Alternative titles; symbols
HGNC Approved Gene Symbol: GABARAPL2
Cytogenetic location: 16q23.1 Genomic coordinates (GRCh38) : 16:75,566,379-75,577,881 (from NCBI)
By database searching for sequences showing homology to GABARAP (605125), Xin et al. (2001) identified GABARAPL2. The deduced protein contains 117 amino acids and has a calculated molecular mass of 13.7 kD. Like GABARAP, it contains a basic N-terminal tubulin binding domain and a GABA-A receptor binding domain. GABARAPL2 shares 57% identity with GABARAP and 100% amino acid sequence identity with bovine brain GATE16 (Golgi-associated ATPase enhancer of 16 kD), rat Gabarapl2, and mouse Gabarapl2. Northern blot analysis revealed ubiquitous expression of a 1.35-kb transcript with high levels in heart, brain, testis, prostate, ovary, spleen, and skeletal muscle, and low levels in lung, thymus, and small intestine. Xin et al. (2001) also cloned the mouse Gabarapl2 gene from a mouse brain cDNA library.
Sagiv et al. (2000) cloned and characterized bovine brain GABARAPL2, which they called GATE16. GABARAPL2 had activity as a soluble transport factor, it interacted with N-ethylmaleimide-sensitive factor (NSF; 601633) and stimulated its ATPase activity, and interacted with the Golgi v-SNARE (GOS28; 604026) in an NSF-dependent manner. Sagiv et al. (2000) proposed that GABARAPL2 modulates intra-Golgi transport by coupling NSF activity and SNARE activation.
Apg8 is a ubiquitin-like protein involved in autophagy in yeast. A cysteine protease, Apg4, cleaves Apg8 to create a C-terminal glycine required for ubiquitin-like modification reactions. There are at least 4 mammalian Apg8 homologs: GATE16, GABARAP, MAP1LC3 (see 601242), and APG8L (GABARAPL1; 607420). Hemelaar et al. (2003) found that mouse Atg4b (611338) acted on the C termini of these 4 Atg8 homologs, and that the reaction required the active-site cysteine of Atg4b. Although the amino acid sequences of these Apg8 homologs differ from one another by as much as 71%, their affinities for Atg4b were roughly comparable in competition experiments.
Behrends et al. (2010) reported a proteomic analysis of the autophagy interaction network (AIN) in human cells under conditions of ongoing (basal) autophagy, revealing a network of 751 interactions among 409 candidate interacting proteins with extensive connectivity among subnetworks. Many new AIN components have roles in vesicle trafficking, protein or lipid phosphorylation, and protein ubiquitination, and affect autophagosome number or flux when depleted by RNA interference. The 6 human orthologs of yeast autophagy-8 (ATG8), MAP1LC3A, MAP1LC3B (609604), MAP1LC3C (609605), GABARAP (605125), GABARAPL1, and GABARAPL2, interact with a cohort of 67 proteins, with extensive binding partner overlap between family members, and frequent involvement of a conserved surface on ATG8 proteins known to interact with LC3-interacting regions in partner proteins. Behrends et al. (2010) concluded that their studies provided a global view of the mammalian autophagy interaction landscape and a resource for mechanistic analysis of this critical protein homeostasis pathway.
By copurification analysis, Pascall et al. (2013) showed that human GIMAP6 (616960) specifically and directly interacted with human GABARAPL2. Mutation analyses revealed that the C-terminal 10 amino acids of GIMAP6 and the N-terminal 10 amino acids of GABARAPL2 were required for the interaction. Overexpression of GIMAP6 in HeLa cells led to induction of GABARAPL2 expression. Overexpressed GIMAP6 was recruited to autophagosomes upon induction of autophagy, and the C-terminal 10 amino acids of GIMAP6 were required for its recruitment to autophagosomes. In agreement, endogenous GIMAP6 relocated to punctate structures in response to starvation of Jurkat T cells and primary human vascular endothelial cells, resulting in degradation of GIMAP6 during starvation-induced autophagy.
Xin et al. (2001) determined that the GABARAPL2 gene contains 4 exons.
By radiation hybrid analysis, Xin et al. (2001) mapped the GABARAPL2 gene to chromosome 16q22.3-q24.1.
Behrends, C., Sowa, M. E., Gygi, S. P., Harper, J. W. Network organization of the human autophagy system. Nature 466: 68-76, 2010. [PubMed: 20562859] [Full Text: https://doi.org/10.1038/nature09204]
Hemelaar, J., Lelyveld, V. S., Kessler, B. M., Ploegh, H. L. A single protease, Apg4B, is specific for the autophagy-related ubiquitin-like proteins GATE-16, MAP1-LC3, GABARAP, and Apg8L. J. Biol. Chem. 278: 51841-51850, 2003. [PubMed: 14530254] [Full Text: https://doi.org/10.1074/jbc.M308762200]
Pascall, J. C., Rotondo, S., Mukadam, A. S., Oxley, D., Webster, J., Walker, S. A., Piron, J., Carter, C., Ktistakis, N. T., Butcher, G. W. The immune system GTPase GIMAP6 interacts with the Atg8 homologue GABARAPl2 and is recruited to autophagosomes. PLoS One 8: e77782, 2013. [PubMed: 24204963] [Full Text: https://doi.org/10.1371/journal.pone.0077782]
Sagiv, Y., Legesse-Miller, A., Porat, A., Elazar, Z. GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J. 19: 1494-1504, 2000. [PubMed: 10747018] [Full Text: https://doi.org/10.1093/emboj/19.7.1494]
Xin, Y., Yu, L., Chen, Z., Zheng, L., Fu, Q., Jiang, J., Zhang, P., Gong, R., Zhao, S. Cloning, expression patterns, and chromosome localization of three human and two mouse homologues of GABA-A receptor-associated protein. Genomics 74: 408-413, 2001. [PubMed: 11414770] [Full Text: https://doi.org/10.1006/geno.2001.6555]