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    TKFC triokinase and FMN cyclase [ Homo sapiens (human) ]

    Gene ID: 26007, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TKFCprovided by HGNC
    Official Full Name
    triokinase and FMN cyclaseprovided by HGNC
    Primary source
    HGNC:HGNC:24552
    See related
    Ensembl:ENSG00000149476 MIM:615844; AllianceGenome:HGNC:24552
    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
    DAK; NET45; TKFCD
    Summary
    This gene is a member of the family of dihydroxyacetone kinases, which have a protein structure distinct from other kinases. The product of this gene phosphorylates dihydroxyacetone, and also catalyzes the formation of riboflavin 4',5'-phosphate (aka cyclin FMN) from FAD. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2017]
    Expression
    Broad expression in duodenum (RPKM 30.4), small intestine (RPKM 22.4) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TKFC in Genome Data Viewer
    Location:
    11q12.2
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (61333228..61353426)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (61322174..61342034)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (61100700..61120898)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:61033788-61034987 Neighboring gene von Willebrand factor C and EGF domains Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:61048939-61049860 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3387 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:61061839-61062541 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3389 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:61067594-61068793 Neighboring gene damage specific DNA binding protein 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61100139-61100661 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61100662-61101184 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:61112523-61113449 Neighboring gene cytochrome b561 family member A3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4795 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:61129243-61129964 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 4797 Neighboring gene transmembrane protein 138 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3391 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61159824-61160785 Neighboring gene transmembrane protein 216

    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. A comprehensive update of the sequence and structure classification of kinases. Cheek S, et al. BMC Struct Biol, 2005 Mar 16. PMID 15771780, Free PMC Article
    2. Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B. Xu MY, et al. J Transl Med, 2013 Sep 27. PMID 24289155, Free PMC Article
    3. Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease. Wortmann SB, et al. Am J Hum Genet, 2020 Feb 6. PMID 32004446, Free PMC Article
    4. Dihydroxyacetone metabolism by human erythrocytes: demonstration of triokinase activity and its characterization. Beutler E, et al. Blood, 1973 Apr. PMID 4688871
    5. Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases. Cabezas A, et al. Biochem Biophys Res Commun, 2005 Dec 30. PMID 16289032

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.
      Title: Bi-allelic Variants in TKFC Encoding Triokinase/FMN Cyclase Are Associated with Cataracts and Multisystem Disease.
    2. The peptide fragment (m/z 520.3) of DAK is a promising biomarker to guide timing of antiviral treatment and to avoid liver biopsy in compensated chronic hepatitis B patients.
      Title: Serum dihydroxyacetone kinase peptide m/z 520.3 as predictor of disease severity in patients with compensated chronic hepatitis B.
    3. analysis of human triokinase/FMN cyclase reveals that kinase activity requires intact homodimers, but cyclase requires only a truncated, single domain subunit
      Title: Bifunctional homodimeric triokinase/FMN cyclase: contribution of protein domains to the activities of the human enzyme and molecular dynamics simulation of domain movements.
    4. DAK, the physiological suppressor of cytoplasmic viral RNA sensor MDA5, specifically inhibits MDA5- but not RNA helicase RIG-I-mediated innate antiviral signaling.
      Title: Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.
    5. Evidence supports that a single protein sustains both FMN cyclase and ATP-dependent Dha kinase activities, probably in a single active center
      Title: Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases.
    Submit: New GeneRIF Correction

    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
    Triokinase and FMN cyclase deficiency syndrome
    MedGen: C5394125 OMIM: 618805 GeneReviews: Not available
    		Compare labs

    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

    Clone Names

    • MGC5621, DKFZp586B1621

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables FAD-AMP lyase (cyclizing) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables glycerone kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables glycerone kinase activity IDA
    Inferred from Direct Assay
    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 
    enables triokinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in carbohydrate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in carbohydrate phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glycerol catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of MDA-5 signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of innate immune response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in nucleus HDA PubMed 

    General protein information

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    Preferred Names
    triokinase/FMN cyclase
    Names
    ATP-dependent dihydroxyacetone kinase
    DHA kinase
    Dha kinase/FMN cyclase
    FAD-AMP lyase cyclic FMN forming
    FAD-AMP lyase cyclizing
    bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing)
    dihydroxyacetone kinase 2 homolog
    glycerone kinase
    testis tissue sperm-binding protein Li 84P
    NP_001338905.1
    NP_001338906.1
    NP_001338907.1
    NP_001338908.1
    NP_001338909.1
    NP_056348.2
    XP_011543214.1
    XP_016873006.1
    XP_016873007.1
    XP_016873008.1
    XP_016873009.1
    XP_047282683.1
    XP_047282684.1
    XP_047282685.1
    XP_047282686.1
    XP_047282687.1
    XP_047282688.1
    XP_047282689.1
    XP_047282690.1
    XP_047282691.1
    XP_054224333.1
    XP_054224334.1
    XP_054224335.1
    XP_054224336.1
    XP_054224337.1
    XP_054224338.1
    XP_054224339.1
    XP_054224340.1
    XP_054224341.1
    XP_054224342.1
    XP_054224343.1
    XP_054224344.1
    XP_054224345.1
    XP_054224346.1
    XP_054224347.1
    XP_054224348.1

    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.

    mRNA and Protein(s)

    1. NM_001351976.2 → NP_001338905.1  triokinase/FMN cyclase isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3), as well as variant 2, encodes isoform b.
      Source sequence(s)
      AP003108
      Consensus CDS
      CCDS8003.1
      UniProtKB/Swiss-Prot
      Q2L9C1, Q3LXA3, Q53EQ9, Q9BVA7, Q9H895
      UniProtKB/TrEMBL
      A0A140VJH7, H0YCY6
      Conserved Domains (1) summary
      TIGR02361
      Location:4 → 558
      dak_ATP; dihydroxyacetone kinase, ATP-dependent

    2. NM_001351977.2 → NP_001338906.1  triokinase/FMN cyclase isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AP003108
      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (1) summary
      cl10557
      Location:4 → 526
      Dak1; Dak1 domain

    3. NM_001351978.2 → NP_001338907.1  triokinase/FMN cyclase isoform c

      Status: REVIEWED

      Source sequence(s)
      AP003108
      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (1) summary
      cl10557
      Location:4 → 525
      Dak1; Dak1 domain

    4. NM_001351979.2 → NP_001338908.1  triokinase/FMN cyclase isoform d

      Status: REVIEWED

      Source sequence(s)
      AP003108
      UniProtKB/TrEMBL
      H0YCY6
      Related
      ENSP00000432539.1, ENST00000529479.5
      Conserved Domains (1) summary
      cl10557
      Location:4 → 526
      Dak1; Dak1 domain

    5. NM_001351980.2 → NP_001338909.1  triokinase/FMN cyclase isoform e

      Status: REVIEWED

      Source sequence(s)
      AP003108
      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (1) summary
      cl10557
      Location:1 → 456
      Dak1; Dak1 domain

    6. NM_015533.4 → NP_056348.2  triokinase/FMN cyclase isoform b

      See identical proteins and their annotated locations for NP_056348.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), as well as variant 3, encodes isoform b.
      Source sequence(s)
      AP003108, BC001341, BF197629, DA932478, DB056724
      Consensus CDS
      CCDS8003.1
      UniProtKB/Swiss-Prot
      Q2L9C1, Q3LXA3, Q53EQ9, Q9BVA7, Q9H895
      UniProtKB/TrEMBL
      A0A140VJH7, H0YCY6
      Related
      ENSP00000378360.3, ENST00000394900.8
      Conserved Domains (1) summary
      TIGR02361
      Location:4 → 558
      dak_ATP; dihydroxyacetone kinase, 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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      61333228..61353426
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047426731.1 → XP_047282687.1  triokinase/FMN cyclase isoform X7

    2. XM_047426732.1 → XP_047282688.1  triokinase/FMN cyclase isoform X7

    3. XM_047426729.1 → XP_047282685.1  triokinase/FMN cyclase isoform X6

      UniProtKB/Swiss-Prot
      Q2L9C1, Q3LXA3, Q53EQ9, Q9BVA7, Q9H895
      UniProtKB/TrEMBL
      A0A140VJH7

    4. XM_047426730.1 → XP_047282686.1  triokinase/FMN cyclase isoform X6

      UniProtKB/Swiss-Prot
      Q2L9C1, Q3LXA3, Q53EQ9, Q9BVA7, Q9H895
      UniProtKB/TrEMBL
      A0A140VJH7

    5. XM_047426733.1 → XP_047282689.1  triokinase/FMN cyclase isoform X8

    6. XM_017017519.3 → XP_016873008.1  triokinase/FMN cyclase isoform X4

      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (3) summary
      TIGR02361
      Location:4 → 526
      dak_ATP; dihydroxyacetone kinase, ATP-dependent
      pfam02733
      Location:19 → 335
      Dak1; Dak1 domain
      pfam02734
      Location:398 → 526
      Dak2; DAK2 domain

    7. XM_047426734.1 → XP_047282690.1  triokinase/FMN cyclase isoform X8

    8. XM_047426735.1 → XP_047282691.1  triokinase/FMN cyclase isoform X8

    9. XM_047426728.1 → XP_047282684.1  triokinase/FMN cyclase isoform X4

    10. XM_047426727.1 → XP_047282683.1  triokinase/FMN cyclase isoform X4

    11. XM_017017518.2 → XP_016873007.1  triokinase/FMN cyclase isoform X3

      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (3) summary
      TIGR02361
      Location:50 → 571
      dak_ATP; dihydroxyacetone kinase, ATP-dependent
      pfam02733
      Location:65 → 381
      Dak1; Dak1 domain
      pfam02734
      Location:444 → 571
      Dak2; DAK2 domain

    12. XM_017017517.2 → XP_016873006.1  triokinase/FMN cyclase isoform X2

      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (3) summary
      TIGR02361
      Location:50 → 604
      dak_ATP; dihydroxyacetone kinase, ATP-dependent
      pfam02733
      Location:65 → 381
      Dak1; Dak1 domain
      pfam02734
      Location:444 → 604
      Dak2; DAK2 domain

    13. XM_017017520.2 → XP_016873009.1  triokinase/FMN cyclase isoform X5

      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (3) summary
      TIGR02361
      Location:50 → 572
      dak_ATP; dihydroxyacetone kinase, ATP-dependent
      pfam02733
      Location:65 → 381
      Dak1; Dak1 domain
      pfam02734
      Location:444 → 572
      Dak2; DAK2 domain

    14. XM_011544912.4 → XP_011543214.1  triokinase/FMN cyclase isoform X1

      See identical proteins and their annotated locations for XP_011543214.1

      UniProtKB/TrEMBL
      H0YCY6
      Conserved Domains (3) summary
      TIGR02361
      Location:50 → 572
      dak_ATP; dihydroxyacetone kinase, ATP-dependent
      pfam02733
      Location:65 → 381
      Dak1; Dak1 domain
      pfam02734
      Location:444 → 572
      Dak2; DAK2 domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      61322174..61342034
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054368369.1 → XP_054224344.1  triokinase/FMN cyclase isoform X7

    2. XM_054368366.1 → XP_054224341.1  triokinase/FMN cyclase isoform X6

    3. XM_054368368.1 → XP_054224343.1  triokinase/FMN cyclase isoform X6

    4. XM_054368371.1 → XP_054224346.1  triokinase/FMN cyclase isoform X8

    5. XM_054368361.1 → XP_054224336.1  triokinase/FMN cyclase isoform X4

    6. XM_054368370.1 → XP_054224345.1  triokinase/FMN cyclase isoform X7

    7. XM_054368367.1 → XP_054224342.1  triokinase/FMN cyclase isoform X6

    8. XM_054368372.1 → XP_054224347.1  triokinase/FMN cyclase isoform X8

    9. XM_054368362.1 → XP_054224337.1  triokinase/FMN cyclase isoform X4

    10. XM_054368373.1 → XP_054224348.1  triokinase/FMN cyclase isoform X8

    11. XM_054368364.1 → XP_054224339.1  triokinase/FMN cyclase isoform X4

    12. XM_054368363.1 → XP_054224338.1  triokinase/FMN cyclase isoform X4

    13. XM_054368360.1 → XP_054224335.1  triokinase/FMN cyclase isoform X3

    14. XM_054368359.1 → XP_054224334.1  triokinase/FMN cyclase isoform X2

    15. XM_054368365.1 → XP_054224340.1  triokinase/FMN cyclase isoform X5

    16. XM_054368358.1 → XP_054224333.1  triokinase/FMN cyclase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q3LXA3.2 GenPept UniProtKB/Swiss-Prot:Q3LXA3

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