Long-chain-fatty-acid--CoA ligase 3 (ACSL3)
The protein contains 720 amino acids for an estimated molecular weight of 80420 Da.
Acyl-CoA synthetases (ACSL) activates long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:22633490). Required for the incorporation of fatty acids into phosphatidylcholine, the major phospholipid located on the surface of VLDL (very low density lipoproteins) (PubMed:18003621). Has mainly an anabolic role in energy metabolism. Mediates hepatic lipogenesis. Preferentially uses myristate, laurate, arachidonate and eicosapentaenoate as substrates. Both isoforms exhibit the same level of activity (By similarity). (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.
- 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, is predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs1046032 |
Biological Process
Brain development
Fatty acid biosynthetic process
Fatty acid metabolic process
Long-chain fatty acid import into cell
Long-chain fatty acid metabolic process
Long-chain fatty-acyl-CoA biosynthetic process
Long-chain fatty-acyl-CoA metabolic process
Neuron differentiation
Positive regulation of Golgi to plasma membrane protein transport
Positive regulation of phosphatidylcholine biosynthetic process
Positive regulation of secretion
Response to nutrient
Response to organic cyclic compound
Very-low-density lipoprotein particle assembly
The reference OMIM entry for this protein is 602371
Acyl-coa synthetase long chain family, member 3; acsl3
Fatty acid coa ligase, long chain 3; facl3
Acyl-coa synthetase 3; acs3
DESCRIPTION
Fatty acids are incorporated into membranes and signaling molecules and have roles in energy storage and metabolism. These essential functions require activation of the fatty acid by acyl-coenzyme A (CoA) synthetases, such as ACSL3, which form an activating thioester linkage between the fatty acid and CoA (Watkins et al., 2007).CLONING
Fujino et al. (1996) cloned rat Acs3 by PCR of a rat brain cDNA library. The deduced 720-amino acid rat protein has a calculated molecular mass of approximately 80 kD. SDS-PAGE of purified Acs3 revealed 2 major proteins with apparent molecular masses of 79 and 80 kD. Northern blot analysis of rat tissues showed that Acs3 was predominantly expressed in brain. Lower expression was detected in lung, adrenal gland, kidney, small intestine, and adipose tissue, and no expression was detected in heart and liver. Minekura et al. (1997) used rat ACS3 cDNA as a probe to isolate a human ACS3 clone from a placenta cDNA library. The predicted 720-amino acid human protein is 92% identical to rat Acs3. By searching databases for sequences containing acyl-CoA synthetase motifs 1 and 2, Watkins et al. (2007) identified a splice variant of human ACSL3 with a different 5-prime UTR. Phylogenetic analysis revealed that ACSL3 belongs to a family of long chain acyl-CoA synthetases.GENE FUNCTION
Fujino et al. (1996) found that rat Acs3 preferentially used myristate, laurate, arachidonate, and eicosapentaenoate as substrates.GENE STRUCTURE
Watkins et al. (2007) determined that the ACSL3 gene contains at least 17 exons.MAPPING
By somatic cell hybrid analysis and FISH, Minekura et al. (1997) mapped the ACS3 gene to chromosome 2q34-q35. Watkins et al. (2007) mapped the ACSL3 gene to the plus strand of chromosome 2q34-q35 by genomic sequence analysis. ... 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 602371 was added.