WIPI2_HUMAN
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 03-AUG-2022, entry version 180.
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; 7MU2; X-ray; 1.85 A; A/C=12-381.
DR PDBsum; 7MU2; -.
DR AlphaFoldDB; Q9Y4P8; -.
DR SMR; Q9Y4P8; -.
DR BioGRID; 117550; 70.
DR IntAct; Q9Y4P8; 47.
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; Q9Y4P8; -.
DR PeptideAtlas; Q9Y4P8; -.
DR PRIDE; 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 Antibodypedia; 11278; 347 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 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; PSRDFAW; -.
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; 36 hits in 1088 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 214 other tissues.
DR ExpressionAtlas; Q9Y4P8; baseline and differential.
DR Genevisible; Q9Y4P8; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
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:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0044804; P:autophagy of nucleus; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; IBA:GO_Central.
DR GO; GO:0061739; P:protein lipidation involved in autophagosome assembly; IEA:Ensembl.
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; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR032911; WIPI2.
DR PANTHER; PTHR11227:SF27; PTHR11227:SF27; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
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 15..20
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 44..51
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 95..103
FT /evidence="ECO:0007829|PDB:7MU2"
FT TURN 104..107
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 121..124
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 126..132
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:7MU2"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 172..177
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 179..188
FT /evidence="ECO:0007829|PDB:7MU2"
FT TURN 189..192
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 193..203
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 225..231
FT /evidence="ECO:0007829|PDB:7MU2"
FT TURN 232..234
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 260..276
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 332..339
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 342..349
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 352..358
FT /evidence="ECO:0007829|PDB:7MU2"
FT TURN 361..363
FT /evidence="ECO:0007829|PDB:7MU2"
FT STRAND 368..374
FT /evidence="ECO:0007829|PDB:7MU2"
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
