UniProtKB - P50053 (KHK_HUMAN)
Protein
Ketohexokinase
Gene
KHK
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the phosphorylation of the ketose sugar fructose to fructose-1-phosphate.1 Publication
Catalytic activityi
- EC:2.7.1.31 Publication
Activity regulationi
Requires potassium. Inhibition by ADP.
Kineticsi
kcat is 7.6 sec(-1).1 Publication
- KM=0.8 mM for D-fructose (at 25 degrees Celsius)1 Publication
- KM=0.15 mM for Mg-ATP (at 25 degrees Celsius)1 Publication
: fructose metabolism Pathwayi
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 15 | Beta-D-fructoseCombined sources1 Publication | 1 | |
Binding sitei | 41 | Beta-D-fructose; via amide nitrogenCombined sources | 1 | |
Binding sitei | 42 | Beta-D-fructoseCombined sources | 1 | |
Binding sitei | 45 | Beta-D-fructoseCombined sources | 1 | |
Binding sitei | 108 | ATPCombined sources1 Publication | 1 | |
Binding sitei | 258 | Beta-D-fructoseCombined sources | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 226 – 229 | ATPCombined sources1 Publication | 4 | |
Nucleotide bindingi | 255 – 258 | ATPCombined sources1 Publication | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- ketohexokinase activity Source: MGI
GO - Biological processi
- fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate Source: Reactome
- fructose metabolic process Source: GO_Central
- regulation of glycogen metabolic process Source: GO_Central
- response to fructose Source: GO_Central
- response to glucose Source: GO_Central
- response to insulin Source: GO_Central
- response to sucrose Source: GO_Central
- response to zinc ion Source: GO_Central
Keywordsi
Molecular function | Kinase, Transferase |
Biological process | Carbohydrate metabolism |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS06437-MONOMER |
BRENDAi | 2.7.1.3, 2681 |
PathwayCommonsi | P50053 |
Reactomei | R-HSA-5657562, Essential fructosuria R-HSA-70350, Fructose catabolism |
SABIO-RKi | P50053 |
UniPathwayi | UPA00202 |
Names & Taxonomyi
Protein namesi | Recommended name: KetohexokinaseImported (EC:2.7.1.31 Publication)Alternative name(s): Hepatic fructokinase |
Gene namesi | Name:KHKImported |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6315, KHK |
MIMi | 614058, gene |
neXtProti | NX_P50053 |
VEuPathDBi | HostDB:ENSG00000138030.12 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Other locations
- cytoplasm Source: LIFEdb
Pathology & Biotechi
Involvement in diseasei
Fructosuria (FRUCT)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionBenign defect of intermediary metabolism.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_006072 | 40 | G → R in FRUCT; loss of ketohexokinase function; insoluble. 2 PublicationsCorresponds to variant dbSNP:rs104893643EnsemblClinVar. | 1 | |
Natural variantiVAR_006073 | 43 | A → 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 variantOrganism-specific databases
DisGeNETi | 3795 |
MalaCardsi | KHK |
MIMi | 229800, phenotype |
OpenTargetsi | ENSG00000138030 |
Orphaneti | 2056, Essential fructosuria |
PharmGKBi | PA30095 |
Miscellaneous databases
Pharosi | P50053, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1275212 |
Genetic variation databases
BioMutai | KHK |
DMDMi | 1730044 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000080088 | 1 – 298 | KetohexokinaseAdd BLAST | 298 |
Proteomic databases
EPDi | P50053 |
jPOSTi | P50053 |
MassIVEi | P50053 |
MaxQBi | P50053 |
PaxDbi | P50053 |
PeptideAtlasi | P50053 |
PRIDEi | P50053 |
ProteomicsDBi | 56192 [P50053-1] 56193 [P50053-2] |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00029488 |
PTM databases
iPTMneti | P50053 |
PhosphoSitePlusi | P50053 |
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
Bgeei | ENSG00000138030, Expressed in right lobe of liver and 179 other tissues |
ExpressionAtlasi | P50053, baseline and differential |
Genevisiblei | P50053, HS |
Organism-specific databases
HPAi | ENSG00000138030, Group enriched (intestine, kidney, liver) |
Interactioni
Subunit structurei
Homodimer.
1 PublicationBinary interactionsi
Hide detailsP50053
With | #Exp. | IntAct |
---|---|---|
LHX9 [Q9NQ69] | 3 | EBI-1053974,EBI-10175218 |
Isoform A [P50053-2]
With | #Exp. | IntAct |
---|---|---|
APPBP2 [Q92624] | 3 | EBI-12204387,EBI-743771 |
LHX2 [P50458] | 3 | EBI-12204387,EBI-12179869 |
LHX9 [Q9NQ69] | 3 | EBI-12204387,EBI-10175218 |
PRPS1 - isoform 1 [P60891-1] | 4 | EBI-12204387,EBI-16205225 |
Protein-protein interaction databases
BioGRIDi | 109996, 24 interactors |
DIPi | DIP-50184N |
IntActi | P50053, 8 interactors |
STRINGi | 9606.ENSP00000260599 |
Chemistry databases
BindingDBi | P50053 |
Miscellaneous databases
RNActi | P50053, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P50053 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P50053 |
Family & Domainsi
Sequence similaritiesi
Belongs to the carbohydrate kinase PfkB family.Curated
Phylogenomic databases
eggNOGi | KOG2947, Eukaryota |
GeneTreei | ENSGT00390000007458 |
HOGENOMi | CLU_027634_3_0_1 |
InParanoidi | P50053 |
OMAi | RMASYKC |
OrthoDBi | 720391at2759 |
TreeFami | TF323942 |
Family and domain databases
CDDi | cd01939, Ketohexokinase, 1 hit |
Gene3Di | 3.40.1190.20, 1 hit |
InterProi | View protein in InterPro IPR034093, KHK IPR011611, PfkB_dom IPR029056, Ribokinase-like |
Pfami | View protein in Pfam PF00294, PfkB, 1 hit |
SUPFAMi | SSF53613, SSF53613, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
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 »Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketC9JDL1 | C9JDL1_HUMAN | Ketohexokinase | KHK | 279 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_006072 | 40 | G → R in FRUCT; loss of ketohexokinase function; insoluble. 2 PublicationsCorresponds to variant dbSNP:rs104893643EnsemblClinVar. | 1 | |
Natural variantiVAR_006073 | 43 | A → 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_006074 | 49 | V → I1 PublicationCorresponds to variant dbSNP:rs2304681EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004669 | 72 – 115 | LVADF…VLHDT → VLDDLRRYSVDLRYTVFQTT GSVPIATVIINEASGSRTIL YYDR in isoform A. CuratedAdd BLAST | 44 |
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 |
CCDSi | CCDS1734.1 [P50053-2] CCDS1735.1 [P50053-1] |
RefSeqi | NP_000212.1, NM_000221.2 [P50053-2] NP_006479.1, NM_006488.2 [P50053-1] |
Genome annotation databases
Ensembli | ENST00000260598; ENSP00000260598; ENSG00000138030 [P50053-1] ENST00000260599; ENSP00000260599; ENSG00000138030 [P50053-2] |
GeneIDi | 3795 |
KEGGi | hsa:3795 |
UCSCi | uc002ril.3, human [P50053-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS1734.1 [P50053-2] CCDS1735.1 [P50053-1] |
RefSeqi | NP_000212.1, NM_000221.2 [P50053-2] NP_006479.1, NM_006488.2 [P50053-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2HLZ | X-ray | 1.85 | A/B/C/D | 5-298 | [»] | |
2HQQ | X-ray | 1.86 | A | 1-298 | [»] | |
2HW1 | X-ray | 2.10 | A | 1-298 | [»] | |
3B3L | X-ray | 2.90 | A/B/C/D | 1-298 | [»] | |
3NBV | X-ray | 2.30 | A/B | 5-298 | [»] | |
3NBW | X-ray | 2.34 | A/B | 5-298 | [»] | |
3NC2 | X-ray | 2.50 | A/B | 5-298 | [»] | |
3NC9 | X-ray | 2.40 | A/B | 5-298 | [»] | |
3NCA | X-ray | 2.60 | A/B | 5-298 | [»] | |
3Q92 | X-ray | 2.80 | A/B | 5-298 | [»] | |
3QA2 | X-ray | 2.52 | A/B | 5-298 | [»] | |
3QAI | X-ray | 2.70 | A/B | 5-298 | [»] | |
3RO4 | X-ray | 2.60 | A/B | 5-298 | [»] | |
5WBM | X-ray | 2.16 | A/B | 5-298 | [»] | |
5WBO | X-ray | 2.25 | A/B | 5-298 | [»] | |
5WBP | X-ray | 2.74 | A/B | 5-298 | [»] | |
5WBQ | X-ray | 2.40 | A/B | 5-298 | [»] | |
5WBR | X-ray | 2.58 | A/B | 5-298 | [»] | |
5WBZ | X-ray | 2.40 | A/B | 5-298 | [»] | |
6W0N | X-ray | 2.41 | A/B | 5-298 | [»] | |
6W0W | X-ray | 2.80 | A/B | 5-298 | [»] | |
6W0X | X-ray | 2.38 | A/B | 5-298 | [»] | |
6W0Y | X-ray | 2.54 | A/B | 5-298 | [»] | |
6W0Z | X-ray | 2.30 | A/B | 5-298 | [»] | |
SMRi | P50053 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109996, 24 interactors |
DIPi | DIP-50184N |
IntActi | P50053, 8 interactors |
STRINGi | 9606.ENSP00000260599 |
Chemistry databases
BindingDBi | P50053 |
ChEMBLi | CHEMBL1275212 |
PTM databases
iPTMneti | P50053 |
PhosphoSitePlusi | P50053 |
Genetic variation databases
BioMutai | KHK |
DMDMi | 1730044 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00029488 |
Proteomic databases
EPDi | P50053 |
jPOSTi | P50053 |
MassIVEi | P50053 |
MaxQBi | P50053 |
PaxDbi | P50053 |
PeptideAtlasi | P50053 |
PRIDEi | P50053 |
ProteomicsDBi | 56192 [P50053-1] 56193 [P50053-2] |
Protocols and materials databases
Antibodypediai | 2054, 475 antibodies |
DNASUi | 3795 |
Genome annotation databases
Ensembli | ENST00000260598; ENSP00000260598; ENSG00000138030 [P50053-1] ENST00000260599; ENSP00000260599; ENSG00000138030 [P50053-2] |
GeneIDi | 3795 |
KEGGi | hsa:3795 |
UCSCi | uc002ril.3, human [P50053-1] |
Organism-specific databases
CTDi | 3795 |
DisGeNETi | 3795 |
GeneCardsi | KHK |
HGNCi | HGNC:6315, KHK |
HPAi | ENSG00000138030, Group enriched (intestine, kidney, liver) |
MalaCardsi | KHK |
MIMi | 229800, phenotype 614058, gene |
neXtProti | NX_P50053 |
OpenTargetsi | ENSG00000138030 |
Orphaneti | 2056, Essential fructosuria |
PharmGKBi | PA30095 |
VEuPathDBi | HostDB:ENSG00000138030.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2947, Eukaryota |
GeneTreei | ENSGT00390000007458 |
HOGENOMi | CLU_027634_3_0_1 |
InParanoidi | P50053 |
OMAi | RMASYKC |
OrthoDBi | 720391at2759 |
TreeFami | TF323942 |
Enzyme and pathway databases
UniPathwayi | UPA00202 |
BioCyci | MetaCyc:HS06437-MONOMER |
BRENDAi | 2.7.1.3, 2681 |
PathwayCommonsi | P50053 |
Reactomei | R-HSA-5657562, Essential fructosuria R-HSA-70350, Fructose catabolism |
SABIO-RKi | P50053 |
Miscellaneous databases
BioGRID-ORCSi | 3795, 8 hits in 989 CRISPR screens |
EvolutionaryTracei | P50053 |
GenomeRNAii | 3795 |
Pharosi | P50053, Tchem |
PROi | PR:P50053 |
RNActi | P50053, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000138030, Expressed in right lobe of liver and 179 other tissues |
ExpressionAtlasi | P50053, baseline and differential |
Genevisiblei | P50053, HS |
Family and domain databases
CDDi | cd01939, Ketohexokinase, 1 hit |
Gene3Di | 3.40.1190.20, 1 hit |
InterProi | View protein in InterPro IPR034093, KHK IPR011611, PfkB_dom IPR029056, Ribokinase-like |
Pfami | View protein in Pfam PF00294, PfkB, 1 hit |
SUPFAMi | SSF53613, SSF53613, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KHK_HUMAN | |
Accessioni | P50053Primary (citable) accession number: P50053 Secondary accession number(s): Q6IBK2 Q9UMN1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | April 29, 2015 | |
Last modified: | April 7, 2021 | |
This is version 196 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families