Reviewed, UniProtKB/Swiss-Prot P50053 (KHK_HUMAN)

Names and origin

Protein names

Recommended name:
    Ketohexokinase
    EC=2.7.1.3
Alternative name(s):
    Hepatic fructokinase

Gene names

Name:

KHK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	298 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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	Dimer of A-A, A-C or C-C Probable.
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 [MIM:229800]. Fructosuria is a benign defect of intermediary metabolism.
Sequence similarities	Belongs to the carbohydrate kinase pfkB family.
Caution	Form C has not yet been fully sequenced in its N-terminal (from 1-69).

Ontologies

Keywords
Biological process	Carbohydrate metabolism
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	carbohydrate metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	ketohexokinase activity Ref.1 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARRB1	P49407	1	EBI-1053974,EBI-743313
CD2BP2	O95400	1	EBI-1053974,EBI-768015
CDK5RAP3	Q96JB5	1	EBI-1053974,EBI-718818
DEDD	O75618	1	EBI-1053974,EBI-1043164
LCN1	P31025	1	EBI-1053974,EBI-1052433
LYZ	P61626	1	EBI-1053974,EBI-355360
RNPS1	Q15287	1	EBI-1053974,EBI-395959
SNRPB	P14678	1	EBI-1053974,EBI-372458

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform A (identifier: P50053-1)

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)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 298	298	Ketohexokinase		PRO_0000080088
Amino acid modifications
	Modified residue	169	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	72 – 115	44	VLDDL…LYYDR → LVADFRRRGVDVSQVAWQSK GDTPSSCCIINNSNGNRTIV LHDT in isoform C.		VSP_004669
	Natural variant	40	1	G → R in fructosuria.		VAR_006072
	Natural variant	43	1	A → T in fructosuria.		VAR_006073
	Natural variant	49	1	V → I: dbSNP rs2304681.		VAR_006074
	Natural variant	159	1	R → G Either a polymorphism or a cloning artifact.		VAR_006075

Sequences

	Sequence		Length	Mass (Da)
	Isoform A [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 1BA47BDC60C1B89F	FASTA	298	32,730
	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
	Isoform C [UniParc]. Checksum: BE77FC325CAC5721		298	32,523
	10 20 30 40 50 60 MEEKQILCVG LVVLDVISLV DKYPKEDSEI RCLSQRWQRG GNASNSCTVL SLLGAPCAFM 70 80 90 100 110 120 GSMAPGHVAD FLVADFRRRG VDVSQVAWQS KGDTPSSCCI INNSNGNRTI VLHDTSLPDV 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

References

	« Hide 'large scale' referencesShow '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 FRUCTOSURIA 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

RefSeq

NP_000212.1.
NP_006479.1.

UniGene

Hs.567297

3D structure databases

PDBMSD

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	[»]

SMR

P50053. Positions 5-298.

ModBase

Search...

Protein-protein interaction databases

IntAct

P50053.

PTM databases

PhosphoSite

P50053.

2-D gel databases

REPRODUCTION-2DPAGE

IPI00029488.

Genome annotation databases

Ensembl

ENSG00000138030. Homo sapiens. [Contig view]

GeneID

3795.

KEGG

hsa:3795.

Organism-specific databases

H-InvDB

HIX0001908.

HGNC

HGNC:6315. KHK.

HPA

HPA007040.

MIM

229800. gene+phenotype.

Orphanet

2056. Fructosuria.

PharmGKB

PA30095.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P50053.

HOVERGEN

P50053.

Enzyme and pathway databases

Reactome

REACT_1709. Metabolism of small molecules.

Gene expression databases

CleanEx

HS_KHK.

GermOnline

ENSG00000138030. Homo sapiens.

Family and domain databases

InterPro

IPR011611. Carb/pur_kinase.
IPR002173. Carboh/pur_kinase_PfkB_CS.
[Graphical view]

Pfam

PF00294. PfkB. 2 hits.
[Graphical view]

PROSITE

PS00583. PFKB_KINASES_1. False negative.
PS00584. PFKB_KINASES_2. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

14897.

SOURCE

Search...

Entry information

Entry name

KHK_HUMAN

Accession

Primary (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:	November 25, 2008
This is version 82 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)