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    PFKL phosphofructokinase, liver type [ Homo sapiens (human) ]

    Gene ID: 5211, updated on 3-Nov-2024

    Summary

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    Official Symbol
    PFKLprovided by HGNC
    Official Full Name
    phosphofructokinase, liver typeprovided by HGNC
    Primary source
    HGNC:HGNC:8876
    See related
    Ensembl:ENSG00000141959 MIM:171860; AllianceGenome:HGNC:8876
    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
    PFK-B; PFK-L; ATP-PFK
    Summary
    This gene encodes the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
    Expression
    Ubiquitous expression in kidney (RPKM 49.4), duodenum (RPKM 37.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PFKL in Genome Data Viewer
    Location:
    21q22.3
    Exon count:
    28
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (44300053..44327373)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (42654110..42681430)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (45719936..45747256)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45670291-45670805 Neighboring gene DNMT3L antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45676001-45676989 Neighboring gene H3K27ac hESC enhancer GRCh37_chr21:45677884-45678384 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45681495-45682054 Neighboring gene DNA methyltransferase 3 like Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45685919-45686548 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45686549-45687178 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45691192-45691798 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18564 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45702827-45703430 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45703431-45704032 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45704033-45704636 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45704637-45705238 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13378 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18565 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18566 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18567 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13379 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13380 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18568 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45724667-45725466 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45725506-45726160 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45726161-45726814 Neighboring gene autoimmune regulator Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45727470-45728123 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13381 Neighboring gene Sharpr-MPRA regulatory region 3786 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18569 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751251-45751752 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45751753-45752252 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18570 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45761314-45761956 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr21:45761957-45762600 Neighboring gene cilia and flagella associated protein 410 Neighboring gene NANOG hESC enhancer GRCh37_chr21:45763343-45763898 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45765021-45765523 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18571 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18572 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:45790067-45790900 Neighboring gene transient receptor potential cation channel subfamily M member 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45797213-45797712 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45797713-45798214 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:45798708-45798913 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:45821987-45822910 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:45825427-45826626 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18573 Neighboring gene TRPM2 antisense RNA

    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 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. Structural basis for allosteric regulation of human phosphofructokinase-1. Lynch EM, et al. Nat Commun, 2024 Aug 25. PMID 39183237, Free PMC Article
    2. Selective activation of PFKL suppresses the phagocytic oxidative burst. Amara N, et al. Cell, 2021 Aug 19. PMID 34320407, Free PMC Article
    3. Cellular distribution of 6-phosphofructo-1-kinase isoenzymes in rat brain. Zeitschel U, et al. J Neurochem, 1996 Dec. PMID 8931492
    4. Gene dosage effects of PFKL in transfected PC12 cells. Elson A, et al. Prog Clin Biol Res, 1993. PMID 8115399
    5. Assignment of the human gene for liver-type 6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic cell hybrids and monoclonal anti-L antibody. Vora S, et al. Proc Natl Acad Sci U S A, 1981 Jun. PMID 6455664, Free PMC Article

    See all (171) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis for allosteric regulation of human phosphofructokinase-1.
      Title: Structural basis for allosteric regulation of human phosphofructokinase-1.
    2. Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.
      Title: Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.
    3. EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL.
      Title: EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL.
    4. miR-21-5p/Tiam1-mediated glycolysis reprogramming drives breast cancer progression via enhancing PFKL stabilization.
      Title: miR-21-5p/Tiam1-mediated glycolysis reprogramming drives breast cancer progression via enhancing PFKL stabilization.
    5. Selective activation of PFKL suppresses the phagocytic oxidative burst.
      Title: Selective activation of PFKL suppresses the phagocytic oxidative burst.
    6. Relocation of phosphofructokinases within epithelial cells is a novel event preceding breast cancer recurrence that accurately predicts patient outcomes.
      Title: Relocation of phosphofructokinases within epithelial cells is a novel event preceding breast cancer recurrence that accurately predicts patient outcomes.
    7. Biochemical and transcript level differences between the three human phosphofructokinases show optimisation of each isoform for specific metabolic niches.
      Title: Biochemical and transcript level differences between the three human phosphofructokinases show optimisation of each isoform for specific metabolic niches.
    8. A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma.
      Title: A20 targets PFKL and glycolysis to inhibit the progression of hepatocellular carcinoma.
    9. (125)I irradiation upregulated the suppression of miR-338 on PFKL to downregulate the Warburg effect.
      Title: (125)I suppressed the Warburg effect viaregulating miR-338/PFKL axis in hepatocellular carcinoma.
    10. TAp73 deficiency results in a pronounced reduction in tumorigenic potential, which can be rescued by forced PFKL expression.
      Title: TAp73-induced phosphofructokinase-1 transcription promotes the Warburg effect and enhances cell proliferation.
    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

    EBI GWAS Catalog

    Description
    The human AIRE gene at chromosome 21q22 is a genetic determinant for the predisposition to rheumatoid arthritis in Japanese population.
    EBI GWAS Catalog

    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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    Replication interactions

    Interaction Pubs
    Knockdown of phosphofructokinase, liver (PFKL) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Rev rev HIV-1 Rev interacting protein, phosphofructokinase, liver (PFKL), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells 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

    Clone Names

    • FLJ30173, FLJ40909, DKFZp686G1648, DKFZp686L2097

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 6-phosphofructokinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 6-phosphofructokinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to 6-phosphofructokinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables fructose binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables fructose-6-phosphate binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables fructose-6-phosphate binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in canonical glycolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fructose 1,6-bisphosphate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fructose 1,6-bisphosphate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fructose 6-phosphate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fructose 6-phosphate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fructose 6-phosphate metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in glycolytic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to glucose IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of 6-phosphofructokinase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of 6-phosphofructokinase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol HDA PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in ficolin-1-rich granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    is_active_in membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in secretory granule lumen TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    ATP-dependent 6-phosphofructokinase, liver type
    Names
    6-phosphofructokinase type B
    6-phosphofructokinase, liver type
    liver-type 1-phosphofructokinase
    phosphofructo-1-kinase isozyme B
    phosphohexokinase
    NP_001002021.2
    NP_002617.3
    XP_005261192.1
    XP_005261194.1
    XP_006724074.1
    XP_011527905.1
    XP_016883858.1
    XP_024307853.1
    XP_047296778.1
    XP_047296779.1
    XP_047296780.1
    XP_047296781.1
    XP_054180520.1
    XP_054180521.1
    XP_054180522.1
    XP_054180523.1
    XP_054180524.1
    XP_054180525.1

    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_034033.1 RefSeqGene

      Range
      5020..32340
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001002021.3 → NP_001002021.2  ATP-dependent 6-phosphofructokinase, liver type isoform a

      See identical proteins and their annotated locations for NP_001002021.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the shorter isoform (a).
      Source sequence(s)
      BC006422, BC018295, BU177678, BX351711, HY111158
      UniProtKB/Swiss-Prot
      P17858
      UniProtKB/TrEMBL
      Q7L2M7
      Conserved Domains (1) summary
      cd00764
      Location:79 → 823
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...

    2. NM_002626.6 → NP_002617.3  ATP-dependent 6-phosphofructokinase, liver type isoform b

      See identical proteins and their annotated locations for NP_002617.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks three alternate exons in the 5' region and initiates translation at an alternate upstream start codon, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is longer than isoform a.
      Source sequence(s)
      BC018295, BU177678, BX351711, CB997055
      Consensus CDS
      CCDS33582.1
      UniProtKB/Swiss-Prot
      P17858, Q96A64, Q96IH4, Q9BR91
      Related
      ENSP00000269848.6, ENST00000349048.9
      Conserved Domains (1) summary
      cd00764
      Location:13 → 773
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      44300053..44327373
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047440822.1 → XP_047296778.1  ATP-dependent 6-phosphofructokinase, liver type isoform X1

    2. XM_024452085.2 → XP_024307853.1  ATP-dependent 6-phosphofructokinase, liver type isoform X2

      Conserved Domains (1) summary
      cd00764
      Location:79 → 823
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...

    3. XM_006724011.2 → XP_006724074.1  ATP-dependent 6-phosphofructokinase, liver type isoform X1

      Conserved Domains (1) summary
      cd00764
      Location:79 → 846
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...

    4. XM_047440825.1 → XP_047296781.1  ATP-dependent 6-phosphofructokinase, liver type isoform X4

    5. XM_017028369.2 → XP_016883858.1  ATP-dependent 6-phosphofructokinase, liver type isoform X5

      Conserved Domains (1) summary
      cd00764
      Location:6 → 750
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...

    6. XM_005261135.4 → XP_005261192.1  ATP-dependent 6-phosphofructokinase, liver type isoform X3

      Conserved Domains (2) summary
      cd00764
      Location:13 → 796
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...
      TIGR02478
      Location:16 → 778
      6PF1K_euk; 6-phosphofructokinase, eukaryotic type

    7. XM_047440824.1 → XP_047296780.1  ATP-dependent 6-phosphofructokinase, liver type isoform X2

    8. XM_047440823.1 → XP_047296779.1  ATP-dependent 6-phosphofructokinase, liver type isoform X1

    9. XM_005261137.5 → XP_005261194.1  ATP-dependent 6-phosphofructokinase, liver type isoform X6

      See identical proteins and their annotated locations for XP_005261194.1

      Conserved Domains (2) summary
      cd00764
      Location:1 → 744
      Eukaryotic_PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to a subfamily of the PFKA family (cd00363) and include eukaryotic ATP-dependent ...
      TIGR02478
      Location:1 → 726
      6PF1K_euk; 6-phosphofructokinase, eukaryotic type

    10. XM_011529603.3 → XP_011527905.1  ATP-dependent 6-phosphofructokinase, liver type isoform X7

      UniProtKB/TrEMBL
      Q7L2M7
      Conserved Domains (1) summary
      cl00204
      Location:3 → 551
      PFK; Phosphofructokinase, a key regulatory enzyme in glycolysis, catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-biphosphate. The members belong to PFK family that includes ATP- and pyrophosphate (PPi)- dependent phosphofructokinases. ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      42654110..42681430
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324545.1 → XP_054180520.1  ATP-dependent 6-phosphofructokinase, liver type isoform X1

    2. XM_054324547.1 → XP_054180522.1  ATP-dependent 6-phosphofructokinase, liver type isoform X3

    3. XM_054324546.1 → XP_054180521.1  ATP-dependent 6-phosphofructokinase, liver type isoform X2

    4. XM_054324548.1 → XP_054180523.1  ATP-dependent 6-phosphofructokinase, liver type isoform X5

    5. XM_054324549.1 → XP_054180524.1  ATP-dependent 6-phosphofructokinase, liver type isoform X6

    6. XM_054324550.1 → XP_054180525.1  ATP-dependent 6-phosphofructokinase, liver type isoform X7

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P17858.6 GenPept UniProtKB/Swiss-Prot:P17858

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