2/CDS1, 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 G22P1/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 (By similarity). Interacts with H2AFX, which requires phosphorylation of H2AFX. Interacts with the MRN complex, composed of MRE11A/MRE11, RAD50, and NBN.

SUBCELLULAR LOCATION: Nucleus. Note=Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires phosphorylation of H2AFX.

DOMAIN: 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).

PTM: 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 (By similarity).

SIMILARITY: Contains 2 BRCT domains.

SIMILARITY: Contains 1 FHA domain.


NCBI GenPept GI number(s): 132626693
Species: Mus musculus

Links to other databases:

Database ID Link
Uniprot Q5PSV9 Q5PSV9
PFAM: - Q5PSV9 (Link - using uniprot id)
InterPro: - Q5PSV9 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MESTQVIDWDAEEEEETELSSGSLGYSVEPIGQLRLFSGTHGPERDFPLY
LGKNVVGRSPDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGTQI
VKPPRVLPPGVSHRLRDQELILFADFPCQYHRLDVPPPLVPRSLLTIEKT
PRIRIESQNSRVLLAADSEEEGDFPSGRCVANGQRNTASPSATVVPESDE
EVSSPAPSVPGPSSPFGLGSDTDEEQGQQPGVEESSLADSSGAAGEAEQP
EANGTTAGIQAQPTEHKLKDTKVKKEAGRAGVSDGSVLERSPTLGEDSDT
EVDEDHKPGFADSETDVEEERIPVTPPVAPVKKNQVLLAVGIGDPEAPGV
AHLQDCLAGSGTDVEDKTALDVPLERNHTPMVINSDTDEEEEEEEEEVSA
ALTLAHLKERGIGLWSRDPGAEEVKSQPQVLVEQSQSASGRDSDTDVEEE
SSGRKREIIPDSPMDVDEALTVTQPESQPPRRPNDADEYMDMSSPGSHLV
VNQASFAVVGKTRAQVEEEVPGPSVILGEKHQVPLEGAQPPEEAWETAVQ
EGSSSPEAAASVRPSQQPVAEDAGTECATAVSEQESTLEVRSQSGSPAAP
VEQVVIHTDTSGDPTLPQREGAQTPTGREREAHVGRTKSAKECCDAEPED
LCLPATQCFVEGESQHPEAVQSLENEPTQLFPCTLPQEPGPSHLSLQTPG
ADTLDVPWEVLATQPFCLREQSETSELHEAHGSQPSLPREPPGHQHLVHT
SPVHTELLRIEGREIQTVEKAMGIPKEMADRMTPEREPLEREIRGRTENS
ERDVIGEELIQGTKDREPKKVLARDSQRKEADKDLEGNRESLEVEIEMSK
DSQKRERKVEKPEPKREWEPADLEVTPDRGVTEEGSHDQKGQIASLTLKP
GVGVKDLEGLASAPIITGSQADGGKGDPLSPGRQQRGRLSCQTTPAGKAS
RGDPEPPDHCLFSSVPEASTQSLLTSQSQKQSTPQPLFSTSSSEIPLPES
LHTKPNVRPRRSSRMTPSPHSSAALKPNTTCPTNQPAASRPTSRPTRGRA
NRSSTRTPELIVPVDPELQPSTSTEQPVIPKLTSQVTEGRVQMPEPLLTG
PEIQSPTSTEQSVTPDRKPRATRGRPSKSPNKTPEPLISTGPELQPPTSI
EQPVIPKPTSRVTRGRPRKSSVRTPESVVSTGPELQPLTSIEQPVIPEPR
ATRGRPSKSSIKTPESVVPTGPELQPLTSAKQPVTPNLTSRASRGRSSKS
IRTPEPVVQTGPEFHPSTSTEQPDTREPSSQARTRRSAVKTPEASVPTTP
ELQPFTSKKQPAPKPTALVTQGRTYKPSTEDCESVGPVAPDFEPSTSTDH
LVTPKVTDQSLTLQSSPLSASPVSSTPDLKPPVPIAQPVTPEPIPQANHQ
RKRRAAGKQGSRTVPLGHKSYSALSEPEPQSSASQSSGASEADSPRQKRP
RRQASQKTVVIKEEPVETEVKEEPQETAIPTPEKRKRDHAEEVTQGKPTR
SRRTKPNQETAPKVLFTGVMDSRGERAVLALGGSLASSVNEASHLVTDRI
RRTVKFLCALGKGIPILSLNWLYQSRKAGCFLPPDDYLVTDPEQEKNFSF
SLRDSLCRARERRLLEDYEIHVTPGVQPPPPQMGEIISCCGGTFLPSMPH
SYKLHRVIITCTEDLPRCAIPSRLGLPLLSPEFLLTGVLKQEATPEAFVL
SNLEMSST

Mdc1 (Mus musculus) belongs to following protein families:
References:

Title Authors Journal
Prediction of the coding sequences of mouse homologues of KIAA gene: III. the complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. Okazaki N, Kikuno R, Ohara R, Inamoto S, Koseki H, Hiraoka S, Saga Y, Nagase T, Ohara O, Koga H DNA Res Aug. 31, 2003
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
Specific association of mouse MDC1/NFBD1 with NBS1 at sites of DNA-damage. Lee AC, Fernandez-Capetillo O, Pisupati V, Jackson SP, Nussenzweig A Cell Cycle Feb. 1, 2005
Large-scale phosphorylation analysis of mouse liver. Villen J, Beausoleil SA, Gerber SA, Gygi SP Proc Natl Acad Sci U S A Feb. 1, 2007
Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry. Dai J, Jin WH, Sheng QH, Shieh CH, Wu JR, Zeng R J Proteome Res Feb. 1, 2007
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007
The phagosomal proteome in interferon-gamma-activated macrophages. Trost M, English L, Lemieux S, Courcelles M, Desjardins M, Thibault P Immunity Feb. 16, 2009
Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry. Sweet SM, Bailey CM, Cunningham DL, Heath JK, Cooper HJ Mol Cell Proteomics May 1, 2009


Last modification of this entry: Oct. 6, 2010.

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