GBRAP_HUMAN
ID GBRAP_HUMAN Reviewed; 117 AA.
AC O95166;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Gamma-aminobutyric acid receptor-associated protein;
DE AltName: Full=GABA(A) receptor-associated protein;
DE AltName: Full=MM46;
DE Flags: Precursor;
GN Name=GABARAP; Synonyms=FLC3B; ORFNames=HT004;
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], FUNCTION, TISSUE SPECIFICITY, AND INTERACTION
RP WITH GABRG2 AND BETA-TUBULIN.
RC TISSUE=Brain;
RX PubMed=9892355; DOI=10.1038/16264;
RA Wang H., Bedford F.K., Brandon N.J., Moss S.J., Olsen R.W.;
RT "GABA(A)-receptor-associated protein links GABA(A) receptors and the
RT cytoskeleton.";
RL Nature 397:69-72(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH ULK1.
RC TISSUE=Frontal cortex;
RX PubMed=11146101; DOI=10.1016/s0169-328x(00)00218-7;
RA Okazaki N., Yan J., Yuasa S., Ueno T., Kominami E., Masuho Y., Koga H.,
RA Muramatsu M.-A.;
RT "Interaction of the Unc-51-like kinase and microtubule-associated protein
RT light chain 3 related proteins in the brain: possible role of vesicular
RT transport in axonal elongation.";
RL Brain Res. Mol. Brain Res. 85:1-12(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Iijima M., Mitsui Y.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Ye M., Fu G., Wu J., Zhou J., Zhang Q., Shen Y., Kan L., He K., Gu B.,
RA Chen S., Mao M., Chen Z.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hypothalamus;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [6]
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 [7]
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 [8]
RP LIPIDATION AT GLY-116, INTERACTION WITH ATG3 AND ATG7, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12507496; DOI=10.1016/s0006-291x(02)02907-8;
RA Tanida I., Komatsu M., Ueno T., Kominami E.;
RT "GATE-16 and GABARAP are authentic modifiers mediated by Apg7 and Apg3.";
RL Biochem. Biophys. Res. Commun. 300:637-644(2003).
RN [9]
RP FUNCTION, CLEAVAGE, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-116.
RX PubMed=15169837; DOI=10.1242/jcs.01131;
RA Kabeya Y., Mizushima N., Yamamoto A., Oshitani-Okamoto S., Ohsumi Y.,
RA Yoshimori T.;
RT "LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on
RT form-II formation.";
RL J. Cell Sci. 117:2805-2812(2004).
RN [10]
RP FUNCTION, AND INTERACTION WITH DDX47.
RX PubMed=15977068; DOI=10.1007/s10529-005-3628-2;
RA Lee J.H., Rho S.B., Chun T.;
RT "GABAA receptor-associated protein (GABARAP) induces apoptosis by
RT interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47).";
RL Biotechnol. Lett. 27:623-628(2005).
RN [11]
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 [12]
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 [13]
RP CLEAVAGE BY ATG4B.
RX PubMed=20818167; DOI=10.4161/auto.6.7.13075;
RA Shu C.W., Drag M., Bekes M., Zhai D., Salvesen G.S., Reed J.C.;
RT "Synthetic substrates for measuring activity of autophagy proteases:
RT autophagins (Atg4).";
RL Autophagy 6:936-947(2010).
RN [14]
RP FUNCTION, INTERACTION WITH TECPR2, AND MUTAGENESIS OF 49-TYR-LEU-50 AND
RP ARG-67.
RX PubMed=20562859; DOI=10.1038/nature09204;
RA Behrends C., Sowa M.E., Gygi S.P., Harper J.W.;
RT "Network organization of the human autophagy system.";
RL Nature 466:68-76(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
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 [17]
RP FUNCTION, AND INTERACTION WITH MAPK15.
RX PubMed=22948227; DOI=10.4161/auto.21857;
RA Colecchia D., Strambi A., Sanzone S., Iavarone C., Rossi M., Dall'Armi C.,
RA Piccioni F., Verrotti di Pianella A., Chiariello M.;
RT "MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP
RT proteins.";
RL Autophagy 8:1724-1740(2012).
RN [18]
RP INTERACTION WITH TP53INP1.
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 [19]
RP INTERACTION WITH ATG13; RB1CC1 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 [20]
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 [21]
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 [22]
RP INTERACTION WITH PCM1.
RX PubMed=24089205; DOI=10.1038/nature12606;
RA Tang Z., Lin M.G., Stowe T.R., Chen S., Zhu M., Stearns T., Franco B.,
RA Zhong Q.;
RT "Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar
RT satellites.";
RL Nature 502:254-257(2013).
RN [23]
RP INTERACTION WITH FLCN.
RX PubMed=25126726; DOI=10.4161/auto.29640;
RA Dunlop E.A., Seifan S., Claessens T., Behrends C., Kamps M.A., Rozycka E.,
RA Kemp A.J., Nookala R.K., Blenis J., Coull B.J., Murray J.T.,
RA van Steensel M.A., Wilkinson S., Tee A.R.;
RT "FLCN, a novel autophagy component, interacts with GABARAP and is regulated
RT by ULK1 phosphorylation.";
RL Autophagy 10:1749-1760(2014).
RN [24]
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 [25]
RP INTERACTION WITH MEFV AND TRIM21.
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 [26]
RP INTERACTION WITH UBA5.
RX PubMed=26929408; DOI=10.1074/jbc.m116.715474;
RA Habisov S., Huber J., Ichimura Y., Akutsu M., Rogova N., Loehr F.,
RA McEwan D.G., Johansen T., Dikic I., Doetsch V., Komatsu M., Rogov V.V.,
RA Kirkin V.;
RT "Structural and functional analysis of a novel interaction motif within
RT UFM1-activating enzyme 5 (UBA5) required for binding to ubiquitin-like
RT proteins and ufmylation.";
RL J. Biol. Chem. 291:9025-9041(2016).
RN [27]
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 [28]
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 [29]
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 [30]
RP LIPIDATION AT GLY-116.
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 [31]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), AND INTERACTION WITH GABRG2;
RP ALPHA-TUBULIN AND BETA-TUBULIN.
RX PubMed=11729197; DOI=10.1074/jbc.m109753200;
RA Knight D., Harris R., McAlister M.S.B., Phelan J.P., Geddes S., Moss S.J.,
RA Driscoll P.C., Keep N.H.;
RT "The X-ray crystal structure and putative ligand-derived peptide binding
RT properties of gamma-aminobutyric acid receptor type A receptor-associated
RT protein.";
RL J. Biol. Chem. 277:5556-5561(2002).
RN [32]
RP STRUCTURE BY NMR.
RX PubMed=11875056; DOI=10.1074/jbc.c200050200;
RA Stangler T., Mayr L.M., Willbold D.;
RT "Solution structure of human GABA(A) receptor-associated protein GABARAP:
RT implications for biological function and its regulation.";
RL J. Biol. Chem. 277:13363-13366(2002).
RN [33]
RP STRUCTURE BY NMR.
RX PubMed=11885988; DOI=10.1023/a:1013884402033;
RA Kouno T., Miura K., Kanematsu T., Shirakawa M., Hirata M., Kawano K.;
RT "1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor
RT associated protein.";
RL J. Biomol. NMR 22:97-98(2002).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS).
RX PubMed=18638487; DOI=10.1016/j.jmb.2008.06.086;
RA Weiergraber O.H., Stangler T., Thielmann Y., Mohrluder J., Wiesehan K.,
RA Willbold D.;
RT "Ligand binding mode of GABAA receptor-associated protein.";
RL J. Mol. Biol. 381:1320-1331(2008).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALR, AND INTERACTION
RP WITH CALR.
RX PubMed=19154346; DOI=10.1111/j.1742-4658.2008.06857.x;
RA Thielmann Y., Weiergraber O.H., Mohrluder J., Willbold D.;
RT "Structural framework of the GABARAP-calreticulin interface -- implications
RT for substrate binding to endoplasmic reticulum chaperones.";
RL FEBS J. 276:1140-1152(2009).
RN [36] {ECO:0007744|PDB:3WIM}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH WDFY3, INTERACTION
RP WITH SQSTM1, AND MUTAGENESIS OF LYS-24; TYR-25 AND ASP-54.
RX PubMed=24668264; DOI=10.1002/embr.201338003;
RA Lystad A.H., Ichimura Y., Takagi K., Yang Y., Pankiv S., Kanegae Y.,
RA Kageyama S., Suzuki M., Saito I., Mizushima T., Komatsu M., Simonsen A.;
RT "Structural determinants in GABARAP required for the selective binding and
RT recruitment of ALFY to LC3B-positive structures.";
RL EMBO Rep. 15:557-565(2014).
RN [37] {ECO:0007744|PDB:4XC2}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 3-116 IN COMPLEX WITH KBTBD6 AIM
RP MOTIF, FUNCTION, AND INTERACTION WITH KBTBD6 AND KBTBD7.
RX PubMed=25684205; DOI=10.1016/j.molcel.2014.12.040;
RA Genau H.M., Huber J., Baschieri F., Akutsu M., Doetsch V., Farhan H.,
RA Rogov V., Behrends C.;
RT "CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to
RT spatially restrict TIAM1-RAC1 signaling.";
RL Mol. Cell 57:995-1010(2015).
CC -!- FUNCTION: Ubiquitin-like modifier that plays a role in intracellular
CC transport of GABA(A) receptors and its interaction with the
CC cytoskeleton (PubMed:9892355). Involved in autophagy: while LC3s are
CC involved in elongation of the phagophore membrane, the GABARAP/GATE-16
CC subfamily is essential for a later stage in autophagosome maturation
CC (PubMed:15169837, PubMed:20562859, PubMed:22948227). 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). Also required for the
CC local activation of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex,
CC regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide
CC exchange factor (GEF) that activates RAC1 and downstream signal
CC transduction (PubMed:25684205). Thereby, regulates different biological
CC processes including the organization of the cytoskeleton, cell
CC migration and proliferation (PubMed:25684205). Involved in apoptosis
CC (PubMed:15977068). {ECO:0000269|PubMed:15169837,
CC ECO:0000269|PubMed:15977068, ECO:0000269|PubMed:20562859,
CC ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:25684205,
CC ECO:0000269|PubMed:31006538, ECO:0000269|PubMed:9892355}.
CC -!- SUBUNIT: Interacts with GPHN and NSF (By similarity). Interacts with
CC ATG3, ATG7, ATG13 (PubMed:11096062, PubMed:11825910, PubMed:12507496,
CC PubMed:23043107). Interacts with alpha- and beta-tubulin
CC (PubMed:9892355, PubMed:11729197). Interacts with GABRG2
CC (PubMed:9892355, PubMed:11729197). Interacts with RB1CC1
CC (PubMed:23043107). Interacts with ULK1 (PubMed:11146101,
CC PubMed:23043107). Interacts with CALR (PubMed:19154346). Interacts with
CC DDX47 (PubMed:15977068). Interacts with TP53INP1 and TP53INP2
CC (PubMed:19056683, PubMed:22421968, PubMed:22470510). Interacts with
CC TBC1D5 and TBC1D25 (PubMed:21383079, PubMed:22354992). Directly
CC interacts with SQSTM1 (PubMed:17580304, PubMed:24668264). Interacts
CC with MAPK15 (PubMed:22948227). Interacts with TECPR2 (PubMed:20562859).
CC Interacts with PCM1 (PubMed:24089205). Interacts with TRIM5 and TRIM21
CC (PubMed:25127057, PubMed:26347139). Interacts with MEFV
CC (PubMed:26347139). Interacts with KIF21B (By similarity). Interacts
CC with WDFY3; this interaction is required for WDFY3 recruitment to
CC MAP1LC3B-positive p62/SQSTM1 bodies (PubMed:24668264). Interacts with
CC the reticulophagy receptor TEX264 (PubMed:31006538). Interacts with
CC UBA5 (PubMed:26929408). Interacts with FLCN; interaction regulates
CC autophagy (PubMed:25126726). Interacts with KBTBD6 and KBTBD7; the
CC interaction is direct and required for the ubiquitination of TIAM1
CC (PubMed:25684205). {ECO:0000250|UniProtKB:P60517,
CC ECO:0000269|PubMed:11096062, ECO:0000269|PubMed:11146101,
CC ECO:0000269|PubMed:11729197, ECO:0000269|PubMed:11825910,
CC ECO:0000269|PubMed:12507496, ECO:0000269|PubMed:15977068,
CC ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19056683,
CC ECO:0000269|PubMed:19154346, ECO:0000269|PubMed:20562859,
CC ECO:0000269|PubMed:21383079, ECO:0000269|PubMed:22354992,
CC ECO:0000269|PubMed:22421968, ECO:0000269|PubMed:22470510,
CC ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:23043107,
CC ECO:0000269|PubMed:24089205, ECO:0000269|PubMed:24668264,
CC ECO:0000269|PubMed:25126726, ECO:0000269|PubMed:25127057,
CC ECO:0000269|PubMed:25684205, ECO:0000269|PubMed:26347139,
CC ECO:0000269|PubMed:26929408, ECO:0000269|PubMed:31006538,
CC ECO:0000269|PubMed:9892355}.
CC -!- INTERACTION:
CC O95166; O75143: ATG13; NbExp=3; IntAct=EBI-712001, EBI-2798775;
CC O95166; Q2TAZ0: ATG2A; NbExp=2; IntAct=EBI-712001, EBI-2514077;
CC O95166; Q9NT62: ATG3; NbExp=5; IntAct=EBI-712001, EBI-988094;
CC O95166; Q9Y4P1: ATG4B; NbExp=8; IntAct=EBI-712001, EBI-712014;
CC O95166; Q9H1Y0: ATG5; NbExp=2; IntAct=EBI-712001, EBI-1047414;
CC O95166; O95352: ATG7; NbExp=8; IntAct=EBI-712001, EBI-987834;
CC O95166; P27797: CALR; NbExp=4; IntAct=EBI-712001, EBI-1049597;
CC O95166; Q9H0S4: DDX47; NbExp=3; IntAct=EBI-712001, EBI-2515241;
CC O95166; Q8WXU2: DNAAF4; NbExp=4; IntAct=EBI-712001, EBI-2946907;
CC O95166; Q96RU3: FNBP1; NbExp=2; IntAct=EBI-712001, EBI-1111248;
CC O95166; Q8TF40: FNIP1; NbExp=5; IntAct=EBI-712001, EBI-2946919;
CC O95166; Q9BQS8: FYCO1; NbExp=2; IntAct=EBI-712001, EBI-2869338;
CC O95166; P18507-2: GABRG2; NbExp=3; IntAct=EBI-712001, EBI-15096952;
CC O95166; P40939: HADHA; NbExp=5; IntAct=EBI-712001, EBI-356720;
CC O95166; O00410: IPO5; NbExp=6; IntAct=EBI-712001, EBI-356424;
CC O95166; Q86V97: KBTBD6; NbExp=3; IntAct=EBI-712001, EBI-2514778;
CC O95166; Q8WVZ9: KBTBD7; NbExp=2; IntAct=EBI-712001, EBI-473695;
CC O95166; Q86YT6: MIB1; NbExp=3; IntAct=EBI-712001, EBI-2129148;
CC O95166; Q14596: NBR1; NbExp=6; IntAct=EBI-712001, EBI-742698;
CC O95166; Q8NI08: NCOA7; NbExp=4; IntAct=EBI-712001, EBI-80799;
CC O95166; P46934: NEDD4; NbExp=6; IntAct=EBI-712001, EBI-726944;
CC O95166; Q8TD19: NEK9; NbExp=5; IntAct=EBI-712001, EBI-1044009;
CC O95166; O75323: NIPSNAP2; NbExp=5; IntAct=EBI-712001, EBI-307133;
CC O95166; Q92636: NSMAF; NbExp=2; IntAct=EBI-712001, EBI-2947053;
CC O95166; Q15154: PCM1; NbExp=8; IntAct=EBI-712001, EBI-741421;
CC O95166; Q9NS23: RASSF1; NbExp=2; IntAct=EBI-712001, EBI-367363;
CC O95166; Q8WWW0: RASSF5; NbExp=2; IntAct=EBI-712001, EBI-367390;
CC O95166; Q13501: SQSTM1; NbExp=16; IntAct=EBI-712001, EBI-307104;
CC O95166; O95210: STBD1; NbExp=6; IntAct=EBI-712001, EBI-2947137;
CC O95166; Q13188: STK3; NbExp=2; IntAct=EBI-712001, EBI-992580;
CC O95166; Q13043: STK4; NbExp=2; IntAct=EBI-712001, EBI-367376;
CC O95166; Q8TC07: TBC1D15; NbExp=5; IntAct=EBI-712001, EBI-1048247;
CC O95166; Q9UPU7: TBC1D2B; NbExp=2; IntAct=EBI-712001, EBI-2947180;
CC O95166; O15040: TECPR2; NbExp=2; IntAct=EBI-712001, EBI-2946991;
CC O95166; Q96A56: TP53INP1; NbExp=3; IntAct=EBI-712001, EBI-9986117;
CC O95166; Q969E8: TSR2; NbExp=5; IntAct=EBI-712001, EBI-746981;
CC O95166; Q9GZZ9: UBA5; NbExp=2; IntAct=EBI-712001, EBI-747805;
CC O95166; Q9Z2F7: Bnip3l; Xeno; NbExp=2; IntAct=EBI-712001, EBI-1774669;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:12507496, ECO:0000269|PubMed:15169837,
CC ECO:0000269|PubMed:17580304, ECO:0000269|PubMed:19056683}. Endomembrane
CC system {ECO:0000250|UniProtKB:P60517}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P60517}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P60517}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:P60517}. Note=Largely associated with
CC intracellular membrane structures including the Golgi apparatus and
CC postsynaptic cisternae. Colocalizes with microtubules (By similarity).
CC Localizes also to discrete punctae along the ciliary axoneme (By
CC similarity). {ECO:0000250|UniProtKB:P60517,
CC ECO:0000250|UniProtKB:Q9DCD6}.
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, liver, skeletal muscle,
CC kidney and pancreas. {ECO:0000269|PubMed:11146101,
CC ECO:0000269|PubMed:9892355}.
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, GABARAP-I (PubMed:15169837, PubMed:20818167, PubMed:30661429).
CC The processed form is then activated by APG7L/ATG7, transferred to ATG3
CC and conjugated to phosphatidylethanolamine (PE) phospholipid to form
CC the membrane-bound form, GABARAP-II (PubMed:15169837). During non-
CC canonical autophagy, the processed form is conjugated to
CC phosphatidylserine (PS) phospholipid (PubMed:33909989). ATG4 proteins
CC also mediate the delipidation of PE-conjugated forms (PubMed:33909989).
CC In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins
CC conjugated to PS during non-canonical autophagy (PubMed:33909989).
CC ATG4B constitutes the major protein for proteolytic activation
CC (PubMed:30661429). ATG4D is the main enzyme for delipidation activity
CC (By similarity). {ECO:0000250|UniProtKB:Q9DCD6,
CC ECO:0000269|PubMed:15169837, ECO:0000269|PubMed:20818167,
CC ECO:0000269|PubMed:30661429, 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:31722778). RavZ
CC is also able to mediate delipidation of ATG8 proteins conjugated to
CC phosphatidylserine (PS) (PubMed:33909989).
CC {ECO:0000269|PubMed:31722778, ECO:0000269|PubMed:33909989}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AF161586; AAD47641.1; -; mRNA.
DR EMBL; AB030711; BAB21549.1; -; mRNA.
DR EMBL; AF044671; AAD02337.1; -; mRNA.
DR EMBL; AF067171; AAD32455.1; -; mRNA.
DR EMBL; AF183425; AAG09694.1; -; mRNA.
DR CCDS; CCDS11092.1; -.
DR RefSeq; NP_009209.1; NM_007278.1.
DR PDB; 1GNU; X-ray; 1.75 A; A=1-117.
DR PDB; 1KLV; NMR; -; A=1-117.
DR PDB; 1KM7; NMR; -; A=1-117.
DR PDB; 1KOT; NMR; -; A=1-117.
DR PDB; 3D32; X-ray; 1.30 A; A/B=1-117.
DR PDB; 3DOW; X-ray; 2.30 A; A=1-117.
DR PDB; 3WIM; X-ray; 2.60 A; A=1-117.
DR PDB; 4XC2; X-ray; 1.90 A; A/B/C/D=3-116.
DR PDB; 5DPS; X-ray; 2.00 A; A/B/C=2-117.
DR PDB; 6HB9; X-ray; 1.30 A; A=3-116.
DR PDB; 6HOG; X-ray; 1.26 A; A=2-112.
DR PDB; 6HOH; X-ray; 2.25 A; A/B/C/D=2-112.
DR PDB; 6HOJ; X-ray; 1.51 A; A/B/C=1-112.
DR PDB; 6HOK; X-ray; 1.61 A; A=1-112.
DR PDB; 6HYL; X-ray; 1.56 A; A/B=1-117.
DR PDB; 6HYM; X-ray; 1.86 A; A/B=1-117.
DR PDB; 6HYN; X-ray; 1.14 A; A=1-117.
DR PDB; 6HYO; X-ray; 1.07 A; A=1-117.
DR PDB; 6YOP; X-ray; 1.10 A; A=1-117.
DR PDB; 7AA8; X-ray; 1.25 A; C=1-117.
DR PDB; 7BRQ; X-ray; 1.40 A; A=1-116.
DR PDB; 7BRT; X-ray; 2.00 A; A/B=1-116.
DR PDB; 7BRU; X-ray; 2.15 A; A/B/C=1-116.
DR PDB; 7BV4; X-ray; 2.00 A; A/B/E/G=1-117.
DR PDB; 7EA7; X-ray; 2.69 A; A/B=1-117.
DR PDB; 7LSW; X-ray; 3.05 A; A/B/C/D/E/F=1-117.
DR PDB; 7LT6; X-ray; 1.80 A; A/B/C=1-117.
DR PDB; 7VEC; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L=1-116.
DR PDB; 7VED; X-ray; 2.02 A; A/B=1-116.
DR PDBsum; 1GNU; -.
DR PDBsum; 1KLV; -.
DR PDBsum; 1KM7; -.
DR PDBsum; 1KOT; -.
DR PDBsum; 3D32; -.
DR PDBsum; 3DOW; -.
DR PDBsum; 3WIM; -.
DR PDBsum; 4XC2; -.
DR PDBsum; 5DPS; -.
DR PDBsum; 6HB9; -.
DR PDBsum; 6HOG; -.
DR PDBsum; 6HOH; -.
DR PDBsum; 6HOJ; -.
DR PDBsum; 6HOK; -.
DR PDBsum; 6HYL; -.
DR PDBsum; 6HYM; -.
DR PDBsum; 6HYN; -.
DR PDBsum; 6HYO; -.
DR PDBsum; 6YOP; -.
DR PDBsum; 7AA8; -.
DR PDBsum; 7BRQ; -.
DR PDBsum; 7BRT; -.
DR PDBsum; 7BRU; -.
DR PDBsum; 7BV4; -.
DR PDBsum; 7EA7; -.
DR PDBsum; 7LSW; -.
DR PDBsum; 7LT6; -.
DR PDBsum; 7VEC; -.
DR PDBsum; 7VED; -.
DR AlphaFoldDB; O95166; -.
DR BMRB; O95166; -.
DR SMR; O95166; -.
DR BioGRID; 116465; 103.
DR DIP; DIP-35050N; -.
DR ELM; O95166; -.
DR IntAct; O95166; 491.
DR MINT; O95166; -.
DR STRING; 9606.ENSP00000306866; -.
DR MoonDB; O95166; Predicted.
DR TCDB; 1.A.9.5.2; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR iPTMnet; O95166; -.
DR PhosphoSitePlus; O95166; -.
DR BioMuta; GABARAP; -.
DR EPD; O95166; -.
DR jPOST; O95166; -.
DR MassIVE; O95166; -.
DR PaxDb; O95166; -.
DR PeptideAtlas; O95166; -.
DR PRIDE; O95166; -.
DR ProteomicsDB; 50679; -.
DR Antibodypedia; 11841; 712 antibodies from 37 providers.
DR DNASU; 11337; -.
DR Ensembl; ENST00000302386.10; ENSP00000306866.5; ENSG00000170296.10.
DR GeneID; 11337; -.
DR KEGG; hsa:11337; -.
DR MANE-Select; ENST00000302386.10; ENSP00000306866.5; NM_007278.2; NP_009209.1.
DR CTD; 11337; -.
DR DisGeNET; 11337; -.
DR GeneCards; GABARAP; -.
DR HGNC; HGNC:4067; GABARAP.
DR HPA; ENSG00000170296; Low tissue specificity.
DR MIM; 605125; gene.
DR neXtProt; NX_O95166; -.
DR OpenTargets; ENSG00000170296; -.
DR PharmGKB; PA28480; -.
DR VEuPathDB; HostDB:ENSG00000170296; -.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000157496; -.
DR HOGENOM; CLU_119276_0_0_1; -.
DR OMA; AVYQEHK; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; O95166; -.
DR TreeFam; TF314556; -.
DR PathwayCommons; O95166; -.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR SABIO-RK; O95166; -.
DR SignaLink; O95166; -.
DR SIGNOR; O95166; -.
DR BioGRID-ORCS; 11337; 68 hits in 1082 CRISPR screens.
DR ChiTaRS; GABARAP; human.
DR EvolutionaryTrace; O95166; -.
DR GeneWiki; GABARAP; -.
DR GenomeRNAi; 11337; -.
DR Pharos; O95166; Tbio.
DR PRO; PR:O95166; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O95166; protein.
DR Bgee; ENSG00000170296; Expressed in right testis and 95 other tissues.
DR ExpressionAtlas; O95166; baseline and differential.
DR Genevisible; O95166; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005776; C:autophagosome; IDA:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; IDA:UniProtKB.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005875; C:microtubule associated complex; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0097225; C:sperm midpiece; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0050811; F:GABA receptor binding; IPI:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
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:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0006605; P:protein targeting; TAS:ProtInc.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IMP:UniProtKB.
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; Apoptosis; Autophagy; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; Golgi apparatus; Lipoprotein; Membrane; Microtubule;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..116
FT /note="Gamma-aminobutyric acid receptor-associated protein"
FT /id="PRO_0000212363"
FT PROPEP 117
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:15169837"
FT /id="PRO_0000423065"
FT REGION 1..22
FT /note="Interaction with beta-tubulin"
FT /evidence="ECO:0000269|PubMed:9892355"
FT REGION 36..117
FT /note="Interaction with GPHN"
FT /evidence="ECO:0000250|UniProtKB:Q9DCD6"
FT REGION 36..68
FT /note="Interaction with GABRG2"
FT /evidence="ECO:0000269|PubMed:9892355"
FT SITE 116..117
FT /note="Cleavage; by ATG4B"
FT /evidence="ECO:0000269|PubMed:15169837"
FT LIPID 116
FT /note="Phosphatidylethanolamine amidated glycine;
FT alternate"
FT /evidence="ECO:0000269|PubMed:12507496,
FT ECO:0000269|PubMed:33909989"
FT LIPID 116
FT /note="Phosphatidylserine amidated glycine; alternate"
FT /evidence="ECO:0000269|PubMed:33909989"
FT MUTAGEN 24
FT /note="K->Q: No effect on WDFY3-binding. Impaired WDFY3-
FT binding, but no effect on SQSTM1-binding; when associated
FT with H-25 and H-54."
FT /evidence="ECO:0000269|PubMed:24668264"
FT MUTAGEN 25
FT /note="Y->H: No effect on WDFY3-binding. Impaired WDFY3-
FT binding, but no effect on SQSTM1-binding; when associated
FT with Q-24 and H-54."
FT /evidence="ECO:0000269|PubMed:24668264"
FT MUTAGEN 49..50
FT /note="YL->AA: Inhibits interaction with TECPR2."
FT /evidence="ECO:0000269|PubMed:20562859"
FT MUTAGEN 54
FT /note="D->H: No effect on WDFY3-binding. Impaired WDFY3-
FT binding, but no effect on SQSTM1-binding; when associated
FT with Q-24 and H-25."
FT /evidence="ECO:0000269|PubMed:24668264"
FT MUTAGEN 67
FT /note="R->A: No effect on interaction with TECPR2."
FT /evidence="ECO:0000269|PubMed:20562859"
FT MUTAGEN 116
FT /note="G->A: Impairs localization at the autophagosomal
FT membrane."
FT /evidence="ECO:0000269|PubMed:15169837"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:6HYO"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:6HYO"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:6HYO"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:6HYO"
FT HELIX 57..67
FT /evidence="ECO:0007829|PDB:6HYO"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:6HYO"
FT STRAND 87..90
FT /evidence="ECO:0007829|PDB:7BV4"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:6HYO"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:1KM7"
FT STRAND 105..114
FT /evidence="ECO:0007829|PDB:6HYO"
SQ SEQUENCE 117 AA; 13918 MW; BC0B84B8A51C1E32 CRC64;
MKFVYKEEHP FEKRRSEGEK IRKKYPDRVP VIVEKAPKAR IGDLDKKKYL VPSDLTVGQF
YFLIRKRIHL RAEDALFFFV NNVIPPTSAT MGQLYQEHHE EDFFLYIAYS DESVYGL
