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Database: UniProt/SWISS-PROT
Entry: HXK2_RAT
LinkDB: HXK2_RAT
Original site: HXK2_RAT 
ID   HXK2_RAT                Reviewed;         917 AA.
AC   P27881; Q9QWR1;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   23-MAY-2018, entry version 145.
DE   RecName: Full=Hexokinase-2;
DE            EC=2.7.1.1;
DE   AltName: Full=Hexokinase type II;
DE            Short=HK II;
GN   Name=Hk2;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 11-18.
RC   TISSUE=Skeletal muscle;
RX   PubMed=1897984; DOI=10.1016/0003-9861(91)90094-Y;
RA   Thelen A.P., Wilson J.E.;
RT   "Complete amino acid sequence of the type II isozyme of rat
RT   hexokinase, deduced from the cloned cDNA: comparison with a hexokinase
RT   from novikoff ascites tumor.";
RL   Arch. Biochem. Biophys. 286:645-651(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RC   STRAIN=Wistar;
RX   PubMed=7873617; DOI=10.1016/0167-4781(94)00226-S;
RA   Shinohara Y., Ichihara J., Kogure K., Terada H.;
RT   "Nucleotide sequence of the 5'-flanking region of the rat type II
RT   hexokinase gene.";
RL   Biochim. Biophys. Acta 1260:365-368(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RC   STRAIN=Sprague-Dawley; TISSUE=Hepatoma;
RX   PubMed=7622509; DOI=10.1074/jbc.270.28.16918;
RA   Mathupala S.P., Rempel A., Pedersen P.L.;
RT   "Glucose catabolism in cancer cells. Isolation, sequence, and activity
RT   of the promoter for type II hexokinase.";
RL   J. Biol. Chem. 270:16918-16925(1995).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-21.
RC   STRAIN=Sprague-Dawley;
RA   Rempel A.;
RT   "Normal type II hexokinase promoter, first exon, and first intron from
RT   hepatocytes.";
RL   Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
CC   -!- CATALYTIC ACTIVITY: ATP + D-hexose = ADP + D-hexose 6-phosphate.
CC   -!- ENZYME REGULATION: Hexokinase is an allosteric enzyme inhibited by
CC       its product Glc-6-P.
CC   -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC   -!- SUBUNIT: Monomer. Interacts with TIGAR; the interaction increases
CC       hexokinase HK2 activity in a hypoxia- and HIF1A-dependent manner.
CC       {ECO:0000250|UniProtKB:P35557, ECO:0000250|UniProtKB:P52789}.
CC   -!- DOMAIN: The N- and C-terminal halves of this hexokinase show
CC       extensive sequence similarity to each other. The catalytic
CC       activity is associated with the C-terminus while regulatory
CC       function is associated with the N-terminus.
CC   -!- MISCELLANEOUS: In vertebrates there are four major glucose-
CC       phosphorylating isoenzymes, designated hexokinase I, II, III and
CC       IV (glucokinase).
CC   -!- SIMILARITY: Belongs to the hexokinase family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01084, ECO:0000305}.
DR   EMBL; M68971; AAA41333.1; -; mRNA.
DR   EMBL; M68972; AAA41334.1; -; mRNA.
DR   EMBL; D26393; BAA05409.1; -; Genomic_DNA.
DR   EMBL; U19605; AAB09025.1; -; Genomic_DNA.
DR   EMBL; AY082375; AAL92551.1; -; Genomic_DNA.
DR   PIR; S15885; S15885.
DR   RefSeq; NP_036867.1; NM_012735.2.
DR   UniGene; Rn.91375; -.
DR   ProteinModelPortal; P27881; -.
DR   SMR; P27881; -.
DR   BioGrid; 247136; 3.
DR   DIP; DIP-37314N; -.
DR   IntAct; P27881; 3.
DR   STRING; 10116.ENSRNOP00000008813; -.
DR   BindingDB; P27881; -.
DR   ChEMBL; CHEMBL5063; -.
DR   iPTMnet; P27881; -.
DR   PhosphoSitePlus; P27881; -.
DR   PaxDb; P27881; -.
DR   PRIDE; P27881; -.
DR   Ensembl; ENSRNOT00000008813; ENSRNOP00000008813; ENSRNOG00000006116.
DR   GeneID; 25059; -.
DR   KEGG; rno:25059; -.
DR   UCSC; RGD:2797; rat.
DR   CTD; 3099; -.
DR   RGD; 2797; Hk2.
DR   eggNOG; KOG1369; Eukaryota.
DR   eggNOG; COG5026; LUCA.
DR   GeneTree; ENSGT00390000017159; -.
DR   HOGENOM; HOG000162671; -.
DR   HOVERGEN; HBG005020; -.
DR   InParanoid; P27881; -.
DR   KO; K00844; -.
DR   OMA; HAIAPVK; -.
DR   OrthoDB; EOG091G08MD; -.
DR   PhylomeDB; P27881; -.
DR   TreeFam; TF314238; -.
DR   BRENDA; 2.7.1.1; 5301.
DR   Reactome; R-RNO-70171; Glycolysis.
DR   SABIO-RK; P27881; -.
DR   UniPathway; UPA00242; -.
DR   PRO; PR:P27881; -.
DR   Proteomes; UP000002494; Chromosome 4.
DR   Bgee; ENSRNOG00000006116; -.
DR   Genevisible; P27881; RN.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005741; C:mitochondrial outer membrane; TAS:RGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR   GO; GO:0005524; F:ATP binding; IDA:RGD.
DR   GO; GO:0008865; F:fructokinase activity; IBA:GO_Central.
DR   GO; GO:0004340; F:glucokinase activity; IBA:GO_Central.
DR   GO; GO:0005536; F:glucose binding; IDA:RGD.
DR   GO; GO:0004396; F:hexokinase activity; IDA:RGD.
DR   GO; GO:0019158; F:mannokinase activity; IBA:GO_Central.
DR   GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl.
DR   GO; GO:0046835; P:carbohydrate phosphorylation; IDA:RGD.
DR   GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR   GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR   GO; GO:0072655; P:establishment of protein localization to mitochondrion; IEA:Ensembl.
DR   GO; GO:0006007; P:glucose catabolic process; TAS:RGD.
DR   GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR   GO; GO:0007595; P:lactation; IEP:RGD.
DR   GO; GO:0072656; P:maintenance of protein location in mitochondrion; IEA:Ensembl.
DR   GO; GO:0035795; P:negative regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR   GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IEA:Ensembl.
DR   GO; GO:0046324; P:regulation of glucose import; IEA:Ensembl.
DR   GO; GO:0002931; P:response to ischemia; IDA:RGD.
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   PROSITE; PS00378; HEXOKINASE_1; 2.
DR   PROSITE; PS51748; HEXOKINASE_2; 2.
PE   1: Evidence at protein level;
KW   Acetylation; Allosteric enzyme; ATP-binding; Complete proteome;
KW   Direct protein sequencing; Glycolysis; Kinase; Nucleotide-binding;
KW   Reference proteome; Repeat; Transferase.
FT   CHAIN         1    917       Hexokinase-2.
FT                                /FTId=PRO_0000197589.
FT   DOMAIN       16    458       Hexokinase 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01084}.
FT   DOMAIN      464    906       Hexokinase 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01084}.
FT   NP_BIND      84     89       ATP 1. {ECO:0000255}.
FT   NP_BIND     425    426       ATP 1. {ECO:0000250}.
FT   NP_BIND     532    537       ATP 2. {ECO:0000250}.
FT   NP_BIND     747    748       ATP 2. {ECO:0000250}.
FT   NP_BIND     784    788       ATP 2. {ECO:0000250}.
FT   NP_BIND     863    867       ATP 2. {ECO:0000250}.
FT   REGION        1     12       Hydrophobic.
FT   REGION       13    475       Regulatory.
FT   REGION       73    207       Hexokinase small subdomain 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION       84     88       Glucose-6-phosphate 1 binding.
FT                                {ECO:0000250}.
FT   REGION      155    156       Substrate 1 binding. {ECO:0000250}.
FT   REGION      172    173       Substrate 1 binding. {ECO:0000250}.
FT   REGION      208    447       Hexokinase large subdomain 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      208    209       Substrate 1 binding. {ECO:0000250}.
FT   REGION      291    294       Substrate 1 binding. {ECO:0000250}.
FT   REGION      413    415       Glucose-6-phosphate 1 binding.
FT                                {ECO:0000250}.
FT   REGION      476    917       Catalytic.
FT   REGION      521    655       Hexokinase small subdomain 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      532    536       Glucose-6-phosphate 2 binding.
FT                                {ECO:0000250}.
FT   REGION      603    604       Substrate 2 binding. {ECO:0000250}.
FT   REGION      620    621       Substrate 2 binding. {ECO:0000250}.
FT   REGION      656    895       Hexokinase large subdomain 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      656    657       Substrate 2 binding. {ECO:0000250}.
FT   REGION      739    742       Substrate 2 binding. {ECO:0000250}.
FT   REGION      861    863       Glucose-6-phosphate 2 binding.
FT                                {ECO:0000250}.
FT   BINDING      30     30       ATP 1. {ECO:0000250}.
FT   BINDING     209    209       Glucose-6-phosphate 1. {ECO:0000250}.
FT   BINDING     232    232       Glucose-6-phosphate 1. {ECO:0000250}.
FT   BINDING     235    235       Substrate 1. {ECO:0000250}.
FT   BINDING     260    260       Substrate 1. {ECO:0000250}.
FT   BINDING     449    449       Glucose-6-phosphate 1. {ECO:0000250}.
FT   BINDING     558    558       ATP 2. {ECO:0000255}.
FT   BINDING     657    657       Glucose-6-phosphate 2. {ECO:0000250}.
FT   BINDING     680    680       ATP 2. {ECO:0000250}.
FT   BINDING     680    680       Glucose-6-phosphate 2. {ECO:0000250}.
FT   BINDING     683    683       Substrate 2. {ECO:0000250}.
FT   BINDING     708    708       Substrate 2. {ECO:0000250}.
FT   BINDING     897    897       Glucose-6-phosphate 2. {ECO:0000250}.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000250|UniProtKB:P52789}.
SQ   SEQUENCE   917 AA;  102544 MW;  764EC189C0F90987 CRC64;
     MIASHMIACL FTELNQNQVQ KVDQFLYHMR LSDETLLEIS RRFRKEMEKG LGATTHPTAA
     VKMLPTFVRS TPDGTEHGEF LALDLGGTNF RVLRVRVTDN GLQRVEMENQ IYAIPEDIMR
     GSGTQLFDHI AECLANFMDK LQIKEKKLPL GFTFSFPCHQ TKLDESFLVS WTKGFKSSGV
     EGRDVVDLIR KAIQRRGDFD IDIVAVVNDT VGTMMTCGYD DQNCEIGLIV GTGSNACYME
     EMRHIDMVEG DEGRMCINME WGAFGDDGTL NDIRTEFDRE IDMGSLNPGK QLFEKMISGM
     YMGELVRLIL VKMAKAELLF QGKLSPELLT TGSFETKDVS DIEEDKDGIE KAYQILMRLG
     LNPLQEDCVA THRICQIVST RSASLCAATL AAVLWRIKEN KGEERLRSTI GVDGSVYKKH
     PHFAKRLHKA VRRLVPDCDV RFLRSEDGSG KGAAMVTAVA YRLADQHRAR QKTLESLKLS
     HEQLLEVKRR MKVEMEQGLS KETHAVAPVK MLPTYVCATP DGTEKGDFLA LDLGGTNFRV
     LLVRVRNGKR RGVEMHNKIY SIPQEVMHGT GEELFDHIVQ CIADFLEYMG MKGVSLPLGF
     TFSFPCQQNS LDQSILLKWT KGFKASGCEG EDVVTLLKEA IHRREEFDLD VVAVVNDTVG
     TMMTCGYEDP HCEVGLIVGT GSNACYMEEM RNVELVDGEE GRMCVNMEWG AFGDNGCLDD
     LRTVFDVAVD ELSLNPGKQR FEKMISGMYL GEIVRNILID FTKRGLLFRG RISERLKTRG
     IFETKFLSQI ESDCLALLQV RAILRHLGLE STCDDSIIVK EVCTVVARRA AQLCGAGMAA
     VVDKIRENRG LDNLKVTVGV DGTLYKLHPH FAKVMHETVR DLAPKCDVSF LESEDGSGKG
     AALITAVACR IREAGQR
//
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