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MDC1

It reports that MDC1 (mediator of DNA damage checkpoint protein1) regulates many aspects of DNA damage response pathways, such as intra-S phase checkpoint, G2/M checkpoint, and radiation-induced apoptosis. Many proteins, such as ATM, BRCA1, and Chk2, interact with MDC1. MDC1 contains several protein-protein interaction domains. MDC1 appears to function as an adaptor protein, recruiting downstream proteins to upstream kinases and facilitating signal transduction following DNA damage.
Protein class

Cancer-related genes

Predicted location

Intracellular

Single cell type specificity

Cell type enriched (Spermatocytes)

Immune cell specificity

Immune cell enriched (NK-cell)

Cell line specificity

Low cell line specificity

Interaction

Homodimer. Interacts with several proteins involved in the DNA damage response, although not all these interactions may be direct. Interacts with H2AX, which requires phosphorylation of H2AX on 'Ser-139'. Interacts with the MRN complex, composed of MRE11, RAD50, and NBN. Interacts with CHEK2, which requires ATM-mediated phosphorylation of 'Thr-68' 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 XRCC6/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. When phosphorylated, interacts with APTX (via FHA-like domain).

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