P52792 (HXK4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Gck
Synonyms:	Gk

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	465 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose concentration. 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 activity	ATP + D-glucose = ADP + D-glucose 6-phosphate.
Subunit structure	Monomer By similarity.
Tissue specificity	Pancreas, anterior pituitary (isoform 1) and liver (isoform 2).
Miscellaneous	In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III and IV (glucokinase).
Sequence similarities	Belongs to the hexokinase family.

Ontologies

Keywords
Biological process	Glycolysis
Coding sequence diversity	Alternative promoter usage Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NADP metabolic process Inferred from mutant phenotype PubMed 9873043. Source: MGI calcium ion import Inferred from mutant phenotype PubMed 18477811. Source: UniProtKB cellular glucose homeostasis Inferred from mutant phenotype PubMed 7553875. Source: MGI cellular response to glucose starvation Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara cellular response to leptin stimulus Inferred from electronic annotation. Source: Compara detection of glucose Inferred from sequence or structural similarity. Source: UniProtKB elevation of cytosolic calcium ion concentration Inferred from electronic annotation. Source: Compara endocrine pancreas development Traceable author statement. Source: Reactome fructose 2,6-bisphosphate metabolic process Inferred from electronic annotation. Source: Compara glycogen biosynthetic process Inferred from electronic annotation. Source: Compara glycolysis Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of epinephrine secretion Inferred from electronic annotation. Source: Compara negative regulation of gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glycogen biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glycolysis Inferred from electronic annotation. Source: Compara positive regulation of insulin secretion Inferred from mutant phenotype PubMed 18477811. Source: UniProtKB positive regulation of phosphorylation Inferred from electronic annotation. Source: Compara regulation of potassium ion transport Inferred from mutant phenotype PubMed 9662046. Source: MGI second-messenger-mediated signaling Inferred from electronic annotation. Source: Compara
Cellular_component	cell cortex part Inferred from electronic annotation. Source: Compara cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome mitochondrion Inferred from direct assay PubMed 12931191PubMed 14651853. Source: MGI nucleoplasm Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 10713097. Source: BHF-UCL secretory granule Inferred from electronic annotation. Source: Compara
Molecular_function	ADP binding Inferred from electronic annotation. Source: Compara ATP binding Inferred from sequence or structural similarity. Source: UniProtKB glucokinase activity Inferred from sequence or structural similarity. Source: UniProtKB glucose binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Note: A number of isoforms are produced by alternative promoter usage. 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.

Isoform 1 (identifier: P52792-1)

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.

Isoform 2 (identifier: P52792-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 465	465	Glucokinase		PRO_0000197594
Regions
	Nucleotide binding	78 – 83	6	ATP Potential
	Nucleotide binding	295 – 296	2	ATP By similarity
	Nucleotide binding	332 – 336	5	ATP By similarity
	Nucleotide binding	411 – 415	5	ATP By similarity
	Region	151 – 152	2	Substrate binding By similarity
	Region	168 – 169	2	Substrate binding By similarity
	Region	204 – 205	2	Substrate binding By similarity
Sites
	Binding site	104	1	ATP Potential
	Binding site	228	1	ATP By similarity
	Binding site	231	1	Substrate By similarity
	Binding site	256	1	Substrate By similarity
	Binding site	290	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 15	15	MLDDR…TKKEK → MAVDTTRRGAQSLTL in isoform 2.		VSP_002076
Experimental info
	Sequence conflict	133	1	F → L in AAA37703. Ref.4
	Sequence conflict	159	1	I → L in AAA37703. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 8C85EED079A52D61	FASTA	465	52,089
	10 20 30 40 50 60 MLDDRARMEA TKKEKVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLKLETH QEASVKMLPT 70 80 90 100 110 120 YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS VKTKHQMYSI PEDAMTGTAE 130 140 150 160 170 180 MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN 190 200 210 220 230 240 IVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN 250 260 270 280 290 300 VELVEGDEGR MCVNTEWGAF GNSGELDEFL LEYDRMVDES SVNPGQQLYE KIIGGKYMGE 310 320 330 340 350 360 LVRLVLLKLV EENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRRQILN ILSTLGLRPS 370 380 390 400 410 420 VADCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK 430 440 450 460 ERFHASVRRL TPNCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ
	Isoform 2 [UniParc]. Checksum: DAC911920818B811	FASTA	465	51,886
	10 20 30 40 50 60 MAVDTTRRGA QSLTLVEQIL AEFQLQEEDL KKVMSRMQKE MDRGLKLETH QEASVKMLPT 70 80 90 100 110 120 YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEAGQWS VKTKHQMYSI PEDAMTGTAE 130 140 150 160 170 180 MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN 190 200 210 220 230 240 IVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDRQC EVGMIVGTGC NACYMEEMQN 250 260 270 280 290 300 VELVEGDEGR MCVNTEWGAF GNSGELDEFL LEYDRMVDES SVNPGQQLYE KIIGGKYMGE 310 320 330 340 350 360 LVRLVLLKLV EENLLFHGEA SEQLRTRGAF ETRFVSQVES DSGDRRQILN ILSTLGLRPS 370 380 390 400 410 420 VADCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK 430 440 450 460 ERFHASVRRL TPNCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Partial structure of the mouse glucokinase gene." Ishimura-Oka K., Nakamuta M., Chu M.J., Sullivan M., Chan L., Oka K. Genomics 29:751-754(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Cloning and characterization of the mouse glucokinase gene locus and identification of distal liver-specific DNase I hypersensitive sites." Postic C., Niswender K.D., Decaux J.F., Shelton K.D., Gouhot B., Petterpher C.C., Granner D.K., Girard J., Magnuson M.A. Genomics 29:740-750(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2). Strain: 129/Sv. Tissue: Liver.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Liver.
[4]	"Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet cells." Hughes S.D., Quaade C., Milburn J.L., Cassidy L., Newgard C.B. J. Biol. Chem. 266:4521-4530(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-166 (ISOFORM 1). Tissue: Pancreas.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L38990 mRNA. Translation: AAB00360.1. L41631 Genomic DNA. Translation: AAC42074.1. BC011139 mRNA. Translation: AAH11139.1. M58755 mRNA. Translation: AAA37703.1.
IPI	IPI00130751. IPI00229807.
PIR	I49693. I49694.
RefSeq	NP_034422.2. NM_010292.4.
UniGene	Mm.220358.
3D structure databases
ProteinModelPortal	P52792.
SMR	P52792. Positions 16-460.
ModBase	Search...
PTM databases
PhosphoSite	P52792.
Proteomic databases
PaxDb	P52792.
PRIDE	P52792.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000102920; ENSMUSP00000099984; ENSMUSG00000041798. ENSMUST00000109822; ENSMUSP00000105447; ENSMUSG00000041798. ENSMUST00000109823; ENSMUSP00000105448; ENSMUSG00000041798.
GeneID	103988.
KEGG	mmu:103988.
Organism-specific databases
CTD	2645.
MGI	MGI:1270854. Gck.
Phylogenomic databases
eggNOG	COG5026.
HOGENOM	HOG000162670.
HOVERGEN	HBG000142.
KO	K12407.
OMA	WARVIEI.
OrthoDB	EOG4N5VWR.
Enzyme and pathway databases
Reactome	REACT_127416. Developmental Biology. REACT_13641. Regulation of Beta-Cell Development.
SABIO-RK	P52792.
Gene expression databases
ArrayExpress	P52792.
Bgee	P52792.
CleanEx	MM_GCK.
Genevestigator	P52792.
GermOnline	ENSMUSG00000041798. Mus musculus.
Family and domain databases
InterPro	IPR001312. Hexokinase. IPR022673. Hexokinase_C. IPR019807. Hexokinase_CS. IPR022672. Hexokinase_N. [Graphical view]
PANTHER	PTHR19443. PTHR19443. 1 hit.
Pfam	PF00349. Hexokinase_1. 1 hit. PF03727. Hexokinase_2. 1 hit. [Graphical view]
PRINTS	PR00475. HEXOKINASE.
PROSITE	PS00378. HEXOKINASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	356305.
SOURCE	Search...

Entry information

Entry name

HXK4_MOUSE

Accession

Primary (citable) accession number: P52792
Secondary accession number(s): P52791

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program