Long-chain-fatty-acid--CoA ligase 5 (ACSL5)
The protein contains 683 amino acids for an estimated molecular weight of 75991 Da.
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:17681178, PubMed:24269233, PubMed:22633490). ACSL5 may activate fatty acids from exogenous sources for the synthesis of triacylglycerol destined for intracellular storage (By similarity). Utilizes a wide range of saturated fatty acids with a preference for C16-C18 unsaturated fatty acids (By similarity). It was suggested that it may also stimulate fatty acid oxidation (By similarity). At the villus tip of the crypt-villus axis of the small intestine may sensitize epithelial cells to apoptosis specifically triggered by the death ligand TRAIL. May have a role in the survival of glioma cells. (updated: July 31, 2019)
Protein identification was indicated in the following studies:
- 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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
No binding partner found
Biological Process
Lipid biosynthetic process
Long-chain fatty acid metabolic process
Long-chain fatty-acyl-CoA biosynthetic process
Positive regulation of long-chain fatty acid import across plasma membrane
Regulation of extrinsic apoptotic signaling pathway
The reference OMIM entry for this protein is 605677
Acyl-coa synthetase long chain family, member 5; acsl5
Fatty acid coa ligase, long chain 5; facl5
Acyl-coa synthetase 5; acs5
DESCRIPTION
Acyl-CoA synthetases (ACSs; EC 6.2.1.3), such as ACSL5, catalyze the formation of acyl-CoA from fatty acid, ATP, and CoA. This reaction is essential in mammalian fatty acid metabolism. In addition, ACSs mediates transportation of fatty acids into cells by cooperating with the fatty acid transporter protein (FATP; 600691) (summary by Watkins et al., 2007).CLONING
Oikawa et al. (1998) cloned rat Acs5 and found that it is highly expressed in proliferating 3T3-L1 cells. By screening a liver cDNA library with rat ACS5 as the probe, Yamashita et al. (2000) isolated a cDNA encoding human ACS5. The deduced 683-amino acid protein shares approximately 80% amino acid identity with the rat sequence. Northern blot analysis detected 2 major ACS5 transcripts of 2.5 and 3.7 kb in a wide range of tissues, with highest expression in uterus and spleen. By searching databases for sequences containing acyl-CoA synthetase motifs 1 and 2, Watkins et al. (2007) identified 3 splice variants of human ACSL5. The full-length protein contains 739 amino acids. The 2 other splice variants differ from each other only in their 5-prime UTRs and encode an N-terminally truncated protein of 683 amino acids. Phylogenetic analysis revealed that ACSL5 belongs to a family of long chain acyl-CoA synthetases.GENE FUNCTION
Markedly increased levels of ACS5 transcripts were detected in a glioma line and in primary gliomas of grade IV malignancy, while ACS5 expression was found to be low in normal brain. Yamashita et al. (2000) found that cultured glioma cells infected with an adenovirus encoding ACS5 displayed induced cell growth on exposure to palmitate. Consistent with the induction of cell growth, the virus-infected cells displayed induced uptake of palmitate. These results demonstrated a novel fatty acid-induced glioma cell growth mediated by ACS5.GENE STRUCTURE
Using BAC and YAC clones, Yamashita et al. (2000) determined that the ACS5 gene spans approximately 46 kb and contains 21 exons.MAPPING
Yamashita et al. (2000) determined that the 3-prime UTR of ACS5 contains a specific STS marker that maps to 10q25.1-q25.2, a region frequently deleted in malignant gliomas (see 601969). Watkins et al. (2007) mapped the ACSL5 gene to the plus strand of chromosome 10q25.1-q25.2 by genomic sequence analysis. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 605677 was added.
Aug. 20, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).