WIPI2

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 WIPI2, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids.

Full Name

WD Repeat Domain, Phosphoinositide Interacting 2

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:20505359, PubMed:28561066).
Involved in an early step of the formation of preautophagosomal structures (PubMed:20505359, PubMed:28561066).
Binds and is activated by phosphatidylinositol 3-phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases (PubMed:28561066).
Mediates ER-isolation membranes contacts by interacting with the ULK1:RB1CC1 complex and PtdIns3P (PubMed:28890335).
Once activated, WIPI2 recruits at phagophore assembly sites the ATG12-ATG5-ATG16L1 complex that directly controls the elongation of the nascent autophagosomal membrane (PubMed:20505359, PubMed:28561066).
Isoform 4
Recruits the ATG12-ATG5-ATG16L1 complex to omegasomes and preautophagosomal structures, resulting in ATG8 family proteins lipidation and starvation-induced autophagy. Isoform 4 is also required for autophagic clearance of pathogenic bacteria. Isoform 4 binds the membrane surrounding Salmonella and recruits the ATG12-5-16L1 complex, initiating LC3 conjugation, autophagosomal membrane formation, and engulfment of Salmonella.

Biological Process

Biological Process autophagosome assembly Source:UniProtKB1 Publication
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 protein lipidation Source:GO_Central1 Publication
Biological Process protein lipidation involved in autophagosome assembly Source:Ensembl
Biological Process protein localization to phagophore assembly site Source:UniProtKB1 Publication
Biological Process xenophagy Source:Ensembl

Cellular Location

Preautophagosomal structure membrane
Localizes to omegasomes membranes which are endoplasmic reticulum connected structures at the origin of preautophagosomal structures. Enriched at preautophagosomal structure membranes in response to PtdIns3P.

Involvement in disease

Intellectual developmental disorder with short stature and variable skeletal anomalies (IDDSSA):
An autosomal recessive disorder characterized by severe intellectual disability, speech and language impairment, developmental delay, and cardiac, thyroid and skeletal abnormalities. Skeletal features include short stature, camptodactyly, fifth finger clinodactyly, thumb hypoplasia, overlapping toes, and kyphosis or lumbar vertebral abnormalities.