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Protein

Hexokinase-2

Gene

HK2

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

Functioni

Miscellaneous

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

Catalytic activityi

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

Activity regulationi

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

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 11 Publication1
Binding sitei232Glucose-6-phosphate 11 Publication1
Binding sitei235Substrate 11
Binding sitei260Substrate 11
Binding sitei449Glucose-6-phosphate 11 Publication1
Binding sitei558ATPSequence analysis1
Binding sitei657Glucose-6-phosphate 21 Publication1
Binding sitei680ATP 2By similarity1
Binding sitei680Glucose-6-phosphate 21 Publication1
Binding sitei708Substrate 21
Binding sitei897Glucose-6-phosphate 21 Publication1

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

  • ATP binding Source: UniProtKB-KW
  • fructokinase activity Source: GO_Central
  • glucokinase activity Source: GO_Central
  • glucose binding Source: Ensembl
  • hexokinase activity Source: ProtInc
  • mannokinase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Transferase
Biological processGlycolysis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08399-MONOMER
BRENDAi2.7.1.1 2681
ReactomeiR-HSA-70171 Glycolysis
SABIO-RKiP52789
UniPathwayi
UPA00242

Names & Taxonomyi

Protein namesi
Recommended name:
Hexokinase-2 (EC:2.7.1.1)
Alternative name(s):
Hexokinase type II
Short name:
HK II
Muscle form hexokinase
Gene namesi
Name:HK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000159399.9
HGNCiHGNC:4923 HK2
MIMi601125 gene
neXtProtiNX_P52789

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3099
OpenTargetsiENSG00000159399
PharmGKBiPA29301

Chemistry databases

ChEMBLiCHEMBL2640

Polymorphism and mutation databases

BioMutaiHK2
DMDMi56405344

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001975871 – 917Hexokinase-2Add BLAST917

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP52789
MaxQBiP52789
PaxDbiP52789
PeptideAtlasiP52789
PRIDEiP52789
ProteomicsDBi56533

PTM databases

iPTMnetiP52789
PhosphoSitePlusiP52789
SwissPalmiP52789

Expressioni

Tissue specificityi

Predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle.

Gene expression databases

BgeeiENSG00000159399 Expressed in 218 organ(s), highest expression level in colon
CleanExiHS_HK2
ExpressionAtlasiP52789 baseline and differential
GenevisibleiP52789 HS

Organism-specific databases

HPAiHPA028587

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with TIGAR; the interaction increases hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner (PubMed:23185017).By similarity1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi109346, 47 interactors
DIPiDIP-50110N
IntActiP52789, 25 interactors
MINTiP52789
STRINGi9606.ENSP00000290573

Chemistry databases

BindingDBiP52789

Structurei

Secondary structure

1917
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP52789
SMRiP52789
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52789

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 binding5
Regioni155 – 156Substrate 1 binding2
Regioni172 – 173Substrate 1 binding2
Regioni208 – 447Hexokinase large subdomain 1PROSITE-ProRule annotationAdd BLAST240
Regioni208 – 209Substrate 1 binding2
Regioni291 – 294Substrate 1 binding4
Regioni413 – 415Glucose-6-phosphate 1 binding3
Regioni476 – 917CatalyticAdd BLAST442
Regioni521 – 655Hexokinase small subdomain 2PROSITE-ProRule annotationAdd BLAST135
Regioni532 – 536Glucose-6-phosphate 2 binding5
Regioni603 – 604Substrate 2 binding2
Regioni620 – 621Substrate 2 binding2
Regioni656 – 895Hexokinase large subdomain 2PROSITE-ProRule annotationAdd BLAST240
Regioni656 – 657Substrate 2 binding2
Regioni682 – 683Substrate 2 binding2
Regioni739 – 742Substrate 2 binding4
Regioni861 – 863Glucose-6-phosphate 2 binding3

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. Each domain can bind a single glucose and Gluc-6-P molecule.

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1369 Eukaryota
COG5026 LUCA
GeneTreeiENSGT00390000017159
HOGENOMiHOG000162671
HOVERGENiHBG005020
InParanoidiP52789
KOiK00844
OMAiGGVEMHN
OrthoDBiEOG091G08MD
PhylomeDBiP52789
TreeFamiTF314238

Family and domain databases

InterProiView protein in InterPro
IPR001312 Hexokinase
IPR019807 Hexokinase_BS
IPR022673 Hexokinase_C
IPR022672 Hexokinase_N
PANTHERiPTHR19443 PTHR19443, 4 hits
PfamiView protein in Pfam
PF00349 Hexokinase_1, 2 hits
PF03727 Hexokinase_2, 2 hits
PROSITEiView protein in PROSITE
PS00378 HEXOKINASE_1, 2 hits
PS51748 HEXOKINASE_2, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P52789-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MIASHLLAYF FTELNHDQVQ KVDQYLYHMR LSDETLLEIS KRFRKEMEKG
60 70 80 90 100
LGATTHPTAA VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLWVKVTDN
110 120 130 140 150
GLQKVEMENQ IYAIPEDIMR GSGTQLFDHI AECLANFMDK LQIKDKKLPL
160 170 180 190 200
GFTFSFPCHQ TKLDESFLVS WTKGFKSSGV EGRDVVALIR KAIQRRGDFD
210 220 230 240 250
IDIVAVVNDT VGTMMTCGYD DHNCEIGLIV GTGSNACYME EMRHIDMVEG
260 270 280 290 300
DEGRMCINME WGAFGDDGSL NDIRTEFDQE IDMGSLNPGK QLFEKMISGM
310 320 330 340 350
YMGELVRLIL VKMAKEELLF GGKLSPELLN TGRFETKDIS DIEGEKDGIR
360 370 380 390 400
KAREVLMRLG LDPTQEDCVA THRICQIVST RSASLCAATL AAVLQRIKEN
410 420 430 440 450
KGEERLRSTI GVDGSVYKKH PHFAKRLHKT VRRLVPGCDV RFLRSEDGSG
460 470 480 490 500
KGAAMVTAVA YRLADQHRAR QKTLEHLQLS HDQLLEVKRR MKVEMERGLS
510 520 530 540 550
KETHASAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV LLVRVRNGKW
560 570 580 590 600
GGVEMHNKIY AIPQEVMHGT GDELFDHIVQ CIADFLEYMG MKGVSLPLGF
610 620 630 640 650
TFSFPCQQNS LDESILLKWT KGFKASGCEG EDVVTLLKEA IHRREEFDLD
660 670 680 690 700
VVAVVNDTVG TMMTCGFEDP HCEVGLIVGT GSNACYMEEM RNVELVEGEE
710 720 730 740 750
GRMCVNMEWG AFGDNGCLDD FRTEFDVAVD ELSLNPGKQR FEKMISGMYL
760 770 780 790 800
GEIVRNILID FTKRGLLFRG RISERLKTRG IFETKFLSQI ESDCLALLQV
810 820 830 840 850
RAILQHLGLE STCDDSIIVK EVCTVVARRA AQLCGAGMAA VVDRIRENRG
860 870 880 890 900
LDALKVTVGV DGTLYKLHPH FAKVMHETVK DLAPKCDVSF LQSEDGSGKG
910
AALITAVACR IREAGQR
Length:917
Mass (Da):102,380
Last modified:December 7, 2004 - v2
Checksum:iF17CE1938CF13880
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PB90E9PB90_HUMAN
Hexokinase-2
HK2
889Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti803I → T in CAA86511 (PubMed:8250948).Curated1
Sequence conflicti870Missing in CAA86476 (PubMed:8786021).Curated1

Polymorphismi

Although found in NIDDM patients, genetic variations of HK2 do not contribute to the disease (PubMed:7883122, PubMed:7883123).2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003691142Q → H Does not affect activity. 4 PublicationsCorresponds to variant dbSNP:rs2229621Ensembl.1
Natural variantiVAR_010577148L → F1 Publication1
Natural variantiVAR_020504274R → C1 PublicationCorresponds to variant dbSNP:rs28363006Ensembl.1
Natural variantiVAR_020505314A → P1 PublicationCorresponds to variant dbSNP:rs28363015Ensembl.1
Natural variantiVAR_010578314A → V1 Publication1
Natural variantiVAR_020506331T → I1 PublicationCorresponds to variant dbSNP:rs28363016Ensembl.1
Natural variantiVAR_010579353R → C1 PublicationCorresponds to variant dbSNP:rs61748096Ensembl.1
Natural variantiVAR_020507387A → S1 PublicationCorresponds to variant dbSNP:rs28363029Ensembl.1
Natural variantiVAR_010580497R → Q1 PublicationCorresponds to variant dbSNP:rs145124653Ensembl.1
Natural variantiVAR_010581775R → Q1 PublicationCorresponds to variant dbSNP:rs185927605Ensembl.1
Natural variantiVAR_020508801R → Q1 PublicationCorresponds to variant dbSNP:rs28363057Ensembl.1
Natural variantiVAR_010582844R → K2 PublicationsCorresponds to variant dbSNP:rs2229629Ensembl.1
Natural variantiVAR_020509881D → N1 PublicationCorresponds to variant dbSNP:rs28363065Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46376 mRNA Translation: CAA86511.1
Z46354
, Z46355, Z46604, Z46356, Z46357, Z46358, Z46359, Z46360, Z46361, Z46362, Z46363, Z46364, Z46365, Z46366, Z46367, Z46368, Z46369 Genomic DNA Translation: CAA86476.2
AF148513 mRNA Translation: AAD30174.1
AY623118 Genomic DNA Translation: AAT38114.1
CH471053 Genomic DNA Translation: EAW99601.1
CH471053 Genomic DNA Translation: EAW99602.1
BC021116 mRNA Translation: AAH21116.1
BC064369 mRNA Translation: AAH64369.1
D25412 Genomic DNA Translation: BAA04999.1
CCDSiCCDS1956.1
PIRiS48809 JC2025
RefSeqiNP_000180.2, NM_000189.4
UniGeneiHs.406266
Hs.591588

Genome annotation databases

EnsembliENST00000290573; ENSP00000290573; ENSG00000159399
GeneIDi3099
KEGGihsa:3099
UCSCiuc002snd.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Hexokinase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46376 mRNA Translation: CAA86511.1
Z46354
, Z46355, Z46604, Z46356, Z46357, Z46358, Z46359, Z46360, Z46361, Z46362, Z46363, Z46364, Z46365, Z46366, Z46367, Z46368, Z46369 Genomic DNA Translation: CAA86476.2
AF148513 mRNA Translation: AAD30174.1
AY623118 Genomic DNA Translation: AAT38114.1
CH471053 Genomic DNA Translation: EAW99601.1
CH471053 Genomic DNA Translation: EAW99602.1
BC021116 mRNA Translation: AAH21116.1
BC064369 mRNA Translation: AAH64369.1
D25412 Genomic DNA Translation: BAA04999.1
CCDSiCCDS1956.1
PIRiS48809 JC2025
RefSeqiNP_000180.2, NM_000189.4
UniGeneiHs.406266
Hs.591588

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NZTX-ray2.45A/B17-916[»]
5HEXX-ray2.73A/B17-917[»]
5HFUX-ray2.92A/B17-917[»]
5HG1X-ray2.76A17-916[»]
ProteinModelPortaliP52789
SMRiP52789
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109346, 47 interactors
DIPiDIP-50110N
IntActiP52789, 25 interactors
MINTiP52789
STRINGi9606.ENSP00000290573

Chemistry databases

BindingDBiP52789
ChEMBLiCHEMBL2640

PTM databases

iPTMnetiP52789
PhosphoSitePlusiP52789
SwissPalmiP52789

Polymorphism and mutation databases

BioMutaiHK2
DMDMi56405344

Proteomic databases

EPDiP52789
MaxQBiP52789
PaxDbiP52789
PeptideAtlasiP52789
PRIDEiP52789
ProteomicsDBi56533

Protocols and materials databases

DNASUi3099
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000290573; ENSP00000290573; ENSG00000159399
GeneIDi3099
KEGGihsa:3099
UCSCiuc002snd.4 human

Organism-specific databases

CTDi3099
DisGeNETi3099
EuPathDBiHostDB:ENSG00000159399.9
GeneCardsiHK2
H-InvDBiHIX0030207
HGNCiHGNC:4923 HK2
HPAiHPA028587
MIMi601125 gene
neXtProtiNX_P52789
OpenTargetsiENSG00000159399
PharmGKBiPA29301
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1369 Eukaryota
COG5026 LUCA
GeneTreeiENSGT00390000017159
HOGENOMiHOG000162671
HOVERGENiHBG005020
InParanoidiP52789
KOiK00844
OMAiGGVEMHN
OrthoDBiEOG091G08MD
PhylomeDBiP52789
TreeFamiTF314238

Enzyme and pathway databases

UniPathwayi
UPA00242

BioCyciMetaCyc:HS08399-MONOMER
BRENDAi2.7.1.1 2681
ReactomeiR-HSA-70171 Glycolysis
SABIO-RKiP52789

Miscellaneous databases

ChiTaRSiHK2 human
EvolutionaryTraceiP52789
GeneWikiiHK2
GenomeRNAii3099
PROiPR:P52789
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000159399 Expressed in 218 organ(s), highest expression level in colon
CleanExiHS_HK2
ExpressionAtlasiP52789 baseline and differential
GenevisibleiP52789 HS

Family and domain databases

InterProiView protein in InterPro
IPR001312 Hexokinase
IPR019807 Hexokinase_BS
IPR022673 Hexokinase_C
IPR022672 Hexokinase_N
PANTHERiPTHR19443 PTHR19443, 4 hits
PfamiView protein in Pfam
PF00349 Hexokinase_1, 2 hits
PF03727 Hexokinase_2, 2 hits
PROSITEiView protein in PROSITE
PS00378 HEXOKINASE_1, 2 hits
PS51748 HEXOKINASE_2, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiHXK2_HUMAN
AccessioniPrimary (citable) accession number: P52789
Secondary accession number(s): D6W5J2, Q8WU87, Q9UN82
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 7, 2004
Last modified: November 7, 2018
This is version 187 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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