GCK

Protein identityUniProt · HPA

UniProt accession

P35557

Gene

GCK

Ensembl

ENSG00000106633

Chromosome

7

Canonical length

465 aa

Protein class

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

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

465 residues, UniProt reviewed canonical sequence.

>P35557|GCK
     1  MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT
    61  YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE
   121  MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN
   181  VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN
   241  VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
   301  LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS
   361  TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK
   421  ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GCK 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

20 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GCK.

Disease | AllUniProt

Conditions GCK is implicated in, by any mechanism.

• Maturity-onset diabetes of the young 2 (MODY2) MIM:125851
• Hyperinsulinemic hypoglycemia, familial, 3 (HHF3) MIM:602485
• Type 2 diabetes mellitus (T2D) MIM:125853
• Diabetes mellitus, permanent neonatal, 1 (PNDM1) MIM:606176

Disease | GeneticClinVar

680 pathogenic / likely-pathogenic of 1,358 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Monogenic diabetes
• Maturity-onset diabetes of the young type 2
• Maturity-onset diabetes of the young
• Hyperinsulinemic hypoglycemia, familial, 3
• Type 2 diabetes mellitus

Disease | ImmuneIEDB

Conditions an epitope on GCK was assayed in.

• type 1 diabetes mellitus T cell

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)

0.44

gnomAD pLI

0.63

gnomAD missense Z

3.07

DepMap mean gene effect

0.01

DepMap dependency class

none

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

• calcium ion import
• canonical glycolysis
• cellular response to insulin stimulus
• cellular response to leptin stimulus
• glucose 6-phosphate metabolic process
• glucose catabolic process
• glucose homeostasis
• glucose metabolic process
• glycolytic process
• intracellular glucose homeostasis
• NADP+ metabolic process
• negative regulation of gluconeogenesis
• positive regulation of glycogen biosynthetic process
• positive regulation of insulin secretion
• regulation of glycolytic process
• regulation of insulin secretion
• regulation of potassium ion transport
• response to glucose

Molecular functions

• ATP binding
• D-glucose binding
• fructokinase activity
• glucokinase activity
• glucose sensor activity
• mannokinase activity

Cellular components

• cytosol
• mitochondrion
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

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

KeywordsUniProt

• Allosteric enzyme
• ATP-binding
• Cytoplasm
• Diabetes mellitus
• Glycolysis
• Kinase
• Mitochondrion
• Nucleotide-binding
• Nucleus
• Transferase

InteractionsUniProt · HPA

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

• GCKR
• MIDN