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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
    mouse all
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    Genomic context

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    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
    		Compare labs

    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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    NEW Try the new Transcript table

    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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