Tbio FBXL2 F-box/LRR-repeat protein 2

Protein Summary

Description

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. 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. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. 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). This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains 12 tandem leucine-rich repeats. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

Uniprot Accession IDs

• Q9UKC9
• B4DQV0
• E9PD06
• Q6IAN3
• Q9NVQ8
• Q9UK27
• Q9UKA5
• Q9Y3Y9

Gene Name

• FBXL2

Ensembl ID

• ENST00000484457
• ENSP00000417601
• ENSG00000153558
• ENST00000538892
• ENSP00000441228

Symbol

• FBL2
• FBL3
• FBL2
• FBL3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
tissue sample	0.68
microRNA	0.56
cell type or tissue	0.52
small molecule perturbation	0.52
histone modification site profile	0.51

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 22.68   (req: < 5)

Gene RIFs: 13   (req: <= 3)

Antibodies: 163   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 22.68   (req: >= 5)

Gene RIFs: 13   (req: > 3)

Antibodies: 163   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 14

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0