Overview
| Uniprot ID | P35557 |
|---|
| Protein Name | Hexokinase-4 |
|---|
| Gene Name | GCK |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 172 |
LNWTKGFKASGAEGN |
Function
Catalyzes the phosphorylation of hexose, such as D-glucose, D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate, D-fructose 6-phosphate and D-mannose 6-phosphate, respectively) (PubMed:11916951, PubMed:15277402, PubMed:17082186, PubMed:18322640, PubMed:19146401, PubMed:25015100, PubMed:7742312, PubMed:8325892). Compared to other hexokinases, has a weak affinity for D-glucose, and is effective only when glucose is abundant (By similarity). Mainly expressed in pancreatic beta cells and the liver and constitutes a rate-limiting step in glucose metabolism in these tissues (PubMed:11916951, PubMed:15277402, PubMed:18322640, PubMed:25015100, PubMed:8325892). Since insulin secretion parallels glucose metabolism and the low glucose affinity of GCK ensures that it can change its enzymatic activity within the physiological range of glucose concentrations, GCK acts as a glucose sensor in the pancreatic beta cell (By similarity). In pancreas, plays an important role in modulating insulin secretion (By similarity). In liver, helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage (By similarity). Required to provide D-glucose 6-phosphate for the synthesis of glycogen (PubMed:8878425). Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:7742312)
Protein Sequence
10
MLDDRARMEA
20
AKKEKVEQIL
30
AEFQLQEEDL
40
KKVMRRMQKE
50
MDRGLRLETH
60
EEASVKMLPT
70
YVRSTPEGSE
80
VGDFLSLDLG
90
GTNFRVMLVK
100
VGEGEEGQWS
110
VKTKHQMYSI
120
PEDAMTGTAE
130
MLFDYISECI
140
SDFLDKHQMK
150
HKKLPLGFTF
160
SFPVRHEDID
170
KGILLNWTKG
180
FKASGAEGNN
190
VVGLLRDAIK
200
RRGDFEMDVV
210
AMVNDTVATM
220
ISCYYEDHQC
230
EVGMIVGTGC
240
NACYMEEMQN
250
VELVEGDEGR
260
MCVNTEWGAF
270
GDSGELDEFL
280
LEYDRLVDES
290
SANPGQQLYE
300
KLIGGKYMGE
310
LVRLVLLRLV
320
DENLLFHGEA
330
SEQLRTRGAF
340
ETRFVSQVES
350
DTGDRKQIYN
360
ILSTLGLRPS
370
TTDCDIVRRA
380
CESVSTRAAH
390
MCSAGLAGVI
400
NRMRESRSED
410
VMRITVGVDG
420
SVYKLHPSFK
430
ERFHASVRRL
440
TPSCEITFIE
450
SEEGSGRGAA
460
LVSAVACKKA
CMLGQ
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0005739 |
mitochondrion |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Molecular Function |
GO:0005524 |
ATP binding |
| Molecular Function |
GO:0005536 |
D-glucose binding |
| Molecular Function |
GO:0008865 |
fructokinase activity |
| Molecular Function |
GO:0004340 |
glucokinase activity |
| Molecular Function |
GO:0141089 |
glucose sensor activity |
| Molecular Function |
GO:0019158 |
mannokinase activity |
| Biological Process |
GO:0070509 |
calcium ion import |
| Biological Process |
GO:0061621 |
canonical glycolysis |
| Biological Process |
GO:0032869 |
cellular response to insulin stimulus |
| Biological Process |
GO:0044320 |
cellular response to leptin stimulus |
| Biological Process |
GO:0051156 |
glucose 6-phosphate metabolic process |
| Biological Process |
GO:0006007 |
glucose catabolic process |
| Biological Process |
GO:0042593 |
glucose homeostasis |
| Biological Process |
GO:0006006 |
glucose metabolic process |
| Biological Process |
GO:0006096 |
glycolytic process |
| Biological Process |
GO:0001678 |
intracellular glucose homeostasis |
| Biological Process |
GO:0045721 |
negative regulation of gluconeogenesis |
| Biological Process |
GO:0045725 |
positive regulation of glycogen biosynthetic process |
| Biological Process |
GO:0032024 |
positive regulation of insulin secretion |
| Biological Process |
GO:0006110 |
regulation of glycolytic process |
| Biological Process |
GO:0050796 |
regulation of insulin secretion |
| Biological Process |
GO:0009749 |
response to glucose |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.