HK1

Protein identityUniProt · HPA

UniProt accession

P19367

Gene

HK1

Ensembl

ENSG00000156515

Chromosome

10

Canonical length

917 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

OverviewNCBI Gene

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. This gene encodes a ubiquitous form of hexokinase which localizes to the outer membrane of mitochondria. Mutations in this gene have been associated with hemolytic anemia due to hexokinase deficiency. Alternative splicing of this gene results in several transcript variants which encode different isoforms, some of which are tissue-specific. [provided by RefSeq, Apr 2016]

Canonical amino-acid sequenceUniProt

917 residues, UniProt reviewed canonical sequence.

>P19367|HK1
     1  MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDETLIDIM TRFRKEMKNG LSRDFNPTAT
    61  VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE KNQNVHMESE VYDTPENIVH
   121  GSGSQLFDHV AECLGDFMEK RKIKDKKLPV GFTFSFPCQQ SKIDEAILIT WTKRFKASGV
   181  EGADVVKLLN KAIKKRGDYD ANIVAVVNDT VGTMMTCGYD DQHCEVGLII GTGTNACYME
   241  ELRHIDLVEG DEGRMCINTE WGAFGDDGSL EDIRTEFDRE IDRGSLNPGK QLFEKMVSGM
   301  YLGELVRLIL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKNKEGLH NAKEILTRLG
   361  VEPSDDDCVS VQHVCTIVSF RSANLVAATL GAILNRLRDN KGTPRLRTTV GVDGSLYKTH
   421  PQYSRRFHKT LRRLVPDSDV RFLLSESGSG KGAAMVTAVA YRLAEQHRQI EETLAHFHLT
   481  KDMLLEVKKR MRAEMELGLR KQTHNNAVVK MLPSFVRRTP DGTENGDFLA LDLGGTNFRV
   541  LLVKIRSGKK RTVEMHNKIY AIPIEIMQGT GEELFDHIVS CISDFLDYMG IKGPRMPLGF
   601  TFSFPCQQTS LDAGILITWT KGFKATDCVG HDVVTLLRDA IKRREEFDLD VVAVVNDTVG
   661  TMMTCAYEEP TCEVGLIVGT GSNACYMEEM KNVEMVEGDQ GQMCINMEWG AFGDNGCLDD
   721  IRTHYDRLVD EYSLNAGKQR YEKMISGMYL GEIVRNILID FTKKGFLFRG QISETLKTRG
   781  IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSRRA AQLCGAGMAA
   841  VVDKIRENRG LDRLNVTVGV DGTLYKLHPH FSRIMHQTVK ELSPKCNVSF LLSEDGSGKG
   901  AALITAVGVR LRTEASS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.21

Highest tissue expression

184 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HK1.

Disease | AllUniProt

Conditions HK1 is implicated in, by any mechanism.

• Anemia, congenital, non-spherocytic hemolytic, 5 (CNSHA5) MIM:235700
• Neuropathy, hereditary motor and sensory, Russe type (HMSNR) MIM:605285
• Retinitis pigmentosa 79 (RP79) MIM:617460
• Neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA) MIM:618547

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 849 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with visual defects and brain anomalies
• Hemolytic anemia due to hexokinase deficiency
• Charcot-Marie-Tooth disease type 4G
• Retinitis pigmentosa 79
• Retinal dystrophy

Disease | ImmuneIEDB

Conditions an epitope on HK1 was assayed in.

• type 1 diabetes mellitus T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against HK1 are reported. Each links to that disease's full target list.

• Liver Cirrhosis, Biliary 3

ReferencesPubMed · IEDB

Publications for HK1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.33

gnomAD pLI

0.91

gnomAD missense Z

3.23

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• canonical glycolysis
• carbohydrate phosphorylation
• establishment of protein localization to mitochondrion
• fructose 6-phosphate metabolic process
• GDP-mannose biosynthetic process
• GDP-mannose biosynthetic process from mannose
• glucose 6-phosphate metabolic process
• glucose metabolic process
• glycolytic process
• inflammatory response
• innate immune response
• intracellular glucose homeostasis
• maintenance of protein location in mitochondrion
• mannose metabolic process
• positive regulation of cytokine production involved in immune response
• positive regulation of interleukin-1 beta production

Molecular functions

• ATP binding
• D-glucose binding
• fructokinase activity
• glucokinase activity
• hexokinase activity
• mannokinase activity
• peptidoglycan binding
• glucosamine kinase activity

Cellular components

• cytosol
• membrane raft
• mitochondrial outer membrane
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Hexokinase
• Hexokinase, binding site
• Hexokinase, N-terminal
• Hexokinase, C-terminal
• ATPase, nucleotide binding domain
• Hexokinase
• Hexokinase

KeywordsUniProt

• Acetylation
• Allosteric enzyme
• ATP-binding
• Charcot-Marie-Tooth disease
• Cytoplasm
• Glycolysis
• Hereditary hemolytic anemia
• Immunity
• Inflammatory response
• Innate immunity
• Intellectual disability
• Kinase
• Membrane
• Mitochondrion
• Mitochondrion outer membrane
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Repeat
• Retinitis pigmentosa
• Transferase

InteractionsUniProt · HPA

Protein binding partners of HK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATF2
• SMAD5
• VDAC1
• RABL2A