ATG9A_HUMAN
ID ATG9A_HUMAN Reviewed; 839 AA.
AC Q7Z3C6; Q3ZAQ6; Q6P0N7; Q7Z317; Q7Z320; Q8NDK6; Q8WU65; Q9BVL5; Q9H6L1;
AC Q9HAG7;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Autophagy-related protein 9A {ECO:0000303|PubMed:20124090};
DE AltName: Full=APG9-like 1 {ECO:0000303|PubMed:15755735};
DE AltName: Full=mATG9 {ECO:0000303|PubMed:19893488, ECO:0000303|PubMed:22456507};
GN Name=ATG9A {ECO:0000303|PubMed:20124090, ECO:0000312|HGNC:HGNC:22408};
GN Synonyms=APG9L1 {ECO:0000303|PubMed:15755735};
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] (ISOFORMS 1 AND 2), AND VARIANT
RP GLY-592.
RC TISSUE=Fetal brain, Lung endothelial cell, Rectum tumor, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain, and Lymph;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-839, AND VARIANT GLY-592.
RC TISSUE=Embryo;
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 IDENTIFICATION.
RX PubMed=15755735; DOI=10.1074/jbc.m413957200;
RA Yamada T., Carson A.R., Caniggia I., Umebayashi K., Yoshimori T.,
RA Nakabayashi K., Scherer S.W.;
RT "Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an
RT autophagy-related protein (APG9-like2) highly expressed in trophoblast.";
RL J. Biol. Chem. 280:18283-18290(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-828, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION AT ASN-99.
RX PubMed=16940348; DOI=10.1242/jcs.03172;
RA Young A.R., Chan E.Y., Hu X.W., Kochl R., Crawshaw S.G., High S.,
RA Hailey D.W., Lippincott-Schwartz J., Tooze S.A.;
RT "Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN
RT and endosomes.";
RL J. Cell Sci. 119:3888-3900(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-18 AND SER-656, AND
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 [10]
RP SUBCELLULAR LOCATION.
RX PubMed=18936157; DOI=10.1128/mcb.01082-08;
RA Chan E.Y.W., Longatti A., McKnight N.C., Tooze S.A.;
RT "Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-
RT terminal domains using an Atg13-independent mechanism.";
RL Mol. Cell. Biol. 29:157-171(2009).
RN [11]
RP INTERACTION WITH SUPT20H.
RX PubMed=19893488; DOI=10.1038/emboj.2009.321;
RA Webber J.L., Tooze S.A.;
RT "Coordinated regulation of autophagy by p38alpha MAPK through mAtg9 and
RT p38IP.";
RL EMBO J. 29:27-40(2010).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=19910472; DOI=10.1074/jbc.m109.054197;
RA Gao W., Kang J.H., Liao Y., Ding W.X., Gambotto A.A., Watkins S.C.,
RA Liu Y.J., Stolz D.B., Yin X.M.;
RT "Biochemical isolation and characterization of the tubulovesicular LC3-
RT positive autophagosomal compartment.";
RL J. Biol. Chem. 285:1371-1383(2010).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=20124090; DOI=10.1369/jhc.2010.955690;
RA Tamura H., Shibata M., Koike M., Sasaki M., Uchiyama Y.;
RT "Atg9A protein, an autophagy-related membrane protein, is localized in the
RT neurons of mouse brains.";
RL J. Histochem. Cytochem. 58:443-453(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-828, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP SUBCELLULAR LOCATION, AND TRAFFICKING.
RX PubMed=21068542; DOI=10.4161/auto.7.1.14015;
RA Takahashi Y., Meyerkord C.L., Hori T., Runkle K., Fox T.E., Kester M.,
RA Loughran T.P., Wang H.G.;
RT "Bif-1 regulates Atg9 trafficking by mediating the fission of Golgi
RT membranes during autophagy.";
RL Autophagy 7:61-73(2011).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-735; SER-738 AND SER-741, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP FUNCTION, AND 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 [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-18; SER-656; SER-735
RP AND SER-828, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-735 AND SER-828, AND
RP IDENTIFICATION BY 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 [22]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-99, AND MUTAGENESIS OF ASN-99
RP AND 711-LEU--MET-713.
RX PubMed=27316455; DOI=10.1016/j.bbamcr.2016.06.007;
RA Staudt C., Gilis F., Boonen M., Jadot M.;
RT "Molecular determinants that mediate the sorting of human ATG9A from the
RT endoplasmic reticulum.";
RL Biochim. Biophys. Acta 1863:2299-2310(2016).
RN [23]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 516-GLY--CYS-519.
RX PubMed=27663665; DOI=10.1016/j.bbrc.2016.09.097;
RA Staudt C., Gilis F., Tevel V., Jadot M., Boonen M.;
RT "A conserved glycine residue in the C-terminal region of human ATG9A is
RT required for its transport from the endoplasmic reticulum to the Golgi
RT apparatus.";
RL Biochem. Biophys. Res. Commun. 479:404-409(2016).
RN [24]
RP FUNCTION.
RX PubMed=27510922; DOI=10.1038/ncomms12420;
RA Karanasios E., Walker S.A., Okkenhaug H., Manifava M., Hummel E.,
RA Zimmermann H., Ahmed Q., Domart M.C., Collinson L., Ktistakis N.T.;
RT "Autophagy initiation by ULK complex assembly on ER tubulovesicular regions
RT marked by ATG9 vesicles.";
RL Nat. Commun. 7:12420-12420(2016).
RN [25]
RP SUBCELLULAR LOCATION, INTERACTION WITH AP4M1, MOTIF, DOMAIN, AND
RP MUTAGENESIS OF TYR-8; GLN-9; ARG-10; LEU-11; GLU-12 AND TYR-15.
RX PubMed=29180427; DOI=10.1073/pnas.1717327114;
RA Mattera R., Park S.Y., De Pace R., Guardia C.M., Bonifacino J.S.;
RT "AP-4 mediates export of ATG9A from the trans-Golgi network to promote
RT autophagosome formation.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E10697-E10706(2017).
RN [26]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29437695; DOI=10.15252/embr.201744837;
RA Soereng K., Munson M.J., Lamb C.A., Bjoerndal G.T., Pankiv S.,
RA Carlsson S.R., Tooze S.A., Simonsen A.;
RT "SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting
RT Dynamin-2.";
RL EMBO Rep. 19:0-0(2018).
RN [27]
RP SUBCELLULAR LOCATION.
RX PubMed=30262884; DOI=10.1038/s41467-018-06172-7;
RA Davies A.K., Itzhak D.N., Edgar J.R., Archuleta T.L., Hirst J.,
RA Jackson L.P., Robinson M.S., Borner G.H.H.;
RT "AP-4 vesicles contribute to spatial control of autophagy via RUSC-
RT dependent peripheral delivery of ATG9A.";
RL Nat. Commun. 9:3958-3958(2018).
RN [28]
RP FUNCTION, AND INTERACTION WITH ARFIP1; ARFIP1; PI4K2A AND PI4KB.
RX PubMed=30917996; DOI=10.1083/jcb.201901115;
RA Judith D., Jefferies H.B.J., Boeing S., Frith D., Snijders A.P.,
RA Tooze S.A.;
RT "ATG9A shapes the forming autophagosome through Arfaptin 2 and
RT phosphatidylinositol 4-kinase IIIbeta.";
RL J. Cell Biol. 218:1634-1652(2019).
RN [29]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=32513819; DOI=10.1242/jcs.246306;
RA Anton Z., Betin V.M.S., Simonetti B., Traer C.J., Attar N., Cullen P.J.,
RA Lane J.D.;
RT "A heterodimeric SNX4--SNX7 SNX-BAR autophagy complex coordinates ATG9A
RT trafficking for efficient autophagosome assembly.";
RL J. Cell Sci. 133:0-0(2020).
RN [30]
RP SUBCELLULAR LOCATION.
RX PubMed=34432599; DOI=10.1080/15548627.2021.1960116;
RA Yan B.R., Li T., Coyaud E., Laurent E.M.N., St-Germain J., Zhou Y.,
RA Kim P.K., Raught B., Brumell J.H.;
RT "C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A
RT localization and stability during mitophagy.";
RL Autophagy 18:829-840(2022).
RN [31]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=33468622; DOI=10.1242/jcs.250670;
RA Ravussin A., Brech A., Tooze S.A., Stenmark H.;
RT "The phosphatidylinositol 3-phosphate-binding protein SNX4 controls ATG9A
RT recycling and autophagy.";
RL J. Cell Sci. 134:0-0(2021).
RN [32]
RP SUBCELLULAR LOCATION.
RX PubMed=32073997; DOI=10.1091/mbc.e19-11-0658;
RA Mattera R., Williamson C.D., Ren X., Bonifacino J.S.;
RT "The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear
RT distribution of AP-4 and its cargo ATG9A.";
RL Mol. Biol. Cell 31:963-979(2020).
RN [33]
RP INTERACTION WITH ATG4A.
RX PubMed=33773106; DOI=10.1016/j.molcel.2021.03.001;
RA Nguyen T.N., Padman B.S., Zellner S., Khuu G., Uoselis L., Lam W.K.,
RA Skulsuppaisarn M., Lindblom R.S.J., Watts E.M., Behrends C., Lazarou M.;
RT "ATG4 family proteins drive phagophore growth independently of the
RT LC3/GABARAP lipidation system.";
RL Mol. Cell 81:2013-2030(2021).
RN [34]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [35] {ECO:0007744|PDB:6WQZ, ECO:0007744|PDB:6WR4}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.80 ANGSTROMS) OF 1-688, FUNCTION,
RP SUBUNIT, TOPOLOGY, DOMAIN, INTERACTION WITH ATG2A, AND MUTAGENESIS OF
RP ASN-265 AND ARG-422.
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 [36] {ECO:0007744|PDB:7JLO, ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 1-578, FUNCTION,
RP CATALYTIC ACTIVITY, SUBUNIT, TOPOLOGY, DOMAIN, INTERACTION WITH ATG2A, AND
RP MUTAGENESIS OF 321-LYS--GLU-323; THR-412 AND THR-419.
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).
CC -!- FUNCTION: Phospholipid scramblase involved in autophagy by mediating
CC autophagosomal membrane expansion (PubMed:22456507, PubMed:27510922,
CC PubMed:29437695, PubMed:32513819, PubMed:33468622, PubMed:33850023,
CC PubMed:32610138, PubMed:33106659). Cycles between the preautophagosomal
CC structure/phagophore assembly site (PAS) and the cytoplasmic vesicle
CC pool and supplies membrane for the growing autophagosome
CC (PubMed:16940348, PubMed:22456507, PubMed:33106659). Lipid scramblase
CC activity plays a key role in preautophagosomal structure/phagophore
CC assembly by distributing the phospholipids that arrive through ATG2
CC (ATG2A or ATG2B) from the cytoplasmic to the luminal leaflet of the
CC bilayer, thereby driving autophagosomal membrane expansion
CC (PubMed:33106659). Also required to supply phosphatidylinositol 4-
CC phosphate to the autophagosome initiation site by recruiting the
CC phosphatidylinositol 4-kinase beta (PI4KB) in a process dependent on
CC ARFIP2, but not ARFIP1 (PubMed:30917996). In addition to autophagy,
CC also plays a role in necrotic cell death (By similarity).
CC {ECO:0000250|UniProtKB:Q68FE2, ECO:0000269|PubMed:16940348,
CC ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27510922,
CC ECO:0000269|PubMed:29437695, ECO:0000269|PubMed:30917996,
CC ECO:0000269|PubMed:32513819, ECO:0000269|PubMed:32610138,
CC ECO:0000269|PubMed:33106659, ECO:0000269|PubMed:33468622,
CC ECO:0000269|PubMed:33850023}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:33106659,
CC ECO:0000269|PubMed:33850023};
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:33106659,
CC ECO:0000269|PubMed:33850023};
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:33106659,
CC ECO:0000269|PubMed:33850023};
CC -!- SUBUNIT: Homotrimer; forms a homotrimer with a central pore that forms
CC a path between the two membrane leaflets (PubMed:32610138,
CC PubMed:33106659). Interacts (via cytoplasmic its C-terminus) with ATG2A
CC (PubMed:32610138, PubMed:33106659). Interacts with SUPT20H
CC (PubMed:19893488). Interacts (via the tyrosine-based sorting signal
CC motif) with AP4M1; promoting association with the AP-4 complex
CC (PubMed:29180427). Interacts with ARFIP1 and ARFIP2 (PubMed:30917996).
CC Interacts with PI4K2A and PI4KB (PubMed:30917996). Interacts with
CC ATG4A; the interaction is direct and promotes ATG9A trafficking
CC (PubMed:33773106). {ECO:0000269|PubMed:19893488,
CC ECO:0000269|PubMed:29180427, ECO:0000269|PubMed:30917996,
CC ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659,
CC ECO:0000269|PubMed:33773106}.
CC -!- INTERACTION:
CC Q7Z3C6; Q96CW1: AP2M1; NbExp=8; IntAct=EBI-727146, EBI-297683;
CC Q7Z3C6; Q2TAZ0: ATG2A; NbExp=4; IntAct=EBI-727146, EBI-2514077;
CC Q7Z3C6; Q15323: KRT31; NbExp=3; IntAct=EBI-727146, EBI-948001;
CC Q7Z3C6; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-727146, EBI-10171774;
CC Q7Z3C6; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-727146, EBI-10172511;
CC Q7Z3C6; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-727146, EBI-3958099;
CC Q7Z3C6; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-727146, EBI-2341787;
CC Q7Z3C6; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-727146, EBI-945833;
CC Q7Z3C6; Q04864: REL; NbExp=3; IntAct=EBI-727146, EBI-307352;
CC Q7Z3C6; Q8NEM7-2: SUPT20H; NbExp=8; IntAct=EBI-727146, EBI-7568679;
CC Q7Z3C6; Q9UHD2: TBK1; NbExp=2; IntAct=EBI-727146, EBI-356402;
CC Q7Z3C6; Q05086-2: UBE3A; NbExp=3; IntAct=EBI-727146, EBI-10175863;
CC Q7Z3C6-3; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-12006308, EBI-10173507;
CC Q7Z3C6-3; Q9NXR5-2: ANKRD10; NbExp=3; IntAct=EBI-12006308, EBI-12102070;
CC Q7Z3C6-3; Q9H5F2: C11orf1; NbExp=3; IntAct=EBI-12006308, EBI-718615;
CC Q7Z3C6-3; Q5T4B2: CERCAM; NbExp=3; IntAct=EBI-12006308, EBI-12261896;
CC Q7Z3C6-3; A0PJX0: CIB4; NbExp=5; IntAct=EBI-12006308, EBI-12868028;
CC Q7Z3C6-3; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12006308, EBI-3867333;
CC Q7Z3C6-3; O95571: ETHE1; NbExp=3; IntAct=EBI-12006308, EBI-715318;
CC Q7Z3C6-3; Q9HD26-2: GOPC; NbExp=5; IntAct=EBI-12006308, EBI-11102276;
CC Q7Z3C6-3; Q9BSH5: HDHD3; NbExp=3; IntAct=EBI-12006308, EBI-745201;
CC Q7Z3C6-3; Q9BS75: KLHL20; NbExp=3; IntAct=EBI-12006308, EBI-10693436;
CC Q7Z3C6-3; Q5T749: KPRP; NbExp=5; IntAct=EBI-12006308, EBI-10981970;
CC Q7Z3C6-3; Q15323: KRT31; NbExp=3; IntAct=EBI-12006308, EBI-948001;
CC Q7Z3C6-3; Q14525: KRT33B; NbExp=3; IntAct=EBI-12006308, EBI-1049638;
CC Q7Z3C6-3; O76011: KRT34; NbExp=3; IntAct=EBI-12006308, EBI-1047093;
CC Q7Z3C6-3; Q92764: KRT35; NbExp=3; IntAct=EBI-12006308, EBI-1058674;
CC Q7Z3C6-3; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-12006308, EBI-11959885;
CC Q7Z3C6-3; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-12006308, EBI-11749135;
CC Q7Z3C6-3; P60410: KRTAP10-8; NbExp=5; IntAct=EBI-12006308, EBI-10171774;
CC Q7Z3C6-3; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-12006308, EBI-1052037;
CC Q7Z3C6-3; Q3SY46: KRTAP13-3; NbExp=5; IntAct=EBI-12006308, EBI-10241252;
CC Q7Z3C6-3; Q8IUB9: KRTAP19-1; NbExp=3; IntAct=EBI-12006308, EBI-12811111;
CC Q7Z3C6-3; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-12006308, EBI-751260;
CC Q7Z3C6-3; Q9BYR6: KRTAP3-3; NbExp=3; IntAct=EBI-12006308, EBI-3957694;
CC Q7Z3C6-3; Q3LI66: KRTAP6-2; NbExp=5; IntAct=EBI-12006308, EBI-11962084;
CC Q7Z3C6-3; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-12006308, EBI-10261141;
CC Q7Z3C6-3; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-12006308, EBI-1044640;
CC Q7Z3C6-3; P50221: MEOX1; NbExp=3; IntAct=EBI-12006308, EBI-2864512;
CC Q7Z3C6-3; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12006308, EBI-16439278;
CC Q7Z3C6-3; P17568: NDUFB7; NbExp=3; IntAct=EBI-12006308, EBI-1246238;
CC Q7Z3C6-3; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-12006308, EBI-22310682;
CC Q7Z3C6-3; Q8TDS5: OXER1; NbExp=3; IntAct=EBI-12006308, EBI-12813389;
CC Q7Z3C6-3; Q04864-2: REL; NbExp=3; IntAct=EBI-12006308, EBI-10829018;
CC Q7Z3C6-3; P15884-3: TCF4; NbExp=3; IntAct=EBI-12006308, EBI-13636688;
CC Q7Z3C6-3; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-12006308, EBI-5235829;
CC Q7Z3C6-3; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-12006308, EBI-12287587;
CC Q7Z3C6-3; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-12006308, EBI-745520;
CC Q7Z3C6-3; Q6ZNG0: ZNF620; NbExp=3; IntAct=EBI-12006308, EBI-4395669;
CC -!- SUBCELLULAR LOCATION: Preautophagosomal structure membrane
CC {ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:32073997,
CC ECO:0000269|PubMed:33106659}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Cytoplasmic
CC vesicle, autophagosome membrane {ECO:0000269|PubMed:19910472}; Multi-
CC pass membrane protein {ECO:0000269|PubMed:32610138,
CC ECO:0000269|PubMed:33106659}. Golgi apparatus, trans-Golgi network
CC membrane {ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:20124090,
CC ECO:0000269|PubMed:21068542, ECO:0000269|PubMed:27316455,
CC ECO:0000269|PubMed:27663665, ECO:0000269|PubMed:29180427,
CC ECO:0000269|PubMed:33468622, ECO:0000305|PubMed:34432599}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:32610138,
CC ECO:0000269|PubMed:33106659}. Late endosome membrane
CC {ECO:0000269|PubMed:16940348, ECO:0000269|PubMed:20124090,
CC ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:32513819,
CC ECO:0000269|PubMed:33468622}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Recycling
CC endosome membrane {ECO:0000269|PubMed:22456507,
CC ECO:0000269|PubMed:29437695}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32610138, ECO:0000269|PubMed:33106659}. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:20124090,
CC ECO:0000269|PubMed:27316455, ECO:0000269|PubMed:27663665}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:32610138,
CC ECO:0000269|PubMed:33106659}. Mitochondrion membrane
CC {ECO:0000305|PubMed:34432599}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Mainly localizes to the trans-Golgi network (TGN)
CC and the endosomal system; cycles between them though vesicle
CC trafficking (PubMed:27316455, PubMed:27663665). Export from the TGN to
CC promote formation of autophagosomes is mediated by the AP-4 complex
CC (PubMed:29180427, PubMed:30262884). Under amino acid starvation or
CC rapamycin treatment, redistributes to preautophagosomal
CC structure/phagophore assembly site (PAS) (PubMed:16940348). The
CC starvation-induced redistribution depends on ULK1, ATG13, as well as
CC SH3GLB1 (PubMed:16940348). Upon autophagy induction, a small portion
CC transiently localizes to the autophagic membranes (PubMed:22456507).
CC Recruited to damaged mitochondria during mitophagy in a RIMOC1-
CC dependent manner (PubMed:34432599). {ECO:0000269|PubMed:16940348,
CC ECO:0000269|PubMed:22456507, ECO:0000269|PubMed:27316455,
CC ECO:0000269|PubMed:27663665, ECO:0000269|PubMed:29180427,
CC ECO:0000269|PubMed:30262884, ECO:0000269|PubMed:34432599}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z3C6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z3C6-2; Sequence=VSP_013396;
CC Name=3;
CC IsoId=Q7Z3C6-3; Sequence=VSP_013397, VSP_013398;
CC -!- DOMAIN: Forms a homotrimer with a solvated central pore, which is
CC connected laterally to the cytosol through the cavity within each
CC protomer (PubMed:32610138, PubMed:33106659). Acts as a lipid scramblase
CC that uses its central pore to function: the central pore opens
CC laterally to accommodate lipid headgroups, thereby enabling lipid
CC flipping and redistribution of lipids added to the outer leaflet of
CC ATG9A-containing vesicles, thereby enabling growth into autophagosomes
CC (PubMed:33106659). {ECO:0000269|PubMed:32610138,
CC ECO:0000269|PubMed:33106659}.
CC -!- DOMAIN: The tyrosine-based sorting signal motif, also named YXX-psi
CC motif, promotes interaction with the AP-4 complex.
CC {ECO:0000269|PubMed:29180427}.
CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ATG9 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13882.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB15246.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB55119.1; Type=Erroneous initiation; Note=Truncated 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; AL833865; CAD38723.1; -; mRNA.
DR EMBL; BX537984; CAD97944.1; -; mRNA.
DR EMBL; BX538192; CAD98061.1; -; mRNA.
DR EMBL; BX538198; CAD98064.1; -; mRNA.
DR EMBL; AC068946; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW70706.1; -; Genomic_DNA.
DR EMBL; BC001098; AAH01098.2; -; mRNA.
DR EMBL; BC021202; AAH21202.2; -; mRNA.
DR EMBL; BC065534; AAH65534.1; -; mRNA.
DR EMBL; AK021732; BAB13882.1; ALT_INIT; mRNA.
DR EMBL; AK027448; BAB55119.1; ALT_INIT; mRNA.
DR EMBL; AK025822; BAB15246.1; ALT_INIT; mRNA.
DR EMBL; BK004018; DAA05199.1; -; mRNA.
DR CCDS; CCDS42820.1; -. [Q7Z3C6-1]
DR RefSeq; NP_001070666.1; NM_001077198.2. [Q7Z3C6-1]
DR RefSeq; NP_076990.4; NM_024085.4. [Q7Z3C6-1]
DR PDB; 6WQZ; EM; 2.80 A; A/B/C/D/E/F=1-688.
DR PDB; 6WR4; EM; 2.90 A; A/B/C=1-839.
DR PDB; 7JLO; EM; 3.40 A; A/B/C=1-578.
DR PDB; 7JLP; EM; 3.40 A; A/B/C=1-578.
DR PDB; 7JLQ; EM; 4.00 A; A/B/C=1-578.
DR PDBsum; 6WQZ; -.
DR PDBsum; 6WR4; -.
DR PDBsum; 7JLO; -.
DR PDBsum; 7JLP; -.
DR PDBsum; 7JLQ; -.
DR AlphaFoldDB; Q7Z3C6; -.
DR SMR; Q7Z3C6; -.
DR BioGRID; 122518; 161.
DR IntAct; Q7Z3C6; 110.
DR MINT; Q7Z3C6; -.
DR STRING; 9606.ENSP00000386710; -.
DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family.
DR GlyGen; Q7Z3C6; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q7Z3C6; -.
DR PhosphoSitePlus; Q7Z3C6; -.
DR BioMuta; ATG9A; -.
DR DMDM; 296439428; -.
DR EPD; Q7Z3C6; -.
DR jPOST; Q7Z3C6; -.
DR MassIVE; Q7Z3C6; -.
DR MaxQB; Q7Z3C6; -.
DR PaxDb; Q7Z3C6; -.
DR PeptideAtlas; Q7Z3C6; -.
DR PRIDE; Q7Z3C6; -.
DR ProteomicsDB; 69026; -. [Q7Z3C6-1]
DR ProteomicsDB; 69027; -. [Q7Z3C6-2]
DR ProteomicsDB; 69028; -. [Q7Z3C6-3]
DR Antibodypedia; 34308; 447 antibodies from 38 providers.
DR DNASU; 79065; -.
DR Ensembl; ENST00000361242.9; ENSP00000355173.4; ENSG00000198925.12. [Q7Z3C6-1]
DR Ensembl; ENST00000396761.6; ENSP00000379983.2; ENSG00000198925.12. [Q7Z3C6-1]
DR Ensembl; ENST00000409033.7; ENSP00000386482.3; ENSG00000198925.12. [Q7Z3C6-3]
DR Ensembl; ENST00000409422.5; ENSP00000386535.1; ENSG00000198925.12. [Q7Z3C6-2]
DR Ensembl; ENST00000409618.5; ENSP00000386710.1; ENSG00000198925.12. [Q7Z3C6-1]
DR GeneID; 79065; -.
DR KEGG; hsa:79065; -.
DR MANE-Select; ENST00000361242.9; ENSP00000355173.4; NM_001077198.3; NP_001070666.1.
DR UCSC; uc002vke.3; human. [Q7Z3C6-1]
DR CTD; 79065; -.
DR DisGeNET; 79065; -.
DR GeneCards; ATG9A; -.
DR HGNC; HGNC:22408; ATG9A.
DR HPA; ENSG00000198925; Low tissue specificity.
DR MIM; 612204; gene.
DR neXtProt; NX_Q7Z3C6; -.
DR OpenTargets; ENSG00000198925; -.
DR PharmGKB; PA134931318; -.
DR VEuPathDB; HostDB:ENSG00000198925; -.
DR eggNOG; KOG2173; Eukaryota.
DR GeneTree; ENSGT00390000014839; -.
DR HOGENOM; CLU_006200_2_2_1; -.
DR InParanoid; Q7Z3C6; -.
DR OMA; MAHFETE; -.
DR PhylomeDB; Q7Z3C6; -.
DR TreeFam; TF313665; -.
DR PathwayCommons; Q7Z3C6; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR SignaLink; Q7Z3C6; -.
DR SIGNOR; Q7Z3C6; -.
DR BioGRID-ORCS; 79065; 134 hits in 1089 CRISPR screens.
DR ChiTaRS; ATG9A; human.
DR GeneWiki; ATG9A; -.
DR GenomeRNAi; 79065; -.
DR Pharos; Q7Z3C6; Tbio.
DR PRO; PR:Q7Z3C6; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q7Z3C6; protein.
DR Bgee; ENSG00000198925; Expressed in gastrocnemius and 95 other tissues.
DR ExpressionAtlas; Q7Z3C6; baseline and differential.
DR Genevisible; Q7Z3C6; HS.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IDA:MGI.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0000407; C:phagophore assembly site; IDA:MGI.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055037; C:recycling endosome; IDA:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IDA:UniProtKB.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IDA:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IDA:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0044805; P:late nucleophagy; IBA:GO_Central.
DR GO; GO:0010940; P:positive regulation of necrotic cell death; ISS:UniProtKB.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IBA:GO_Central.
DR DisProt; DP01730; -.
DR InterPro; IPR007241; Autophagy-rel_prot_9.
DR PANTHER; PTHR13038; PTHR13038; 1.
DR Pfam; PF04109; ATG9; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Autophagy;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Golgi apparatus; Lipid transport; Membrane; Mitochondrion; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..839
FT /note="Autophagy-related protein 9A"
FT /id="PRO_0000119820"
FT TOPO_DOM 2..61
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 62..84
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLO,
FT ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 85..128
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 129..154
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLO,
FT ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 155..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 291..301
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLP,
FT ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 302..319
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 320..328
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLO,
FT ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 329..371
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 372..397
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLO,
FT ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 398..406
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..424
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:6WR4, ECO:0007744|PDB:7JLO,
FT ECO:0007744|PDB:7JLP, ECO:0007744|PDB:7JLQ"
FT TOPO_DOM 425..470
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 471..480
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0007744|PDB:6WQZ"
FT TOPO_DOM 481..483
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 484..492
FT /evidence="ECO:0000269|PubMed:32610138,
FT ECO:0000269|PubMed:33106659, ECO:0007744|PDB:6WQZ,
FT ECO:0007744|PDB:7JLP"
FT TOPO_DOM 493..839
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 656..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 717..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 8..11
FT /note="Tyrosine-based sorting signal"
FT /evidence="ECO:0000269|PubMed:29180427"
FT COMPBIAS 720..740
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FE2"
FT MOD_RES 18
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 656
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 735
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 741
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 828
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16940348,
FT ECO:0000269|PubMed:27316455"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_013396"
FT VAR_SEQ 455..528
FT /note="NAHRSQTRDEFAQLFQYKAVFILEELLSPIVTPLILIFCLRPRALEIIDFFR
FT NFTVEVVGVGDTCSFAQMDVRQ -> VHFGRVAEPHCHTPHPHLLPAPTGPGDYRLLPK
FT LHRGGRWCGRYLLLCSDGCSPAWSSPVAICWADRGLSVPAS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013397"
FT VAR_SEQ 529..839
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013398"
FT VARIANT 592
FT /note="S -> G (in dbSNP:rs2276635)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_021835"
FT VARIANT 659
FT /note="Q -> H (in dbSNP:rs2276634)"
FT /id="VAR_055534"
FT MUTAGEN 8
FT /note="Y->A: Abolished interaction with the AP-4 complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 9
FT /note="Q->A: Abolished interaction with the AP-4 complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 10
FT /note="R->A: Does not affect interaction with the AP-4
FT complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 11
FT /note="L->A: Abolished interaction with the AP-4 complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 12
FT /note="E->A: Abolished interaction with the AP-4 complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 15
FT /note="Y->A: Does not affect interaction with the AP-4
FT complex."
FT /evidence="ECO:0000269|PubMed:29180427"
FT MUTAGEN 99
FT /note="N->D: Abolished N-glycosylation."
FT /evidence="ECO:0000269|PubMed:27316455"
FT MUTAGEN 265
FT /note="N->W: Impaired autophagy."
FT /evidence="ECO:0000269|PubMed:32610138"
FT MUTAGEN 321..323
FT /note="KRE->LLL: Reduced lipid scramblase activity and
FT autophagy. Strongly reduced autophagy; when associated with
FT W-412. Strongly reduced lipid scramblase activity and
FT autophagy; when associated with W-419."
FT /evidence="ECO:0000269|PubMed:33106659"
FT MUTAGEN 412
FT /note="T->W: Does not affect lipid scramblase activity.
FT Strongly reduced autophagy; when associated with L-321--L-
FT 323."
FT /evidence="ECO:0000269|PubMed:33106659"
FT MUTAGEN 419
FT /note="T->W: Strongly reduced lipid scramblase activity and
FT autophagy; when associated with L-321--L-323."
FT /evidence="ECO:0000269|PubMed:33106659"
FT MUTAGEN 422
FT /note="R->W: Impaired autophagy."
FT /evidence="ECO:0000269|PubMed:32610138"
FT MUTAGEN 516..519
FT /note="GDTC->ADTA: Impaired transport from the endoplasmic
FT reticulum to the Golgi apparatus without affecting
FT homooligomerization."
FT /evidence="ECO:0000269|PubMed:27663665"
FT MUTAGEN 711..713
FT /note="LYM->AAA: Impaired transport through the Golgi
FT apparatus."
FT /evidence="ECO:0000269|PubMed:27316455"
FT CONFLICT 39
FT /note="H -> R (in Ref. 1; CAD97944)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="L -> P (in Ref. 1; CAD97944)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="A -> T (in Ref. 4; AAH65534)"
FT /evidence="ECO:0000305"
FT CONFLICT 519
FT /note="C -> R (in Ref. 1; CAD98061)"
FT /evidence="ECO:0000305"
FT CONFLICT 567
FT /note="W -> R (in Ref. 1; CAD98061)"
FT /evidence="ECO:0000305"
FT CONFLICT 669
FT /note="H -> N (in Ref. 5; BAB15246)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="A -> V (in Ref. 1; CAD97944)"
FT /evidence="ECO:0000305"
FT HELIX 43..55
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 59..85
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 89..93
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 130..167
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 180..193
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:7JLO"
FT HELIX 207..224
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 237..241
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 262..269
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:7JLP"
FT HELIX 279..322
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 326..328
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 334..337
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 347..356
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 358..365
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:6WR4"
FT HELIX 371..397
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 401..404
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 407..424
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 434..445
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 456..458
FT /evidence="ECO:0007829|PDB:7JLO"
FT HELIX 459..469
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 472..480
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 482..492
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 498..507
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:6WQZ"
FT TURN 513..515
FT /evidence="ECO:0007829|PDB:6WQZ"
FT STRAND 516..518
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:6WQZ"
FT TURN 526..528
FT /evidence="ECO:0007829|PDB:6WQZ"
FT TURN 532..534
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 552..563
FT /evidence="ECO:0007829|PDB:6WQZ"
FT HELIX 571..586
FT /evidence="ECO:0007829|PDB:6WQZ"
SQ SEQUENCE 839 AA; 94447 MW; 69BE087CA550DC42 CRC64;
MAQFDTEYQR LEASYSDSPP GEEDLLVHVA EGSKSPWHHI ENLDLFFSRV YNLHQKNGFT
CMLIGEIFEL MQFLFVVAFT TFLVSCVDYD ILFANKMVNH SLHPTEPVKV TLPDAFLPAQ
VCSARIQENG SLITILVIAG VFWIHRLIKF IYNICCYWEI HSFYLHALRI PMSALPYCTW
QEVQARIVQT QKEHQICIHK RELTELDIYH RILRFQNYMV ALVNKSLLPL RFRLPGLGEA
VFFTRGLKYN FELILFWGPG SLFLNEWSLK AEYKRGGQRL ELAQRLSNRI LWIGIANFLL
CPLILIWQIL YAFFSYAEVL KREPGALGAR CWSLYGRCYL RHFNELEHEL QSRLNRGYKP
ASKYMNCFLS PLLTLLAKNG AFFAGSILAV LIALTIYDED VLAVEHVLTT VTLLGVTVTV
CRSFIPDQHM VFCPEQLLRV ILAHIHYMPD HWQGNAHRSQ TRDEFAQLFQ YKAVFILEEL
LSPIVTPLIL IFCLRPRALE IIDFFRNFTV EVVGVGDTCS FAQMDVRQHG HPQWLSAGQT
EASVYQQAED GKTELSLMHF AITNPGWQPP RESTAFLGFL KEQVQRDGAA ASLAQGGLLP
ENALFTSIQS LQSESEPLSL IANVVAGSSC RGPPLPRDLQ GSRHRAEVAS ALRSFSPLQP
GQAPTGRAHS TMTGSGVDAR TASSGSSVWE GQLQSLVLSE YASTEMSLHA LYMHQLHKQQ
AQAEPERHVW HRRESDESGE SAPDEGGEGA RAPQSIPRSA SYPCAAPRPG APETTALHGG
FQRRYGGITD PGTVPRVPSH FSRLPLGGWA EDGQSASRHP EPVPEEGSED ELPPQVHKV
