WIPI2 explained

WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene.^{[1] [2]}

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.^{[1] [2]}

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.^[3] 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

• WIPI protein family

References

* 20505359 . 10.4161/auto.6.4.11863 . 6 . Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation . 2010 . Autophagy . 506–22 . Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbé S, Clague MJ, Tooze SA . 4 . free .

Further reading

• Mehrle A . The LIFEdb database in 2006 . Nucleic Acids Res. . 34 . Database issue . D415–8 . 2006 . 16381901 . 10.1093/nar/gkj139 . 1347501 . Rosenfelder H . Schupp I . 3 . Del Val . C . Arlt . D . Hahne . F . Bechtel . S . Simpson . J . Hofmann . O .
• Wiemann S . From ORFeome to Biology: A Functional Genomics Pipeline . Genome Res. . 14 . 10B . 2136–44 . 2004 . 15489336 . 10.1101/gr.2576704 . 528930 . Arlt D . Huber W . 3 . Wellenreuther . R . Schleeger . S . Mehrle . A . Bechtel . S . Sauermann . M . Korf . U .
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R .
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free .
• Hillier LW . The DNA sequence of human chromosome 7 . Nature . 424 . 6945 . 157–64 . 2003 . 12853948 . 10.1038/nature01782 . Fulton RS . Fulton LA . 3 . Graves . Tina A. . Pepin . Kymberlie H. . Wagner-Mcpherson . Caryn . Layman . Dan . Maas . Jason . Jaeger . Sara . 2003Natur.424..157H . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Simpson JC . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Rep. . 1 . 3 . 287–92 . 2001 . 11256614 . 10.1093/embo-reports/kvd058 . 1083732 . Wellenreuther R . Poustka A . 3 . Pepperkok . R . Wiemann . S .
• Wiemann S . Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 . Weil B . Wellenreuther R . 3 . Gassenhuber . J . Glassl . S . Ansorge . W . Böcher . M . Blöcker . H . Bauersachs . S .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Lai CH . Identification of Novel Human Genes Evolutionarily Conserved in Caenorhabditis elegans by Comparative Proteomics . Genome Res. . 10 . 5 . 703–13 . 2000 . 10810093 . 10.1101/gr.10.5.703 . 310876 . Chou CY . Ch'ang LY . 3 . Liu . CS . Lin . W .
• Toward a complete human genome sequence . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097 . . free .

Notes and References

1. Proikas-Cezanne T, Waddell S, Gaugel A, Frickey T, Lupas A, Nordheim A . 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 . Dec 2004 . 15602573 . 10.1038/sj.onc.1208331 . 22642893 .
2. Web site: Entrez Gene: WIPI2 WD repeat domain, phosphoinositide interacting 2.
3. Orsi A, Polson HE, Tooze SA . Membrane trafficking events that partake in autophagy . Curr Opin Cell Biol . 22. 2. 150–6. December 2009 . 20036114 . 10.1016/j.ceb.2009.11.013 .