GABARAP

GABARAP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GNU, 1KLV, 1KM7, 1KOT, 3D32, 3DOW, 3WIM, 4XC2
Identifiers
Aliases	GABARAP , ATG8A, GABARAP-a, MM46, GABA type A receptor-associated protein
External IDs	OMIM: 605125; MGI: 1861742; HomoloGene: 134119; GeneCards: GABARAP; OMA:GABARAP - orthologs
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17p13.1 Start 7,240,008 bp [1] End 7,242,449 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11 B3|11 42.95 cM Start 69,881,969 bp [2] End 69,885,777 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right testis left testis pituitary gland anterior pituitary monocyte right adrenal gland blood right adrenal cortex left adrenal cortex C1 segment Top expressed in molar calvaria granulocyte parotid gland seminal vesicula optic nerve spermatid atrium blood efferent ductule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function microtubule binding protein binding beta-tubulin binding ubiquitin protein ligase binding GABA receptor binding Cellular component cytoplasm cell body Golgi apparatus membrane Golgi membrane plasma membrane microtubule associated complex smooth endoplasmic reticulum autophagosome autophagosome membrane actin cytoskeleton perinuclear region of cytoplasm axoneme lysosome sperm midpiece cytoskeleton microtubule cytoplasmic vesicle endomembrane system cytosol Biological process chemical synaptic transmission protein targeting autophagy protein transport macroautophagy microtubule cytoskeleton organization extrinsic apoptotic signaling pathway via death domain receptors apoptotic process autophagosome maturation autophagosome assembly autophagy of mitochondrion cellular response to nitrogen starvation Sources:Amigo / QuickGO
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: 69.88 – 69.89 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

References

1. GRCh38: Ensembl release 89: ENSG00000170296 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000018567 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. S2CID   204990449.
6. "Entrez Gene: GABARAP GABA(A) receptor-associated protein".
7. 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.
8. Green F, O'Hare T, Blackwell A, Enns CA (May 2002). "Association of human transferrin receptor with GABARAP" (PDF). FEBS Letters. 518 (1–3): 101–106. doi: 10.1016/S0014-5793(02)02655-8 . PMID   11997026. S2CID   29391940.
9. 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. PMC   1847948 . PMID   17353931.
10. 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.
11. 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. S2CID   38049055.
12. 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. S2CID   14487823.
13. Irwin BW, Vukovic S, Payne MC, ElGamacy M, Chau PL (Dec 2018). "Prediction of GABARAP interaction with the GABA type A receptor". Proteins. 86 (12): 1251–1264. doi:10.1002/prot.25589. PMC   6492159 . PMID   30218455.

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. S2CID   86634862.
• 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. Bibcode:2000PNAS...97.8594K. 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. Bibcode:2000PNAS...97.9543H. 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. Bibcode:2000PNAS...9711557C. 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. S2CID   43244403.
• 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. S2CID   31757286.
• 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. S2CID   82224217.
• 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. S2CID   14487823.
• 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 biological function 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. S2CID   82980835.
• 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. S2CID   38049055.