GBRAP_MOUSE
ID GBRAP_MOUSE Reviewed; 117 AA.
AC Q9DCD6; B1AR49; Q9QUI7;
DT 01-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Gamma-aminobutyric acid receptor-associated protein;
DE AltName: Full=GABA(A) receptor-associated protein;
DE Flags: Precursor;
GN Name=Gabarap;
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], SUBCELLULAR LOCATION, AND INTERACTION WITH
RP BETA-TUBULIN.
RX PubMed=10899939; DOI=10.1046/j.1471-4159.2000.0750644.x;
RA Wang H., Olsen R.W.;
RT "Binding of the GABA(A) receptor-associated protein (GABARAP) to
RT microtubules and microfilaments suggests involvement of the cytoskeleton in
RT GABARAPGABA(A) receptor interaction.";
RL J. Neurochem. 75:644-655(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, 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 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver, and 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 [5]
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 [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 INTERACTION WITH GPHN.
RX PubMed=10900017; DOI=10.1073/pnas.97.15.8594;
RA Kneussel M., Haverkamp S., Fuhrmann J.C., Wang H., Waessle H., Olsen R.W.,
RA Betz H.;
RT "The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein
RT GABARAP interacts with gephyrin but is not involved in receptor anchoring
RT at the synapse.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8594-8599(2000).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Pancreas, 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 [9]
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 [10]
RP SUBCELLULAR LOCATION.
RX PubMed=24089209; DOI=10.1038/nature12639;
RA Pampliega O., Orhon I., Patel B., Sridhar S., Diaz-Carretero A., Beau I.,
RA Codogno P., Satir B.H., Satir P., Cuervo A.M.;
RT "Functional interaction between autophagy and ciliogenesis.";
RL Nature 502:194-200(2013).
RN [11]
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 that plays a role in intracellular
CC transport of GABA(A) receptors and its interaction with the
CC cytoskeleton. Involved in autophagy: 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. Also required for the local activation
CC of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating
CC ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange
CC factor (GEF) that activates RAC1 and downstream signal transduction.
CC Thereby, regulates different biological processes including the
CC organization of the cytoskeleton, cell migration and proliferation.
CC Involved in apoptosis. {ECO:0000250|UniProtKB:O95166}.
CC -!- SUBUNIT: Interacts with GPHN (PubMed:10900017). Interacts with NSF (By
CC similarity). Interacts with ATG7 (PubMed:11890701). Interacts with ATG3
CC and ATG13 (By similarity). Interacts with alpha-tubulin (By
CC similarity). Interacts with beta-tubulin (PubMed:10899939). Interacts
CC with GABRG2 (By similarity). Interacts with RB1CC1 (By similarity).
CC Interacts with ULK1 (By similarity). Interacts with CALR (By
CC similarity). Interacts with DDX47 (By similarity). Interacts with
CC TP53INP1 and TP53INP2 (By similarity). Interacts with TBC1D5 (By
CC similarity). Interacts with TBC1D25 (PubMed:21383079). Directly
CC interacts with SQSTM1 (By similarity). Interacts with MAPK15 (By
CC similarity). Interacts with TECPR2 (By similarity). Interacts with PCM1
CC (By similarity). Interacts with TRIM5 and TRIM21 (By similarity).
CC Interacts with MEFV (By similarity). Interacts with KIF21B (By
CC similarity). Interacts with WDFY3; this interaction is required for
CC WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies (By
CC similarity). Interacts with FLCN; interaction regulates autophagy (By
CC similarity). Interacts with UBA5 (By similarity). Interacts with KBTBD6
CC and KBTBD7; the interaction is direct and required for the
CC ubiquitination of TIAM1 (By similarity). {ECO:0000250|UniProtKB:O95166,
CC ECO:0000250|UniProtKB:P60517, ECO:0000269|PubMed:10899939,
CC ECO:0000269|PubMed:10900017, ECO:0000269|PubMed:11890701,
CC ECO:0000269|PubMed:21383079}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000269|PubMed:14530254}. Endomembrane system
CC {ECO:0000250|UniProtKB:P60517}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:10899939}. 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
CC (PubMed:10899939). Localizes also to discrete punctae along the ciliary
CC axoneme (PubMed:24089209). {ECO:0000269|PubMed:10899939,
CC ECO:0000269|PubMed:14530254, ECO:0000269|PubMed:24089209}.
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:14530254). The processed form is then activated
CC by APG7L/ATG7, transferred to ATG3 and conjugated to
CC phosphatidylethanolamine (PE) phospholipid to form the membrane-bound
CC form, GABARAP-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:O95166, ECO:0000269|PubMed:14530254,
CC ECO:0000269|PubMed:33795848}.
CC -!- SIMILARITY: Belongs to the ATG8 family. {ECO:0000305}.
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DR EMBL; AF161587; AAD47642.1; -; mRNA.
DR EMBL; AK002879; BAB22426.1; -; mRNA.
DR EMBL; AK011731; BAB27806.1; -; mRNA.
DR EMBL; AL596185; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002126; AAH02126.1; -; mRNA.
DR EMBL; BC024621; AAH24621.1; -; mRNA.
DR EMBL; BC030350; AAH30350.1; -; mRNA.
DR CCDS; CCDS24928.1; -.
DR RefSeq; NP_062723.1; NM_019749.4.
DR PDB; 5YIR; X-ray; 2.75 A; A/B/D=1-117.
DR PDB; 6A9X; X-ray; 2.20 A; D=1-117.
DR PDB; 7FB5; X-ray; 2.84 A; A=1-117.
DR PDBsum; 5YIR; -.
DR PDBsum; 6A9X; -.
DR PDBsum; 7FB5; -.
DR AlphaFoldDB; Q9DCD6; -.
DR BMRB; Q9DCD6; -.
DR SMR; Q9DCD6; -.
DR BioGRID; 208012; 17.
DR ELM; Q9DCD6; -.
DR IntAct; Q9DCD6; 2.
DR MINT; Q9DCD6; -.
DR STRING; 10090.ENSMUSP00000018711; -.
DR iPTMnet; Q9DCD6; -.
DR PhosphoSitePlus; Q9DCD6; -.
DR EPD; Q9DCD6; -.
DR MaxQB; Q9DCD6; -.
DR PaxDb; Q9DCD6; -.
DR PeptideAtlas; Q9DCD6; -.
DR PRIDE; Q9DCD6; -.
DR ProteomicsDB; 266780; -.
DR Antibodypedia; 11841; 712 antibodies from 37 providers.
DR DNASU; 56486; -.
DR Ensembl; ENSMUST00000018711; ENSMUSP00000018711; ENSMUSG00000018567.
DR GeneID; 56486; -.
DR KEGG; mmu:56486; -.
DR UCSC; uc007jtg.2; mouse.
DR CTD; 11337; -.
DR MGI; MGI:1861742; Gabarap.
DR VEuPathDB; HostDB:ENSMUSG00000018567; -.
DR eggNOG; KOG1654; Eukaryota.
DR GeneTree; ENSGT00940000157496; -.
DR HOGENOM; CLU_119276_0_0_1; -.
DR InParanoid; Q9DCD6; -.
DR OMA; AVYQEHK; -.
DR OrthoDB; 1508198at2759; -.
DR PhylomeDB; Q9DCD6; -.
DR TreeFam; TF314556; -.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-8854214; TBC/RABGAPs.
DR BioGRID-ORCS; 56486; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Gabarap; mouse.
DR PRO; PR:Q9DCD6; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9DCD6; protein.
DR Bgee; ENSMUSG00000018567; Expressed in molar tooth and 268 other tissues.
DR ExpressionAtlas; Q9DCD6; baseline and differential.
DR Genevisible; Q9DCD6; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:MGI.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0000421; C:autophagosome membrane; ISO:MGI.
DR GO; GO:0005930; C:axoneme; IDA:UniProtKB.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0005875; C:microtubule associated complex; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:MGI.
DR GO; GO:0097225; C:sperm midpiece; IDA:MGI.
DR GO; GO:0048487; F:beta-tubulin binding; ISO:MGI.
DR GO; GO:0050811; F:GABA receptor binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; 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:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IDA:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:1902524; P:positive regulation of protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; ISO:MGI.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; ISS: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_0000212364"
FT PROPEP 117
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:14530254"
FT /id="PRO_0000423066"
FT REGION 1..22
FT /note="Interaction with beta-tubulin"
FT /evidence="ECO:0000269|PubMed:10899939"
FT REGION 36..117
FT /note="Interaction with GPHN"
FT /evidence="ECO:0000269|PubMed:10900017"
FT REGION 36..68
FT /note="Interaction with GABRG2"
FT /evidence="ECO:0000250|UniProtKB:O95166"
FT SITE 116..117
FT /note="Cleavage; by ATG4B"
FT /evidence="ECO:0000269|PubMed:14530254"
FT LIPID 116
FT /note="Phosphatidylethanolamine amidated glycine;
FT alternate"
FT /evidence="ECO:0000250|UniProtKB:O95166"
FT LIPID 116
FT /note="Phosphatidylserine amidated glycine; alternate"
FT /evidence="ECO:0000250|UniProtKB:O95166"
FT CONFLICT 12
FT /note="E -> D (in Ref. 2; BAB22426)"
FT /evidence="ECO:0000305"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:6A9X"
FT HELIX 11..24
FT /evidence="ECO:0007829|PDB:6A9X"
FT STRAND 28..35
FT /evidence="ECO:0007829|PDB:6A9X"
FT STRAND 47..52
FT /evidence="ECO:0007829|PDB:6A9X"
FT HELIX 57..68
FT /evidence="ECO:0007829|PDB:6A9X"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:6A9X"
FT HELIX 91..98
FT /evidence="ECO:0007829|PDB:6A9X"
FT STRAND 105..114
FT /evidence="ECO:0007829|PDB:6A9X"
SQ SEQUENCE 117 AA; 13918 MW; BC0B84B8A51C1E32 CRC64;
MKFVYKEEHP FEKRRSEGEK IRKKYPDRVP VIVEKAPKAR IGDLDKKKYL VPSDLTVGQF
YFLIRKRIHL RAEDALFFFV NNVIPPTSAT MGQLYQEHHE EDFFLYIAYS DESVYGL
