ID KHK_HUMAN Reviewed; 298 AA. AC P50053; Q6IBK2; Q99532; Q9BRJ3; Q9UMN1; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 16-APR-2014, entry version 134. 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 FRUCT ARG-40 AND THR-43, AND RP VARIANT ILE-49. RX 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]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26 AND 71-298, AND ALTERNATIVE RP SPLICING. 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 [7] RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH FRUCTOSE AND RP AMP-PNP, X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF ISOFORM C, SUBUNIT, RP AND SUBSTRATE-BINDING SITES. RX PubMed=19237742; DOI=10.1107/S0907444908041115; RA Trinh C.H., Asipu A., Bonthron D.T., Phillips S.E.; RT "Structures of alternatively spliced isoforms of human RT ketohexokinase."; RL Acta Crystallogr. D 65:201-211(2009). 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: Homodimer. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; Synonyms=Central, hepatic/renal/intestinal; CC IsoId=P50053-1; Sequence=Displayed; CC Name=C; Synonyms=Peripheral; CC IsoId=P50053-2; Sequence=VSP_004669; CC Note=More widely distributed but with a low expression level; 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: Fructosuria (FRUCT) [MIM:229800]: Benign defect of CC intermediary metabolism. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family. 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; CR456801; CAG33082.1; -; mRNA. DR EMBL; AC013403; AAX93167.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00643.1; -; Genomic_DNA. 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 RefSeq; NP_000212.1; NM_000221.2. DR RefSeq; NP_006479.1; NM_006488.2. 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 PDB; 3NBV; X-ray; 2.30 A; A/B=5-298. DR PDB; 3NBW; X-ray; 2.34 A; A/B=5-298. DR PDB; 3NC2; X-ray; 2.50 A; A/B=5-298. DR PDB; 3NC9; X-ray; 2.40 A; A/B=5-298. DR PDB; 3NCA; X-ray; 2.60 A; A/B=5-298. DR PDB; 3Q92; X-ray; 2.80 A; A/B=5-298. DR PDB; 3QA2; X-ray; 2.52 A; A/B=5-298. DR PDB; 3QAI; X-ray; 2.70 A; A/B=5-298. DR PDB; 3RO4; X-ray; 2.60 A; A/B=5-298. DR PDBsum; 2HLZ; -. DR PDBsum; 2HQQ; -. DR PDBsum; 2HW1; -. DR PDBsum; 3B3L; -. DR PDBsum; 3NBV; -. DR PDBsum; 3NBW; -. DR PDBsum; 3NC2; -. DR PDBsum; 3NC9; -. DR PDBsum; 3NCA; -. DR PDBsum; 3Q92; -. DR PDBsum; 3QA2; -. DR PDBsum; 3QAI; -. DR PDBsum; 3RO4; -. DR ProteinModelPortal; P50053; -. DR SMR; P50053; 5-298. DR BioGrid; 109996; 12. DR STRING; 9606.ENSP00000260598; -. DR BindingDB; P50053; -. DR ChEMBL; CHEMBL1275212; -. DR PhosphoSite; P50053; -. DR DMDM; 1730044; -. DR REPRODUCTION-2DPAGE; IPI00029488; -. DR PaxDb; P50053; -. DR PRIDE; P50053; -. DR DNASU; 3795; -. DR Ensembl; ENST00000260598; ENSP00000260598; ENSG00000138030. [P50053-2] DR Ensembl; ENST00000260599; ENSP00000260599; ENSG00000138030. [P50053-1] DR GeneID; 3795; -. DR KEGG; hsa:3795; -. DR UCSC; uc002ril.2; human. [P50053-1] DR UCSC; uc002rim.2; human. [P50053-2] DR CTD; 3795; -. DR GeneCards; GC02P027309; -. DR HGNC; HGNC:6315; KHK. DR HPA; HPA007040; -. DR MIM; 229800; phenotype. DR MIM; 614058; gene. DR neXtProt; NX_P50053; -. DR Orphanet; 2056; Essential fructosuria. DR PharmGKB; PA30095; -. DR eggNOG; COG0524; -. DR HOGENOM; HOG000212926; -. DR HOVERGEN; HBG003335; -. DR InParanoid; P50053; -. DR KO; K00846; -. DR OMA; HVADFLV; -. DR OrthoDB; EOG7K6PV6; -. DR PhylomeDB; P50053; -. DR TreeFam; TF323942; -. DR BioCyc; MetaCyc:HS06437-MONOMER; -. DR BRENDA; 2.7.1.3; 2681. DR Reactome; REACT_111217; Metabolism. DR SABIO-RK; P50053; -. DR UniPathway; UPA00202; -. DR EvolutionaryTrace; P50053; -. DR GenomeRNAi; 3795; -. DR NextBio; 14897; -. DR PRO; PR:P50053; -. DR ArrayExpress; P50053; -. DR Bgee; P50053; -. DR CleanEx; HS_KHK; -. DR Genevestigator; P50053; -. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004454; F:ketohexokinase activity; EXP:Reactome. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome. DR GO; GO:0046835; P:carbohydrate phosphorylation; EXP:GOC. DR GO; GO:0006001; P:fructose catabolic process; TAS:Reactome. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR InterPro; IPR011611; PfkB_dom. DR Pfam; PF00294; PfkB; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; KW Carbohydrate metabolism; Complete proteome; Disease mutation; Kinase; KW Nucleotide-binding; Polymorphism; Reference proteome; Transferase. FT CHAIN 1 298 Ketohexokinase. FT /FTId=PRO_0000080088. FT NP_BIND 255 258 ATP. FT BINDING 15 15 D-fructose. FT BINDING 41 41 D-fructose; via amide nitrogen. FT BINDING 42 42 D-fructose. FT BINDING 45 45 D-fructose. FT BINDING 108 108 ATP. FT BINDING 258 258 D-fructose. 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 FRUCT). FT /FTId=VAR_006072. FT VARIANT 43 43 A -> T (in FRUCT). 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. FT STRAND 5 10 FT STRAND 13 22 FT STRAND 29 31 FT STRAND 33 41 FT HELIX 42 53 FT STRAND 57 63 FT HELIX 67 78 FT STRAND 86 88 FT STRAND 90 92 FT STRAND 96 102 FT TURN 103 105 FT STRAND 108 113 FT HELIX 122 126 FT HELIX 130 132 FT STRAND 133 139 FT HELIX 143 157 FT HELIX 162 164 FT STRAND 167 172 FT HELIX 177 184 FT STRAND 185 191 FT HELIX 193 198 FT HELIX 204 211 FT HELIX 212 214 FT STRAND 220 224 FT HELIX 226 228 FT STRAND 230 233 FT STRAND 239 242 FT HELIX 256 269 FT HELIX 274 289 FT STRAND 291 294 FT HELIX 295 297 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 //