Khk ketohexokinase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Khkprovided by MGI
Official Full Name: ketohexokinaseprovided by MGI
Primary source: MGI:MGI:1096353
See related: Ensembl:ENSMUSG00000029162 AllianceGenome:MGI:1096353
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables ketohexokinase activity. Acts upstream of or within fructose metabolic process and regulation of glycogen metabolic process. Located in cytoplasm and nucleus. Is expressed in alimentary system; central nervous system; liver; and retina. Human ortholog(s) of this gene implicated in essential fructosuria. Orthologous to human KHK (ketohexokinase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in kidney adult (RPKM 274.9), liver adult (RPKM 172.1) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 B1; 5 16.9 cM

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (31078780..31088592)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (30921436..30931248)

Chromosome 5 - NC_000071.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.
Title: Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD.
Ketohexokinase-C regulates global protein acetylation to decrease carnitine palmitoyltransferase 1a-mediated fatty acid oxidation.
Title: Ketohexokinase-C regulates global protein acetylation to decrease carnitine palmitoyltransferase 1a-mediated fatty acid oxidation.
Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction.
Title: Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction.
studies suggest that it is the inhibition of the Khk C isoform, not the A isoform, that protects animals from Hereditary fructose intolerance.
Title: Ketohexokinase C blockade ameliorates fructose-induced metabolic dysfunction in fructose-sensitive mice.
Manual correction of the input Khk gene model provided a much more accurate estimation of relative Khk isoform expression when compared to quantitative PCR.
Title: Correction of gene model annotations improves isoform abundance estimates: the example of ketohexokinase ( Khk).
These results suggest that KHK-C might play a deleterious role in diabetic kidney disease progression through endogenous fructose metabolism, and that KHK-A plays a unique protective role against the development of diabetic kidney disease.
Title: Lacking ketohexokinase-A exacerbates renal injury in streptozotocin-induced diabetic mice.
This studies provided the first evidence that fructokinase modulates vasopressin synthesis in the SON and secretion from the posterior pituitary into circulation.
Title: Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice.
Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys.
Title: Aging-associated renal disease in mice is fructokinase dependent.
Feedforward upregulation of fructolytic and gluconeogenic enzymes specifically requires GLUT5 and KHK and may proactively enhance the intestine's ability to process anticipated increases in dietary fructose concentrations.
Title: Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK.
Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose.
Title: Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK-/- and GLUT5-/- mice.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (8) 1 citation
Endonuclease-mediated (4)

General gene information

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Markers

Khk (e-PCR), detects polymorphism
- UniSTS:143691

AW229038 (e-PCR)
- UniSTS:179151

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ketohexokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ketohexokinase activity	IDA Inferred from Direct Assay more info	PubMed
enables ketohexokinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ketohexokinase activity	ISO Inferred from Sequence Orthology more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in fructose catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in fructose catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate	IC Inferred by Curator more info	PubMed
involved_in fructose catabolic process to hydroxyacetone phosphate and glyceraldehyde-3-phosphate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fructose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within fructose metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in fructose metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within glycolytic process through fructose-1-phosphate	IC Inferred by Curator more info	PubMed
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of glycogen metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of glycogen metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to fructose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to glucose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to glucose	ISO Inferred from Sequence Orthology more info
involved_in response to insulin	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to insulin	ISO Inferred from Sequence Orthology more info
involved_in response to sucrose	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to sucrose	ISO Inferred from Sequence Orthology more info
involved_in response to zinc ion	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to zinc ion	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ketohexokinase

Names: hepatic fructokinase

NP_001297453.1

EC 2.7.1.3

NP_001297454.1

EC 2.7.1.3

NP_001335995.1

EC 2.7.1.3

NP_032465.2

EC 2.7.1.3

XP_006503811.1

EC 2.7.1.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001310524.1 → NP_001297453.1 ketohexokinase isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AC109606

Consensus CDS

CCDS80243.1

UniProtKB/Swiss-Prot

P97328, Q91WU8

UniProtKB/TrEMBL

E9Q1Q9

Related

ENSMUSP00000031053.10, ENSMUST00000031053.15

Conserved Domains (1) summary

cd01939
Location:5 → 340

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
NM_001310525.1 → NP_001297454.1 ketohexokinase isoform 3

See identical proteins and their annotated locations for NP_001297454.1

Status: VALIDATED

Description

Transcript Variant: This variant (3) lacks two alternate in-frame exons compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AC109606

UniProtKB/Swiss-Prot

P97328, Q91WU8

UniProtKB/TrEMBL

A0A0J9YUK6

Related

ENSMUSP00000144226.2, ENSMUST00000201571.4

Conserved Domains (1) summary

cd01939
Location:5 → 250

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
NM_001349066.1 → NP_001335995.1 ketohexokinase isoform 4

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 1. The encoded isoform (4) is shorter than isoform 1.

Source sequence(s)

AC109606

UniProtKB/Swiss-Prot

P97328, Q91WU8

Related

ENSMUSP00000143850.2, ENSMUST00000202752.2

Conserved Domains (1) summary

cd01939
Location:5 → 295

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...
NM_008439.4 → NP_032465.2 ketohexokinase isoform 2

See identical proteins and their annotated locations for NP_032465.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC109606

Consensus CDS

CCDS39050.1

UniProtKB/Swiss-Prot

P97328, Q91WU8

UniProtKB/TrEMBL

A0A0J9YU79

Related

ENSMUSP00000144050.2, ENSMUST00000201621.4

Conserved Domains (1) summary

cd01939
Location:5 → 295

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

31078780..31088592

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006503748.2 → XP_006503811.1 ketohexokinase isoform X1

UniProtKB/Swiss-Prot

P97328, Q91WU8

Conserved Domains (1) summary

cd01939
Location:5 → 302

Ketohexokinase; Ketohexokinase (fructokinase, KHK) catalyzes the phosphorylation of fructose to fructose-1-phosphate (F1P), the first step in the metabolism of dietary fructose. KHK can also phosphorylate several other furanose sugars. It is found in higher eukaryotes ...