ID KHK_HUMAN Reviewed; 298 AA. AC P50053; Q99532; Q9BRJ3; Q9UMN1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 16-JUN-2009, entry version 88. DE RecName: Full=Ketohexokinase; DE EC=2.7.1.3; DE AltName: Full=Hepatic fructokinase; GN Name=KHK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS FRUCTOSURIA ARG-40 AND THR-43, RP AND VARIANT ILE-49. RX MEDLINE=95135420; PubMed=7833921; DOI=10.1093/hmg/3.9.1627; RA Bonthron D.T., Brady N., Donaldson I.A., Steinmann B.; RT "Molecular basis of essential fructosuria: molecular cloning and RT mutational analysis of human ketohexokinase (fructokinase)."; RL Hum. Mol. Genet. 3:1627-1631(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26 AND 71-298, AND ALTERNATIVE RP SPLICING. RX MEDLINE=99013450; PubMed=9799106; RX 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). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose = ADP + D-fructose 1- CC phosphate. CC -!- ENZYME REGULATION: Requires potassium. Inhibition by ADP. CC -!- PATHWAY: Carbohydrate metabolism; fructose metabolism. CC -!- SUBUNIT: Dimer of A-A, A-C or C-C (Probable). CC -!- INTERACTION: CC P49407:ARRB1; NbExp=1; IntAct=EBI-1053974, EBI-743313; CC O95400:CD2BP2; NbExp=1; IntAct=EBI-1053974, EBI-768015; CC Q96JB5:CDK5RAP3; NbExp=1; IntAct=EBI-1053974, EBI-718818; CC O75618:DEDD; NbExp=1; IntAct=EBI-1053974, EBI-1043164; CC P31025:LCN1; NbExp=1; IntAct=EBI-1053974, EBI-1052433; CC P61626:LYZ; NbExp=1; IntAct=EBI-1053974, EBI-355360; CC Q15287:RNPS1; NbExp=1; IntAct=EBI-1053974, EBI-395959; CC P14678:SNRPB; NbExp=1; IntAct=EBI-1053974, EBI-372458; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=P50053-1; Sequence=Displayed; CC Name=C; CC IsoId=P50053-2; Sequence=VSP_004669; CC -!- TISSUE SPECIFICITY: Most abundant in liver, kidney, gut, spleen CC and pancreas. Low levels also found in adrenal, muscle, brain and CC eye. CC -!- DISEASE: Defects in KHK are the cause of fructosuria [MIM:229800]. CC Fructosuria is a benign defect of intermediary metabolism. CC -!- SIMILARITY: Belongs to the carbohydrate kinase pfkB family. CC -!- CAUTION: Form C has not yet been fully sequenced in its N-terminal CC (from 1-69). CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X78678; CAA55347.1; -; mRNA. DR EMBL; X78677; CAA55346.1; -; mRNA. DR EMBL; BC006233; AAH06233.1; -; mRNA. DR EMBL; Y09336; CAA70516.1; -; Genomic_DNA. DR EMBL; Y09341; CAA70522.1; -; Genomic_DNA. DR EMBL; Y09341; CAA70523.1; -; Genomic_DNA. DR EMBL; Y09340; CAA70521.1; -; Genomic_DNA. DR EMBL; AJ005168; CAA06409.1; -; Genomic_DNA. DR IPI; IPI00029488; -. DR IPI; IPI00216136; -. DR RefSeq; NP_000212.1; -. DR RefSeq; NP_006479.1; -. DR UniGene; Hs.567297; -. DR PDB; 2HLZ; X-ray; 1.85 A; A/B/C/D=5-298. DR PDB; 2HQQ; X-ray; 1.86 A; A=1-298. DR PDB; 2HW1; X-ray; 2.10 A; A=1-298. DR PDB; 3B3L; X-ray; 2.90 A; A/B/C/D=1-298. DR PDBsum; 2HLZ; -. DR PDBsum; 2HQQ; -. DR PDBsum; 2HW1; -. DR PDBsum; 3B3L; -. DR SMR; P50053; 5-298. DR IntAct; P50053; 11. DR PhosphoSite; P50053; -. DR REPRODUCTION-2DPAGE; IPI00029488; -. DR PRIDE; P50053; -. DR Ensembl; ENSG00000138030; Homo sapiens. DR GeneID; 3795; -. DR KEGG; hsa:3795; -. DR GeneCards; GC02P027221; -. DR H-InvDB; HIX0001908; -. DR HGNC; HGNC:6315; KHK. DR HPA; HPA007040; -. DR MIM; 229800; gene+phenotype. DR Orphanet; 2056; Fructosuria. DR PharmGKB; PA30095; -. DR HOGENOM; P50053; -. DR HOVERGEN; P50053; -. DR OMA; P50053; TILYYDR. DR BRENDA; 2.7.1.3; 247. DR Reactome; REACT_474; Metabolism of carbohydrates. DR NextBio; 14897; -. DR Bgee; P50053; -. DR CleanEx; HS_KHK; -. DR GermOnline; ENSG00000138030; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004454; F:ketohexokinase activity; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW. DR InterPro; IPR011611; Carb/pur_kinase. DR InterPro; IPR002173; Carboh/pur_kinase_PfkB_CS. DR Pfam; PF00294; PfkB; 2. DR PROSITE; PS00583; PFKB_KINASES_1; FALSE_NEG. DR PROSITE; PS00584; PFKB_KINASES_2; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; KW Carbohydrate metabolism; Disease mutation; Kinase; Nucleotide-binding; KW Phosphoprotein; Polymorphism; Transferase. FT CHAIN 1 298 Ketohexokinase. FT /FTId=PRO_0000080088. FT MOD_RES 169 169 Phosphoserine (By similarity). FT VAR_SEQ 72 115 VLDDLRRYSVDLRYTVFQTTGSVPIATVIINEASGSRTILY FT YDR -> LVADFRRRGVDVSQVAWQSKGDTPSSCCIINNSN FT GNRTIVLHDT (in isoform C). FT /FTId=VSP_004669. FT VARIANT 40 40 G -> R (in fructosuria). FT /FTId=VAR_006072. FT VARIANT 43 43 A -> T (in fructosuria). FT /FTId=VAR_006073. FT VARIANT 49 49 V -> I (in dbSNP:rs2304681). FT /FTId=VAR_006074. FT VARIANT 159 159 R -> G (either a polymorphism or a FT cloning artifact). FT /FTId=VAR_006075. SQ SEQUENCE 298 AA; 32730 MW; 1BA47BDC60C1B89F CRC64; MEEKQILCVG LVVLDVISLV DKYPKEDSEI RCLSQRWQRG GNASNSCTVL SLLGAPCAFM GSMAPGHVAD FVLDDLRRYS VDLRYTVFQT TGSVPIATVI INEASGSRTI LYYDRSLPDV SATDFEKVDL TQFKWIHIEG RNASEQVKML QRIDAHNTRQ PPEQKIRVSV EVEKPREELF QLFGYGDVVF VSKDVAKHLG FQSAEEALRG LYGRVRKGAV LVCAWAEEGA DALGPDGKLL HSDAFPPPRV VDTLGAGDTF NASVIFSLSQ GRSVQEALRF GCQVAGKKCG LQGFDGIV //