HK1

Domain

The N- and C-terminal halves of this hexokinase contain a hexokinase domain (PubMed:10574795, PubMed:9493266, PubMed:9735292). The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus (PubMed:10574795, PubMed:9493266, PubMed:9735292). Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule (PubMed:9493266).

Function

Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively) (PubMed:1637300, PubMed:25316723, PubMed:27374331). Does not phosphorylate N-acetyl-D-glucosamine (PubMed:27374331). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity). Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan (PubMed:27374331). When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331).

Involvement in disease

Hexokinase deficiency

HK deficiency

Rare autosomal recessive disease with nonspherocytic hemolytic anemia as the predominant clinical feature.

None

The disease is caused by variants affecting the gene represented in this entry.

Neuropathy, hereditary motor and sensory, Russe type

HMSNR

An autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy.

None

The disease is caused by variants affecting the gene represented in this entry.

Retinitis pigmentosa 79

RP79

A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP79 inheritance is autosomal dominant.

None

The disease is caused by variants affecting the gene represented in this entry.

Neurodevelopmental disorder with visual defects and brain anomalies

NEDVIBA

A disorder characterized by global developmental delay, speech delay, intellectual disability, structural brain abnormalities, and visual impairments including retinitis pigmentosa and optic atrophy.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Carbohydrate metabolism; hexose metabolism.

Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4.

Sequence similarities

Belongs to the hexokinase family.

Tissue specificity

Isoform 2: Erythrocyte specific (Ref.6). Isoform 3: Testis-specific (PubMed:10978502). Isoform 4: Testis-specific (PubMed:10978502).

Cellular localization

• Mitochondrion outer membrane
• Peripheral membrane protein
• Cytoplasm
• Cytosol
• The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (Probable). Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331).

Alternative names

• Hexokinase-1
• Brain form hexokinase
• Hexokinase type I
• Hexokinase-A
• HK I
• HK1

Database links

• entrezGene:3098
• omim:142600
• swissprot:P19367

Target type

Proteins

Primary research area

Neuroscience

Other research areas

• Immunology & Infectious Disease

Molecular weight

102486Da