Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.[5]

GABARAP
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGABARAP, ATG8A, GABARAP-a, MM46, GABA type A receptor-associated protein
External IDsOMIM: 605125; MGI: 1861742; HomoloGene: 134119; GeneCards: GABARAP; OMA:GABARAP - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_007278

NM_019749

RefSeq (protein)

NP_009209

NP_062723

Location (UCSC)Chr 17: 7.24 – 7.24 MbChr 11: 69.88 – 69.89 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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

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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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000170296Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000018567Ensembl, 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. ^ a b 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

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