KIAA0040 encodes a 99-amino-acid protein of unknown function conserved among mammals (PANTHER PTHR40382, KIAA0040-like). It has a predicted single N-terminal transmembrane helix (residues 27-47) followed by a disordered, highly basic C-terminal tail containing a poly-lysine run. The transcript is broadly expressed and enriched in placenta, and is induced in primary immune cells by microbial stimuli. Common variants at the locus have been associated with alcohol dependence in genome-wide studies. One study in glioma cell lines reported that KIAA0040 is overexpressed in high-grade tumours and that its knockdown reduces proliferation, migration and invasion with lower JAK2/STAT3 activation. Its membrane of residence, topology, partners and molecular activity are unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping of UniProt's sequence-inferred location 'Membrane; Single-pass membrane protein'. Reason: Correct but uninformative. The predicted 21-residue hydrophobic helix supports membrane integration. No experiment has localised the endogenous protein to an organelle; the Human Protein Atlas antibody gives nucleoplasm, which conflicts with the transmembrane prediction and has not been confirmed, so the generic term is the most specific one supportable. Supporting Evidence: UniProt:Q15053 SUBCELLULAR LOCATION: Membrane |
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Download this section (compressed HTML)Q: Is KIAA0040 an integral membrane protein (as its hydrophobic segment predicts) or nucleoplasmic (as the HPA antibody suggests), and does the poly-lysine tail act as a nuclear localisation signal?
Q: How could a 99-residue single-pass protein enhance JAK2/STAT3 signalling: by binding a cytokine receptor or JAK2 directly, or indirectly?
Experiment: Localise endogenously tagged KIAA0040 in placental trophoblast (e.g. BeWo) cells by co-staining with organelle markers, test membrane integration by carbonate extraction, and immunoprecipitate it to identify partners, checking specifically for JAK2 or cytokine receptors.
Hypothesis: KIAA0040 is a membrane protein whose basic tail faces the cytosol.
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