TKFC_RAT
ID TKFC_RAT Reviewed; 578 AA.
AC Q4KLZ6;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Triokinase/FMN cyclase;
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; Synonyms=Dak;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Brown Norway; TISSUE=Testis;
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 FUNCTION, AND FAD-AMP LYASE ACTIVITY.
RX PubMed=16289032; DOI=10.1016/j.bbrc.2005.10.142;
RA Cabezas A., Costas M.J., Pinto R.M., Couto A., Cameselle J.C.;
RT "Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-
RT dependent dihydroxyacetone kinases.";
RL Biochem. Biophys. Res. Commun. 338:1682-1689(2005).
RN [3]
RP COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11695920; DOI=10.1021/bi0157159;
RA Cabezas A., Pinto R.M., Fraiz F., Canales J., Gonzalez-Santiago S.,
RA Cameselle J.C.;
RT "Purification, characterization, and substrate and inhibitor structure-
RT activity studies of rat liver FAD-AMP lyase (cyclizing): preference for FAD
RT and specificity for splitting ribonucleoside diphosphate-X into
RT ribonucleotide and a five-atom cyclic phosphodiester of X, either a
RT monocyclic compound or a cis-bicyclic phosphodiester-pyranose fusion.";
RL Biochemistry 40:13710-13722(2001).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-511 AND SER-545, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (PubMed:16289032).
CC Represses IFIH1-mediated cellular antiviral response (By similarity).
CC {ECO:0000250|UniProtKB:F1RKQ4, ECO:0000250|UniProtKB:Q3LXA3,
CC ECO:0000269|PubMed:16289032}.
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;
CC Evidence={ECO:0000269|PubMed:11695920};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:11695920};
CC Note=Manganese or cobalt are requested for FAD-AMP lyase activity.
CC {ECO:0000269|PubMed:11695920};
CC -!- ACTIVITY REGULATION: Each activity is inhibited by the substrate(s) of
CC the other.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.8 uM for FAD with manganese {ECO:0000269|PubMed:11695920};
CC KM=12.5 uM for ADP-glucose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=652 uM for UDP-glucose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=606 uM for UDP-galactose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=714 uM for UDP-xylose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=107 uM for UDP-glucuronate with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=108 uM for UDP-galacturonate with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=416 uM for CDP-glucose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=795 uM for CDP-glycerol with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=784 uM for GDP-glucose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=343 uM for GDP-alpha-L-fucose with manganese
CC {ECO:0000269|PubMed:11695920};
CC KM=114 uM for FAD with cobalt {ECO:0000269|PubMed:11695920};
CC KM=120 uM for ADP-glucose with cobalt {ECO:0000269|PubMed:11695920};
CC KM=2550 uM for UDP-glucose with cobalt {ECO:0000269|PubMed:11695920};
CC KM=3661 uM for UDP-galactose with cobalt
CC {ECO:0000269|PubMed:11695920};
CC KM=2354 uM for UDP-xylose with cobalt {ECO:0000269|PubMed:11695920};
CC KM=539 uM for UDP-glucuronate with cobalt
CC {ECO:0000269|PubMed:11695920};
CC KM=759 uM for UDP-galacturonate with cobalt
CC {ECO:0000269|PubMed:11695920};
CC KM=3703 uM for CDP-glucose with cobalt {ECO:0000269|PubMed:11695920};
CC KM=2031 uM for CDP-glycerol with cobalt
CC {ECO:0000269|PubMed:11695920};
CC KM=2246 uM for GDP-glucose with cobalt {ECO:0000269|PubMed:11695920};
CC KM=991 uM for GDP-alpha-L-fucose with cobalt
CC {ECO:0000269|PubMed:11695920};
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; BC098925; AAH98925.1; -; mRNA.
DR RefSeq; NP_001034120.1; NM_001039031.1.
DR RefSeq; XP_006231118.1; XM_006231056.3.
DR AlphaFoldDB; Q4KLZ6; -.
DR SMR; Q4KLZ6; -.
DR STRING; 10116.ENSRNOP00000028102; -.
DR iPTMnet; Q4KLZ6; -.
DR PhosphoSitePlus; Q4KLZ6; -.
DR jPOST; Q4KLZ6; -.
DR PaxDb; Q4KLZ6; -.
DR PRIDE; Q4KLZ6; -.
DR Ensembl; ENSRNOT00000028102; ENSRNOP00000028102; ENSRNOG00000020704.
DR GeneID; 361730; -.
DR KEGG; rno:361730; -.
DR UCSC; RGD:1311026; rat.
DR CTD; 26007; -.
DR RGD; 1311026; Tkfc.
DR eggNOG; KOG2426; Eukaryota.
DR GeneTree; ENSGT00390000015415; -.
DR HOGENOM; CLU_017054_6_2_1; -.
DR InParanoid; Q4KLZ6; -.
DR OMA; TALNMNG; -.
DR OrthoDB; 472175at2759; -.
DR PhylomeDB; Q4KLZ6; -.
DR TreeFam; TF313821; -.
DR BioCyc; MetaCyc:MON-15866; -.
DR Reactome; R-RNO-70350; Fructose catabolism.
DR PRO; PR:Q4KLZ6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020704; Expressed in duodenum and 19 other tissues.
DR Genevisible; Q4KLZ6; RN.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0034012; F:FAD-AMP lyase (cyclizing) activity; ISO:RGD.
DR GO; GO:0004371; F:glycerone kinase activity; ISO:RGD.
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:RGD.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; ISO:RGD.
DR GO; GO:0061624; P:fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate; ISO:RGD.
DR GO; GO:0019563; P:glycerol catabolic process; IBA:GO_Central.
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:RGD.
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_0000121527"
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:22673903"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 578 AA; 59444 MW; C343482447F9770B CRC64;
MSSKKMVNSV EGCAGDALAG FVACNPDLQL LQGYRVALRS DLDSLKGRVA LLSGGGSGHE
PAHAGFIGKG MLTGVIAGAV FASPAVGSIL AAIRAVAQAG TAGTLLIVKN YTGDRLNFGL
AMEQAKAEGI SVEMVVIEDD SAFTVLKKAG RRGLCGTILI HKVAGALAEE GMGLEEITKK
VSVIAKAIGT LGVSLSPCSV PGTKPTFELA ADEMELGLGI HGEAGVRRIK LVPVDQIVTL
MLDHMTDTSN ISHVPVKSGS SVVLMVNNLG GLSFLELGII ADAAIRLLEG RGVKVARALV
GTFMSALEMR GVSLTLMLVD EPLLKLIDAE TNAKAWPHMS KVSVTGRNRI RAAPTEPAEA
PEATAAGGVA SKQMTLVLDR ISTTLIGLEE HLNALDRAAG DGDCGSTHSR AAKAIQGWLK
EGPTPASPAQ VLSKLSVLLL EKMGGSSGAL YGLFLTAAAQ PLKANTDLPA WSAAMDAGLK
AMQKYGKAAP GDRTMLDSLW AAAQELQAWK SPGASLLPVL TKAVKSAEAA AEATKNMEAG
AGRASYISSA QLDQPDPGAV AAAAIFRAIL EVLQTKAA
