Very long-chain acyl-CoA synthetase (SLC27A2)
The protein contains 620 amino acids for an estimated molecular weight of 70312 Da.
Acyl CoA synthetase that activates long-chain and very long-chain fatty acids (VLCFAs) by catalyzing the formation of fatty acyl-CoA (PubMed:10198260, PubMed:10749848, PubMed:11980911). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (PubMed:10198260). Does not activate C24 bile acids, cholate and chenodeoxycholate (PubMed:11980911). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (PubMed:11980911). Exhibits long-chain fatty acids (LCFA) transport activity and plays an important role in hepatic fatty acid uptake (PubMed:20530735).', 'Exhibits both long-chain fatty acids (LCFA) transport activity and acyl CoA synthetase towards very long-chain fatty acids (PubMed:21768100). Shows a preference for generating CoA derivatives of n-3 fatty acids, which are preferentially trafficked into phosphatidylinositol (PubMed:21768100).', 'Exhibits long-chain fatty acids (LCFA) transport activity but lacks acyl CoA synthetase towards very long-chain fatty acids. (updated: April 22, 2020)
Protein identification was indicated in the following studies:
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.
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| Variant | Description |
|---|---|
| dbSNP:rs1648348 |
Biological Process
Bile acid biosynthetic process
Fatty acid alpha-oxidation
Fatty acid beta-oxidation
Long-chain fatty acid import into cell
Long-chain fatty acid metabolic process
Methyl-branched fatty acid metabolic process
Neutrophil degranulation
Protein localization
Protein targeting to peroxisome
Very long-chain fatty acid catabolic process
Cellular Component
Cytosol
Endoplasmic reticulum
Endoplasmic reticulum lumen
Endoplasmic reticulum membrane
Extracellular exosome
Integral component of endoplasmic reticulum membrane
Integral component of peroxisomal membrane
Peroxisomal membrane
Plasma membrane
Specific granule membrane
Molecular Function
Acyl-CoA ligase activity
Arachidonate-CoA ligase activity
ATP binding
Cholate-CoA ligase activity
Decanoate-CoA ligase activity
Enzyme binding
Fatty acid transmembrane transporter activity
Long-chain fatty acid transporter activity
Long-chain fatty acid-CoA ligase activity
Phytanate-CoA ligase activity
Pristanate-CoA ligase activity
Signaling receptor binding
Very long-chain fatty acid-CoA ligase activity
The reference OMIM entry for this protein is 603247
Solute carrier family 27 (fatty acid transporter), member 2; slc27a2
Fatty acid transport protein 2; fatp2
Fatty acid coa ligase, very long chain 1; facvl1
Very long chain acyl-coa synthetase; vlacs; vlcs
Acyl-coa synthetase very long chain f
DESCRIPTION
In mammals, oxidation of very long chain fatty acids (VLCFAs) containing more than 22 carbons takes place primarily in peroxisomes. Very long chain acyl-CoA synthetase (VLACS, or SLC27A2), a peroxisomal and microsomal enzyme, catalyzes a crucial step in this pathway, the activation of VLCFAs to their CoA thioesters (summary by Uchiyama et al., 1996).CLONING
Uchiyama et al. (1996) cloned cDNAs encoding rat Vlacs. The predicted protein is 40% identical to mouse Fatp (see 600691), a fatty acid transport protein. Two of the regions conserved between these proteins are thought to be ATP-binding and/or hydrolysis domains. By immunoblot analysis of subcellular fractions, the authors demonstrated that VLACS is located in peroxisomes and microsomes but not mitochondria. Northern blot analysis revealed that VLACS is expressed only in rat liver and kidney. Wakui et al. (1998) stated that the nucleotide sequence of human VLACS has been deposited in GenBank (GENBANK D88308). The predicted human and rat proteins each have 620 amino acids and share 82% sequence identity. Using an expression cloning strategy, Schaffer and Lodish (1994) identified a membrane protein, which they termed fatty acid transport protein, or FATP, from murine adipocytes. FATP facilitates the uptake of long chain fatty acids. Hirsch et al. (1998) identified a large family of FATPs characterized by the presence of an FATP signature sequence. They identified 5 distinct FATPs in mouse and 6 different FATPs in human, which they designated FATP1 (SLC27A1), -2 (SLC27A2), -3 (SLC27A3; 604193), -4 (SLC27A4; 604194), -5 (SLC27A5; 603314), and -6 (SLC27A6; 604196). Human and mouse FATPs have unique expression patterns and are found in major organs of fatty acid metabolism, such as adipose tissue, liver, heart, and kidney.GENE FUNCTION
Heinzer et al. (2002) demonstrated highest levels of Vlcs activity in mouse liver and kidney, tissues that showed highest expression of Vlcs by Northern blot and RT-PCR analyses. They used the mouse model of X-linked adrenoleukodystrophy (ALD; 300100) to test the hypothesis that the ALD protein (ABCD1; 300371) is required for proper expression or localization of VLCS. Their results indicated that, although the beta-oxidation defect in mouse ALD fibroblasts improved with overexpression and targeting of Vlcs to peroxisomes, Ald protein was not necessary for the proper expression or localization of Vlcs, and the control of very long chain fatty acid levels did not depend on the direct interaction between Vlcs and Ald protein.GENE STRUCTURE
Watkins et al. (2007) determined that the SLC27A2 gene contains 10 exons.MAPPING
By fluorescence in situ hybridization, Wakui et al. (1998) mapped the FACVL1 gene to 15q21.2. Watkins et al. (2007) mapped the SLC27A2 gene to the plus strand of chromosome 15q21.2 by genomic sequence analysis.ANIMAL MODEL
Heinzer et al. (2003) characterized a Vlcs knockout mouse that exhibited decreased peroxisomal VLCS activity and VLCFA beta-oxidation but did not accumulate VLCFAs. They generated mice doubly null for Vlcs and Abcd1, the gene mutant in human X-linked ALD; the double knockout mice had the biochemical abnormalities observed in the individual knockout mice but did not display a more severe X-linked ALD phenotype. Heinzer et al. (2003) concluded that VLCFA levels are independent of peroxisomal fatty acid beta-oxidation, that there is no ABCD1/VLCS in ... More on the omim web site
April 25, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Sept. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 603247 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).