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P17710 (HXK1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hexokinase-1

EC=2.7.1.1
Alternative name(s):
Hexokinase type I
Short name=HK I
Hexokinase, tumor isozyme
Gene names
Name:Hk1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length974 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. Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 By similarity. Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Ref.7

Subcellular location

Isoform HK1: Mitochondrion outer membrane; Peripheral membrane protein Ref.5.

Isoform HK1-SC: Membrane. Note: Isoform HK1-SC is an integral membrane protein. Ref.5

Tissue specificity

In rapidly growing tumor cells exhibiting high glucose catabolic rates, isoform HK1 is markedly elevated. Isoform HK1-SA, isoform HK1-SB and isoform HK1-SC are found only in spermatogenic cells. Isoform HK1-SC is detected in round spermatids, condensing spermatids and mature sperm where it is found in the head membranes, mitochondria of the midpiece and the fibrous sheath of the flagellum. Expressed within the principal piece and midpiece of sperm tail (at protein level). Ref.7

Developmental stage

Isoform HK1-SA is first expressed during meiosis and continues to be present in postmeiotic germ cells while isoform HK1-SB is present only in postmeiotic germ cells. Ref.2 Ref.5

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 By similarity.

Post-translational modification

Isoform HK1-SC is tyrosine-phosphorylated. Ref.5

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 diversityAlternative initiation
Alternative splicing
   DomainRepeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Transferase
   PTMPhosphoprotein
   Technical termAllosteric enzyme
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate phosphorylation

Inferred from direct assay PubMed 15155459PubMed 18165236. Source: GOC

cellular glucose homeostasis

Inferred from Biological aspect of Ancestor. Source: RefGenome

glucose 6-phosphate metabolic process

Inferred from direct assay PubMed 18509164. Source: GOC

glycolytic process

Traceable author statement PubMed 12420306. Source: MGI

hexose metabolic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

   Cellular_componentcilium

Inferred from direct assay PubMed 16687649. Source: MGI

cytosol

Inferred from direct assay PubMed 12420306. Source: MGI

membrane raft

Inferred from direct assay PubMed 19144954. Source: MGI

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from direct assay PubMed 12420306PubMed 14651853PubMed 17069463PubMed 18614015. Source: MGI

nucleus

Inferred from electronic annotation. Source: Ensembl

sperm principal piece

Inferred from direct assay PubMed 19889946. 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 direct assay PubMed 18509164. Source: MGI

hexokinase activity

Inferred from direct assay PubMed 15155459PubMed 18165236. Source: MGI

mannokinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 19889946Ref.7. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]
Isoform HK1-SA (identifier: P17710-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform HK1-SB (identifier: P17710-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
     400-400: T → TGWELSPDRRWYQAYMRCTQDTHR
Note: Produced by alternative splicing and alternative initiation at Met-53 of isoform HK1-SA.
Isoform HK1 (identifier: P17710-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: MGWGAPLLSR...PKIRPPLTEE → MIAAQLLAYYFTELKDDQVK
Isoform HK1-SC (identifier: P17710-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: Missing.
Note: Produced by alternative initiation at Met-53 of isoform HK1-SA.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 974974Hexokinase-1
PRO_0000013399

Regions

Domain75 – 277203Hexokinase type-1 1
Domain279 – 518240Hexokinase type-2 1
Domain521 – 724204Hexokinase type-1 2
Domain728 – 965238Hexokinase type-2 2
Nucleotide binding140 – 1456ATP 1 Potential
Nucleotide binding481 – 4822ATP 1 By similarity
Nucleotide binding588 – 5936ATP 2 By similarity
Nucleotide binding803 – 8042ATP 2 By similarity
Nucleotide binding840 – 8445ATP 2 By similarity
Nucleotide binding919 – 9235ATP 2 By similarity
Region1 – 5252Hydrophobic
Region53 – 531479Regulatory
Region140 – 1445Glucose-6-phosphate 1 binding By similarity
Region228 – 2292Substrate 1 binding By similarity
Region264 – 2652Substrate 1 binding By similarity
Region347 – 3504Substrate 1 binding By similarity
Region469 – 4713Glucose-6-phosphate 1 binding By similarity
Region532 – 974443Catalytic
Region588 – 5925Glucose-6-phosphate 2 binding By similarity
Region659 – 6602Substrate 2 binding By similarity
Region676 – 6772Substrate 2 binding By similarity
Region712 – 7132Substrate 2 binding By similarity
Region917 – 9193Glucose-6-phosphate 2 binding By similarity

Sites

Binding site861ATP 1 By similarity
Binding site2111Substrate 1 By similarity
Binding site2651Glucose-6-phosphate 1 By similarity
Binding site2881Glucose-6-phosphate 1 By similarity
Binding site2911Substrate 1 By similarity
Binding site3161Substrate 1 By similarity
Binding site5051Glucose-6-phosphate 1 By similarity
Binding site6591Glucose-6-phosphate 2 By similarity
Binding site7131Glucose-6-phosphate 2 By similarity
Binding site7361ATP 2 By similarity
Binding site7361Glucose-6-phosphate 2 By similarity
Binding site7391Substrate 2 By similarity
Binding site7641Substrate 2 By similarity
Binding site7981Substrate 2 By similarity
Binding site9531Glucose-6-phosphate 2 By similarity

Natural variations

Alternative sequence1 – 7676MGWGA…PLTEE → MIAAQLLAYYFTELKDDQVK in isoform HK1.
VSP_007327
Alternative sequence1 – 5252Missing in isoform HK1-SB and isoform HK1-SC.
VSP_018747
Alternative sequence4001T → TGWELSPDRRWYQAYMRCTQ DTHR in isoform HK1-SB.
VSP_007328

Experimental info

Mutagenesis671P → A: Disrupts targeting to membrane; when associated with N-68; Q-70; P-73; A-74 and Q-75. Ref.6
Mutagenesis681K → N: Disrupts targeting to membrane; when associated with A-67; Q-70; P-73; A-74 and Q-75. Ref.6
Mutagenesis701R → Q: Disrupts targeting to membrane; when associated with A-67; N-68; P-73; A-74 and Q-75. Ref.6
Mutagenesis731L → P: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; A-74 and Q-75. Ref.6
Mutagenesis741T → A: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and Q-75. Ref.6
Mutagenesis751E → Q: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and A-74. Ref.6
Sequence conflict8701D → S in AAA37804. Ref.1
Sequence conflict8991E → Q in AAB57759. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform HK1-SA [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 6122505622F7BA3D

FASTA974108,303
        10         20         30         40         50         60 
MGWGAPLLSR MLHGPGQAGE TSPVPERQSG SENPASEDRR PLEKQCSHHL YTMGQNCQRG 

        70         80         90        100        110        120 
QAVDVEPKIR PPLTEEKIDK YLYAMRLSDE ILIDILTRFK KEMKNGLSRD YNPTASVKML 

       130        140        150        160        170        180 
PTFVRSIPDG SEKGDFIALD LGGSSFRILR VQVNHEKSQN VSMESEVYDT PENIVHGSGS 

       190        200        210        220        230        240 
QLFDHVAECL GDFMEKRKIK DKKLPVGFTF SFPCRQSKID EAVLITWTKR FKASGVEGAD 

       250        260        270        280        290        300 
VVKLLNKAIK KRGDYDANIV AVVNDTVGTM MTCGYDDQQC EVGLIIGTGT NACYMEELRH 

       310        320        330        340        350        360 
IDLVEGDEGR MCINTEWGAF GDDGSLEDIR TEFDRELDRG SLNPGKQLFE KMVSGMYMGE 

       370        380        390        400        410        420 
LVRLILVKMA KESLLFEGRI TPELLTRGKF TTSDVAAIET DKEGVQNAKE ILTRLGVEPS 

       430        440        450        460        470        480 
HDDCVSVQHV CTIVSFRSAN LVAATLGAIL NRLRDNKGTP RLRTTVGVDG SLYKMHPQYS 

       490        500        510        520        530        540 
RRFHKTLRRL VPDSDVRFLL SESGSGKGAA MVTAVAYRLA EQHRQIEETL SHFRLSKQAL 

       550        560        570        580        590        600 
MEVKKKLRSE MEMGLRKETN SRATVKMLPS YVRSIPDGTE HGDFLALDLG GTNFRVLLVK 

       610        620        630        640        650        660 
IRSGKKRTVE MHNKIYSIPL EIMQGTGDEL FDHIVSCISD FLDYMGIKGP RMPLGFTFSF 

       670        680        690        700        710        720 
PCKQTSLDCG ILITWTKGFK ATDCVGHDVA TLLRDAVKRR EEFDLDVVAV VNDTVGTMMT 

       730        740        750        760        770        780 
CAYEEPSCEI GLIVGTGSNA CYMEEMKNVE MVEGNQGQMC INMEWGAFGD NGCLDDIRTD 

       790        800        810        820        830        840 
FDKVVDEYSL NSGKQRFEKM ISGMYLGEIV RNILIDFTKK GFLFRGQISE PLKTRGIFET 

       850        860        870        880        890        900 
KFLSQIESDR LALLQVRAIL QQLGLNSTCD DSILVKTVCG VVSKRAAQLC GAGMAAVVEK 

       910        920        930        940        950        960 
IRENRGLDHL NVTVGVDGTL YKLHPHFSRI MHQTVKELSP KCTVSFLLSE DGSGKGAALI 

       970 
TAVGVRLRGD PTNA 

« Hide

Isoform HK1-SB [UniParc].

Checksum: 770DED5C144B9DE7
Show »

FASTA945105,575
Isoform HK1 [UniParc].

Checksum: 4F0E6923F1EEC9B5
Show »

FASTA918102,302
Isoform HK1-SC [UniParc].

Checksum: 4449779BF37D6EB7
Show »

FASTA922102,637

References

« Hide 'large scale' references
[1]"Glucose phosphorylation in tumor cells. Cloning, sequencing, and overexpression in active form of a full-length cDNA encoding a mitochondrial bindable form of hexokinase."
Arora K.K., Fanciulli M., Pedersen P.L.
J. Biol. Chem. 265:6481-6488(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM HK1).
[2]"Unique hexokinase messenger ribonucleic acids lacking the porin-binding domain are developmentally expressed in mouse spermatogenic cells."
Mori C., Welch J.E., Fulcher K.D., O'Brien D.A., Eddy E.M.
Biol. Reprod. 49:191-203(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS HK1-SA; HK1-SB AND HK1-SC), DEVELOPMENTAL STAGE.
Strain: CD-1.
Tissue: Testis.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[4]Lubec G., Kang S.U.
Submitted (APR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 81-98; 110-118; 134-147; 203-215; 219-229; 233-243; 300-310; 352-363; 372-409; 415-437; 438-452; 464-474; 489-518; 538-544; 549-595; 652-663; 681-694; 784-794; 800-819; 826-833; 842-884; 906-922 AND 942-974.
Strain: C57BL/6.
Tissue: Brain.
[5]"Targeting of a germ cell-specific type 1 hexokinase lacking a porin-binding domain to the mitochondria as well as to the head and fibrous sheath of murine spermatozoa."
Travis A.J., Foster J.A., Rosenbaum N.A., Visconti P.E., Gerton G.L., Kopf G.S., Moss S.B.
Mol. Biol. Cell 9:263-276(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, PHOSPHORYLATION.
[6]"A novel NH(2)-terminal, nonhydrophobic motif targets a male germ cell-specific hexokinase to the endoplasmic reticulum and plasma membrane."
Travis A.J., Sui D., Riedel K.D., Hofmann N.R., Moss S.B., Wilson J.E., Kopf G.S.
J. Biol. Chem. 274:34467-34475(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-67; LYS-68; ARG-70; LEU-73; THR-74 AND GLU-75.
[7]"RAB-like 2 has an essential role in male fertility, sperm intra-flagellar transport, and tail assembly."
Lo J.C., Jamsai D., O'Connor A.E., Borg C., Clark B.J., Whisstock J.C., Field M.C., Adams V., Ishikawa T., Aitken R.J., Whittle B., Goodnow C.C., Ormandy C.J., O'Bryan M.K.
PLoS Genet. 8:E1002969-E1002969(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RABL2, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J05277 mRNA. Translation: AAA37804.1.
L16948 mRNA. Translation: AAB57760.1.
L16949 mRNA. Translation: AAB57759.1.
L16950 mRNA. Translation: AAA53036.1.
AC126428 Genomic DNA. No translation available.
AC145297 Genomic DNA. No translation available.
CCDSCCDS48577.1. [P17710-3]
CCDS48578.1. [P17710-2]
PIRA35244.
I49744.
RefSeqXP_006513305.1. XM_006513242.1. [P17710-1]
XP_006513306.1. XM_006513243.1. [P17710-4]
XP_006513307.1. XM_006513244.1. [P17710-4]
XP_006513308.1. XM_006513245.1. [P17710-4]
UniGeneMm.196605.

3D structure databases

ProteinModelPortalP17710.
SMRP17710. Positions 76-967.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP17710. 6 interactions.
MINTMINT-1847872.

PTM databases

PhosphoSiteP17710.

Proteomic databases

MaxQBP17710.
PaxDbP17710.
PRIDEP17710.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000072357; ENSMUSP00000072195; ENSMUSG00000037012. [P17710-2]
ENSMUST00000099691; ENSMUSP00000097282; ENSMUSG00000037012. [P17710-3]
ENSMUST00000116238; ENSMUSP00000111946; ENSMUSG00000037012. [P17710-2]
GeneID15275.
KEGGmmu:15275.
UCSCuc007fgz.2. mouse. [P17710-2]

Organism-specific databases

CTD3098.
MGIMGI:96103. Hk1.

Phylogenomic databases

eggNOGCOG5026.
GeneTreeENSGT00390000017159.
HOGENOMHOG000162671.
HOVERGENHBG005020.
InParanoidP17710.
KOK00844.
OMAKFKASGV.
OrthoDBEOG7S21X5.
TreeFamTF314238.

Enzyme and pathway databases

SABIO-RKP17710.
UniPathwayUPA00242.

Gene expression databases

ArrayExpressP17710.
BgeeP17710.
CleanExMM_HK1.
GenevestigatorP17710.

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

PROP17710.
SOURCESearch...

Entry information

Entry nameHXK1_MOUSE
AccessionPrimary (citable) accession number: P17710
Secondary accession number(s): E9PXQ3 expand/collapse secondary AC list , Q61659, Q64476, Q64479
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot