Switch #: SWTI000312

Switch type: Pre-assembly

Switch subtype: Composite binding site formation

Description:
Binding of Cyclin-dependent kinase inhibitor 1B (CDKN1B) (p27) to the SCF-Skp2 ubiquitin ligase complex requires phosphorylation of p27 (CDKN1B) at T187, and association of the F-box protein S-phase kinase-associated protein 2 (SKP2) with the regulatory Cyclin-dependent kinases regulatory subunit 1 (CKS1B). SKP2 and CKS1B together generate a composite binding site for p27 (CDKN1B). While some residues, including the phosphorylated T187, bind to CKS1B and others to SKP2, the E185 makes contact with residues of both CKS1B and SKP2.

Participants:
(1) Cyclin-dependent kinases regulatory subunit 1 (CKS1B)
(2) S-phase kinase-associated protein 2 (SKP2)
(3) Cyclin-dependent kinase inhibitor 1B (CDKN1B)
(4) Cyclin-dependent kinase 2 (CDK2)

This is a sequential switch. The interactions in this switch take place in a defined order. The order is defined by numbers to the left of each interaction. More than one interaction can occur in each step, these interactions occur independently but are necessary for future step

1Interaction #1 CKS1B - SKP2

Interfaces
(1) Cyclin-dependent kinase regulatory subunit in Cyclin-dependent kinases regulatory subunit 1 (CKS1B)
(2) Leucine rich repeat _(205-229) and _(230-254) and _(255-284) and _(309-334) and _(335-359) in S-phase kinase-associated protein 2 (SKP2)
Additional Information
Affinity : 0.006 µM
Structural information: 2ASS

1Interaction #2 CDKN1B - CDK2

Interfaces
(3) MOD_CDK_1 motif (₁₈₄₁₉₀) in Cyclin-dependent kinase inhibitor 1B (CDKN1B)
(4) Protein kinase domain _(4-286) in Cyclin-dependent kinase 2 (CDK2)

2Interaction #3 CDKN1B - Interaction #1 CKS1B - SKP2

Requires Interaction #1 CKS1B - SKP2
Requires Interaction #2 CDKN1B - CDK2

Interfaces
(5) DEG_SCF_SKP2-CKS1_1 motif (₁₈₃₁₉₀) in Cyclin-dependent kinase inhibitor 1B (CDKN1B)
(6) Interaction #1 CKS1B - SKP2

Interaction Regulation
PTM-dependent Induction (Phosphorylation of T₁₈₇ on Cyclin-dependent kinase inhibitor 1B (CDKN1B)) of the Cyclin-dependent kinase inhibitor 1B (CDKN1B) DEG_SCF_SKP2-CKS1_1 motif - interaction

Regulatory Enzymes for switch
Modifying enzymes for residue: T₁₈₇: Cyclin-dependent kinase 2 (CDK2)

Additional Information
Affinity : 7 µM
Structural information: 2AST

(1) Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.
Hao et al. Mol. Cell (2005)

Other switches involving participants
Cyclin-dependent kinase inhibitor 1B (CDKN1B) - 4 more (view)
Cyclin-dependent kinases regulatory subunit 1 (CKS1B) - 1 more (view)
S-phase kinase-associated protein 2 (SKP2) - 3 more (view)
Cyclin-dependent kinase 2 (CDK2) - 1 more (view)

Other switches involving interfaces
Protein kinase domain - 35 more (view)
Cyclin-dependent kinase regulatory subunit - 2 more (view)
Leucine rich repeat - 2 more (view)
MOD_CDK_1 - 3 more (view)
DEG_SCF_SKP2-CKS1_1 - 2 more (view)