ID ATG2A_HUMAN Reviewed; 1938 AA. AC Q2TAZ0; O43154; Q14DM2; Q6ZTV2; Q7Z6K8; Q8IVY5; Q8TAI8; Q96HH7; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 27-MAR-2024, entry version 137. DE RecName: Full=Autophagy-related protein 2 homolog A {ECO:0000303|PubMed:21887408}; GN Name=ATG2A {ECO:0000303|PubMed:21887408, ECO:0000312|HGNC:HGNC:29028}; GN Synonyms=KIAA0404 {ECO:0000303|PubMed:9455477}; 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 [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-656. RC TISSUE=Brain; RX PubMed=9455477; DOI=10.1093/dnares/4.5.307; RA Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. VIII. 78 RT new cDNA clones from brain which code for large proteins in vitro."; RL DNA Res. 4:307-313(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Thymus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 1189-1938 (ISOFORM 2), AND VARIANT ARG-656. RC TISSUE=Cervix, Hippocampus, 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 [5] RP IDENTIFICATION BY 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 [6] RP SUBCELLULAR LOCATION. RX PubMed=21887408; RA Romanyuk D., Polak A., Maleszewska A., Sienko M., Grynberg M., Zoladek T.; RT "Human hAtg2A protein expressed in yeast is recruited to preautophagosomal RT structure but does not complement autophagy defects of atg2Delta strain."; RL Acta Biochim. Pol. 58:365-374(2011). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=22219374; DOI=10.1091/mbc.e11-09-0785; RA Velikkakath A.K., Nishimura T., Oita E., Ishihara N., Mizushima N.; RT "Mammalian Atg2 proteins are essential for autophagosome formation and RT important for regulation of size and distribution of lipid droplets."; RL Mol. Biol. Cell 23:896-909(2012). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1301; SER-1309 AND SER-1402, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-765, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP INTERACTION WITH WDR45. RX PubMed=28820312; DOI=10.1080/15548627.2017.1359381; RA Zheng J.X., Li Y., Ding Y.H., Liu J.J., Zhang M.J., Dong M.Q., Wang H.W., RA Yu L.; RT "Architecture of the ATG2B-WDR45 complex and an aromatic Y/HF motif crucial RT for complex formation."; RL Autophagy 13:1870-1883(2017). RN [11] RP FUNCTION, AND INTERACTION WITH WDR45. 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 [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=31271352; DOI=10.7554/elife.45777; RA Maeda S., Otomo C., Otomo T.; RT "The autophagic membrane tether ATG2A transfers lipids between membranes."; RL Elife 8:0-0(2019). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS RP OF LEU-54; ILE-80; VAL-82; LEU-101; LEU-103; ILE-167; PHE-171; VAL-193; RP TYR-200; LEU-223; MET-259; LEU-285; VAL-304 AND TRP-328. RX PubMed=30952800; DOI=10.1083/jcb.201811139; RA Valverde D.P., Yu S., Boggavarapu V., Kumar N., Lees J.A., Walz T., RA Reinisch K.M., Melia T.J.; RT "ATG2 transports lipids to promote autophagosome biogenesis."; RL J. Cell Biol. 218:1787-1798(2019). RN [14] RP INTERACTION WITH ATG9A. RX PubMed=32610138; DOI=10.1016/j.celrep.2020.107837; RA Guardia C.M., Tan X.F., Lian T., Rana M.S., Zhou W., Christenson E.T., RA Lowry A.J., Faraldo-Gomez J.D., Bonifacino J.S., Jiang J., Banerjee A.; RT "Structure of human ATG9A, the only transmembrane protein of the core RT autophagy machinery."; RL Cell Rep. 31:107837-107837(2020). RN [15] RP INTERACTION WITH ATG9A. RX PubMed=33106659; DOI=10.1038/s41594-020-00520-2; RA Maeda S., Yamamoto H., Kinch L.N., Garza C.M., Takahashi S., Otomo C., RA Grishin N.V., Forli S., Mizushima N., Otomo T.; RT "Structure, lipid scrambling activity and role in autophagosome formation RT of ATG9A."; RL Nat. Struct. Mol. Biol. 27:1194-1201(2020). RN [16] RP INTERACTION WITH ATG9A; TMEM41B AND VMP1. RX PubMed=33850023; DOI=10.1073/pnas.2101562118; RA Ghanbarpour A., Valverde D.P., Melia T.J., Reinisch K.M.; RT "A model for a partnership of lipid transfer proteins and scramblases in RT membrane expansion and organelle biogenesis."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [17] {ECO:0007744|PDB:6KLR} RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 1374-1404 IN COMPLEX WITH WDR45B, RP INTERACTION WITH WDR45 AND WDR45B, AND MUTAGENESIS OF VAL-1381; THR-1382; RP ILE-1389; TYR-1395 AND PHE-1396. RX PubMed=32483132; DOI=10.1038/s41467-020-16523-y; RA Ren J., Liang R., Wang W., Zhang D., Yu L., Feng W.; RT "Multi-site-mediated entwining of the linear WIR-motif around WIPI beta- RT propellers for autophagy."; RL Nat. Commun. 11:2702-2702(2020). CC -!- FUNCTION: Lipid transfer protein involved in autophagosome assembly CC (PubMed:28561066, PubMed:31271352, PubMed:30952800). Tethers the edge CC of the isolation membrane (IM) to the endoplasmic reticulum (ER) and CC mediates direct lipid transfer from ER to IM for IM expansion CC (PubMed:31271352, PubMed:30952800). Binds to the ER exit site (ERES), CC which is the membrane source for autophagosome formation, and extracts CC phospholipids from the membrane source and transfers them to ATG9 CC (ATG9A or ATG9B) to the IM for membrane expansion (PubMed:31271352, CC PubMed:30952800). Lipid transfer activity is enhanced by WIPI1 and CC WDR45/WIPI4, which promote ATG2A-association with phosphatidylinositol CC 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Also CC regulates lipid droplets morphology and distribution within the cell CC (PubMed:22219374, PubMed:28561066). {ECO:0000269|PubMed:22219374, CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:30952800, CC ECO:0000269|PubMed:31271352}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl- CC sn-glycero-3-phospho-L-serine(out); Xref=Rhea:RHEA:38663, CC ChEBI:CHEBI:57262; Evidence={ECO:0000269|PubMed:30952800}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2- CC diacyl-sn-glycero-3-phosphoethanolamine(out); Xref=Rhea:RHEA:38895, CC ChEBI:CHEBI:64612; Evidence={ECO:0000269|PubMed:30952800, CC ECO:0000269|PubMed:31271352}; CC -!- SUBUNIT: Interacts with ATG9A (via C-terminus) (PubMed:32610138, CC PubMed:33106659, PubMed:33850023). Interacts (via WIPI-interacting CC region) with WDR45B/WIPI3 (PubMed:32483132). Interacts (via WIPI- CC interacting region) with WDR45/WIPI4 (PubMed:28820312, CC PubMed:32483132). Interacts with TMEM41B (PubMed:33850023). Interacts CC with VMP1 (PubMed:33850023). {ECO:0000269|PubMed:28820312, CC ECO:0000269|PubMed:32483132, ECO:0000269|PubMed:32610138, CC ECO:0000269|PubMed:33106659, ECO:0000269|PubMed:33850023}. CC -!- INTERACTION: CC Q2TAZ0; Q7Z3C6: ATG9A; NbExp=4; IntAct=EBI-2514077, EBI-727146; CC Q2TAZ0; O95166: GABARAP; NbExp=2; IntAct=EBI-2514077, EBI-712001; CC Q2TAZ0; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-2514077, EBI-746969; CC Q2TAZ0; P60520: GABARAPL2; NbExp=2; IntAct=EBI-2514077, EBI-720116; CC Q2TAZ0; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-2514077, EBI-373144; CC Q2TAZ0; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2514077, EBI-16439278; CC Q2TAZ0; O96008: TOMM40; NbExp=7; IntAct=EBI-2514077, EBI-1057581; CC Q2TAZ0; Q9Y484: WDR45; NbExp=5; IntAct=EBI-2514077, EBI-2682844; CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane CC {ECO:0000269|PubMed:30952800}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:Q96BY7}. Lipid droplet CC {ECO:0000250|UniProtKB:Q96BY7}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:30952800}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P53855}. Note=Localizes to endoplasmic CC reticulum-autophagosome contact sites. {ECO:0000269|PubMed:30952800}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q2TAZ0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q2TAZ0-3; Sequence=VSP_030515; CC Name=3; CC IsoId=Q2TAZ0-4; Sequence=VSP_030510, VSP_030516; CC Name=4; CC IsoId=Q2TAZ0-5; Sequence=VSP_030511, VSP_030512; CC -!- DOMAIN: The chorein N-terminal domain mediates lipid transfer activity. CC {ECO:0000269|PubMed:30952800}. CC -!- SIMILARITY: Belongs to the ATG2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA23700.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AB007864; BAA23700.1; ALT_INIT; mRNA. DR EMBL; AK126181; BAC86477.1; -; mRNA. DR EMBL; AP001187; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008593; AAH08593.1; -; mRNA. DR EMBL; BC027481; AAH27481.1; -; mRNA. DR EMBL; BC053596; AAH53596.1; -; mRNA. DR EMBL; BC110650; AAI10651.1; -; mRNA. DR EMBL; BC113091; AAI13092.1; -; mRNA. DR CCDS; CCDS31602.1; -. [Q2TAZ0-1] DR PIR; T00051; T00051. DR RefSeq; NP_055919.2; NM_015104.2. [Q2TAZ0-1] DR RefSeq; XP_011543165.1; XM_011544863.2. [Q2TAZ0-3] DR PDB; 6KLR; X-ray; 2.21 A; A/B=1374-1404. DR PDBsum; 6KLR; -. DR AlphaFoldDB; Q2TAZ0; -. DR SMR; Q2TAZ0; -. DR BioGRID; 116748; 45. DR IntAct; Q2TAZ0; 101. DR STRING; 9606.ENSP00000366475; -. DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family. DR GlyGen; Q2TAZ0; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q2TAZ0; -. DR PhosphoSitePlus; Q2TAZ0; -. DR BioMuta; ATG2A; -. DR DMDM; 296439433; -. DR EPD; Q2TAZ0; -. DR jPOST; Q2TAZ0; -. DR MassIVE; Q2TAZ0; -. DR MaxQB; Q2TAZ0; -. DR PaxDb; 9606-ENSP00000366475; -. DR PeptideAtlas; Q2TAZ0; -. DR ProteomicsDB; 61475; -. [Q2TAZ0-1] DR ProteomicsDB; 61476; -. [Q2TAZ0-3] DR ProteomicsDB; 61477; -. [Q2TAZ0-4] DR ProteomicsDB; 61478; -. [Q2TAZ0-5] DR Pumba; Q2TAZ0; -. DR Antibodypedia; 44102; 202 antibodies from 24 providers. DR DNASU; 23130; -. DR Ensembl; ENST00000377264.8; ENSP00000366475.3; ENSG00000110046.14. [Q2TAZ0-1] DR GeneID; 23130; -. DR KEGG; hsa:23130; -. DR MANE-Select; ENST00000377264.8; ENSP00000366475.3; NM_015104.3; NP_055919.2. DR UCSC; uc001obx.4; human. [Q2TAZ0-1] DR AGR; HGNC:29028; -. DR CTD; 23130; -. DR DisGeNET; 23130; -. DR GeneCards; ATG2A; -. DR HGNC; HGNC:29028; ATG2A. DR HPA; ENSG00000110046; Low tissue specificity. DR MIM; 616225; gene. DR neXtProt; NX_Q2TAZ0; -. DR OpenTargets; ENSG00000110046; -. DR PharmGKB; PA162377101; -. DR VEuPathDB; HostDB:ENSG00000110046; -. DR eggNOG; KOG2993; Eukaryota. DR GeneTree; ENSGT00620000087966; -. DR HOGENOM; CLU_001781_0_0_1; -. DR InParanoid; Q2TAZ0; -. DR OMA; CADSCAM; -. DR OrthoDB; 5476854at2759; -. DR PhylomeDB; Q2TAZ0; -. DR TreeFam; TF313482; -. DR PathwayCommons; Q2TAZ0; -. DR SignaLink; Q2TAZ0; -. DR SIGNOR; Q2TAZ0; -. DR BioGRID-ORCS; 23130; 41 hits in 1165 CRISPR screens. DR ChiTaRS; ATG2A; human. DR GenomeRNAi; 23130; -. DR Pharos; Q2TAZ0; Tbio. DR PRO; PR:Q2TAZ0; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q2TAZ0; Protein. DR Bgee; ENSG00000110046; Expressed in right lobe of liver and 192 other cell types or tissues. DR ExpressionAtlas; Q2TAZ0; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell. DR GO; GO:0044232; C:organelle membrane contact site; IDA:UniProtKB. DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central. DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell. DR GO; GO:0120013; F:lipid transfer activity; IDA:UniProtKB. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IBA:GO_Central. DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB. DR GO; GO:0044804; P:nucleophagy; IBA:GO_Central. DR GO; GO:0034727; P:piecemeal microautophagy of the nucleus; IBA:GO_Central. DR GO; GO:2000786; P:positive regulation of autophagosome assembly; IDA:UniProtKB. DR GO; GO:0061709; P:reticulophagy; IBA:GO_Central. DR DisProt; DP02142; -. DR InterPro; IPR026849; ATG2. DR InterPro; IPR015412; Atg2/VPS13_C. DR InterPro; IPR026854; VPS13-like_N. DR PANTHER; PTHR13190; AUTOPHAGY-RELATED 2, ISOFORM A; 1. DR PANTHER; PTHR13190:SF21; AUTOPHAGY-RELATED PROTEIN 2 HOMOLOG A; 1. DR Pfam; PF09333; ATG2-VPS13_C; 1. DR Pfam; PF12624; Chorein_N; 1. DR Genevisible; Q2TAZ0; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Endoplasmic reticulum; KW Lipid droplet; Lipid transport; Membrane; Phosphoprotein; KW Reference proteome; Transport. FT CHAIN 1..1938 FT /note="Autophagy-related protein 2 homolog A" FT /id="PRO_0000315234" FT DOMAIN 14..111 FT /note="Chorein N-terminal" FT /evidence="ECO:0000255" FT REGION 1242..1272 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1315..1359 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1358..1404 FT /note="WIPI-interacting" FT /evidence="ECO:0000269|PubMed:32483132" FT REGION 1438..1476 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1614..1657 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1344..1359 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1449..1474 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1622..1649 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 765 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 878 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6P4T0" FT MOD_RES 892 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6P4T0" FT MOD_RES 894 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6P4T0" FT MOD_RES 1266 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6P4T0" FT MOD_RES 1301 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1309 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1402 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..1607 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030510" FT VAR_SEQ 58..121 FT /note="SVNEVLESMESPLELVEGFVGSIEVAVPWAALLTDHCTVRVSGLQLTLQPRR FT GPAPGAADSQSW -> VRSQARVQEVCERGAGVNGVTAGAGGRLRGLHRGGRALGCSAH FT RPLHSARVRPPAHLAAPPGSR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_030511" FT VAR_SEQ 122..1938 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_030512" FT VAR_SEQ 1259 FT /note="K -> KVQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030515" FT VAR_SEQ 1608..1724 FT /note="INPVVPGETSAEARPETRAQPSSPLEGQAEGVETTGSQEAPGGGHSPSPPDQ FT QPIYFREFRFTSEVPIWLDYHGKHVTMDQVGTFAGLLIGLAQLNCSELKLKRLCCRHGL FT LGVDKV -> MAVAMVKLCERAGLPLLAAPLLRSLLPRAPQPGPAQPRSVQGQRCPARH FT PPGNLVCERGAGVNGVTAGAGGRLRGLHRGGRALGCSAHRPLHSARVRPPAHLAAPPGS FT SARGCRLTE (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030516" FT VARIANT 175 FT /note="V -> I (in dbSNP:rs12293826)" FT /id="VAR_038158" FT VARIANT 394 FT /note="R -> C (in dbSNP:rs35115827)" FT /id="VAR_061027" FT VARIANT 404 FT /note="A -> V (in dbSNP:rs60711419)" FT /id="VAR_061028" FT VARIANT 627 FT /note="A -> V (in dbSNP:rs2285347)" FT /id="VAR_038159" FT VARIANT 656 FT /note="P -> R (in dbSNP:rs656195)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:9455477" FT /id="VAR_061029" FT VARIANT 948 FT /note="G -> R (in dbSNP:rs11827140)" FT /id="VAR_038160" FT MUTAGEN 54 FT /note="L->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-82, E-101, R-167, E-171, FT R-193, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 80 FT /note="I->E: In Mutant 2; abolished lipid transfer FT activity; when associated with D-103, K-167, R-171, E-193, FT K-259, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 82 FT /note="V->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, E-101, R-167, E-171, FT R-193, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 101 FT /note="L->E: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, R-167, E-171, FT R-193, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 103 FT /note="L->D: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80,K-167, R-171, E-193, FT K-259, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 167 FT /note="I->K: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80, D-103, R-171, E-193, FT K-259, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 167 FT /note="I->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, E-171, FT R-193, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 171 FT /note="F->E: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT R-193, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 171 FT /note="F->R: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80, D-103, K-167, E-193, FT K-259, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 193 FT /note="V->E: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80, D-103, K-167, R-171, FT K-259, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 193 FT /note="V->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-200, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 200 FT /note="Y->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-193, E-223, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 223 FT /note="L->E: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-193, R-200, R-285, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 259 FT /note="M->K: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80, D-103, K-167, R-171, FT E-193, E-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 285 FT /note="L->E: In Mutant 2; abolished lipid transfer FT activity; when associated with E-80, D-103, K-167, R-171, FT E-193, K-259 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 285 FT /note="L->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-193, R-200, E-223, R-304 and R-328." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 304 FT /note="V->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-193, R-200, E-223, R-285 and R-328. In Mutant 2; FT abolished lipid transfer activity; when associated with FT E-80, D-103, K-167, R-171, E-193, K-259 and E-285." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 328 FT /note="W->R: In Mutant 1; abolished lipid transfer FT activity; when associated with R-54, R-82, E-101, R-167, FT E-171, R-193, R-200, E-223, R-285 and R-304." FT /evidence="ECO:0000269|PubMed:30952800" FT MUTAGEN 1381 FT /note="V->Q: Decreased interaction with WDR45/WIPI4 and FT ability to promote autophagy." FT /evidence="ECO:0000269|PubMed:32483132" FT MUTAGEN 1382 FT /note="T->Q: Decreased interaction with WDR45/WIPI4 and FT ability to promote autophagy." FT /evidence="ECO:0000269|PubMed:32483132" FT MUTAGEN 1389 FT /note="I->Q: Decreased interaction with WDR45/WIPI4 and FT ability to promote autophagy." FT /evidence="ECO:0000269|PubMed:32483132" FT MUTAGEN 1395 FT /note="Y->A: Decreased interaction with WDR45/WIPI4 and FT ability to promote autophagy." FT /evidence="ECO:0000269|PubMed:32483132" FT MUTAGEN 1396 FT /note="F->A: Decreased interaction with WDR45/WIPI4 and FT ability to promote autophagy." FT /evidence="ECO:0000269|PubMed:32483132" FT CONFLICT 1286 FT /note="A -> S (in Ref. 4; AAI10651)" FT /evidence="ECO:0000305" FT STRAND 1380..1383 FT /evidence="ECO:0007829|PDB:6KLR" SQ SEQUENCE 1938 AA; 212860 MW; B0072E075E305A33 CRC64; MSRWLWPWSN CVKERVCRYL LHHYLGHFFQ EHLSLDQLSL DLYKGSVALR DIHLEIWSVN EVLESMESPL ELVEGFVGSI EVAVPWAALL TDHCTVRVSG LQLTLQPRRG PAPGAADSQS WASCMTTSLQ LAQECLRDGL PEPSEPPQPL EGLEMFAQTI ETVLRRIKVT FLDTVVRVEH SPGDGERGVA VEVRVQRLEY CDEAVRDPSQ APPVDVHQPP AFLHKLLQLA GVRLHYEELP AQEEPPEPPL QIGSCSGYME LMVKLKQNEA FPGPKLEVAG QLGSLHLLLT PRQLQQLQEL LSAVSLTDHE GLADKLNKSR PLGAEDLWLI EQDLNQQLQA GAVAEPLSPD PLTNPLLNLD NTDLFFSMAG LTSSVASALS ELSLSDVDLA SSVRSDMASR RLSAQAHPAG KMAPNPLLDT MRPDSLLKMT LGGVTLTLLQ TSAPSSGPPD LATHFFTEFD ATKDGPFGSR DFHHLRPRFQ RACPCSHVRL TGTAVQLSWE LRTGSRGRRT TSMEVHFGQL EVLECLWPRG TSEPEYTEIL TFPGTLGSQA SARPCAHLRH TQILRRVPKS RPRRSVACHC HSELALDLAN FQADVELGAL DRLAALLRLA TVPAEPPAGL LTEPLPAMEQ QTVFRLSAPR ATLRLRFPIA DLRPEPDPWA GQAVRAEQLR LELSEPQFRS ELSSGPGPPV PTHLELTCSD LHGIYEDGGK PPVPCLRVSK ALDPKSTGRK YFLPQVVVTV NPQSSSTQWE VAPEKGEELE LSVESPCELR EPEPSPFSSK RTMYETEEMV IPGDPEEMRT FQSRTLALSR CSLEVILPSV HIFLPSKEVY ESIYNRINND LLMWEPADLL PTPDPAAQPS GFPGPSGFWH DSFKMCKSAF KLANCFDLTP DSDSDDEDAH FFSVGASGGP QAAAPEAPSL HLQSTFSTLV TVLKGRITAL CETKDEGGKR LEAVHGELVL DMEHGTLFSV SQYCGQPGLG YFCLEAEKAT LYHRAAVDDY PLPSHLDLPS FAPPAQLAPT IYPSEEGVTE RGASGRKGQG RGPHMLSTAV RIHLDPHKNV KEFLVTLRLH KATLRHYMAL PEQSWHSQLL EFLDVLDDPV LGYLPPTVIT ILHTHLFSCS VDYRPLYLPV RVLITAETFT LSSNIIMDTS TFLLRFILDD SALYLSDKCE VETLDLRRDY VCVLDVDLLE LVIKTWKGST EGKLSQPLFE LRCSNNVVHV HSCADSCALL VNLLQYVMST GDLHPPPRPP SPTEIAGQKL SESPASLPSC PPVETALINQ RDLADALLDT ERSLRELAQP SGGHLPQASP ISVYLFPGER SGAPPPSPPV GGPAGSLGSC SEEKEDEREE EGDGDTLDSD EFCILDAPGL GIPPRDGEPV VTQLHPGPIV VRDGYFSRPI GSTDLLRAPA HFPVPSTRVV LREVSLVWHL YGGRDFGPHP GHRARTGLSG PRSSPSRCSG PNRPQNSWRT QGGSGRQHHV LMEIQLSKVS FQHEVYPAEP ATGPAAPSQE LEERPLSRQV FIVQELEVRD RLASSQINKF LYLHTSERMP RRAHSNMLTI KALHVAPTTN LGGPECCLRV SLMPLRLNVD QDALFFLKDF FTSLVAGINP VVPGETSAEA RPETRAQPSS PLEGQAEGVE TTGSQEAPGG GHSPSPPDQQ PIYFREFRFT SEVPIWLDYH GKHVTMDQVG TFAGLLIGLA QLNCSELKLK RLCCRHGLLG VDKVLGYALN EWLQDIRKNQ LPGLLGGVGP MHSVVQLFQG FRDLLWLPIE QYRKDGRLMR GLQRGAASFG SSTASAALEL SNRLVQAIQA TAETVYDILS PAAPVSRSLQ DKRSARRLRR GQQPADLREG VAKAYDTVRE GILDTAQTIC DVASRGHEQK GLTGAVGGVI RQLPPTVVKP LILATEATSS LLGGMRNQIV PDAHKDHALK WRSDSAQD //