TCDB is operated by the Saier Lab Bioinformatics Group
Transporter Information:
Name: solute carrier family 27 (fatty acid transporter), member 5
Symbol: SLC27A5
TC: 9.B.17.1.5
Locations: 19q13.43
MGI: MGI:1347100
GenBank: AF064255
Swiss-Prot: Q9Y2P5
Accession Number: NM_012254
PubMed (10479480): Steinberg SJ, Wang SJ, McGuinness MC, Watkins PA. Human liver-specific very-long-chain acyl-coenzyme A synthetase: cDNA cloningand characterization of a second enzymatically active protein.Mol Genet Metab. 1999 Sep;68(1):32-42. PMID: 10479480 [PubMed - indexed for MEDLINE]

Activation of fatty acids, catalyzed by acyl-coenzyme A (acyl-CoA) synthetases, is required for their subsequent metabolism. Peroxisomes and microsomes contain very-long-chain acyl-CoA synthetases (VLCSs) capable of activating fatty acids with a chain length of 22 or more carbons. Decreased peroxisomal VLCS activity is, in part, responsible for the biochemical pathology in X-linked adrenoleukodystrophy (X-ALD), illustrating the importance of VLCSs in cellular fatty acid homeostasis. We previously cloned two human genes encoding proteins homologous to rat peroxisomal VLCS; one (hVLCS) is the human ortholog to the rat VLCS gene and another (hVLCS-H1) encodes a related heart-specific protein. Here, we report the cloning of a third gene (hVLCS-H2) and characterization of its protein product. The hVLCS-H2 gene is located on human chromosome 19 and encodes a 690-amino-acid protein. The amino acid sequence of hVLCS-H2 is 44-45% identical and 67-69% similar to those of both hVLCS and hVLCS-H1. COS-1 cells transiently overexpressing hVLCS-H2 activated the very-long-chain fatty acid lignocerate (C24:0) at a rate >1.5-fold higher than that of nontransfected cells (P < 0.002). The hVLCS-H2-dependent activation of long- and branched-chain fatty acids following transient transfection was less striking. However, hVLCS-H2-dependent acyl-CoA synthetase activity with long- and very-long-chain fatty acid substrates was detected in COS-1 cells stably expressing hVLCS-H2. For all substrates tested (C18:0, C20:0, C24:0, C26:0), the hVLCS-H2 catalyzed activity was significantly increased (P < 0.01 to P < 0.0001). By both Northern analysis and reverse transcription polymerase chain reaction, hVLCS-H2 is expressed primarily in liver. Indirect immunofluorescence of COS-1 cells or human hepatoma-derived HepG2 cells expressing epitope-tagged hVLCS-H2 revealed that the protein was associated with the endoplasmic reticulum but not with peroxisomes. Thus, the primary role of hVLCS-H2 is likely to be in fatty acid elongation or complex lipid synthesis rather than in degradation.

PubMed (10749848): Steinberg SJ, Mihalik SJ, Kim DG, Cuebas DA, Watkins PA. The human liver-specific homolog of very long-chain acyl-CoA synthetase ischolate:CoA ligase.J Biol Chem. 2000 May 26;275(21):15605-8. PMID: 10749848 [PubMed - indexed for MEDLINE]

Unconjugated bile acids must be activated to their CoA thioesters before conjugation to taurine or glycine can occur. A human homolog of very long-chain acyl-CoA synthetase, hVLCS-H2, has two requisite properties of a bile acid:CoA ligase, liver specificity and an endoplasmic reticulum subcellular localization. We investigated the ability of this enzyme to activate the primary bile acid, cholic acid, to its CoA derivative. When expressed in COS-1 cells, hVLCS-H2 exhibited cholate:CoA ligase (choloyl-CoA synthetase) activity with both non-isotopic and radioactive assays. Other long- and very long-chain acyl-CoA synthetases were incapable of activating cholate. Endogenous choloyl-CoA synthetase activity was also detected in liver-derived HepG2 cells but not in kidney-derived COS-1 cells. Our results are consistent with a role for hVLCS-H2 in the re-activation and re-conjugation of bile acids entering liver from the enterohepatic circulation rather than in de novo bile acid synthesis.

>sp|Q9Y2P5|S27A5_HUMAN Bile acyl-CoA synthetase OS=Homo sapiens GN=SLC27A5 PE=1 SV=1