Long-chain-fatty-acid--CoA ligase 6 (ACSL6)
The protein contains 697 amino acids for an estimated molecular weight of 77752 Da.
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490, PubMed:24269233). Plays an important role in fatty acid metabolism in brain and the acyl-CoAs produced may be utilized exclusively for the synthesis of the brain lipid. (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.
- 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.
- 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, is predicted to be membranous by TOPCONS.
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Biological Process
Acyl-CoA metabolic process
Cellular lipid metabolic process
Cellular response to insulin stimulus
Fatty acid transport
Lipid biosynthetic process
Long-chain fatty acid metabolic process
Long-chain fatty-acyl-CoA biosynthetic process
Neuroblast proliferation
Neuron development
Phospholipid biosynthetic process
Positive regulation of long-chain fatty acid import across plasma membrane
Positive regulation of neuron projection development
Positive regulation of triglyceride biosynthetic process
Response to gravity
Response to hypoxia
Response to nutrient
Response to steroid hormone
Small molecule metabolic process
Triglyceride biosynthetic process
Very long-chain fatty acid metabolic process
The reference OMIM entry for this protein is 604443
Acyl-coa synthetase long chain family, member 6; acsl6
Fatty acid coa ligase, long chain 6; facl6
Long chain acyl-coa synthetase 2; lacs2
Long chain acyl-coa synthetase 5; lacs5
Acyl-coa synthetase 2; acs2
Kiaa0837 acs2/etv6 fusion gene, in
DESCRIPTION
Long chain acyl-CoA synthetases (EC 6.2.1.3), such as ACSL6, catalyze the formation of acyl-CoA from fatty acids, ATP, and CoA (Malhotra et al., 1999).CLONING
By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1998) cloned ACSL6, which they designated KIAA0837. The transcript contains repetitive elements in its 3-prime region, and the deduced 745-amino acid protein shares a high degree of similarity with rat brain long chain fatty acid CoA ligase. RT-PCR ELISA detected very high ACSL6 expression in whole adult brain and in all specific adult brain regions examined. Expression was lower in heart and fetal brain, and much lower in all other tissues examined. In a patient with refractory anemia with excess blasts with basophilia, a patient with acute myelogenous leukemia (AML) with eosinophilia, and a patient with acute eosinophilic leukemia (AEL), Yagasaki et al. (1999) identified ACSL6, which they called ACS2, as an ETV6 (600618) fusion partner in a recurrent t(5;12)(q31;p13) translocation. Northern blot analysis detected high levels of ACS2 expression in brain, fetal liver, and bone marrow, and the gene was found to be highly conserved in man and rat. Using degenerate primers based on conserved regions of acyl-CoA synthetases, Malhotra et al. (1999) cloned ACSL6, which they called LACS5, from a K562 erythroid cell line cDNA library. The deduced 697-amino acid protein has a calculated molecular mass of 77.6 kD. It has a transmembrane region and a predicted extended cytoplasmic tail of 657 amino acids. Northern blot analysis detected variable expression of 2.9- and 6.3-kb transcripts in K562 cells, fetal blood derived from liver cells, reticulocytes, bone marrow, and cord blood. LACS5 was also expressed in human brain as transcripts of 9.4 kb and 2.9 kb. Western blot analysis of human erythrocyte ghosts detected LACS5 at an apparent molecular mass of 78 kD. Using the central portion of mouse Pahx (PHYH; 602026) as bait in a yeast 2-hybrid screen of a mouse brain cDNA library, Kee et al. (2003) cloned Acsl6. The deduced 722-amino acid mouse protein has a calculated molecular mass of 81 kD. Northern blot analysis detected high expression of a 2.6-kb transcript in brain and testis, with weaker expression in heart and skeletal muscle. A transcript of about 6.5 kb was also detected in brain. Expression of the 6.5-kb transcript in brain began at birth and increased to a maximum level in adult mice. Western blot analysis detected a 95-kD Acsl6 protein in brain, heart, and testis. By searching databases for sequences containing acyl-CoA synthetase motifs 1 and 2, Watkins et al. (2007) identified 2 splice variants of human ACSL6 that result from the use of alternative exons 11. Both variants encode proteins of 722 amino acids that differ internally within acyl-CoA synthetase motif 4. Phylogenetic analysis revealed that ACSL5 belongs to a family of long chain acyl-CoA synthetases.GENE STRUCTURE
Watkins et al. (2007) determined that the ACSL6 gene contains 22 exons, including 2 alternative exons 11.MAPPING
By sequence analysis, Yagasaki et al. (1999) mapped the ACSL6 gene to chromosome 5q31.GENE FUNCTION
Malhotra et al. (1999) showed that recombinant human LACS5 had acyl-CoA synthetase activity with palmitic acid, oleic acid, and arachidonic acid. Kee et al. (2003) found that expression of Acsl6 increased in PC12 rat pheochromocytoma cells d ... More on the omim web site
Aug. 20, 2019: 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 604443 was added.