HXK3_MOUSE
ID HXK3_MOUSE Reviewed; 922 AA.
AC Q3TRM8; Q3TAX6; Q3UDP1; Q3UEA4;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Hexokinase-3 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000250|UniProtKB:P27926};
DE AltName: Full=Hexokinase type III {ECO:0000250|UniProtKB:P27926};
DE Short=HK III {ECO:0000250|UniProtKB:P27926};
DE AltName: Full=Hexokinase-C {ECO:0000250|UniProtKB:P27926};
GN Name=Hk3 {ECO:0000312|MGI:MGI:2670962};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone, and Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the phosphorylation of hexose, such as D-glucose
CC and D-fructose, to hexose 6-phosphate (D-glucose 6-phosphate and D-
CC fructose 6-phosphate, respectively). Mediates the initial step of
CC glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-
CC phosphate. {ECO:0000250|UniProtKB:P27926}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-hexose = ADP + D-hexose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:22740, ChEBI:CHEBI:4194, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61567, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-fructose = ADP + D-fructose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:16125, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:37721, ChEBI:CHEBI:61527, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-glucose = ADP + D-glucose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:17825, ChEBI:CHEBI:4167, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61548, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000250|UniProtKB:P27926};
CC -!- ACTIVITY REGULATION: Hexokinase is an allosteric enzyme inhibited by
CC its product D-glucose 6-phosphate. {ECO:0000250|UniProtKB:P52790}.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000250|UniProtKB:P27926}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000250|UniProtKB:P27926}.
CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase contain a
CC hexokinase domain. The catalytic activity is associated with the C-
CC terminus while regulatory function is associated with the N-terminus.
CC {ECO:0000250|UniProtKB:P19367}.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
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DR EMBL; AK149651; BAE29007.1; -; mRNA.
DR EMBL; AK149992; BAE29220.1; -; mRNA.
DR EMBL; AK154603; BAE32706.1; -; mRNA.
DR EMBL; AK162637; BAE37000.1; -; mRNA.
DR EMBL; AK171580; BAE42538.1; -; mRNA.
DR CCDS; CCDS26538.1; -.
DR RefSeq; NP_001028417.1; NM_001033245.4.
DR RefSeq; NP_001193319.1; NM_001206390.1.
DR AlphaFoldDB; Q3TRM8; -.
DR SMR; Q3TRM8; -.
DR BioGRID; 229281; 1.
DR STRING; 10090.ENSMUSP00000051215; -.
DR iPTMnet; Q3TRM8; -.
DR PhosphoSitePlus; Q3TRM8; -.
DR SwissPalm; Q3TRM8; -.
DR MaxQB; Q3TRM8; -.
DR PaxDb; Q3TRM8; -.
DR PRIDE; Q3TRM8; -.
DR ProteomicsDB; 273332; -.
DR Antibodypedia; 29158; 457 antibodies from 35 providers.
DR DNASU; 212032; -.
DR Ensembl; ENSMUST00000052949; ENSMUSP00000051215; ENSMUSG00000025877.
DR Ensembl; ENSMUST00000126234; ENSMUSP00000123233; ENSMUSG00000025877.
DR GeneID; 212032; -.
DR KEGG; mmu:212032; -.
DR UCSC; uc007qpr.2; mouse.
DR CTD; 3101; -.
DR MGI; MGI:2670962; Hk3.
DR VEuPathDB; HostDB:ENSMUSG00000025877; -.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR InParanoid; Q3TRM8; -.
DR OMA; VRPCEVG; -.
DR OrthoDB; 1153545at2759; -.
DR PhylomeDB; Q3TRM8; -.
DR TreeFam; TF314238; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-70171; Glycolysis.
DR SABIO-RK; Q3TRM8; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR BioGRID-ORCS; 212032; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q3TRM8; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q3TRM8; protein.
DR Bgee; ENSMUSG00000025877; Expressed in granulocyte and 84 other tissues.
DR ExpressionAtlas; Q3TRM8; baseline and differential.
DR Genevisible; Q3TRM8; MM.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0008865; F:fructokinase activity; ISS:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; ISS:UniProtKB.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0004396; F:hexokinase activity; ISO:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; ISS:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; ISO:MGI.
DR InterPro; IPR043129; ATPase_NBD.
DR InterPro; IPR001312; Hexokinase.
DR InterPro; IPR019807; Hexokinase_BS.
DR InterPro; IPR022673; Hexokinase_C.
DR InterPro; IPR022672; Hexokinase_N.
DR PANTHER; PTHR19443; PTHR19443; 4.
DR Pfam; PF00349; Hexokinase_1; 2.
DR Pfam; PF03727; Hexokinase_2; 2.
DR SUPFAM; SSF53067; SSF53067; 4.
DR PROSITE; PS00378; HEXOKINASE_1; 2.
DR PROSITE; PS51748; HEXOKINASE_2; 2.
PE 1: Evidence at protein level;
KW Allosteric enzyme; ATP-binding; Glycolysis; Kinase; Nucleotide-binding;
KW Reference proteome; Repeat; Transferase.
FT CHAIN 1..922
FT /note="Hexokinase-3"
FT /id="PRO_0000197591"
FT DOMAIN 25..469
FT /note="Hexokinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT DOMAIN 475..911
FT /note="Hexokinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..218
FT /note="Hexokinase small subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 219..458
FT /note="Hexokinase large subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 529..660
FT /note="Hexokinase small subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 661..900
FT /note="Hexokinase large subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 93..102
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 93..100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 166
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 183..184
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 219..220
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 220
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 243
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 246
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 271
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 302..305
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 424..426
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 436..437
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 540..545
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 540..544
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 608..609
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 625..626
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 661..662
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 662
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 685
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 685
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 687..688
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 713
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 747
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P52790"
FT BINDING 752..753
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 789..793
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 866..868
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 868..872
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 902
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT CONFLICT 203
FT /note="A -> S (in Ref. 1; BAE37000)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="Y -> C (in Ref. 1; BAE29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="K -> E (in Ref. 1; BAE29220)"
FT /evidence="ECO:0000305"
FT CONFLICT 442
FT /note="V -> I (in Ref. 1; BAE29007)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="G -> E (in Ref. 1; BAE29007)"
FT /evidence="ECO:0000305"
FT CONFLICT 860
FT /note="T -> A (in Ref. 1; BAE29007)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 922 AA; 100101 MW; 38F4E024630C45E5 CRC64;
MATIGPSGLH PGERASVCPH EGVPRPSGSL ELECLQQFKV TRTQLQQIQA SLLCSMEQAL
KGQDSPAPSV RMLPTYVRST PHGTEQGDFL VLELGATGAS LRVLWVTLTG TKECRVEPRS
REFVIPQEVI LGAGQQLFDF AARCLSEFLD AYPVENQGLK LGFNFSFPCH QTGLDRSTLI
SWTKGFRCSG VEGQDVVQLL RDAIQRQGTY RIDVVAMVND TVGTMMGCEL GTRPCEVGLI
VDTGTNACYM EEARHVAALD EDRGRTCVSI EWGSFYDEDA LGPVLTTFDS ALDRESLTPG
AQRFEKMIGG LYLGELVRLV LVHLTQHGVL FDGCASPALL SQGCILLDHV AEMEDTATGT
ARVHTILQDL GLSPRASDAE LVQYVCVAVC TRAAQLCAAA LAAVLSRLQH SREQQTLQVA
VATGGRVFER HPRFLRILKE TVTLLAPNCD VSFIPSVDGG GRGVAMVTAV AARLAAHRRI
LEETLAPFQL TLEQMTVVQA QMREAMIRGL QGEASSLRML PTYVRATPDG SERGDFLALD
LGGTNFRVLL VRVAEGSVQI INQVYSIPEC RAQGSGQKLF DHIVDCIVDF QKRQGLSGQS
LPLGFTFSFP CKQLGLDQGI LLNWTKGFNA SGCEGQDVVY LLREAIRRRQ AVELNVVAIV
NDTVGTMMSC GYDDPRCEMG LIVGTGTNAC YMEELRNVAS VPGDSGLMCI NMEWGAFGDD
GSLGTLSTRF DTSVDQASIN PGKQRFEKMI SGMYLGEIVR HILLHLTNLG VLFRGQKTQC
LQARDIFKTK FLSEIESDSL ALRQVRAILE DLGLTLTSDD ALMVLEVCQA VSRRAAQLCG
AGVAAVVEKI RENRGLQELT VSVGVDGTLY KLHPHFSKLV SATVRKLAPQ CTVTFLQSED
GSGKGAALVT AVACRLTQMA HV
