Hexokinase-2 - Homo sapiens (Human)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	917 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Coding sequence diversity	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome
Gene Ontology (GO)
Biological process	glycolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Ref.2 Inferred from Experiment. Source: Reactome mitochondrial outer membrane Non-traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW hexokinase activity Ref.2 Inferred from Experiment. Source: Reactome
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 917

917

Hexokinase-2

PRO_0000197587

Regions

Nucleotide binding

84 – 89

6

ATP 1 Potential

Nucleotide binding

425 – 426

2

ATP 1 By similarity

Nucleotide binding

532 – 537

6

ATP 2 By similarity

Nucleotide binding

747 – 748

2

ATP 2 By similarity

Nucleotide binding

784 – 788

5

ATP 2 By similarity

Nucleotide binding

863 – 867

5

ATP 2 By similarity

Region

1 – 12

12

Hydrophobic

Region

13 – 475

463

Regulatory

Region

84 – 88

5

Glucose-6-phosphate 1 binding

Region

155 – 156

2

Substrate 1 binding

Region

172 – 173

2

Substrate 1 binding

Region

208 – 209

2

Substrate 1 binding

Region

291 – 294

4

Substrate 1 binding

Region

413 – 415

3

Glucose-6-phosphate 1 binding

Region

476 – 917

442

Catalytic

Region

532 – 536

5

Glucose-6-phosphate 2 binding

Region

603 – 604

2

Substrate 2 binding

Region

620 – 621

2

Substrate 2 binding

Region

656 – 657

2

Substrate 2 binding

Region

682 – 683

2

Substrate 2 binding

Region

739 – 742

4

Substrate 2 binding

Region

861 – 863

3

Glucose-6-phosphate 2 binding

Sites

Binding site

30

1

ATP 1 By similarity

Binding site

209

1

Glucose-6-phosphate 1

Binding site

232

1

Glucose-6-phosphate 1

Binding site

235

1

Substrate 1

Binding site

260

1

Substrate 1

Binding site

449

1

Glucose-6-phosphate 1

Binding site

558

1

ATP Potential

Binding site

657

1

Glucose-6-phosphate 2

Binding site

680

1

ATP 2 By similarity

Binding site

680

1

Glucose-6-phosphate 2

Binding site

708

1

Substrate 2

Binding site

897

1

Glucose-6-phosphate 2

Amino acid modifications

Modified residue

461

1

Phosphotyrosine By similarity

Natural variations

Natural variant

142

1

Q → H Does not affect activity. dbSNP rs2229621. Ref.2 Ref.4 Ref.10 Ref.11

VAR_003691

Natural variant

148

1

L → F

VAR_010577

Natural variant

274

1

R → C: dbSNP rs28363006. Ref.4

VAR_020504

Natural variant

314

1

A → P: dbSNP rs28363015. Ref.4

VAR_020505

Natural variant

314

1

A → V

VAR_010578

Natural variant

331

1

T → I: dbSNP rs28363016. Ref.4

VAR_020506

Natural variant

353

1

R → C

VAR_010579

Natural variant

387

1

A → S: dbSNP rs28363029. Ref.4

VAR_020507

Natural variant

497

1

R → Q: dbSNP rs2229625. Ref.11

VAR_010580

Natural variant

775

1

R → Q

VAR_010581

Natural variant

801

1

R → Q: dbSNP rs28363057. Ref.4

VAR_020508

Natural variant

844

1

R → K: dbSNP rs2229629. Ref.4 Ref.11

VAR_010582

Natural variant

881

1

D → N: dbSNP rs28363065. Ref.4

VAR_020509

Experimental info

Sequence conflict

803

1

I → T in CAA86511. Ref.1

Sequence conflict

870

1

Missing in CAA86476. Ref.2

Secondary structure

1

.

917

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P52789-1 [UniParc].

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

917

102,380

        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

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References

	« Hide 'large scale' referencesShow '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: 8250948] [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: 8786021] [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]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta and Testis.
[6]	"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: 7518342] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 614-739.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"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.
[9]	"Amino acid substitutions in hexokinase II among patients with NIDDM." Laakso M., Malkki M., Deeb S.S. Diabetes 44:330-334(1995) [PubMed: 7883120] [Abstract] Cited for: VARIANTS VAL-314; CYS-353 AND GLN-775.
[10]	"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: 7883122] [Abstract] Cited for: VARIANT HIS-142.
[11]	"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: 7883123] [Abstract] Cited for: VARIANTS HIS-142; PHE-148; GLN-497 AND LYS-844.
+	Additional computationally mapped references.

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Web resources

NIEHS-SNPs

Wikipedia

Hexokinase entry

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z46376 mRNA. Translation: CAA86511.1.
Z46354

Z46369 Genomic DNA. Translation: CAA86476.2.
AF148513 mRNA. Translation: AAD30174.1.
AY623118 Genomic DNA. Translation: AAT38114.1.
BC021116 mRNA. Translation: AAH21116.1.
BC064369 mRNA. Translation: AAH64369.1.
D25412 Genomic DNA. Translation: BAA04999.1.

IPI

IPI00102864.

PIR

JC2025. S48809.

RefSeq

NP_000180.2.

UniGene

Hs.406266
Hs.591588

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2NZT	X-ray	2.45	A/B	17-916	[»]

ModBase

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Protein-protein interaction databases

IntAct

P52789. 2 interactions.

STRING

P52789.

PTM databases

PhosphoSite

P52789.

Proteomic databases

PeptideAtlas

P52789.

PRIDE

P52789.

Genome annotation databases

Ensembl

ENST00000290573; ENSP00000290573; ENSG00000159399; Homo sapiens. [Genome view]

GeneID

3099.

KEGG

hsa:3099.

NMPDR

fig|9606.3.peg.18107.

UCSC

uc002snd.1. human.

Organism-specific databases

CTD

3099.

GeneCards

GC02P074971.

H-InvDB

HIX0002196.

HGNC

HGNC:4923. HK2.

MIM

601125. gene.

PharmGKB

PA29301.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG18449.

HOGENOM

HBG446386.

HOVERGEN

P52789.

InParanoid

P52789.

OMA

EMRHIDM.

OrthoDB

EOG9SBHH8.

PhylomeDB

P52789.

Enzyme and pathway databases

BRENDA

2.7.1.1. 247.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P52789.

Bgee

P52789.

CleanEx

HS_HK2.

Genevestigator

P52789.

GermOnline

ENSG00000159399. Homo sapiens.

Family and domain databases

InterPro

IPR001312. Hexokinase.
IPR019807. Hexokinase_CS.
[Graphical view]

PANTHER

PTHR19443. Hexokinase. 1 hit.

Pfam

PF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]

PRINTS

PR00475. HEXOKINASE.

PROSITE

PS00378. HEXOKINASES. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

12305.

SOURCE

Search...

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Entry information

Entry name

HXK2_HUMAN

Accession

Primary (citable) accession number: P52789
Secondary accession number(s): Q8WU87, Q9UN82

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	December 7, 2004
Last modified:	January 19, 2010
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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