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Details on Person UniProt:Q9UKC9 FBXL2

Class:Id	ReferenceGeneProduct:90467
_chainChangeLog	chain:1-423 added on Fri February 6 2015
_displayName	UniProt:Q9UKC9 FBXL2
_timestamp	2026-02-20 22:09:40
chain	chain:1-423
checksum	61938E434618BA3D
comment	FUNCTION Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:22020328, PubMed:22323446, PubMed:31209342). Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin (PubMed:22020328, PubMed:22323446). This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin (PubMed:22020328, PubMed:22323446). Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (PubMed:22020328, PubMed:22323446). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity). The SCF(FBXL2) complex acts as a regulator of inflammation by mediating ubiquitination and degradation of TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (By similarity). The SCF(FBXL2) complex acts as a negative regulator of the NLRP3 inflammasome by mediating ubiquitination and degradation of NLRP3 (PubMed:26037928). The GGTase-3 complex, composed of PTAR1 and RABGGTB, geranylgeranylates and targets FBXL2 to the cellular membranes, where FBXL2 forms part of the SCF(FBXL2) complex that mediates the degradation of membrane-anchored proteins (PubMed:31209342, PubMed:32128853).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2 (PubMed:10531037, PubMed:31209342, PubMed:32128853). Interacts with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2) (PubMed:22020328). May interact with PIK3R1 (PubMed:23604317). Interacts with PTPN13 (PubMed:23604317).SUBUNIT (Microbial infection) Interacts with hepatitis C virus non-structural protein 5A (NS5A) and less efficiently, with hepatitis C virus non-structural protein 5B (NS5B); a reaction crucial for hepatitis C virus RNA replication.INTERACTION Expressed in brain, heart, kidney, liver, lung, pancreas and placenta.DOMAIN The CAAX motif is a signal for the geranylgeranylation of FBXL2 and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.PTM Phosphorylated by GSK-beta (GSK3B), promoting recognition by FBXO3, leading to its ubiquitination by the SCF(FBXO3) complex.PTM Ubiquitinated at Lys-201 by the SCF(FBXO3) complex in response to lipopolysaccharide (LPS), leading to its degradation by the proteasome.PTM Geranylgeranylation at Cys-420 is mediated by the GGTase-3 complex and is required for its association with cell membranes and the recruitment of substrates to the active SCF(FBXL2) complex.MISCELLANEOUS Deletion of the F-box domain creates a dominant-negative protein that inhibits replication of hepatitis C virus RNA when overexpressed in a hepatoma cell line; this inhibition could be overcome by NS5A coexpression.SEQUENCE CAUTION Extended N-terminus.
description	recommendedName: fullName evidence="16"F-box/LRR-repeat protein 2 alternativeName: fullName evidence="14"F-box and leucine-rich repeat protein 2 alternativeName: fullName evidence="12"F-box protein FBL2/FBL3
geneName	FBXL2 FBL2 FBL3
identifier	Q9UKC9
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Calcium Calmodulin-binding Host-virus interaction Isopeptide bond Leucine-rich repeat Lipoprotein Membrane Phosphoprotein Prenylation Proteomics identification Reference proteome Repeat Ubl conjugation Ubl conjugation pathway
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	FBXL2
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8995974] ENSEMBL:ENSG00000153558 FBXL2 [Homo sapiens]
secondaryIdentifier	FBXL2_HUMAN B4DQV0 E9PD06 Q6IAN3 Q9NVQ8 Q9UK27 Q9UKA5 Q9Y3Y9
sequenceLength	423
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8972395] UniProt:Q9UKC9-1 FBXL2 [Homo sapiens] [ReferenceIsoform:8972396] UniProt:Q9UKC9-2 FBXL2 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:8862605] FBXL2 [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:9748664] FBXL2 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q9UKC9 FBXL2 (90467)