FBXL4

Protein identityUniProt · HPA

UniProt accession

Q9UKA2

Gene

FBXL4

Ensembl

ENSG00000112234

Chromosome

6

Canonical length

621 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins

Subcellular location

Nuclear speckles

OverviewNCBI Gene

This gene encodes a member of the F-box protein family, which are characterized by an approximately 40 amino acid motif, the F-box. F-box proteins constitute one subunit of modular E3 ubiquitin ligase complexes, called SCF complexes, which function in phosphorylation-dependent ubiquitination. The F-box domain mediates protein-protein interactions and binds directly to S-phase kinase-associated protein 1. In addition to an F-box domain, the encoded protein contains at least 9 tandem leucine-rich repeats. The ubiquitin ligase complex containing the encoded protein may function in cell-cycle control by regulating levels of lysine-specific demethylase 4A. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

Canonical amino-acid sequenceUniProt

621 residues, UniProt reviewed canonical sequence.

>Q9UKA2|FBXL4
     1  MSPVFPMLTV LTMFYYICLR RRARTATRGE MMNTHRAIES NSQTSPLNAE VVQYAKEVVD
    61  FSSHYGSENS MSYTMWNLAG VPNVFPSSGD FTQTAVFRTY GTWWDQCPSA SLPFKRTPPN
   121  FQSQDYVELT FEQQVYPTAV HVLETYHPGA VIRILACSAN PYSPNPPAEV RWEILWSERP
   181  TKVNASQARQ FKPCIKQINF PTNLIRLEVN SSLLEYYTEL DAVVLHGVKD KPVLSLKTSL
   241  IDMNDIEDDA YAEKDGCGMD SLNKKFSSAV LGEGPNNGYF DKLPYELIQL ILNHLTLPDL
   301  CRLAQTCKLL SQHCCDPLQY IHLNLQPYWA KLDDTSLEFL QSRCTLVQWL NLSWTGNRGF
   361  ISVAGFSRFL KVCGSELVRL ELSCSHFLNE TCLEVISEMC PNLQALNLSS CDKLPPQAFN
   421  HIAKLCSLKR LVLYRTKVEQ TALLSILNFC SELQHLSLGS CVMIEDYDVI ASMIGAKCKK
   481  LRTLDLWRCK NITENGIAEL ASGCPLLEEL DLGWCPTLQS STGCFTRLAH QLPNLQKLFL
   541  TANRSVCDTD IDELACNCTR LQQLDILGTR MVSPASLRKL LESCKDLSLL DVSFCSQIDN
   601  RAVLELNASF PKVFIKKSFT Q

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FBXL4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

15 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FBXL4.

Disease | AllUniProt

Conditions FBXL4 is implicated in, by any mechanism.

• Mitochondrial DNA depletion syndrome 13 (MTDPS13) MIM:615471

Disease | GeneticClinVar

84 pathogenic / likely-pathogenic of 642 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mitochondrial DNA depletion syndrome 13
• Inborn genetic diseases
• Leigh syndrome
• Mitochondrial DNA depletion syndrome
• Developmental and epileptic encephalopathy, 85, with or without midline brain defects

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.92

gnomAD pLI

0

gnomAD missense Z

0.55

DepMap mean gene effect

-0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy of mitochondrion
• negative regulation of mitophagy
• SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
• ubiquitin-dependent protein catabolic process

Molecular functions

• ubiquitin-like ligase-substrate adaptor activity

Cellular components

• cytosol
• mitochondrial intermembrane space
• mitochondrial outer membrane
• mitochondrion
• nuclear speck
• SCF ubiquitin ligase complex
• ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

• F-box domain
• Leucine-rich repeat, cysteine-containing subtype
• Leucine-rich repeat domain superfamily
• F-box-like domain superfamily
• F-box/LRR-repeat protein 15-like, leucin rich repeat domain
• F-box-like
• F-box/LRR-repeat protein 15, leucine rich repeat domain

KeywordsUniProt

• Cytoplasm
• Leucine-rich repeat
• Membrane
• Methylation
• Mitochondrion
• Mitochondrion outer membrane
• Nucleus
• Primary mitochondrial disease
• Repeat
• Ubl conjugation pathway

InteractionsUniProt · HPA

Protein binding partners of FBXL4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PPTC7
• VCP
• SKP1