TKFC_MOUSE
ID TKFC_MOUSE Reviewed; 578 AA.
AC Q8VC30;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Triokinase/FMN cyclase {ECO:0000312|MGI:MGI:2385084};
DE AltName: Full=Bifunctional ATP-dependent dihydroxyacetone kinase/FAD-AMP lyase (cyclizing);
DE Includes:
DE RecName: Full=ATP-dependent dihydroxyacetone kinase;
DE Short=DHA kinase;
DE EC=2.7.1.28;
DE EC=2.7.1.29;
DE AltName: Full=Glycerone kinase;
DE AltName: Full=Triokinase;
DE AltName: Full=Triose kinase;
DE Includes:
DE RecName: Full=FAD-AMP lyase (cyclizing);
DE EC=4.6.1.15;
DE AltName: Full=FAD-AMP lyase (cyclic FMN forming);
DE AltName: Full=FMN cyclase;
GN Name=Tkfc {ECO:0000312|MGI:MGI:2385084};
GN Synonyms=Dak {ECO:0000312|MGI:MGI:2385084};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes both the phosphorylation of dihydroxyacetone and of
CC glyceraldehyde, and the splitting of ribonucleoside diphosphate-X
CC compounds among which FAD is the best substrate. Represses IFIH1-
CC mediated cellular antiviral response. {ECO:0000250|UniProtKB:F1RKQ4,
CC ECO:0000250|UniProtKB:Q3LXA3, ECO:0000250|UniProtKB:Q4KLZ6}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + dihydroxyacetone = ADP + dihydroxyacetone phosphate +
CC H(+); Xref=Rhea:RHEA:15773, ChEBI:CHEBI:15378, ChEBI:CHEBI:16016,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57642, ChEBI:CHEBI:456216;
CC EC=2.7.1.29;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-glyceraldehyde = ADP + D-glyceraldehyde 3-phosphate +
CC H(+); Xref=Rhea:RHEA:13941, ChEBI:CHEBI:15378, ChEBI:CHEBI:17378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:59776, ChEBI:CHEBI:456216;
CC EC=2.7.1.28;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=FAD = AMP + H(+) + riboflavin cyclic-4',5'-phosphate;
CC Xref=Rhea:RHEA:13729, ChEBI:CHEBI:15378, ChEBI:CHEBI:57692,
CC ChEBI:CHEBI:76202, ChEBI:CHEBI:456215; EC=4.6.1.15;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828; Evidence={ECO:0000250};
CC Note=Manganese or cobalt are requested for FAD-AMP lyase activity.
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: Each activity is inhibited by the substrate(s) of
CC the other. {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with IFIH1 (via the CARD
CC domains), the interaction is inhibited by viral infection (By
CC similarity). {ECO:0000250|UniProtKB:F1RKQ4,
CC ECO:0000250|UniProtKB:Q3LXA3}.
CC -!- DOMAIN: DhaK and DhaL domains have differential roles, individually
CC DhaK is inactive and DhaL displays cyclase but not kinase activity.
CC {ECO:0000250|UniProtKB:Q3LXA3}.
CC -!- SIMILARITY: Belongs to the dihydroxyacetone kinase (DAK) family.
CC {ECO:0000305}.
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DR EMBL; BC021917; AAH21917.1; -; mRNA.
DR CCDS; CCDS37914.1; -.
DR RefSeq; NP_663471.1; NM_145496.1.
DR RefSeq; XP_006527005.1; XM_006526942.2.
DR RefSeq; XP_006527006.1; XM_006526943.3.
DR RefSeq; XP_006527007.1; XM_006526944.3.
DR AlphaFoldDB; Q8VC30; -.
DR SMR; Q8VC30; -.
DR BioGRID; 230448; 7.
DR STRING; 10090.ENSMUSP00000044556; -.
DR iPTMnet; Q8VC30; -.
DR PhosphoSitePlus; Q8VC30; -.
DR SwissPalm; Q8VC30; -.
DR REPRODUCTION-2DPAGE; IPI00310669; -.
DR REPRODUCTION-2DPAGE; Q8VC30; -.
DR EPD; Q8VC30; -.
DR jPOST; Q8VC30; -.
DR MaxQB; Q8VC30; -.
DR PaxDb; Q8VC30; -.
DR PeptideAtlas; Q8VC30; -.
DR PRIDE; Q8VC30; -.
DR ProteomicsDB; 259030; -.
DR Antibodypedia; 28186; 191 antibodies from 31 providers.
DR DNASU; 225913; -.
DR Ensembl; ENSMUST00000037678; ENSMUSP00000044556; ENSMUSG00000034371.
DR Ensembl; ENSMUST00000236607; ENSMUSP00000157520; ENSMUSG00000034371.
DR Ensembl; ENSMUST00000236950; ENSMUSP00000158068; ENSMUSG00000034371.
DR GeneID; 225913; -.
DR KEGG; mmu:225913; -.
DR UCSC; uc008gql.1; mouse.
DR CTD; 26007; -.
DR MGI; MGI:2385084; Tkfc.
DR VEuPathDB; HostDB:ENSMUSG00000034371; -.
DR eggNOG; KOG2426; Eukaryota.
DR GeneTree; ENSGT00390000015415; -.
DR HOGENOM; CLU_017054_6_2_1; -.
DR InParanoid; Q8VC30; -.
DR OMA; TALNMNG; -.
DR OrthoDB; 472175at2759; -.
DR PhylomeDB; Q8VC30; -.
DR TreeFam; TF313821; -.
DR BRENDA; 2.7.1.28; 3474.
DR Reactome; R-MMU-70350; Fructose catabolism.
DR BioGRID-ORCS; 225913; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Tkfc; mouse.
DR PRO; PR:Q8VC30; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8VC30; protein.
DR Bgee; ENSMUSG00000034371; Expressed in spermatocyte and 75 other tissues.
DR ExpressionAtlas; Q8VC30; baseline and differential.
DR Genevisible; Q8VC30; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034012; F:FAD-AMP lyase (cyclizing) activity; ISO:MGI.
DR GO; GO:0004371; F:glycerone kinase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050354; F:triokinase activity; IDA:MGI.
DR GO; GO:0046835; P:carbohydrate phosphorylation; ISO:MGI.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0061624; P:fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate; IMP:MGI.
DR GO; GO:0019563; P:glycerol catabolic process; IBA:GO_Central.
DR GO; GO:0061625; P:glycolytic process through fructose-1-phosphate; IC:MGI.
DR GO; GO:0039534; P:negative regulation of MDA-5 signaling pathway; ISS:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; ISO:MGI.
DR Gene3D; 1.25.40.340; -; 1.
DR InterPro; IPR012734; DhaK_ATP.
DR InterPro; IPR004006; DhaK_dom.
DR InterPro; IPR004007; DhaL_dom.
DR InterPro; IPR036117; DhaL_dom_sf.
DR Pfam; PF02733; Dak1; 1.
DR Pfam; PF02734; Dak2; 1.
DR SMART; SM01120; Dak2; 1.
DR SUPFAM; SSF101473; SSF101473; 1.
DR TIGRFAMs; TIGR02361; dak_ATP; 1.
DR PROSITE; PS51481; DHAK; 1.
DR PROSITE; PS51480; DHAL; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cobalt; FAD; Flavoprotein; Kinase; Lyase; Magnesium;
KW Manganese; Metal-binding; Multifunctional enzyme; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..578
FT /note="Triokinase/FMN cyclase"
FT /id="PRO_0000121526"
FT DOMAIN 9..336
FT /note="DhaK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00814"
FT DOMAIN 372..571
FT /note="DhaL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00813"
FT ACT_SITE 221
FT /note="Tele-hemiaminal-histidine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00814"
FT BINDING 56..59
FT /ligand="dihydroxyacetone"
FT /ligand_id="ChEBI:CHEBI:16016"
FT /evidence="ECO:0000250"
FT BINDING 109
FT /ligand="dihydroxyacetone"
FT /ligand_id="ChEBI:CHEBI:16016"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00814"
FT BINDING 114
FT /ligand="dihydroxyacetone"
FT /ligand_id="ChEBI:CHEBI:16016"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00814"
FT BINDING 401..404
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 446..447
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 486
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 494..495
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 556..558
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4KLZ6"
SQ SEQUENCE 578 AA; 59691 MW; 5C6FCABDD6F2EF2A CRC64;
MSSKKMVNSV EGCADDALAG LVASNPDLQL LQGHRVALRS DLDTLKGRVA LLSGGGSGHE
PAHAGFIGKG MLTGVIAGSV FASPPVGSIL AAIRAVAQAG TVGTLLIVKN YTGDRLNFGL
AMEQAKAEGI SVEMVIVEDD SAFTVLKKAG RRGLCGTVLI HKVAGALAEE GMGLEEITKR
VSVIAKTMGT LGVSLSSCSV PGATHTFELA ADEIELGLGI HGEAGVRRIK IAPVDQIVTL
MLDHMTNTSN IFHVPVRSGS SVVLIVNNLG GLSFLELGII ADAAIRLLEG RGVKVARALV
GTFMSALEMP GVSLTLMLVD EPVLKLIDAE TTAKAWPHMA KVSVTGRKRI RAAPTEPPEA
PEATAAGGVT SKQMALVLDR ICTTLIGLEE HLNALDRAAG DGDCGSTHSR AAKAIQGWLK
EGPSLTSPAQ VLSRLSVLLL ERMGGSSGAL YGLFLTAAAQ PLKAKTDLPT WSAAMDAGLE
SMQKYGKAAP GDRTMLDSLW AAAQEFQAWK SPGASLLPVL TKAVKSAEAA AEATKNMEAG
AGRASYISSA QLDQPDPGAV AAAAIFRAIL EVLQTQGA
