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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

  1. ATP binding Source: UniProtKB-KW
  2. FAD-AMP lyase (cyclizing) activity Source: UniProtKB
  3. glycerone kinase activity Source: UniProtKB
  4. metal ion binding Source: UniProtKB-KW
  5. triokinase activity Source: UniProtKB

GO - Biological processi

  1. carbohydrate phosphorylation Source: UniProtKB
  2. cellular carbohydrate metabolic process Source: UniProtKB
  3. glycerol metabolic process Source: InterPro
  4. innate immune response Source: Reactome
  5. 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

BRENDAi2.7.1.29. 2681.
ReactomeiREACT_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: Chromosome 11

Organism-specific databases

HGNCiHGNC:24552. DAK.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProtKB
  3. nucleus Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142672014.

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.
GenevestigatoriQ3LXA3.

Organism-specific databases

HPAiHPA039486.
HPA048186.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi117481. 22 interactions.
DIPiDIP-60967N.
MINTiMINT-5001370.
STRINGi9606.ENSP00000310493.

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]
XP_006718559.1. XM_006718496.1. [Q3LXA3-1]
UniGeneiHs.6278.

Genome annotation databases

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

Polymorphism databases

DMDMi311033370.

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_006718559.1. XM_006718496.1. [Q3LXA3-1]
UniGeneiHs.6278.

3D structure databases

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

Protein-protein interaction databases

BioGridi117481. 22 interactions.
DIPiDIP-60967N.
MINTiMINT-5001370.
STRINGi9606.ENSP00000310493.

PTM databases

PhosphoSiteiQ3LXA3.

Polymorphism databases

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.
ReactomeiREACT_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.
GenevestigatoriQ3LXA3.

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: March 4, 2015
This is version 96 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.