ATP-citrate synthase (ACLY)
The protein contains 1101 amino acids for an estimated molecular weight of 120839 Da.
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis. (updated: July 31, 2019)
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.
- 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.
- 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.
- 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.
| 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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs2304497 |
Biological Process
Acetyl-CoA biosynthetic process
Cellular carbohydrate metabolic process
Cellular lipid metabolic process
Cholesterol biosynthetic process
Citrate metabolic process
Coenzyme A metabolic process
Energy reserve metabolic process
Fatty acid biosynthetic process
Fatty-acyl-CoA biosynthetic process
Lipid biosynthetic process
Long-chain fatty-acyl-CoA biosynthetic process
Neutrophil degranulation
Oxaloacetate metabolic process
Positive regulation of cellular metabolic process
Small molecule metabolic process
Triglyceride biosynthetic process
The reference OMIM entry for this protein is 108728
Atp citrate lyase; acly
Clatp
Atpcl
Acl
DESCRIPTION
ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine.CLONING
Cloning of cDNAs has been reported for murine (Sul et al., 1984), rat (Elshourbagy et al., 1990), and human (Elshourbagy et al., 1992) ATP citrate lyase. Elshourbagy et al. (1992) found that the subunits of the enzyme have 1,105 amino acids and a calculated molecular mass of 121,419 Da. The human and rat ATPCL cDNAs showed 96.3% amino acid identity.GENE FUNCTION
Wellen et al. (2009) showed that histone acetylation in mammalian cells is dependent on ATP-citrate lyase (ACL), the enzyme that converts glucose-derived citrate into acetyl-CoA. They found that ACL is required for increases in histone acetylation in response to growth factor stimulation and during differentiation, and that glucose availability can affect histone acetylation in an ACL-dependent manner. Wellen et al. (2009) concluded that ACL activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression.MAPPING
Remmers et al. (1992) found that the genes for growth hormone (139250), pancreatic polypeptide (167780), ERBB2 (164870), sex hormone binding globulin (182205), embryonic skeletal myosin heavy chain (160720), and asialoglycoprotein receptor (108360) map to human chromosome 17 and rat chromosome 10. Many of the same genes are known to be located on mouse chromosome 11. Furthermore, Remmers et al. (1992) showed that in the rat the gene for ATP citrate lyase is closely linked to the gene for PPY, which in turn is close to the GH gene, on chromosome 10. They predicted, therefore, that the homologous gene in the human would be located on chromosome 17, probably close to PPY which is situated at 17q22-q24. Couch et al. (1994) mapped the ACLY gene to 17q12-q21 by PCR analysis of a panel of human/rodent somatic cell hybrids and localized it to 17q21.1 by PCR on a panel of radiation hybrids. The radiation hybrid panel indicated that the most likely position of ACLY on 17q21.1 is between gastrin (137250) and D17S856 at a distance of 170 to 290 kb from the GAS locus. ... More on the omim web site
Aug. 19, 2019: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 108728 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed