WIPI1

WD40 repeat proteins are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins, such as WIPI1, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids (Proikas-Cezanne et al., 2004 [PubMed 15602573]).[supplied by OMIM

Full Name

WD repeat domain, phosphoinositide interacting 1

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 (PubMed:15602573, PubMed:20114074, PubMed:20484055, PubMed:20639694, PubMed:23088497, PubMed:28561066, PubMed:31271352).
Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy (PubMed:28561066).
Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated (PubMed:28561066).
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 (PubMed:28561066, PubMed:31271352, PubMed:33499712).
There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane (PubMed:28561066).
Together with WDR45/WIPI4, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352).
Involved in xenophagy of Staphylococcus aureus (PubMed:22829830).
Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation (PubMed:22829830).
Also plays a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy (PubMed:21317285).
May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway (PubMed:15020712).

Biological Process

Biological Process autophagosome assembly Source:UniProtKB1 Publication
Biological Process autophagy Source:UniProtKB2 Publications
Biological Process autophagy of mitochondrion Source:GO_Central1 Publication
Biological Process autophagy of nucleus Source:GO_Central1 Publication
Biological Process cellular response to starvation Source:UniProtKB1 Publication
Biological Process positive regulation of autophagosome assembly Source:UniProtKB1 Publication
Biological Process protein lipidation Source:GO_Central1 Publication
Biological Process protein localization to phagophore assembly site Source:GO_Central1 Publication
Biological Process vesicle targeting, trans-Golgi to endosome Source:UniProtKB1 Publication

Cellular Location

Golgi apparatus, trans-Golgi network
Endosome
Cytoplasmic vesicle, clathrin-coated vesicle
Preautophagosomal structure membrane
Cytoplasm, cytoskeleton
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.