ID WIPI2_HUMAN Reviewed; 454 AA. AC Q9Y4P8; B3KNC2; Q5MNZ8; Q6FI96; Q75L50; Q96IE4; Q9Y364; DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=WD repeat domain phosphoinositide-interacting protein 2 {ECO:0000305}; DE Short=WIPI-2; DE AltName: Full=WIPI49-like protein 2; GN Name=WIPI2 {ECO:0000312|HGNC:HGNC:32225}; ORFNames=CGI-50; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5), ALTERNATIVE SPLICING, AND RP TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=15602573; DOI=10.1038/sj.onc.1208331; RA Proikas-Cezanne T., Waddell S., Gaugel A., Frickey T., Lupas A., RA Nordheim A.; RT "WIPI-1alpha (WIPI49), a member of the novel 7-bladed WIPI protein family, RT is aberrantly expressed in human cancer and is linked to starvation-induced RT autophagy."; RL Oncogene 23:9314-9325(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4). RC TISSUE=Lymphoma, Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1; 2; 3; 4; 5 AND 6), RP PHOSPHOINOSITIDES-BINDING, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=20505359; DOI=10.4161/auto.6.4.11863; RA Polson H.E., de Lartigue J., Rigden D.J., Reedijk M., Urbe S., Clague M.J., RA Tooze S.A.; RT "Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and RT positively regulates LC3 lipidation."; RL Autophagy 6:506-522(2010). RN [11] RP INTERACTION WITH TECPR1. RX PubMed=21575909; DOI=10.1016/j.chom.2011.04.010; RA Ogawa M., Yoshikawa Y., Kobayashi T., Mimuro H., Fukumatsu M., Kiga K., RA Piao Z., Ashida H., Yoshida M., Kakuta S., Koyama T., Goto Y., Nagatake T., RA Nagai S., Kiyono H., Kawalec M., Reichhart J.M., Sasakawa C.; RT "A Tecpr1-dependent selective autophagy pathway targets bacterial RT pathogens."; RL Cell Host Microbe 9:376-389(2011). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=21564513; DOI=10.1111/j.1582-4934.2011.01339.x; RA Proikas-Cezanne T., Robenek H.; RT "Freeze-fracture replica immunolabelling reveals human WIPI-1 and WIPI-2 as RT membrane proteins of autophagosomes."; RL J. Cell. Mol. Med. 15:2007-2010(2011). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=22456507; DOI=10.1091/mbc.e11-09-0746; RA Orsi A., Razi M., Dooley H.C., Robinson D., Weston A.E., Collinson L.M., RA Tooze S.A.; RT "Dynamic and transient interactions of Atg9 with autophagosomes, but not RT membrane integration, are required for autophagy."; RL Mol. Biol. Cell 23:1860-1873(2012). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=23916833; DOI=10.1016/j.bbamcr.2013.07.020; RA Manzoni C., Mamais A., Dihanich S., Abeti R., Soutar M.P., Plun-Favreau H., RA Giunti P., Tooze S.A., Bandopadhyay R., Lewis P.A.; RT "Inhibition of LRRK2 kinase activity stimulates macroautophagy."; RL Biochim. Biophys. Acta 1833:2900-2910(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-413, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP INDUCTION. RX PubMed=23434374; DOI=10.1016/j.molcel.2013.01.024; RA Chauhan S., Goodwin J.G., Chauhan S., Manyam G., Wang J., Kamat A.M., RA Boyd D.D.; RT "ZKSCAN3 is a master transcriptional repressor of autophagy."; RL Mol. Cell 50:16-28(2013). RN [17] RP FUNCTION, INTERACTION WITH ATG16L1 AND ATG5, DOMAIN, AND MUTAGENESIS OF RP ARG-126; ARG-143; ARG-242 AND ARG-243. RX PubMed=24954904; DOI=10.1016/j.molcel.2014.05.021; RA Dooley H.C., Razi M., Polson H.E., Girardin S.E., Wilson M.I., Tooze S.A.; RT "WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and RT pathogen clearance by recruiting Atg12-5-16L1."; RL Mol. Cell 55:238-252(2014). RN [18] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ULK1 AND RB1CC1. RX PubMed=28890335; DOI=10.1016/j.molcel.2017.08.005; RA Zhao Y.G., Chen Y., Miao G., Zhao H., Qu W., Li D., Wang Z., Liu N., Li L., RA Chen S., Liu P., Feng D., Zhang H.; RT "The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity RT to Control ER-Isolation Membrane Contacts for Autophagosome Formation."; RL Mol. Cell 67:974.e6-989.e6(2017). RN [19] RP FUNCTION, PHOSPHOINOSITIDES-BINDING, INTERACTION WITH ATG16L1; NUDC; WIPI1 RP AND WDR45, AND SUBCELLULAR LOCATION. RX PubMed=28561066; DOI=10.1038/ncomms15637; RA Bakula D., Mueller A.J., Zuleger T., Takacs Z., Franz-Wachtel M., RA Thost A.K., Brigger D., Tschan M.P., Frickey T., Robenek H., Macek B., RA Proikas-Cezanne T.; RT "WIPI3 and WIPI4 beta-propellers are scaffolds for LKB1-AMPK-TSC signalling RT circuits in the control of autophagy."; RL Nat. Commun. 8:15637-15637(2017). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=33499712; DOI=10.1080/15548627.2021.1874133; RA Kojima W., Yamano K., Kosako H., Imai K., Kikuchi R., Tanaka K., RA Matsuda N.; RT "Mammalian BCAS3 and C16orf70 associate with the phagophore assembly site RT in response to selective and non-selective autophagy."; RL Autophagy 1:1-26(2021). RN [21] RP INVOLVEMENT IN IDDSSA, FUNCTION, VARIANT IDDSSA MET-249, AND RP CHARACTERIZATION OF VARIANT IDDSSA MET-249. RX PubMed=30968111; DOI=10.1093/brain/awz075; RA Jelani M., Dooley H.C., Gubas A., Mohamoud H.S.A., Khan M.T.M., Ali Z., RA Kang C., Rahim F., Jan A., Vadgama N., Khan M.I., Al-Aama J.Y., Khan A., RA Tooze S.A., Nasir J.; RT "A mutation in the major autophagy gene, WIPI2, associated with global RT developmental abnormalities."; RL Brain 142:1242-1254(2019). CC -!- FUNCTION: Component of the autophagy machinery that controls the major CC intracellular degradation process by which cytoplasmic materials are CC packaged into autophagosomes and delivered to lysosomes for degradation CC (PubMed:20505359, PubMed:28561066). Involved in an early step of the CC formation of preautophagosomal structures (PubMed:20505359, CC PubMed:28561066). Binds and is activated by phosphatidylinositol 3- CC phosphate (PtdIns3P) forming on membranes of the endoplasmic reticulum CC upon activation of the upstream ULK1 and PI3 kinases (PubMed:28561066). CC Mediates ER-isolation membranes contacts by interacting with the CC ULK1:RB1CC1 complex and PtdIns3P (PubMed:28890335). Once activated, CC WIPI2 recruits at phagophore assembly sites the ATG12-ATG5-ATG16L1 CC complex that directly controls the elongation of the nascent CC autophagosomal membrane (PubMed:20505359, PubMed:28561066). CC {ECO:0000269|PubMed:20505359, ECO:0000269|PubMed:28561066, CC ECO:0000269|PubMed:28890335, ECO:0000269|PubMed:30968111}. CC -!- FUNCTION: [Isoform 4]: Recruits the ATG12-ATG5-ATG16L1 complex to CC omegasomes and preautophagosomal structures, resulting in ATG8 family CC proteins lipidation and starvation-induced autophagy. Isoform 4 is also CC required for autophagic clearance of pathogenic bacteria. Isoform 4 CC binds the membrane surrounding Salmonella and recruits the ATG12-5-16L1 CC complex, initiating LC3 conjugation, autophagosomal membrane formation, CC and engulfment of Salmonella. {ECO:0000269|PubMed:24954904}. CC -!- SUBUNIT: Interacts with TECPR1 (PubMed:21575909). Interacts with CC ATG16L1 (PubMed:24954904, PubMed:28561066). Interacts with ATG5 CC (PubMed:24954904). Interacts with WIPI1 (PubMed:28561066). Interacts CC with WDR45 (PubMed:28561066). May interact with NUDC (PubMed:28561066). CC Interacts with ULK1 and RB1CC1 (PubMed:28890335). CC {ECO:0000269|PubMed:21575909, ECO:0000269|PubMed:24954904, CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335}. CC -!- INTERACTION: CC Q9Y4P8; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-719396, EBI-714543; CC Q9Y4P8; Q9NUX5: POT1; NbExp=2; IntAct=EBI-719396, EBI-752420; CC Q9Y4P8; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-719396, EBI-712367; CC Q9Y4P8-4; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-12205107, EBI-12831978; CC Q9Y4P8-4; Q9Y680: FKBP7; NbExp=3; IntAct=EBI-12205107, EBI-3918971; CC Q9Y4P8-4; Q96E11: MRRF; NbExp=3; IntAct=EBI-12205107, EBI-2855755; CC Q9Y4P8-4; Q9UI14: RABAC1; NbExp=3; IntAct=EBI-12205107, EBI-712367; CC Q9Y4P8-4; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-12205107, EBI-14065960; CC Q9Y4P8-4; P08247: SYP; NbExp=3; IntAct=EBI-12205107, EBI-9071725; CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane CC {ECO:0000269|PubMed:20505359, ECO:0000269|PubMed:21564513, CC ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:23916833, CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:28890335, CC ECO:0000269|PubMed:33499712}; Peripheral membrane protein CC {ECO:0000269|PubMed:20505359, ECO:0000269|PubMed:21564513, CC ECO:0000269|PubMed:22456507}; Cytoplasmic side CC {ECO:0000269|PubMed:20505359, ECO:0000269|PubMed:21564513, CC ECO:0000269|PubMed:22456507}. Note=Localizes to omegasomes membranes CC which are endoplasmic reticulum connected structures at the origin of CC preautophagosomal structures. Enriched at preautophagosomal structure CC membranes in response to PtdIns3P. {ECO:0000269|PubMed:24954904}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=WIPI-2 alpha, WIPI2a; CC IsoId=Q9Y4P8-1; Sequence=Displayed; CC Name=2; Synonyms=WIPI-2 beta, WIPI2d; CC IsoId=Q9Y4P8-2; Sequence=VSP_016972, VSP_016974; CC Name=3; Synonyms=WIPI2e; CC IsoId=Q9Y4P8-3; Sequence=VSP_016970, VSP_016973, VSP_016974; CC Name=4; Synonyms=WIPI2b; CC IsoId=Q9Y4P8-4; Sequence=VSP_016972; CC Name=5; Synonyms=WIPI-2 delta; CC IsoId=Q9Y4P8-5; Sequence=VSP_016971, VSP_016974; CC Name=6; Synonyms=WIPI2c; CC IsoId=Q9Y4P8-6; Sequence=VSP_016974; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (at protein level). Highly CC expressed in heart, skeletal muscle and pancreas. Expression is down- CC regulated in pancreatic and in kidney tumors. CC {ECO:0000269|PubMed:15602573, ECO:0000269|PubMed:20505359}. CC -!- INDUCTION: Expression is repressed by ZKSCAN3. CC {ECO:0000269|PubMed:23434374}. CC -!- DOMAIN: The L/FRRG motif is required for recruitment to PtdIns3P. CC {ECO:0000269|PubMed:24954904}. CC -!- DISEASE: Intellectual developmental disorder with short stature and CC variable skeletal anomalies (IDDSSA) [MIM:618453]: An autosomal CC recessive disorder characterized by severe intellectual disability, CC speech and language impairment, developmental delay, and cardiac, CC thyroid and skeletal abnormalities. Skeletal features include short CC stature, camptodactyly, fifth finger clinodactyly, thumb hypoplasia, CC overlapping toes, and kyphosis or lumbar vertebral abnormalities. CC {ECO:0000269|PubMed:30968111}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the WD repeat PROPPIN family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY691425; AAV80761.1; -; mRNA. DR EMBL; AY691426; AAV80762.1; -; mRNA. DR EMBL; AF151808; AAD34045.1; -; mRNA. DR EMBL; AL080155; CAB45746.1; -; mRNA. DR EMBL; CR533530; CAG38561.1; -; mRNA. DR EMBL; AK024279; BAG51284.1; -; mRNA. DR EMBL; AC093376; AAQ96865.1; -; Genomic_DNA. DR EMBL; AC093376; AAQ96866.1; -; Genomic_DNA. DR EMBL; AC093376; AAQ96867.1; -; Genomic_DNA. DR EMBL; CH471144; EAW87328.1; -; Genomic_DNA. DR EMBL; BC004116; AAH04116.1; -; mRNA. DR EMBL; BC007596; AAH07596.1; -; mRNA. DR EMBL; BC021068; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC021200; AAH21200.1; -; mRNA. DR CCDS; CCDS34593.1; -. [Q9Y4P8-4] DR CCDS; CCDS47531.1; -. [Q9Y4P8-6] DR CCDS; CCDS47532.1; -. [Q9Y4P8-2] DR CCDS; CCDS47533.1; -. [Q9Y4P8-3] DR CCDS; CCDS5339.1; -. [Q9Y4P8-1] DR PIR; T12539; T12539. DR RefSeq; NP_001028690.1; NM_001033518.1. [Q9Y4P8-6] DR RefSeq; NP_001028691.1; NM_001033519.1. [Q9Y4P8-2] DR RefSeq; NP_001028692.1; NM_001033520.1. [Q9Y4P8-3] DR RefSeq; NP_001265228.1; NM_001278299.1. DR RefSeq; NP_056425.1; NM_015610.3. [Q9Y4P8-1] DR RefSeq; NP_057087.2; NM_016003.3. [Q9Y4P8-4] DR PDB; 7F69; X-ray; 1.50 A; A=13-379. DR PDB; 7MU2; X-ray; 1.85 A; A/C=12-381. DR PDB; 7XFR; X-ray; 1.76 A; A/C=13-380. DR PDBsum; 7F69; -. DR PDBsum; 7MU2; -. DR PDBsum; 7XFR; -. DR AlphaFoldDB; Q9Y4P8; -. DR SMR; Q9Y4P8; -. DR BioGRID; 117550; 78. DR IntAct; Q9Y4P8; 48. DR MINT; Q9Y4P8; -. DR STRING; 9606.ENSP00000288828; -. DR GlyGen; Q9Y4P8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y4P8; -. DR PhosphoSitePlus; Q9Y4P8; -. DR BioMuta; WIPI2; -. DR DMDM; 74762063; -. DR EPD; Q9Y4P8; -. DR jPOST; Q9Y4P8; -. DR MassIVE; Q9Y4P8; -. DR MaxQB; Q9Y4P8; -. DR PaxDb; 9606-ENSP00000288828; -. DR PeptideAtlas; Q9Y4P8; -. DR ProteomicsDB; 86236; -. [Q9Y4P8-1] DR ProteomicsDB; 86237; -. [Q9Y4P8-2] DR ProteomicsDB; 86238; -. [Q9Y4P8-3] DR ProteomicsDB; 86239; -. [Q9Y4P8-4] DR ProteomicsDB; 86240; -. [Q9Y4P8-5] DR ProteomicsDB; 86241; -. [Q9Y4P8-6] DR Pumba; Q9Y4P8; -. DR Antibodypedia; 11278; 385 antibodies from 33 providers. DR DNASU; 26100; -. DR Ensembl; ENST00000288828.9; ENSP00000288828.4; ENSG00000157954.15. [Q9Y4P8-1] DR Ensembl; ENST00000382384.6; ENSP00000371821.2; ENSG00000157954.15. [Q9Y4P8-2] DR Ensembl; ENST00000401525.7; ENSP00000384945.3; ENSG00000157954.15. [Q9Y4P8-4] DR Ensembl; ENST00000404704.7; ENSP00000385297.3; ENSG00000157954.15. [Q9Y4P8-6] DR Ensembl; ENST00000484262.1; ENSP00000429654.1; ENSG00000157954.15. [Q9Y4P8-3] DR GeneID; 26100; -. DR KEGG; hsa:26100; -. DR MANE-Select; ENST00000288828.9; ENSP00000288828.4; NM_015610.4; NP_056425.1. DR UCSC; uc003snv.4; human. [Q9Y4P8-1] DR AGR; HGNC:32225; -. DR CTD; 26100; -. DR DisGeNET; 26100; -. DR GeneCards; WIPI2; -. DR HGNC; HGNC:32225; WIPI2. DR HPA; ENSG00000157954; Low tissue specificity. DR MalaCards; WIPI2; -. DR MIM; 609225; gene. DR MIM; 618453; phenotype. DR neXtProt; NX_Q9Y4P8; -. DR OpenTargets; ENSG00000157954; -. DR PharmGKB; PA142670576; -. DR VEuPathDB; HostDB:ENSG00000157954; -. DR eggNOG; KOG2110; Eukaryota. DR GeneTree; ENSGT00940000155537; -. DR HOGENOM; CLU_025895_1_1_1; -. DR InParanoid; Q9Y4P8; -. DR OMA; SDHCYLA; -. DR OrthoDB; 391429at2759; -. DR PhylomeDB; Q9Y4P8; -. DR TreeFam; TF314879; -. DR PathwayCommons; Q9Y4P8; -. DR Reactome; R-HSA-1632852; Macroautophagy. DR SignaLink; Q9Y4P8; -. DR SIGNOR; Q9Y4P8; -. DR BioGRID-ORCS; 26100; 38 hits in 1166 CRISPR screens. DR ChiTaRS; WIPI2; human. DR GeneWiki; WIPI2; -. DR GenomeRNAi; 26100; -. DR Pharos; Q9Y4P8; Tbio. DR PRO; PR:Q9Y4P8; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q9Y4P8; Protein. DR Bgee; ENSG00000157954; Expressed in middle temporal gyrus and 216 other cell types or tissues. DR ExpressionAtlas; Q9Y4P8; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0019898; C:extrinsic component of membrane; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000407; C:phagophore assembly site; IDA:UniProtKB. DR GO; GO:0034045; C:phagophore assembly site membrane; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:LIFEdb. DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB. DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB. DR GO; GO:0044804; P:nucleophagy; IBA:GO_Central. DR GO; GO:0034497; P:protein localization to phagophore assembly site; IMP:UniProtKB. DR GO; GO:0098792; P:xenophagy; IEA:Ensembl. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR048720; PROPPIN. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR11227:SF27; WD REPEAT DOMAIN PHOSPHOINOSITIDE-INTERACTING PROTEIN 2; 1. DR PANTHER; PTHR11227; WD-REPEAT PROTEIN INTERACTING WITH PHOSPHOINOSIDES WIPI -RELATED; 1. DR Pfam; PF21032; PROPPIN; 1. DR SMART; SM00320; WD40; 3. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR Genevisible; Q9Y4P8; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Disease variant; KW Intellectual disability; Lipid-binding; Membrane; Phosphoprotein; KW Reference proteome; Repeat; WD repeat. FT CHAIN 1..454 FT /note="WD repeat domain phosphoinositide-interacting FT protein 2" FT /id="PRO_0000051440" FT REPEAT 15..60 FT /note="WD 1" FT /evidence="ECO:0000255" FT REPEAT 67..104 FT /note="WD 2" FT /evidence="ECO:0000255" FT REPEAT 110..142 FT /note="WD 3" FT /evidence="ECO:0000255" FT REPEAT 149..189 FT /note="WD 4" FT /evidence="ECO:0000255" FT REPEAT 193..232 FT /note="WD 5" FT /evidence="ECO:0000255" FT REPEAT 238..277 FT /note="WD 6" FT /evidence="ECO:0000255" FT REPEAT 320..359 FT /note="WD 7" FT /evidence="ECO:0000255" FT MOTIF 241..244 FT /note="L/FRRG motif" FT /evidence="ECO:0000303|PubMed:24954904" FT MOD_RES 413 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..71 FT /note="MNLASQSGEAGAGQLLFANFNQDNTEVKGASRAAGLGRRAVVWSLAVGSKSG FT YKFFSLSSVDKLEQIYECT -> MLLRLQRIKTLRPPGCPHPMTTCSAGTLSAVPCVSP FT RQVFVFERRFCLWHSHVEMFTHVLPFVISA (in isoform 5)" FT /evidence="ECO:0000303|PubMed:10810093, FT ECO:0000303|PubMed:15602573" FT /id="VSP_016971" FT VAR_SEQ 1..59 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_016970" FT VAR_SEQ 26..43 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15602573" FT /id="VSP_016972" FT VAR_SEQ 60..71 FT /note="SVDKLEQIYECT -> MFTHVLPFVISA (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_016973" FT VAR_SEQ 407..417 FT /note="Missing (in isoform 2, isoform 3, isoform 5 and FT isoform 6)" FT /evidence="ECO:0000303|PubMed:10810093, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:15602573" FT /id="VSP_016974" FT VARIANT 249 FT /note="V -> M (in IDDSSA; altered autophagosome assembly FT shown in patient cells; dbSNP:rs756429763)" FT /evidence="ECO:0000269|PubMed:30968111" FT /id="VAR_082589" FT MUTAGEN 126 FT /note="R->E: Impairs interaction with ATG16L1." FT /evidence="ECO:0000269|PubMed:24954904" FT MUTAGEN 143 FT /note="R->E: Decreasess interaction with ATG16L1." FT /evidence="ECO:0000269|PubMed:24954904" FT MUTAGEN 242 FT /note="R->T: Impairs preautophagosomal localization; when FT associated with T-243." FT /evidence="ECO:0000269|PubMed:24954904" FT MUTAGEN 243 FT /note="R->T: Impairs preautophagosomal localization; when FT associated with T-242." FT /evidence="ECO:0000269|PubMed:24954904" FT CONFLICT 139 FT /note="I -> T (in Ref. 1; CAG38561)" FT /evidence="ECO:0000305" FT CONFLICT 165 FT /note="S -> P (in Ref. 1; AAV80761)" FT /evidence="ECO:0000305" FT CONFLICT 380 FT /note="E -> K (in Ref. 2; AAD34045)" FT /evidence="ECO:0000305" FT STRAND 14..20 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 52..57 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 61..63 FT /evidence="ECO:0007829|PDB:7MU2" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 75..81 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 85..92 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 95..103 FT /evidence="ECO:0007829|PDB:7F69" FT TURN 104..107 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 108..114 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 121..124 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 126..132 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 134..141 FT /evidence="ECO:0007829|PDB:7F69" FT TURN 142..144 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 147..153 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:7MU2" FT STRAND 172..177 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 179..188 FT /evidence="ECO:0007829|PDB:7F69" FT TURN 189..192 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 198..203 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 205..210 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 214..223 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 225..231 FT /evidence="ECO:0007829|PDB:7F69" FT TURN 232..234 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 237..242 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 244..247 FT /evidence="ECO:0007829|PDB:7MU2" FT STRAND 253..256 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 260..266 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 268..277 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 320..324 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 333..339 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 342..348 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 352..358 FT /evidence="ECO:0007829|PDB:7F69" FT TURN 361..363 FT /evidence="ECO:0007829|PDB:7F69" FT STRAND 369..374 FT /evidence="ECO:0007829|PDB:7F69" SQ SEQUENCE 454 AA; 49408 MW; B69CEC399B56F35C CRC64; MNLASQSGEA GAGQLLFANF NQDNTEVKGA SRAAGLGRRA VVWSLAVGSK SGYKFFSLSS VDKLEQIYEC TDTEDVCIVE RLFSSSLVAI VSLKAPRKLK VCHFKKGTEI CNYSYSNTIL AVKLNRQRLI VCLEESLYIH NIRDMKVLHT IRETPPNPAG LCALSINNDN CYLAYPGSAT IGEVQVFDTI NLRAANMIPA HDSPLAALAF DASGTKLATA SEKGTVIRVF SIPEGQKLFE FRRGVKRCVS ICSLAFSMDG MFLSASSNTE TVHIFKLETV KEKPPEEPTT WTGYFGKVLM ASTSYLPSQV TEMFNQGRAF ATVRLPFCGH KNICSLATIQ KIPRLLVGAA DGYLYMYNLD PQEGGECALM KQHRLDGSLE TTNEILDSAS HDCPLVTQTY GAAAGKGTYV PSSPTRLAYT DDLGAVGGAC LEDEASALRL DEDSEHPPMI LRTD //