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Protein

Bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing)

Gene

DAK

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.2 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

    pH dependencei

    Optimum pH is 6.6.1 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

    • 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

    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

    BRENDAi2.7.1.29. 2681.
    4.6.1.15. 2681.
    ReactomeiREACT_1571. Fructose catabolism.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    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:DAK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:24552. DAK.

    Subcellular locationi

    GO - Cellular componenti

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

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA142672014.

    Polymorphism and mutation databases

    BioMutaiDAK.
    DMDMi311033370.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 575575Bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing)PRO_0000121525Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei350 – 3501Phosphoserine1 Publication
    Modified residuei511 – 5111Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ3LXA3.
    PaxDbiQ3LXA3.
    PRIDEiQ3LXA3.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00551024.

    PTM databases

    PhosphoSiteiQ3LXA3.

    Miscellaneous databases

    PMAP-CutDBQ3LXA3.

    Expressioni

    Tissue specificityi

    Detected in erythrocytes (at protein level).1 Publication

    Gene expression databases

    BgeeiQ3LXA3.
    CleanExiHS_DAK.
    ExpressionAtlasiQ3LXA3. baseline and differential.
    GenevisibleiQ3LXA3. HS.

    Organism-specific databases

    HPAiHPA039486.
    HPA048186.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi117481. 22 interactions.
    DIPiDIP-60967N.
    IntActiQ3LXA3. 1 interaction.
    MINTiMINT-5001370.
    STRINGi9606.ENSP00000378360.

    Structurei

    3D structure databases

    ProteinModelPortaliQ3LXA3.
    SMRiQ3LXA3. Positions 3-553.
    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

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiCOG2376.
    GeneTreeiENSGT00390000015415.
    HOGENOMiHOG000234158.
    HOVERGENiHBG079502.
    InParanoidiQ3LXA3.
    KOiK00863.
    OMAiVEMVIVA.
    OrthoDBiEOG71K630.
    PhylomeDBiQ3LXA3.
    TreeFamiTF313821.

    Family and domain databases

    InterProiIPR004006. Dak1.
    IPR012734. DhaK_ATP.
    IPR004007. DhaL_dom.
    [Graphical view]
    PfamiPF02733. Dak1. 1 hit.
    PF02734. 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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti7 – 71V → A in BAB14722 (PubMed:14702039).Curated
    Sequence conflicti19 – 191A → S in BAD97300 (Ref. 4) Curated
    Sequence conflicti75 – 751V → A in BAB14722 (PubMed:14702039).Curated
    Sequence conflicti376 – 3761L → P in BAB14722 (PubMed:14702039).Curated
    Sequence conflicti497 – 4971D → G in BAB14722 (PubMed:14702039).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti185 – 1851A → T.4 Publications
    Corresponds to variant rs2260655 [ dbSNP | Ensembl ].
    VAR_028108
    Natural varianti334 – 3341A → G.
    Corresponds to variant rs35723406 [ dbSNP | Ensembl ].
    VAR_054780

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei526 – 57550SAEAA…EVLQS → EGGGLVICP in isoform 2. 1 PublicationVSP_057181Add
    BLAST

    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]
    UniGeneiHs.6278.

    Genome annotation databases

    EnsembliENST00000394900; ENSP00000378360; ENSG00000149476. [Q3LXA3-1]
    GeneIDi26007.
    KEGGihsa:26007.
    UCSCiuc001nre.3. 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]
    UniGeneiHs.6278.

    3D structure databases

    ProteinModelPortaliQ3LXA3.
    SMRiQ3LXA3. Positions 3-553.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi117481. 22 interactions.
    DIPiDIP-60967N.
    IntActiQ3LXA3. 1 interaction.
    MINTiMINT-5001370.
    STRINGi9606.ENSP00000378360.

    PTM databases

    PhosphoSiteiQ3LXA3.

    Polymorphism and mutation databases

    BioMutaiDAK.
    DMDMi311033370.

    2D gel databases

    REPRODUCTION-2DPAGEIPI00551024.

    Proteomic databases

    MaxQBiQ3LXA3.
    PaxDbiQ3LXA3.
    PRIDEiQ3LXA3.

    Protocols and materials databases

    DNASUi26007.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000394900; ENSP00000378360; ENSG00000149476. [Q3LXA3-1]
    GeneIDi26007.
    KEGGihsa:26007.
    UCSCiuc001nre.3. human. [Q3LXA3-1]

    Organism-specific databases

    CTDi26007.
    GeneCardsiGC11P061100.
    HGNCiHGNC:24552. DAK.
    HPAiHPA039486.
    HPA048186.
    MIMi615844. gene.
    neXtProtiNX_Q3LXA3.
    PharmGKBiPA142672014.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG2376.
    GeneTreeiENSGT00390000015415.
    HOGENOMiHOG000234158.
    HOVERGENiHBG079502.
    InParanoidiQ3LXA3.
    KOiK00863.
    OMAiVEMVIVA.
    OrthoDBiEOG71K630.
    PhylomeDBiQ3LXA3.
    TreeFamiTF313821.

    Enzyme and pathway databases

    BRENDAi2.7.1.29. 2681.
    4.6.1.15. 2681.
    ReactomeiREACT_1571. Fructose catabolism.
    REACT_25359. RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways.

    Miscellaneous databases

    ChiTaRSiDAK. human.
    GeneWikiiDAK_(gene).
    GenomeRNAii26007.
    NextBioi47741.
    PMAP-CutDBQ3LXA3.
    PROiQ3LXA3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ3LXA3.
    CleanExiHS_DAK.
    ExpressionAtlasiQ3LXA3. baseline and differential.
    GenevisibleiQ3LXA3. HS.

    Family and domain databases

    InterProiIPR004006. Dak1.
    IPR012734. DhaK_ATP.
    IPR004007. DhaL_dom.
    [Graphical view]
    PfamiPF02733. Dak1. 1 hit.
    PF02734. 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. "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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, FAD-AMP LYASE ACTIVITY, VARIANT THR-185.
      Tissue: Brain.
    2. "Human brain Dha kinase/FMN cyclase splice variant mRNA encoding a shorter protein inactive as Dha kinase and FMN cyclase."
      Cabezas A., Costas M.J., Pinto R.M., Couto A., Cameselle J.C.
      Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT THR-185, ALTERNATIVE SPLICING.
      Tissue: Brain.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-185.
      Tissue: Thyroid.
    4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
      Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT THR-185.
      Tissue: Kidney.
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM 1).
      Tissue: Cervix.
    7. "Dihydroxyacetone metabolism by human erythrocytes: demonstration of triokinase activity and its characterization."
      Beutler E., Guinto E.
      Blood 41:559-568(1973) [PubMed] [Europe PMC] [Abstract]
      Cited for: CATALYTIC ACTIVITY, FUNCTION, IDENTITY OF TRIOKINASE AND DIHYDROXYACETONE KINASE, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350 AND SER-511, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.

    Entry informationi

    Entry nameiDHAK_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: June 24, 2015
    This is version 100 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

    External Data

    Dasty 3

    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 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.