Bifunctional coenzyme A synthase (COASY)
The protein contains 564 amino acids for an estimated molecular weight of 62329 Da.
Bifunctional enzyme that catalyzes the fourth and fifth sequential steps of CoA biosynthetic pathway. The fourth reaction is catalyzed by the phosphopantetheine adenylyltransferase, coded by the coaD domain; the fifth reaction is catalyzed by the dephospho-CoA kinase, coded by the coaE domain. May act as a point of CoA biosynthesis regulation. (updated: April 1, 2015)
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.
- 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs615942 | |
| NBIA6 | |
| NBIA6; unknown pathological significance |
Biological Process
Coenzyme A biosynthetic process
Obsolete coenzyme biosynthetic process
Pantothenate metabolic process
Small molecule metabolic process
Vitamin metabolic process
Water-soluble vitamin metabolic process
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Mitochondrial matrix
Mitochondrial outer membrane
Nucleoplasm
The reference OMIM entry for this protein is 609855
Coenzyme a synthase; coasy
Phosphopantetheine adenylyltransferase/dephosphocoenzyme a kinase
Ppat/dpck
DESCRIPTION
Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. COASY is a bifunctional enzyme that catalyzes the 2 last steps in CoA synthesis. These activities are performed by 2 separate enzymes, phosphopantetheine adenylyltransferase (PPAT; EC 2.7.7.3) and dephospho-CoA kinase (DPCK; EC 2.7.1.24), in prokaryotes (Daugherty et al., 2002).CLONING
By searching for sequences similar to E. coli CoA biosynthesis enzymes, followed by PCR of a brain cDNA library, Daugherty et al. (2002) cloned COASY, which they called PPAT/DPCK. The deduced 565-amino acid protein has an N-terminal domain, a central PPAT domain, and a C-terminal DPCK domain. The PPAT domain contains the conserved HxxH motif characteristic of nucleotidyltransferases. Northern blot analysis detected 2.2- and 2.6-kb COASY transcripts in most tissues and tumor cell lines examined. Expression was highest in kidney and liver and lowest in peripheral blood leukocytes. By searching for sequences similar to pig Coasy, followed by RT-PCR of a hepatoma cell line cDNA library, Aghajanian and Worrall (2002) cloned human COASY. The deduced protein has a calculated molecular mass of 62.3 kD and shares more than 96% amino acid identity with the pig and mouse proteins. Aghajanian and Worrall (2002) identified a conserved Walker A-type kinase motif, which is involved in ATP binding, in the C-terminal DPCK domain of COASY. Size-exclusion chromatography showed that recombinant human COASY assumed a monomeric native structure with an apparent molecular mass of 62 kD. Using full-length ribosomal S6 kinase alpha-II (RPS6KA2; 601685) as bait in a yeast 2-hybrid screen of a mouse embryo cDNA library, Zhyvoloup et al. (2002) cloned mouse Coasy, which encodes a deduced 563-amino acid protein. Bioinformatic analysis indicated that the N-terminal extension is only present in eukaryotes. There are 3 splice variants of human COASY: 60-kD COASY-alpha is ubiquitously expressed; COASY-beta has a 29-amino acid extension at the N terminus and is predominantly expressed in the brain; and COASY-gamma is predicted to code for the C-terminal region of CoA synthase corresponding to DPCK (summary by Dusi et al., 2014).GENE FUNCTION
Daugherty et al. (2002) showed that recombinant COASY functioned as the last enzyme within the CoA synthetic pathway, and they verified COASY function by complementation in E. coli. Incubation of PPCS (609853), PPCDC (609854), and COASY with the necessary substrates and cofactors reconstituted the 4-step biochemical transformation of phosphopantothenate to CoA. Mutation analysis confirmed the bifunctional activity of COASY. Zhyvoloup et al. (2002) confirmed that mouse Coasy is a bifunctional enzyme. Mutation of his203 to ala in the catalytic pocket of the PPAT domain inactivated PPAT activity. Zhyvoloup et al. (2003) demonstrated that full-length CoA synthase is associated with the outer mitochondrial membrane and that the removal of the N-terminal region relocated the enzyme to the cytosol. The activity of CoA synthase was regulated by phospholipids. In HeLa cells, Dusi et al. (2014) determined that the COASY protein is mainly present in the mitochondrial matrix, probably anchored to the inner mitochondrial membrane, but that it is also present in cell lysate.GENE STRUCTURE
Aghajanian and Worrall (2002) determined that the COASY gene contains 10 exons.MAPP ... More on the omim web site
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 609855 was added.