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WIPI1

OverviewProducts

Domain

The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P).

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:28561066). 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: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). Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Plays also 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.

Sequence similarities

Belongs to the WD repeat SVP1 family.

Tissue specificity

Ubiquitously expressed. Highly expressed in skeletal muscle, heart, testis, pancreas and placenta. Highly expressed in G361, Sk-mel-28, Sk-mel-13, WM852 and WM451 cells. Up-regulated in a variety of tumor tissues.

Cellular localization

  • Golgi apparatus
  • Trans-Golgi network
  • Endosome
  • Cytoplasmic vesicle
  • Clathrin-coated vesicle
  • Preautophagosomal structure membrane
  • Peripheral membrane protein
  • 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.

Alternative names

  • WD repeat domain phosphoinositide-interacting protein 1
  • WIPI-1
  • Atg18 protein homolog
  • WD40 repeat protein interacting with phosphoinositides of 49 kDa
  • WIPI 49 kDa
  • WIPI49
  • WIPI1

Database links

Target type

Proteins

Molecular weight

48673Da