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Protein

Hexokinase-2

Gene

Hk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

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

Enzyme regulationi

Hexokinase is an allosteric enzyme inhibited by its product Glc-6-P.By similarity

Pathwayi: hexose metabolism

This protein is involved in the pathway hexose metabolism, which is part of Carbohydrate metabolism.
View all proteins of this organism that are known to be involved in the pathway hexose metabolism and in Carbohydrate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei30ATP 1By similarity1
Binding sitei209Glucose-6-phosphate 1By similarity1
Binding sitei232Glucose-6-phosphate 1By similarity1
Binding sitei235Substrate 1By similarity1
Binding sitei260Substrate 1By similarity1
Binding sitei449Glucose-6-phosphate 1By similarity1
Binding sitei558ATP 2Sequence analysis1
Binding sitei657Glucose-6-phosphate 2By similarity1
Binding sitei680ATP 2By similarity1
Binding sitei680Glucose-6-phosphate 2By similarity1
Binding sitei683Substrate 2By similarity1
Binding sitei708Substrate 2By similarity1
Binding sitei897Glucose-6-phosphate 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi84 – 89ATP 1Sequence analysis6
Nucleotide bindingi425 – 426ATP 1By similarity2
Nucleotide bindingi532 – 537ATP 2By similarity6
Nucleotide bindingi747 – 748ATP 2By similarity2
Nucleotide bindingi784 – 788ATP 2By similarity5
Nucleotide bindingi863 – 867ATP 2By similarity5

GO - Molecular functioni

GO - Biological processi

  • apoptotic mitochondrial changes Source: MGI
  • carbohydrate phosphorylation Source: MGI
  • cellular glucose homeostasis Source: GO_Central
  • establishment of protein localization to mitochondrion Source: MGI
  • glucose metabolic process Source: MGI
  • glycolytic process Source: GO_Central
  • lactation Source: Ensembl
  • maintenance of protein location in mitochondrion Source: MGI
  • negative regulation of mitochondrial membrane permeability Source: CACAO
  • negative regulation of reactive oxygen species metabolic process Source: CACAO
  • positive regulation of mitophagy in response to mitochondrial depolarization Source: MGI
  • regulation of glucose import Source: MGI
  • response to ischemia Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-70153. Glucose transport.
R-MMU-70171. Glycolysis.
SABIO-RKO08528.
UniPathwayiUPA00242.

Names & Taxonomyi

Protein namesi
Recommended name:
Hexokinase-2 (EC:2.7.1.1)
Alternative name(s):
Hexokinase type II
Short name:
HK II
Gene namesi
Name:Hk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1315197. Hk2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: GO_Central
  • membrane Source: MGI
  • mitochondrial outer membrane Source: MGI
  • mitochondrion Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975881 – 917Hexokinase-2Add BLAST917

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO08528.
MaxQBiO08528.
PaxDbiO08528.
PeptideAtlasiO08528.
PRIDEiO08528.

PTM databases

iPTMnetiO08528.
PhosphoSitePlusiO08528.
SwissPalmiO08528.

Expressioni

Gene expression databases

BgeeiENSMUSG00000000628.
CleanExiMM_HK2.
ExpressionAtlasiO08528. baseline and differential.
GenevisibleiO08528. MM.

Interactioni

Subunit structurei

Monomer. Interacts with TIGAR; the interaction increases hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner.By similarity

Protein-protein interaction databases

BioGridi200316. 3 interactors.
DIPiDIP-41484N.
IntActiO08528. 1 interactor.
MINTiMINT-262872.
STRINGi10090.ENSMUSP00000000642.

Structurei

3D structure databases

ProteinModelPortaliO08528.
SMRiO08528.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini16 – 458Hexokinase 1PROSITE-ProRule annotationAdd BLAST443
Domaini464 – 906Hexokinase 2PROSITE-ProRule annotationAdd BLAST443

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 12HydrophobicAdd BLAST12
Regioni13 – 475RegulatoryAdd BLAST463
Regioni73 – 207Hexokinase small subdomain 1PROSITE-ProRule annotationAdd BLAST135
Regioni84 – 88Glucose-6-phosphate 1 bindingBy similarity5
Regioni155 – 156Substrate 1 bindingBy similarity2
Regioni172 – 173Substrate 1 bindingBy similarity2
Regioni208 – 447Hexokinase large subdomain 1PROSITE-ProRule annotationAdd BLAST240
Regioni208 – 209Substrate 1 bindingBy similarity2
Regioni291 – 294Substrate 1 bindingBy similarity4
Regioni413 – 415Glucose-6-phosphate 1 bindingBy similarity3
Regioni476 – 917CatalyticAdd BLAST442
Regioni521 – 655Hexokinase small subdomain 2PROSITE-ProRule annotationAdd BLAST135
Regioni532 – 536Glucose-6-phosphate 2 bindingBy similarity5
Regioni603 – 604Substrate 2 bindingBy similarity2
Regioni620 – 621Substrate 2 bindingBy similarity2
Regioni656 – 895Hexokinase large subdomain 2PROSITE-ProRule annotationAdd BLAST240
Regioni656 – 657Substrate 2 bindingBy similarity2
Regioni739 – 742Substrate 2 bindingBy similarity4
Regioni861 – 863Glucose-6-phosphate 2 bindingBy similarity3

Domaini

The N- and C-terminal halves of this hexokinase show extensive sequence similarity to each other. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus.

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated
Contains 2 hexokinase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162671.
HOVERGENiHBG005020.
InParanoidiO08528.
KOiK00844.
OMAiHHLGLES.
OrthoDBiEOG091G08MD.
PhylomeDBiO08528.
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. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 2 hits.
PS51748. HEXOKINASE_2. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08528-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIASHMIACL FTELNQNQVQ KVDQYLYHMR LSDETLLEIS RRFRKEMEKG
60 70 80 90 100
LGATTHPTAA VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLRVRVTDN
110 120 130 140 150
GLQRVEMENQ IYAIPEDIMR GSGTQLFDHI AECLANFMDK LQIKEKKLPL
160 170 180 190 200
GFTFSFPCHQ TKLDESFLVS WTKGFKSSGV EGRDVVDLIR KAIQRRGDFD
210 220 230 240 250
IDIVAVVNDT VGTMMTCGYD DQNCEIGLIV GTGSNACYME EMRHIDMVEG
260 270 280 290 300
DEGRMCINME WGAFGDDGTL NDIRTEFDRE IDMGSLNPGK QLFEKMISGM
310 320 330 340 350
YMGELVRLIL VKMAKAELLF QGKLSPELLT TGSFETKDVS DIEDDKDGIQ
360 370 380 390 400
KAYQILVRLG LSPLQEDCVA THRICQIVST RSASLCAATL AAVLWRIKEN
410 420 430 440 450
KGEERLRSTI GVDGSVYKKH PHFAKRLHKA VRRLVPDCDV RFLRSEDGSG
460 470 480 490 500
KGAAMVTAVA YRLADQHRAR QKTLESLKLS HEQLLEVKRR MKVEMEQGLS
510 520 530 540 550
KETHEAAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV LLVRVRNGKR
560 570 580 590 600
RGVEMHNKIY SIPQEVMHGT GEELFDHIVQ CIADFLEYMG MKGVSLPLGF
610 620 630 640 650
TFSFPCQQNS LDQSILLKWT KGFKASGCEG EDVVTLLKEA IRRREEFDLD
660 670 680 690 700
VVAVVNDTVG TMMTCGYEDP HCEVGLIVGT GSNACYMEEM RNVELVDGEE
710 720 730 740 750
GRMCVNMEWG AFGDNGCLDD LRTVFDVAVD ELSLNPGKQR FEKMISGMYL
760 770 780 790 800
GEIVRNILID FTKRGLLFRG RISERLKTRG IFETKFLSQI ESDCLALLQV
810 820 830 840 850
RAILRHLGLE STCDDSIIVK EVCTVVARRA AQLCGAGMAA VVDKIRENRG
860 870 880 890 900
LDNLKVTVGV DGTLYKLHPH FAKVMHETVR DLAPKCDVSF LESEDGSGKG
910
AALITAVACR IREAGQR
Length:917
Mass (Da):102,535
Last modified:July 1, 1997 - v1
Checksum:i44293E7A92D724B3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11666, Y11667, Y11668 Genomic DNA. Translation: CAA72366.1.
AJ238540 mRNA. Translation: CAB72257.1.
BC054472 mRNA. Translation: AAH54472.1.
CCDSiCCDS20263.1.
RefSeqiNP_038848.1. NM_013820.3.
UniGeneiMm.255848.
Mm.469167.

Genome annotation databases

EnsembliENSMUST00000000642; ENSMUSP00000000642; ENSMUSG00000000628.
GeneIDi15277.
KEGGimmu:15277.
UCSCiuc009cll.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y11666, Y11667, Y11668 Genomic DNA. Translation: CAA72366.1.
AJ238540 mRNA. Translation: CAB72257.1.
BC054472 mRNA. Translation: AAH54472.1.
CCDSiCCDS20263.1.
RefSeqiNP_038848.1. NM_013820.3.
UniGeneiMm.255848.
Mm.469167.

3D structure databases

ProteinModelPortaliO08528.
SMRiO08528.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200316. 3 interactors.
DIPiDIP-41484N.
IntActiO08528. 1 interactor.
MINTiMINT-262872.
STRINGi10090.ENSMUSP00000000642.

PTM databases

iPTMnetiO08528.
PhosphoSitePlusiO08528.
SwissPalmiO08528.

Proteomic databases

EPDiO08528.
MaxQBiO08528.
PaxDbiO08528.
PeptideAtlasiO08528.
PRIDEiO08528.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000000642; ENSMUSP00000000642; ENSMUSG00000000628.
GeneIDi15277.
KEGGimmu:15277.
UCSCiuc009cll.2. mouse.

Organism-specific databases

CTDi3099.
MGIiMGI:1315197. Hk2.

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162671.
HOVERGENiHBG005020.
InParanoidiO08528.
KOiK00844.
OMAiHHLGLES.
OrthoDBiEOG091G08MD.
PhylomeDBiO08528.
TreeFamiTF314238.

Enzyme and pathway databases

UniPathwayiUPA00242.
ReactomeiR-MMU-70153. Glucose transport.
R-MMU-70171. Glycolysis.
SABIO-RKO08528.

Miscellaneous databases

ChiTaRSiHk2. mouse.
PROiO08528.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000000628.
CleanExiMM_HK2.
ExpressionAtlasiO08528. baseline and differential.
GenevisibleiO08528. MM.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 2 hits.
PS51748. HEXOKINASE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHXK2_MOUSE
AccessioniPrimary (citable) accession number: O08528
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: November 30, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.