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Protein

Glucokinase

Gene

GCK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an insulin-sensitive determinant of hepatic glucose usage.

Catalytic activityi

ATP + D-glucose = ADP + D-glucose 6-phosphate.

Enzyme regulationi

The use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining glucose homeostasis. Subject to allosteric regulation. Low glucose and high fructose-6-phosphate triggers association with the inhibitor GKRP followed by sequestration in the nucleus.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei104ATPSequence analysis1
Binding sitei228ATPBy similarity1
Binding sitei231Substrate1
Binding sitei256Substrate1
Binding sitei290Substrate1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi78 – 83ATPBy similarity6
Nucleotide bindingi295 – 296ATPBy similarity2
Nucleotide bindingi332 – 336ATPBy similarity5
Nucleotide bindingi411 – 415ATPBy similarity5

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • glucokinase activity Source: UniProtKB
  • glucose binding Source: UniProtKB

GO - Biological processi

  • calcium ion import Source: Ensembl
  • canonical glycolysis Source: Reactome
  • cellular glucose homeostasis Source: GO_Central
  • cellular response to insulin stimulus Source: BHF-UCL
  • cellular response to leptin stimulus Source: BHF-UCL
  • detection of glucose Source: UniProtKB
  • glucose homeostasis Source: UniProtKB
  • glucose transport Source: Reactome
  • glycolytic process Source: GO_Central
  • NADP metabolic process Source: Ensembl
  • negative regulation of gluconeogenesis Source: UniProtKB
  • positive regulation of glycogen biosynthetic process Source: UniProtKB
  • positive regulation of insulin secretion Source: UniProtKB
  • regulation of glucose transport Source: Reactome
  • regulation of glycolytic process Source: BHF-UCL
  • regulation of insulin secretion Source: BHF-UCL
  • regulation of potassium ion transport Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02935-MONOMER.
ZFISH:HS02935-MONOMER.
BRENDAi2.7.1.1. 2681.
2.7.1.2. 2681.
ReactomeiR-HSA-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-HSA-210745. Regulation of gene expression in beta cells.
R-HSA-5619107. Defective TRP may confer susceptibility towards thyroid papillary carcinoma (TPC).
R-HSA-70153. Glucose transport.
R-HSA-70171. Glycolysis.
SABIO-RKP35557.

Names & Taxonomyi

Protein namesi
Recommended name:
Glucokinase (EC:2.7.1.2)
Alternative name(s):
Hexokinase type IV
Short name:
HK IV
Hexokinase-4
Short name:
HK4
Hexokinase-D
Gene namesi
Name:GCK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4195. GCK.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Maturity-onset diabetes of the young 2 (MODY2)13 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
See also OMIM:125851
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01058436R → W in MODY2. 1 PublicationCorresponds to variant rs762263694dbSNPEnsembl.1
Natural variantiVAR_07522043R → H in MODY2; unknown pathological significance; no change in glucokinase activity. 1 PublicationCorresponds to variant rs764232985dbSNPEnsembl.1
Natural variantiVAR_01058553A → S in MODY2. 1
Natural variantiVAR_07522168G → D in MODY2; unknown pathological significance; found in some patients that also carry an H-43; mildly increases glucokinase activity. 1 PublicationCorresponds to variant rs373418736dbSNPEnsembl.1
Natural variantiVAR_00369370E → K in MODY2; large increase in Km for glucose. 1 Publication1
Natural variantiVAR_00369480G → A in MODY2. 1
Natural variantiVAR_00369580G → S in MODY2. 1 Publication1
Natural variantiVAR_010586108Y → H in MODY2. 1 Publication1
Natural variantiVAR_012352110I → T in MODY2. 1 Publication1
Natural variantiVAR_012353119A → D in MODY2. 1 Publication1
Natural variantiVAR_003697131S → P in MODY2; significant increase in the Km and in the affinity for ATP. 2 PublicationsCorresponds to variant rs104894010dbSNPEnsembl.1
Natural variantiVAR_010587137H → R in MODY2. 1
Natural variantiVAR_010588150F → S in MODY2. 1 PublicationCorresponds to variant rs193922297dbSNPEnsembl.1
Natural variantiVAR_012350164L → P in MODY2. 1 Publication1
Natural variantiVAR_010589168T → P in MODY2. 1
Natural variantiVAR_003698175G → R in MODY2. Corresponds to variant rs587780344dbSNPEnsembl.1
Natural variantiVAR_003699182V → M in MODY2. Corresponds to variant rs587780345dbSNPEnsembl.1
Natural variantiVAR_003700188A → T in MODY2; large increase in Km for glucose. 1 PublicationCorresponds to variant rs751279776dbSNPEnsembl.1
Natural variantiVAR_003701203V → A in MODY2. 1
Natural variantiVAR_010590209T → M in MODY2. 1 Publication1
Natural variantiVAR_012351210M → K in MODY2. 1 PublicationCorresponds to variant rs80356654dbSNPEnsembl.1
Natural variantiVAR_010591210M → T in MODY2. 1
Natural variantiVAR_010592213C → R in MODY2. 1
Natural variantiVAR_075222217D → N in MODY2; associated with R-261; loss of glucokinase activity when associated with R-261. 1 PublicationCorresponds to variant rs147065275dbSNPEnsembl.1
Natural variantiVAR_003702221E → K in MODY2. 1 PublicationCorresponds to variant rs193922317dbSNPEnsembl.1
Natural variantiVAR_075223225I → M in MODY2; associated with K-248; loss of glucokinase activity when associated with K-248. 1 Publication1
Natural variantiVAR_003703226V → M in MODY2. Corresponds to variant rs148311934dbSNPEnsembl.1
Natural variantiVAR_003704227G → C in MODY2. 1 Publication1
Natural variantiVAR_003705228T → M in MODY2. 2 PublicationsCorresponds to variant rs80356655dbSNPEnsembl.1
Natural variantiVAR_075224248E → K in MODY2; associated with M-225; loss of glucokinase activity when associated with M-225. 1 PublicationCorresponds to variant rs759421263dbSNPEnsembl.1
Natural variantiVAR_003706256E → K in MODY2. Corresponds to variant rs769268803dbSNPEnsembl.1
Natural variantiVAR_003707257W → R in MODY2; almost complete loss of activity. 1 Publication1
Natural variantiVAR_010593259A → T in MODY2. 1 Publication1
Natural variantiVAR_010594261G → E in MODY2. 1 Publication1
Natural variantiVAR_003708261G → R in MODY2; associated with N-217 in some patients; loss of glucokinase activity when associated with R-217; highly decreases glucokinase activity when found as single mutation. 3 PublicationsCorresponds to variant rs104894008dbSNPEnsembl.1
Natural variantiVAR_003709279E → Q in MODY2. Corresponds to variant rs104894005dbSNPEnsembl.1
Natural variantiVAR_003710299G → R in MODY2. 2 PublicationsCorresponds to variant rs104894009dbSNPEnsembl.1
Natural variantiVAR_003712300E → K in MODY2. 1
Natural variantiVAR_003711300E → Q in MODY2. 1
Natural variantiVAR_003713309L → P in MODY2. 1
Natural variantiVAR_010595336S → L in MODY2. 1
Natural variantiVAR_010596367V → M in MODY2. 1
Natural variantiVAR_010597382C → Y in MODY2. 1 Publication1
Natural variantiVAR_010598384A → T in MODY2. 1 Publication1
Natural variantiVAR_012354385G → V in MODY2. 1 Publication1
Natural variantiVAR_010599392R → C in MODY2. 1 Publication1
Natural variantiVAR_003714414K → E in MODY2; large increase in Km for glucose. 1 PublicationCorresponds to variant rs193922272dbSNPEnsembl.1
Familial hyperinsulinemic hypoglycemia 3 (HHF3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMost common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
See also OMIM:602485
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003715455V → M in HHF3. 1 PublicationCorresponds to variant rs104894012dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi177E → K: Small change in activity. 1
Mutagenesisi217D → N: Mildly increases glucokinase activity. 1 Publication1
Mutagenesisi225I → M: Highly decreases glucokinase activity. 1 Publication1
Mutagenesisi248E → K: Highly decreases glucokinase activity. 1 Publication1
Mutagenesisi256E → A: Inactive enzyme. 1
Mutagenesisi414K → A: Small change in activity. 1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi2645.
MalaCardsiGCK.
MIMi125851. phenotype.
602485. phenotype.
606391. phenotype.
OpenTargetsiENSG00000106633.
Orphaneti79299. Hyperinsulinism due to glucokinase deficiency.
552. MODY.
99885. Permanent neonatal diabetes mellitus.
PharmGKBiPA28610.

Chemistry databases

ChEMBLiCHEMBL3820.
GuidetoPHARMACOLOGYi2798.

Polymorphism and mutation databases

BioMutaiGCK.
DMDMi547696.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975931 – 465GlucokinaseAdd BLAST465

Proteomic databases

PaxDbiP35557.
PeptideAtlasiP35557.
PRIDEiP35557.

PTM databases

iPTMnetiP35557.
PhosphoSitePlusiP35557.

Expressioni

Tissue specificityi

Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver.

Gene expression databases

BgeeiENSG00000106633.
CleanExiHS_GCK.
ExpressionAtlasiP35557. baseline and differential.
GenevisibleiP35557. HS.

Organism-specific databases

HPAiHPA007034.
HPA007093.

Interactioni

Subunit structurei

Monomer.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GCKRQ143972EBI-709928,EBI-709948
PFKFB1P161182EBI-709928,EBI-709807

Protein-protein interaction databases

BioGridi108915. 9 interactors.
IntActiP35557. 6 interactors.
STRINGi9606.ENSP00000223366.

Chemistry databases

BindingDBiP35557.

Structurei

Secondary structure

1465
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi12 – 20Combined sources9
Helixi21 – 23Combined sources3
Helixi27 – 45Combined sources19
Turni47 – 52Combined sources6
Beta strandi58 – 65Combined sources8
Turni66 – 68Combined sources3
Beta strandi72 – 92Combined sources21
Beta strandi95 – 97Combined sources3
Beta strandi99 – 109Combined sources11
Helixi112 – 115Combined sources4
Beta strandi116 – 118Combined sources3
Helixi119 – 136Combined sources18
Beta strandi140 – 142Combined sources3
Beta strandi145 – 150Combined sources6
Beta strandi154 – 158Combined sources5
Beta strandi161 – 164Combined sources4
Helixi181 – 192Combined sources12
Beta strandi198 – 203Combined sources6
Helixi205 – 214Combined sources10
Beta strandi220 – 237Combined sources18
Helixi238 – 240Combined sources3
Beta strandi248 – 254Combined sources7
Helixi257 – 259Combined sources3
Turni260 – 263Combined sources4
Beta strandi264 – 266Combined sources3
Helixi267 – 269Combined sources3
Helixi272 – 280Combined sources9
Beta strandi281 – 283Combined sources3
Helixi288 – 291Combined sources4
Helixi295 – 311Combined sources17
Helixi316 – 318Combined sources3
Turni322 – 325Combined sources4
Helixi332 – 339Combined sources8
Beta strandi340 – 342Combined sources3
Beta strandi343 – 345Combined sources3
Helixi346 – 354Combined sources9
Helixi361 – 396Combined sources36
Beta strandi400 – 409Combined sources10
Helixi411 – 415Combined sources5
Beta strandi416 – 418Combined sources3
Helixi419 – 430Combined sources12
Beta strandi434 – 440Combined sources7
Helixi444 – 456Combined sources13
Turni457 – 459Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GLKmodel-A1-465[»]
1V4SX-ray2.30A16-465[»]
1V4TX-ray3.40A16-465[»]
3A0IX-ray2.20X16-465[»]
3F9MX-ray1.50A12-465[»]
3FGUX-ray2.15A12-465[»]
3FR0X-ray2.70A16-465[»]
3GOIX-ray2.52A16-465[»]
3H1VX-ray2.11X16-465[»]
3ID8X-ray2.40A12-465[»]
3IDHX-ray2.14A12-465[»]
3IMXX-ray2.00A16-465[»]
3QICX-ray2.20A12-465[»]
3S41X-ray2.18A12-465[»]
3VEVX-ray1.80A12-465[»]
3VEYX-ray2.25A16-465[»]
3VF6X-ray1.86A12-465[»]
4DCHX-ray1.79A1-465[»]
4DHYX-ray2.38A12-465[»]
4ISEX-ray1.78A16-465[»]
4ISFX-ray2.09A16-465[»]
4ISGX-ray2.64A16-465[»]
4IWVX-ray2.10A16-465[»]
4IXCX-ray2.00A16-465[»]
4L3QX-ray2.70A16-465[»]
4LC9X-ray3.40B3-465[»]
4MLEX-ray2.60A16-465[»]
4MLHX-ray2.90A16-465[»]
4NO7X-ray1.70A12-465[»]
4RCHX-ray2.30A16-465[»]
ProteinModelPortaliP35557.
SMRiP35557.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35557.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini10 – 454HexokinasePROSITE-ProRule annotationAdd BLAST445

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni67 – 203Hexokinase small subdomainPROSITE-ProRule annotationAdd BLAST137
Regioni151 – 152Substrate binding2
Regioni168 – 169Substrate binding2
Regioni204 – 443Hexokinase large subdomainPROSITE-ProRule annotationAdd BLAST240
Regioni204 – 205Substrate binding2

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated
Contains 1 hexokinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162670.
HOVERGENiHBG000142.
InParanoidiP35557.
KOiK12407.
OMAiAHMCGAG.
OrthoDBiEOG091G08MD.
PhylomeDBiP35557.
TreeFamiTF314238.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 1 hit.
PS51748. HEXOKINASE_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35557-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH
60 70 80 90 100
EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS
110 120 130 140 150
VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF
160 170 180 190 200
SFPVRHEDID KGILLNWTKG FKASGAEGNN VVGLLRDAIK RRGDFEMDVV
210 220 230 240 250
AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR
260 270 280 290 300
MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
310 320 330 340 350
LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN
360 370 380 390 400
ILSTLGLRPS TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED
410 420 430 440 450
VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPSCEITFIE SEEGSGRGAA
460
LVSAVACKKA CMLGQ
Length:465
Mass (Da):52,191
Last modified:June 1, 1994 - v1
Checksum:i094D4A2F78096724
GO
Isoform 2 (identifier: P35557-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLDDRARMEAAKKEK → MAMDVTRSQAQTALTL

Show »
Length:466
Mass (Da):52,136
Checksum:iA44B768452105627
GO
Isoform 3 (identifier: P35557-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MLDDRARMEAAKKEK → MPRPRSQLPQPNSQ

Show »
Length:464
Mass (Da):52,035
Checksum:i5FA1020BBF98A4E9
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0036924D → N.1 PublicationCorresponds to variant rs202091228dbSNPEnsembl.1
Natural variantiVAR_01058311A → T.1 PublicationCorresponds to variant rs116093166dbSNPEnsembl.1
Natural variantiVAR_01058436R → W in MODY2. 1 PublicationCorresponds to variant rs762263694dbSNPEnsembl.1
Natural variantiVAR_07522043R → H in MODY2; unknown pathological significance; no change in glucokinase activity. 1 PublicationCorresponds to variant rs764232985dbSNPEnsembl.1
Natural variantiVAR_01058553A → S in MODY2. 1
Natural variantiVAR_07522168G → D in MODY2; unknown pathological significance; found in some patients that also carry an H-43; mildly increases glucokinase activity. 1 PublicationCorresponds to variant rs373418736dbSNPEnsembl.1
Natural variantiVAR_00369370E → K in MODY2; large increase in Km for glucose. 1 Publication1
Natural variantiVAR_00369480G → A in MODY2. 1
Natural variantiVAR_00369580G → S in MODY2. 1 Publication1
Natural variantiVAR_003696107M → T.2 Publications1
Natural variantiVAR_010586108Y → H in MODY2. 1 Publication1
Natural variantiVAR_012352110I → T in MODY2. 1 Publication1
Natural variantiVAR_012353119A → D in MODY2. 1 Publication1
Natural variantiVAR_003697131S → P in MODY2; significant increase in the Km and in the affinity for ATP. 2 PublicationsCorresponds to variant rs104894010dbSNPEnsembl.1
Natural variantiVAR_010587137H → R in MODY2. 1
Natural variantiVAR_010588150F → S in MODY2. 1 PublicationCorresponds to variant rs193922297dbSNPEnsembl.1
Natural variantiVAR_012350164L → P in MODY2. 1 Publication1
Natural variantiVAR_010589168T → P in MODY2. 1
Natural variantiVAR_003698175G → R in MODY2. Corresponds to variant rs587780344dbSNPEnsembl.1
Natural variantiVAR_003699182V → M in MODY2. Corresponds to variant rs587780345dbSNPEnsembl.1
Natural variantiVAR_003700188A → T in MODY2; large increase in Km for glucose. 1 PublicationCorresponds to variant rs751279776dbSNPEnsembl.1
Natural variantiVAR_003701203V → A in MODY2. 1
Natural variantiVAR_010590209T → M in MODY2. 1 Publication1
Natural variantiVAR_012351210M → K in MODY2. 1 PublicationCorresponds to variant rs80356654dbSNPEnsembl.1
Natural variantiVAR_010591210M → T in MODY2. 1
Natural variantiVAR_010592213C → R in MODY2. 1
Natural variantiVAR_075222217D → N in MODY2; associated with R-261; loss of glucokinase activity when associated with R-261. 1 PublicationCorresponds to variant rs147065275dbSNPEnsembl.1
Natural variantiVAR_003702221E → K in MODY2. 1 PublicationCorresponds to variant rs193922317dbSNPEnsembl.1
Natural variantiVAR_075223225I → M in MODY2; associated with K-248; loss of glucokinase activity when associated with K-248. 1 Publication1
Natural variantiVAR_003703226V → M in MODY2. Corresponds to variant rs148311934dbSNPEnsembl.1
Natural variantiVAR_003704227G → C in MODY2. 1 Publication1
Natural variantiVAR_003705228T → M in MODY2. 2 PublicationsCorresponds to variant rs80356655dbSNPEnsembl.1
Natural variantiVAR_075224248E → K in MODY2; associated with M-225; loss of glucokinase activity when associated with M-225. 1 PublicationCorresponds to variant rs759421263dbSNPEnsembl.1
Natural variantiVAR_003706256E → K in MODY2. Corresponds to variant rs769268803dbSNPEnsembl.1
Natural variantiVAR_003707257W → R in MODY2; almost complete loss of activity. 1 Publication1
Natural variantiVAR_010593259A → T in MODY2. 1 Publication1
Natural variantiVAR_010594261G → E in MODY2. 1 Publication1
Natural variantiVAR_003708261G → R in MODY2; associated with N-217 in some patients; loss of glucokinase activity when associated with R-217; highly decreases glucokinase activity when found as single mutation. 3 PublicationsCorresponds to variant rs104894008dbSNPEnsembl.1
Natural variantiVAR_003709279E → Q in MODY2. Corresponds to variant rs104894005dbSNPEnsembl.1
Natural variantiVAR_003710299G → R in MODY2. 2 PublicationsCorresponds to variant rs104894009dbSNPEnsembl.1
Natural variantiVAR_003712300E → K in MODY2. 1
Natural variantiVAR_003711300E → Q in MODY2. 1
Natural variantiVAR_003713309L → P in MODY2. 1
Natural variantiVAR_010595336S → L in MODY2. 1
Natural variantiVAR_066615342T → P.1 Publication1
Natural variantiVAR_010596367V → M in MODY2. 1
Natural variantiVAR_010597382C → Y in MODY2. 1 Publication1
Natural variantiVAR_010598384A → T in MODY2. 1 Publication1
Natural variantiVAR_012354385G → V in MODY2. 1 Publication1
Natural variantiVAR_010599392R → C in MODY2. 1 Publication1
Natural variantiVAR_003714414K → E in MODY2; large increase in Km for glucose. 1 PublicationCorresponds to variant rs193922272dbSNPEnsembl.1
Natural variantiVAR_003715455V → M in HHF3. 1 PublicationCorresponds to variant rs104894012dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0020741 – 15MLDDR…AKKEK → MAMDVTRSQAQTALTL in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0020751 – 15MLDDR…AKKEK → MPRPRSQLPQPNSQ in isoform 3. CuratedAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88011 mRNA. Translation: AAA51824.1.
M69051 mRNA. Translation: AAB59563.1. Sequence problems.
M90298 Genomic DNA. Translation: AAA67541.1. Different termination.
M90298 Genomic DNA. Translation: AAA67542.1. Different termination.
M90299 mRNA. Translation: AAA52562.1.
AF041022
, AF041012, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97680.1.
AF041022
, AF041013, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97681.1.
AF041022
, AF041014, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97682.1.
AK122876 mRNA. Translation: BAG53774.1.
CH236960 Genomic DNA. Translation: EAL23765.1.
CH236960 Genomic DNA. Translation: EAL23766.1.
CH471128 Genomic DNA. Translation: EAW61114.1.
CH471128 Genomic DNA. Translation: EAW61116.1.
BC001890 mRNA. Translation: AAH01890.1.
CCDSiCCDS5479.1. [P35557-1]
CCDS5480.1. [P35557-2]
CCDS5481.1. [P35557-3]
PIRiA46157.
B46157.
C46157.
RefSeqiNP_000153.1. NM_000162.3. [P35557-1]
NP_277042.1. NM_033507.1. [P35557-2]
NP_277043.1. NM_033508.1. [P35557-3]
UniGeneiHs.1270.

Genome annotation databases

EnsembliENST00000345378; ENSP00000223366; ENSG00000106633. [P35557-2]
ENST00000395796; ENSP00000379142; ENSG00000106633. [P35557-3]
ENST00000403799; ENSP00000384247; ENSG00000106633. [P35557-1]
ENST00000616242; ENSP00000482149; ENSG00000106633. [P35557-3]
GeneIDi2645.
KEGGihsa:2645.
UCSCiuc003tkj.2. human. [P35557-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Glucokinase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88011 mRNA. Translation: AAA51824.1.
M69051 mRNA. Translation: AAB59563.1. Sequence problems.
M90298 Genomic DNA. Translation: AAA67541.1. Different termination.
M90298 Genomic DNA. Translation: AAA67542.1. Different termination.
M90299 mRNA. Translation: AAA52562.1.
AF041022
, AF041012, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97680.1.
AF041022
, AF041013, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97681.1.
AF041022
, AF041014, AF041015, AF041016, AF041017, AF041018, AF041019, AF041020, AF041021 Genomic DNA. Translation: AAB97682.1.
AK122876 mRNA. Translation: BAG53774.1.
CH236960 Genomic DNA. Translation: EAL23765.1.
CH236960 Genomic DNA. Translation: EAL23766.1.
CH471128 Genomic DNA. Translation: EAW61114.1.
CH471128 Genomic DNA. Translation: EAW61116.1.
BC001890 mRNA. Translation: AAH01890.1.
CCDSiCCDS5479.1. [P35557-1]
CCDS5480.1. [P35557-2]
CCDS5481.1. [P35557-3]
PIRiA46157.
B46157.
C46157.
RefSeqiNP_000153.1. NM_000162.3. [P35557-1]
NP_277042.1. NM_033507.1. [P35557-2]
NP_277043.1. NM_033508.1. [P35557-3]
UniGeneiHs.1270.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1GLKmodel-A1-465[»]
1V4SX-ray2.30A16-465[»]
1V4TX-ray3.40A16-465[»]
3A0IX-ray2.20X16-465[»]
3F9MX-ray1.50A12-465[»]
3FGUX-ray2.15A12-465[»]
3FR0X-ray2.70A16-465[»]
3GOIX-ray2.52A16-465[»]
3H1VX-ray2.11X16-465[»]
3ID8X-ray2.40A12-465[»]
3IDHX-ray2.14A12-465[»]
3IMXX-ray2.00A16-465[»]
3QICX-ray2.20A12-465[»]
3S41X-ray2.18A12-465[»]
3VEVX-ray1.80A12-465[»]
3VEYX-ray2.25A16-465[»]
3VF6X-ray1.86A12-465[»]
4DCHX-ray1.79A1-465[»]
4DHYX-ray2.38A12-465[»]
4ISEX-ray1.78A16-465[»]
4ISFX-ray2.09A16-465[»]
4ISGX-ray2.64A16-465[»]
4IWVX-ray2.10A16-465[»]
4IXCX-ray2.00A16-465[»]
4L3QX-ray2.70A16-465[»]
4LC9X-ray3.40B3-465[»]
4MLEX-ray2.60A16-465[»]
4MLHX-ray2.90A16-465[»]
4NO7X-ray1.70A12-465[»]
4RCHX-ray2.30A16-465[»]
ProteinModelPortaliP35557.
SMRiP35557.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108915. 9 interactors.
IntActiP35557. 6 interactors.
STRINGi9606.ENSP00000223366.

Chemistry databases

BindingDBiP35557.
ChEMBLiCHEMBL3820.
GuidetoPHARMACOLOGYi2798.

PTM databases

iPTMnetiP35557.
PhosphoSitePlusiP35557.

Polymorphism and mutation databases

BioMutaiGCK.
DMDMi547696.

Proteomic databases

PaxDbiP35557.
PeptideAtlasiP35557.
PRIDEiP35557.

Protocols and materials databases

DNASUi2645.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345378; ENSP00000223366; ENSG00000106633. [P35557-2]
ENST00000395796; ENSP00000379142; ENSG00000106633. [P35557-3]
ENST00000403799; ENSP00000384247; ENSG00000106633. [P35557-1]
ENST00000616242; ENSP00000482149; ENSG00000106633. [P35557-3]
GeneIDi2645.
KEGGihsa:2645.
UCSCiuc003tkj.2. human. [P35557-1]

Organism-specific databases

CTDi2645.
DisGeNETi2645.
GeneCardsiGCK.
GeneReviewsiGCK.
HGNCiHGNC:4195. GCK.
HPAiHPA007034.
HPA007093.
MalaCardsiGCK.
MIMi125851. phenotype.
138079. gene.
602485. phenotype.
606391. phenotype.
neXtProtiNX_P35557.
OpenTargetsiENSG00000106633.
Orphaneti79299. Hyperinsulinism due to glucokinase deficiency.
552. MODY.
99885. Permanent neonatal diabetes mellitus.
PharmGKBiPA28610.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162670.
HOVERGENiHBG000142.
InParanoidiP35557.
KOiK12407.
OMAiAHMCGAG.
OrthoDBiEOG091G08MD.
PhylomeDBiP35557.
TreeFamiTF314238.

Enzyme and pathway databases

BioCyciMetaCyc:HS02935-MONOMER.
ZFISH:HS02935-MONOMER.
BRENDAi2.7.1.1. 2681.
2.7.1.2. 2681.
ReactomeiR-HSA-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-HSA-210745. Regulation of gene expression in beta cells.
R-HSA-5619107. Defective TRP may confer susceptibility towards thyroid papillary carcinoma (TPC).
R-HSA-70153. Glucose transport.
R-HSA-70171. Glycolysis.
SABIO-RKP35557.

Miscellaneous databases

ChiTaRSiGCK. human.
EvolutionaryTraceiP35557.
GeneWikiiGlucokinase.
GenomeRNAii2645.
PROiP35557.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106633.
CleanExiHS_GCK.
ExpressionAtlasiP35557. baseline and differential.
GenevisibleiP35557. HS.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 1 hit.
PF03727. Hexokinase_2. 1 hit.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 1 hit.
PS51748. HEXOKINASE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHXK4_HUMAN
AccessioniPrimary (citable) accession number: P35557
Secondary accession number(s): A4D2J2, A4D2J3, Q05810
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: November 30, 2016
This is version 184 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).

Keywords - Technical termi

3D-structure, Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.