Gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAPL1)
The protein contains 117 amino acids for an estimated molecular weight of 14044 Da.
Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor (PubMed:16431922). Involved in formation of autophagosomal vacuoles (PubMed:20404487). While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation (PubMed:20404487). Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover (PubMed:31006538, PubMed:31006537). (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.
- 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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Biological Process
Autophagosome assembly
Autophagosome maturation
Autophagy of mitochondrion
Autophagy of nucleus
Cellular response to nitrogen starvation
Macroautophagy
Membrane fusion
The reference OMIM entry for this protein is 607420
Gaba-a receptor-associated protein-like protein 1; gabarapl1
Gabarap-like protein 1
Glandular epithelial cell protein 1; gec1
Apg8-like; apg8l
CLONING
Pellerin et al. (1993) cloned guinea pig Gabarapl1, which they called Gec1, through a differential screen of estrogen-regulated sequences expressed by endometrial glandular epithelial cells. Using the guinea pig sequence as probe, Vernier-Magnin et al. (2001) cloned human GABARAPL1, which they called GEC1, from a placenta cDNA library. The deduced 117-amino acid protein shares 100% amino acid identity with guinea pig Gabarapl1 and 87% identity with GABARAP (605125). Northern blot analysis revealed a 1.9-kb transcript in all tissues examined. By Northern blot analysis, Xin et al. (2001) found a 2.3-kb GABARAPL1 transcript expressed in all tissues examined, with highest levels in brain, heart, peripheral blood leukocytes, liver, kidney, placenta, and skeletal muscle. Moderate expression was found in pancreas, prostate, testis, ovary, lung, spleen, and colon, and low expression was found in thymus and small intestine. In addition, a 4.2-kb transcript was found in low abundance in ovary, peripheral blood leukocytes, and liver, and a 1.7-kb transcript was found in placenta at low levels. Xin et al. (2001) noted that the amino acid sequence of the human and mouse proteins are identical. Northern blot analysis of mouse tissues revealed high levels of a 1.8-kb transcript in brain and kidney, and high levels of a 1.3-kb transcript in testis and heart.GENE FUNCTION
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 (GABARAPL2; 607452), GABARAP, MAP1LC3 (see 601242), and APG8L. 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 (601242), 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 GABARAPL1 gene contains 4 exons.MAPPING
By genomic sequence analysis, Vernier-Magnin et al. (2001) mapped the GABARAPL1 gene to chromosome 12. By radiation hybrid analysis, Xin et al. (2001) mapped the GABARAPL1 gene to chromosome 12p12.3. ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for GABARAPL1
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607420 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed