Gamma-aminobutyric acid receptor-associated protein (GABARAP)

The protein contains 117 amino acids for an estimated molecular weight of 13918 Da.

 

Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton (PubMed:9892355). Involved in autophagy: 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:15169837, PubMed:20562859, PubMed:22948227). 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). Also required for the local activition of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction (PubMed:25684205). Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation (PubMed:25684205). Involved in apoptosis (PubMed:15977068). (updated: June 2, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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The reference OMIM entry for this protein is 605125

Gaba-a receptor-associated protein; gabarap

CLONING

Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid) (see 137160) are ligand-gated chloride channels that mediate inhibitory neurotransmission. By performing a yeast 2-hybrid screen on a fetal brain cDNA library using the intracellular loop of the GABA-A receptor gamma-2S subunit (GABRG2; 137164) as bait, followed by screening an adult brain cDNA library, Wang et al. (1999) identified a cDNA encoding GABARAP. Sequence analysis predicted that the 117-amino acid, 13.9-kD GABARAP protein contains a basic N terminus and an acidic C terminus, with an overall pI of 9.6. Northern blot analysis detected a 0.9-kb GABARAP transcript in all tissues tested, namely heart, brain, placenta, lung, liver, skeletal muscle, kidney, and pancreas. Western blot analysis also detected GABARAP expression in all tissues tested, suggesting that GABARAP is also involved in biologic events other than interaction with GABA-A receptors.

MAPPING

Komoike et al. (2010) noted that the GABARAP gene maps to chromosome 17p13.1.

GENE FUNCTION

Binding analysis by Wang et al. (1999) showed that the N-terminal 21 amino acids of GABARAP formed an alpha helix that interacted with tubulin (see TUBA1; 191110). Immunoprecipitation and immunohistochemical analysis in rat brain tissues demonstrated association and colocalization of GABARAP and GABA-A receptors. 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 (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. Using coimmunoprecipitation and mass spectrometric analyses, Lee et al. (2005) identified DDX47 (615428) as a binding partner of GABARAP in human 2774 and SKOV-3 ovarian tumor cell lysates. Yeast 2-hybrid analysis confirmed the interaction. Overexpression of either DDX47 or GABARAP alone had no effect on proliferation of SKOV-3 cells; however, their coexpression inhibited cell proliferation and induced apoptosis. 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, 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 analysi ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

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.

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 605125 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed