PRA1 family protein 3 (ARL6IP5)

The protein contains 188 amino acids for an estimated molecular weight of 21615 Da.

 

Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. Plays a role in the retention of SLC1A1/EAAC1 in the endoplasmic reticulum. (updated: Feb. 10, 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. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 45%
Model score: 0

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The reference OMIM entry for this protein is 605709

Adp-ribosylation-like factor 6-interacting protein 5; arl6ip5
Pra1 domain family, member 3; praf3
Glutamate transporter eaac1-associated protein
Gtrap3-18
Jwa

CLONING

Using the C-terminal intracellular domain of EAAC1 (SLC1A1; 133550) (the last 87 amino acids) as bait in a yeast 2-hybrid screen of an adult rat brain cDNA library, Lin et al. (2001) identified a clone, which they designated E18. They noted that JWA protein, a human differentially displayed vitamin A-responsive gene, is 95% identical to E18, suggesting that E18 is a JWA protein homolog of rat. Lin et al. (2001) designated the deduced 188-amino acid rat protein GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues. It localizes to the cell membrane and cytoplasm. Butchbach et al. (2002) cloned mouse Gtrap3-18 from a cerebral cortex cDNA library. The deduced 188-amino acid protein is highly basic and has a number of potential phosphorylation sites, but no apparent transmembrane domains. Gtrap3-18 shares 95.2% similarity with human GTRAP3-18 and appeared to be evolutionarily conserved. RT-PCR and EST database analysis revealed ubiquitous Gtrap3-18 expression in mouse. Immunohistochemical analysis of mouse brain revealed localization of Gtrap3-18 predominantly in neuron-rich regions such as stratum pyramidale of hippocampus and Purkinje cells of the cerebellum. Western blot analysis showed that Gtrap3-18 formed dimers, trimers, and higher order multimers, even under reducing conditions.

GENE FUNCTION

Lin et al. (2001) showed that rat GTRAP3-18 specifically interacts with the carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. Lin et al. (2001) concluded that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1. By transfecting HEK293 cells with mouse cDNAs, Butchbach et al. (2002) showed that Gtrap3-18 inhibited Eaac1-mediated Na(+)-dependent glutamate transport in a dose-dependent manner. Huang et al. (2006) found that the expression of JWA was increased in a time-dependent manner in most myeloid leukemia cell lines induced to differentiate along different lineages by all-trans retinoic acid and other chemical inducers. Inhibition of JWA by RNA interference reduced the degree of differentiation.

GENE STRUCTURE

Butchbach et al. (2002) determined that the ARL6IP5 gene contains 3 exons. This gene structure is highly conserved in mouse and pufferfish.

MAPPING

By genomic sequence analysis, Butchbach et al. (2002) mapped the ARL6IP5 gene to chromosome 3p14. They mapped the mouse Arl6ip5 gene to a region of chromosome 6D3 that shares homology of synteny with human chromosome 3p14. ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: 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. 10, 2018: 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

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605709 was added.

Feb. 25, 2016: Protein entry updated
Automatic update: model status changed

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

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed