ACSL4 (acyl-CoA synthetase long chain family member 4)

Gene

• Entrez ID: 2182
• Gene name: Acyl-CoA synthetase long chain family member 4
• Gene symbol: ACSL4
• Synonyms: ACS4, FACL4, LACS4, MRX63, MRX68, XLID63
• Chromosome: X
• Chromosome location: Xq23
• Summary: The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation. This isozyme preferentially utilizes arachidonate as substrate. The absence of this enzyme may contribute to the cognitive disability or Alport syndrome. Alternative splicing of this gene generates multiple transcript variants. [provided by RefSeq, Jan 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs122458138	G>T	Pathogenic	Coding sequence variant, missense variant
rs122458139	G>A	Pathogenic	Coding sequence variant, missense variant
rs183171123	T>C	Conflicting-interpretations-of-pathogenicity, benign	Intron variant
rs200451158	T>C	Conflicting-interpretations-of-pathogenicity, likely-benign	Missense variant, coding sequence variant
rs886042180	AT>-	Pathogenic	Frameshift variant, coding sequence variant
rs1569423317	T>C	Pathogenic	Splice acceptor variant
rs1603401125	A>C	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT020060	hsa-miR-375	Microarray	20215506
MIRT025215	hsa-miR-34a-5p	Proteomics, Reporter assay;Proteomics	21566225
MIRT028658	hsa-miR-30a-5p	Proteomics	18668040
MIRT043925	hsa-miR-378a-3p	CLASH	23622248
MIRT054569	hsa-miR-205-5p	Luciferase reporter assay, qRT-PCR, Western blot	24576478
MIRT108438	hsa-miR-129-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT108446	hsa-miR-200b-3p	PAR-CLIP	22100165
MIRT108447	hsa-miR-200c-3p	PAR-CLIP	22100165
MIRT108448	hsa-miR-429	PAR-CLIP	22100165
MIRT108449	hsa-miR-507	PAR-CLIP, HITS-CLIP	21572407
MIRT108450	hsa-miR-557	PAR-CLIP, HITS-CLIP	21572407
MIRT124869	hsa-miR-190a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT124869	hsa-miR-190a-3p	HITS-CLIP	23824327
MIRT124873	hsa-miR-5011-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT124873	hsa-miR-5011-5p	HITS-CLIP	23824327
MIRT175287	hsa-miR-450b-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175300	hsa-miR-4789-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175300	hsa-miR-4789-3p	HITS-CLIP	23824327
MIRT175328	hsa-miR-448	PAR-CLIP, HITS-CLIP	21572407
MIRT175328	hsa-miR-448	HITS-CLIP	23824327
MIRT175377	hsa-miR-8084	PAR-CLIP	22100165
MIRT175378	hsa-miR-17-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175379	hsa-miR-20a-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175380	hsa-miR-93-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175381	hsa-miR-106a-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175384	hsa-miR-106b-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175396	hsa-miR-20b-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175400	hsa-miR-519c-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175402	hsa-miR-526b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175403	hsa-miR-519b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175406	hsa-miR-519d-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175408	hsa-miR-519a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT175420	hsa-miR-548t-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT175430	hsa-miR-4477a	PAR-CLIP, HITS-CLIP	21572407
MIRT175442	hsa-miR-548az-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT441285	hsa-miR-142-3p	HITS-CLIP	22473208
MIRT444489	hsa-miR-578	PAR-CLIP	22100165
MIRT444490	hsa-miR-1298-5p	PAR-CLIP	22100165
MIRT444491	hsa-miR-374b-5p	PAR-CLIP	22100165
MIRT444492	hsa-miR-374a-5p	PAR-CLIP	22100165
MIRT444493	hsa-miR-5692c	PAR-CLIP	22100165
MIRT444494	hsa-miR-5692b	PAR-CLIP	22100165
MIRT444495	hsa-miR-369-3p	PAR-CLIP	22100165
MIRT549440	hsa-miR-3680-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549441	hsa-miR-3658	PAR-CLIP, HITS-CLIP	21572407
MIRT549442	hsa-miR-33b-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT549443	hsa-miR-33a-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT549444	hsa-miR-527	PAR-CLIP, HITS-CLIP	21572407
MIRT549445	hsa-miR-518a-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT549446	hsa-miR-3653-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549447	hsa-miR-16-1-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549448	hsa-miR-586	PAR-CLIP, HITS-CLIP	21572407
MIRT549448	hsa-miR-586	HITS-CLIP	23824327
MIRT549449	hsa-miR-410-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549450	hsa-miR-3163	PAR-CLIP, HITS-CLIP	21572407
MIRT549451	hsa-miR-8485	PAR-CLIP, HITS-CLIP	21572407
MIRT549451	hsa-miR-8485	HITS-CLIP	23824327
MIRT549452	hsa-miR-580-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT549453	hsa-miR-6507-5p	PAR-CLIP, HITS-CLIP	21572407
MIRT549454	hsa-miR-212-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549455	hsa-miR-132-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549456	hsa-miR-186-5p	PAR-CLIP	21572407
MIRT549457	hsa-miR-3662	PAR-CLIP, HITS-CLIP	21572407
MIRT549458	hsa-miR-301b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549459	hsa-miR-130b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549460	hsa-miR-130a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549461	hsa-miR-4295	PAR-CLIP, HITS-CLIP	21572407
MIRT549462	hsa-miR-301a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549463	hsa-miR-454-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549464	hsa-miR-3666	PAR-CLIP, HITS-CLIP	21572407
MIRT549465	hsa-miR-19b-3p	HITS-CLIP	22473208
MIRT549465	hsa-miR-19b-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549466	hsa-miR-19a-3p	HITS-CLIP	22473208
MIRT549466	hsa-miR-19a-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT549467	hsa-miR-144-3p	PAR-CLIP, HITS-CLIP	21572407
MIRT733092	hsa-miR-26a-1-3p	Luciferase reporter assay, qRT-PCR, Western blot	25961460

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001676	Process	Long-chain fatty acid metabolic process	IBA	21873635
GO:0001676	Process	Long-chain fatty acid metabolic process	IDA	24269233
GO:0001676	Process	Long-chain fatty acid metabolic process	IMP	22633490
GO:0004467	Function	Long-chain fatty acid-CoA ligase activity	IBA	21873635
GO:0004467	Function	Long-chain fatty acid-CoA ligase activity	IDA	10669417, 24269233
GO:0004467	Function	Long-chain fatty acid-CoA ligase activity	IMP	22633490
GO:0005524	Function	ATP binding	IEA
GO:0005737	Component	Cytoplasm	IDA	11889465
GO:0005741	Component	Mitochondrial outer membrane	IEA
GO:0005778	Component	Peroxisomal membrane	IEA
GO:0005783	Component	Endoplasmic reticulum	IBA	21873635
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005811	Component	Lipid droplet	IBA	21873635
GO:0005811	Component	Lipid droplet	IDA	14741744
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0006629	Process	Lipid metabolic process	IDA	9598324
GO:0007584	Process	Response to nutrient	IEA
GO:0015908	Process	Fatty acid transport	IEA
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IBA	21873635
GO:0016021	Component	Integral component of membrane	IEA
GO:0019432	Process	Triglyceride biosynthetic process	IEA
GO:0030182	Process	Neuron differentiation	IBA	21873635
GO:0031957	Function	Very long-chain fatty acid-CoA ligase activity	IMP	11889465
GO:0032024	Process	Positive regulation of insulin secretion	ISS
GO:0035336	Process	Long-chain fatty-acyl-CoA metabolic process	IBA	21873635
GO:0035338	Process	Long-chain fatty-acyl-CoA biosynthetic process	TAS
GO:0043025	Component	Neuronal cell body	IEA
GO:0044233	Component	Mitochondria-associated endoplasmic reticulum membrane	IDA	23455425
GO:0047676	Function	Arachidonate-CoA ligase activity	IBA	21873635
GO:0047676	Function	Arachidonate-CoA ligase activity	IDA	9598324
GO:0060136	Process	Embryonic process involved in female pregnancy	IEA
GO:0060996	Process	Dendritic spine development	IEA
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337
GO:0070672	Process	Response to interleukin-15	IEA

Other IDs

• MIM: 300157
• HGNC: 3571
• e!Ensembl: ENSG00000068366

Protein

• UniProt ID: O60488
• Protein name: Long-chain-fatty-acid--CoA ligase 4 (EC 6.2.1.3) (Arachidonate--CoA ligase) (EC 6.2.1.15) (Long-chain acyl-CoA synthetase 4) (LACS 4)
• Protein function: 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).
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00501	AMP-binding	103 → 578	AMP-binding enzyme	Family

• Sequence:

  MKLKLNVLTIILLPVHLLITIYSALIFIPWYFLTNAKKKNAMAKRIKAKPTSDKPGSPYR
  SVTHFDSLAVIDIPGADTLDKLFDHAVSKFGKKDSLGTREILSEENEMQPNGKVFKKLIL
  GNYKWMNYLEVNRRVNNFGSGLTALGLKPKNTIAIFCETRAEWMIAAQTCFKYNFPLVTL
  YATLGKEAVVHGLNESEASYLITSVELLESKLKTALLDISCVKHIIYVDNKAINKAEYPE
  GFEIHSMQSVEELGSNPENLGIPPSRPTPSDMAIVMYTSGSTGRPKGVMMHHSNLIAGMT
  GQCERIPGLGPKDTYIGYLPLAHVLELTAEISCFTYGCRIGYSSPLTLSDQSSKIKKGSK
  GDCTVLKPTLMAAVPEIMDRIYKNVMSKVQEMNYIQKTLFKIGYDYKLEQIKKGYDAPLC
  NLLLFKKVKALLGGNVRMMLSGGAPLSPQTHRFMNVCFCCPIGQGYGLTESCGAGTVTEV
  TDYTTGRVGAPLICCEIKLKDWQEGGYTINDKPNPRGEIVIGGQNISMGYFKNEEKTAED
  YSVDENGQRWFCTGDIGEFHPDGCLQIIDRKKDLVKLQAGEYVSLGKVEAALKNCPLIDN
  ICAFAKSDQSYVISFVVPNQKRLTLLAQQKGVEGTWVDICNNPAMEAEILKEIREAANAM
  KLERFEIPIKVRLSPEPWTPETGLVTDAFKLKRKELRNHYLKDIERMYGGK

• Sequence length: 711