Seroatlas · Human Serome Atlas

FBXW4

F-box/WD repeat-containing protein 4

Also known as: dactylin, Fbw4, FBXW4_HUMAN, SHFM3

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P57775
Gene: FBXW4
Ensembl: ENSG00000107829
Chromosome: 10
Canonical length: 412 aa
Protein class: Disease related genes, Predicted intracellular proteins
Subcellular location: Golgi apparatus

OverviewNCBI Gene

This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

412 residues, UniProt reviewed canonical sequence.

>P57775|FBXW4
     1  MAAAAGEEEE EEEAARESAA RPAAGPALWR LPEELLLLIC SYLDMRALGR LAQVCRWLRR
    61  FTSCDLLWRR IARASLNSGF TRLGTDLMTS VPVKERVKVS QNWRLGRCRE GILLKWRCSQ
   121  MPWMQLEDDS LYISQANFIL AYQFRPDGAS LNRRPLGVFA GHDEDVCHFV LANSHIVSAG
   181  GDGKIGIHKI HSTFTVKYSA HEQEVNCVDC KGGIIVSGSR DRTAKVWPLA SGRLGQCLHT
   241  IQTEDRVWSI AISPLLSSFV TGTACCGHFS PLRIWDLNSG QLMTHLGSDF PPGAGVLDVM
   301  YESPFTLLSC GYDTYVRYWD LRTSVRKCVM EWEEPHDSTL YCLQTDGNHL LATGSSYYGV
   361  VRLWDRRQRA CLHAFPLTST PLSSPVYCLR LTTKHLYAAL SYNLHVLDFQ NP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FBXW4 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: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.26
Highest tissue expression: 136 nTPM

Expression across tissuesHPA

Tissue

spinal cord: 136 nTPM
midbrain: 124 nTPM
hippocampal formation: 92 nTPM
basal ganglia: 90 nTPM
amygdala: 85 nTPM
skeletal muscle: 81 nTPM

Single-cell type

thyrotrophs: 216 nCPM
cardiomyocytes: 196 nCPM
lactotrophs: 194 nCPM
gonadotrophs: 189 nCPM
somatotrophs: 188 nCPM
renal collecting duct intercalated cells: 148 nCPM

Immune cell

naive B-cell: 4.9 nTPM
naive CD4 T-cell: 4.6 nTPM
gdT-cell: 4.4 nTPM
memory CD4 T-cell: 4.3 nTPM
NK-cell: 4.3 nTPM
memory CD8 T-cell: 4.2 nTPM

Brain region

white matter: 78 nTPM
basal ganglia: 75 nTPM
spinal cord: 74 nTPM
thalamus: 73 nTPM
medulla oblongata: 68 nTPM
midbrain: 66 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FBXW4.

Disease | AllUniProt

Conditions FBXW4 is implicated in, by any mechanism.

Split-hand/foot malformation 3 (SHFM3) MIM:246560

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): 0.72
gnomAD pLI: 0
gnomAD missense Z: 1.43
DepMap mean gene effect: -0.1
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of FBXW4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads FBXW4 as an antibody target. Whether an autoantibody or antibody against FBXW4 could matter depends on whether native FBXW4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

FBXW4 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label FBXW4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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