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Protein

Ketohexokinase

Gene

KHK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.1 Publication

Catalytic activityi

ATP + D-fructose = ADP + D-fructose 1-phosphate.1 Publication

Enzyme regulationi

Requires potassium. Inhibition by ADP.

Kineticsi

kcat is 7.6 sec(-1).1 Publication
  1. KM=0.8 mM for D-fructose (at 25 degrees Celsius)1 Publication
  2. KM=0.15 mM for Mg-ATP (at 25 degrees Celsius)1 Publication

    Pathwayi: fructose metabolism

    This protein is involved in the pathway fructose metabolism, which is part of Carbohydrate metabolism.
    View all proteins of this organism that are known to be involved in the pathway fructose metabolism and in Carbohydrate metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei15D-fructose1
    Binding sitei41D-fructose; via amide nitrogen1
    Binding sitei42D-fructose1
    Binding sitei45D-fructose1
    Binding sitei108ATP1
    Binding sitei258D-fructose1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi255 – 258ATP4

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • ketohexokinase activity Source: MGI

    GO - Biological processi

    Keywordsi

    Molecular functionKinase, Transferase
    Biological processCarbohydrate metabolism
    LigandATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06437-MONOMER
    BRENDAi2.7.1.3 2681
    ReactomeiR-HSA-5657562 Essential fructosuria
    R-HSA-70350 Fructose catabolism
    SABIO-RKP50053
    UniPathwayiUPA00202

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    KetohexokinaseImported (EC:2.7.1.31 Publication)
    Alternative name(s):
    Hepatic fructokinase
    Gene namesi
    Name:KHKImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000138030.12
    HGNCiHGNC:6315 KHK
    MIMi614058 gene
    neXtProtiNX_P50053

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Pathology & Biotechi

    Involvement in diseasei

    Fructosuria (FRUCT)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionBenign defect of intermediary metabolism.
    See also OMIM:229800
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_00607240G → R in FRUCT; loss of ketohexokinase function; insoluble. 2 PublicationsCorresponds to variant dbSNP:rs104893643EnsemblClinVar.1
    Natural variantiVAR_00607343A → T in FRUCT; no effect on ketohexokinase function; decreases enzyme activity but no effect in substrate affinity; decreases thermal stability. 2 PublicationsCorresponds to variant dbSNP:rs104893644EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi3795
    MalaCardsiKHK
    MIMi229800 phenotype
    OpenTargetsiENSG00000138030
    Orphaneti2056 Essential fructosuria
    PharmGKBiPA30095

    Chemistry databases

    ChEMBLiCHEMBL1275212

    Polymorphism and mutation databases

    BioMutaiKHK
    DMDMi1730044

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000800881 – 298KetohexokinaseAdd BLAST298

    Proteomic databases

    EPDiP50053
    MaxQBiP50053
    PaxDbiP50053
    PeptideAtlasiP50053
    PRIDEiP50053

    2D gel databases

    REPRODUCTION-2DPAGEIPI00029488

    PTM databases

    iPTMnetiP50053
    PhosphoSitePlusiP50053

    Expressioni

    Tissue specificityi

    Most abundant in liver, kidney, gut, spleen and pancreas. Low levels also found in adrenal, muscle, brain and eye.1 Publication

    Gene expression databases

    BgeeiENSG00000138030
    CleanExiHS_KHK
    ExpressionAtlasiP50053 baseline and differential
    GenevisibleiP50053 HS

    Organism-specific databases

    HPAiHPA007040

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Binary interactionsi

    Show more details

    Protein-protein interaction databases

    BioGridi109996, 20 interactors
    DIPiDIP-50184N
    IntActiP50053, 4 interactors
    STRINGi9606.ENSP00000260598

    Chemistry databases

    BindingDBiP50053

    Structurei

    Secondary structure

    1298
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi5 – 10Combined sources6
    Beta strandi13 – 22Combined sources10
    Beta strandi29 – 31Combined sources3
    Beta strandi33 – 41Combined sources9
    Helixi42 – 53Combined sources12
    Beta strandi57 – 63Combined sources7
    Helixi67 – 78Combined sources12
    Beta strandi86 – 88Combined sources3
    Beta strandi90 – 92Combined sources3
    Beta strandi96 – 102Combined sources7
    Turni103 – 105Combined sources3
    Beta strandi108 – 113Combined sources6
    Helixi122 – 126Combined sources5
    Helixi130 – 132Combined sources3
    Beta strandi133 – 139Combined sources7
    Helixi143 – 157Combined sources15
    Helixi162 – 164Combined sources3
    Beta strandi167 – 172Combined sources6
    Helixi177 – 184Combined sources8
    Beta strandi185 – 191Combined sources7
    Helixi193 – 198Combined sources6
    Helixi204 – 211Combined sources8
    Helixi212 – 214Combined sources3
    Beta strandi220 – 224Combined sources5
    Helixi226 – 228Combined sources3
    Beta strandi230 – 233Combined sources4
    Beta strandi239 – 242Combined sources4
    Helixi256 – 269Combined sources14
    Helixi274 – 289Combined sources16
    Beta strandi291 – 294Combined sources4
    Helixi295 – 297Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2HLZX-ray1.85A/B/C/D5-298[»]
    2HQQX-ray1.86A1-298[»]
    2HW1X-ray2.10A1-298[»]
    3B3LX-ray2.90A/B/C/D1-298[»]
    3NBVX-ray2.30A/B5-298[»]
    3NBWX-ray2.34A/B5-298[»]
    3NC2X-ray2.50A/B5-298[»]
    3NC9X-ray2.40A/B5-298[»]
    3NCAX-ray2.60A/B5-298[»]
    3Q92X-ray2.80A/B5-298[»]
    3QA2X-ray2.52A/B5-298[»]
    3QAIX-ray2.70A/B5-298[»]
    3RO4X-ray2.60A/B5-298[»]
    5WBMX-ray2.16A/B5-298[»]
    5WBOX-ray2.25A/B5-298[»]
    5WBPX-ray2.74A/B5-298[»]
    5WBQX-ray2.40A/B5-298[»]
    5WBRX-ray2.58A/B5-298[»]
    5WBZX-ray2.40A/B5-298[»]
    ProteinModelPortaliP50053
    SMRiP50053
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP50053

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the carbohydrate kinase PfkB family.Curated

    Phylogenomic databases

    eggNOGiKOG2947 Eukaryota
    ENOG4111F4Q LUCA
    GeneTreeiENSGT00390000007458
    HOGENOMiHOG000212926
    HOVERGENiHBG003335
    InParanoidiP50053
    KOiK00846
    OMAiCNKDYPQ
    OrthoDBiEOG091G0EV7
    TreeFamiTF323942

    Family and domain databases

    CDDicd01939 Ketohexokinase, 1 hit
    Gene3Di3.40.1190.20, 1 hit
    InterProiView protein in InterPro
    IPR034093 KHK
    IPR011611 PfkB_dom
    IPR029056 Ribokinase-like
    PfamiView protein in Pfam
    PF00294 PfkB, 1 hit
    SUPFAMiSSF53613 SSF53613, 1 hit

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform C1 Publication (identifier: P50053-1) [UniParc]FASTAAdd to basket
    Also known as: Central, hepatic/renal/intestinal1 Publication

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MEEKQILCVG LVVLDVISLV DKYPKEDSEI RCLSQRWQRG GNASNSCTVL
    60 70 80 90 100
    SLLGAPCAFM GSMAPGHVAD FLVADFRRRG VDVSQVAWQS KGDTPSSCCI
    110 120 130 140 150
    INNSNGNRTI VLHDTSLPDV SATDFEKVDL TQFKWIHIEG RNASEQVKML
    160 170 180 190 200
    QRIDAHNTRQ PPEQKIRVSV EVEKPREELF QLFGYGDVVF VSKDVAKHLG
    210 220 230 240 250
    FQSAEEALRG LYGRVRKGAV LVCAWAEEGA DALGPDGKLL HSDAFPPPRV
    260 270 280 290
    VDTLGAGDTF NASVIFSLSQ GRSVQEALRF GCQVAGKKCG LQGFDGIV
    Length:298
    Mass (Da):32,523
    Last modified:April 29, 2015 - v2
    Checksum:iBE77FC325CAC5721
    GO
    Isoform A1 Publication (identifier: P50053-2) [UniParc]FASTAAdd to basket
    Also known as: Peripheral1 Publication

    The sequence of this isoform differs from the canonical sequence as follows:
         72-115: LVADFRRRGV...GNRTIVLHDT → VLDDLRRYSV...GSRTILYYDR

    Note: More widely distributed but with a low expression level. KM=7 mM for D-fructose (at 25 degrees Celsius). KM=036 mM for Mg-ATP (at 25 degrees Celsius). kcat is 6.9 sec(-1).1 Publication
    Show »
    Length:298
    Mass (Da):32,730
    Checksum:i1BA47BDC60C1B89F
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_00607240G → R in FRUCT; loss of ketohexokinase function; insoluble. 2 PublicationsCorresponds to variant dbSNP:rs104893643EnsemblClinVar.1
    Natural variantiVAR_00607343A → T in FRUCT; no effect on ketohexokinase function; decreases enzyme activity but no effect in substrate affinity; decreases thermal stability. 2 PublicationsCorresponds to variant dbSNP:rs104893644EnsemblClinVar.1
    Natural variantiVAR_00607449V → I1 PublicationCorresponds to variant dbSNP:rs2304681EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_00466972 – 115LVADF…VLHDT → VLDDLRRYSVDLRYTVFQTT GSVPIATVIINEASGSRTIL YYDR in isoform A. CuratedAdd BLAST44

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X78678 mRNA Translation: CAA55347.1
    X78677 mRNA Translation: CAA55346.1
    CR456801 mRNA Translation: CAG33082.1
    AC013403 Genomic DNA Translation: AAX93167.1
    CH471053 Genomic DNA Translation: EAX00643.1
    BC006233 mRNA Translation: AAH06233.1
    Y09336 Genomic DNA Translation: CAA70516.1
    Y09341 Genomic DNA Translation: CAA70522.1
    Y09341 Genomic DNA Translation: CAA70523.1
    Y09340 Genomic DNA Translation: CAA70521.1
    AJ005168 Genomic DNA Translation: CAA06409.1
    CCDSiCCDS1734.1 [P50053-2]
    CCDS1735.1 [P50053-1]
    RefSeqiNP_000212.1, NM_000221.2 [P50053-2]
    NP_006479.1, NM_006488.2 [P50053-1]
    UniGeneiHs.567297

    Genome annotation databases

    EnsembliENST00000260598; ENSP00000260598; ENSG00000138030 [P50053-1]
    ENST00000260599; ENSP00000260599; ENSG00000138030 [P50053-2]
    GeneIDi3795
    KEGGihsa:3795
    UCSCiuc002ril.3 human [P50053-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Similar proteinsi

    Entry informationi

    Entry nameiKHK_HUMAN
    AccessioniPrimary (citable) accession number: P50053
    Secondary accession number(s): Q6IBK2
    , Q99532, Q9BRJ3, Q9UMN1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: April 29, 2015
    Last modified: May 23, 2018
    This is version 174 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health