Full text data of GABARAP
GABARAP
(FLC3B)
[Confidence: low (only semi-automatic identification from reviews)]
Gamma-aminobutyric acid receptor-associated protein (GABA(A) receptor-associated protein; MM46; Flags: Precursor)
Gamma-aminobutyric acid receptor-associated protein (GABA(A) receptor-associated protein; MM46; Flags: Precursor)
UniProt
O95166
ID GBRAP_HUMAN Reviewed; 117 AA.
AC O95166;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 113.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH
RP 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
RP 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.,
RA Koga H., Muramatsu M.-A.;
RT "Interaction of the Unc-51-like kinase and microtubule-associated
RT protein light chain 3 related proteins in the brain: possible role of
RT vesicular 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.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis 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,
RT GATE-16, 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
RT conjugation of hApg12p to hApg5p.";
RL J. Biol. Chem. 277:13739-13744(2002).
RN [8]
RP POST-TRANSLATIONAL MODIFICATION, INTERACTION WITH ATG3 AND ATG7, AND
RP SUBCELLULAR 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
RT Apg3.";
RL Biochem. Biophys. Res. Commun. 300:637-644(2003).
RN [9]
RP 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
RT on 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
RT 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.,
RA Pebusque M.J., 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 INTERACTION WITH TECPR2, AND MUTAGENESIS OF 49-TYR-LEU-50 AND 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 [14]
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.,
RA Buerckstuemmer T., 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 [15]
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
RT autophagosomal maturation.";
RL J. Cell Biol. 192:839-853(2011).
RN [16]
RP INTERACTION WITH MAPK15.
RX PubMed=22948227; DOI=10.4161/auto.21857;
RA Colecchia D., Strambi A., Sanzone S., Iavarone C., Rossi M.,
RA Dall'Armi C., 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 [17]
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
RT proteins through the LC3-interacting region (LIR) and promotes
RT autophagy-dependent cell death.";
RL Cell Death Differ. 19:1525-1535(2012).
RN [18]
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
RT complex: sequence requirements for LC3-interacting region (LIR)
RT motifs.";
RL J. Biol. Chem. 287:39275-39290(2012).
RN [19]
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.,
RA Lamark T., Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U.,
RA Palacin M., Johansen T., Zorzano A.;
RT "DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding
RT dual regulators of autophagy and transcription.";
RL PLoS ONE 7:E34034-E34034(2012).
RN [20]
RP INTERACTION 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
RT centriolar satellites.";
RL Nature 502:254-257(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), AND INTERACTION WITH GABRG2;
RP TUBULIN ALPHA AND TUBULIN BETA.
RX PubMed=11729197; DOI=10.1074/jbc.M109753200;
RA Knight D., Harris R., McAlister M.S.B., Phelan J.P., Geddes S.,
RA Moss S.J., Driscoll P.C., Keep N.H.;
RT "The X-ray crystal structure and putative ligand-derived peptide
RT binding properties of gamma-aminobutyric acid receptor type A
RT receptor-associated protein.";
RL J. Biol. Chem. 277:5556-5561(2002).
RN [22]
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
RT GABARAP: implications for biological function and its regulation.";
RL J. Biol. Chem. 277:13363-13366(2002).
RN [23]
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 [24]
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.,
RA Wiesehan K., Willbold D.;
RT "Ligand binding mode of GABAA receptor-associated protein.";
RL J. Mol. Biol. 381:1320-1331(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALR, AND
RP INTERACTION 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 --
RT implications for substrate binding to endoplasmic reticulum
RT chaperones.";
RL FEBS J. 276:1140-1152(2009).
CC -!- FUNCTION: Ubiquitin-like modifier that plays a role in
CC intracellular transport of GABA(A) receptors and its interaction
CC with the cytoskeleton. Involved in apoptosis. Involved in
CC autophagy. Whereas LC3s are involved in elongation of the
CC phagophore membrane, the GABARAP/GATE-16 subfamily is essential
CC for a later stage in autophagosome maturation.
CC -!- SUBUNIT: Interacts with GPHN and NSF (By similarity). Interacts
CC with ATG3, ATG7, ATG13, RB1CC1, GABRG2, beta-tubulin and ULK1.
CC Interacts with CALR. Interacts with DDX47. Interacts with TP53INP1
CC and TP53INP2. Interacts with TBC1D25. Directly interacts with
CC SQSTM1. Interacts with MAPK15. Interacts with TECPR2 and PCM1.
CC -!- INTERACTION:
CC Q2TAZ0:ATG2A; NbExp=2; IntAct=EBI-712001, EBI-2514077;
CC Q9NT62:ATG3; NbExp=5; IntAct=EBI-712001, EBI-988094;
CC Q9Y4P1:ATG4B; NbExp=8; IntAct=EBI-712001, EBI-712014;
CC Q9H1Y0:ATG5; NbExp=2; IntAct=EBI-712001, EBI-1047414;
CC O95352:ATG7; NbExp=8; IntAct=EBI-712001, EBI-987834;
CC Q9Z2F7:Bnip3l (xeno); NbExp=2; IntAct=EBI-712001, EBI-1774669;
CC Q9H0S4:DDX47; NbExp=3; IntAct=EBI-712001, EBI-2515241;
CC Q8WXU2:DYX1C1; NbExp=4; IntAct=EBI-712001, EBI-2946907;
CC Q96RU3:FNBP1; NbExp=2; IntAct=EBI-712001, EBI-1111248;
CC Q8TF40:FNIP1; NbExp=5; IntAct=EBI-712001, EBI-2946919;
CC Q9BQS8:FYCO1; NbExp=2; IntAct=EBI-712001, EBI-2869338;
CC O75323:GBAS; NbExp=5; IntAct=EBI-712001, EBI-307133;
CC P40939:HADHA; NbExp=5; IntAct=EBI-712001, EBI-356720;
CC O00410:IPO5; NbExp=6; IntAct=EBI-712001, EBI-356424;
CC Q86V97:KBTBD6; NbExp=3; IntAct=EBI-712001, EBI-2514778;
CC Q8WVZ9:KBTBD7; NbExp=2; IntAct=EBI-712001, EBI-473695;
CC Q14596:NBR1; NbExp=5; IntAct=EBI-712001, EBI-742698;
CC Q8NI08:NCOA7; NbExp=4; IntAct=EBI-712001, EBI-80799;
CC P46934:NEDD4; NbExp=6; IntAct=EBI-712001, EBI-726944;
CC Q8TD19:NEK9; NbExp=5; IntAct=EBI-712001, EBI-1044009;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-712001, EBI-2947053;
CC Q9NS23:RASSF1; NbExp=2; IntAct=EBI-712001, EBI-367363;
CC Q8WWW0:RASSF5; NbExp=2; IntAct=EBI-712001, EBI-367390;
CC Q13501:SQSTM1; NbExp=10; IntAct=EBI-712001, EBI-307104;
CC O95210:STBD1; NbExp=5; IntAct=EBI-712001, EBI-2947137;
CC Q13188:STK3; NbExp=2; IntAct=EBI-712001, EBI-992580;
CC Q13043:STK4; NbExp=2; IntAct=EBI-712001, EBI-367376;
CC Q8TC07:TBC1D15; NbExp=5; IntAct=EBI-712001, EBI-1048247;
CC Q9UPU7:TBC1D2B; NbExp=2; IntAct=EBI-712001, EBI-2947180;
CC O15040:TECPR2; NbExp=2; IntAct=EBI-712001, EBI-2946991;
CC Q9GZZ9:UBA5; NbExp=2; IntAct=EBI-712001, EBI-747805;
CC -!- SUBCELLULAR LOCATION: Endomembrane system (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Golgi apparatus membrane
CC (By similarity). Cytoplasmic vesicle, autophagosome. Note=Largely
CC associated with intracellular membrane structures including the
CC Golgi apparatus and postsynaptic cisternae. Colocalizes with
CC microtubules (By similarity). Localizes also to discrete punctae
CC along the ciliary axoneme (By similarity).
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, liver, skeletal
CC muscle, kidney and pancreas.
CC -!- PTM: The precursor molecule is cleaved by ATG4B to form the
CC cytosolic form, GABARAP-I. This is activated by APG7L/ATG7,
CC transferred to ATG3 and conjugated to phospholipid to form the
CC membrane-bound form, GABARAP-II.
CC -!- SIMILARITY: Belongs to the ATG8 family.
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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 RefSeq; NP_009209.1; NM_007278.1.
DR UniGene; Hs.647421; -.
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 PDBsum; 1GNU; -.
DR PDBsum; 1KLV; -.
DR PDBsum; 1KM7; -.
DR PDBsum; 1KOT; -.
DR PDBsum; 3D32; -.
DR PDBsum; 3DOW; -.
DR ProteinModelPortal; O95166; -.
DR SMR; O95166; 1-116.
DR IntAct; O95166; 474.
DR MINT; MINT-206256; -.
DR STRING; 9606.ENSP00000306866; -.
DR TCDB; 1.A.9.5.2; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR PhosphoSite; O95166; -.
DR PaxDb; O95166; -.
DR PRIDE; O95166; -.
DR DNASU; 11337; -.
DR Ensembl; ENST00000302386; ENSP00000306866; ENSG00000170296.
DR GeneID; 11337; -.
DR KEGG; hsa:11337; -.
DR UCSC; uc002gfb.3; human.
DR CTD; 11337; -.
DR GeneCards; GC17M007143; -.
DR HGNC; HGNC:4067; GABARAP.
DR MIM; 605125; gene.
DR neXtProt; NX_O95166; -.
DR PharmGKB; PA28480; -.
DR eggNOG; NOG263746; -.
DR HOGENOM; HOG000232034; -.
DR HOVERGEN; HBG051706; -.
DR InParanoid; O95166; -.
DR KO; K08341; -.
DR OMA; TTMGQLY; -.
DR OrthoDB; EOG70KGRK; -.
DR ChiTaRS; GABARAP; human.
DR EvolutionaryTrace; O95166; -.
DR GeneWiki; GABARAP; -.
DR GenomeRNAi; 11337; -.
DR NextBio; 43075; -.
DR PMAP-CutDB; O95166; -.
DR PRO; PR:O95166; -.
DR ArrayExpress; O95166; -.
DR Bgee; O95166; -.
DR CleanEx; HS_GABARAP; -.
DR Genevestigator; O95166; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0000421; C:autophagic vacuole membrane; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0006605; P:protein targeting; TAS:ProtInc.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR004241; Atg8_like.
DR PANTHER; PTHR10969; PTHR10969; 1.
DR Pfam; PF02991; Atg8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Autophagy; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Lipoprotein;
KW Membrane; Microtubule; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 116 Gamma-aminobutyric acid receptor-
FT associated protein.
FT /FTId=PRO_0000212363.
FT PROPEP 117 117 Removed in mature form.
FT /FTId=PRO_0000423065.
FT REGION 1 22 Interaction with beta-tubulin.
FT REGION 36 117 Interaction with GPHN (By similarity).
FT REGION 36 68 Interaction with GABRG2 (Potential).
FT SITE 116 117 Cleavage; by ATG4B.
FT LIPID 116 116 Phosphatidylethanolamine amidated
FT glycine.
FT MUTAGEN 49 50 YL->AA: Inhibits interaction with TECPR2.
FT MUTAGEN 67 67 R->A: No effect on interaction with
FT TECPR2.
FT MUTAGEN 116 116 G->A: Impairs localization at the
FT autophagosomal membrane.
FT HELIX 4 8
FT HELIX 11 24
FT STRAND 28 35
FT STRAND 47 52
FT HELIX 57 68
FT STRAND 77 80
FT STRAND 87 90
FT HELIX 91 98
FT STRAND 101 103
FT STRAND 105 111
SQ SEQUENCE 117 AA; 13918 MW; BC0B84B8A51C1E32 CRC64;
MKFVYKEEHP FEKRRSEGEK IRKKYPDRVP VIVEKAPKAR IGDLDKKKYL VPSDLTVGQF
YFLIRKRIHL RAEDALFFFV NNVIPPTSAT MGQLYQEHHE EDFFLYIAYS DESVYGL
//
ID GBRAP_HUMAN Reviewed; 117 AA.
AC O95166;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-1999, sequence version 1.
DT 22-JAN-2014, entry version 113.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH
RP 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
RP 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.,
RA Koga H., Muramatsu M.-A.;
RT "Interaction of the Unc-51-like kinase and microtubule-associated
RT protein light chain 3 related proteins in the brain: possible role of
RT vesicular 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.,
RA Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J.,
RA Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M.,
RA Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal
RT axis 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,
RT GATE-16, 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
RT conjugation of hApg12p to hApg5p.";
RL J. Biol. Chem. 277:13739-13744(2002).
RN [8]
RP POST-TRANSLATIONAL MODIFICATION, INTERACTION WITH ATG3 AND ATG7, AND
RP SUBCELLULAR 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
RT Apg3.";
RL Biochem. Biophys. Res. Commun. 300:637-644(2003).
RN [9]
RP 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
RT on 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
RT 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.,
RA Pebusque M.J., 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 INTERACTION WITH TECPR2, AND MUTAGENESIS OF 49-TYR-LEU-50 AND 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 [14]
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.,
RA Buerckstuemmer T., 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 [15]
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
RT autophagosomal maturation.";
RL J. Cell Biol. 192:839-853(2011).
RN [16]
RP INTERACTION WITH MAPK15.
RX PubMed=22948227; DOI=10.4161/auto.21857;
RA Colecchia D., Strambi A., Sanzone S., Iavarone C., Rossi M.,
RA Dall'Armi C., 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 [17]
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
RT proteins through the LC3-interacting region (LIR) and promotes
RT autophagy-dependent cell death.";
RL Cell Death Differ. 19:1525-1535(2012).
RN [18]
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
RT complex: sequence requirements for LC3-interacting region (LIR)
RT motifs.";
RL J. Biol. Chem. 287:39275-39290(2012).
RN [19]
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.,
RA Lamark T., Macias M.J., Desalle R., Royo M., Sala D., Chicote J.U.,
RA Palacin M., Johansen T., Zorzano A.;
RT "DOR/Tp53inp2 and Tp53inp1 constitute a metazoan gene family encoding
RT dual regulators of autophagy and transcription.";
RL PLoS ONE 7:E34034-E34034(2012).
RN [20]
RP INTERACTION 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
RT centriolar satellites.";
RL Nature 502:254-257(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), AND INTERACTION WITH GABRG2;
RP TUBULIN ALPHA AND TUBULIN BETA.
RX PubMed=11729197; DOI=10.1074/jbc.M109753200;
RA Knight D., Harris R., McAlister M.S.B., Phelan J.P., Geddes S.,
RA Moss S.J., Driscoll P.C., Keep N.H.;
RT "The X-ray crystal structure and putative ligand-derived peptide
RT binding properties of gamma-aminobutyric acid receptor type A
RT receptor-associated protein.";
RL J. Biol. Chem. 277:5556-5561(2002).
RN [22]
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
RT GABARAP: implications for biological function and its regulation.";
RL J. Biol. Chem. 277:13363-13366(2002).
RN [23]
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 [24]
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.,
RA Wiesehan K., Willbold D.;
RT "Ligand binding mode of GABAA receptor-associated protein.";
RL J. Mol. Biol. 381:1320-1331(2008).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALR, AND
RP INTERACTION 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 --
RT implications for substrate binding to endoplasmic reticulum
RT chaperones.";
RL FEBS J. 276:1140-1152(2009).
CC -!- FUNCTION: Ubiquitin-like modifier that plays a role in
CC intracellular transport of GABA(A) receptors and its interaction
CC with the cytoskeleton. Involved in apoptosis. Involved in
CC autophagy. Whereas LC3s are involved in elongation of the
CC phagophore membrane, the GABARAP/GATE-16 subfamily is essential
CC for a later stage in autophagosome maturation.
CC -!- SUBUNIT: Interacts with GPHN and NSF (By similarity). Interacts
CC with ATG3, ATG7, ATG13, RB1CC1, GABRG2, beta-tubulin and ULK1.
CC Interacts with CALR. Interacts with DDX47. Interacts with TP53INP1
CC and TP53INP2. Interacts with TBC1D25. Directly interacts with
CC SQSTM1. Interacts with MAPK15. Interacts with TECPR2 and PCM1.
CC -!- INTERACTION:
CC Q2TAZ0:ATG2A; NbExp=2; IntAct=EBI-712001, EBI-2514077;
CC Q9NT62:ATG3; NbExp=5; IntAct=EBI-712001, EBI-988094;
CC Q9Y4P1:ATG4B; NbExp=8; IntAct=EBI-712001, EBI-712014;
CC Q9H1Y0:ATG5; NbExp=2; IntAct=EBI-712001, EBI-1047414;
CC O95352:ATG7; NbExp=8; IntAct=EBI-712001, EBI-987834;
CC Q9Z2F7:Bnip3l (xeno); NbExp=2; IntAct=EBI-712001, EBI-1774669;
CC Q9H0S4:DDX47; NbExp=3; IntAct=EBI-712001, EBI-2515241;
CC Q8WXU2:DYX1C1; NbExp=4; IntAct=EBI-712001, EBI-2946907;
CC Q96RU3:FNBP1; NbExp=2; IntAct=EBI-712001, EBI-1111248;
CC Q8TF40:FNIP1; NbExp=5; IntAct=EBI-712001, EBI-2946919;
CC Q9BQS8:FYCO1; NbExp=2; IntAct=EBI-712001, EBI-2869338;
CC O75323:GBAS; NbExp=5; IntAct=EBI-712001, EBI-307133;
CC P40939:HADHA; NbExp=5; IntAct=EBI-712001, EBI-356720;
CC O00410:IPO5; NbExp=6; IntAct=EBI-712001, EBI-356424;
CC Q86V97:KBTBD6; NbExp=3; IntAct=EBI-712001, EBI-2514778;
CC Q8WVZ9:KBTBD7; NbExp=2; IntAct=EBI-712001, EBI-473695;
CC Q14596:NBR1; NbExp=5; IntAct=EBI-712001, EBI-742698;
CC Q8NI08:NCOA7; NbExp=4; IntAct=EBI-712001, EBI-80799;
CC P46934:NEDD4; NbExp=6; IntAct=EBI-712001, EBI-726944;
CC Q8TD19:NEK9; NbExp=5; IntAct=EBI-712001, EBI-1044009;
CC Q92636:NSMAF; NbExp=2; IntAct=EBI-712001, EBI-2947053;
CC Q9NS23:RASSF1; NbExp=2; IntAct=EBI-712001, EBI-367363;
CC Q8WWW0:RASSF5; NbExp=2; IntAct=EBI-712001, EBI-367390;
CC Q13501:SQSTM1; NbExp=10; IntAct=EBI-712001, EBI-307104;
CC O95210:STBD1; NbExp=5; IntAct=EBI-712001, EBI-2947137;
CC Q13188:STK3; NbExp=2; IntAct=EBI-712001, EBI-992580;
CC Q13043:STK4; NbExp=2; IntAct=EBI-712001, EBI-367376;
CC Q8TC07:TBC1D15; NbExp=5; IntAct=EBI-712001, EBI-1048247;
CC Q9UPU7:TBC1D2B; NbExp=2; IntAct=EBI-712001, EBI-2947180;
CC O15040:TECPR2; NbExp=2; IntAct=EBI-712001, EBI-2946991;
CC Q9GZZ9:UBA5; NbExp=2; IntAct=EBI-712001, EBI-747805;
CC -!- SUBCELLULAR LOCATION: Endomembrane system (By similarity).
CC Cytoplasm, cytoskeleton (By similarity). Golgi apparatus membrane
CC (By similarity). Cytoplasmic vesicle, autophagosome. Note=Largely
CC associated with intracellular membrane structures including the
CC Golgi apparatus and postsynaptic cisternae. Colocalizes with
CC microtubules (By similarity). Localizes also to discrete punctae
CC along the ciliary axoneme (By similarity).
CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, liver, skeletal
CC muscle, kidney and pancreas.
CC -!- PTM: The precursor molecule is cleaved by ATG4B to form the
CC cytosolic form, GABARAP-I. This is activated by APG7L/ATG7,
CC transferred to ATG3 and conjugated to phospholipid to form the
CC membrane-bound form, GABARAP-II.
CC -!- SIMILARITY: Belongs to the ATG8 family.
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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 RefSeq; NP_009209.1; NM_007278.1.
DR UniGene; Hs.647421; -.
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 PDBsum; 1GNU; -.
DR PDBsum; 1KLV; -.
DR PDBsum; 1KM7; -.
DR PDBsum; 1KOT; -.
DR PDBsum; 3D32; -.
DR PDBsum; 3DOW; -.
DR ProteinModelPortal; O95166; -.
DR SMR; O95166; 1-116.
DR IntAct; O95166; 474.
DR MINT; MINT-206256; -.
DR STRING; 9606.ENSP00000306866; -.
DR TCDB; 1.A.9.5.2; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR PhosphoSite; O95166; -.
DR PaxDb; O95166; -.
DR PRIDE; O95166; -.
DR DNASU; 11337; -.
DR Ensembl; ENST00000302386; ENSP00000306866; ENSG00000170296.
DR GeneID; 11337; -.
DR KEGG; hsa:11337; -.
DR UCSC; uc002gfb.3; human.
DR CTD; 11337; -.
DR GeneCards; GC17M007143; -.
DR HGNC; HGNC:4067; GABARAP.
DR MIM; 605125; gene.
DR neXtProt; NX_O95166; -.
DR PharmGKB; PA28480; -.
DR eggNOG; NOG263746; -.
DR HOGENOM; HOG000232034; -.
DR HOVERGEN; HBG051706; -.
DR InParanoid; O95166; -.
DR KO; K08341; -.
DR OMA; TTMGQLY; -.
DR OrthoDB; EOG70KGRK; -.
DR ChiTaRS; GABARAP; human.
DR EvolutionaryTrace; O95166; -.
DR GeneWiki; GABARAP; -.
DR GenomeRNAi; 11337; -.
DR NextBio; 43075; -.
DR PMAP-CutDB; O95166; -.
DR PRO; PR:O95166; -.
DR ArrayExpress; O95166; -.
DR Bgee; O95166; -.
DR CleanEx; HS_GABARAP; -.
DR Genevestigator; O95166; -.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0000421; C:autophagic vacuole membrane; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IDA:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0006605; P:protein targeting; TAS:ProtInc.
DR GO; GO:0007268; P:synaptic transmission; TAS:ProtInc.
DR InterPro; IPR004241; Atg8_like.
DR PANTHER; PTHR10969; PTHR10969; 1.
DR Pfam; PF02991; Atg8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Autophagy; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Cytoskeleton; Golgi apparatus; Lipoprotein;
KW Membrane; Microtubule; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 116 Gamma-aminobutyric acid receptor-
FT associated protein.
FT /FTId=PRO_0000212363.
FT PROPEP 117 117 Removed in mature form.
FT /FTId=PRO_0000423065.
FT REGION 1 22 Interaction with beta-tubulin.
FT REGION 36 117 Interaction with GPHN (By similarity).
FT REGION 36 68 Interaction with GABRG2 (Potential).
FT SITE 116 117 Cleavage; by ATG4B.
FT LIPID 116 116 Phosphatidylethanolamine amidated
FT glycine.
FT MUTAGEN 49 50 YL->AA: Inhibits interaction with TECPR2.
FT MUTAGEN 67 67 R->A: No effect on interaction with
FT TECPR2.
FT MUTAGEN 116 116 G->A: Impairs localization at the
FT autophagosomal membrane.
FT HELIX 4 8
FT HELIX 11 24
FT STRAND 28 35
FT STRAND 47 52
FT HELIX 57 68
FT STRAND 77 80
FT STRAND 87 90
FT HELIX 91 98
FT STRAND 101 103
FT STRAND 105 111
SQ SEQUENCE 117 AA; 13918 MW; BC0B84B8A51C1E32 CRC64;
MKFVYKEEHP FEKRRSEGEK IRKKYPDRVP VIVEKAPKAR IGDLDKKKYL VPSDLTVGQF
YFLIRKRIHL RAEDALFFFV NNVIPPTSAT MGQLYQEHHE EDFFLYIAYS DESVYGL
//
MIM
605125
*RECORD*
*FIELD* NO
605125
*FIELD* TI
*605125 GABA-A RECEPTOR-ASSOCIATED PROTEIN; GABARAP
*FIELD* TX
CLONING
Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid)
read more(see 137160) are ligand-gated chloride channels that mediate inhibitory
neurotransmission. By performing a yeast 2-hybrid screen on a fetal
brain cDNA library using the intracellular loop of the GABA-A receptor
gamma-2S subunit (GABRG2; 137164) as bait, followed by screening an
adult brain cDNA library, Wang et al. (1999) identified a cDNA encoding
GABARAP. Sequence analysis predicted that the 117-amino acid, 13.9-kD
GABARAP protein contains a basic N terminus and an acidic C terminus,
with an overall pI of 9.6. Northern blot analysis detected a 0.9-kb
GABARAP transcript in all tissues tested, namely heart, brain, placenta,
lung, liver, skeletal muscle, kidney, and pancreas. Western blot
analysis also detected GABARAP expression in all tissues tested,
suggesting that GABARAP is also involved in biologic events other than
interaction with GABA-A receptors.
MAPPING
Komoike et al. (2010) noted that the GABARAP gene maps to chromosome
17p13.1.
GENE FUNCTION
Binding analysis by Wang et al. (1999) showed that the N-terminal 21
amino acids of GABARAP formed an alpha helix that interacted with
tubulin (see TUBA1; 191110). Immunoprecipitation and immunohistochemical
analysis in rat brain tissues demonstrated association and
colocalization of GABARAP and GABA-A receptors.
Apg8 is a ubiquitin-like protein involved in autophagy in yeast. A
cysteine protease, Apg4, cleaves Apg8 to create a C-terminal glycine
required for ubiquitin-like modification reactions. There are at least 4
mammalian Apg8 homologs: GATE16 (GABARAPL2; 607452), GABARAP, MAP1LC3
(see 601242), and APG8L (GABARAPL1; 607420). Hemelaar et al. (2003)
found that mouse Atg4b (611338) acted on the C termini of these 4 Atg8
homologs, and that the reaction required the active-site cysteine of
Atg4b. Although the amino acid sequences of these Apg8 homologs differ
from one another by as much as 71%, their affinities for Atg4b were
roughly comparable in competition experiments.
Using coimmunoprecipitation and mass spectrometric analyses, Lee et al.
(2005) identified DDX47 (615428) as a binding partner of GABARAP in
human 2774 and SKOV-3 ovarian tumor cell lysates. Yeast 2-hybrid
analysis confirmed the interaction. Overexpression of either DDX47 or
GABARAP alone had no effect on proliferation of SKOV-3 cells; however,
their coexpression inhibited cell proliferation and induced apoptosis.
Behrends et al. (2010) reported a proteomic analysis of the autophagy
interaction network (AIN) in human cells under conditions of ongoing
(basal) autophagy, revealing a network of 751 interactions among 409
candidate interacting proteins with extensive connectivity among
subnetworks. Many new AIN components have roles in vesicle trafficking,
protein or lipid phosphorylation, and protein ubiquitination, and affect
autophagosome number or flux when depleted by RNA interference. The 6
human orthologs of yeast autophagy-8 (ATG8), MAP1LC3A, MAP1LC3B
(609604), MAP1LC3C (609605), GABARAP, GABARAPL1, and GABARAPL2, interact
with a cohort of 67 proteins, with extensive binding partner overlap
between family members, and frequent involvement of a conserved surface
on ATG8 proteins known to interact with LC3-interacting regions in
partner proteins. Behrends et al. (2010) concluded that their studies
provided a global view of the mammalian autophagy interaction landscape
and a resource for mechanistic analysis of this critical protein
homeostasis pathway.
ANIMAL MODEL
Komoike et al. (2010) found that Gabarap was expressed in the
telencephalon, hindbrain, and rhombomere of zebrafish during development
and later expressed in other brain regions. Knockdown of Gabarap
resulted in dwarfism of the entire zebrafish body, as well as a severely
hypoplastic head and mandible. The findings suggested that the Gabarap
gene plays a role in brain development in zebrafish.
*FIELD* RF
1. Behrends, C.; Sowa, M. E.; Gygi, S. P.; Harper, J. W.: Network
organization of the human autophagy system. Nature 466: 68-76, 2010.
2. Hemelaar, J.; Lelyveld, V. S.; Kessler, B. M.; Ploegh, H. L.:
A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like
proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278:
51841-51850, 2003.
3. Komoike, Y.; Shimojima, K.; Liang, J.-S.; Fujii, H.; Maegaki, Y.;
Osawa, M.; Fujii, S.; Higashinakagawa, T.; Yamamoto, T.: A functional
analysis of GABARAP on 17p13.1 by knockdown zebrafish. J. Hum. Genet. 55:
155-162, 2010.
4. Lee, J. H.; Rho, S. B.; Chun, T.: GABA-A receptor-associated protein
(GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His)
box polypeptide 47 (DDX 47). Biotech. Lett. 27: 623-628, 2005.
5. Wang, H.; Bedford, F. K.; Brandon, N. J.; Moss, S. J.; Olsen, R.
W.: GABA(A)-receptor-associated protein links GABA(A) receptors and
the cytoskeleton. Nature 397: 69-72, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 09/24/2013
Ada Hamosh - updated: 9/28/2010
Cassandra L. Kniffin - updated: 4/20/2010
Ada Hamosh - updated: 8/6/2007
*FIELD* CD
Paul J. Converse: 7/11/2000
*FIELD* ED
mgross: 09/24/2013
alopez: 9/28/2010
wwang: 4/29/2010
ckniffin: 4/20/2010
carol: 12/11/2009
mgross: 8/16/2007
terry: 8/6/2007
mgross: 7/11/2000
*RECORD*
*FIELD* NO
605125
*FIELD* TI
*605125 GABA-A RECEPTOR-ASSOCIATED PROTEIN; GABARAP
*FIELD* TX
CLONING
Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid)
read more(see 137160) are ligand-gated chloride channels that mediate inhibitory
neurotransmission. By performing a yeast 2-hybrid screen on a fetal
brain cDNA library using the intracellular loop of the GABA-A receptor
gamma-2S subunit (GABRG2; 137164) as bait, followed by screening an
adult brain cDNA library, Wang et al. (1999) identified a cDNA encoding
GABARAP. Sequence analysis predicted that the 117-amino acid, 13.9-kD
GABARAP protein contains a basic N terminus and an acidic C terminus,
with an overall pI of 9.6. Northern blot analysis detected a 0.9-kb
GABARAP transcript in all tissues tested, namely heart, brain, placenta,
lung, liver, skeletal muscle, kidney, and pancreas. Western blot
analysis also detected GABARAP expression in all tissues tested,
suggesting that GABARAP is also involved in biologic events other than
interaction with GABA-A receptors.
MAPPING
Komoike et al. (2010) noted that the GABARAP gene maps to chromosome
17p13.1.
GENE FUNCTION
Binding analysis by Wang et al. (1999) showed that the N-terminal 21
amino acids of GABARAP formed an alpha helix that interacted with
tubulin (see TUBA1; 191110). Immunoprecipitation and immunohistochemical
analysis in rat brain tissues demonstrated association and
colocalization of GABARAP and GABA-A receptors.
Apg8 is a ubiquitin-like protein involved in autophagy in yeast. A
cysteine protease, Apg4, cleaves Apg8 to create a C-terminal glycine
required for ubiquitin-like modification reactions. There are at least 4
mammalian Apg8 homologs: GATE16 (GABARAPL2; 607452), GABARAP, MAP1LC3
(see 601242), and APG8L (GABARAPL1; 607420). Hemelaar et al. (2003)
found that mouse Atg4b (611338) acted on the C termini of these 4 Atg8
homologs, and that the reaction required the active-site cysteine of
Atg4b. Although the amino acid sequences of these Apg8 homologs differ
from one another by as much as 71%, their affinities for Atg4b were
roughly comparable in competition experiments.
Using coimmunoprecipitation and mass spectrometric analyses, Lee et al.
(2005) identified DDX47 (615428) as a binding partner of GABARAP in
human 2774 and SKOV-3 ovarian tumor cell lysates. Yeast 2-hybrid
analysis confirmed the interaction. Overexpression of either DDX47 or
GABARAP alone had no effect on proliferation of SKOV-3 cells; however,
their coexpression inhibited cell proliferation and induced apoptosis.
Behrends et al. (2010) reported a proteomic analysis of the autophagy
interaction network (AIN) in human cells under conditions of ongoing
(basal) autophagy, revealing a network of 751 interactions among 409
candidate interacting proteins with extensive connectivity among
subnetworks. Many new AIN components have roles in vesicle trafficking,
protein or lipid phosphorylation, and protein ubiquitination, and affect
autophagosome number or flux when depleted by RNA interference. The 6
human orthologs of yeast autophagy-8 (ATG8), MAP1LC3A, MAP1LC3B
(609604), MAP1LC3C (609605), GABARAP, GABARAPL1, and GABARAPL2, interact
with a cohort of 67 proteins, with extensive binding partner overlap
between family members, and frequent involvement of a conserved surface
on ATG8 proteins known to interact with LC3-interacting regions in
partner proteins. Behrends et al. (2010) concluded that their studies
provided a global view of the mammalian autophagy interaction landscape
and a resource for mechanistic analysis of this critical protein
homeostasis pathway.
ANIMAL MODEL
Komoike et al. (2010) found that Gabarap was expressed in the
telencephalon, hindbrain, and rhombomere of zebrafish during development
and later expressed in other brain regions. Knockdown of Gabarap
resulted in dwarfism of the entire zebrafish body, as well as a severely
hypoplastic head and mandible. The findings suggested that the Gabarap
gene plays a role in brain development in zebrafish.
*FIELD* RF
1. Behrends, C.; Sowa, M. E.; Gygi, S. P.; Harper, J. W.: Network
organization of the human autophagy system. Nature 466: 68-76, 2010.
2. Hemelaar, J.; Lelyveld, V. S.; Kessler, B. M.; Ploegh, H. L.:
A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like
proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278:
51841-51850, 2003.
3. Komoike, Y.; Shimojima, K.; Liang, J.-S.; Fujii, H.; Maegaki, Y.;
Osawa, M.; Fujii, S.; Higashinakagawa, T.; Yamamoto, T.: A functional
analysis of GABARAP on 17p13.1 by knockdown zebrafish. J. Hum. Genet. 55:
155-162, 2010.
4. Lee, J. H.; Rho, S. B.; Chun, T.: GABA-A receptor-associated protein
(GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His)
box polypeptide 47 (DDX 47). Biotech. Lett. 27: 623-628, 2005.
5. Wang, H.; Bedford, F. K.; Brandon, N. J.; Moss, S. J.; Olsen, R.
W.: GABA(A)-receptor-associated protein links GABA(A) receptors and
the cytoskeleton. Nature 397: 69-72, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 09/24/2013
Ada Hamosh - updated: 9/28/2010
Cassandra L. Kniffin - updated: 4/20/2010
Ada Hamosh - updated: 8/6/2007
*FIELD* CD
Paul J. Converse: 7/11/2000
*FIELD* ED
mgross: 09/24/2013
alopez: 9/28/2010
wwang: 4/29/2010
ckniffin: 4/20/2010
carol: 12/11/2009
mgross: 8/16/2007
terry: 8/6/2007
mgross: 7/11/2000