MLP3A_MOUSE
ID MLP3A_MOUSE Reviewed; 121 AA.
AC Q91VR7; A2AVS1; Q9DC74;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
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 [4]
RP SUBCELLULAR LOCATION.
RX PubMed=11266458; DOI=10.1083/jcb.152.4.657;
RA Mizushima N., Yamamoto A., Hatano M., Kobayashi Y., Kabeya Y., Suzuki K.,
RA Tokuhisa T., Ohsumi Y., Yoshimori T.;
RT "Dissection of autophagosome formation using Apg5-deficient mouse embryonic
RT stem cells.";
RL J. Cell Biol. 152:657-668(2001).
RN [5]
RP SUBCELLULAR LOCATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=12207896; DOI=10.1016/s0006-291x(02)02057-0;
RA Tanida I., Nishitani T., Nemoto T., Ueno T., Kominami E.;
RT "Mammalian Apg12p, but not the Apg12p.Apg5p conjugate, facilitates LC3
RT processing.";
RL Biochem. Biophys. Res. Commun. 296:1164-1170(2002).
RN [6]
RP CLEAVAGE BY ATG4B, AND SUBCELLULAR LOCATION.
RX PubMed=14530254; DOI=10.1074/jbc.m308762200;
RA Hemelaar J., Lelyveld V.S., Kessler B.M., Ploegh H.L.;
RT "A single protease, Apg4B, is specific for the autophagy-related ubiquitin-
RT like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L.";
RL J. Biol. Chem. 278:51841-51850(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP LIPIDATION, AND DELIPIDATION.
RX PubMed=33795848; DOI=10.1038/s41418-021-00776-1;
RA Tamargo-Gomez I., Martinez-Garcia G.G., Suarez M.F., Rey V., Fueyo A.,
RA Codina-Martinez H., Bretones G., Caravia X.M., Morel E., Dupont N.,
RA Cabo R., Tomas-Zapico C., Souquere S., Pierron G., Codogno P.,
RA Lopez-Otin C., Fernandez A.F., Marino G.;
RT "ATG4D is the main ATG8 delipidating enzyme in mammalian cells and protects
RT against cerebellar neurodegeneration.";
RL Cell Death Differ. 28:2651-2672(2021).
CC -!- FUNCTION: Ubiquitin-like modifier involved in formation of
CC autophagosomal vacuoles (autophagosomes). While LC3s are involved in
CC elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is
CC essential for a later stage in autophagosome maturation. 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. {ECO:0000250|UniProtKB:Q9H492}.
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. Directly interacts with SQSTM1; this interaction leads to
CC MAP1LC3A recruitment to inclusion bodies containing polyubiquitinated
CC protein aggregates and to inclusion body degradation by autophagy.
CC Interacts with ATG13. Interacts with ULK1. Interacts with TBC1D5. Found
CC in a complex with UBQLN1 and UBQLN2. Interacts with UBQLN4 (via STI1 1
CC and 2 domains). Interacts with UBQLN1 in the presence of UBQLN4.
CC Interacts with TRIM5. Interacts with MEFV. Interacts with RETREG1,
CC RETREG2 and RETREG3. Interacts with PICALM. Interacts with the
CC reticulophagy receptor TEX264. Interacts with MOAP1 (via LIR motif) (By
CC similarity). {ECO:0000250|UniProtKB:Q62625,
CC ECO:0000250|UniProtKB:Q9H492}.
CC -!- INTERACTION:
CC Q91VR7; Q811T9: Disc1; NbExp=2; IntAct=EBI-2933755, EBI-2298259;
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000269|PubMed:14530254}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q9H492}. Cytoplasmic vesicle, autophagosome
CC membrane {ECO:0000269|PubMed:11266458, ECO:0000269|PubMed:12207896};
CC Lipid-anchor {ECO:0000250|UniProtKB:Q9H492}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000250|UniProtKB:Q9H492}. Cytoplasm, cytoskeleton
CC {ECO:0000305|PubMed:14530254}. Note=LC3-II binds to the autophagic
CC membranes. {ECO:0000250|UniProtKB:Q9H492}.
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:12207896, PubMed:14530254). 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 (By similarity). During non-canonical autophagy, the
CC processed form is conjugated to phosphatidylserine (PS) phospholipid
CC (By similarity). ATG4 proteins also mediate the delipidation of PE-
CC conjugated forms (PubMed:33795848). In addition, ATG4B and ATG4D
CC mediate delipidation of ATG8 proteins conjugated to PS during non-
CC canonical autophagy (By similarity). ATG4B constitutes the major
CC protein for proteolytic activation (By similarity). ATG4D is the main
CC enzyme for delipidation activity (PubMed:33795848).
CC {ECO:0000250|UniProtKB:Q9H492, ECO:0000269|PubMed:12207896,
CC ECO:0000269|PubMed:14530254, ECO:0000269|PubMed:33795848}.
CC -!- PTM: Phosphorylation at Ser-12 by PKA inhibits conjugation to
CC phosphatidylethanolamine (PE). {ECO:0000250|UniProtKB:Q9H492}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AK003122; BAB22582.1; -; mRNA.
DR EMBL; AL929588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC010596; AAH10596.1; -; mRNA.
DR CCDS; CCDS16945.1; -.
DR RefSeq; NP_080011.1; NM_025735.3.
DR AlphaFoldDB; Q91VR7; -.
DR SMR; Q91VR7; -.
DR BioGRID; 211680; 28.
DR IntAct; Q91VR7; 5.
DR MINT; Q91VR7; -.
DR STRING; 10090.ENSMUSP00000029128; -.
DR iPTMnet; Q91VR7; -.
DR PhosphoSitePlus; Q91VR7; -.
DR MaxQB; Q91VR7; -.
DR PaxDb; Q91VR7; -.
DR PeptideAtlas; Q91VR7; -.
DR PRIDE; Q91VR7; -.
DR ProteomicsDB; 295915; -.
DR Antibodypedia; 1970; 1396 antibodies from 43 providers.
DR DNASU; 66734; -.
DR Ensembl; ENSMUST00000029128; ENSMUSP00000029128; ENSMUSG00000027602.
DR GeneID; 66734; -.
DR KEGG; mmu:66734; -.
DR UCSC; uc012cha.2; mouse.
DR CTD; 84557; -.
DR MGI; MGI:1915661; Map1lc3a.
DR VEuPathDB; HostDB:ENSMUSG00000027602; -.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000158853; -.
DR HOGENOM; CLU_119276_1_0_1; -.
DR InParanoid; Q91VR7; -.
DR OMA; VNERSMV; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; Q91VR7; -.
DR TreeFam; TF312964; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-MMU-8934903; Receptor Mediated Mitophagy.
DR BioGRID-ORCS; 66734; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Map1lc3a; mouse.
DR PRO; PR:Q91VR7; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q91VR7; protein.
DR Bgee; ENSMUSG00000027602; Expressed in lip and 250 other tissues.
DR Genevisible; Q91VR7; MM.
DR GO; GO:0044754; C:autolysosome; ISO:MGI.
DR GO; GO:0005776; C:autophagosome; IDA:MGI.
DR GO; GO:0000421; C:autophagosome membrane; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISO:MGI.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI.
DR GO; GO:0031090; C:organelle membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISO:MGI.
DR GO; GO:0005543; F:phospholipid binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0097352; P:autophagosome maturation; ISO:MGI.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0000422; P:autophagy of mitochondrion; ISO: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; ISO:MGI.
DR GO; GO:0016236; P:macroautophagy; ISO:MGI.
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 Autophagy; Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Lipoprotein;
KW Membrane; Microtubule; Phosphoprotein; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..120
FT /note="Microtubule-associated proteins 1A/1B light chain
FT 3A"
FT /id="PRO_0000017194"
FT PROPEP 121
FT /note="Removed in mature form"
FT /evidence="ECO:0000305"
FT /id="PRO_0000017195"
FT REGION 49..53
FT /note="Important for interaction with ATG13 and for
FT autophagosome formation"
FT /evidence="ECO:0000250|UniProtKB:Q9H492"
FT SITE 120..121
FT /note="Cleavage; by ATG4B"
FT /evidence="ECO:0000250|UniProtKB:Q9H492"
FT MOD_RES 12
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q9H492"
FT LIPID 120
FT /note="Phosphatidylethanolamine amidated glycine;
FT alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H492"
FT LIPID 120
FT /note="Phosphatidylserine amidated glycine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H492"
FT CONFLICT 12
FT /note="S -> T (in Ref. 1; BAB22582)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 121 AA; 14272 MW; 48C1FBE8F7892AF3 CRC64;
MPSDRPFKQR RSFADRCKEV QQIRDQHPSK IPVIIERYKG EKQLPVLDKT KFLVPDHVNM
SELVKIIRRR LQLNPTQAFF LLVNQHSMVS VSTPIADIYE QEKDEDGFLY MVYASQETFG
F
