MGP Database

MGP005366

UniProt Annotations

Entry Information
Gene NameWD repeat domain, phosphoinositide interacting 1
Protein EntryWIPI1_HUMAN
UniProt IDQ5MNZ9
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; Synonyms=WIPI-1 alpha; IsoId=Q5MNZ9-1; Sequence=Displayed; Name=2; Synonyms=WIPI-1 beta; IsoId=Q5MNZ9-2; Sequence=VSP_016966;
DomainThe 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). {ECO:0000269|PubMed:23088497}.
FunctionPlays an important role in autophagy and in particular starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions upstream of the ATG12-ATG5-ATG16L1 complex and LC3, and downstream of the ULK1 and PI3-kinase complexes. 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. {ECO:0000269|PubMed:15020712, ECO:0000269|PubMed:15602573, ECO:0000269|PubMed:20114074, ECO:0000269|PubMed:20484055, ECO:0000269|PubMed:20639694, ECO:0000269|PubMed:21317285, ECO:0000269|PubMed:22829830, ECO:0000269|PubMed:23088497}.
SimilarityBelongs to the WD repeat SVP1 family. {ECO:0000305}.
SimilarityContains 3 WD repeats. {ECO:0000305}.
Subcellular LocationGolgi apparatus, trans-Golgi network. Endosome. Cytoplasmic vesicle, clathrin-coated vesicle. Preautophagosomal structure membrane; Peripheral membrane protein. Cytoplasm, cytoskeleton. 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.
SubunitInteracts with androgen receptor (AR) and the estrogen receptors ESR1 and ESR2. Binds PtdIns3P and to a lesser extent, PtdIns3,5P2 and PtdIns5P in vitro. Interaction with PtdIns3P is required for recruitment to membranes. {ECO:0000269|PubMed:15602573}.
Tissue SpecificityUbiquitously 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. {ECO:0000269|PubMed:15602573}.
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