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Protein

Triokinase/FMN cyclase

Gene

TKFC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

    • ATP binding Source: UniProtKB-KW
    • FAD-AMP lyase (cyclizing) activity Source: UniProtKB
    • glycerone kinase activity Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • triokinase activity Source: UniProtKB

    GO - Biological processi

    • carbohydrate phosphorylation Source: UniProtKB
    • cellular carbohydrate metabolic process Source: UniProtKB
    • fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate Source: Reactome
    • glycerol metabolic process Source: InterPro
    • innate immune response Source: Reactome
    • negative regulation of MDA-5 signaling pathway Source: UniProtKB
    • regulation of innate immune response Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Lyase, Transferase

    Keywords - Ligandi

    ATP-binding, Cobalt, FAD, Flavoprotein, Magnesium, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS07615-MONOMER.
    BRENDAi2.7.1.29. 2681.
    4.6.1.15. 2681.
    ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
    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

    HGNCiHGNC:24552. TKFC.

    Subcellular locationi

    GO - Cellular componenti

    • cytosol Source: Reactome
    • extracellular exosome Source: UniProtKB
    • nucleus Source: UniProtKB
    Complete GO annotation...

    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

    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.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00551024.

    PTM databases

    iPTMnetiQ3LXA3.
    PhosphoSitePlusiQ3LXA3.

    Miscellaneous databases

    PMAP-CutDBQ3LXA3.

    Expressioni

    Tissue specificityi

    Detected in erythrocytes (at protein level).1 Publication

    Gene expression databases

    BgeeiENSG00000149476.
    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

    WithEntry#Exp.IntActNotes
    SDCBPO005603EBI-4291069,EBI-727004

    Protein-protein interaction databases

    BioGridi117481. 25 interactors.
    DIPiDIP-60967N.
    IntActiQ3LXA3. 1 interactor.
    MINTiMINT-5001370.
    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

    Contains 1 DhaK domain.PROSITE-ProRule annotation
    Contains 1 DhaL domain.PROSITE-ProRule annotation

    Phylogenomic databases

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

    Family and domain databases

    InterProiIPR012734. DhaK_ATP.
    IPR004006. DhaK_dom.
    IPR004007. DhaL_dom.
    [Graphical view]
    PfamiPF02733. Dak1. 1 hit.
    PF02734. Dak2. 1 hit.
    [Graphical view]
    SMARTiSM01120. Dak2. 1 hit.
    [Graphical view]
    SUPFAMiSSF101473. SSF101473. 1 hit.
    TIGRFAMsiTIGR02361. dak_ATP. 1 hit.
    PROSITEiPS51481. DHAK. 1 hit.
    PS51480. DHAL. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    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

    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 → T.4 PublicationsCorresponds to variant rs2260655dbSNPEnsembl.1
    Natural variantiVAR_054780334A → G.Corresponds to variant rs35723406dbSNPEnsembl.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. [Q3LXA3-1]
    XP_016873012.1. XM_017017523.1. [Q3LXA3-2]
    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

    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. [Q3LXA3-1]
    XP_016873012.1. XM_017017523.1. [Q3LXA3-2]
    UniGeneiHs.6278.

    3D structure databases

    ProteinModelPortaliQ3LXA3.
    SMRiQ3LXA3.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi117481. 25 interactors.
    DIPiDIP-60967N.
    IntActiQ3LXA3. 1 interactor.
    MINTiMINT-5001370.
    STRINGi9606.ENSP00000378360.

    PTM databases

    iPTMnetiQ3LXA3.
    PhosphoSitePlusiQ3LXA3.

    Polymorphism and mutation databases

    BioMutaiDAK.
    DMDMi311033370.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00551024.

    Proteomic databases

    EPDiQ3LXA3.
    MaxQBiQ3LXA3.
    PaxDbiQ3LXA3.
    PeptideAtlasiQ3LXA3.
    PRIDEiQ3LXA3.

    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.
    GeneCardsiTKFC.
    HGNCiHGNC:24552. TKFC.
    HPAiHPA039486.
    HPA048186.
    MIMi615844. gene.
    neXtProtiNX_Q3LXA3.
    OpenTargetsiENSG00000149476.
    PharmGKBiPA142672014.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:HS07615-MONOMER.
    BRENDAi2.7.1.29. 2681.
    4.6.1.15. 2681.
    ReactomeiR-HSA-168928. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.
    R-HSA-70350. Fructose catabolism.

    Miscellaneous databases

    ChiTaRSiDAK. human.
    GeneWikiiDAK_(gene).
    GenomeRNAii26007.
    PMAP-CutDBQ3LXA3.
    PROiQ3LXA3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000149476.
    CleanExiHS_DAK.
    ExpressionAtlasiQ3LXA3. baseline and differential.
    GenevisibleiQ3LXA3. HS.

    Family and domain databases

    InterProiIPR012734. DhaK_ATP.
    IPR004006. DhaK_dom.
    IPR004007. DhaL_dom.
    [Graphical view]
    PfamiPF02733. Dak1. 1 hit.
    PF02734. Dak2. 1 hit.
    [Graphical view]
    SMARTiSM01120. Dak2. 1 hit.
    [Graphical view]
    SUPFAMiSSF101473. SSF101473. 1 hit.
    TIGRFAMsiTIGR02361. dak_ATP. 1 hit.
    PROSITEiPS51481. DHAK. 1 hit.
    PS51480. DHAL. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiTKFC_HUMAN
    AccessioniPrimary (citable) accession number: Q3LXA3
    Secondary accession number(s): Q2L9C1
    , Q53EQ9, Q9BVA7, Q9H895
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 24, 2006
    Last sequence update: November 2, 2010
    Last modified: November 2, 2016
    This is version 113 of the entry and version 2 of the sequence. [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, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    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. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.