Switches.ELM

Switch #:

SWTI000460

Switch type:
Cumulative

Switch subtype:
Rheostatic

Description:
Phosphorylation of T238 in MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) by Cyclin-dependent kinase 1 (CDK1) primes for phosphorylation of T234 by Glycogen synthase kinase-3 beta (GSK3B), which primes for phosphorylation of S230 by Glycogen synthase kinase-3 beta (GSK3B). Triple-phosphorylated hNIFK (MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)) binds strongly to Antigen KI-67 (MKI67). See also switch details

Participants:
(1) MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)
(2) Antigen KI-67 (MKI67)

Interactions

Interaction #1 MKI67IP - MKI67

Interfaces
(1) LIG_FHA_2 motif (₂₃₈TPTFLER₂₄₄) in MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)
(2) FHA domain_(27-91) in Antigen KI-67 (MKI67)

Interaction Regulation
PTM-dependent Enhancement (Phosphorylation of S₂₃₀ and T₂₃₄ on MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP)) of the MKI67 FHA domain-interacting nucleolar phosphoprotein (MKI67IP) LIG_FHA_2 motif - Antigen KI-67 (MKI67) FHA domain interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: S₂₃₀: Glycogen synthase kinase-3 beta (GSK3B); T₂₃₄: Glycogen synthase kinase-3 beta (GSK3B)

Inferred Regulatory Enzymes for switch
Putative modifying enzymes for residue: S₂₃₀ : Glycogen synthase kinase-3 alpha (GSK3A), Glycogen synthase kinase-3 beta (GSK3B). T₂₃₄ : Glycogen synthase kinase-3 alpha (GSK3A), Glycogen synthase kinase-3 beta (GSK3B).

Additional Information
Affinity : S230-T234-T238: 109 µM, S230-T234-pT238: 131 µM, S230-pT234-pT238: 0.17 µM, pS230-pT234-pT238: 0.077 µM
Structural information: 2AFF

Context

Switch localisation
ELM curated: nucleus, Replication fork

Inferred: cytoplasm, nucleolus

References

(1) Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67.
Byeon et al. Nat. Struct. Mol. Biol. (2005)