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P50053 (KHK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ketohexokinase

EC=2.7.1.3
Alternative name(s):
Hepatic fructokinase
Gene names
Name:KHK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

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.7

Tissue specificity

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

Involvement in disease

Fructosuria (FRUCT) [MIM:229800]: Benign defect of intermediary metabolism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.7

Sequence similarities

Belongs to the carbohydrate kinase PfkB family.

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

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

......................................................... 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS FRUCT ARG-40 AND THR-43, VARIANT ILE-49.
[2]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Structure and alternative splicing of the ketohexokinase gene."
Hayward B.E., Bonthron D.T.
Eur. J. Biochem. 257:85-91(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-26 AND 71-298, ALTERNATIVE SPLICING.
[7]"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] [Europe PMC] [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.
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.
CCDSCCDS1734.1. [P50053-1]
CCDS1735.1. [P50053-2]
RefSeqNP_000212.1. NM_000221.2. [P50053-1]
NP_006479.1. NM_006488.2. [P50053-2]
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[»]
3Q92X-ray2.80A/B5-298[»]
3QA2X-ray2.52A/B5-298[»]
3QAIX-ray2.70A/B5-298[»]
3RO4X-ray2.60A/B5-298[»]
ProteinModelPortalP50053.
SMRP50053. Positions 5-298.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109996. 12 interactions.
STRING9606.ENSP00000260598.

Chemistry

BindingDBP50053.
ChEMBLCHEMBL1275212.

PTM databases

PhosphoSiteP50053.

Polymorphism databases

DMDM1730044.

2D gel databases

REPRODUCTION-2DPAGEIPI00029488.

Proteomic databases

MaxQBP50053.
PaxDbP50053.
PRIDEP50053.

Protocols and materials databases

DNASU3795.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260598; ENSP00000260598; ENSG00000138030. [P50053-2]
ENST00000260599; ENSP00000260599; ENSG00000138030. [P50053-1]
GeneID3795.
KEGGhsa:3795.
UCSCuc002ril.2. human. [P50053-1]
uc002rim.2. human. [P50053-2]

Organism-specific databases

CTD3795.
GeneCardsGC02P027309.
HGNCHGNC:6315. KHK.
HPAHPA007040.
MIM229800. phenotype.
614058. gene.
neXtProtNX_P50053.
Orphanet2056. Essential fructosuria.
PharmGKBPA30095.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0524.
HOGENOMHOG000212926.
HOVERGENHBG003335.
InParanoidP50053.
KOK00846.
OMAHVADFLV.
OrthoDBEOG7K6PV6.
PhylomeDBP50053.
TreeFamTF323942.

Enzyme and pathway databases

BioCycMetaCyc:HS06437-MONOMER.
BRENDA2.7.1.3. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP50053.
UniPathwayUPA00202.

Gene expression databases

ArrayExpressP50053.
BgeeP50053.
CleanExHS_KHK.
GenevestigatorP50053.

Family and domain databases

Gene3D3.40.1190.20. 1 hit.
InterProIPR011611. PfkB_dom.
IPR029056. Ribokinase-like.
[Graphical view]
PfamPF00294. PfkB. 1 hit.
[Graphical view]
SUPFAMSSF53613. SSF53613. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP50053.
GenomeRNAi3795.
NextBio14897.
PROP50053.
SOURCESearch...

Entry information

Entry nameKHK_HUMAN
AccessionPrimary (citable) accession number: P50053
Secondary accession number(s): Q6IBK2 expand/collapse secondary AC list , Q99532, Q9BRJ3, Q9UMN1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 137 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

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