Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Triokinase/FMN cyclase

Gene

Tkfc

Organism
Rattus norvegicus (Rat)
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 (PubMed:16289032). Represses IFIH1-mediated cellular antiviral response (By similarity).By similarity1 Publication

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Mg2+By similarity
  • Mn2+1 Publication, Co2+1 PublicationNote: Manganese or cobalt are requested for FAD-AMP lyase activity.1 Publication

Enzyme regulationi

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

Kineticsi

  1. KM=8.8 µM for FAD with manganese1 Publication
  2. KM=12.5 µM for ADP-glucose with manganese1 Publication
  3. KM=652 µM for UDP-glucose with manganese1 Publication
  4. KM=606 µM for UDP-galactose with manganese1 Publication
  5. KM=714 µM for UDP-xylose with manganese1 Publication
  6. KM=107 µM for UDP-glucuronate with manganese1 Publication
  7. KM=108 µM for UDP-galacturonate with manganese1 Publication
  8. KM=416 µM for CDP-glucose with manganese1 Publication
  9. KM=795 µM for CDP-glycerol with manganese1 Publication
  10. KM=784 µM for GDP-glucose with manganese1 Publication
  11. KM=343 µM for GDP-alpha-L-fucose with manganese1 Publication
  12. KM=114 µM for FAD with cobalt1 Publication
  13. KM=120 µM for ADP-glucose with cobalt1 Publication
  14. KM=2550 µM for UDP-glucose with cobalt1 Publication
  15. KM=3661 µM for UDP-galactose with cobalt1 Publication
  16. KM=2354 µM for UDP-xylose with cobalt1 Publication
  17. KM=539 µM for UDP-glucuronate with cobalt1 Publication
  18. KM=759 µM for UDP-galacturonate with cobalt1 Publication
  19. KM=3703 µM for CDP-glucose with cobalt1 Publication
  20. KM=2031 µM for CDP-glycerol with cobalt1 Publication
  21. KM=2246 µM for GDP-glucose with cobalt1 Publication
  22. KM=991 µM for GDP-alpha-L-fucose with cobalt1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei109 – 1091DihydroxyacetonePROSITE-ProRule annotation
    Binding sitei114 – 1141DihydroxyacetonePROSITE-ProRule annotation
    Active sitei221 – 2211Tele-hemiaminal-histidine intermediatePROSITE-ProRule annotation
    Binding sitei486 – 4861ATP; via carbonyl oxygenBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi401 – 4044ATPBy similarity
    Nucleotide bindingi446 – 4472ATPBy similarity
    Nucleotide bindingi494 – 4952ATPBy similarity
    Nucleotide bindingi556 – 5583ATPBy similarity

    GO - Molecular functioni

    GO - Biological processi

    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

    BioCyciMetaCyc:MONOMER-15866.
    ReactomeiR-RNO-70350. Fructose catabolism.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Triokinase/FMN cyclase
    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:Tkfc
    Synonyms:Dak
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    Proteomesi
    • UP000002494 Componenti: Chromosome 1

    Organism-specific databases

    RGDi1311026. Tkfc.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 578578Triokinase/FMN cyclasePRO_0000121527Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei511 – 5111PhosphoserineCombined sources
    Modified residuei545 – 5451PhosphoserineCombined sources

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ4KLZ6.
    PRIDEiQ4KLZ6.

    PTM databases

    iPTMnetiQ4KLZ6.
    PhosphoSiteiQ4KLZ6.

    Expressioni

    Gene expression databases

    GenevisibleiQ4KLZ6. RN.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    MINTiMINT-4580965.
    STRINGi10116.ENSRNOP00000028102.

    Structurei

    3D structure databases

    ProteinModelPortaliQ4KLZ6.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 336328DhaKPROSITE-ProRule annotationAdd
    BLAST
    Domaini372 – 571200DhaLPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni56 – 594Dihydroxyacetone bindingBy similarity

    Domaini

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

    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.
    InParanoidiQ4KLZ6.
    KOiK00863.
    OMAiEPAHVGF.
    OrthoDBiEOG71K630.
    PhylomeDBiQ4KLZ6.
    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]

    Sequencei

    Sequence statusi: Complete.

    Q4KLZ6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSSKKMVNSV EGCAGDALAG FVACNPDLQL LQGYRVALRS DLDSLKGRVA
    60 70 80 90 100
    LLSGGGSGHE PAHAGFIGKG MLTGVIAGAV FASPAVGSIL AAIRAVAQAG
    110 120 130 140 150
    TAGTLLIVKN YTGDRLNFGL AMEQAKAEGI SVEMVVIEDD SAFTVLKKAG
    160 170 180 190 200
    RRGLCGTILI HKVAGALAEE GMGLEEITKK VSVIAKAIGT LGVSLSPCSV
    210 220 230 240 250
    PGTKPTFELA ADEMELGLGI HGEAGVRRIK LVPVDQIVTL MLDHMTDTSN
    260 270 280 290 300
    ISHVPVKSGS SVVLMVNNLG GLSFLELGII ADAAIRLLEG RGVKVARALV
    310 320 330 340 350
    GTFMSALEMR GVSLTLMLVD EPLLKLIDAE TNAKAWPHMS KVSVTGRNRI
    360 370 380 390 400
    RAAPTEPAEA PEATAAGGVA SKQMTLVLDR ISTTLIGLEE HLNALDRAAG
    410 420 430 440 450
    DGDCGSTHSR AAKAIQGWLK EGPTPASPAQ VLSKLSVLLL EKMGGSSGAL
    460 470 480 490 500
    YGLFLTAAAQ PLKANTDLPA WSAAMDAGLK AMQKYGKAAP GDRTMLDSLW
    510 520 530 540 550
    AAAQELQAWK SPGASLLPVL TKAVKSAEAA AEATKNMEAG AGRASYISSA
    560 570
    QLDQPDPGAV AAAAIFRAIL EVLQTKAA
    Length:578
    Mass (Da):59,444
    Last modified:August 2, 2005 - v1
    Checksum:iC343482447F9770B
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    BC098925 mRNA. Translation: AAH98925.1.
    RefSeqiNP_001034120.1. NM_001039031.1.
    XP_006231118.1. XM_006231056.2.
    UniGeneiRn.55630.

    Genome annotation databases

    EnsembliENSRNOT00000028102; ENSRNOP00000028102; ENSRNOG00000020704.
    GeneIDi361730.
    KEGGirno:361730.
    UCSCiRGD:1311026. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    BC098925 mRNA. Translation: AAH98925.1.
    RefSeqiNP_001034120.1. NM_001039031.1.
    XP_006231118.1. XM_006231056.2.
    UniGeneiRn.55630.

    3D structure databases

    ProteinModelPortaliQ4KLZ6.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    MINTiMINT-4580965.
    STRINGi10116.ENSRNOP00000028102.

    PTM databases

    iPTMnetiQ4KLZ6.
    PhosphoSiteiQ4KLZ6.

    Proteomic databases

    PaxDbiQ4KLZ6.
    PRIDEiQ4KLZ6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSRNOT00000028102; ENSRNOP00000028102; ENSRNOG00000020704.
    GeneIDi361730.
    KEGGirno:361730.
    UCSCiRGD:1311026. rat.

    Organism-specific databases

    CTDi26007.
    RGDi1311026. Tkfc.

    Phylogenomic databases

    eggNOGiKOG2426. Eukaryota.
    COG2376. LUCA.
    GeneTreeiENSGT00390000015415.
    HOGENOMiHOG000234158.
    HOVERGENiHBG079502.
    InParanoidiQ4KLZ6.
    KOiK00863.
    OMAiEPAHVGF.
    OrthoDBiEOG71K630.
    PhylomeDBiQ4KLZ6.
    TreeFamiTF313821.

    Enzyme and pathway databases

    BioCyciMetaCyc:MONOMER-15866.
    ReactomeiR-RNO-70350. Fructose catabolism.

    Miscellaneous databases

    PROiQ4KLZ6.

    Gene expression databases

    GenevisibleiQ4KLZ6. RN.

    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...

    Publicationsi

    « Hide 'large scale' publications
    1. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: Brown Norway.
      Tissue: Testis.
    2. "Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases."
      Cabezas A., Costas M.J., Pinto R.M., Couto A., Cameselle J.C.
      Biochem. Biophys. Res. Commun. 338:1682-1689(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, FAD-AMP LYASE ACTIVITY.
    3. "Purification, characterization, and substrate and inhibitor structure-activity studies of rat liver FAD-AMP lyase (cyclizing): preference for FAD and specificity for splitting ribonucleoside diphosphate-X into ribonucleotide and a five-atom cyclic phosphodiester of X, either a monocyclic compound or a cis-bicyclic phosphodiester-pyranose fusion."
      Cabezas A., Pinto R.M., Fraiz F., Canales J., Gonzalez-Santiago S., Cameselle J.C.
      Biochemistry 40:13710-13722(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES.
    4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
      Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
      Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511 AND SER-545, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiTKFC_RAT
    AccessioniPrimary (citable) accession number: Q4KLZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 24, 2006
    Last sequence update: August 2, 2005
    Last modified: June 8, 2016
    This is version 85 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. 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.