F-box protein

F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the SCF complex, which mediates ubiquitination of proteins targeted for degradation by the 26S proteasome.

F-box linker domain
Structure of the LRR linker domain of Skp2 in the Skp1-Skp2 complex.[1]
Identifiers
Symbol	F-box
Pfam	PF00646
Pfam clan	CL0271
InterPro	IPR001810
SMART	SM00256
PROSITE	PS50181
SCOP2	1fs2 / SCOPe / SUPFAM
Membranome	630
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Core components

F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. It has consensus sequence and varies in few positions. It was first identified in cyclin F.^[2] The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1.^[3] F-box domains commonly exist in proteins in cancer with other protein–protein interaction motifs such as leucine-rich repeats (illustrated in the Figure) and WD repeats, which are thought to mediate interactions with SCF substrates.^[4]

Function

F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.^[5] In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference.^[6] F-box proteins are involved in many plant vegetative and reproduction growth and development. For example, F-box protein-FOA1 involved in abscisic acid (ABA) signaling to affect the seed germination.^[7] ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.^[8]

In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.^[9]

Regulation

F-box protein levels can be regulated by different mechanisms. The regulation can occur via protein degradation process and association with SCF complex . For example, in yeast, the F-box protein Met30 can be ubiquitinated in a cullin-dependent manner.^[10][11]