Long-chain fatty acid transport protein 4 (SLC27A4)

The protein contains 643 amino acids for an estimated molecular weight of 72064 Da.

 

Involved in translocation of long-chain fatty acids (LFCA) across the plasma membrane (PubMed:12556534, PubMed:21395585). Has acyl-CoA ligase activity for long-chain and very-long-chain fatty acids (VLCFAs) (PubMed:24269233). Appears to be the principal fatty acid transporter in small intestinal enterocytes. Plays a role in the formation of the epidermal barrier. Required for fat absorption in early embryogenesis (By similarity). Probably involved in fatty acid transport across the blood barrier (PubMed:21395585). Indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Prevents light-induced degeneration of rods and cones (By similarity). (updated: April 22, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 7%
Model score: 43
MODL_I-TASSER-3.0

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VariantDescription
IPS
Correlates with lower body mass index, triglyceride concentrations, syst
IPS
IPS
IPS
IPS

No binding partner found

The reference OMIM entry for this protein is 604194

Solute carrier family 27 (fatty acid transporter), member 4; slc27a4
Fatty acid transport protein 4; fatp4
Acyl-coa synthetase very long chain family, member 5; acsvl5

CLONING

Using an expression cloning strategy, Schaffer and Lodish (1994) identified a membrane protein, which they termed fatty acid transport protein, or FATP (SLC27A1; 600691), 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; 600691), -2 (SLC27A2; 603247), -3 (SLC27A3; 604193), -4 (SLC27A4), -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. By database analysis, Watkins et al. (2007) identified SLC27A4, which they called ACSVL5. The deduced 643-amino acid protein contains all 5 motifs characteristic of acyl-CoA synthetases. Phylogenetic analysis revealed that ACSVL5 belongs to a family of very long chain acyl-CoA synthetases.

GENE STRUCTURE

Gertow et al. (2004) stated that the FATP4 gene contains 12 coding exons spanning more than 17 kb of genomic DNA. Watkins et al. (2007) determined that the SLC27A4 gene contains 13 exons.

MAPPING

Gertow et al. (2004) stated that the FATP4 gene maps to chromosome 9q34. Watkins et al. (2007) mapped the SLC27A4 gene to the plus strand of chromosome 9q34.11 by genomic sequence analysis.

GENE FUNCTION

Stahl et al. (1999) showed that FATP4 is expressed at high levels on the apical side of mature enterocytes in the small intestine. Furthermore, overexpression of FATP4 in 293 cells facilitated uptake of long chain fatty acids with the same specificity as enterocytes, while reduction of FATP4 expression in primary enterocytes by antisense oligonucleotides inhibited fatty acid uptake by 50%. These results suggested that FATP4 is the principal fatty acid transporter in enterocytes and may constitute a novel target for antiobesity therapy. Klar et al. (2009) demonstrated that FATP4 deficiency in human fibroblasts is associated with reduced VLCFA-CoA synthetase activity and a reduced incorporation of VLCFA into neutral and polar lipids.

MOLECULAR GENETICS

- Ichthyosis Prematurity Syndrome Klar et al. (2009) performed sequence analysis of the FATP4 gene in a North African family, a Middle Eastern family, and 18 families of Scandinavian origin segregating ichthyosis prematurity syndrome (IPS; 608649). They identified 7 different mutations. All affected members of the Scandinavian families were homozygous or compound heterozygous for a nonsense mutation (C168X; 604194.0001), indicating a founder effect. A splice site mutation (604194.0002) and a missense mutation (604194.0007) were identified in homozygosity in affected members of the North African and the Middle Eastern families, respectively. None of the mutations were found in 120 healthy control individuals. - Insulin Resistance Syndrome Gertow et al. (2004) investigated polymorphisms in the FATP4 gene with respect to associations with fasting and postprandial lipid and lipoprotein variables and markers of insulin resistance in 608 healthy, middle-aged Swedish men. Heterozygotes for a gly209-to-ser (G209S) polymorphism (ser allele frequency 0.05) had significantly lower body mass index (BMI) and, correcting for BMI, significantly lower triglyceride concentrations, systolic blood pressure, insulin ... More on the omim web site

Subscribe to this protein entry history

April 25, 2020: 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 604194 was added.