Activator of 90 kDa heat shock protein ATPase homolog 1 (AHSA1)

The protein contains 338 amino acids for an estimated molecular weight of 38274 Da.

 

Acts as a co-chaperone of HSP90AA1 (PubMed:29127155). Activates the ATPase activity of HSP90AA1 leading to increase in its chaperone activity (PubMed:29127155). Competes with the inhibitory co-chaperone FNIP1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:27353360). Competes with the inhibitory co-chaperone TSC1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). (updated: April 25, 2018)

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.

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: 42%
Model score: 35

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The reference OMIM entry for this protein is 608466

Activator of heat-shock 90-kd protein atpase 1; ahsa1
Aha1

CLONING

The vesicular stomatitis virus glycoprotein (VSVG) is a model transmembrane glycoprotein used to study the exocytotic pathway. Using the protein-sorting motifs in the VSVG tail as bait in a yeast 2-hybrid screen of a HeLa cell cDNA library, followed by EST database analysis, Sevier and Machamer (2001) cloned AHSA1, which they called p38. The deduced 338-amino acid protein has a calculated molecular mass of 38.3 kD. Northern blot analysis detected a 1.5-kb transcript in brain, heart, skeletal muscle, and kidney; lower levels were detected in liver and placenta. Expression was below the level of detection in colon, thymus, spleen, small intestine, lung, and peripheral blood leukocytes. However, the authors identified AHSA1 sequences in colon, thymus, small intestine, lung, and blood EST databases, suggesting that AHSA1 expression is ubiquitous but variable. Western blot analysis detected endogenous AHSA1 at an apparent molecular mass of 40 kD in HeLa cells. AHSA1 was primarily found in the cytosolic fraction of HeLa cell homogenates, with some in the microsomal membrane pellet. Immunofluorescence microscopy revealed strong cytosolic staining. When proteins were crosslinked prior to visualization, AHSA1 staining showed a more reticular pattern, suggesting that the crosslinker may have stabilized an association of AHSA1 with a tethering protein in the endoplasmic reticulum membrane. By searching databases for sequences similar to an S. cerevisiae Hsp90 (140571) suppressor, Hch1, Lotz et al. (2003) identified AHSA1. The deduced protein contains a putative N-terminal domain that is homologous to Hch1 and a putative C-terminal domain.

GENE FUNCTION

Lotz et al. (2003) determined that interaction of HSP90 and AHSA1 required a region of HSP90 that links its N-terminal and middle domains. They found that AHSA1 stimulated the intrinsic ATPase activity of HSP90 5-fold. Cystic fibrosis (CF; 219700) is an inherited childhood disease primarily triggered by defective folding and export of the CFTR (606421) protein from the endoplasmic reticulum (ER). Using proteomics to assess global CFTR protein interactions, Wang et al. (2006) showed that HSP90 cochaperones modulated HSP90-dependent stability of CFTR protein folding in the ER. Small interfering RNA-mediated partial silencing of the HSP90 cochaperone AHA1 in human embryonic kidney and lung cell lines rescued delivery of the most common disease-causing ER-restricted CFTR delta-F508 variant (602421.0001) to the cell surface. Wang et al. (2006) proposed that failure of CFTR delta-F508 to achieve an energetically favorable fold in response to steady-state dynamics of the chaperone folding environment is responsible for the pathophysiology of CF.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the AHSA1 gene to chromosome 14 (TMAP WI-15374). ... More on the omim web site

Subscribe to this protein entry history

April 27, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 5, 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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608466 was added.

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