Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
The protein contains 711 amino acids for an estimated molecular weight of 79188 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:24269233, PubMed:22633490, PubMed:21242590). Preferentially activates arachidonate and eicosapentaenoate as substrates (PubMed:21242590). Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose-stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion (PubMed:21242590). (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 annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| a colorectal cancer sample | |
| MRX63 | |
| empty |
Biological Process
Cellular lipid metabolic process
Dendritic spine development
Embryonic process involved in female pregnancy
Fatty acid metabolic process
Fatty acid transport
Lipid biosynthetic process
Lipid metabolic process
Long-chain fatty acid metabolic process
Long-chain fatty-acyl-CoA biosynthetic process
Long-chain fatty-acyl-CoA metabolic process
Negative regulation of prostaglandin secretion
Neuron differentiation
Positive regulation of cell growth
Positive regulation of insulin secretion
Response to interleukin-15
Response to nutrient
Small molecule metabolic process
Triglyceride biosynthetic process
Triglyceride metabolic process
The reference OMIM entry for this protein is 300157
Acyl-coa synthetase long chain family, member 4; acsl4
Fatty acid coa ligase, long chain 4; facl4
Acyl-coa synthetase 4; acs4
DESCRIPTION
Long chain acyl-CoA synthetase (LACS), or long chain fatty acid-CoA ligase (FACL; EC 6.2.1.3), converts free long chain fatty acids into fatty acyl-CoA esters, which are key intermediates in the synthesis of complex lipids. The ACSL4 gene encodes a form of LACS and is expressed in several tissues, including brain (Cao et al., 1998; Piccini et al., 1998).CLONING
Kang et al. (1997) identified rat Acsl4, which they called Acs4. By searching databases with rat Acs4 as query, Cao et al. (1998) identified ESTs encoding human ACSL4, which they called FACL4. They used the ESTs to identify a brain cDNA containing the remainder of the FACL4 coding region. The predicted 670-amino acid human protein is 97% identical to rat Acs4. Independently, Piccini et al. (1998) cloned FACL4 cDNAs. Northern blot analysis revealed that FACL4 was expressed as a 5-kb mRNA in a variety of tissues. The transcript in brain appeared to be slightly larger. Sequence analysis of FACL4 cDNAs showed that the larger mRNAs result from alternative splicing and encode a predicted protein with 41 additional N-terminal amino acids. The authors stated that the 41-amino acid peptide is hydrophobic and suggested that it may change the intracellular localization of FACL4 or its fatty acid specificity. Meloni et al. (2002) found that FACL4 was highly expressed in adult human brain, especially in cerebellum and hippocampus, and showed a distribution similar to that obtained in mouse. A strong cytoplasmic staining was found in Purkinje and granular cells of cerebellum and in the pyramidal layer of hippocampus, indicating that FACL4 is specifically expressed in neurons and not in glial cells. Within the neuron, FACL4 was found primarily in neuronal soma and proximal dendrites. Vitelli et al. (2000) cloned the mouse Facl4 gene.GENE STRUCTURE
Minekura et al. (2001) determined that the ACSL4 gene contains 16 exons and spans approximately 90 kb. The 5-prime flanking region does not have a typical TATA box, but it has a CCAAT box and transcription factor-binding sites for AP2 (see 107580), AP4 (600743), and CREB (123810). Minekura et al. (2001) identified several other potential binding sites. Watkins et al. (2007) determined that the ACSL4 gene contains at least 17 exons.MAPPING
By somatic cell hybrid analysis and FISH, Cao et al. (1998) mapped the ACSL4 gene to chromosome Xq23. Piccini et al. (1998) further refined the map position to chromosome Xq22.3 by showing that the ACSL4 gene was contained within a YAC contig from that region. Watkins et al. (2007) mapped the ACSL4 gene to the minus strand of chromosome Xq22.3-q23 by genomic sequence analysis. Vitelli et al. (2000) mapped the mouse Acsl4 gene to chromosome XF1-F3 by FISH.GENE FUNCTION
Kang et al. (1997) showed that rat Acs4 preferentially used arachidonate and eicosapentaenoate as substrates. Cao et al. (1998) showed that human FACL4 exhibited FACL activity with a preference for arachidonic acid as substrate when expressed in mammalian cells.MOLECULAR GENETICS
Piccini et al. (1998) reported that the 2 patients with Alport syndrome, elliptocytosis, and mental retardation described by Jonsson et al. (1998) (300194) carried a large deletion of the COL4A5 (303630) region that included the contiguous FACL4. Piccini et al. (1998) suggested that the absence of FACL4 might play a role in the development of mental retardation or other signs associated with Alpo ... 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 300157 was added.