GABARAP
GABARAP (GABA type A receptor-associated protein, also known as MM46 and ATG8A) is a ubiquitin-like modifier of the ATG8 family. It links GABA(A) receptor transport to the cytoskeleton and acts at a late stage of autophagosome maturation. Browse Assay Genie's current range of GABARAP research reagents below, or read on for the biology behind the target.
GABARAP is a ubiquitin-like modifier with roles in intracellular transport of GABA(A) receptors and in their interaction with the cytoskeleton. GABA(A) receptors are ligand-gated chloride channels that mediate inhibitory neurotransmission, and GABARAP clusters neurotransmitter receptors by mediating interaction with the cytoskeleton. In autophagy, LC3 proteins are involved in elongation of the phagophore membrane, whereas the GABARAP/GATE-16 subfamily is essential for a later stage of autophagosome maturation.
GABARAP also acts through selective receptors and adaptors. Through its interaction with the reticulophagy receptor TEX264, it participates in remodelling subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for ER turnover. Interaction with UBAC2 promotes recruitment of UBAC2-associated ER fragments to autophagosomes. Beyond autophagy, GABARAP regulates lysosome biogenesis: by binding FNIP1 (or FNIP2) it sequesters the FLCN-FNIP complex and prevents non-canonical mTORC1 signalling, leading to activation of the transcription factors TFEB and TFE3.
GABARAP is also required for local activation of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, which drives ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor that activates RAC1. Through this route it influences cytoskeleton organisation, cell migration and proliferation, and it is also involved in apoptosis. The GABARAP gene encodes a protein whose N-terminus is highly positively charged and which shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. It was named for its association with GABA(A) receptors and is a member of the ATG8 family.
GABARAP acts at a later stage of autophagosome maturation than the LC3 proteins, making it a useful subject for dissecting autophagosome biogenesis.
Interactions with TEX264 and UBAC2 place GABARAP in the delivery of endoplasmic reticulum fragments to autophagosomes and lysosomal turnover.
By sequestering the FLCN-FNIP complex, GABARAP influences non-canonical mTORC1 signalling and the activation of TFEB and TFE3.
GABARAP supports intracellular transport and cytoskeletal clustering of GABA(A) receptors, which mediate inhibitory neurotransmission.
GABARAP is a ubiquitin-like modifier involved in GABA(A) receptor transport and cytoskeletal interaction. It is essential for a later stage of autophagosome maturation, takes part in ER-phagy, regulates lysosome biogenesis via FNIP1/FNIP2, and supports CUL3(KBTBD6/7)-mediated degradation of TIAM1.
GABARAP stands for GABA type A receptor-associated protein. Its HGNC aliases and previous symbols are MM46 and ATG8A, and a previous name is GABA(A) receptor-associated protein. UniProt lists it as gamma-aminobutyric acid receptor-associated protein, and it belongs to the ATG8 family.
Mouse and rat both have a Gabarap ortholog. The human protein belongs to the ATG8 family and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. Check the datasheet of any product for its validated reactivity.
Other ATG8 family members and autophagy-related targets with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt O95166; product specifications from Assay Genie datasheets.