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P52789 (HXK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hexokinase-2

EC=2.7.1.1
Alternative name(s):
Hexokinase type II
Short name=HK II
Muscle form hexokinase
Gene names
Name:HK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length917 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Enzyme regulation

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

Pathway

Carbohydrate metabolism; hexose metabolism.

Subunit structure

Monomer By similarity.

Subcellular location

Mitochondrion outer membrane By similarity. Note: Its hydrophobic N-terminal sequence may be involved in membrane binding By similarity.

Tissue specificity

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

Domain

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.

Polymorphism

Although found in NIDDM patients, genetic variations of HK2 do not contribute to the disease.

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.

Contains 2 hexokinase type-1 domains.

Contains 2 hexokinase type-2 domains.

Ontologies

Keywords
   Biological processGlycolysis
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
   Coding sequence diversityPolymorphism
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   Technical term3D-structure
Allosteric enzyme
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic mitochondrial changes

Inferred from direct assay PubMed 18350175. Source: MGI

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular glucose homeostasis

Inferred from Biological aspect of Ancestor. Source: RefGenome

glucose 6-phosphate metabolic process

Inferred from Biological aspect of Ancestor. Source: GOC

glucose transport

Traceable author statement. Source: Reactome

glycolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

hexose transport

Traceable author statement. Source: Reactome

lactation

Inferred from electronic annotation. Source: Ensembl

regulation of glucose import

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

mitochondrial outer membrane

Inferred from direct assay PubMed 18350175. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

fructokinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glucokinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glucose binding

Inferred from electronic annotation. Source: Ensembl

hexokinase activity

Traceable author statement PubMed 9278438. Source: ProtInc

mannokinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 917917Hexokinase-2
PRO_0000197587

Regions

Domain17 – 221205Hexokinase type-1 1
Domain223 – 462240Hexokinase type-2 1
Domain465 – 669205Hexokinase type-1 2
Domain671 – 910240Hexokinase type-2 2
Nucleotide binding84 – 896ATP 1 Potential
Nucleotide binding425 – 4262ATP 1 By similarity
Nucleotide binding532 – 5376ATP 2 By similarity
Nucleotide binding747 – 7482ATP 2 By similarity
Nucleotide binding784 – 7885ATP 2 By similarity
Nucleotide binding863 – 8675ATP 2 By similarity
Region1 – 1212Hydrophobic
Region13 – 475463Regulatory
Region84 – 885Glucose-6-phosphate 1 binding
Region155 – 1562Substrate 1 binding
Region172 – 1732Substrate 1 binding
Region208 – 2092Substrate 1 binding
Region291 – 2944Substrate 1 binding
Region413 – 4153Glucose-6-phosphate 1 binding
Region476 – 917442Catalytic
Region532 – 5365Glucose-6-phosphate 2 binding
Region603 – 6042Substrate 2 binding
Region620 – 6212Substrate 2 binding
Region656 – 6572Substrate 2 binding
Region682 – 6832Substrate 2 binding
Region739 – 7424Substrate 2 binding
Region861 – 8633Glucose-6-phosphate 2 binding

Sites

Binding site301ATP 1 By similarity
Binding site2091Glucose-6-phosphate 1
Binding site2321Glucose-6-phosphate 1
Binding site2351Substrate 1
Binding site2601Substrate 1
Binding site4491Glucose-6-phosphate 1
Binding site5581ATP Potential
Binding site6571Glucose-6-phosphate 2
Binding site6801ATP 2 By similarity
Binding site6801Glucose-6-phosphate 2
Binding site7081Substrate 2
Binding site8971Glucose-6-phosphate 2

Natural variations

Natural variant1421Q → H Does not affect activity. Ref.2 Ref.4 Ref.11 Ref.12
Corresponds to variant rs2229621 [ dbSNP | Ensembl ].
VAR_003691
Natural variant1481L → F. Ref.12
VAR_010577
Natural variant2741R → C. Ref.4
Corresponds to variant rs28363006 [ dbSNP | Ensembl ].
VAR_020504
Natural variant3141A → P. Ref.4
Corresponds to variant rs28363015 [ dbSNP | Ensembl ].
VAR_020505
Natural variant3141A → V. Ref.10
VAR_010578
Natural variant3311T → I. Ref.4
Corresponds to variant rs28363016 [ dbSNP | Ensembl ].
VAR_020506
Natural variant3531R → C. Ref.10
Corresponds to variant rs61748096 [ dbSNP | Ensembl ].
VAR_010579
Natural variant3871A → S. Ref.4
Corresponds to variant rs28363029 [ dbSNP | Ensembl ].
VAR_020507
Natural variant4971R → Q. Ref.12
Corresponds to variant rs2229625 [ dbSNP | Ensembl ].
VAR_010580
Natural variant7751R → Q. Ref.10
Corresponds to variant rs185927605 [ dbSNP | Ensembl ].
VAR_010581
Natural variant8011R → Q. Ref.4
Corresponds to variant rs28363057 [ dbSNP | Ensembl ].
VAR_020508
Natural variant8441R → K. Ref.4 Ref.12
Corresponds to variant rs2229629 [ dbSNP | Ensembl ].
VAR_010582
Natural variant8811D → N. Ref.4
Corresponds to variant rs28363065 [ dbSNP | Ensembl ].
VAR_020509

Experimental info

Sequence conflict8031I → T in CAA86511. Ref.1
Sequence conflict8701Missing in CAA86476. Ref.2

Secondary structure

.................................................................................................................................... 917
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P52789 [UniParc].

Last modified December 7, 2004. Version 2.
Checksum: F17CE1938CF13880

FASTA917102,380
        10         20         30         40         50         60 
MIASHLLAYF FTELNHDQVQ KVDQYLYHMR LSDETLLEIS KRFRKEMEKG LGATTHPTAA 

        70         80         90        100        110        120 
VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLWVKVTDN GLQKVEMENQ IYAIPEDIMR 

       130        140        150        160        170        180 
GSGTQLFDHI AECLANFMDK LQIKDKKLPL GFTFSFPCHQ TKLDESFLVS WTKGFKSSGV 

       190        200        210        220        230        240 
EGRDVVALIR KAIQRRGDFD IDIVAVVNDT VGTMMTCGYD DHNCEIGLIV GTGSNACYME 

       250        260        270        280        290        300 
EMRHIDMVEG DEGRMCINME WGAFGDDGSL NDIRTEFDQE IDMGSLNPGK QLFEKMISGM 

       310        320        330        340        350        360 
YMGELVRLIL VKMAKEELLF GGKLSPELLN TGRFETKDIS DIEGEKDGIR KAREVLMRLG 

       370        380        390        400        410        420 
LDPTQEDCVA THRICQIVST RSASLCAATL AAVLQRIKEN KGEERLRSTI GVDGSVYKKH 

       430        440        450        460        470        480 
PHFAKRLHKT VRRLVPGCDV RFLRSEDGSG KGAAMVTAVA YRLADQHRAR QKTLEHLQLS 

       490        500        510        520        530        540 
HDQLLEVKRR MKVEMERGLS KETHASAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV 

       550        560        570        580        590        600 
LLVRVRNGKW GGVEMHNKIY AIPQEVMHGT GDELFDHIVQ CIADFLEYMG MKGVSLPLGF 

       610        620        630        640        650        660 
TFSFPCQQNS LDESILLKWT KGFKASGCEG EDVVTLLKEA IHRREEFDLD VVAVVNDTVG 

       670        680        690        700        710        720 
TMMTCGFEDP HCEVGLIVGT GSNACYMEEM RNVELVEGEE GRMCVNMEWG AFGDNGCLDD 

       730        740        750        760        770        780 
FRTEFDVAVD ELSLNPGKQR FEKMISGMYL GEIVRNILID FTKRGLLFRG RISERLKTRG 

       790        800        810        820        830        840 
IFETKFLSQI ESDCLALLQV RAILQHLGLE STCDDSIIVK EVCTVVARRA AQLCGAGMAA 

       850        860        870        880        890        900 
VVDRIRENRG LDALKVTVGV DGTLYKLHPH FAKVMHETVK DLAPKCDVSF LQSEDGSGKG 

       910 
AALITAVACR IREAGQR 

« Hide

References

« Hide 'large scale' references
[1]"Human hexokinase II: sequence and homology to other hexokinases."
Deeb S.S., Malkki M., Laakso M.
Biochem. Biophys. Res. Commun. 197:68-74(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[2]"Human hexokinase II gene: exon-intron organization, mutation screening in NIDDM, and its relationship to muscle hexokinase activity."
Lehto M., Huang X., Davis E.M., Le Beau M.M., Laurila E., Eriksson K.F., Bell G.I., Groop L.C.
Diabetologia 38:1466-1474(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-142.
Tissue: Blood, Muscle and Placenta.
[3]Malkki M., Heikkinen S., Deeb S.S., Laakso M.
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Skeletal muscle.
[4]NIEHS SNPs program
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-142; CYS-274; PRO-314; ILE-331; SER-387; GLN-801; LYS-844 AND ASN-881.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
Tissue: Placenta and Testis.
[7]"Steady state transcript levels of the type II hexokinase and type 1 glucose transporter in human tumor cell lines."
Shinohara Y., Yamamoto K., Kogure K., Ichihara J., Terada H.
Cancer Lett. 82:27-32(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 614-739.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Crystal structure of human hexokinase II."
Structural genomics consortium (SGC)
Submitted (DEC-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 17-916 IN COMPLEX WITH GLUCOSE AND GLUCOSE-6-PHOSPHATE.
[10]"Amino acid substitutions in hexokinase II among patients with NIDDM."
Laakso M., Malkki M., Deeb S.S.
Diabetes 44:330-334(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-314; CYS-353 AND GLN-775.
[11]"Analysis of the hexokinase II gene in subjects with insulin resistance and NIDDM and detection of a Gln142-->His substitution."
Vidal-Puig A., Printz R.L., Stratton I.M., Granner D.K., Moller D.E.
Diabetes 44:340-346(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-142.
[12]"Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity."
Echwald S.M., Bjoerbaek C., Hansen T., Clausen J.O., Vestergaard H., Zierath J.R., Printz R.L., Granner D.K., Pedersen O.
Diabetes 44:347-353(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HIS-142; PHE-148; GLN-497 AND LYS-844.
+Additional computationally mapped references.

Web resources

NIEHS-SNPs
Wikipedia

Hexokinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z46376 mRNA. Translation: CAA86511.1.
Z46354 expand/collapse EMBL AC list , 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.
PIRJC2025. S48809.
RefSeqNP_000180.2. NM_000189.4.
UniGeneHs.406266.
Hs.591588.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2NZTX-ray2.45A/B17-916[»]
ProteinModelPortalP52789.
SMRP52789. Positions 17-913.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109346. 22 interactions.
DIPDIP-50110N.
IntActP52789. 4 interactions.
MINTMINT-1461614.
STRING9606.ENSP00000290573.

Chemistry

BindingDBP52789.
ChEMBLCHEMBL2640.

PTM databases

PhosphoSiteP52789.

Polymorphism databases

DMDM56405344.

Proteomic databases

PaxDbP52789.
PeptideAtlasP52789.
PRIDEP52789.

Protocols and materials databases

DNASU3099.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290573; ENSP00000290573; ENSG00000159399.
GeneID3099.
KEGGhsa:3099.
UCSCuc002snd.3. human.

Organism-specific databases

CTD3099.
GeneCardsGC02P075059.
H-InvDBHIX0030207.
HGNCHGNC:4923. HK2.
HPAHPA028587.
MIM601125. gene.
neXtProtNX_P52789.
PharmGKBPA29301.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5026.
HOGENOMHOG000162671.
HOVERGENHBG005020.
InParanoidP52789.
KOK00844.
OMAHHLGLES.
OrthoDBEOG7S21X5.
PhylomeDBP52789.
TreeFamTF314238.

Enzyme and pathway databases

BioCycMetaCyc:HS08399-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.
SABIO-RKP52789.
UniPathwayUPA00242.

Gene expression databases

ArrayExpressP52789.
BgeeP52789.
CleanExHS_HK2.
GenevestigatorP52789.

Family and domain databases

InterProIPR001312. Hexokinase.
IPR022673. Hexokinase_C.
IPR019807. Hexokinase_CS.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERPTHR19443. PTHR19443. 1 hit.
PfamPF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PRINTSPR00475. HEXOKINASE.
PROSITEPS00378. HEXOKINASES. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP52789.
GeneWikiHK2.
GenomeRNAi3099.
NextBio12305.
PROP52789.
SOURCESearch...

Entry information

Entry nameHXK2_HUMAN
AccessionPrimary (citable) accession number: P52789
Secondary accession number(s): D6W5J2, Q8WU87, Q9UN82
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: December 7, 2004
Last modified: April 16, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM