Switches.ELM

Switch #:

SWTI000273

Switch type:
Cumulative

Switch subtype:
Rheostatic

Description:
Two Bifunctional polynucleotide phosphatase/kinase (PNKP) molecules interact with two FHA-binding motifs in DNA repair protein XRCC1 (XRCC1) upon phosphorylation of T519 and T523 in the motifs. Additional phosphorylation of S518 and S525 further increases the affinity of the interaction. S518 and T523 are consensus CK2 phosphorylation sites, T519 and S525 atypical.

Participants:
(1) DNA repair protein XRCC1 (XRCC1)
(2) Bifunctional polynucleotide phosphatase/kinase (PNKP)

Interactions

Interaction #1 XRCC1 - PNKP

Interfaces
(1) LIG_FHA_2 motif (₅₁₇GSTDENT₅₂₃ and ₅₂₁ENTDSEE₅₂₇) in DNA repair protein XRCC1 (XRCC1)
(2) Bifunctional polynucleotide phosphatase/kinase (PNKP)

Interaction Regulation
PTM-dependent Enhancement (Phosphorylation of S₅₁₈, T₅₁₉, T₅₂₃ and S₅₂₅ on DNA repair protein XRCC1 (XRCC1)) of the DNA repair protein XRCC1 (XRCC1) LIG_FHA_2 motif - Bifunctional polynucleotide phosphatase/kinase (PNKP) interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₅₁₈: Casein kinase II subunit alpha (CSNK2A1); T₅₁₉: Casein kinase II subunit alpha (CSNK2A1); T₅₂₃: Casein kinase II subunit alpha (CSNK2A1); S₅₂₅: Casein kinase II subunit alpha (CSNK2A1)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₅₁₈ : Casein kinase II subunit alpha' (CSNK2A2), Casein kinase II subunit alpha (CSNK2A1). T₅₁₉ : Casein kinase II subunit alpha' (CSNK2A2), Casein kinase II subunit alpha (CSNK2A1). T₅₂₃ : Casein kinase II subunit alpha' (CSNK2A2), Casein kinase II subunit alpha (CSNK2A1). S₅₂₅ : Casein kinase II subunit alpha (CSNK2A1).

Additional Information
Affinity : pT519: 10.58 µM, pT523: 13.49 µM, pT519-pT523: 0.76 µM, pS518-pT519: 1.23 µM, pS518-pT519-pT523: 0.19 µM, pS518-pT519-pT523-pS525: 0.14 µM, pS518-pT523: 24.18 µM
Structural information: 2W3O

Context

Switch localisation
ELM curated: nucleus, Replication fork

References

(1) Specific recognition of a multiply phosphorylated motif in the DNA repair scaffold XRCC1 by the FHA domain of human PNK.
Ali et al. Nucleic Acids Res. (2009)

(2) The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks.
Loizou et al. Cell (2004)

(3) A new XRCC1-containing complex and its role in cellular survival of methyl methanesulfonate treatment.
Luo et al. Mol. Cell. Biol. (2004)