P52790 (HXK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hexokinase-3
EC=2.7.1.1

Alternative name(s):
Hexokinase type III
Short name=HK III

Gene names

Name:

HK3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	923 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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.
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	Polymorphism
Domain	Repeat
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	3D-structure Allosteric enzyme Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular glucose homeostasis Inferred from Biological aspect of Ancestor. Source: RefGenome glucose transport Traceable author statement. Source: Reactome glycolysis Non-traceable author statement. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome membrane Non-traceable author statement. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: Compara protein complex Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB fructokinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome glucokinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome hormone binding Inferred from electronic annotation. Source: Compara mannokinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 923

923

Hexokinase-3

PRO_0000197590

Regions

Nucleotide binding

95 – 100

6

ATP Potential

Nucleotide binding

542 – 547

6

ATP Potential

Region

1 – 488

488

Regulatory

Region

162 – 188

27

Glucose-binding Potential

Region

489 – 923

435

Catalytic

Region

603 – 629

27

Glucose-binding Potential

Natural variations

Natural variant

281

1

G → R.
Corresponds to variant rs35610191 [ dbSNP | Ensembl ].

VAR_034004

Natural variant

480

1

R → W in a colorectal cancer sample; somatic mutation. Ref.5

VAR_036186

Natural variant

499

1

A → V in a breast cancer sample; somatic mutation. Ref.5

VAR_036187

Experimental info

Sequence conflict

277

1

F → L in AAC50732. Ref.1

Sequence conflict

420

1

Q → L in AAC50422. Ref.4

Sequence conflict

431

1

E → Q in AAC50422. Ref.4

Sequence conflict

439

1

V → I in AAC50422. Ref.4

Sequence conflict

510

1

K → R in AAC50422. Ref.4

Sequence conflict

512 – 513

2

LR → SE in AAC50422. Ref.4

Sequence conflict

516

1

A → S in AAC50422. Ref.4

Sequence conflict

519

1

L → S in AAC50422. Ref.4

Sequence conflict

530 – 531

2

PD → LT in AAC50422. Ref.4

Sequence conflict

577 – 578

2

GQ → AE in AAC50422. Ref.4

Sequence conflict

604

1

L → T in AAC50422. Ref.4

Sequence conflict

708

1

R → H in AAC50422. Ref.4

Sequence conflict

718

1

F → L in AAC50422. Ref.4

Sequence conflict

728

1

S → R in AAC50422. Ref.4

Sequence conflict

750

1

M → I in AAC50422. Ref.4

Sequence conflict

831

1

A → V in AAC50422. Ref.4

Sequence conflict

836

1

A → P in AAC50422. Ref.4

Sequence conflict

853

1

E → G in AAC50732. Ref.1

Sequence conflict

918

1

A → T in AAC50422. Ref.4

Secondary structure

1

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923

Helix Strand Turn

Details...

Helix

480 – 487

8

Helix

488 – 490

3

Helix

494 – 513

20

Beta strand

536 – 566

31

Helix

570 – 573

4

Helix

577 – 595

19

Beta strand

604 – 608

5

Helix

639 – 649

11

Beta strand

657 – 661

5

Helix

663 – 672

10

Beta strand

678 – 695

18

Helix

696 – 698

3

Beta strand

706 – 712

7

Helix

715 – 717

3

Turn

718 – 727

10

Helix

730 – 737

8

Beta strand

739 – 741

3

Helix

748 – 750

3

Helix

753 – 769

17

Helix

774 – 776

3

Helix

780 – 783

4

Helix

790 – 796

7

Helix

803 – 811

9

Turn

812 – 814

3

Helix

819 – 854

36

Beta strand

858 – 867

10

Helix

869 – 873

5

Helix

877 – 888

12

Beta strand

892 – 898

7

Helix

903 – 918

16

Sequences

	Sequence		Length	Mass (Da)
	P52790 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: DA75F2A9DBB895FF	FASTA	923	99,025
	10 20 30 40 50 60 MDSIGSSGLR QGEETLSCSE EGLPGPSDSS ELVQECLQQF KVTRAQLQQI QASLLGSMEQ 70 80 90 100 110 120 ALRGQASPAP AVRMLPTYVG STPHGTEQGD FVVLELGATG ASLRVLWVTL TGIEGHRVEP 130 140 150 160 170 180 RSQEFVIPQE VMLGAGQQLF DFAAHCLSEF LDAQPVNKQG LQLGFSFSFP CHQTGLDRST 190 200 210 220 230 240 LISWTKGFRC SGVEGQDVVQ LLRDAIRRQG AYNIDVVAVV NDTVGTMMGC EPGVRPCEVG 250 260 270 280 290 300 LVVDTGTNAC YMEEARHVAV LDEDRGRVCV SVEWGSFSDD GALGPVLTTF DHTLDHESLN 310 320 330 340 350 360 PGAQRFEKMI GGLYLGELVR LVLAHLARCG VLFGGCTSPA LLSQGSILLE HVAEMEDPST 370 380 390 400 410 420 GAARVHAILQ DLGLSPGASD VELVQHVCAA VCTRAAQLCA AALAAVLSCL QHSREQQTLQ 430 440 450 460 470 480 VAVATGGRVC ERHPRFCSVL QGTVMLLAPE CDVSLIPSVD GGGRGVAMVT AVAARLAAHR 490 500 510 520 530 540 RLLEETLAPF RLNHDQLAAV QAQMRKAMAK GLRGEASSLR MLPTFVRATP DGSERGDFLA 550 560 570 580 590 600 LDLGGTNFRV LLVRVTTGVQ ITSEIYSIPE TVAQGSGQQL FDHIVDCIVD FQQKQGLSGQ 610 620 630 640 650 660 SLPLGFTFSF PCRQLGLDQG ILLNWTKGFK ASDCEGQDVV SLLREAITRR QAVELNVVAI 670 680 690 700 710 720 VNDTVGTMMS CGYEDPRCEI GLIVGTGTNA CYMEELRNVA GVPGDSGRMC INMEWGAFGD 730 740 750 760 770 780 DGSLAMLSTR FDASVDQASI NPGKQRFEKM ISGMYLGEIV RHILLHLTSL GVLFRGQQIQ 790 800 810 820 830 840 RLQTRDIFKT KFLSEIESDS LALRQVRAIL EDLGLPLTSD DALMVLEVCQ AVSQRAAQLC 850 860 870 880 890 900 GAGVAAVVEK IRENRGLEEL AVSVGVDGTL YKLHPRFSSL VAATVRELAP RCVVTFLQSE 910 920 DGSGKGAALV TAVACRLAQL TRV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of human hexokinase III cDNA and assignment of the human hexokinase III gene (HK3) to chromosome band 5q35.2 by fluorescence in situ hybridization." Furuta H., Nishi S., Le Beau M.M., Fernald A.A., Yano H., Bell G.I. Genomics 36:206-209(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	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. , 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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]. Tissue: Blood.
[4]	"Purification and characterization of the carboxyl-domain of human hexokinase type III expressed as fusion protein." Palma F., Agostini D., Mason P., Dacha M., Piccoli G., Biagiarelli B., Fiorani M., Stocchi V. Mol. Cell. Biochem. 155:23-29(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 358-923. Tissue: Liver.
[5]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TRP-480 AND VAL-499.
+	Additional computationally mapped references.

Web resources

Wikipedia

Hexokinase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U51333 mRNA. Translation: AAC50732.1.
CH471195 Genomic DNA. Translation: EAW85048.1.
BC028129 mRNA. Translation: AAH28129.1.
U42303 mRNA. Translation: AAC50422.1.

IPI

IPI00005118.

RefSeq

NP_002106.2. NM_002115.2.

UniGene

Hs.411695.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3HM8	X-ray	2.80	A/B/C/D	480-922	[»]

ProteinModelPortal

P52790.

ModBase

Search...

Protein-protein interaction databases

IntAct

P52790. 3 interactions.

STRING

9606.ENSP00000292432.

PTM databases

PhosphoSite

P52790.

Polymorphism databases

DMDM

206729871.

Proteomic databases

PaxDb

P52790.

PRIDE

P52790.

Protocols and materials databases

DNASU

3101.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000292432; ENSP00000292432; ENSG00000160883.

GeneID

3101.

KEGG

hsa:3101.

UCSC

uc003mez.3. human.

Organism-specific databases

CTD

3101.

GeneCards

GC05M176240.

HGNC

HGNC:4925. HK3.

MIM

142570. gene.

neXtProt

NX_P52790.

PharmGKB

PA29303.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5026.

HOGENOM

HOG000162671.

HOVERGEN

HBG005020.

InParanoid

P52790.

KO

K00844.

OMA

PHGTEQG.

OrthoDB

EOG4R23T4.

PhylomeDB

P52790.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.

SABIO-RK

P52790.

UniPathway

UPA00242.

Gene expression databases

ArrayExpress

P52790.

Bgee

P52790.

CleanEx

HS_HK3.

Genevestigator

P52790.

GermOnline

ENSG00000160883. Homo sapiens.

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

PRINTS

PR00475. HEXOKINASE.

PROSITE

PS00378. HEXOKINASES. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P52790.

ChEMBL

CHEMBL2709.

EvolutionaryTrace

P52790.

GenomeRNAi

3101.

NextBio

12311.

SOURCE

Search...

Entry information

Entry name

HXK3_HUMAN

Accession

Primary (citable) accession number: P52790
Secondary accession number(s): Q8N1E7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	September 23, 2008
Last modified:	May 1, 2013
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.