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Protein

Triokinase/FMN cyclase

Gene

TKFC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes both the phosphorylation of dihydroxyacetone and of glyceraldehyde, and the splitting of ribonucleoside diphosphate-X compounds among which FAD is the best substrate. Represses IFIH1-mediated cellular antiviral response (PubMed:17600090).By similarity3 Publications

Catalytic activityi

ATP + glycerone = ADP + glycerone phosphate.1 Publication
ATP + D-glyceraldehyde = ADP + D-glyceraldehyde 3-phosphate.1 Publication
FAD = AMP + riboflavin cyclic-4',5'-phosphate.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarity
  • Mn2+By similarity, Co2+By similarityNote: Manganese or cobalt are requested for FAD-AMP lyase activity.By similarity

Activity regulationi

Each activity is inhibited by the substrate(s) of the other.

Kineticsi

  1. KM=0.5 µM for dihydroxyacetone1 Publication
  2. KM=11 µM for glyceraldehyde1 Publication
  3. KM=1.55 µM for dihydroxyacetone1 Publication
  4. KM=43.2 µM for ATP1 Publication
  5. KM=18.1 µM for glyceraldehyde1 Publication
  6. KM=7 µM for FAD1 Publication
  7. KM=12 µM for ADP-glucose1 Publication
  8. KM=317 µM for UDP-glucose1 Publication
  9. KM=263 µM for UDP-galactose1 Publication

    pH dependencei

    Optimum pH is 6.6.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei109DihydroxyacetonePROSITE-ProRule annotation1
    Binding sitei114DihydroxyacetonePROSITE-ProRule annotation1
    Active sitei221Tele-hemiaminal-histidine intermediatePROSITE-ProRule annotation1
    Binding sitei486ATP; via carbonyl oxygenBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi401 – 404ATPBy similarity4
    Nucleotide bindingi446 – 447ATPBy similarity2
    Nucleotide bindingi494 – 495ATPBy similarity2
    Nucleotide bindingi556 – 558ATPBy similarity3

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Lyase, Multifunctional enzyme, Transferase
    LigandATP-binding, Cobalt, FAD, Flavoprotein, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.1.29 2681
    4.6.1.15 2681
    ReactomeiR-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
    R-HSA-70350 Fructose catabolism

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Triokinase/FMN cyclaseImported
    Alternative name(s):
    Bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing)
    Including the following 2 domains:
    ATP-dependent dihydroxyacetone kinase (EC:2.7.1.28, EC:2.7.1.29)
    Short name:
    DHA kinase
    Alternative name(s):
    Glycerone kinase
    Triokinase
    Triose kinase
    FAD-AMP lyase (cyclizing) (EC:4.6.1.15)
    Alternative name(s):
    FAD-AMP lyase (cyclic FMN forming)
    FMN cyclase
    Gene namesi
    Name:TKFCImported
    Synonyms:DAKImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 11

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000149476.14
    HGNCiHGNC:24552 TKFC
    MIMi615844 gene
    neXtProtiNX_Q3LXA3

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi112T → A: Highly decreases kinase activity. No effect on FMN cyclase activity. 1 Publication1
    Mutagenesisi204K → A: Slightly decreases kinase activity. No effect on FMN cyclase activity. 1 Publication1
    Mutagenesisi221H → A: Abolishes kinase activity but not FMN cyclase activity. 1 Publication1
    Mutagenesisi401D → A: Abolishes both kinase and FMN cyclase activities. 1 Publication1
    Mutagenesisi403D → A: Abolishes both kinase and FMN cyclase activities. 1 Publication1
    Mutagenesisi404C → A: Decreases both kinase and FMN cyclase activities. 1 Publication1
    Mutagenesisi446S → A: Decreases both kinase and FMN cyclase activities. 1 Publication1
    Mutagenesisi556D → A: Abolishes both kinase and FMN cyclase activities. 1 Publication1

    Organism-specific databases

    DisGeNETi26007
    OpenTargetsiENSG00000149476
    PharmGKBiPA142672014

    Polymorphism and mutation databases

    BioMutaiDAK
    DMDMi311033370

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001215251 – 575Triokinase/FMN cyclaseAdd BLAST575

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei350PhosphoserineCombined sources1
    Modified residuei511PhosphoserineCombined sources1
    Modified residuei545PhosphoserineBy similarity1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    EPDiQ3LXA3
    MaxQBiQ3LXA3
    PaxDbiQ3LXA3
    PeptideAtlasiQ3LXA3
    PRIDEiQ3LXA3
    ProteomicsDBi61779

    2D gel databases

    REPRODUCTION-2DPAGEiIPI00551024

    PTM databases

    iPTMnetiQ3LXA3
    PhosphoSitePlusiQ3LXA3

    Miscellaneous databases

    PMAP-CutDBiQ3LXA3

    Expressioni

    Tissue specificityi

    Detected in erythrocytes (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000149476 Expressed in 165 organ(s), highest expression level in right adrenal gland
    CleanExiHS_DAK
    ExpressionAtlasiQ3LXA3 baseline and differential
    GenevisibleiQ3LXA3 HS

    Organism-specific databases

    HPAiHPA039486
    HPA048186

    Interactioni

    Subunit structurei

    Homodimer (By similarity). Interacts with IFIH1 (via the CARD domains), the interaction is inhibited by viral infection (PubMed:17600090).By similarity1 Publication

    Binary interactionsi

    Protein-protein interaction databases

    BioGridi117481, 28 interactors
    DIPiDIP-60967N
    IntActiQ3LXA3, 3 interactors
    STRINGi9606.ENSP00000378360

    Structurei

    3D structure databases

    ProteinModelPortaliQ3LXA3
    SMRiQ3LXA3
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini9 – 336DhaKPROSITE-ProRule annotationAdd BLAST328
    Domaini372 – 571DhaLPROSITE-ProRule annotationAdd BLAST200

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni56 – 59Dihydroxyacetone bindingBy similarity4

    Domaini

    DhaK and DhaL domains have differential roles, individually DhaK is inactive and DhaL displays cyclase but not kinase activity.1 Publication

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiKOG2426 Eukaryota
    COG2376 LUCA
    GeneTreeiENSGT00390000015415
    HOGENOMiHOG000234158
    HOVERGENiHBG079502
    InParanoidiQ3LXA3
    KOiK00863
    OMAiAWPNVAK
    PhylomeDBiQ3LXA3
    TreeFamiTF313821

    Family and domain databases

    Gene3Di1.25.40.340, 1 hit
    InterProiView protein in InterPro
    IPR012734 DhaK_ATP
    IPR004006 DhaK_dom
    IPR004007 DhaL_dom
    IPR036117 DhaL_dom_sf
    PfamiView protein in Pfam
    PF02733 Dak1, 1 hit
    PF02734 Dak2, 1 hit
    SMARTiView protein in SMART
    SM01120 Dak2, 1 hit
    SUPFAMiSSF101473 SSF101473, 1 hit
    TIGRFAMsiTIGR02361 dak_ATP, 1 hit
    PROSITEiView protein in PROSITE
    PS51481 DHAK, 1 hit
    PS51480 DHAL, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q3LXA3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MTSKKLVNSV AGCADDALAG LVACNPNLQL LQGHRVALRS DLDSLKGRVA
    60 70 80 90 100
    LLSGGGSGHE PAHAGFIGKG MLTGVIAGAV FTSPAVGSIL AAIRAVAQAG
    110 120 130 140 150
    TVGTLLIVKN YTGDRLNFGL AREQARAEGI PVEMVVIGDD SAFTVLKKAG
    160 170 180 190 200
    RRGLCGTVLI HKVAGALAEA GVGLEEIAKQ VNVVAKAMGT LGVSLSSCSV
    210 220 230 240 250
    PGSKPTFELS ADEVELGLGI HGEAGVRRIK MATADEIVKL MLDHMTNTTN
    260 270 280 290 300
    ASHVPVQPGS SVVMMVNNLG GLSFLELGII ADATVRSLEG RGVKIARALV
    310 320 330 340 350
    GTFMSALEMP GISLTLLLVD EPLLKLIDAE TTAAAWPNVA AVSITGRKRS
    360 370 380 390 400
    RVAPAEPQEA PDSTAAGGSA SKRMALVLER VCSTLLGLEE HLNALDRAAG
    410 420 430 440 450
    DGDCGTTHSR AARAIQEWLK EGPPPASPAQ LLSKLSVLLL EKMGGSSGAL
    460 470 480 490 500
    YGLFLTAAAQ PLKAKTSLPA WSAAMDAGLE AMQKYGKAAP GDRTMLDSLW
    510 520 530 540 550
    AAGQELQAWK SPGADLLQVL TKAVKSAEAA AEATKNMEAG AGRASYISSA
    560 570
    RLEQPDPGAV AAAAILRAIL EVLQS
    Length:575
    Mass (Da):58,947
    Last modified:November 2, 2010 - v2
    Checksum:i4DB8C5326F65122C
    GO
    Isoform 2 (identifier: Q3LXA3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         526-575: SAEAAAEATKNMEAGAGRASYISSARLEQPDPGAVAAAAILRAILEVLQS → EGGGLVICP

    Note: Inactive as DHA kinase and FMN cyclase.
    Show »
    Length:534
    Mass (Da):54,793
    Checksum:i6BC7E1EA00D32EC4
    GO

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    H0YCY6H0YCY6_HUMAN
    Triokinase/FMN cyclase
    TKFC
    533Annotation score:
    I3L252I3L252_HUMAN
    Triokinase/FMN cyclase
    TKFC
    219Annotation score:
    E9PJG8E9PJG8_HUMAN
    Triokinase/FMN cyclase
    TKFC
    162Annotation score:
    E9PQR1E9PQR1_HUMAN
    Triokinase/FMN cyclase
    TKFC
    57Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti7V → A in BAB14722 (PubMed:14702039).Curated1
    Sequence conflicti19A → S in BAD97300 (Ref. 4) Curated1
    Sequence conflicti75V → A in BAB14722 (PubMed:14702039).Curated1
    Sequence conflicti376L → P in BAB14722 (PubMed:14702039).Curated1
    Sequence conflicti497D → G in BAB14722 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_028108185A → T4 PublicationsCorresponds to variant dbSNP:rs2260655Ensembl.1
    Natural variantiVAR_054780334A → G. Corresponds to variant dbSNP:rs35723406Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_057181526 – 575SAEAA…EVLQS → EGGGLVICP in isoform 2. 1 PublicationAdd BLAST50

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    DQ138290 mRNA Translation: ABA10576.1
    DQ344550 mRNA Translation: ABC70184.1
    AK023915 mRNA Translation: BAB14722.1
    AK223580 mRNA Translation: BAD97300.1
    AP003108 Genomic DNA No translation available.
    BC001341 mRNA Translation: AAH01341.1
    CCDSiCCDS8003.1 [Q3LXA3-1]
    RefSeqiNP_056348.2, NM_015533.3 [Q3LXA3-1]
    XP_016873010.1, XM_017017521.1
    XP_016873012.1, XM_017017523.1
    UniGeneiHs.6278

    Genome annotation databases

    EnsembliENST00000394900; ENSP00000378360; ENSG00000149476 [Q3LXA3-1]
    GeneIDi26007
    KEGGihsa:26007
    UCSCiuc001nre.4 human [Q3LXA3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    DQ138290 mRNA Translation: ABA10576.1
    DQ344550 mRNA Translation: ABC70184.1
    AK023915 mRNA Translation: BAB14722.1
    AK223580 mRNA Translation: BAD97300.1
    AP003108 Genomic DNA No translation available.
    BC001341 mRNA Translation: AAH01341.1
    CCDSiCCDS8003.1 [Q3LXA3-1]
    RefSeqiNP_056348.2, NM_015533.3 [Q3LXA3-1]
    XP_016873010.1, XM_017017521.1
    XP_016873012.1, XM_017017523.1
    UniGeneiHs.6278

    3D structure databases

    ProteinModelPortaliQ3LXA3
    SMRiQ3LXA3
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi117481, 28 interactors
    DIPiDIP-60967N
    IntActiQ3LXA3, 3 interactors
    STRINGi9606.ENSP00000378360

    PTM databases

    iPTMnetiQ3LXA3
    PhosphoSitePlusiQ3LXA3

    Polymorphism and mutation databases

    BioMutaiDAK
    DMDMi311033370

    2D gel databases

    REPRODUCTION-2DPAGEiIPI00551024

    Proteomic databases

    EPDiQ3LXA3
    MaxQBiQ3LXA3
    PaxDbiQ3LXA3
    PeptideAtlasiQ3LXA3
    PRIDEiQ3LXA3
    ProteomicsDBi61779

    Protocols and materials databases

    DNASUi26007
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000394900; ENSP00000378360; ENSG00000149476 [Q3LXA3-1]
    GeneIDi26007
    KEGGihsa:26007
    UCSCiuc001nre.4 human [Q3LXA3-1]

    Organism-specific databases

    CTDi26007
    DisGeNETi26007
    EuPathDBiHostDB:ENSG00000149476.14
    GeneCardsiTKFC
    HGNCiHGNC:24552 TKFC
    HPAiHPA039486
    HPA048186
    MIMi615844 gene
    neXtProtiNX_Q3LXA3
    OpenTargetsiENSG00000149476
    PharmGKBiPA142672014
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2426 Eukaryota
    COG2376 LUCA
    GeneTreeiENSGT00390000015415
    HOGENOMiHOG000234158
    HOVERGENiHBG079502
    InParanoidiQ3LXA3
    KOiK00863
    OMAiAWPNVAK
    PhylomeDBiQ3LXA3
    TreeFamiTF313821

    Enzyme and pathway databases

    BRENDAi2.7.1.29 2681
    4.6.1.15 2681
    ReactomeiR-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
    R-HSA-70350 Fructose catabolism

    Miscellaneous databases

    ChiTaRSiTKFC human
    GeneWikiiDAK_(gene)
    GenomeRNAii26007
    PMAP-CutDBiQ3LXA3
    PROiPR:Q3LXA3
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000149476 Expressed in 165 organ(s), highest expression level in right adrenal gland
    CleanExiHS_DAK
    ExpressionAtlasiQ3LXA3 baseline and differential
    GenevisibleiQ3LXA3 HS

    Family and domain databases

    Gene3Di1.25.40.340, 1 hit
    InterProiView protein in InterPro
    IPR012734 DhaK_ATP
    IPR004006 DhaK_dom
    IPR004007 DhaL_dom
    IPR036117 DhaL_dom_sf
    PfamiView protein in Pfam
    PF02733 Dak1, 1 hit
    PF02734 Dak2, 1 hit
    SMARTiView protein in SMART
    SM01120 Dak2, 1 hit
    SUPFAMiSSF101473 SSF101473, 1 hit
    TIGRFAMsiTIGR02361 dak_ATP, 1 hit
    PROSITEiView protein in PROSITE
    PS51481 DHAK, 1 hit
    PS51480 DHAL, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiTKFC_HUMAN
    AccessioniPrimary (citable) accession number: Q3LXA3
    Secondary accession number(s): Q2L9C1
    , Q53EQ9, Q9BVA7, Q9H895
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2006
    Last sequence update: November 2, 2010
    Last modified: September 12, 2018
    This is version 125 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. SIMILARITY comments
      Index of protein domains and families
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
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