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ACSL4 acyl-CoA synthetase long chain family member 4 [ Homo sapiens (human) ]

Gene ID: 2182, updated on 16-Apr-2024

Summary

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Official Symbol
ACSL4provided by HGNC
Official Full Name
acyl-CoA synthetase long chain family member 4provided by HGNC
Primary source
HGNC:HGNC:3571
See related
Ensembl:ENSG00000068366 MIM:300157; AllianceGenome:HGNC:3571
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ACS4; FACL4; LACS4; MRX63; MRX68; XLID63
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]
Expression
Ubiquitous expression in adrenal (RPKM 24.5), appendix (RPKM 24.0) and 25 other tissues See more
Orthologs
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Genomic context

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See ACSL4 in Genome Data Viewer
Location:
Xq23
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (109641335..109733257, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (108089125..108181021, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (108884564..108976486, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene potassium voltage-gated channel subfamily E regulatory subunit 5 Neighboring gene protein phosphatase 6 catalytic subunit pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29845 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29846 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20936 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:108976221-108976341 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29848 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29847 Neighboring gene uncharacterized LOC105373311 Neighboring gene Sharpr-MPRA regulatory region 2605 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:109083294-109083806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29849 Neighboring gene Sharpr-MPRA regulatory region 2184 Neighboring gene RPS5 pseudogene 7 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20938 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:109246549-109247204 Neighboring gene transmembrane protein 164 Neighboring gene microRNA 652

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. ACSL4: a double-edged sword target in multiple myeloma, promotes cell proliferation and sensitizes cell to ferroptosis. Zhang J, et al. Carcinogenesis, 2023 May 27. PMID 36999754
  2. Combination of serum ACSL4 levels and low-dose 256-slice spiral CT exhibits the potential in the early screening of lung cancer. Yu W, et al. Medicine (Baltimore), 2023 Feb 3. PMID 36749237, Free PMC Article
  3. iTRAQ-based Proteomic Analysis Unveils ACSL4 as a Novel Potential Regulator of Human Endometrial Receptivity. Hu S, et al. Endocrinology, 2023 Jan 9. PMID 36652382
  4. ACSL4 is overexpressed in psoriasis and enhances inflammatory responses by activating ferroptosis. Liu L, et al. Biochem Biophys Res Commun, 2022 Oct 1. PMID 35868067
  5. Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion. Tuo QZ, et al. Signal Transduct Target Ther, 2022 Feb 23. PMID 35197442, Free PMC Article

See all (145) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. METTL3 promotes trophoblast ferroptosis in preeclampsia by stabilizing the ACSL4 m[6]A modification.
    Title: METTL3 promotes trophoblast ferroptosis in preeclampsia by stabilizing the ACSL4 m(6)A modification.
  2. Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.
    Title: Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.
  3. The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.
    Title: The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.
  4. Loss of nephric augmenter of liver regeneration facilitates acute kidney injury via ACSL4-mediated ferroptosis.
    Title: Loss of nephric augmenter of liver regeneration facilitates acute kidney injury via ACSL4-mediated ferroptosis.
  5. Serum ACSL4 levels in patients with ST-segment elevation myocardial infarction (STEMI) and its association with one-year major adverse cardiovascular events (MACE): A prospective cohort study.
    Title: Serum ACSL4 levels in patients with ST-segment elevation myocardial infarction (STEMI) and its association with one-year major adverse cardiovascular events (MACE): A prospective cohort study.
  6. RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4.
    Title: RBM45 reprograms lipid metabolism promoting hepatocellular carcinoma via Rictor and ACSL1/ACSL4.
  7. SENP1 inhibits ferroptosis and promotes head and neck squamous cell carcinoma by regulating ACSL4 protein stability via SUMO1.
    Title: SENP1 inhibits ferroptosis and promotes head and neck squamous cell carcinoma by regulating ACSL4 protein stability via SUMO1.
  8. miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4.
    Title: miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4.
  9. Methylation Regulation of LPCAT3 Improves Osteoarthritis by Regulating ACSL4 to Inhibit Chondrocyte Ferroptosis.
    Title: Methylation Regulation of LPCAT3 Improves Osteoarthritis by Regulating ACSL4 to Inhibit Chondrocyte Ferroptosis.
  10. MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis.
    Title: MMD collaborates with ACSL4 and MBOAT7 to promote polyunsaturated phosphatidylinositol remodeling and susceptibility to ferroptosis.
Submit: New GeneRIF Correction See all GeneRIFs (74)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Intellectual disability, X-linked 63
MedGen: C1845672 OMIM: 300387 GeneReviews: Not available
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Copy number response

Description
Copy number response
Haploinsufficency

Little evidence for dosage pathogenicity (Last evaluated 2021-04-28)

ClinGen Genome Curation PagePubMed
Triplosensitivity

No evidence available (Last evaluated 2021-04-28)

ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables arachidonate-CoA ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables arachidonate-CoA ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables long-chain fatty acid-CoA ligase activity EXP
Inferred from Experiment
more info
 PubMed 
enables long-chain fatty acid-CoA ligase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables long-chain fatty acid-CoA ligase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables palmitoyl-CoA ligase activity TAS
Traceable Author Statement
more info
  
enables very long-chain fatty acid-CoA ligase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
involved_in embryonic process involved in female pregnancy IEA
Inferred from Electronic Annotation
more info
  
involved_in fatty acid metabolic process TAS
Traceable Author Statement
more info
  
involved_in lipid metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in long-chain fatty acid metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in long-chain fatty acid metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in long-chain fatty acid metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in long-chain fatty-acyl-CoA biosynthetic process TAS
Traceable Author Statement
more info
  
involved_in long-chain fatty-acyl-CoA metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of insulin secretion ISS
Inferred from Sequence or Structural Similarity
more info
  
Component Evidence Code Pubs
located_in cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in lipid droplet IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lipid droplet IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane HDA PubMed 
located_in mitochondria-associated endoplasmic reticulum membrane contact site IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial outer membrane TAS
Traceable Author Statement
more info
  
located_in peroxisomal membrane IEA
Inferred from Electronic Annotation
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
long-chain-fatty-acid--CoA ligase 4
Names
acyl-CoA synthetase 4
arachidonate--CoA ligase
fatty-acid-Coenzyme A ligase, long-chain 4
lignoceroyl-CoA synthase
long-chain acyl-CoA synthetase 4
long-chain fatty-acid-Coenzyme A ligase 4
NP_001305438.1
NP_001305439.1
NP_004449.1
NP_075266.1
XP_005262166.1
XP_006724698.1
XP_011529190.1
XP_011529191.1
XP_024308119.1
XP_047297874.1
XP_047297875.1
XP_054182658.1
XP_054182659.1
XP_054182660.1
XP_054182661.1
XP_054182662.1
XP_054182663.1
XP_054182664.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008053.1 RefSeqGene

    Range
    5136..97058
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001318509.2 → NP_001305438.1  long-chain-fatty-acid--CoA ligase 4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region compared to variant 1. The encoded isoform (2) has a longer N-terminus compared to isoform 1. Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AF030555, AK307566, AL118496, AL138968, BQ022679
    Consensus CDS
    CCDS14548.1
    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000419171.2, ENST00000469796.7
    Conserved Domains (1) summary
    cd17639
    Location:121 → 696
    LC_FACS_euk1; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS), including fungal proteins

  2. NM_001318510.2 → NP_001305439.1  long-chain-fatty-acid--CoA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variant 1 and 4 encode the same isoform (1).
    Source sequence(s)
    AF030555, AK292070, BC034959
    Consensus CDS
    CCDS14549.1
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000500273.1, ENST00000672401.1
    Conserved Domains (1) summary
    cd05927
    Location:80 → 667
    LC-FACS_euk; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS)

  3. NM_004458.3 → NP_004449.1  long-chain-fatty-acid--CoA ligase 4 isoform 1

    See identical proteins and their annotated locations for NP_004449.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform 1. Variants 1 and 4 encode the same isoform (1).
    Source sequence(s)
    AF030555, BC034959, BQ016115, CN310691, DR004263
    Consensus CDS
    CCDS14549.1
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000262835.7, ENST00000348502.10
    Conserved Domains (1) summary
    cd05927
    Location:80 → 667
    LC-FACS_euk; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS)

  4. NM_022977.3 → NP_075266.1  long-chain-fatty-acid--CoA ligase 4 isoform 2

    See identical proteins and their annotated locations for NP_075266.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region compared to variant 1. The encoded isoform (2) has a longer N-terminus compared to isoform 1. Variants 2 and 3 encode the same isoform (2).
    Source sequence(s)
    AF030555, BC034959, BQ016115, CN310691, DR004263, Y13058
    Consensus CDS
    CCDS14548.1
    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000339787.2, ENST00000340800.7
    Conserved Domains (1) summary
    cd17639
    Location:121 → 696
    LC_FACS_euk1; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS), including fungal proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    109641335..109733257 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047441919.1 → XP_047297875.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

  2. XM_006724635.3 → XP_006724698.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

    See identical proteins and their annotated locations for XP_006724698.1

    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000500678.1, ENST00000672282.1
    Conserved Domains (1) summary
    cd05927
    Location:80 → 667
    LC-FACS_euk; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS)

  3. XM_011530889.3 → XP_011529191.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    See identical proteins and their annotated locations for XP_011529191.1

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8
    UniProtKB/TrEMBL
    Q8TAF6
    Conserved Domains (1) summary
    cd17639
    Location:121 → 696
    LC_FACS_euk1; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS), including fungal proteins

  4. XM_005262109.3 → XP_005262166.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    See identical proteins and their annotated locations for XP_005262166.1

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000425408.2, ENST00000502391.6
    Conserved Domains (1) summary
    cd17639
    Location:121 → 696
    LC_FACS_euk1; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS), including fungal proteins

  5. XM_047441918.1 → XP_047297874.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

  6. XM_011530888.3 → XP_011529190.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    See identical proteins and their annotated locations for XP_011529190.1

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8
    UniProtKB/TrEMBL
    Q8TAF6
    Related
    ENSP00000500897.1, ENST00000671846.1
    Conserved Domains (1) summary
    cd17639
    Location:121 → 696
    LC_FACS_euk1; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS), including fungal proteins

  7. XM_024452351.2 → XP_024308119.1  long-chain-fatty-acid--CoA ligase 4 isoform X1

    UniProtKB/TrEMBL
    Q8TAF6
    Conserved Domains (1) summary
    cd05927
    Location:127 → 714
    LC-FACS_euk; Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    108089125..108181021 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054326689.1 → XP_054182664.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

  2. XM_054326688.1 → XP_054182663.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

  3. XM_054326684.1 → XP_054182659.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8

  4. XM_054326686.1 → XP_054182661.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8

  5. XM_054326687.1 → XP_054182662.1  long-chain-fatty-acid--CoA ligase 4 isoform X3

  6. XM_054326685.1 → XP_054182660.1  long-chain-fatty-acid--CoA ligase 4 isoform X2

    UniProtKB/Swiss-Prot
    D3DUY2, O60488, O60848, O60849, Q5JWV8

  7. XM_054326683.1 → XP_054182658.1  long-chain-fatty-acid--CoA ligase 4 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O60488.2 GenPept UniProtKB/Swiss-Prot:O60488

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