MLP3A_HUMAN
ID MLP3A_HUMAN Reviewed; 121 AA.
AC Q9H492; E1P5P4; E1P5P5; Q9BXW5;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Microtubule-associated proteins 1A/1B light chain 3A;
DE AltName: Full=Autophagy-related protein LC3 A;
DE AltName: Full=Autophagy-related ubiquitin-like modifier LC3 A;
DE AltName: Full=MAP1 light chain 3-like protein 1;
DE AltName: Full=MAP1A/MAP1B light chain 3 A;
DE Short=MAP1A/MAP1B LC3 A;
DE AltName: Full=Microtubule-associated protein 1 light chain 3 alpha;
DE Flags: Precursor;
GN Name=MAP1LC3A;
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), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF GLY-120.
RX PubMed=12740394; DOI=10.1074/jbc.m303800200;
RA He H., Dang Y., Dai F., Guo Z., Wu J., She X., Pei Y., Chen Y., Ling W.,
RA Wu C., Zhao S., Liu J.O., Yu L.;
RT "Post-translational modifications of three members of the human MAP1LC3
RT family and detection of a novel type of modification for MAP1LC3B.";
RL J. Biol. Chem. 278:29278-29287(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Amygdala;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
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 [7]
RP INTERACTION WITH ATG7.
RX PubMed=11096062; DOI=10.1074/jbc.c000752200;
RA Tanida I., Tanida-Miyake E., Ueno T., Kominami E.;
RT "The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-
RT activating enzyme for multiple substrates including human Apg12p, GATE-16,
RT GABARAP, and MAP-LC3.";
RL J. Biol. Chem. 276:1701-1706(2001).
RN [8]
RP INTERACTION WITH ATG3.
RX PubMed=11825910; DOI=10.1074/jbc.m200385200;
RA Tanida I., Tanida-Miyake E., Komatsu M., Ueno T., Kominami E.;
RT "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple
RT substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation
RT of hApg12p to hApg5p.";
RL J. Biol. Chem. 277:13739-13744(2002).
RN [9]
RP LIPIDATION AT GLY-120, AND CLEAVAGE BY APG4B.
RX PubMed=15187094; DOI=10.1074/jbc.m401461200;
RA Tanida I., Sou Y.-S., Ezaki J., Minematsu-Ikeguchi N., Ueno T.,
RA Kominami E.;
RT "HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human
RT Atg8 homologues and delipidates microtubule-associated protein light chain
RT 3- and GABAA receptor-associated protein-phospholipid conjugates.";
RL J. Biol. Chem. 279:36268-36276(2004).
RN [10]
RP INTERACTION WITH SQSTM1, AND SUBCELLULAR LOCATION.
RX PubMed=17580304; DOI=10.1074/jbc.m702824200;
RA Pankiv S., Clausen T.H., Lamark T., Brech A., Bruun J.A., Outzen H.,
RA Overvatn A., Bjorkoy G., Johansen T.;
RT "p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of
RT ubiquitinated protein aggregates by autophagy.";
RL J. Biol. Chem. 282:24131-24145(2007).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TP53INP2.
RX PubMed=19056683; DOI=10.1091/mbc.e08-07-0671;
RA Nowak J., Archange C., Tardivel-Lacombe J., Pontarotti P., Pebusque M.J.,
RA Vaccaro M.I., Velasco G., Dagorn J.C., Iovanna J.L.;
RT "The TP53INP2 protein is required for autophagy in mammalian cells.";
RL Mol. Biol. Cell 20:870-881(2009).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH UBQLN1 AND UBQLN2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20529957; DOI=10.1093/hmg/ddq231;
RA Rothenberg C., Srinivasan D., Mah L., Kaushik S., Peterhoff C.M.,
RA Ugolino J., Fang S., Cuervo A.M., Nixon R.A., Monteiro M.J.;
RT "Ubiquilin functions in autophagy and is degraded by chaperone-mediated
RT autophagy.";
RL Hum. Mol. Genet. 19:3219-3232(2010).
RN [13]
RP PHOSPHORYLATION AT SER-12 BY PKA, AND FUNCTION.
RX PubMed=20713600; DOI=10.1083/jcb.201002108;
RA Cherra S.J. III, Kulich S.M., Uechi G., Balasubramani M., Mountzouris J.,
RA Day B.W., Chu C.T.;
RT "Regulation of the autophagy protein LC3 by phosphorylation.";
RL J. Cell Biol. 190:533-539(2010).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=22421968; DOI=10.1038/cdd.2012.30;
RA Seillier M., Peuget S., Gayet O., Gauthier C., N'guessan P., Monte M.,
RA Carrier A., Iovanna J.L., Dusetti N.J.;
RT "TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins
RT through the LC3-interacting region (LIR) and promotes autophagy-dependent
RT cell death.";
RL Cell Death Differ. 19:1525-1535(2012).
RN [15]
RP INTERACTION WITH ATG13 AND ULK1.
RX PubMed=23043107; DOI=10.1074/jbc.m112.378109;
RA Alemu E.A., Lamark T., Torgersen K.M., Birgisdottir A.B., Larsen K.B.,
RA Jain A., Olsvik H., Overvatn A., Kirkin V., Johansen T.;
RT "ATG8 family proteins act as scaffolds for assembly of the ULK complex:
RT sequence requirements for LC3-interacting region (LIR) motifs.";
RL J. Biol. Chem. 287:39275-39290(2012).
RN [16]
RP INTERACTION WITH TBC1D5.
RX PubMed=22354992; DOI=10.1128/mcb.06717-11;
RA Popovic D., Akutsu M., Novak I., Harper J.W., Behrends C., Dikic I.;
RT "Rab GTPase-activating proteins in autophagy: regulation of endocytic and
RT autophagy pathways by direct binding to human ATG8 modifiers.";
RL Mol. Cell. Biol. 32:1733-1744(2012).
RN [17]
RP INTERACTION WITH TP53INP1 AND TP53INP2.
RX PubMed=22470510; DOI=10.1371/journal.pone.0034034;
RA Sancho A., Duran J., Garcia-Espana A., Mauvezin C., Alemu E.A., Lamark T.,
RA Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U., Palacin M.,
RA Johansen T., Zorzano A.;
RT "DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding dual
RT regulators of autophagy and transcription.";
RL PLoS ONE 7:E34034-E34034(2012).
RN [18]
RP DECONJUGATION BY LEGIONELLA RAVZ (MICROBIAL INFECTION).
RX PubMed=23112293; DOI=10.1126/science.1227026;
RA Choy A., Dancourt J., Mugo B., O'Connor T.J., Isberg R.R., Melia T.J.,
RA Roy C.R.;
RT "The Legionella effector RavZ inhibits host autophagy through irreversible
RT Atg8 deconjugation.";
RL Science 338:1072-1076(2012).
RN [19]
RP INTERACTION WITH UBQLN1 AND UBQLN4, AND SUBCELLULAR LOCATION.
RX PubMed=23459205; DOI=10.1038/embor.2013.22;
RA Lee D.Y., Arnott D., Brown E.J.;
RT "Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy
RT machinery.";
RL EMBO Rep. 14:373-381(2013).
RN [20]
RP INTERACTION WITH PICALM.
RX PubMed=24067654; DOI=10.1073/pnas.1315110110;
RA Tian Y., Chang J.C., Fan E.Y., Flajolet M., Greengard P.;
RT "Adaptor complex AP2/PICALM, through interaction with LC3, targets
RT Alzheimer's APP-CTF for terminal degradation via autophagy.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:17071-17076(2013).
RN [21]
RP INTERACTION WITH TRIM5.
RX PubMed=25127057; DOI=10.1016/j.devcel.2014.06.013;
RA Mandell M.A., Jain A., Arko-Mensah J., Chauhan S., Kimura T., Dinkins C.,
RA Silvestri G., Munch J., Kirchhoff F., Simonsen A., Wei Y., Levine B.,
RA Johansen T., Deretic V.;
RT "TRIM proteins regulate autophagy and can target autophagic substrates by
RT direct recognition.";
RL Dev. Cell 30:394-409(2014).
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 PROTEOLYTIC CLEAVAGE.
RX PubMed=30661429; DOI=10.1080/15548627.2019.1569925;
RA Agrotis A., Pengo N., Burden J.J., Ketteler R.;
RT "Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP
RT processing revealed in cells.";
RL Autophagy 15:976-997(2019).
RN [24]
RP INTERACTION WITH TEX264; FUNCTION.
RX PubMed=31006538; DOI=10.1016/j.molcel.2019.03.033;
RA Chino H., Hatta T., Natsume T., Mizushima N.;
RT "Intrinsically disordered protein TEX264 mediates ER-phagy.";
RL Mol. Cell 0:0-0(2019).
RN [25]
RP INTERACTION WITH TEX264; FUNCTION.
RX PubMed=31006537; DOI=10.1016/j.molcel.2019.03.034;
RA An H., Ordureau A., Paulo J.A., Shoemaker C.J., Denic V., Harper J.W.;
RT "TEX264 is an endoplasmic reticulum-resident ATG8-interacting protein
RT critical for ER remodeling during nutrient stress.";
RL Mol. Cell 0:0-0(2019).
RN [26]
RP DECONJUGATION BY ATG4B, DECONJUGATION BY LEGIONELLA RAVZ (MICROBIAL
RP INFECTION), AND MUTAGENESIS OF 116-GLN--PHE-119; 116-GLN--THR-118;
RP 116-GLN-GLU-117; GLN-116; GLU-117; THR-118; PHE-119 AND GLY-120.
RX PubMed=32686895; DOI=10.1002/cbic.202000359;
RA Yang A., Pantoom S., Wu Y.W.;
RT "Distinct mechanisms for processing autophagy protein LC3-PE by RavZ and
RT ATG4B.";
RL ChemBioChem 21:3377-3382(2020).
RN [27]
RP DECONJUGATION BY LEGIONELLA RAVZ (MICROBIAL INFECTION).
RX PubMed=31722778; DOI=10.5483/bmbrep.2019.52.12.211;
RA Park S.W., Jun Y.W., Jeon P., Lee Y.K., Park J.H., Lee S.H., Lee J.A.,
RA Jang D.J.;
RT "LIR motifs and the membrane-targeting domain are complementary in the
RT function of RavZ.";
RL BMB Rep. 52:700-705(2019).
RN [28]
RP INTERACTION WITH MOAP1.
RX PubMed=33783314; DOI=10.1080/15548627.2021.1896157;
RA Chang H.C., Tao R.N., Tan C.T., Wu Y.J., Bay B.H., Yu V.C.;
RT "The BAX-binding protein MOAP1 associates with LC3 and promotes closure of
RT the phagophore.";
RL Autophagy 17:3725-3739(2021).
RN [29]
RP LIPIDATION AT GLY-120.
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 [30] {ECO:0007744|PDB:3WAL, ECO:0007744|PDB:3WAN}
RP X-RAY CRYSTALLOGRAPHY (1.77 ANGSTROMS) OF 2-121, INTERACTION WITH ATG13,
RP MUTAGENESIS OF LYS-49; LYS-51 AND LEU-53, AND FUNCTION.
RX PubMed=24290141; DOI=10.1016/j.str.2013.09.023;
RA Suzuki H., Tabata K., Morita E., Kawasaki M., Kato R., Dobson R.C.,
RA Yoshimori T., Wakatsuki S.;
RT "Structural basis of the autophagy-related LC3/Atg13 LIR complex:
RT recognition and interaction mechanism.";
RL Structure 22:47-58(2014).
RN [31] {ECO:0007744|PDB:4ZDV}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-120, AND INTERACTION WITH
RP RETREG1; RETREG2 AND RETREG3.
RX PubMed=26040720; DOI=10.1038/nature14498;
RA Khaminets A., Heinrich T., Mari M., Grumati P., Huebner A.K., Akutsu M.,
RA Liebmann L., Stolz A., Nietzsche S., Koch N., Mauthe M., Katona I.,
RA Qualmann B., Weis J., Reggiori F., Kurth I., Huebner C.A., Dikic I.;
RT "Regulation of endoplasmic reticulum turnover by selective autophagy.";
RL Nature 522:354-358(2015).
CC -!- FUNCTION: Ubiquitin-like modifier involved in formation of
CC autophagosomal vacuoles (autophagosomes) (PubMed:20713600,
CC PubMed:24290141). While LC3s are involved in elongation of the
CC phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a
CC later stage in autophagosome maturation (PubMed:20713600). Through its
CC interaction with the reticulophagy receptor TEX264, participates in the
CC remodeling of subdomains of the endoplasmic reticulum into
CC autophagosomes upon nutrient stress, which then fuse with lysosomes for
CC endoplasmic reticulum turnover (PubMed:31006538, PubMed:31006537).
CC {ECO:0000269|PubMed:20713600, ECO:0000269|PubMed:24290141,
CC ECO:0000269|PubMed:31006537, ECO:0000269|PubMed:31006538}.
CC -!- SUBUNIT: 3 different light chains, LC1, LC2 and LC3, can associate with
CC MAP1A and MAP1B proteins (By similarity). Interacts with TP53INP1 and
CC TP53INP2 (PubMed:19056683, PubMed:22470510). Directly interacts with
CC SQSTM1; this interaction leads to MAP1LC3A recruitment to inclusion
CC bodies containing polyubiquitinated protein aggregates and to inclusion
CC body degradation by autophagy (PubMed:17580304). Interacts with ATG13
CC (PubMed:24290141, PubMed:23043107). Interacts with ULK1
CC (PubMed:23043107). Interacts with TBC1D5 (PubMed:22354992). Found in a
CC complex with UBQLN1 and UBQLN2 (PubMed:20529957). Interacts with UBQLN4
CC (via STI1 1 and 2 domains). Interacts with UBQLN1 in the presence of
CC UBQLN4 (PubMed:23459205). Interacts with TRIM5 (PubMed:25127057).
CC Interacts with MEFV (PubMed:26347139). Interacts with RETREG1, RETREG2
CC and RETREG3 (PubMed:26040720). Interacts with PICALM. Interacts with
CC the reticulophagy receptor TEX264 (PubMed:31006538, PubMed:31006537).
CC Interacts with MOAP1 (via LIR motif) (PubMed:33783314).
CC {ECO:0000250|UniProtKB:Q62625, ECO:0000269|PubMed:11096062,
CC ECO:0000269|PubMed:11825910, ECO:0000269|PubMed:17580304,
CC ECO:0000269|PubMed:19056683, ECO:0000269|PubMed:20529957,
CC ECO:0000269|PubMed:22354992, ECO:0000269|PubMed:22470510,
CC ECO:0000269|PubMed:23043107, ECO:0000269|PubMed:23459205,
CC ECO:0000269|PubMed:24067654, ECO:0000269|PubMed:24290141,
CC ECO:0000269|PubMed:25127057, ECO:0000269|PubMed:26040720,
CC ECO:0000269|PubMed:26347139, ECO:0000269|PubMed:31006537,
CC ECO:0000269|PubMed:31006538, ECO:0000269|PubMed:33783314}.
CC -!- INTERACTION:
CC Q9H492; Q12802: AKAP13; NbExp=2; IntAct=EBI-720768, EBI-1373806;
CC Q9H492; Q9Y4P1: ATG4B; NbExp=6; IntAct=EBI-720768, EBI-712014;
CC Q9H492; O60238: BNIP3L; NbExp=2; IntAct=EBI-720768, EBI-849893;
CC Q9H492; Q9HAW4: CLSPN; NbExp=2; IntAct=EBI-720768, EBI-1369377;
CC Q9H492; Q8IVP5: FUNDC1; NbExp=4; IntAct=EBI-720768, EBI-3059266;
CC Q9H492; Q8WZA9: IRGQ; NbExp=3; IntAct=EBI-720768, EBI-1055331;
CC Q9H492; O14654: IRS4; NbExp=2; IntAct=EBI-720768, EBI-356594;
CC Q9H492; Q9BQD3: KXD1; NbExp=6; IntAct=EBI-720768, EBI-739657;
CC Q9H492; P78559: MAP1A; NbExp=6; IntAct=EBI-720768, EBI-929047;
CC Q9H492; Q66K74: MAP1S; NbExp=3; IntAct=EBI-720768, EBI-2133734;
CC Q9H492; Q14596: NBR1; NbExp=5; IntAct=EBI-720768, EBI-742698;
CC Q9H492; Q96PU5: NEDD4L; NbExp=2; IntAct=EBI-720768, EBI-717962;
CC Q9H492; Q8TD19: NEK9; NbExp=2; IntAct=EBI-720768, EBI-1044009;
CC Q9H492; P35372-10: OPRM1; NbExp=3; IntAct=EBI-720768, EBI-12807478;
CC Q9H492; P29350: PTPN6; NbExp=2; IntAct=EBI-720768, EBI-78260;
CC Q9H492; Q86VR2: RETREG3; NbExp=9; IntAct=EBI-720768, EBI-10192441;
CC Q9H492; Q13501: SQSTM1; NbExp=12; IntAct=EBI-720768, EBI-307104;
CC Q9H492; Q7Z6L1: TECPR1; NbExp=2; IntAct=EBI-720768, EBI-2946676;
CC Q9H492; Q15025: TNIP1; NbExp=7; IntAct=EBI-720768, EBI-357849;
CC Q9H492; Q9H0E2: TOLLIP; NbExp=3; IntAct=EBI-720768, EBI-74615;
CC Q9H492; Q8WZ42: TTN; NbExp=3; IntAct=EBI-720768, EBI-681210;
CC Q9H492; Q9NRR5: UBQLN4; NbExp=3; IntAct=EBI-720768, EBI-711226;
CC Q9H492; Q9Y2B5: VPS9D1; NbExp=6; IntAct=EBI-720768, EBI-9031083;
CC Q9H492; Q9Z2F7: Bnip3l; Xeno; NbExp=7; IntAct=EBI-720768, EBI-1774669;
CC Q9H492-1; O75143: ATG13; NbExp=7; IntAct=EBI-16082793, EBI-2798775;
CC Q9H492-1; Q9H6L5-1: RETREG1; NbExp=2; IntAct=EBI-16082793, EBI-16159046;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:12740394, ECO:0000269|PubMed:15187094,
CC ECO:0000269|PubMed:19056683, ECO:0000269|PubMed:20529957,
CC ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:23459205}; Lipid-anchor
CC {ECO:0000269|PubMed:15187094}. Endomembrane system
CC {ECO:0000269|PubMed:12740394}; Lipid-anchor
CC {ECO:0000269|PubMed:15187094}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q91VR7}. Note=LC3-II binds to the autophagic
CC membranes. {ECO:0000269|PubMed:15187094}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H492-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H492-2; Sequence=VSP_013660;
CC -!- TISSUE SPECIFICITY: Most abundant in heart, brain, liver, skeletal
CC muscle and testis but absent in thymus and peripheral blood leukocytes.
CC {ECO:0000269|PubMed:12740394}.
CC -!- PTM: The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or
CC ATG4D) to expose the glycine at the C-terminus and form the cytosolic
CC form, LC3-I (PubMed:15187094, PubMed:30661429). The processed form is
CC then activated by APG7L/ATG7, transferred to ATG3 and conjugated to
CC phosphatidylethanolamine (PE) phospholipid to form the membrane-bound
CC form, LC3-II (PubMed:15187094). During non-canonical autophagy, the
CC processed form is conjugated to phosphatidylserine (PS) phospholipid
CC (PubMed:33909989). ATG4 proteins also mediate the delipidation of PE-
CC conjugated forms (PubMed:32686895, PubMed:33909989). In addition, ATG4B
CC and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during
CC non-canonical autophagy (PubMed:33909989). ATG4B constitutes the major
CC protein for proteolytic activation (PubMed:30661429, PubMed:33909989).
CC ATG4D is the main enzyme for delipidation activity (By similarity).
CC {ECO:0000250|UniProtKB:Q91VR7, ECO:0000269|PubMed:15187094,
CC ECO:0000269|PubMed:30661429, ECO:0000269|PubMed:32686895,
CC ECO:0000269|PubMed:33909989}.
CC -!- PTM: (Microbial infection) The Legionella effector RavZ is a
CC deconjugating enzyme that hydrolyzes the amide bond between the C-
CC terminal glycine residue and an adjacent aromatic residue in ATG8
CC proteins conjugated to phosphatidylethanolamine (PE), producing an ATG8
CC protein that is resistant to reconjugation by the host machinery due to
CC the cleavage of the reactive C-terminal glycine (PubMed:23112293,
CC PubMed:32686895, PubMed:31722778). RavZ is also able to mediate
CC delipidation of ATG8 proteins conjugated to phosphatidylserine (PS)
CC (PubMed:33909989). {ECO:0000269|PubMed:23112293,
CC ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:32686895,
CC ECO:0000269|PubMed:33909989}.
CC -!- PTM: Phosphorylation at Ser-12 by PKA inhibits conjugation to
CC phosphatidylethanolamine (PE). {ECO:0000269|PubMed:20713600}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AF276658; AAK35151.1; -; mRNA.
DR EMBL; BT007452; AAP36120.1; -; mRNA.
DR EMBL; AL833855; CAD38714.1; -; mRNA.
DR EMBL; AL118520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76263.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76264.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76265.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76266.1; -; Genomic_DNA.
DR EMBL; BC015810; AAH15810.1; -; mRNA.
DR CCDS; CCDS13237.1; -. [Q9H492-2]
DR CCDS; CCDS13238.1; -. [Q9H492-1]
DR RefSeq; NP_115903.1; NM_032514.3. [Q9H492-1]
DR RefSeq; NP_852610.1; NM_181509.2. [Q9H492-2]
DR PDB; 3ECI; X-ray; 2.65 A; A/B=1-121.
DR PDB; 3WAL; X-ray; 2.00 A; A=2-121.
DR PDB; 3WAN; X-ray; 1.77 A; A/B=2-121.
DR PDB; 4ZDV; X-ray; 1.80 A; A=2-120.
DR PDB; 5CX3; X-ray; 2.30 A; A/B/C/D=1-121.
DR PDB; 5DPR; X-ray; 2.50 A; A/B/C/D=2-121.
DR PDB; 6TBE; X-ray; 1.67 A; A=4-119.
DR PDB; 7R9W; X-ray; 1.75 A; A=1-120.
DR PDB; 7R9Z; X-ray; 1.72 A; A=1-120.
DR PDB; 7RA0; X-ray; 1.36 A; A=1-120.
DR PDBsum; 3ECI; -.
DR PDBsum; 3WAL; -.
DR PDBsum; 3WAN; -.
DR PDBsum; 4ZDV; -.
DR PDBsum; 5CX3; -.
DR PDBsum; 5DPR; -.
DR PDBsum; 6TBE; -.
DR PDBsum; 7R9W; -.
DR PDBsum; 7R9Z; -.
DR PDBsum; 7RA0; -.
DR AlphaFoldDB; Q9H492; -.
DR SMR; Q9H492; -.
DR BioGRID; 124137; 188.
DR CORUM; Q9H492; -.
DR DIP; DIP-49052N; -.
DR ELM; Q9H492; -.
DR IntAct; Q9H492; 562.
DR MINT; Q9H492; -.
DR STRING; 9606.ENSP00000363970; -.
DR iPTMnet; Q9H492; -.
DR PhosphoSitePlus; Q9H492; -.
DR BioMuta; MAP1LC3A; -.
DR DMDM; 85701362; -.
DR EPD; Q9H492; -.
DR jPOST; Q9H492; -.
DR MassIVE; Q9H492; -.
DR MaxQB; Q9H492; -.
DR PaxDb; Q9H492; -.
DR PeptideAtlas; Q9H492; -.
DR PRIDE; Q9H492; -.
DR ProteomicsDB; 80798; -. [Q9H492-1]
DR ProteomicsDB; 80799; -. [Q9H492-2]
DR Antibodypedia; 1970; 1396 antibodies from 43 providers.
DR DNASU; 84557; -.
DR Ensembl; ENST00000360668.8; ENSP00000353886.3; ENSG00000101460.13. [Q9H492-1]
DR Ensembl; ENST00000374837.7; ENSP00000363970.3; ENSG00000101460.13. [Q9H492-2]
DR Ensembl; ENST00000397709.1; ENSP00000380821.1; ENSG00000101460.13. [Q9H492-1]
DR GeneID; 84557; -.
DR KEGG; hsa:84557; -.
DR MANE-Select; ENST00000360668.8; ENSP00000353886.3; NM_032514.4; NP_115903.1.
DR UCSC; uc002xap.3; human. [Q9H492-1]
DR CTD; 84557; -.
DR DisGeNET; 84557; -.
DR GeneCards; MAP1LC3A; -.
DR HGNC; HGNC:6838; MAP1LC3A.
DR HPA; ENSG00000101460; Tissue enhanced (brain).
DR MIM; 601242; gene.
DR neXtProt; NX_Q9H492; -.
DR OpenTargets; ENSG00000101460; -.
DR PharmGKB; PA30582; -.
DR VEuPathDB; HostDB:ENSG00000101460; -.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000158853; -.
DR HOGENOM; CLU_119276_1_0_1; -.
DR InParanoid; Q9H492; -.
DR OMA; VNERSMV; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; Q9H492; -.
DR TreeFam; TF312964; -.
DR PathwayCommons; Q9H492; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-HSA-8934903; Receptor Mediated Mitophagy.
DR SignaLink; Q9H492; -.
DR SIGNOR; Q9H492; -.
DR BioGRID-ORCS; 84557; 25 hits in 1075 CRISPR screens.
DR ChiTaRS; MAP1LC3A; human.
DR EvolutionaryTrace; Q9H492; -.
DR GeneWiki; MAP1LC3A; -.
DR GenomeRNAi; 84557; -.
DR Pharos; Q9H492; Tbio.
DR PRO; PR:Q9H492; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9H492; protein.
DR Bgee; ENSG00000101460; Expressed in right hemisphere of cerebellum and 171 other tissues.
DR Genevisible; Q9H492; HS.
DR GO; GO:0044754; C:autolysosome; IDA:MGI.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005770; C:late endosome; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0031090; C:organelle membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0008017; F:microtubule binding; IBA:GO_Central.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IMP:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; IDA:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IGI:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IEA:Ensembl.
DR GO; GO:0071280; P:cellular response to copper ion; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IDA:UniProtKB.
DR GO; GO:0010040; P:response to iron(II) ion; IEA:Ensembl.
DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; IEA:Ensembl.
DR InterPro; IPR004241; Atg8-like.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR10969; PTHR10969; 1.
DR Pfam; PF02991; ATG8; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Lipoprotein; Membrane; Microtubule;
KW Phosphoprotein; Reference proteome; Ubl conjugation pathway.
FT CHAIN 1..120
FT /note="Microtubule-associated proteins 1A/1B light chain
FT 3A"
FT /id="PRO_0000017192"
FT PROPEP 121
FT /note="Removed in mature form"
FT /id="PRO_0000017193"
FT REGION 49..53
FT /note="Important for interaction with ATG13 and for
FT autophagosome formation"
FT /evidence="ECO:0000269|PubMed:24290141"
FT SITE 120..121
FT /note="Cleavage; by ATG4B"
FT /evidence="ECO:0000305|PubMed:15187094"
FT MOD_RES 12
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:20713600"
FT LIPID 120
FT /note="Phosphatidylethanolamine amidated glycine;
FT alternate"
FT /evidence="ECO:0000269|PubMed:33909989,
FT ECO:0000305|PubMed:15187094"
FT LIPID 120
FT /note="Phosphatidylserine amidated glycine; alternate"
FT /evidence="ECO:0000269|PubMed:33909989"
FT VAR_SEQ 1..13
FT /note="MPSDRPFKQRRSF -> MKMRFFSSPCGKAAVDP (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_013660"
FT MUTAGEN 49
FT /note="K->A: Increases interaction with ATG13 and strongly
FT reduces autophagosome formation."
FT /evidence="ECO:0000269|PubMed:24290141"
FT MUTAGEN 51
FT /note="K->A: Decreases interaction with ATG13 and strongly
FT reduces autophagosome formation."
FT /evidence="ECO:0000269|PubMed:24290141"
FT MUTAGEN 53
FT /note="L->A: Decreases interaction with ATG13."
FT /evidence="ECO:0000269|PubMed:24290141"
FT MUTAGEN 116..119
FT /note="QETF->AAAA: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by both Legionella RavZ and
FT ATG4B."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 116..118
FT /note="QET->AAA: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by both Legionella RavZ and
FT ATG4B."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 116..117
FT /note="QE->AA: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by ATG4B, without affecting
FT deconjugation by Legionella RavZ."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 116
FT /note="Q->A: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by ATG4B, without affecting
FT deconjugation by Legionella RavZ."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 117
FT /note="E->A: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by Legionella RavZ, without
FT affecting deconjugation by ATG4B."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 118
FT /note="T->A: Does not affect deconjugation of
FT phosphatidylethanolamine (PE)."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 119
FT /note="F->A: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by both Legionella RavZ and
FT ATG4B."
FT /evidence="ECO:0000269|PubMed:32686895"
FT MUTAGEN 120
FT /note="G->A: No processing of precursor."
FT /evidence="ECO:0000269|PubMed:12740394"
FT MUTAGEN 120
FT /note="Missing: Abolished deconjugation of
FT phosphatidylethanolamine (PE) by both Legionella RavZ and
FT ATG4B."
FT /evidence="ECO:0000269|PubMed:32686895"
FT HELIX 2..4
FT /evidence="ECO:0007829|PDB:3WAN"
FT HELIX 7..10
FT /evidence="ECO:0007829|PDB:7RA0"
FT HELIX 13..26
FT /evidence="ECO:0007829|PDB:7RA0"
FT STRAND 30..37
FT /evidence="ECO:0007829|PDB:7RA0"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3WAN"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:7RA0"
FT HELIX 60..71
FT /evidence="ECO:0007829|PDB:7RA0"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:7R9Z"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:7RA0"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3WAN"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:3WAN"
FT HELIX 95..102
FT /evidence="ECO:0007829|PDB:7RA0"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:7RA0"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:5CX3"
SQ SEQUENCE 121 AA; 14272 MW; 48C1FBE8F7892AF3 CRC64;
MPSDRPFKQR RSFADRCKEV QQIRDQHPSK IPVIIERYKG EKQLPVLDKT KFLVPDHVNM
SELVKIIRRR LQLNPTQAFF LLVNQHSMVS VSTPIADIYE QEKDEDGFLY MVYASQETFG
F
