KHK_RAT
ID KHK_RAT Reviewed; 298 AA.
AC Q02974; P97550; P97551;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Ketohexokinase {ECO:0000312|RGD:2966};
DE EC=2.7.1.3 {ECO:0000269|PubMed:8471037};
DE AltName: Full=Hepatic fructokinase;
GN Name=Khk {ECO:0000312|RGD:2966};
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 [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=8471037; DOI=10.1042/bj2910179;
RA Donaldson I.A., Doyle T.C., Matas N.;
RT "Expression of rat liver ketohexokinase in yeast results in fructose
RT intolerance.";
RL Biochem. J. 291:179-186(1993).
RN [2]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=9799106; DOI=10.1046/j.1432-1327.1998.2570085.x;
RA Hayward B.E., Bonthron D.T.;
RT "Structure and alternative splicing of the ketohexokinase gene.";
RL Eur. J. Biochem. 257:85-91(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
RC TISSUE=Kidney;
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).
CC -!- FUNCTION: Catalyzes the phosphorylation of the ketose sugar fructose to
CC fructose-1-phosphate. {ECO:0000269|PubMed:8471037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-D-fructose = ADP + beta-D-fructose 1-phosphate +
CC H(+); Xref=Rhea:RHEA:18145, ChEBI:CHEBI:15378, ChEBI:CHEBI:28645,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:138881, ChEBI:CHEBI:456216;
CC EC=2.7.1.3; Evidence={ECO:0000269|PubMed:8471037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18146;
CC Evidence={ECO:0000269|PubMed:8471037};
CC -!- ACTIVITY REGULATION: Requires potassium. Inhibition by ADP.
CC -!- PATHWAY: Carbohydrate metabolism; fructose metabolism.
CC {ECO:0000305|PubMed:8471037}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P50053}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=C {ECO:0000269|PubMed:9799106}; Synonyms=Central,
CC hepatic/renal/intestinal {ECO:0000269|PubMed:9799106};
CC IsoId=Q02974-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:9799106}; Synonyms=Peripheral
CC {ECO:0000269|PubMed:9799106};
CC IsoId=Q02974-2; Sequence=VSP_004670;
CC -!- TISSUE SPECIFICITY: Isoform C is most abundant in liver, kidney, gut,
CC spleen and pancreas. Low levels of isoform A found in adrenal, spleen
CC and brain. {ECO:0000269|PubMed:9799106}.
CC -!- PTM: The N-terminus is blocked.
CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family.
CC {ECO:0000305}.
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DR EMBL; X63658; CAA45198.1; -; mRNA.
DR EMBL; Y09337; CAA70517.1; -; Genomic_DNA.
DR EMBL; Y09338; CAA70518.1; -; Genomic_DNA.
DR EMBL; Y09338; CAA70519.1; -; Genomic_DNA.
DR EMBL; Y09339; CAA70520.1; -; Genomic_DNA.
DR EMBL; BC078752; AAH78752.1; -; mRNA.
DR PIR; S32426; S32426.
DR RefSeq; NP_114061.1; NM_031855.3. [Q02974-1]
DR AlphaFoldDB; Q02974; -.
DR SMR; Q02974; -.
DR IntAct; Q02974; 4.
DR STRING; 10116.ENSRNOP00000046296; -.
DR BindingDB; Q02974; -.
DR ChEMBL; CHEMBL4105923; -.
DR PRIDE; Q02974; -.
DR GeneID; 25659; -.
DR KEGG; rno:25659; -.
DR CTD; 3795; -.
DR RGD; 2966; Khk.
DR VEuPathDB; HostDB:ENSRNOG00000008047; -.
DR eggNOG; KOG2947; Eukaryota.
DR HOGENOM; CLU_027634_3_0_1; -.
DR InParanoid; Q02974; -.
DR OMA; GCTEVDY; -.
DR OrthoDB; 1008502at2759; -.
DR PhylomeDB; Q02974; -.
DR TreeFam; TF323942; -.
DR BRENDA; 2.7.1.3; 5301.
DR Reactome; R-RNO-70350; Fructose catabolism.
DR SABIO-RK; Q02974; -.
DR UniPathway; UPA00202; -.
DR PRO; PR:Q02974; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000008047; Expressed in kidney and 19 other tissues.
DR Genevisible; Q02974; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004454; F:ketohexokinase activity; IDA:RGD.
DR GO; GO:0016052; P:carbohydrate catabolic process; TAS:RGD.
DR GO; GO:0061624; P:fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate; ISO:RGD.
DR GO; GO:0006000; P:fructose metabolic process; IDA:RGD.
DR GO; GO:0070873; P:regulation of glycogen metabolic process; ISO:RGD.
DR GO; GO:0009750; P:response to fructose; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IDA:RGD.
DR GO; GO:0032868; P:response to insulin; IDA:RGD.
DR GO; GO:0009744; P:response to sucrose; IDA:RGD.
DR GO; GO:0010043; P:response to zinc ion; IDA:RGD.
DR CDD; cd01939; Ketohexokinase; 1.
DR Gene3D; 3.40.1190.20; -; 1.
DR InterPro; IPR034093; KHK.
DR InterPro; IPR011611; PfkB_dom.
DR InterPro; IPR029056; Ribokinase-like.
DR Pfam; PF00294; PfkB; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Carbohydrate metabolism;
KW Direct protein sequencing; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT CHAIN 1..298
FT /note="Ketohexokinase"
FT /id="PRO_0000080091"
FT BINDING 15
FT /ligand="beta-D-fructose"
FT /ligand_id="ChEBI:CHEBI:28645"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 41
FT /ligand="beta-D-fructose"
FT /ligand_id="ChEBI:CHEBI:28645"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 42
FT /ligand="beta-D-fructose"
FT /ligand_id="ChEBI:CHEBI:28645"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 45
FT /ligand="beta-D-fructose"
FT /ligand_id="ChEBI:CHEBI:28645"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 108
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 226..229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 255..258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT BINDING 258
FT /ligand="beta-D-fructose"
FT /ligand_id="ChEBI:CHEBI:28645"
FT /evidence="ECO:0000250|UniProtKB:P50053"
FT VAR_SEQ 72..114
FT /note="LVADFRRRGVDVSQVAWQSQGDTPCSCCIVNNSNGSRTIILYD -> VLDDL
FT RRHSVDLRYAVLQTEGSIPTSTVIVNEASGSRTILHAY (in isoform A)"
FT /evidence="ECO:0000305"
FT /id="VSP_004670"
FT CONFLICT 232
FT /note="A -> T (in Ref. 2; CAA70517)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 298 AA; 32749 MW; F85C787FF047DF70 CRC64;
MEEKQILCVG LVVLDIINVV DKYPEEDTDR RCLSQRWQRG GNASNSCTVL SLLGARCAFM
GSLAHGHVAD FLVADFRRRG VDVSQVAWQS QGDTPCSCCI VNNSNGSRTI ILYDTNLPDV
SAKDFEKVDL TRFKWIHIEG RNASEQVKML QRIEQYNATQ PLQQKVRVSV EIEKPREELF
QLFGYGEVVF VSKDVAKHLG FRSAGEALKG LYSRVKKGAT LICAWAEEGA DALGPDGQLL
HSDAFPPPRV VDTLGAGDTF NASVIFSLSK GNSMQEALRF GCQVAGKKCG LQGFDGIV
