GABARAP

Last updated
GABARAP
Protein GABARAP PDB 1gnu.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GABARAP , ATG8A, GABARAP-a, MM46, GABA type A receptor-associated protein
External IDs OMIM: 605125 MGI: 1861742 HomoloGene: 134119 GeneCards: GABARAP
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 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]

Contents

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]

Related Research Articles

γ-Aminobutyric acid Main inhibitory neurotransmitter in the mammalian brain

γ-Aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

<span class="mw-page-title-main">GABA receptor</span> Receptors that respond to gamma-aminobutyric acid

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels ; whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.

GABA<sub>A</sub> receptor Ionotropic receptor and ligand-gated ion channel

The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl) and, to a lesser extent, bicarbonate ions (HCO3). Depending on the membrane potential and the ionic concentration difference, this can result in ionic fluxes across the pore. If the membrane potential is higher than the equilibrium potential (also known as the reversal potential) for chloride ions, when the receptor is activated Cl will flow into the cell. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring at the postsynaptic cell. The reversal potential of the GABAA-mediated inhibitory postsynaptic potential (IPSP) in normal solution is −70 mV, contrasting the GABAB IPSP (-100 mV).

<span class="mw-page-title-main">Gephyrin</span> Type of protein

Gephyrin is a protein that in humans is encoded by the GPHN gene.

<span class="mw-page-title-main">GABBR1</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid B receptor, 1 (GABAB1), is a G-protein coupled receptor subunit encoded by the GABBR1 gene.

<span class="mw-page-title-main">Gamma-aminobutyric acid receptor subunit gamma-2</span>

Gamma-aminobutyric acid receptor subunit gamma-2 is a protein that in humans is encoded by the GABRG2 gene.

<span class="mw-page-title-main">Gamma-aminobutyric acid receptor subunit alpha-1</span>

Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.

<span class="mw-page-title-main">GABRB3</span>

Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.

<span class="mw-page-title-main">GABBR2</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid (GABA) B receptor, 2 (GABAB2) is a G-protein coupled receptor subunit encoded by the GABBR2 gene in humans.

<span class="mw-page-title-main">GABRB1</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor subunit beta-1 is a protein that in humans is encoded by the GABRB1 gene.

<span class="mw-page-title-main">MAP1LC3B</span>

Microtubule-associated proteins 1A/1B light chain 3B is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.

<span class="mw-page-title-main">GABRR1</span>

Gamma-aminobutyric acid receptor subunit rho-1 is a protein that in humans is encoded by the GABRR1 gene.

<span class="mw-page-title-main">ATG4B</span>

Cysteine protease ATG4B is an enzyme that in humans is encoded by the ATG4B gene.

<span class="mw-page-title-main">GABARAPL2</span>

Gamma-aminobutyric acid receptor-associated protein-like 2 is a protein that in humans is encoded by the GABARAPL2 gene.

<span class="mw-page-title-main">ATG12</span> Protein-coding gene in the species Homo sapiens

Autophagy related 12 is a protein that in humans is encoded by the ATG12 gene.

<span class="mw-page-title-main">GABRA5</span>

Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.

<span class="mw-page-title-main">ATG7</span> Protein-coding gene in the species Homo sapiens

Autophagy related 7 is a protein in humans encoded by ATG7 gene. Related to GSA7; APG7L; APG7-LIKE.

<span class="mw-page-title-main">GABRG3</span>

GABAA receptor-γ3, also known as GABRG3, is a protein which in humans is encoded by the GABRG3 gene.

<span class="mw-page-title-main">GABRG1</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid receptor subunit gamma-1 is a protein that in humans is encoded by the GABRG1 gene. The protein encoded by this gene is a subunit of the GABAA receptor.

<span class="mw-page-title-main">ATG8</span>

Autophagy-related protein 8 (Atg8) is a ubiquitin-like protein required for the formation of autophagosomal membranes. The transient conjugation of Atg8 to the autophagosomal membrane through a ubiquitin-like conjugation system is essential for autophagy in eukaryotes. Even though there are homologues in animals, this article mainly focuses on its role in lower eukaryotes such as Saccharomyces cerevisiae.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000170296 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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