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Protein

Hexokinase-1

Gene

Hk1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

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

Enzyme 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 sitei86ATP 1By similarity1
Binding sitei211Substrate 1By similarity1
Binding sitei265Glucose-6-phosphate 1By similarity1
Binding sitei288Glucose-6-phosphate 1By similarity1
Binding sitei291Substrate 1By similarity1
Binding sitei316Substrate 1By similarity1
Binding sitei505Glucose-6-phosphate 1By similarity1
Binding sitei659Glucose-6-phosphate 2By similarity1
Binding sitei713Glucose-6-phosphate 2By similarity1
Binding sitei736ATP 2By similarity1
Binding sitei736Glucose-6-phosphate 2By similarity1
Binding sitei739Substrate 2By similarity1
Binding sitei764Substrate 2By similarity1
Binding sitei798Substrate 2By similarity1
Binding sitei953Glucose-6-phosphate 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi140 – 145ATP 1Sequence analysis6
Nucleotide bindingi481 – 482ATP 1By similarity2
Nucleotide bindingi588 – 593ATP 2By similarity6
Nucleotide bindingi803 – 804ATP 2By similarity2
Nucleotide bindingi840 – 844ATP 2By similarity5
Nucleotide bindingi919 – 923ATP 2By similarity5

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • fructokinase activity Source: GO_Central
  • glucokinase activity Source: MGI
  • glucose binding Source: InterPro
  • hexokinase activity Source: MGI
  • mannokinase activity Source: GO_Central

GO - Biological processi

  • canonical glycolysis Source: MGI
  • cellular glucose homeostasis Source: GO_Central
  • establishment of protein localization to mitochondrion Source: MGI
  • glycolytic process Source: MGI
  • maintenance of protein location in mitochondrion Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-70153. Glucose transport.
R-MMU-70171. Glycolysis.
SABIO-RKP17710.
UniPathwayiUPA00242.

Names & Taxonomyi

Protein namesi
Recommended name:
Hexokinase-1 (EC:2.7.1.1)
Alternative name(s):
Hexokinase type I
Short name:
HK I
Hexokinase, tumor isozyme
Gene namesi
Name:Hk1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96103. Hk1.

Subcellular locationi

Isoform HK1-SC :

GO - Cellular componenti

  • cilium Source: MGI
  • cytosol Source: MGI
  • membrane raft Source: MGI
  • mitochondrial outer membrane Source: UniProtKB-SubCell
  • mitochondrion Source: MGI
  • sperm principal piece Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67P → A: Disrupts targeting to membrane; when associated with N-68; Q-70; P-73; A-74 and Q-75. 1 Publication1
Mutagenesisi68K → N: Disrupts targeting to membrane; when associated with A-67; Q-70; P-73; A-74 and Q-75. 1 Publication1
Mutagenesisi70R → Q: Disrupts targeting to membrane; when associated with A-67; N-68; P-73; A-74 and Q-75. 1 Publication1
Mutagenesisi73L → P: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; A-74 and Q-75. 1 Publication1
Mutagenesisi74T → A: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and Q-75. 1 Publication1
Mutagenesisi75E → Q: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and A-74. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000133991 – 974Hexokinase-1Add BLAST974

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei393PhosphoserineBy similarity1

Post-translational modificationi

Isoform HK1-SC is tyrosine-phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP17710.
PaxDbiP17710.
PeptideAtlasiP17710.
PRIDEiP17710.

PTM databases

iPTMnetiP17710.
PhosphoSitePlusiP17710.
SwissPalmiP17710.

Expressioni

Tissue specificityi

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).1 Publication

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiENSMUSG00000037012.
CleanExiMM_HK1.
ExpressionAtlasiP17710. baseline and differential.
GenevisibleiP17710. MM.

Interactioni

Subunit structurei

Monomer. Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2. Interacts (via N-terminal spermatogenic cell-specific region) with PFKM isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946).By similarity2 Publications

Protein-protein interaction databases

BioGridi200315. 2 interactors.
IntActiP17710. 7 interactors.
MINTiMINT-1847872.
STRINGi10090.ENSMUSP00000072195.

Structurei

3D structure databases

ProteinModelPortaliP17710.
SMRiP17710.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 514Hexokinase 1PROSITE-ProRule annotationAdd BLAST443
Domaini520 – 962Hexokinase 2PROSITE-ProRule annotationAdd BLAST443

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 52HydrophobicAdd BLAST52
Regioni53 – 531RegulatoryAdd BLAST479
Regioni129 – 263Hexokinase small subdomain 1PROSITE-ProRule annotationAdd BLAST135
Regioni140 – 144Glucose-6-phosphate 1 bindingBy similarity5
Regioni228 – 229Substrate 1 bindingBy similarity2
Regioni264 – 503Hexokinase large subdomain 1PROSITE-ProRule annotationAdd BLAST240
Regioni264 – 265Substrate 1 bindingBy similarity2
Regioni347 – 350Substrate 1 bindingBy similarity4
Regioni469 – 471Glucose-6-phosphate 1 bindingBy similarity3
Regioni532 – 974CatalyticAdd BLAST443
Regioni577 – 711Hexokinase small subdomain 2PROSITE-ProRule annotationAdd BLAST135
Regioni588 – 592Glucose-6-phosphate 2 bindingBy similarity5
Regioni659 – 660Substrate 2 bindingBy similarity2
Regioni676 – 677Substrate 2 bindingBy similarity2
Regioni712 – 951Hexokinase large subdomain 2PROSITE-ProRule annotationAdd BLAST240
Regioni712 – 713Substrate 2 bindingBy similarity2
Regioni917 – 919Glucose-6-phosphate 2 bindingBy similarity3

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 (By similarity).By similarity

Sequence similaritiesi

Belongs to the hexokinase family.PROSITE-ProRule annotationCurated
Contains 2 hexokinase domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162671.
HOVERGENiHBG005020.
InParanoidiP17710.
OMAiHMESEIY.
OrthoDBiEOG091G08MD.
TreeFamiTF314238.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 2 hits.
PS51748. HEXOKINASE_2. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform HK1-SA (identifier: P17710-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGWGAPLLSR MLHGPGQAGE TSPVPERQSG SENPASEDRR PLEKQCSHHL
60 70 80 90 100
YTMGQNCQRG QAVDVEPKIR PPLTEEKIDK YLYAMRLSDE ILIDILTRFK
110 120 130 140 150
KEMKNGLSRD YNPTASVKML PTFVRSIPDG SEKGDFIALD LGGSSFRILR
160 170 180 190 200
VQVNHEKSQN VSMESEVYDT PENIVHGSGS QLFDHVAECL GDFMEKRKIK
210 220 230 240 250
DKKLPVGFTF SFPCRQSKID EAVLITWTKR FKASGVEGAD VVKLLNKAIK
260 270 280 290 300
KRGDYDANIV AVVNDTVGTM MTCGYDDQQC EVGLIIGTGT NACYMEELRH
310 320 330 340 350
IDLVEGDEGR MCINTEWGAF GDDGSLEDIR TEFDRELDRG SLNPGKQLFE
360 370 380 390 400
KMVSGMYMGE LVRLILVKMA KESLLFEGRI TPELLTRGKF TTSDVAAIET
410 420 430 440 450
DKEGVQNAKE ILTRLGVEPS HDDCVSVQHV CTIVSFRSAN LVAATLGAIL
460 470 480 490 500
NRLRDNKGTP RLRTTVGVDG SLYKMHPQYS RRFHKTLRRL VPDSDVRFLL
510 520 530 540 550
SESGSGKGAA MVTAVAYRLA EQHRQIEETL SHFRLSKQAL MEVKKKLRSE
560 570 580 590 600
MEMGLRKETN SRATVKMLPS YVRSIPDGTE HGDFLALDLG GTNFRVLLVK
610 620 630 640 650
IRSGKKRTVE MHNKIYSIPL EIMQGTGDEL FDHIVSCISD FLDYMGIKGP
660 670 680 690 700
RMPLGFTFSF PCKQTSLDCG ILITWTKGFK ATDCVGHDVA TLLRDAVKRR
710 720 730 740 750
EEFDLDVVAV VNDTVGTMMT CAYEEPSCEI GLIVGTGSNA CYMEEMKNVE
760 770 780 790 800
MVEGNQGQMC INMEWGAFGD NGCLDDIRTD FDKVVDEYSL NSGKQRFEKM
810 820 830 840 850
ISGMYLGEIV RNILIDFTKK GFLFRGQISE PLKTRGIFET KFLSQIESDR
860 870 880 890 900
LALLQVRAIL QQLGLNSTCD DSILVKTVCG VVSKRAAQLC GAGMAAVVEK
910 920 930 940 950
IRENRGLDHL NVTVGVDGTL YKLHPHFSRI MHQTVKELSP KCTVSFLLSE
960 970
DGSGKGAALI TAVGVRLRGD PTNA
Length:974
Mass (Da):108,303
Last modified:July 27, 2011 - v3
Checksum:i6122505622F7BA3D
GO
Isoform HK1-SB (identifier: P17710-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:945
Mass (Da):105,575
Checksum:i770DED5C144B9DE7
GO
Isoform HK1 (identifier: P17710-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: MGWGAPLLSR...PKIRPPLTEE → MIAAQLLAYYFTELKDDQVK

Show »
Length:918
Mass (Da):102,302
Checksum:i4F0E6923F1EEC9B5
GO
Isoform HK1-SC (identifier: P17710-4) [UniParc]FASTAAdd to basket

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.
Show »
Length:922
Mass (Da):102,637
Checksum:i4449779BF37D6EB7
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti870D → S in AAA37804 (PubMed:2318862).Curated1
Sequence conflicti899E → Q in AAB57759 (PubMed:8396993).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0073271 – 76MGWGA…PLTEE → MIAAQLLAYYFTELKDDQVK in isoform HK1. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_0187471 – 52Missing in isoform HK1-SB and isoform HK1-SC. 1 PublicationAdd BLAST52
Alternative sequenceiVSP_007328400T → TGWELSPDRRWYQAYMRCTQ DTHR in isoform HK1-SB. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS48577.1. [P17710-3]
CCDS48578.1. [P17710-2]
PIRiA35244.
I49744.
RefSeqiXP_006513305.1. XM_006513242.1. [P17710-1]
XP_006513306.1. XM_006513243.3. [P17710-4]
XP_006513307.1. XM_006513244.3. [P17710-4]
XP_006513308.1. XM_006513245.3. [P17710-4]
UniGeneiMm.196605.

Genome annotation databases

EnsembliENSMUST00000072357; ENSMUSP00000072195; ENSMUSG00000037012. [P17710-2]
ENSMUST00000099691; ENSMUSP00000097282; ENSMUSG00000037012. [P17710-3]
ENSMUST00000116238; ENSMUSP00000111946; ENSMUSG00000037012. [P17710-2]
GeneIDi15275.
UCSCiuc007fgz.2. mouse. [P17710-2]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS48577.1. [P17710-3]
CCDS48578.1. [P17710-2]
PIRiA35244.
I49744.
RefSeqiXP_006513305.1. XM_006513242.1. [P17710-1]
XP_006513306.1. XM_006513243.3. [P17710-4]
XP_006513307.1. XM_006513244.3. [P17710-4]
XP_006513308.1. XM_006513245.3. [P17710-4]
UniGeneiMm.196605.

3D structure databases

ProteinModelPortaliP17710.
SMRiP17710.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200315. 2 interactors.
IntActiP17710. 7 interactors.
MINTiMINT-1847872.
STRINGi10090.ENSMUSP00000072195.

PTM databases

iPTMnetiP17710.
PhosphoSitePlusiP17710.
SwissPalmiP17710.

Proteomic databases

MaxQBiP17710.
PaxDbiP17710.
PeptideAtlasiP17710.
PRIDEiP17710.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000072357; ENSMUSP00000072195; ENSMUSG00000037012. [P17710-2]
ENSMUST00000099691; ENSMUSP00000097282; ENSMUSG00000037012. [P17710-3]
ENSMUST00000116238; ENSMUSP00000111946; ENSMUSG00000037012. [P17710-2]
GeneIDi15275.
UCSCiuc007fgz.2. mouse. [P17710-2]

Organism-specific databases

CTDi3098.
MGIiMGI:96103. Hk1.

Phylogenomic databases

eggNOGiKOG1369. Eukaryota.
COG5026. LUCA.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162671.
HOVERGENiHBG005020.
InParanoidiP17710.
OMAiHMESEIY.
OrthoDBiEOG091G08MD.
TreeFamiTF314238.

Enzyme and pathway databases

UniPathwayiUPA00242.
ReactomeiR-MMU-70153. Glucose transport.
R-MMU-70171. Glycolysis.
SABIO-RKP17710.

Miscellaneous databases

PROiP17710.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000037012.
CleanExiMM_HK1.
ExpressionAtlasiP17710. baseline and differential.
GenevisibleiP17710. MM.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR019807. Hexokinase_BS.
IPR022673. Hexokinase_C.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PROSITEiPS00378. HEXOKINASE_1. 2 hits.
PS51748. HEXOKINASE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHXK1_MOUSE
AccessioniPrimary (citable) accession number: P17710
Secondary accession number(s): E9PXQ3
, Q61659, Q64476, Q64479
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 169 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

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

Keywords - Technical termi

Allosteric enzyme, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.