GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:29348145

FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and cell migration.

FBXL13 is enriched at centrosomes, interacts with Centrin-2, Centrin-3, CEP152 and CEP192, and specifically targets CEP192 for proteasomal degradation, downregulating centrosomal gamma-tubulin, disrupting microtubule arrays and promoting cell migration.

PMID:33234069

The FBXL family of F-box proteins: variations on a theme.

FBXL-family F-box proteins serve as substrate-recognition subunits of SCF E3 ubiquitin ligases, using their LRR domains for substrate binding and the F-box for SKP1/CUL1 recruitment.

PMID:37258679

Axonemal structures reveal mechanoregulatory and disease mechanisms.

Cryo-EM atomic models of the 96-nm axonemal repeat place DRC6 (FBXL13) at the distal tip of the nexin-dynein regulatory complex (N-DRC), where its lysine-rich terminus helps form the electrostatic link to the neighbouring doublet microtubule.

file:human/FBXL13/FBXL13-deep-research-falcon.md

Falcon deep research report for human FBXL13

FBXL13 is a centrosome-enriched SCF substrate receptor whose strongest mechanistic evidence is targeting CEP192 (isoform 3) for ubiquitin-proteasome degradation; SKP1 binding requires the F-box.

"FBXL13 acts as a **substrate-recognition subunit of an SCF E3 ubiquitin ligase** that targets **CEP192 (isoform 3)** for polyubiquitylation and proteasome-mediated degradation, thereby regulating centrosome composition and downstream phenotypes including microtubule regrowth and 2D migration in cultured human cells."
FBXL13 interacts with Centrin-2, Centrin-3, CEP152 and CEP192, with Centrin binding mapping to the N-terminus and CEP192 binding requiring the C-terminus; only CEP192 is detectably degraded.

"FBXL13 interacts with Centrin-2, Centrin-3, CEP152, and CEP192; Centrin binding maps to the amino-terminal region, whereas CEP192 binding requires the carboxy-terminus."
FBXL13 is diffusely cytoplasmic with clear centrosomal enrichment, and fine-tunes CEP192 abundance to regulate centrosomal gamma-tubulin and microtubule nucleation.

"FBXL13 is diffusely cytoplasmic but enriched at centrosomes."
Mouse Fbxl13/Drc6 knockouts are viable with normal spermatogenesis, sperm morphology, motility and tracheal multicilia, indicating the N-DRC/ciliary role may be dispensable or redundant.

"Fbxl13−/− mice show **no overt abnormalities**, have **normal spermatogenesis and sperm morphology**, and sperm motility/velocity parameters (VAP/VSL/VCL) are reported as not significantly different; tracheal multicilia show preserved axonemal ‘9+2’ arrangement and normal morphology."

Reactome:R-HSA-8952618

AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8952620

NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8955241

CAND1 binds cytosolic CRL E3 ubiquitin ligases

Reactome:R-HSA-8955289

COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956040

COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956200

MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-983140

Transfer of Ub from E2 to substrate and release of E2

Reactome:R-HSA-983147

Release of E3 from polyubiquitinated substrate

Reactome:R-HSA-983156

Polyubiquitination of substrate

Reactome:R-HSA-983157

Interaction of E3 with substrate and E2-Ub complex