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P17710

- HXK1_MOUSE

UniProt

P17710 - HXK1_MOUSE

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Protein

Hexokinase-1

Gene
Hk1
Organism
Mus musculus (Mouse)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei86 – 861ATP 1 By similarity
Binding sitei211 – 2111Substrate 1 By similarity
Binding sitei265 – 2651Glucose-6-phosphate 1 By similarity
Binding sitei288 – 2881Glucose-6-phosphate 1 By similarity
Binding sitei291 – 2911Substrate 1 By similarity
Binding sitei316 – 3161Substrate 1 By similarity
Binding sitei505 – 5051Glucose-6-phosphate 1 By similarity
Binding sitei659 – 6591Glucose-6-phosphate 2 By similarity
Binding sitei713 – 7131Glucose-6-phosphate 2 By similarity
Binding sitei736 – 7361ATP 2 By similarity
Binding sitei736 – 7361Glucose-6-phosphate 2 By similarity
Binding sitei739 – 7391Substrate 2 By similarity
Binding sitei764 – 7641Substrate 2 By similarity
Binding sitei798 – 7981Substrate 2 By similarity
Binding sitei953 – 9531Glucose-6-phosphate 2 By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi140 – 1456ATP 1 Reviewed prediction
Nucleotide bindingi481 – 4822ATP 1 By similarity
Nucleotide bindingi588 – 5936ATP 2 By similarity
Nucleotide bindingi803 – 8042ATP 2 By similarity
Nucleotide bindingi840 – 8445ATP 2 By similarity
Nucleotide bindingi919 – 9235ATP 2 By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. fructokinase activity Source: RefGenome
  3. glucokinase activity Source: MGI
  4. hexokinase activity Source: MGI
  5. mannokinase activity Source: RefGenome
  6. protein binding Source: MGI

GO - Biological processi

  1. canonical glycolysis Source: MGI
  2. carbohydrate phosphorylation Source: GOC
  3. cellular glucose homeostasis Source: RefGenome
  4. glucose 6-phosphate metabolic process Source: GOC
  5. glycolytic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Glycolysis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

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
ProteomesiUP000000589: Chromosome 10

Organism-specific databases

MGIiMGI:96103. Hk1.

Subcellular locationi

Isoform HK1 : Mitochondrion outer membrane; Peripheral membrane protein 1 Publication
Isoform HK1-SC : Membrane
Note: Isoform HK1-SC is an integral membrane protein.1 Publication

GO - Cellular componenti

  1. cilium Source: MGI
  2. cytosol Source: MGI
  3. membrane raft Source: MGI
  4. mitochondrial outer membrane Source: UniProtKB-SubCell
  5. mitochondrion Source: MGI
  6. nucleus Source: Ensembl
  7. sperm principal piece Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion outer membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi67 – 671P → A: Disrupts targeting to membrane; when associated with N-68; Q-70; P-73; A-74 and Q-75. 1 Publication
Mutagenesisi68 – 681K → N: Disrupts targeting to membrane; when associated with A-67; Q-70; P-73; A-74 and Q-75. 1 Publication
Mutagenesisi70 – 701R → Q: Disrupts targeting to membrane; when associated with A-67; N-68; P-73; A-74 and Q-75. 1 Publication
Mutagenesisi73 – 731L → P: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; A-74 and Q-75. 1 Publication
Mutagenesisi74 – 741T → A: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and Q-75. 1 Publication
Mutagenesisi75 – 751E → Q: Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and A-74. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 974974Hexokinase-1PRO_0000013399Add
BLAST

Post-translational modificationi

Isoform HK1-SC is tyrosine-phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP17710.
PaxDbiP17710.
PRIDEiP17710.

PTM databases

PhosphoSiteiP17710.

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

ArrayExpressiP17710.
BgeeiP17710.
CleanExiMM_HK1.
GenevestigatoriP17710.

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 RABL2.1 Publication

Protein-protein interaction databases

IntActiP17710. 6 interactions.
MINTiMINT-1847872.

Structurei

3D structure databases

ProteinModelPortaliP17710.
SMRiP17710. Positions 76-967.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 277203Hexokinase type-1 1Add
BLAST
Domaini279 – 518240Hexokinase type-2 1Add
BLAST
Domaini521 – 724204Hexokinase type-1 2Add
BLAST
Domaini728 – 965238Hexokinase type-2 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5252HydrophobicAdd
BLAST
Regioni53 – 531479RegulatoryAdd
BLAST
Regioni140 – 1445Glucose-6-phosphate 1 binding By similarity
Regioni228 – 2292Substrate 1 binding By similarity
Regioni264 – 2652Substrate 1 binding By similarity
Regioni347 – 3504Substrate 1 binding By similarity
Regioni469 – 4713Glucose-6-phosphate 1 binding By similarity
Regioni532 – 974443CatalyticAdd
BLAST
Regioni588 – 5925Glucose-6-phosphate 2 binding By similarity
Regioni659 – 6602Substrate 2 binding By similarity
Regioni676 – 6772Substrate 2 binding By similarity
Regioni712 – 7132Substrate 2 binding By similarity
Regioni917 – 9193Glucose-6-phosphate 2 binding By similarity

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.

Sequence similaritiesi

Belongs to the hexokinase family.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiCOG5026.
GeneTreeiENSGT00390000017159.
HOGENOMiHOG000162671.
HOVERGENiHBG005020.
InParanoidiP17710.
KOiK00844.
OMAiKFKASGV.
OrthoDBiEOG7S21X5.
TreeFamiTF314238.

Family and domain databases

InterProiIPR001312. Hexokinase.
IPR022673. Hexokinase_C.
IPR019807. Hexokinase_CS.
IPR022672. Hexokinase_N.
[Graphical view]
PANTHERiPTHR19443. PTHR19443. 1 hit.
PfamiPF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view]
PRINTSiPR00475. HEXOKINASE.
PROSITEiPS00378. HEXOKINASES. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. Align

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

MGWGAPLLSR MLHGPGQAGE TSPVPERQSG SENPASEDRR PLEKQCSHHL    50
YTMGQNCQRG QAVDVEPKIR PPLTEEKIDK YLYAMRLSDE ILIDILTRFK 100
KEMKNGLSRD YNPTASVKML PTFVRSIPDG SEKGDFIALD LGGSSFRILR 150
VQVNHEKSQN VSMESEVYDT PENIVHGSGS QLFDHVAECL GDFMEKRKIK 200
DKKLPVGFTF SFPCRQSKID EAVLITWTKR FKASGVEGAD VVKLLNKAIK 250
KRGDYDANIV AVVNDTVGTM MTCGYDDQQC EVGLIIGTGT NACYMEELRH 300
IDLVEGDEGR MCINTEWGAF GDDGSLEDIR TEFDRELDRG SLNPGKQLFE 350
KMVSGMYMGE LVRLILVKMA KESLLFEGRI TPELLTRGKF TTSDVAAIET 400
DKEGVQNAKE ILTRLGVEPS HDDCVSVQHV CTIVSFRSAN LVAATLGAIL 450
NRLRDNKGTP RLRTTVGVDG SLYKMHPQYS RRFHKTLRRL VPDSDVRFLL 500
SESGSGKGAA MVTAVAYRLA EQHRQIEETL SHFRLSKQAL MEVKKKLRSE 550
MEMGLRKETN SRATVKMLPS YVRSIPDGTE HGDFLALDLG GTNFRVLLVK 600
IRSGKKRTVE MHNKIYSIPL EIMQGTGDEL FDHIVSCISD FLDYMGIKGP 650
RMPLGFTFSF PCKQTSLDCG ILITWTKGFK ATDCVGHDVA TLLRDAVKRR 700
EEFDLDVVAV VNDTVGTMMT CAYEEPSCEI GLIVGTGSNA CYMEEMKNVE 750
MVEGNQGQMC INMEWGAFGD NGCLDDIRTD FDKVVDEYSL NSGKQRFEKM 800
ISGMYLGEIV RNILIDFTKK GFLFRGQISE PLKTRGIFET KFLSQIESDR 850
LALLQVRAIL QQLGLNSTCD DSILVKTVCG VVSKRAAQLC GAGMAAVVEK 900
IRENRGLDHL NVTVGVDGTL YKLHPHFSRI MHQTVKELSP KCTVSFLLSE 950
DGSGKGAALI TAVGVRLRGD PTNA 974
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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7676MGWGA…PLTEE → MIAAQLLAYYFTELKDDQVK in isoform HK1. VSP_007327Add
BLAST
Alternative sequencei1 – 5252Missing in isoform HK1-SB and isoform HK1-SC. VSP_018747Add
BLAST
Alternative sequencei400 – 4001T → TGWELSPDRRWYQAYMRCTQ DTHR in isoform HK1-SB. VSP_007328

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti870 – 8701D → S in AAA37804. 1 Publication
Sequence conflicti899 – 8991E → Q in AAB57759. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006513243.1. [P17710-4]
XP_006513307.1. XM_006513244.1. [P17710-4]
XP_006513308.1. XM_006513245.1. [P17710-4]
UniGeneiMm.196605.

Genome annotation databases

EnsembliENSMUST00000072357; ENSMUSP00000072195; ENSMUSG00000037012. [P17710-2]
ENSMUST00000099691; ENSMUSP00000097282; ENSMUSG00000037012. [P17710-3]
ENSMUST00000116238; ENSMUSP00000111946; ENSMUSG00000037012. [P17710-2]
GeneIDi15275.
KEGGimmu:15275.
UCSCiuc007fgz.2. mouse. [P17710-2]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS48577.1. [P17710-3 ]
CCDS48578.1. [P17710-2 ]
PIRi A35244.
I49744.
RefSeqi XP_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 ]
UniGenei Mm.196605.

3D structure databases

ProteinModelPortali P17710.
SMRi P17710. Positions 76-967.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi P17710. 6 interactions.
MINTi MINT-1847872.

PTM databases

PhosphoSitei P17710.

Proteomic databases

MaxQBi P17710.
PaxDbi P17710.
PRIDEi P17710.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000072357 ; ENSMUSP00000072195 ; ENSMUSG00000037012 . [P17710-2 ]
ENSMUST00000099691 ; ENSMUSP00000097282 ; ENSMUSG00000037012 . [P17710-3 ]
ENSMUST00000116238 ; ENSMUSP00000111946 ; ENSMUSG00000037012 . [P17710-2 ]
GeneIDi 15275.
KEGGi mmu:15275.
UCSCi uc007fgz.2. mouse. [P17710-2 ]

Organism-specific databases

CTDi 3098.
MGIi MGI:96103. Hk1.

Phylogenomic databases

eggNOGi COG5026.
GeneTreei ENSGT00390000017159.
HOGENOMi HOG000162671.
HOVERGENi HBG005020.
InParanoidi P17710.
KOi K00844.
OMAi KFKASGV.
OrthoDBi EOG7S21X5.
TreeFami TF314238.

Enzyme and pathway databases

UniPathwayi UPA00242 .
SABIO-RK P17710.

Miscellaneous databases

PROi P17710.
SOURCEi Search...

Gene expression databases

ArrayExpressi P17710.
Bgeei P17710.
CleanExi MM_HK1.
Genevestigatori P17710.

Family and domain databases

InterProi IPR001312. Hexokinase.
IPR022673. Hexokinase_C.
IPR019807. Hexokinase_CS.
IPR022672. Hexokinase_N.
[Graphical view ]
PANTHERi PTHR19443. PTHR19443. 1 hit.
Pfami PF00349. Hexokinase_1. 2 hits.
PF03727. Hexokinase_2. 2 hits.
[Graphical view ]
PRINTSi PR00475. HEXOKINASE.
PROSITEi PS00378. HEXOKINASES. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. Lubec G., Kang S.U.
    Submitted (APR-2007) to UniProtKB
    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.

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: September 3, 2014
This is version 147 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

External Data

Dasty 3

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