Gamma-aminobutyric acid receptor-associated protein-like 2 (GABARAPL2)
The protein contains 117 amino acids for an estimated molecular weight of 13667 Da.
Ubiquitin-like modifier involved in intra-Golgi traffic (By similarity). Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation (By similarity). It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy (PubMed:20418806, PubMed:23209295). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production (PubMed:20418806, PubMed:23209295). Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:20418806, PubMed:23209295). (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs11556291 |
Biological Process
Autophagosome assembly
Autophagosome maturation
Autophagy
Autophagy of mitochondrion
Autophagy of nucleus
Cellular response to nitrogen starvation
Intra-Golgi vesicle-mediated transport
Macroautophagy
Membrane fusion
Negative regulation of proteasomal protein catabolic process
Positive regulation of ATPase activity
Protein localization to endoplasmic reticulum
Protein transport
The reference OMIM entry for this protein is 607452
Gaba-a receptor-associated protein-like protein 2; gabarapl2
Gate16, bovine, homolog of; gate16
CLONING
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.GENE FUNCTION
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.GENE STRUCTURE
Xin et al. (2001) determined that the GABARAPL2 gene contains 4 exons.MAPPING
By radiation hybrid analysis, Xin et al. (2001) mapped the GABARAPL2 gene to chromosome 16q22.3-q24.1. ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607452 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed