Protein: WD repeat domain phosphoinositide-interacting protein 1 (WIPI-1) (WD40 repeat protein interacting with phosphoinositides of 49 kDa) (WIPI 49 kDa) (Q8R3E3)
Organism: Mus musculus (Mouse)
Function: Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and maybe other phosphoinositides including PtdIns3,5P2 and PtdIns5P, and is recruited to phagophore assembly sites at the endoplasmic reticulum membranes. There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane. Together with WDR45/WIPI4, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Also plays a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway (By similarity).
Subcellular location: Golgi apparatus, trans-Golgi network {ECO:0000250|UniProtKB:Q5MNZ9}. Endosome {ECO:0000250|UniProtKB:Q5MNZ9}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000250|UniProtKB:Q5MNZ9}. Preautophagosomal structure membrane {ECO:0000269|PubMed:21896713}; Peripheral membrane protein {ECO:0000269|PubMed:21896713}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q5MNZ9}. Note=Trans elements of the Golgi and peripheral endosomes. Dynamically cycles through these compartments and is susceptible to conditions that modulate membrane flux. Enriched in clathrin-coated vesicles. Upon starvation-induced autophagy, accumulates at subcellular structures in the cytoplasm: enlarged vesicular and lasso-like structures, and large cup-shaped structures predominantly around the nucleus. Recruitment to autophagic membranes is controlled by MTMR14. Labile microtubules specifically recruit markers of autophagosome formation like WIPI1, whereas mature autophagosomes may bind to stable microtubules. {ECO:0000250|UniProtKB:Q5MNZ9}.
Interaction partners:
- Autophagy-related protein 2 homolog A
- Autophagy-related protein 16-1
- Autophagy-related protein 2 homolog B
- Protein Atg16l2
- Autophagy-related protein 9A
- WD repeat domain phosphoinositide-interacting protein 2
- Ubiquitin-like protein ATG12
- Autophagy protein 5
- Autophagy-related protein 9B
- Serine/threonine-protein kinase ULK2
Sequence:
MEAEAADAPPGRVEAALSCFSFNQDCTSLAIGTKAGYKLFSLSSVEQLDQVHGSNEIPDVYIVERLFSSSLVVVVSHTKPRQMNVYHFKKGTEICNYSYSSNILSIRLNRQRLLVCLEESIYIHNIKDMKLLKTVLDIPSNPTGLCALSINHSNSYLAYPGSQSTGEIVLYDGNSLKTVCTIAAHEGTLAAITFNSSGSKLASASEKGTVIRVFSVPEGQKLYEFRRGMKRYVTISSLVFSMDSQFLCASSNTETVHIFKMEHLTDSRPEEPSTWSGYMGKMFMAATNYLPAQVSDMMNQDRAFATGRLNFSGQKNICTLSTIQKLPRLLVASSDGHLYIYNLDPQDGGECVLIKTHSLLSSGTTEENKENDLRPSLPPSYAATVARPSTSAASTVPGYSEDGGALRGEVIPEHEFATGPVCLDDENEFPPIILCRGSQKGKTKQS