ATPase GET3 (ASNA1)

The protein contains 348 amino acids for an estimated molecular weight of 38793 Da.

 

ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1/WRB and CAMLG/GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting. May be involved in insulin signaling. (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. 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.

Interpro domains
Total structural coverage: 100%
Model score: 51

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VariantDescription
dbSNP:rs8177499

The reference OMIM entry for this protein is 601913

Arsa arsenite transporter, atp-binding, e. coli, homolog of, 1; asna1
Arsa1
Transmembrane domain recognition complex, 40-kd; trc40

DESCRIPTION

ASNA1 is the human homolog of the bacterial arsA gene. In E. coli, ArsA ATPase is the catalytic component of a multisubunit oxyanion pump that is responsible for resistance to arsenicals and antimonials.

CLONING

Kurdi-Haidar et al. (1996) used degenerate PCR to clone a human homolog of the bacterial arsA gene. The human ARSA1 cDNA was isolated from a human ovarian carcinoma library and found to encode a 332-amino acid polypeptide having an N-terminal ATP-binding cassette (ABC) domain and a C-terminal domain of unknown function. The protein sequence is highly homologous throughout both domains to hypothetical arsA proteins of C. elegans and yeast. Northern blot analysis revealed that the ARSA1 gene is ubiquitously expressed. Southern blot analysis indicated the existence of 2 closely related ARSA genes in the human genome. The existence of a second human ARSA protein was further supported by Western blot analysis, which demonstrated that anti-ARSA1 antibodies identify 2 proteins of 37 and 42 kD. Kurdi-Haidar et al. (1996) expressed ARSA1 and found that the resulting 37-kD protein had ATPase activity. Kurdi-Haidar et al. (1998) found that ASNA1 shows a cytoplasmic, perinuclear, and nucleolar distribution. By cell fractionation and extensive use of double-label immunolocalizations, they demonstrated that the cytoplasmic protein was soluble, the perinuclear protein was associated with invaginations of the nuclear membranes rather than with the endoplasmic reticulum, and that the nucleolar signal colocalized with known nucleolar markers. Bhattacharjee et al. (2001) cloned mouse Asna1 which encodes a 348-amino acid protein sharing 27% and 99% identity with the E. coli and human proteins, respectively. Northern blot analysis detected a 1.3-kb transcript in mouse at highest levels in kidney and testis, moderate levels in brain, liver, lung, and skin, low levels in heart, small intestine, spleen, stomach, and thymus, and negligible levels in skeletal muscle.

GENE FUNCTION

Kurdi-Haidar et al. (1998) characterized purified recombinant ASNA1. They determined that the ATPase activity increases in the presence of sodium arsenite and that Vmax rather than ATP affinity is enhanced. Unlike the E. coli homolog in which arsenite or antimonite allosterically activates arsA ATPase activity, potassium antimonite had no effect on the ATPase activity of human ASNA1. Through chemical crosslinking of recombinant protein and by nonreducing PAGE analysis of ASNA1 overexpressed in human kidney cells, they found that the active species is likely a dimer or tetramer. Mariappan et al. (2010) identified a conserved 3-protein complex composed of BAT3 (142590), TRC35 (612056), and UBL4A (312070) that facilitates tail-anchored protein capture by TRC40. This BAT3 complex is recruited to ribosomes synthesizing membrane proteins, interacts with the transmembrane domains of newly released tail-anchored proteins, and transfers them to TRC40 for targeting. Depletion of the BAT3 complex allows non-TRC40 factors to compete for tail-anchored proteins, explaining their mislocalization in the analogous yeast deletion strains. Thus, the BAT3 complex acts as a transmembrane domain-selective chaperone that effectively channels tail-anchored proteins to the TRC40 insertion pathway.

GENE STRUCTURE

Kurdi-Haidar et al. (1998) determined that the ASNA1 gene contains 4 exons and spans 6 kb. Bhattacharjee et al. (2001) determined that th ... 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.

April 25, 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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601913 was added.