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Protein

Hexokinase-1

Gene

Hk1

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

Functioni

Miscellaneous

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

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
  • peptidoglycan binding Source: CAFA

GO - Biological processi

  • canonical glycolysis Source: MGI
  • carbohydrate phosphorylation Source: CAFA
  • 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
  • positive regulation of cytokine secretion involved in immune response Source: CAFA
  • positive regulation of interleukin-1 beta secretion Source: CAFA

Keywordsi

Molecular functionAllosteric enzyme, Kinase, Transferase
Biological processGlycolysis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-70171 Glycolysis
SABIO-RKP17710
UniPathwayiUPA00242

Protein family/group databases

MoonProtiP17710

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:96103 Hk1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
MINTiP17710
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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1369 Eukaryota
COG5026 LUCA
GeneTreeiENSGT00390000017159
HOGENOMiHOG000162671
HOVERGENiHBG005020
InParanoidiP17710
OMAiYDDQQCE
OrthoDBiEOG091G08MD
TreeFamiTF314238

Family and domain databases

InterProiView protein in InterPro
IPR001312 Hexokinase
IPR019807 Hexokinase_BS
IPR022673 Hexokinase_C
IPR022672 Hexokinase_N
PANTHERiPTHR19443 PTHR19443, 4 hits
PfamiView protein in Pfam
PF00349 Hexokinase_1, 2 hits
PF03727 Hexokinase_2, 2 hits
PROSITEiView protein in PROSITE
PS00378 HEXOKINASE_1, 2 hits
PS51748 HEXOKINASE_2, 2 hits

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

Similar proteinsi

Entry informationi

Entry nameiHXK1_MOUSE
AccessioniPrimary (citable) accession number: P17710
Secondary accession number(s): E9PXQ3
, Q61659, Q64476, Q64479
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: July 27, 2011
Last modified: April 25, 2018
This is version 178 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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