GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

PMID:18203720

Diversity in tissue expression, substrate binding, and SCF complex formation for a lectin family of ubiquitin ligases.

FBXO27 is a member of the FBA/FBG lectin family of F-box proteins; it binds glycoproteins via a conserved hydrophobic pocket in the FBA/G domain (the aromatic residues at 262-263 in FBXO27), assembles with SKP1, Cullin1 and RBX1 into the canonical SCF E3 ubiquitin ligase complex, and as an F-box protein has no intrinsic catalytic activity.

PMID:32296183

A reference map of the human binary protein interactome.

HuRI binary interactome map; captures the FBXO27-SKP1 (P63208) interaction.

PMID:34445249

The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.

Review of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complexes; variable F-box proteins determine substrate specificity and the complexes poly-ubiquitinate substrates for proteasomal degradation.

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

file:human/FBXO27/FBXO27-deep-research-falcon.md

Falcon deep research report for human FBXO27

FBXO27 (Fbs3/FBG5) is the substrate-recognition subunit of an SCF-type E3 ubiquitin ligase (SCF^FBXO27), directing ubiquitylation of substrates that present accessible N-glycans.

"FBXO27 functions as the **substrate-recognition subunit** of an SCF-type E3 ubiquitin ligase (**SCF^FBXO27**), directing ubiquitylation of substrates that present accessible **N-glycans**."
After lysosomal membrane rupture, SCF^FBXO27 ubiquitylates luminally glycosylated regions of lysosomal membrane proteins, prominently LAMP2 (and LAMP1), recruiting p62 and LC3 to promote lysophagy.

"after lysosomal membrane rupture, SCF^FBXO27 ubiquitylates **luminally glycosylated regions** of lysosomal membrane proteins, prominently **LAMP2** (and also LAMP1). In LLOMe-induced lysosomal damage models, FBXO27-dependent ubiquitylation of LAMP2 facilitates recruitment of autophagy machinery (e.g., p62 and LC3), thereby promoting lysophagy."
FBXO27 is N-terminally myristoylated and membrane-associated, which is required for efficient recruitment to damaged lysosomes; myristoylation-defective mutants become cytosolic and fail to be recruited.

"FBXO27 is distinguished among glycoprotein-binding F-box proteins by **N-terminal myristoylation**, conferring **membrane association** that is required for efficient recruitment to damaged lysosomes. In the PNAS lysophagy study, myristoylation-defective mutants become cytosolic and fail to support normal damage-site recruitment."
FBXO27 is a damage-triggered adaptor acting on a set of exposed glycoproteins (also VAMP3, VAMP7, GNS, PSAP, TMEM192) rather than a single substrate.

"Proteomics in the same framework also highlighted additional candidate glycoprotein targets associated with damaged lysosomes (e.g., VAMP3, VAMP7, GNS, PSAP, TMEM192), supporting a model where FBXO27 is a damage-triggered adaptor acting on a set of exposed glycoproteins rather than a single substrate."
FBXO27 accounts for only part of damage-induced lysosomal ubiquitylation and is not ubiquitously expressed, implying cell-type specificity and redundancy with other lysophagy ligases.

"The review emphasizes **partial contribution** of FBXO27 to total lysosomal ubiquitylation and notes **non-ubiquitous expression**, suggesting **cell-type specificity** and/or redundancy among ligases."