GBRL2_MOUSE
ID GBRL2_MOUSE Reviewed; 117 AA.
AC P60521; O08765; Q9DCP8; Q9UQF7;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Gamma-aminobutyric acid receptor-associated protein-like 2;
DE AltName: Full=GABA(A) receptor-associated protein-like 2;
DE AltName: Full=Golgi-associated ATPase enhancer of 16 kDa;
DE Short=GATE-16;
DE Flags: Precursor;
GN Name=Gabarapl2;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11414770; DOI=10.1006/geno.2001.6555;
RA Xin Y., Yu L., Chen Z., Zheng L., Fu Q., Jiang J., Zhang P., Gong R.,
RA Zhao S.;
RT "Cloning, expression patterns, and chromosome localization of three human
RT and two mouse homologues of GABA(A) receptor-associated protein.";
RL Genomics 74:408-413(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, and Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and 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 [4]
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, and Testis;
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 [6]
RP INTERACTION WITH TBC1D25.
RX PubMed=21383079; DOI=10.1083/jcb.201008107;
RA Itoh T., Kanno E., Uemura T., Waguri S., Fukuda M.;
RT "OATL1, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal
RT maturation.";
RL J. Cell Biol. 192:839-853(2011).
RN [7]
RP INTERACTION WITH ATG7.
RX PubMed=11890701; DOI=10.1006/bbrc.2002.6645;
RA Tanida I., Tanida-Miyake E., Nishitani T., Komatsu M., Yamazaki H.,
RA Ueno T., Kominami E.;
RT "Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p
RT homologs.";
RL Biochem. Biophys. Res. Commun. 292:256-262(2002).
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 intra-Golgi traffic.
CC Modulates intra-Golgi transport through coupling between NSF activity
CC and SNAREs activation. It first stimulates the ATPase activity of NSF
CC which in turn stimulates the association with GOSR1 (By similarity).
CC Involved in autophagy. Plays a role in mitophagy which contributes to
CC regulate mitochondrial quantity and quality by eliminating the
CC mitochondria to a basal level to fulfill cellular energy requirements
CC and preventing excess ROS production. Whereas 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 (By
CC similarity). {ECO:0000250|UniProtKB:P60519,
CC ECO:0000250|UniProtKB:P60520}.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with ATG3, ATG13 and ULK1
CC (By similarity). Interacts with ATG7 (PubMed:11890701). Interacts with
CC TP53INP1 and TP53INP2 (By similarity). Interacts with TBC1D25
CC (PubMed:21383079). Directly interacts with SQSTM1 and BNIP3 (By
CC similarity). Interacts with TECPR2 and PCM1 (By similarity). Interacts
CC with TBC1D5 (By similarity). Interacts with TRIM5 (By similarity).
CC Interacts with MEFV and TRIM21 (By similarity). Interacts with WDFY3
CC (By similarity). Interacts with UBA5; promoting recruitment of UBA5 to
CC the endoplasmic reticulum membrane (By similarity). Interacts with
CC GOSR1 (By similarity). Interacts with KBTBD6 AND KBTBD7; the
CC interaction is direct (By similarity). {ECO:0000250|UniProtKB:P60519,
CC ECO:0000250|UniProtKB:P60520, ECO:0000269|PubMed:11890701,
CC ECO:0000269|PubMed:21383079}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome
CC {ECO:0000269|PubMed:14530254}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P60520}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P60519}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. A high level expression is seen in
CC brain, thymus, lung, heart, liver and kidney.
CC {ECO:0000269|PubMed:11414770}.
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, GABARAPL2-I (PubMed:14530254). The processed form is then
CC activated by APG7L/ATG7, transferred to ATG3 and conjugated to
CC phosphatidylethanolamine (PE) phospholipid to form the membrane-bound
CC form, GABARAPL2-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 required for GABARAPL2 recycling when autophagosomes
CC fuse with lysosomes (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:P60520, ECO:0000269|PubMed:14530254,
CC ECO:0000269|PubMed:33795848}.
CC -!- PTM: Phosphorylation at Ser-87 and Ser-88 by TBK1 prevents interaction
CC with ATG4 (ATG4A, ATG4B, ATG4C or ATG4D). Phosphorylation by TBK1 on
CC autophagosomes prevents their delipidation by ATG4 and premature
CC removal from nascent autophagosomes. {ECO:0000250|UniProtKB:P60520}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AF190644; AAK16238.1; -; mRNA.
DR EMBL; AK002596; BAB22217.1; -; mRNA.
DR EMBL; AK049819; BAC33933.1; -; mRNA.
DR EMBL; BC026798; AAH26798.1; -; mRNA.
DR EMBL; BC081436; AAH81436.1; -; mRNA.
DR CCDS; CCDS40480.1; -.
DR RefSeq; NP_080969.2; NM_026693.5.
DR AlphaFoldDB; P60521; -.
DR SMR; P60521; -.
DR BioGRID; 220282; 23.
DR ELM; P60521; -.
DR STRING; 10090.ENSMUSP00000034428; -.
DR iPTMnet; P60521; -.
DR PhosphoSitePlus; P60521; -.
DR SwissPalm; P60521; -.
DR EPD; P60521; -.
DR MaxQB; P60521; -.
DR PaxDb; P60521; -.
DR PeptideAtlas; P60521; -.
DR PRIDE; P60521; -.
DR ProteomicsDB; 268853; -.
DR Antibodypedia; 30328; 587 antibodies from 35 providers.
DR DNASU; 93739; -.
DR Ensembl; ENSMUST00000034428; ENSMUSP00000034428; ENSMUSG00000031950.
DR GeneID; 93739; -.
DR KEGG; mmu:93739; -.
DR UCSC; uc009nnb.2; mouse.
DR CTD; 11345; -.
DR MGI; MGI:1890602; Gabarapl2.
DR VEuPathDB; HostDB:ENSMUSG00000031950; -.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000155010; -.
DR HOGENOM; CLU_119276_0_1_1; -.
DR InParanoid; P60521; -.
DR OMA; AKMKWMF; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; P60521; -.
DR TreeFam; TF312964; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-8854214; TBC/RABGAPs.
DR BioGRID-ORCS; 93739; 9 hits in 71 CRISPR screens.
DR ChiTaRS; Gabarapl2; mouse.
DR PRO; PR:P60521; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P60521; protein.
DR Bgee; ENSMUSG00000031950; Expressed in morula and 62 other tissues.
DR Genevisible; P60521; MM.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IDA:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0000422; P:autophagy of mitochondrion; IBA:GO_Central.
DR GO; GO:0006995; P:cellular response to nitrogen starvation; IBA:GO_Central.
DR GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; ISO:MGI.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISO:MGI.
DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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 Acetylation; Autophagy; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Golgi apparatus; Lipoprotein; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..116
FT /note="Gamma-aminobutyric acid receptor-associated protein-
FT like 2"
FT /id="PRO_0000212374"
FT PROPEP 117
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:14530254"
FT /id="PRO_0000423071"
FT SITE 116..117
FT /note="Cleavage; by ATG4B"
FT /evidence="ECO:0000269|PubMed:14530254"
FT MOD_RES 24
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT MOD_RES 88
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT LIPID 116
FT /note="Phosphatidylethanolamine amidated glycine;
FT alternate"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT LIPID 116
FT /note="Phosphatidylserine amidated glycine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P60520"
FT CONFLICT 83
FT /note="T -> A (in Ref. 2; BAB22217)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 117 AA; 13667 MW; 17ACB540FD5B975B CRC64;
MKWMFKEDHS LEHRCVESAK IRAKYPDRVP VIVEKVSGSQ IVDIDKRKYL VPSDITVAQF
MWIIRKRIQL PSEKAIFLFV DKTVPQSSLT MGQLYEKEKD EDGFLYVAYS GENTFGF
