F-box and leucine-rich repeat protein 19 (FBXL19)

**F-box and leucine-rich repeat protein 19 (FBXL19)** is a member of the Skp1-Cullin-F-box (SCF) family of E3 ubiquitin ligases and is characterized by a CXXC-PHD domain, an F-box domain, and leucine-rich repeats[1][3]. Unlike other F-box paralogues such as KDM2A and KDM2B, FBXL19 lacks a JmjC domain, meaning it does not possess histone demethylase activity, despite some earlier misannotations[2][3]. FBXL19 plays a critical role in the ubiquitin–proteasome system by targeting specific proteins (such as Rac1, RhoA, and ST2L) for degradation, thereby influencing cell proliferation, migration, and apoptosis[1]. It is predominantly a nuclear protein in embryonic stem cells, where it binds CpG islands through its ZF-CxxC domain and recruits the CDK-Mediator complex to chromatin, priming associated genes for proper activation during differentiation[3]. Loss or disruption of FBXL19 function impairs gene expression programs required for normal development and is embryonic lethal in mice[3]. FBXL19 may also be implicated in human malignancies through its regulation of pathways affecting cell proliferation and differentiation, but it remains a relatively undercharacterized protein regarding therapeutic targeting[1][3]. No drugs are currently known to interact directly with FBXL19, and there are no established clinical biomarkers for its activity. **Note:** Despite some aliases (like JHDM1C, CXXC11), FBXL19 does not have a JmjC domain and is not a histone demethylase[2][3].

Other names

FBL19DKFZp434K0410JHDM1CCXXC11F-box/LRR-repeat protein 19

No approved or known direct-targeting drugs as of current knowledge. Experimental modulation would likely involve inhibition or modulation of protein-protein interactions, or the ubiquitin-proteasome pathway. (Inferred from function) Potentially, drugs could affect FBXL19’s ability to recruit the Mediator complex to chromatin.