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Rabbit Anti-phospho-MDC1 (Ser964) antibody
The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 SLCterminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. [provided by RefSeq, Jul 2008]
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.
Subcellular Location:
Nucleus. Associated with chromatin. Relocalizes to discrete nuclear foci following DNA damage, this requires 'Ser-139' phosphorylation of H2AFX. Colocalizes with APTX at sites of DNA double-strand breaks.
Tissue Specificity:
Highly expressed in testis.
Post-translational modifications:
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.
Similarity:
Contains 2 BRCT domains.
Contains 1 FHA domain.
SWISS:
Q14676
Gene ID:
9656
Database links:
Entrez Gene: 9656 Human
GenBank: NP_055456 Human
Omim: 607593 Human
SwissProt: Q14676 Human
Unigene: 433653 Human
Unigene: 653495 Human
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