The following text describes a protein:
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. 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. 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/p53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1. 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. Required for the repair of DSBs via homologous recombination by promoting recruitment of NBN component of the MRN complex to DSBs.
Subcellular Localization:
Nucleus. Chromosome. Note=Associated with chromatin (By similarity). Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AX (By similarity). Colocalizes with APTX at sites of DNA double-strand breaks (By similarity).
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 H2AX.
Sequence:
MESTQVIDWDAEEEEETELSSGSLGYSVEPIGQLRLFSGTHGPERDFPLYLGKNVVGRSPDCSVALPFPSISKQHAVIEISAWNKAPILQDCGSLNGTQIVKPPRVLPPGVSHRLRDQELILFADFPCQYHRLDVPPPLVPRSLLTIEKTPRIRIESQNSRVLLAADSEEEGDFPSGRCVANGQRNTASPSATVVPESDEEVSSPAPSVPGPSSPFGLGSDTDEEQGQQPGVEESSLADSSGAAGEAEQPEANGTTAGIQAQPTEHKLKDTKVKKEAGRAGVSDGSVLERSPTLGEDSDTEVDEDHKPGFADSETDVEEERIPVTPPVAPVKKNQVLLAVGIGDPEAPGVAHLQDCLAGSGTDVEDKTALDVPLERNHTPMVINSDTDEEEEEEEEVSAALTLAHLKERGIGLWSRDPGAEEVKSQPQVLVEQSQSASGRDSDTDVEEESSGRKREIIPDSPMDVDEALTVTQPESQPPRRPNDADEYMDMSSPGSHLVVNQASFAVVGKTRAQVEEEVPGPSVILGEKHQVPLEGAQPPEEAWETAVQEGSSSPEAAASVRPSQQPVAEDAGTECATAVSEQESTLEVRSQSGSPAAPVEQVVIHTDTSGDPTLPQREGAQTPTGREREAHVGRTKSAKECCDAEPEDLCLPATQCFVEGESQHPEAVQSLENEPTQLFPCTLPQEPGPSHLSLQTPGADTLDVPWEVLATQPFCLREQSETSELHEAHGSQPSLPREPPGHQHLVHTSPVHTELLRIEGREIQTVEKAMGIPKEMADRMTPEREPLEREIRGRTENSERDVIGEELIQGTKDREPKKVLARDSQRKEADKDLEGNRESLEVEIEMSKDSQKRERKVEKPEPKREWEPADLEVTPDRGVTEEGSHDQKGQIASLTLKPGVGVKDLEGLASAPIITGSQADGGKGDPLSPGRQQRGRLSCQTTPAGKASRGDPEPPDHCLFSSVPEASTQSLLTSQSQKQSTPQPLFSTSSSEIPLPESLHTKPNVRPRRSSRMTPSPHSSAALKPNTTCPTNQPAASRPTSRPTRGRANRSSTRTPELIVPVDPELQPSTSTEQPVIPKLTSQVTEGRVQMPEPLLTGPEIQSPTSTEQSVTPDRKPRATRGRPSKSPNKTPEPLISTGPELQPPTSIEQPVIPKPTSRVTRGRPRKSSVRTPESVVSTGPELQPLTSIEQPVIPEPRATRGRPSKSSIKTPESVVPTGPELQPLTSAKQPVTPNLTSRASRGRSSKSIRTPEPVVQTGPEFHPSTSTEQPDTREPSSQARTRRSAVKTPEASVPTTPELQPFTSKKQPAPKPTALVTQGRTYKPSTEDCESVGPVAPDFEPSTSTDHLVTPKVTDQSLTLQSSPLSASPVSSTPDLKPPVPIAQPVTPEPIPQANHQRKRRAAGKQGSRTVPLGHKSYSALSEPEPQSSASQSSGASEADSPRQKRPRRQASQKTVVIKEEPVETEVKEEPQETAIPTPEKRKRDHAEEVTQGKPTRSRRTKPNQETAPKVLFTGVMDSRGERAVLALGGSLASSVNEASHLVTDRIRRTVKFLCALGKGIPILSLNWLYQSRKAGCFLPPDDYLVTDPEQEKNFSFSLRDSLCRARERRLLEDYEIHVTPGVQPPPPQMGEIISCCGGTFLPSMPHSYKLHRVIITCTEDLPRCAIPSRLGLPLLSPEFLLTGVLKQEATPEAFVLSNLEMSST