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P17710

- HXK1_MOUSE

UniProt

P17710 - HXK1_MOUSE

Protein

Hexokinase-1

Gene

Hk1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 3 (27 Jul 2011)
      Previous versions | rss
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    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 1By similarity
    Binding sitei211 – 2111Substrate 1By similarity
    Binding sitei265 – 2651Glucose-6-phosphate 1By similarity
    Binding sitei288 – 2881Glucose-6-phosphate 1By similarity
    Binding sitei291 – 2911Substrate 1By similarity
    Binding sitei316 – 3161Substrate 1By similarity
    Binding sitei505 – 5051Glucose-6-phosphate 1By similarity
    Binding sitei659 – 6591Glucose-6-phosphate 2By similarity
    Binding sitei713 – 7131Glucose-6-phosphate 2By similarity
    Binding sitei736 – 7361ATP 2By similarity
    Binding sitei736 – 7361Glucose-6-phosphate 2By similarity
    Binding sitei739 – 7391Substrate 2By similarity
    Binding sitei764 – 7641Substrate 2By similarity
    Binding sitei798 – 7981Substrate 2By similarity
    Binding sitei953 – 9531Glucose-6-phosphate 2By similarity

    Regions

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

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

    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

    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.By similarity1 Publication

    Protein-protein interaction databases

    IntActiP17710. 6 interactions.
    MINTiMINT-1847872.

    Structurei

    3D structure databases

    ProteinModelPortaliP17710.
    SMRiP17710. Positions 76-967.
    ModBaseiSearch...
    MobiDBiSearch...

    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 bindingBy similarity
    Regioni228 – 2292Substrate 1 bindingBy similarity
    Regioni264 – 2652Substrate 1 bindingBy similarity
    Regioni347 – 3504Substrate 1 bindingBy similarity
    Regioni469 – 4713Glucose-6-phosphate 1 bindingBy similarity
    Regioni532 – 974443CatalyticAdd
    BLAST
    Regioni588 – 5925Glucose-6-phosphate 2 bindingBy similarity
    Regioni659 – 6602Substrate 2 bindingBy similarity
    Regioni676 – 6772Substrate 2 bindingBy similarity
    Regioni712 – 7132Substrate 2 bindingBy similarity
    Regioni917 – 9193Glucose-6-phosphate 2 bindingBy 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.By similarity

    Sequence similaritiesi

    Belongs to the hexokinase family.Curated
    Contains 2 hexokinase type-1 domains.Curated
    Contains 2 hexokinase type-2 domains.Curated

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti870 – 8701D → S in AAA37804. (PubMed:2318862)Curated
    Sequence conflicti899 – 8991E → Q in AAB57759. (PubMed:8396993)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 7676MGWGA…PLTEE → MIAAQLLAYYFTELKDDQVK in isoform HK1. 1 PublicationVSP_007327Add
    BLAST
    Alternative sequencei1 – 5252Missing in isoform HK1-SB and isoform HK1-SC. 1 PublicationVSP_018747Add
    BLAST
    Alternative sequencei400 – 4001T → TGWELSPDRRWYQAYMRCTQ DTHR in isoform HK1-SB. 1 PublicationVSP_007328

    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

    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: October 1, 2014
    This is version 148 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