Switches.ELM

Switch #:

SWTI000123

Switch type:
Binary

Switch subtype:
Physicochemical compatibility

Description:
Phosphorylation of S140 in the BRCT-binding motif of Histone H2A.x (H2AFX) induces binding to the Mediator of DNA damage checkpoint protein 1 (MDC1) protein.

Participants:
(1) Histone H2A.x (H2AFX)
(2) Mediator of DNA damage checkpoint protein 1 (MDC1)

Interactions

Interaction #1 H2AFX - MDC1

Interfaces
(1) LIG_BRCT_MDC1_1 motif (₁₃₉ASQEY₁₄₃) in Histone H2A.x (H2AFX)
(2) BRCA1 C Terminus (BRCT) domain_(1883-1960) and _(1993-2072) in Mediator of DNA damage checkpoint protein 1 (MDC1)

Interaction Regulation
PTM-dependent Induction (Phosphorylation of S₁₄₀ on Histone H2A.x (H2AFX)) of the Histone H2A.x (H2AFX) LIG_BRCT_MDC1_1 motif - Mediator of DNA damage checkpoint protein 1 (MDC1) BRCA1 C Terminus (BRCT) domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₁₄₀: Serine-protein kinase ATM (ATM),DNA-dependent protein kinase catalytic subunit (PRKDC)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₁₄₀ : Serine-protein kinase ATM (ATM), DNA-dependent protein kinase catalytic subunit (PRKDC), Serine/threonine-protein kinase 4 (STK4).

Additional Information
Structural information: 2AZM

Context

Switch localisation
ELM curated: nucleus

References

(1) MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks.
Stucki et al. Cell (2005)

(2) ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation.
Stiff et al. Cancer Res. (2004)