Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAPgene.[5]
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.[6]
Moreover, GABARAP has an 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.[7] In addition, GABARAP can mediate 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,[8]ULK1[9][10] and GABRG2.[5][11][12] A bound structure for GABARAP to GABRG2 consistent with experimental observations has been computationally derived.[13]
^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. PMID25684710.
^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 (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC1847948. PMID17353931.
^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. PMID11146101.
^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. PMID11948245. S2CID38049055.
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. PMID11146101.
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. PMID11414770.
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. PMID11461150. S2CID43244403.
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. PMID11727985. S2CID31757286.
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. PMID11727986. S2CID82224217.
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. PMID11885988. S2CID82980835.
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. PMID11890701.
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. PMID11948245. S2CID38049055.
PDB gallery
1gnu: GABA(A) RECEPTOR ASSOCIATED PROTEIN GABARAP
1kjt: Crystal Structure of the GABA(A) Receptor Associated Protein, GABARAP
1klv: Solution Structure and Backbone Dynamics of GABARAP, GABAA Receptor associated protein
1km7: Solution Structure and Backbone Dynamics of GABARAP, GABAA Receptor Associated Protein
1kot: Solution Structure of Human GABA Receptor Associated Protein GABARAP
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