A16L1_HUMAN
ID A16L1_HUMAN Reviewed; 607 AA.
AC Q676U5; A3EXK9; A3EXL0; B6ZDH0; Q6IPN1; Q6UXW4; Q6ZVZ5; Q8NCY2; Q96JV5;
AC Q9H619;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2005, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Autophagy-related protein 16-1 {ECO:0000305};
DE AltName: Full=APG16-like 1 {ECO:0000303|PubMed:17200669};
GN Name=ATG16L1 {ECO:0000303|PubMed:17200669, ECO:0000312|HGNC:HGNC:21498};
GN Synonyms=APG16L {ECO:0000303|PubMed:15620219};
GN ORFNames=UNQ9393/PRO34307 {ECO:0000303|PubMed:12975309};
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] (ISOFORM 1), AND VARIANT ALA-300.
RC TISSUE=Fetal brain;
RX PubMed=15620219; DOI=10.1080/10425170400004104;
RA Zheng H., Ji C., Li J., Jiang H., Ren M., Lu Q., Gu S., Mao Y., Xie Y.;
RT "Cloning and analysis of human Apg16L.";
RL DNA Seq. 15:303-305(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 5), INVOLVEMENT IN
RP SUSCEPTIBILITY TO IBD10, AND VARIANT IBD10 ALA-300.
RX PubMed=17200669; DOI=10.1038/ng1954;
RA Hampe J., Franke A., Rosenstiel P., Till A., Teuber M., Huse K.,
RA Albrecht M., Mayr G., De La Vega F.M., Briggs J., Guenther S.,
RA Prescott N.J., Onnie C.M., Haesler R., Sipos B., Foelsch U.R., Lengauer T.,
RA Platzer M., Mathew C.G., Krawczak M., Schreiber S.;
RT "A genome-wide association scan of nonsynonymous SNPs identifies a
RT susceptibility variant for Crohn disease in ATG16L1.";
RL Nat. Genet. 39:207-211(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 55-607 (ISOFORM 2).
RC TISSUE=Brain, Placenta, and Small intestine;
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 [5]
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 [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 114-607 (ISOFORM 2).
RC TISSUE=Mammary gland;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 513-607.
RC TISSUE=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 [9]
RP FUNCTION.
RX PubMed=18849966; DOI=10.1038/nature07416;
RA Cadwell K., Liu J.Y., Brown S.L., Miyoshi H., Loh J., Lennerz J.K.,
RA Kishi C., Kc W., Carrero J.A., Hunt S., Stone C.D., Brunt E.M.,
RA Xavier R.J., Sleckman B.P., Li E., Mizushima N., Stappenbeck T.S.,
RA Virgin H.W. IV;
RT "A key role for autophagy and the autophagy gene Atg16l1 in mouse and human
RT intestinal Paneth cells.";
RL Nature 456:259-263(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, 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 [11]
RP FUNCTION, AND INTERACTION WITH NOD2.
RX PubMed=20637199; DOI=10.1053/j.gastro.2010.07.006;
RA Homer C.R., Richmond A.L., Rebert N.A., Achkar J.P., McDonald C.;
RT "ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway
RT implicated in Crohn's disease pathogenesis.";
RL Gastroenterology 139:1630-1641(2010).
RN [12]
RP INTERACTION WITH CLTC, AND SUBCELLULAR LOCATION.
RX PubMed=20639872; DOI=10.1038/ncb2078;
RA Ravikumar B., Moreau K., Jahreiss L., Puri C., Rubinsztein D.C.;
RT "Plasma membrane contributes to the formation of pre-autophagosomal
RT structures.";
RL Nat. Cell Biol. 12:747-757(2010).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-269 AND SER-287, AND
RP IDENTIFICATION BY 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 [14]
RP INTERACTION WITH RAB33B.
RX PubMed=21808068; DOI=10.1074/jbc.m111.261115;
RA Nottingham R.M., Ganley I.G., Barr F.A., Lambright D.G., Pfeffer S.R.;
RT "RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32
RT and Rab33B proteins.";
RL J. Biol. Chem. 286:33213-33222(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH TUFM.
RX PubMed=22749352; DOI=10.1016/j.immuni.2012.03.025;
RA Lei Y., Wen H., Yu Y., Taxman D.J., Zhang L., Widman D.G., Swanson K.V.,
RA Wen K.W., Damania B., Moore C.B., Giguere P.M., Siderovski D.P.,
RA Hiscott J., Razani B., Semenkovich C.F., Chen X., Ting J.P.;
RT "The mitochondrial proteins NLRX1 and TUFM form a complex that regulates
RT type I interferon and autophagy.";
RL Immunity 36:933-946(2012).
RN [16]
RP FUNCTION, AND INTERACTION WITH TMEM59; TLR2 AND NOD2.
RX PubMed=23376921; DOI=10.1038/emboj.2013.8;
RA Boada-Romero E., Letek M., Fleischer A., Pallauf K., Ramon-Barros C.,
RA Pimentel-Muinos F.X.;
RT "TMEM59 defines a novel ATG16L1-binding motif that promotes local
RT activation of LC3.";
RL EMBO J. 32:566-582(2013).
RN [17]
RP FUNCTION, INTERACTION WITH RB1CC1, AND SUBCELLULAR LOCATION.
RX PubMed=23392225; DOI=10.1038/embor.2013.6;
RA Nishimura T., Kaizuka T., Cadwell K., Sahani M.H., Saitoh T., Akira S.,
RA Virgin H.W., Mizushima N.;
RT "FIP200 regulates targeting of Atg16L1 to the isolation membrane.";
RL EMBO Rep. 14:284-291(2013).
RN [18]
RP FUNCTION.
RX PubMed=24238340; DOI=10.1016/j.immuni.2013.10.013;
RA Sorbara M.T., Ellison L.K., Ramjeet M., Travassos L.H., Jones N.L.,
RA Girardin S.E., Philpott D.J.;
RT "The protein ATG16L1 suppresses inflammatory cytokines induced by the
RT intracellular sensors Nod1 and Nod2 in an autophagy-independent manner.";
RL Immunity 39:858-873(2013).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, 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 [20]
RP INTERACTION WITH RB1CC1.
RX PubMed=23262492; DOI=10.1038/nsmb.2475;
RA Gammoh N., Florey O., Overholtzer M., Jiang X.;
RT "Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex-
RT dependent and -independent autophagy.";
RL Nat. Struct. Mol. Biol. 20:144-149(2013).
RN [21]
RP INTERACTION WITH ATG5-ATG12 COMPLEX AND PPP1CA, PHOSPHORYLATION AT SER-139,
RP AND MUTAGENESIS OF SER-139; VAL-540 AND PHE-542.
RX PubMed=26083323; DOI=10.1080/15548627.2015.1060386;
RA Song H., Pu J., Wang L., Wu L., Xiao J., Liu Q., Chen J., Zhang M., Liu Y.,
RA Ni M., Mo J., Zheng Y., Wan D., Cai X., Cao Y., Xiao W., Ye L., Tu E.,
RA Lin Z., Wen J., Lu X., He J., Peng Y., Su J., Zhang H., Zhao Y., Lin M.,
RA Zhang Z.;
RT "ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2
RT and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes
RT during hypoxia/reoxygenation.";
RL Autophagy 11:1308-1325(2015).
RN [22]
RP INTERACTION WITH MEFV.
RX PubMed=26347139; DOI=10.1083/jcb.201503023;
RA Kimura T., Jain A., Choi S.W., Mandell M.A., Schroder K., Johansen T.,
RA Deretic V.;
RT "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate
RT immunity.";
RL J. Cell Biol. 210:973-989(2015).
RN [23]
RP INTERACTION WITH WIPI1 AND WIPI2.
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 [24]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATG5-ATG12 COMPLEX,
RP DOMAIN, AND MUTAGENESIS OF PHE-467 AND LYS-490.
RX PubMed=29317426; DOI=10.15252/embj.201797840;
RA Fletcher K., Ulferts R., Jacquin E., Veith T., Gammoh N., Arasteh J.M.,
RA Mayer U., Carding S.R., Wileman T., Beale R., Florey O.;
RT "The WD40 domain of ATG16L1 is required for its non-canonical role in
RT lipidation of LC3 at single membranes.";
RL EMBO J. 37:0-0(2018).
RN [25]
RP INTERACTION WITH TRIM16.
RX PubMed=30143514; DOI=10.15252/embj.201798358;
RA Jena K.K., Kolapalli S.P., Mehto S., Nath P., Das B., Sahoo P.K., Ahad A.,
RA Syed G.H., Raghav S.K., Senapati S., Chauhan S., Chauhan S.;
RT "TRIM16 controls assembly and degradation of protein aggregates by
RT modulating the p62-NRF2 axis and autophagy.";
RL EMBO J. 37:0-0(2018).
RN [26]
RP FUNCTION, INTERACTION WITH ATG5-ATG12 COMPLEX, AND MUTAGENESIS OF
RP 32-PHE--ILE-36; 308-VAL--VAL-310 AND PHE-467.
RX PubMed=30778222; DOI=10.1038/s41556-019-0274-9;
RA Lystad A.H., Carlsson S.R., de la Ballina L.R., Kauffman K.J., Nag S.,
RA Yoshimori T., Melia T.J., Simonsen A.;
RT "Distinct functions of ATG16L1 isoforms in membrane binding and LC3B
RT lipidation in autophagy-related processes.";
RL Nat. Cell Biol. 21:372-383(2019).
RN [27]
RP INTERACTION WITH SPATA33.
RX PubMed=33087875; DOI=10.1038/s41418-020-00638-2;
RA Zhang Y., Xu X., Hu M., Wang X., Cheng H., Zhou R.;
RT "SPATA33 is an autophagy mediator for cargo selectivity in germline
RT mitophagy.";
RL Cell Death Differ. 28:1076-1090(2021).
RN [28]
RP FUNCTION, AND MUTAGENESIS OF LYS-490.
RX PubMed=33909989; DOI=10.1016/j.molcel.2021.03.020;
RA Durgan J., Lystad A.H., Sloan K., Carlsson S.R., Wilson M.I., Marcassa E.,
RA Ulferts R., Webster J., Lopez-Clavijo A.F., Wakelam M.J., Beale R.,
RA Simonsen A., Oxley D., Florey O.;
RT "Non-canonical autophagy drives alternative ATG8 conjugation to
RT phosphatidylserine.";
RL Mol. Cell 81:2031-2040(2021).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 11-43 IN COMPLEX WITH ATG5 AND
RP ATG12, AND INTERACTION WITH ATG5.
RX PubMed=23202584; DOI=10.1038/nsmb.2431;
RA Otomo C., Metlagel Z., Takaesu G., Otomo T.;
RT "Structure of the human ATG12-ATG5 conjugate required for LC3 lipidation in
RT autophagy.";
RL Nat. Struct. Mol. Biol. 20:59-66(2013).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.19 ANGSTROMS) OF 11-43 IN COMPLEX WITH ATG5 AND
RP ATG12, AND INTERACTION WITH ATG5.
RX PubMed=24191030; DOI=10.1073/pnas.1314755110;
RA Metlagel Z., Otomo C., Takaesu G., Otomo T.;
RT "Structural basis of ATG3 recognition by the autophagic ubiquitin-like
RT protein ATG12.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:18844-18849(2013).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-69, SUBUNIT, INTERACTION WITH
RP ATG5, AND MUTAGENESIS OF ILE-17; LEU-21; ARG-24 AND ILE-36.
RX PubMed=25484072; DOI=10.4161/15548627.2014.984276;
RA Kim J.H., Hong S.B., Lee J.K., Han S., Roh K.H., Lee K.E., Kim Y.K.,
RA Choi E.J., Song H.K.;
RT "Insights into autophagosome maturation revealed by the structures of ATG5
RT with its interacting partners.";
RL Autophagy 11:75-87(2015).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 1-69, AND INTERACTION WITH ATG5.
RX PubMed=26812546; DOI=10.7554/elife.12245;
RA Kim M., Sandford E., Gatica D., Qiu Y., Liu X., Zheng Y., Schulman B.A.,
RA Xu J., Semple I., Ro S.H., Kim B., Mavioglu R.N., Tolun A., Jipa A.,
RA Takats S., Karpati M., Li J.Z., Yapici Z., Juhasz G., Lee J.H.,
RA Klionsky D.J., Burmeister M.;
RT "Mutation in ATG5 reduces autophagy and leads to ataxia with developmental
RT delay.";
RL Elife 5:0-0(2016).
RN [33]
RP VARIANT IBD10 ALA-300.
RX PubMed=17484864; DOI=10.1053/j.gastro.2007.03.034;
RA Prescott N.J., Fisher S.A., Franke A., Hampe J., Onnie C.M., Soars D.,
RA Bagnall R., Mirza M.M., Sanderson J., Forbes A., Mansfield J.C.,
RA Lewis C.M., Schreiber S., Mathew C.G.;
RT "A nonsynonymous SNP in ATG16L1 predisposes to ileal Crohn's disease and is
RT independent of CARD15 and IBD5.";
RL Gastroenterology 132:1665-1671(2007).
RN [34]
RP INVOLVEMENT IN SUSCEPTIBILITY TO IBD10, AND VARIANT IBD10 ALA-300.
RX PubMed=17435756; DOI=10.1038/ng2032;
RA Rioux J.D., Xavier R.J., Taylor K.D., Silverberg M.S., Goyette P.,
RA Huett A., Green T., Kuballa P., Barmada M.M., Datta L.W., Shugart Y.Y.,
RA Griffiths A.M., Targan S.R., Ippoliti A.F., Bernard E.-J., Mei L.,
RA Nicolae D.L., Regueiro M., Schumm L.P., Steinhart A.H., Rotter J.I.,
RA Duerr R.H., Cho J.H., Daly M.J., Brant S.R.;
RT "Genome-wide association study identifies new susceptibility loci for Crohn
RT disease and implicates autophagy in disease pathogenesis.";
RL Nat. Genet. 39:596-604(2007).
RN [35]
RP VARIANT IBD10 ALA-300.
RX PubMed=18047540; DOI=10.1111/j.1572-0241.2007.01660.x;
RA Weersma R.K., Zhernakova A., Nolte I.M., Lefebvre C., Rioux J.D.,
RA Mulder F., van Dullemen H.M., Kleibeuker J.H., Wijmenga C., Dijkstra G.;
RT "ATG16L1 and IL23R are associated with inflammatory bowel diseases but not
RT with celiac disease in the Netherlands.";
RL Am. J. Gastroenterol. 103:621-627(2008).
RN [36]
RP VARIANT IBD10 ALA-300.
RX PubMed=18499543; DOI=10.1016/j.dld.2008.03.022;
RG Hungarian IBD Study Group;
RA Lakatos P.L., Szamosi T., Szilvasi A., Molnar E., Lakatos L., Kovacs A.,
RA Molnar T., Altorjay I., Papp M., Tulassay Z., Miheller P., Papp J.,
RA Tordai A., Andrikovics H.;
RT "ATG16L1 and IL23 receptor (IL23R) genes are associated with disease
RT susceptibility in Hungarian CD patients.";
RL Dig. Liver Dis. 40:867-873(2008).
RN [37]
RP VARIANT IBD10 ALA-300.
RX PubMed=19659808; DOI=10.1111/j.1651-2227.2009.01438.x;
RA Lacher M., Schroepf S., Ballauff A., Lohse P., von Schweinitz D.,
RA Kappler R., Koletzko S.;
RT "Autophagy 16-like 1 rs2241880 G allele is associated with Crohn's disease
RT in German children.";
RL Acta Paediatr. 98:1835-1840(2009).
RN [38]
RP VARIANT IBD10 ALA-300.
RX PubMed=18985712; DOI=10.1002/ibd.20785;
RA Amre D.K., Mack D.R., Morgan K., Krupoves A., Costea I., Lambrette P.,
RA Grimard G., Dong J., Feguery H., Bucionis V., Deslandres C., Levy E.,
RA Seidman E.G.;
RT "Autophagy gene ATG16L1 but not IRGM is associated with Crohn's disease in
RT Canadian children.";
RL Inflamm. Bowel Dis. 15:501-507(2009).
RN [39]
RP VARIANT IBD10 ALA-300.
RX PubMed=24656308; DOI=10.1016/j.dld.2014.02.016;
RA Strisciuglio C., Auricchio R., Martinelli M., Staiano A., Giugliano F.P.,
RA Andreozzi M., De Rosa M., Giannetti E., Gianfrani C., Izzo P., Troncone R.,
RA Miele E.;
RT "Autophagy genes variants and paediatric Crohn's disease phenotype: a
RT single-centre experience.";
RL Dig. Liver Dis. 46:512-517(2014).
RN [40]
RP CHARACTERIZATION OF VARIANT IBD10 ALA-300, FUNCTION IN AUTOPHAGY, CLEAVAGE
RP BY CASP3, AND MUTAGENESIS OF ASP-299.
RX PubMed=24553140; DOI=10.1038/nature13044;
RA Murthy A., Li Y., Peng I., Reichelt M., Katakam A.K., Noubade R.,
RA Roose-Girma M., Devoss J., Diehl L., Graham R.R., van Lookeren Campagne M.;
RT "A Crohn's disease variant in Atg16l1 enhances its degradation by caspase
RT 3.";
RL Nature 506:456-462(2014).
RN [41]
RP FUNCTION, INTERACTION WITH WIPI2 AND RB1CC1, DOMAIN, AND MUTAGENESIS OF
RP GLU-226 AND GLU-230.
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 [42]
RP CHARACTERIZATION OF VARIANT IBD10 ALA-300, AND FUNCTION.
RX PubMed=25645662; DOI=10.1136/gutjnl-2014-308735;
RA Grimm W.A., Messer J.S., Murphy S.F., Nero T., Lodolce J.P., Weber C.R.,
RA Logsdon M.F., Bartulis S., Sylvester B.E., Springer A., Dougherty U.,
RA Niewold T.B., Kupfer S.S., Ellis N., Huo D., Bissonnette M., Boone D.L.;
RT "The Thr300Ala variant in ATG16L1 is associated with improved survival in
RT human colorectal cancer and enhanced production of type I interferon.";
RL Gut 65:456-464(2016).
RN [43]
RP CHARACTERIZATION OF VARIANT IBD10 ALA-300, FUNCTION, AND INTERACTION WITH
RP TMEM59.
RX PubMed=27273576; DOI=10.1038/ncomms11821;
RA Boada-Romero E., Serramito-Gomez I., Sacristan M.P., Boone D.L.,
RA Xavier R.J., Pimentel-Muinos F.X.;
RT "The T300A Crohn's disease risk polymorphism impairs function of the WD40
RT domain of ATG16L1.";
RL Nat. Commun. 7:11821-11821(2016).
CC -!- FUNCTION: Plays an essential role in both canonical and non-canonical
CC autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8
CC family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and
CC GABARAP) (PubMed:23376921, PubMed:23392225, PubMed:29317426,
CC PubMed:30778222, PubMed:33909989, PubMed:24553140, PubMed:24954904,
CC PubMed:27273576). Acts as a molecular hub, coordinating autophagy
CC pathways via distinct domains that support either canonical or non-
CC canonical signaling (PubMed:29317426, PubMed:30778222). During
CC canonical autophagy, interacts with ATG12-ATG5 to mediate the
CC conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to
CC produce a membrane-bound activated form of ATG8 (PubMed:23376921,
CC PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576).
CC Thereby, controls the elongation of the nascent autophagosomal membrane
CC (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904,
CC PubMed:27273576). Also involved in non-canonical autophagy, a parallel
CC pathway involving conjugation of ATG8 proteins to single membranes at
CC endolysosomal compartments, probably by catalyzing conjugation of
CC phosphatidylserine (PS) to ATG8 (PubMed:33909989). Non-canonical
CC autophagy plays a key role in epithelial cells to limit lethal
CC infection by influenza A (IAV) virus (By similarity). Regulates
CC mitochondrial antiviral signaling (MAVS)-dependent type I interferon
CC (IFN-I) production (PubMed:22749352, PubMed:25645662). Negatively
CC regulates NOD1- and NOD2-driven inflammatory cytokine response
CC (PubMed:24238340). Instead, promotes with NOD2 an autophagy-dependent
CC antibacterial pathway (PubMed:20637199). Plays a role in regulating
CC morphology and function of Paneth cell (PubMed:18849966).
CC {ECO:0000250|UniProtKB:Q8C0J2, ECO:0000269|PubMed:18849966,
CC ECO:0000269|PubMed:20637199, ECO:0000269|PubMed:22749352,
CC ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:23392225,
CC ECO:0000269|PubMed:24238340, ECO:0000269|PubMed:24553140,
CC ECO:0000269|PubMed:24954904, ECO:0000269|PubMed:25645662,
CC ECO:0000269|PubMed:27273576, ECO:0000269|PubMed:29317426,
CC ECO:0000269|PubMed:30778222, ECO:0000269|PubMed:33909989}.
CC -!- SUBUNIT: Homodimer (PubMed:25484072). Homooligomer (By similarity).
CC Heterooligomer with ATG16L2 (By similarity). Interacts with WIPI1
CC (PubMed:28561066). Interacts with WIPI2 (PubMed:24954904,
CC PubMed:28561066). Interacts with RB1CC1; the interaction is required
CC for ULK1 complex-dependent autophagy (PubMed:23262492, PubMed:24954904,
CC PubMed:23392225). Interacts with ATG5 (PubMed:23202584,
CC PubMed:24191030, PubMed:25484072, PubMed:26812546). Part of either the
CC minor and major complexes respectively composed of 4 sets of ATG12-ATG5
CC and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa)
CC (PubMed:26083323, PubMed:29317426, PubMed:30778222, PubMed:23202584,
CC PubMed:24191030). Interacts with RAB33B (PubMed:21808068). Interacts
CC (via WD repeats) with TMEM59; the interaction mediates unconventional
CC autophagic activity of TMEM59 (PubMed:23376921, PubMed:27273576).
CC Interacts with TLR2 and NOD2 (PubMed:23376921). Interacts (via WD
CC repeats) with MEFV (PubMed:26347139). Interacts with PPP1CA; the
CC interaction dephosphorylates ATG16L1 causing dissociation of ATG12-
CC ATG5-ATG16L1 complex (PubMed:26083323). Interacts (via N-terminal) with
CC CLTC (PubMed:20639872). Interacts with NOD2 (PubMed:20637199).
CC Interacts with TUFM (PubMed:22749352). Interacts with TRIM16
CC (PubMed:30143514). Interacts (via WD repeats) with SPATA33
CC (PubMed:33087875). {ECO:0000250|UniProtKB:Q8C0J2,
CC ECO:0000269|PubMed:20639872, ECO:0000269|PubMed:21808068,
CC ECO:0000269|PubMed:22749352, ECO:0000269|PubMed:23202584,
CC ECO:0000269|PubMed:23262492, ECO:0000269|PubMed:23376921,
CC ECO:0000269|PubMed:23392225, ECO:0000269|PubMed:24191030,
CC ECO:0000269|PubMed:24954904, ECO:0000269|PubMed:25484072,
CC ECO:0000269|PubMed:26083323, ECO:0000269|PubMed:26347139,
CC ECO:0000269|PubMed:26812546, ECO:0000269|PubMed:27273576,
CC ECO:0000269|PubMed:28561066, ECO:0000269|PubMed:29317426,
CC ECO:0000269|PubMed:30143514, ECO:0000269|PubMed:30778222,
CC ECO:0000269|PubMed:33087875}.
CC -!- INTERACTION:
CC Q676U5; Q676U5: ATG16L1; NbExp=2; IntAct=EBI-535909, EBI-535909;
CC Q676U5; Q9H1Y0: ATG5; NbExp=7; IntAct=EBI-535909, EBI-1047414;
CC Q676U5; P60520: GABARAPL2; NbExp=2; IntAct=EBI-535909, EBI-720116;
CC Q676U5; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-535909, EBI-373144;
CC Q676U5; Q9BXW4: MAP1LC3C; NbExp=4; IntAct=EBI-535909, EBI-2603996;
CC Q676U5; Q14088: RAB33A; NbExp=3; IntAct=EBI-535909, EBI-744685;
CC Q676U5; Q9H082: RAB33B; NbExp=3; IntAct=EBI-535909, EBI-3048549;
CC Q676U5; Q8TDY2: RB1CC1; NbExp=6; IntAct=EBI-535909, EBI-1047793;
CC Q676U5; Q9BXS4: TMEM59; NbExp=6; IntAct=EBI-535909, EBI-7054441;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23392225}.
CC Preautophagosomal structure membrane {ECO:0000269|PubMed:20639872,
CC ECO:0000269|PubMed:23392225}; Peripheral membrane protein
CC {ECO:0000305}. Endosome membrane {ECO:0000269|PubMed:29317426};
CC Peripheral membrane protein {ECO:0000305}. Lysosome membrane
CC {ECO:0000269|PubMed:29317426}; Peripheral membrane protein
CC {ECO:0000305}. Note=Recruited to omegasomes membranes by WIPI2 (By
CC similarity). Omegasomes are endoplasmic reticulum connected strutures
CC at the origin of preautophagosomal structures (By similarity).
CC Localized to preautophagosomal structure (PAS) where it is involved in
CC the membrane targeting of ATG5 (By similarity). Localizes also to
CC discrete punctae along the ciliary axoneme (By similarity). Upon
CC activation of non-canonical autophagy, recruited to single-membrane
CC endolysosomal compartments (PubMed:29317426).
CC {ECO:0000250|UniProtKB:Q8C0J2, ECO:0000269|PubMed:29317426}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1; Synonyms=APG16L beta;
CC IsoId=Q676U5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q676U5-2; Sequence=VSP_013386;
CC Name=3;
CC IsoId=Q676U5-3; Sequence=VSP_013387, VSP_013388;
CC Name=4;
CC IsoId=Q676U5-4; Sequence=VSP_013389, VSP_013390;
CC Name=5;
CC IsoId=Q676U5-5; Sequence=VSP_013389, VSP_013386;
CC -!- DOMAIN: The WD repeats are required for non-canonical autophagy but not
CC for canonical autophagy. {ECO:0000269|PubMed:29317426}.
CC -!- PTM: Proteolytic cleavage by activated CASP3 leads to degradation and
CC may regulate autophagy upon cellular stress and apoptotic stimuli.
CC {ECO:0000269|PubMed:24553140}.
CC -!- PTM: Phosphorylation at Ser-139 promotes association with the ATG12-
CC ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex.
CC {ECO:0000269|PubMed:26083323}.
CC -!- DISEASE: Inflammatory bowel disease 10 (IBD10) [MIM:611081]: A chronic,
CC relapsing inflammation of the gastrointestinal tract with a complex
CC etiology. It is subdivided into Crohn disease and ulcerative colitis
CC phenotypes. Crohn disease may affect any part of the gastrointestinal
CC tract from the mouth to the anus, but most frequently it involves the
CC terminal ileum and colon. Bowel inflammation is transmural and
CC discontinuous; it may contain granulomas or be associated with
CC intestinal or perianal fistulas. In contrast, in ulcerative colitis,
CC the inflammation is continuous and limited to rectal and colonic
CC mucosal layers; fistulas and granulomas are not observed. Both diseases
CC include extraintestinal inflammation of the skin, eyes, or joints.
CC {ECO:0000269|PubMed:17200669, ECO:0000269|PubMed:17435756,
CC ECO:0000269|PubMed:17484864, ECO:0000269|PubMed:18047540,
CC ECO:0000269|PubMed:18499543, ECO:0000269|PubMed:18985712,
CC ECO:0000269|PubMed:19659808, ECO:0000269|PubMed:24553140,
CC ECO:0000269|PubMed:24656308, ECO:0000269|PubMed:25645662,
CC ECO:0000269|PubMed:27273576}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
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 WD repeat ATG16 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15448.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=BAB55412.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY398617; AAR32130.1; -; mRNA.
DR EMBL; EF079889; ABN48554.1; -; mRNA.
DR EMBL; EF079890; ABN48555.1; -; mRNA.
DR EMBL; AY358182; AAQ88549.1; -; mRNA.
DR EMBL; AK026330; BAB15448.1; ALT_SEQ; mRNA.
DR EMBL; AK027854; BAB55412.1; ALT_INIT; mRNA.
DR EMBL; AK123876; BAC85713.1; -; mRNA.
DR EMBL; AC013726; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471063; EAW71034.1; -; Genomic_DNA.
DR EMBL; BC071846; AAH71846.1; -; mRNA.
DR EMBL; AL834526; CAD39182.1; -; mRNA.
DR CCDS; CCDS2502.2; -. [Q676U5-2]
DR CCDS; CCDS2503.2; -. [Q676U5-1]
DR CCDS; CCDS54438.1; -. [Q676U5-5]
DR RefSeq; NP_001177195.1; NM_001190266.1.
DR RefSeq; NP_001177196.1; NM_001190267.1.
DR RefSeq; NP_060444.3; NM_017974.3. [Q676U5-2]
DR RefSeq; NP_110430.5; NM_030803.6. [Q676U5-1]
DR RefSeq; NP_942593.2; NM_198890.2. [Q676U5-5]
DR PDB; 4GDK; X-ray; 2.70 A; C/F=11-43.
DR PDB; 4GDL; X-ray; 2.88 A; C=11-43.
DR PDB; 4NAW; X-ray; 2.20 A; C/G/K/O=11-43.
DR PDB; 4TQ0; X-ray; 2.70 A; B/D/F=1-69.
DR PDB; 5D7G; X-ray; 3.00 A; B/D/F/H=1-69.
DR PDB; 5NPV; X-ray; 3.10 A; B/D=11-307.
DR PDB; 5NPW; X-ray; 3.10 A; B/D/F/H=11-307.
DR PDB; 5NUV; X-ray; 1.55 A; A=303-607.
DR PDB; 5ZYX; NMR; -; A=12-31.
DR PDBsum; 4GDK; -.
DR PDBsum; 4GDL; -.
DR PDBsum; 4NAW; -.
DR PDBsum; 4TQ0; -.
DR PDBsum; 5D7G; -.
DR PDBsum; 5NPV; -.
DR PDBsum; 5NPW; -.
DR PDBsum; 5NUV; -.
DR PDBsum; 5ZYX; -.
DR AlphaFoldDB; Q676U5; -.
DR SMR; Q676U5; -.
DR BioGRID; 120375; 751.
DR ComplexPortal; CPX-200; ATG12-ATG5-ATG16L1 complex.
DR CORUM; Q676U5; -.
DR DIP; DIP-27552N; -.
DR DIP; DIP-50290N; -.
DR IntAct; Q676U5; 45.
DR MINT; Q676U5; -.
DR STRING; 9606.ENSP00000375872; -.
DR TCDB; 9.A.15.2.1; the autophagy-related phagophore-formation transporter (apt) family.
DR iPTMnet; Q676U5; -.
DR PhosphoSitePlus; Q676U5; -.
DR SwissPalm; Q676U5; -.
DR BioMuta; ATG16L1; -.
DR DMDM; 62510482; -.
DR EPD; Q676U5; -.
DR jPOST; Q676U5; -.
DR MassIVE; Q676U5; -.
DR MaxQB; Q676U5; -.
DR PaxDb; Q676U5; -.
DR PeptideAtlas; Q676U5; -.
DR PRIDE; Q676U5; -.
DR ProteomicsDB; 65982; -. [Q676U5-1]
DR ProteomicsDB; 65983; -. [Q676U5-2]
DR ProteomicsDB; 65984; -. [Q676U5-3]
DR ProteomicsDB; 65985; -. [Q676U5-4]
DR ProteomicsDB; 65986; -. [Q676U5-5]
DR Antibodypedia; 1969; 878 antibodies from 43 providers.
DR DNASU; 55054; -.
DR Ensembl; ENST00000347464.9; ENSP00000318259.6; ENSG00000085978.22. [Q676U5-5]
DR Ensembl; ENST00000373525.9; ENSP00000362625.5; ENSG00000085978.22. [Q676U5-4]
DR Ensembl; ENST00000392017.9; ENSP00000375872.4; ENSG00000085978.22. [Q676U5-1]
DR Ensembl; ENST00000392020.8; ENSP00000375875.4; ENSG00000085978.22. [Q676U5-2]
DR Ensembl; ENST00000625501.3; ENSP00000487542.1; ENSG00000281089.3. [Q676U5-1]
DR Ensembl; ENST00000626623.2; ENSP00000487298.1; ENSG00000281089.3. [Q676U5-5]
DR Ensembl; ENST00000630066.2; ENSP00000487446.1; ENSG00000281089.3. [Q676U5-2]
DR Ensembl; ENST00000630204.2; ENSP00000487455.1; ENSG00000281089.3. [Q676U5-4]
DR GeneID; 55054; -.
DR KEGG; hsa:55054; -.
DR MANE-Select; ENST00000392017.9; ENSP00000375872.4; NM_030803.7; NP_110430.5.
DR UCSC; uc002vtx.3; human. [Q676U5-1]
DR CTD; 55054; -.
DR DisGeNET; 55054; -.
DR GeneCards; ATG16L1; -.
DR HGNC; HGNC:21498; ATG16L1.
DR HPA; ENSG00000085978; Low tissue specificity.
DR MalaCards; ATG16L1; -.
DR MIM; 610767; gene.
DR MIM; 611081; phenotype.
DR neXtProt; NX_Q676U5; -.
DR OpenTargets; ENSG00000085978; -.
DR Orphanet; 206; NON RARE IN EUROPE: Crohn disease.
DR PharmGKB; PA134902949; -.
DR VEuPathDB; HostDB:ENSG00000085978; -.
DR eggNOG; KOG0288; Eukaryota.
DR GeneTree; ENSGT00940000153936; -.
DR HOGENOM; CLU_000288_57_10_1; -.
DR InParanoid; Q676U5; -.
DR OMA; LFVWEVN; -.
DR PhylomeDB; Q676U5; -.
DR TreeFam; TF315541; -.
DR PathwayCommons; Q676U5; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR SignaLink; Q676U5; -.
DR SIGNOR; Q676U5; -.
DR BioGRID-ORCS; 55054; 18 hits in 1087 CRISPR screens.
DR ChiTaRS; ATG16L1; human.
DR GeneWiki; ATG16L1; -.
DR GenomeRNAi; 55054; -.
DR Pharos; Q676U5; Tbio.
DR PRO; PR:Q676U5; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q676U5; protein.
DR Bgee; ENSG00000085978; Expressed in right hemisphere of cerebellum and 147 other tissues.
DR ExpressionAtlas; Q676U5; baseline and differential.
DR Genevisible; Q676U5; HS.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; IDA:UniProtKB.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; IDA:UniProtKB.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0036020; C:endolysosome membrane; IDA:UniProtKB.
DR GO; GO:0034045; C:phagophore assembly site membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISS:UniProtKB.
DR GO; GO:0120095; C:vacuole-isolation membrane contact site; IDA:UniProtKB.
DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019787; F:ubiquitin-like protein transferase activity; TAS:Reactome.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0006501; P:C-terminal protein lipidation; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0016237; P:lysosomal microautophagy; IDA:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IDA:UniProtKB.
DR GO; GO:0039689; P:negative stranded viral RNA replication; IBA:GO_Central.
DR GO; GO:0010508; P:positive regulation of autophagy; IEA:Ensembl.
DR GO; GO:0006497; P:protein lipidation; IDA:ComplexPortal.
DR GO; GO:0061739; P:protein lipidation involved in autophagosome assembly; IEA:Ensembl.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IEA:Ensembl.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0098792; P:xenophagy; IEA:Ensembl.
DR DisProt; DP02148; -.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR045160; ATG16.
DR InterPro; IPR013923; Autophagy-rel_prot_16_dom.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR19878; PTHR19878; 1.
DR Pfam; PF08614; ATG16; 1.
DR Pfam; PF00400; WD40; 5.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 3.
DR PROSITE; PS50082; WD_REPEATS_2; 6.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Coiled coil; Cytoplasm;
KW Endosome; Lysosome; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport; WD repeat.
FT CHAIN 1..607
FT /note="Autophagy-related protein 16-1"
FT /id="PRO_0000050848"
FT REPEAT 320..359
FT /note="WD 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 364..403
FT /note="WD 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 406..445
FT /note="WD 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 447..484
FT /note="WD 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 486..525
FT /note="WD 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 532..573
FT /note="WD 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REPEAT 575..607
FT /note="WD 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00221"
FT REGION 13..43
FT /note="Interaction with ATG5"
FT /evidence="ECO:0000269|PubMed:25484072"
FT REGION 207..230
FT /note="WIPI2-binding"
FT /evidence="ECO:0000269|PubMed:24954904"
FT REGION 230..242
FT /note="RB1CC1-binding"
FT /evidence="ECO:0000269|PubMed:23392225,
FT ECO:0000269|PubMed:24954904"
FT COILED 78..230
FT /evidence="ECO:0000255"
FT MOTIF 296..299
FT /note="Caspase cleavage"
FT /evidence="ECO:0000269|PubMed:24553140"
FT MOD_RES 139
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:26083323"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 287
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 70..213
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17200669"
FT /id="VSP_013389"
FT VAR_SEQ 266..284
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17200669"
FT /id="VSP_013386"
FT VAR_SEQ 334..368
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_013390"
FT VAR_SEQ 443..470
FT /note="IKTVFAGSSCNDIVCTEQCVMSGHFDKK -> EEIQSLCLCICLDVSVEVCV
FT CTSEPAFM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013387"
FT VAR_SEQ 471..607
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_013388"
FT VARIANT 300
FT /note="T -> A (in IBD10; has no effect on the stability of
FT the protein under normal conditions; enhances the cleavage
FT and the degradation mediated by activated CASP3; results in
FT reduced autophagy and defective clearance of intestinal
FT pathogens; impairs interaction with TMEM59; slows TMEM59
FT intracellular trafficking; increases production of type I
FT IFNs; dbSNP:rs2241880)"
FT /evidence="ECO:0000269|PubMed:15620219,
FT ECO:0000269|PubMed:17200669, ECO:0000269|PubMed:17484864,
FT ECO:0000269|PubMed:18047540, ECO:0000269|PubMed:18499543,
FT ECO:0000269|PubMed:18985712, ECO:0000269|PubMed:19659808,
FT ECO:0000269|PubMed:24553140, ECO:0000269|PubMed:24656308,
FT ECO:0000269|PubMed:25645662, ECO:0000269|PubMed:27273576"
FT /id="VAR_021834"
FT VARIANT 307
FT /note="E -> K (in dbSNP:rs1866878)"
FT /id="VAR_053386"
FT MUTAGEN 17
FT /note="I->W: Abolishes interaction with ATG5."
FT /evidence="ECO:0000269|PubMed:25484072"
FT MUTAGEN 21
FT /note="L->W: Abolishes interaction with ATG5."
FT /evidence="ECO:0000269|PubMed:25484072"
FT MUTAGEN 24
FT /note="R->D: Abolishes interaction with ATG5."
FT /evidence="ECO:0000269|PubMed:25484072"
FT MUTAGEN 32..36
FT /note="FEEII->AEEAA: In FII mutant; abolished binding to
FT membranes and lipidation to ATG8 family proteins."
FT /evidence="ECO:0000269|PubMed:30778222"
FT MUTAGEN 36
FT /note="I->W: Reduces interaction with ATG5."
FT /evidence="ECO:0000269|PubMed:25484072"
FT MUTAGEN 139
FT /note="S->A: Abolishes phosphorylation. Impairs interaction
FT with ATG12-ATG5 complex."
FT /evidence="ECO:0000269|PubMed:26083323"
FT MUTAGEN 226
FT /note="E->R: Impairs interaction with WIPI2."
FT /evidence="ECO:0000269|PubMed:24954904"
FT MUTAGEN 230
FT /note="E->R: Impairs interaction with WIPI2."
FT /evidence="ECO:0000269|PubMed:24954904"
FT MUTAGEN 299
FT /note="D->E: Prevents cleavage by activated CASP3."
FT /evidence="ECO:0000269|PubMed:24553140"
FT MUTAGEN 308..310
FT /note="VRV->AAA: In VRV mutant; abolished binding to
FT membranes and lipidation to ATG8 family proteins."
FT /evidence="ECO:0000269|PubMed:30778222"
FT MUTAGEN 467
FT /note="F->A: Abolished non-canonical autophagy without
FT affecting canonical autophagy."
FT /evidence="ECO:0000269|PubMed:29317426,
FT ECO:0000269|PubMed:30778222"
FT MUTAGEN 490
FT /note="K->A: Abolished non-canonical autophagy without
FT affecting canonical autophagy. Impaired conjugation of
FT phosphatidylserine (PS) to LC3 proteins."
FT /evidence="ECO:0000269|PubMed:29317426,
FT ECO:0000269|PubMed:33909989"
FT MUTAGEN 540
FT /note="V->A: Impairs interaction with PPP1CA; when
FT associated with A-542."
FT /evidence="ECO:0000269|PubMed:26083323"
FT MUTAGEN 542
FT /note="F->A: Impairs interaction with PPP1CA; when
FT associated with A-540."
FT /evidence="ECO:0000269|PubMed:26083323"
FT CONFLICT 151
FT /note="K -> R (in Ref. 6; BAB55412)"
FT /evidence="ECO:0000305"
FT CONFLICT 328
FT /note="V -> A (in Ref. 6; BAB55412)"
FT /evidence="ECO:0000305"
FT CONFLICT 529
FT /note="P -> T (in Ref. 6; BAB55412)"
FT /evidence="ECO:0000305"
FT HELIX 12..28
FT /evidence="ECO:0007829|PDB:4NAW"
FT HELIX 30..42
FT /evidence="ECO:0007829|PDB:4NAW"
FT STRAND 313..319
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 325..330
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 334..341
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 346..351
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 356..362
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 369..374
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 378..385
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 390..394
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 395..398
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 399..404
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 411..416
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 422..427
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 430..436
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 437..440
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 441..447
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 459..466
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 469..475
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 476..479
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 480..486
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 502..507
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 508..510
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 511..516
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 517..520
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 521..526
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 546..552
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 558..562
FT /evidence="ECO:0007829|PDB:5NUV"
FT TURN 563..565
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 568..572
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 580..585
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 592..596
FT /evidence="ECO:0007829|PDB:5NUV"
FT STRAND 599..605
FT /evidence="ECO:0007829|PDB:5NUV"
SQ SEQUENCE 607 AA; 68265 MW; 5A5816AE2CF03CA0 CRC64;
MSSGLRAADF PRWKRHISEQ LRRRDRLQRQ AFEEIILQYN KLLEKSDLHS VLAQKLQAEK
HDVPNRHEIS PGHDGTWNDN QLQEMAQLRI KHQEELTELH KKRGELAQLV IDLNNQMQRK
DREMQMNEAK IAECLQTISD LETECLDLRT KLCDLERANQ TLKDEYDALQ ITFTALEGKL
RKTTEENQEL VTRWMAEKAQ EANRLNAENE KDSRRRQARL QKELAEAAKE PLPVEQDDDI
EVIVDETSDH TEETSPVRAI SRAATKRLSQ PAGGLLDSIT NIFGRRSVSS FPVPQDNVDT
HPGSGKEVRV PATALCVFDA HDGEVNAVQF SPGSRLLATG GMDRRVKLWE VFGEKCEFKG
SLSGSNAGIT SIEFDSAGSY LLAASNDFAS RIWTVDDYRL RHTLTGHSGK VLSAKFLLDN
ARIVSGSHDR TLKLWDLRSK VCIKTVFAGS SCNDIVCTEQ CVMSGHFDKK IRFWDIRSES
IVREMELLGK ITALDLNPER TELLSCSRDD LLKVIDLRTN AIKQTFSAPG FKCGSDWTRV
VFSPDGSYVA AGSAEGSLYI WSVLTGKVEK VLSKQHSSSI NAVAWSPSGS HVVSVDKGCK
AVLWAQY
