GABARAP

GABA(A) receptor-associated protein
PDB rendering based on 1gnu.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1GNU​, 1KLV​, 1KM7​, 1KOT​, 3D32​, 3DOW​, 3WIM​, 4XC2​
Identifiers
Symbols	GABARAP ; ATG8A; GABARAP-a; MM46
External IDs	OMIM: 605125 MGI: 1861742 HomoloGene: 134119 GeneCards: GABARAP Gene
Gene ontology Molecular function • protein binding • microtubule binding • ubiquitin protein ligase binding • beta-tubulin binding • GABA receptor binding Cellular component • Golgi membrane • pre-autophagosomal structure • autophagosome membrane • lysosome • autophagosome • smooth endoplasmic reticulum • cytosol • microtubule • microtubule associated complex • plasma membrane • axoneme • actin cytoskeleton • extrinsic component of membrane • cytoplasmic vesicle • cell body • perinuclear region of cytoplasm Biological process • autophagosome assembly • microtubule cytoskeleton organization • mitophagy • protein targeting • synaptic transmission • extrinsic apoptotic signaling pathway via death domain receptors • nucleophagy • membrane fusion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	11337	56486
Ensembl	ENSG00000170296	ENSMUSG00000018567
UniProt	O95166	Q9DCD6
RefSeq (mRNA)	NM_007278	NM_019749
RefSeq (protein)	NP_009209	NP_062723
Location (UCSC)	Chr 17: 7.24 – 7.24 Mb	Chr 11: 69.99 – 69.99 Mb
PubMed search

Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.^[1]

Function

Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton.^[2]

Moreover, GABARAP has a important function in autophagosome mediated autophagy, since it is crucial for autophagosome formation and sequestration of cytosolic cargo into double-membrane vesicles, leading to subsequent degradation after fusion with lysosomes.^[3] In addition, GABARAP can mediated selective autophagy because it binds to so-called autophagic receptors (e.g. p62, NBr1), which bind and recruit specific cargo.

Interactions

GABARAP has been shown to interact with TFRC,^[4] ULK1^[5][6] and GABRG2.^[1][7][8]

References

1. Wang H, Bedford FK, Brandon NJ, Moss SJ, Olsen RW (Jan 1999). "GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton". Nature 397 (6714): 69–72. doi:10.1038/16264. PMID 9892355.
2. "Entrez Gene: GABARAP GABA(A) receptor-associated protein".
3. Szalai P, Hagen LK, Sætre F, Luhr M, Sponheim M, Øverbye A, Mills IG, Seglen PO, Engedal N (2015). "Autophagic bulk sequestration of cytosolic cargo is independent of LC3, but requires GABARAPs". Experimental Cell Research 333 (1): 21–38. doi:10.1016/j.yexcr.2015.02.003. PMID 25684710.
4. Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP". FEBS Letters 518 (1-3): 101–106. doi:10.1016/S0014-5793(02)02655-8. PMID 11997026.
5. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
6. Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M (Dec 2000). "Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation". Brain Research. Molecular Brain Research 85 (1-2): 1–12. doi:10.1016/S0169-328X(00)00218-7. PMID 11146101.
7. Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (Mar 2002). "Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors". Journal of Neurochemistry 80 (5): 815–823. doi:10.1046/j.0022-3042.2002.00762.x. PMID 11948245.
8. Coyle JE, Qamar S, Rajashankar KR, Nikolov DB (Jan 2002). "Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding". Neuron 33 (1): 63–74. doi:10.1016/S0896-6273(01)00558-X. PMID 11779480.

Further reading

• Kanematsu T, Hirata M (Apr 2002). "[The analysis of protein-protein interaction with special reference to PRIP-1]". Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica 119 (4): 241–6. doi:10.1254/fpj.119.241. PMID 11979730.
• Paz Y, Elazar Z, Fass D (Aug 2000). "Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p". The Journal of Biological Chemistry 275 (33): 25445–25450. doi:10.1074/jbc.C000307200. PMID 10856287.
• Wang H, Olsen RW (Aug 2000). "Binding of the GABA(A) receptor-associated protein (GABARAP) to microtubules and microfilaments suggests involvement of the cytoskeleton in GABARAPGABA(A) receptor interaction". Journal of Neurochemistry 75 (2): 644–655. doi:10.1046/j.1471-4159.2000.0750644.x. PMID 10899939.
• Kneussel M, Haverkamp S, Fuhrmann JC, Wang H, Wässle H, Olsen RW, Betz H (Jul 2000). "The gamma-aminobutyric acid type A receptor (GABAAR)-associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse". Proceedings of the National Academy of Sciences of the United States of America 97 (15): 8594–8599. doi:10.1073/pnas.97.15.8594. PMC 26993. PMID 10900017.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (Aug 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America 97 (17): 9543–9548. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
• Chen L, Wang H, Vicini S, Olsen RW (Oct 2000). "The gamma-aminobutyric acid type A (GABAA) receptor-associated protein (GABARAP) promotes GABAA receptor clustering and modulates the channel kinetics". Proceedings of the National Academy of Sciences of the United States of America 97 (21): 11557–11562. doi:10.1073/pnas.190133497. PMC 17239. PMID 10984509.
• Zhang QH, Ye M, Wu XY, Ren SX, Zhao M, Zhao CJ, Fu G, Shen Y, Fan HY, Lu G, Zhong M, Xu XR, Han ZG, Zhang JW, Tao J, Huang QH, Zhou J, Hu GX, Gu J, Chen SJ, Chen Z (Oct 2000). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Research 10 (10): 1546–1560. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
• Okazaki N, Yan J, Yuasa S, Ueno T, Kominami E, Masuho Y, Koga H, Muramatsu M (Dec 2000). "Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation". Brain Research. Molecular Brain Research 85 (1-2): 1–12. doi:10.1016/S0169-328X(00)00218-7. PMID 11146101.
• Xin Y, Yu L, Chen Z, Zheng L, Fu Q, Jiang J, Zhang P, Gong R, Zhao S (Jun 2001). "Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA(A) receptor-associated protein". Genomics 74 (3): 408–413. doi:10.1006/geno.2001.6555. PMID 11414770.
• Kittler JT, Rostaing P, Schiavo G, Fritschy JM, Olsen R, Triller A, Moss SJ (Jul 2001). "The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABA(A) receptors". Molecular and Cellular Neurosciences 18 (1): 13–25. doi:10.1006/mcne.2001.1005. PMID 11461150.
• Stangler T, Mayr LM, Dingley AJ, Luge C, Willbold D (Oct 2001). "Sequence-specific 1H, 13C and 15N resonance assignments of human GABA receptor associated protein". Journal of Biomolecular NMR 21 (2): 183–4. doi:10.1023/A:1012416810974. PMID 11727985.
• Harris R, McAlister MS, Sankar A, Phelan JP, Moss SJ, Keep NH, Driscoll PC (Oct 2001). "Backbone 1H, 13C, and 15N resonance assignments for a 14 kD protein, GABA(A) receptor associated protein (GABARAP)". Journal of Biomolecular NMR 21 (2): 185–6. doi:10.1023/A:1012473609468. PMID 11727986.
• Knight D, Harris R, McAlister MS, Phelan JP, Geddes S, Moss SJ, Driscoll PC, Keep NH (Feb 2002). "The X-ray crystal structure and putative ligand-derived peptide binding properties of gamma-aminobutyric acid receptor type A receptor-associated protein". The Journal of Biological Chemistry 277 (7): 5556–5561. doi:10.1074/jbc.M109753200. PMID 11729197.
• Coyle JE, Qamar S, Rajashankar KR, Nikolov DB (Jan 2002). "Structure of GABARAP in two conformations: implications for GABA(A) receptor localization and tubulin binding". Neuron 33 (1): 63–74. doi:10.1016/S0896-6273(01)00558-X. PMID 11779480.
• Tanida I, Tanida-Miyake E, Komatsu M, Ueno T, Kominami E (Apr 2002). "Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation of hApg12p to hApg5p". The Journal of Biological Chemistry 277 (16): 13739–13744. doi:10.1074/jbc.M200385200. PMID 11825910.
• Stangler T, Mayr LM, Willbold D (Apr 2002). "Solution structure of human GABA(A) receptor-associated protein GABARAP: implications for biolgoical funcrion and its regulation". The Journal of Biological Chemistry 277 (16): 13363–13366. doi:10.1074/jbc.C200050200. PMID 11875056.
• Kouno T, Miura K, Kanematsu T, Shirakawa M, Hirata M, Kawano K (Jan 2002). "1H, 13C and '5N resonance assignments of GABARAP, GABAA receptor associated protein". Journal of Biomolecular NMR 22 (1): 97–98. doi:10.1023/A:1013884402033. PMID 11885988.
• Tanida I, Tanida-Miyake E, Nishitani T, Komatsu M, Yamazaki H, Ueno T, Kominami E (Mar 2002). "Murine Apg12p has a substrate preference for murine Apg7p over three Apg8p homologs". Biochemical and Biophysical Research Communications 292 (1): 256–262. doi:10.1006/bbrc.2002.6645. PMID 11890701.
• Nymann-Andersen J, Wang H, Chen L, Kittler JT, Moss SJ, Olsen RW (Mar 2002). "Subunit specificity and interaction domain between GABA(A) receptor-associated protein (GABARAP) and GABA(A) receptors". Journal of Neurochemistry 80 (5): 815–823. doi:10.1046/j.0022-3042.2002.00762.x. PMID 11948245.