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    CYP4F3 cytochrome P450 family 4 subfamily F member 3 [ Homo sapiens (human) ]

    Gene ID: 4051, updated on 3-Apr-2024

    Summary

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    Official Symbol
    CYP4F3provided by HGNC
    Official Full Name
    cytochrome P450 family 4 subfamily F member 3provided by HGNC
    Primary source
    HGNC:HGNC:2646
    See related
    Ensembl:ENSG00000186529 MIM:601270; AllianceGenome:HGNC:2646
    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
    CPF3; CYP4F; LTB4H; CYPIVF3
    Summary
    This gene, CYP4F3, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]
    Expression
    Biased expression in liver (RPKM 51.6), bone marrow (RPKM 29.9) and 6 other tissues See more
    Orthologs
    all
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    Genomic context

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    Location:
    19p13.12
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (15640897..15662825)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (15766167..15788209)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (15751707..15773635)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ribosomal protein L23a pseudogene 2 Neighboring gene cytochrome P450 family 4 subfamily F member 8 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10286 Neighboring gene cytochrome P450 family 4 subfamily F member 10, pseudogene Neighboring gene cytochrome P450 family 4 subfamily F member 12

    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. Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study. Ananthakrishnan AN, et al. Inflamm Bowel Dis, 2017 Nov. PMID 28991856, Free PMC Article
    2. Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus. Yin J, et al. Mol Carcinog, 2017 Jun. PMID 28150878, Free PMC Article
    3. Human cytochrome P450 4F3: structure, functions, and prospects. Corcos L, et al. Drug Metabol Drug Interact, 2012 Apr 19. PMID 22706230
    4. LTB4 can stimulate human osteoclast differentiation dependent of RANKL. Chen ZK, et al. Artif Cells Blood Substit Immobil Biotechnol, 2010. PMID 20047521
    5. Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke. Mao JT, et al. Cancer Prev Res (Phila), 2008 Sep. PMID 19138970

    See all (30) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. High n3:n6 polyunsaturated fatty acids (PUFA) intake was associated with a reduced risk of ulcerative colitis (UC) in individuals with the GG/AG genotype at a single nucleotide polymorphism in CYP4F3 but not those with the AA genotype. The association between dietary n3:n6 PUFA intake and risk of UC may be modified variants at CYP4F3.
      Title: Genetic Polymorphisms in Fatty Acid Metabolism Modify the Association Between Dietary n3: n6 Intake and Risk of Ulcerative Colitis: A Prospective Cohort Study.
    2. The results suggest that a potentially functional single-nucleotide polymorphisms in CYP4F3 (rs4646904) may contribute to the etiology of lung cancer, especially in smokers.
      Title: Pathway-analysis of published genome-wide association studies of lung cancer: A potential role for the CYP4F3 locus.
    3. Children who consumed a higher dietary ratio of omega6/omega3 were susceptible for Crohn's disease if they were also carriers of specific variants of CYP4F3 and FADS2 genes.
      Title: Interactions between the dietary polyunsaturated fatty acid ratio and genetic factors determine susceptibility to pediatric Crohn's disease.
    4. In this short review, emphasis will be placed on the regulation and the functional roles of human CYP4F3--{REVIEW}
      Title: Human cytochrome P450 4F3: structure, functions, and prospects.
    5. can directly stimulate osteoclast differentiation dependent of RANKL
      Title: LTB4 can stimulate human osteoclast differentiation dependent of RANKL.
    6. CYP4F3B is the key enzyme to produce 20-HETE by omega-hydroxylation of arachidonic acid in liver cells
      Title: CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis.
    7. Observational study of gene-disease association. (HuGE Navigator)
      Title: New genetic associations detected in a host response study to hepatitis B vaccine.
    8. By regulating the balance of LTB4 in the lung, LTB4OH may function as a suppressor of lung carcinogenesis.
      Title: Differential modulation of leukotriene B4 synthesis and degradation in human bronchoalveolar lavage cells by lipopolysaccharide and tobacco smoke.
    9. Main fatty acid pathway is the omega-hydroxylation of polyunsaturated fatty acids.
      Title: Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism.
    10. 3-hydroxystearate and 3-hydroxypalmitate are converted to omega-hydroxylated 3-OHDCA precursors in liver; CYP4F11 and, to a lesser extent, CYP4F2 catalyzed omega-hydroxylation of 3-hydroxystearate; CYP4F3b, CYP4F12, and CYP4A11 had negligible activity.
      Title: Omega oxidation of 3-hydroxy fatty acids by the human CYP4F gene subfamily enzyme CYP4F11.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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

    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

    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 20-aldehyde-leukotriene B4 20-monooxygenase activity TAS
    Traceable Author Statement
    more info
    		  
    enables 20-hydroxy-leukotriene B4 omega oxidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables aromatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables heme binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables iron ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables leukotriene-B4 20-monooxygenase activity TAS
    Traceable Author Statement
    more info
    		  
    enables monooxygenase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in arachidonic acid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in icosanoid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in leukotriene B4 catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in leukotriene metabolic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    cytochrome P450 4F3
    Names
    20-HETE synthase
    20-hydroxyeicosatetraenoic acid synthase
    cytochrome P-450
    cytochrome P450, family 4, subfamily F, polypeptide 3
    cytochrome P450, subfamily IVF, polypeptide 3 (leukotriene B4 omega hydroxylase)
    cytochrome P450-LTB-omega
    docosahexaenoic acid omega-hydroxylase CYP4F3
    leukotriene B4 omega hydroxylase
    leukotriene-B(4) 20-monooxygenase 2
    leukotriene-B(4) omega-hydroxylase 2
    leukotriene-B4 20-monooxygenase
    NP_000887.2
    NP_001186137.1
    NP_001186138.1
    NP_001356625.1
    XP_011526316.1
    XP_016882304.1
    XP_047294796.1
    XP_054177005.1
    XP_054177006.1
    XP_054177007.1

    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_007964.2 RefSeqGene

      Range
      5002..26930
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000896.3 → NP_000887.2  cytochrome P450 4F3 isoform a

      See identical proteins and their annotated locations for NP_000887.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform a, which is the same length but has internal differences compared to isoform b.
      Source sequence(s)
      AB002454, AD000685, D12621
      Consensus CDS
      CCDS12332.1
      UniProtKB/Swiss-Prot
      B7Z8Z3, O60634, Q08477, Q5U740
      UniProtKB/TrEMBL
      A0A0A0MQR0
      Related
      ENSP00000221307.6, ENST00000221307.13
      Conserved Domains (1) summary
      pfam00067
      Location:52 → 515
      p450; Cytochrome P450

    2. NM_001199208.2 → NP_001186137.1  cytochrome P450 4F3 isoform b

      See identical proteins and their annotated locations for NP_001186137.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon and contains another alternate in-frame exon compared to variant 1. The resulting isoform (b) is the same length but has a different internal segment compared to isoform a. Variants 2, 3, and 4 all encode the same isoform (b).
      Source sequence(s)
      AB002454, AD000685, BC136299, DB184202
      Consensus CDS
      CCDS59362.1
      UniProtKB/TrEMBL
      B7Z442
      Related
      ENSP00000466988.1, ENST00000591058.5
      Conserved Domains (1) summary
      pfam00067
      Location:52 → 515
      p450; Cytochrome P450

    3. NM_001199209.2 → NP_001186138.1  cytochrome P450 4F3 isoform b

      See identical proteins and their annotated locations for NP_001186138.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks an alternate in-frame exon, and contains another alternate in-frame exon compared to variant 1. The resulting isoform (b) is the same length but has a different internal segment compared to isoform a. Variants 2, 3, and 4 all encode the same isoform (b).
      Source sequence(s)
      AD000685, AK316136, BC136299, DB184202
      Consensus CDS
      CCDS59362.1
      UniProtKB/TrEMBL
      B7Z442
      Related
      ENSP00000466395.1, ENST00000586182.6
      Conserved Domains (1) summary
      pfam00067
      Location:52 → 515
      p450; Cytochrome P450

    4. NM_001369696.1 → NP_001356625.1  cytochrome P450 4F3 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), as well as variants 2 and 3, encodes isoform b.
      Source sequence(s)
      AD000685
      Consensus CDS
      CCDS59362.1
      UniProtKB/TrEMBL
      B7Z442
      Related
      ENSP00000468105.1, ENST00000585846.1
      Conserved Domains (1) summary
      pfam00067
      Location:52 → 515
      p450; Cytochrome P450

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      15640897..15662825
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047438840.1 → XP_047294796.1  cytochrome P450 4F3 isoform X2

    2. XM_017026815.2 → XP_016882304.1  cytochrome P450 4F3 isoform X1

      Conserved Domains (1) summary
      pfam00067
      Location:52 → 378
      p450; Cytochrome P450

    3. XM_011528014.4 → XP_011526316.1  cytochrome P450 4F3 isoform X2

      See identical proteins and their annotated locations for XP_011526316.1

      UniProtKB/TrEMBL
      B7Z449
      Conserved Domains (1) summary
      pfam00067
      Location:1 → 366
      p450; Cytochrome P450

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      15766167..15788209
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054321031.1 → XP_054177006.1  cytochrome P450 4F3 isoform X2

    2. XM_054321030.1 → XP_054177005.1  cytochrome P450 4F3 isoform X1

    3. XM_054321032.1 → XP_054177007.1  cytochrome P450 4F3 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q08477.2 GenPept UniProtKB/Swiss-Prot:Q08477

    Gene LinkOut

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