WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene.
Function
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.34
WIPI2 is the mammalian homolog of Atg18, not Atg21, along with the closely related protein, WIPI1. WIPI2 mRNA is readily detectable in several commonly used laboratory cell lines (HEK293A, HeLa, A431) and several cancer cell lines, while WIPI1 expression is limited to cancer cells (but is also detected in many human tissues).
The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving periods of nutrient deprivation and also plays a role in cancer, neurodegeneration and immune responses to a diverse range of pathogens.5 WIPI2 is recruited early to the forming autophagosome, along with DFCP-1, ULK-1 and Atg16, where it positively regulates the lipidation of Atg8 (LC3). This is not true for WIPI1. It was shown the WIPI2 players an important role in lysosomes regulation.
See also
* Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbé S, Clague MJ, Tooze SA (2010). "Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation". Autophagy. 6 (4): 506–22. doi:10.4161/auto.6.4.11863. PMID 20505359.Further reading
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- Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
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- Lai CH, Chou CY, Ch'ang LY, et al. (2000). "Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics". Genome Res. 10 (5): 703–13. doi:10.1101/gr.10.5.703. PMC 310876. PMID 10810093.
- <Please add first missing authors to populate metadata.> (1999). "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. doi:10.1101/gr.8.11.1097. PMID 9847074.
References
Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A (Dec 2004). "WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy". Oncogene. 23 (58): 9314–25. doi:10.1038/sj.onc.1208331. PMID 15602573. S2CID 22642893. /wiki/Doi_(identifier) ↩
"Entrez Gene: WIPI2 WD repeat domain, phosphoinositide interacting 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=26100 ↩
Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A (Dec 2004). "WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy". Oncogene. 23 (58): 9314–25. doi:10.1038/sj.onc.1208331. PMID 15602573. S2CID 22642893. /wiki/Doi_(identifier) ↩
"Entrez Gene: WIPI2 WD repeat domain, phosphoinositide interacting 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=26100 ↩
Orsi A, Polson HE, Tooze SA (December 2009). "Membrane trafficking events that partake in autophagy". Curr Opin Cell Biol. 22 (2): 150–6. doi:10.1016/j.ceb.2009.11.013. PMID 20036114. /wiki/Doi_(identifier) ↩