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P50053 (KHK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Ketohexokinase
EC=2.7.1.3
Alternative name(s):
Hepatic fructokinase
Gene names
Name:KHK
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length298 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Enzyme regulation

Requires potassium. Inhibition by ADP.

Pathway

Carbohydrate metabolism; fructose metabolism.

Subunit structure

Homodimer. Ref.4

Tissue specificity

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

Involvement in disease

Defects in KHK are the cause of fructosuria (FRUCT) [MIM:229800]. Benign defect of intermediary metabolism. Ref.1 Ref.4

Sequence similarities

Belongs to the carbohydrate kinase pfkB family.

Ontologies

Keywords
   Biological processCarbohydrate metabolism
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological processfructose catabolic process

Traceable author statement. Source: Reactome

   Cellular componentcytosol

Traceable author statement. Source: Reactome

   Molecular functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ketohexokinase activity

Traceable author statement. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: P50053-1)

Also known as: Central; hepatic/renal/intestinal;

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.
Isoform C (identifier: P50053-2)

Also known as: Peripheral;

The sequence of this isoform differs from the canonical sequence as follows:
     72-115: VLDDLRRYSV...GSRTILYYDR → LVADFRRRGV...GNRTIVLHDT
Note: More widely distributed but with a low expression level.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 298298Ketohexokinase
PRO_0000080088

Regions

Nucleotide binding255 – 2584ATP

Sites

Binding site151D-fructose
Binding site411D-fructose; via amide nitrogen
Binding site421D-fructose
Binding site451D-fructose
Binding site1081ATP
Binding site2581D-fructose

Amino acid modifications

Modified residue1691Phosphoserine By similarity

Natural variations

Alternative sequence72 – 11544VLDDL…LYYDR → LVADFRRRGVDVSQVAWQSK GDTPSSCCIINNSNGNRTIV LHDT in isoform C.
VSP_004669
Natural variant401G → R in FRUCT. Ref.1
VAR_006072
Natural variant431A → T in FRUCT. Ref.1
VAR_006073
Natural variant491V → I. Ref.1
Corresponds to variant rs2304681 [ dbSNP | Ensembl ].
VAR_006074
Natural variant1591R → G Either a polymorphism or a cloning artifact.
VAR_006075

Secondary structure

1 .............................................. 298
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A (Central) (hepatic/renal/intestinal) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 1BA47BDC60C1B89F

FASTA29832,730
        10         20         30         40         50         60 
MEEKQILCVG LVVLDVISLV DKYPKEDSEI RCLSQRWQRG GNASNSCTVL SLLGAPCAFM 

        70         80         90        100        110        120 
GSMAPGHVAD FVLDDLRRYS VDLRYTVFQT TGSVPIATVI INEASGSRTI LYYDRSLPDV 

       130        140        150        160        170        180 
SATDFEKVDL TQFKWIHIEG RNASEQVKML QRIDAHNTRQ PPEQKIRVSV EVEKPREELF 

       190        200        210        220        230        240 
QLFGYGDVVF VSKDVAKHLG FQSAEEALRG LYGRVRKGAV LVCAWAEEGA DALGPDGKLL 

       250        260        270        280        290 
HSDAFPPPRV VDTLGAGDTF NASVIFSLSQ GRSVQEALRF GCQVAGKKCG LQGFDGIV

« Hide

Isoform C (Peripheral) [UniParc].

Checksum: BE77FC325CAC5721
Show »

FASTA29832,523

References

« Hide 'large scale' references
[1]"Molecular basis of essential fructosuria: molecular cloning and mutational analysis of human ketohexokinase (fructokinase)."
Bonthron D.T., Brady N., Donaldson I.A., Steinmann B.
Hum. Mol. Genet. 3:1627-1631(1994) [PubMed: 7833921] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS FRUCT ARG-40 AND THR-43, VARIANT ILE-49.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[3]"Structure and alternative splicing of the ketohexokinase gene."
Hayward B.E., Bonthron D.T.
Eur. J. Biochem. 257:85-91(1998) [PubMed: 9799106] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26 AND 71-298, ALTERNATIVE SPLICING.
[4]"Structures of alternatively spliced isoforms of human ketohexokinase."
Trinh C.H., Asipu A., Bonthron D.T., Phillips S.E.
Acta Crystallogr. D 65:201-211(2009) [PubMed: 19237742] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH FRUCTOSE AND AMP-PNP, X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF ISOFORM C, SUBUNIT, SUBSTRATE-BINDING SITES.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		X78678 mRNA. Translation: CAA55347.1.
X78677 mRNA. Translation: CAA55346.1.
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.
IPIIPI00029488.
IPI00216136.
RefSeqNP_000212.1. NM_000221.2.
NP_006479.1. NM_006488.2.
UniGeneHs.567297.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
3RO4X-ray2.60A/B5-298[»]
ProteinModelPortalP50053.
SMRP50053. Positions 5-298.
ModBaseSearch...

Protein-protein interaction databases

STRINGP50053.

PTM databases

PhosphoSiteP50053.

Polymorphism databases

DMDM1730044.

2D gel databases

REPRODUCTION-2DPAGEIPI00029488.

Proteomic databases

PRIDEP50053.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260599; ENSP00000260599; ENSG00000138030.
GeneID3795.
KEGGhsa:3795.
UCSCuc002ril.2. human.
uc002rim.2. human.

Organism-specific databases

CTD3795.
GeneCardsGC02P027309.
H-InvDBHIX0001908.
HGNCHGNC:6315. KHK.
HPAHPA007040.
MIM229800. phenotype.
614058. gene.
neXtProtNX_P50053.
Orphanet2056. Fructosuria.
PharmGKBPA30095.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG05220.
HOGENOMHBG730500.
HOVERGENHBG003335.
InParanoidP50053.
OMARTIILYD.
OrthoDBEOG4F7NKS.
PhylomeDBP50053.

Enzyme and pathway databases

BioCycMetaCyc:HS06437-MONOMER.
BRENDA2.7.1.3. 2681.
ReactomeREACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpressP50053.
BgeeP50053.
CleanExHS_KHK.
GenevestigatorP50053.
GermOnlineENSG00000138030. Homo sapiens.

Family and domain databases

InterProIPR011611. Carb/pur_kinase.
[Graphical view]
KOK00846.
PfamPF00294. PfkB. 1 hit.
[Graphical view]
PROSITEPS00583. PFKB_KINASES_1. False negative.
PS00584. PFKB_KINASES_2. False negative.
[Graphical view]
ProtoNetSearch...

Other

NextBio14897.
SOURCESearch...

Entry information

Entry nameKHK_HUMAN
AccessionPrimary (citable) accession number: P50053
Secondary accession number(s): Q99532, Q9BRJ3, Q9UMN1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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

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