Protein Degradation: F-Box Domain

The F-Box domain from human Skp2.

Domain Binding and Function

The F-Box domain is a 42–48 conserved amino acid domain found at the N-terminus of F-Box proteins. F-Box proteins act as modular E3 ubiquitin ligase adaptor proteins within the SCF complex responsible for phosphorylation-mediated ubiquitination. The F-Box domain mediates interaction with SKP1, which links F-Box proteins to the core ubiquitin-ligase complex that is composed of Rbx1, cdc53/Cul1 and the E2 conjugating enzyme cdc34. The C-terminal region of F-Box proteins is also composed of various modular domains that interact with target substrates, often in a phosphorylation-dependent manner.

Structure Reference

  1. Schulman, B.A. et al. (2000) Nature 408(6810), 381–386.

Examples of Domain Proteins

Protein Degradation: F-Box Domain

Binding Examples

F-Box Domain Proteins Binding Partners C-terminal Binding Partners
Cdc4 (Yeast) Skp1, Rbx1 Sic1, CDK inhibitor
Grr1 (Yeast) Skp1, Rbx1 Cyclin (CLN) 1,2
TrCp (Yeast) Skp1, Rbx1 IΚB, NF-ΚB regulator