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Database: UniProt/SWISS-PROT
Entry: HXK1_RAT
LinkDB: HXK1_RAT
Original site: HXK1_RAT 
ID   HXK1_RAT                Reviewed;         918 AA.
AC   P05708;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 4.
DT   05-DEC-2018, entry version 163.
DE   RecName: Full=Hexokinase-1;
DE            EC=2.7.1.1;
DE   AltName: Full=Brain form hexokinase;
DE   AltName: Full=Hexokinase type I;
DE            Short=HK I;
GN   Name=Hk1;
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] OF 1-466.
RC   TISSUE=Brain;
RX   PubMed=2704734; DOI=10.1073/pnas.86.8.2563;
RA   Schwab D.A., Wilson J.E.;
RT   "Complete amino acid sequence of rat brain hexokinase, deduced from
RT   the cloned cDNA, and proposed structure of a mammalian hexokinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:2563-2567(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE OF 467-918.
RC   TISSUE=Brain;
RX   PubMed=3277968;
RA   Schwab D.A., Wilson J.E.;
RT   "The complete amino acid sequence of the catalytic domain of rat brain
RT   hexokinase, deduced from the cloned cDNA.";
RL   J. Biol. Chem. 263:3220-3224(1988).
RN   [3]
RP   SEQUENCE REVISION.
RA   Wilson J.E.;
RL   Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   PROTEIN SEQUENCE OF 597-617; 625-636 AND 802-816.
RC   TISSUE=Brain;
RX   PubMed=3631958; DOI=10.1016/0003-9861(87)90536-4;
RA   Schirch D.M., Wilson J.E.;
RT   "Rat brain hexokinase: amino acid sequence at the substrate hexose
RT   binding site is homologous to that of yeast hexokinase.";
RL   Arch. Biochem. Biophys. 257:1-12(1987).
RN   [5]
RP   NUCLEOTIDE SEQUENCE OF 1-21.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RA   White J.A., Liu W., Wilson J.E.;
RL   Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE OF 221-246 AND 631-668.
RA   White J.A., Wilson J.E.;
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   SUBSTRATE-BINDING SITE.
RX   PubMed=3579310; DOI=10.1016/0003-9861(87)90116-0;
RA   Schirch D.M., Wilson J.E.;
RT   "Rat brain hexokinase: location of the substrate hexose binding site
RT   in a structural domain at the C-terminus of the enzyme.";
RL   Arch. Biochem. Biophys. 254:385-396(1987).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND TISSUE SPECIFICITY.
RX   PubMed=19423663; DOI=10.1530/REP-09-0052;
RA   Khan S.A., Suryawanshi A.R., Ranpura S.A., Jadhav S.V., Khole V.V.;
RT   "Identification of novel immunodominant epididymal sperm proteins
RT   using combinatorial approach.";
RL   Reproduction 138:81-93(2009).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-337, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH GLUCOSE AND
RP   GLUCOSE-6-PHOSPHATE.
RX   PubMed=9665168; DOI=10.1038/811;
RA   Mulichak A.M., Wilson J.E., Padmanabhan K., Garavito R.M.;
RT   "The structure of mammalian hexokinase-1.";
RL   Nat. Struct. Biol. 5:555-560(1998).
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;
CC         EC=2.7.1.1;
CC   -!- ACTIVITY REGULATION: Hexokinase is an allosteric enzyme inhibited
CC       by its product Glc-6-P.
CC   -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC   -!- SUBUNIT: Monomer. Interacts with VDAC1. The HK1-VDAC1 complex
CC       interacts with ATF2 (By similarity). Interacts with RABL2/RABL2A;
CC       binds preferentially to GTP-bound RABL2 (By similarity). Interacts
CC       (via N-terminal spermatogenic cell-specific region) with PFKM (via
CC       C-terminus) (By similarity). {ECO:0000250,
CC       ECO:0000250|UniProtKB:P17710}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane. Note=Its
CC       hydrophobic N-terminal sequence may be involved in membrane
CC       binding.
CC   -!- TISSUE SPECIFICITY: Expressed in flagella of epididymal sperm.
CC       {ECO:0000269|PubMed:19423663}.
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. Each domain can bind a
CC       single glucose and Gluc-6-P molecule.
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; J04526; AAC20075.1; -; mRNA.
DR   EMBL; U27319; AAC52945.1; -; Genomic_DNA.
DR   EMBL; U89160; AAB71376.1; -; Genomic_DNA.
DR   EMBL; U89158; AAB71374.1; -; Genomic_DNA.
DR   PIR; A32521; A32521.
DR   PIR; B32521; B32521.
DR   PIR; C32521; C32521.
DR   PIR; C59226; C59226.
DR   RefSeq; NP_036866.1; NM_012734.1.
DR   UniGene; Rn.11017; -.
DR   PDB; 1BG3; X-ray; 2.80 A; A/B=1-918.
DR   PDBsum; 1BG3; -.
DR   ProteinModelPortal; P05708; -.
DR   SMR; P05708; -.
DR   BioGrid; 247135; 3.
DR   IntAct; P05708; 1.
DR   MINT; P05708; -.
DR   STRING; 10116.ENSRNOP00000066611; -.
DR   ChEMBL; CHEMBL4783; -.
DR   iPTMnet; P05708; -.
DR   PhosphoSitePlus; P05708; -.
DR   World-2DPAGE; 0004:P05708; -.
DR   PaxDb; P05708; -.
DR   PRIDE; P05708; -.
DR   GeneID; 25058; -.
DR   KEGG; rno:25058; -.
DR   CTD; 3098; -.
DR   RGD; 2796; Hk1.
DR   HOVERGEN; HBG005020; -.
DR   InParanoid; P05708; -.
DR   KO; K00844; -.
DR   PhylomeDB; P05708; -.
DR   BRENDA; 2.7.1.1; 5301.
DR   SABIO-RK; P05708; -.
DR   UniPathway; UPA00242; -.
DR   EvolutionaryTrace; P05708; -.
DR   PRO; PR:P05708; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005901; C:caveola; IDA:RGD.
DR   GO; GO:0005829; C:cytosol; IDA:RGD.
DR   GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IDA:CACAO.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0005524; F:ATP binding; IDA:RGD.
DR   GO; GO:0016887; F:ATPase activity; IC:RGD.
DR   GO; GO:0008865; F:fructokinase activity; IBA:GO_Central.
DR   GO; GO:0004340; F:glucokinase activity; IDA:RGD.
DR   GO; GO:0005536; F:glucose binding; IDA:RGD.
DR   GO; GO:0004396; F:hexokinase activity; IDA:CACAO.
DR   GO; GO:0019158; F:mannokinase activity; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:RGD.
DR   GO; GO:0004672; F:protein kinase activity; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0046835; P:carbohydrate phosphorylation; IDA:RGD.
DR   GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR   GO; GO:0006096; P:glycolytic process; IDA:RGD.
DR   GO; GO:0019318; P:hexose metabolic process; IEA:UniProtKB-UniPathway.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:RGD.
DR   GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:RGD.
DR   GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:RGD.
DR   GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR   GO; GO:0010359; P:regulation of anion channel activity; IDA:RGD.
DR   GO; GO:0009741; P:response to brassinosteroid; IEP:RGD.
DR   GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR   GO; GO:0002931; P:response to ischemia; IDA:RGD.
DR   GO; GO:1901986; P:response to ketamine; IEP: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   3D-structure; Acetylation; Allosteric enzyme; ATP-binding;
KW   Complete proteome; Direct protein sequencing; Glycolysis; Kinase;
KW   Membrane; Mitochondrion; Mitochondrion outer membrane;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW   Transferase.
FT   CHAIN         1    918       Hexokinase-1.
FT                                /FTId=PRO_0000197586.
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   REGION      172    173       Substrate 1 binding.
FT   REGION      208    447       Hexokinase large subdomain 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      208    209       Substrate 1 binding.
FT   REGION      291    294       Substrate 1 binding.
FT   REGION      413    415       Glucose-6-phosphate 1 binding.
FT   REGION      476    918       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   REGION      620    621       Substrate 2 binding.
FT   REGION      656    895       Hexokinase large subdomain 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      656    657       Substrate 2 binding.
FT   REGION      861    863       Glucose-6-phosphate 2 binding.
FT   BINDING      30     30       ATP 1. {ECO:0000250}.
FT   BINDING     155    155       Substrate 1.
FT   BINDING     209    209       Glucose-6-phosphate 1.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     232    232       Glucose-6-phosphate 1.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     235    235       Substrate 1.
FT   BINDING     260    260       Substrate 1.
FT   BINDING     449    449       Glucose-6-phosphate 1.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     603    603       Glucose-6-phosphate 2.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     657    657       Glucose-6-phosphate 2.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     680    680       ATP 2. {ECO:0000250}.
FT   BINDING     680    680       Glucose-6-phosphate 2.
FT                                {ECO:0000269|PubMed:9665168}.
FT   BINDING     683    683       Substrate 2.
FT   BINDING     708    708       Substrate 2.
FT   BINDING     742    742       Substrate 2.
FT   BINDING     897    897       Glucose-6-phosphate 2.
FT                                {ECO:0000269|PubMed:9665168}.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000250|UniProtKB:P19367}.
FT   MOD_RES     337    337       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   HELIX         2     25       {ECO:0000244|PDB:1BG3}.
FT   HELIX        27     29       {ECO:0000244|PDB:1BG3}.
FT   HELIX        33     51       {ECO:0000244|PDB:1BG3}.
FT   TURN         53     55       {ECO:0000244|PDB:1BG3}.
FT   HELIX        56     58       {ECO:0000244|PDB:1BG3}.
FT   STRAND       78     97       {ECO:0000244|PDB:1BG3}.
FT   STRAND      106    108       {ECO:0000244|PDB:1BG3}.
FT   HELIX       123    140       {ECO:0000244|PDB:1BG3}.
FT   STRAND      144    146       {ECO:0000244|PDB:1BG3}.
FT   STRAND      149    154       {ECO:0000244|PDB:1BG3}.
FT   HELIX       185    196       {ECO:0000244|PDB:1BG3}.
FT   STRAND      202    207       {ECO:0000244|PDB:1BG3}.
FT   HELIX       209    220       {ECO:0000244|PDB:1BG3}.
FT   STRAND      224    241       {ECO:0000244|PDB:1BG3}.
FT   HELIX       242    244       {ECO:0000244|PDB:1BG3}.
FT   STRAND      252    258       {ECO:0000244|PDB:1BG3}.
FT   HELIX       261    263       {ECO:0000244|PDB:1BG3}.
FT   TURN        264    273       {ECO:0000244|PDB:1BG3}.
FT   HELIX       276    283       {ECO:0000244|PDB:1BG3}.
FT   STRAND      285    287       {ECO:0000244|PDB:1BG3}.
FT   HELIX       294    297       {ECO:0000244|PDB:1BG3}.
FT   TURN        299    301       {ECO:0000244|PDB:1BG3}.
FT   HELIX       302    315       {ECO:0000244|PDB:1BG3}.
FT   HELIX       320    322       {ECO:0000244|PDB:1BG3}.
FT   HELIX       326    329       {ECO:0000244|PDB:1BG3}.
FT   HELIX       336    342       {ECO:0000244|PDB:1BG3}.
FT   TURN        345    347       {ECO:0000244|PDB:1BG3}.
FT   HELIX       348    358       {ECO:0000244|PDB:1BG3}.
FT   HELIX       365    401       {ECO:0000244|PDB:1BG3}.
FT   STRAND      404    406       {ECO:0000244|PDB:1BG3}.
FT   STRAND      409    413       {ECO:0000244|PDB:1BG3}.
FT   HELIX       415    419       {ECO:0000244|PDB:1BG3}.
FT   HELIX       423    434       {ECO:0000244|PDB:1BG3}.
FT   STRAND      441    444       {ECO:0000244|PDB:1BG3}.
FT   HELIX       450    474       {ECO:0000244|PDB:1BG3}.
FT   HELIX       475    477       {ECO:0000244|PDB:1BG3}.
FT   HELIX       481    499       {ECO:0000244|PDB:1BG3}.
FT   TURN        501    503       {ECO:0000244|PDB:1BG3}.
FT   HELIX       504    506       {ECO:0000244|PDB:1BG3}.
FT   STRAND      511    513       {ECO:0000244|PDB:1BG3}.
FT   STRAND      526    537       {ECO:0000244|PDB:1BG3}.
FT   STRAND      539    545       {ECO:0000244|PDB:1BG3}.
FT   STRAND      548    550       {ECO:0000244|PDB:1BG3}.
FT   STRAND      553    559       {ECO:0000244|PDB:1BG3}.
FT   HELIX       564    567       {ECO:0000244|PDB:1BG3}.
FT   HELIX       571    589       {ECO:0000244|PDB:1BG3}.
FT   STRAND      596    602       {ECO:0000244|PDB:1BG3}.
FT   HELIX       633    644       {ECO:0000244|PDB:1BG3}.
FT   STRAND      649    655       {ECO:0000244|PDB:1BG3}.
FT   HELIX       657    666       {ECO:0000244|PDB:1BG3}.
FT   STRAND      672    689       {ECO:0000244|PDB:1BG3}.
FT   HELIX       690    692       {ECO:0000244|PDB:1BG3}.
FT   STRAND      700    707       {ECO:0000244|PDB:1BG3}.
FT   HELIX       709    711       {ECO:0000244|PDB:1BG3}.
FT   STRAND      714    716       {ECO:0000244|PDB:1BG3}.
FT   TURN        717    721       {ECO:0000244|PDB:1BG3}.
FT   HELIX       724    731       {ECO:0000244|PDB:1BG3}.
FT   STRAND      733    735       {ECO:0000244|PDB:1BG3}.
FT   HELIX       740    743       {ECO:0000244|PDB:1BG3}.
FT   TURN        747    749       {ECO:0000244|PDB:1BG3}.
FT   HELIX       750    763       {ECO:0000244|PDB:1BG3}.
FT   HELIX       768    770       {ECO:0000244|PDB:1BG3}.
FT   HELIX       774    777       {ECO:0000244|PDB:1BG3}.
FT   HELIX       784    790       {ECO:0000244|PDB:1BG3}.
FT   STRAND      793    795       {ECO:0000244|PDB:1BG3}.
FT   HELIX       797    806       {ECO:0000244|PDB:1BG3}.
FT   HELIX       813    848       {ECO:0000244|PDB:1BG3}.
FT   STRAND      857    861       {ECO:0000244|PDB:1BG3}.
FT   HELIX       863    867       {ECO:0000244|PDB:1BG3}.
FT   HELIX       871    882       {ECO:0000244|PDB:1BG3}.
FT   STRAND      889    892       {ECO:0000244|PDB:1BG3}.
FT   HELIX       896    909       {ECO:0000244|PDB:1BG3}.
SQ   SEQUENCE   918 AA;  102408 MW;  D2200820F0FC41EE CRC64;
     MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDEILIDIL TRFKKEMKNG LSRDYNPTAS
     VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE KNQNVSMESE IYDTPENIVH
     GSGTQLFDHV ADCLGDFMEK KKIKDKKLPV GFTFSFPCRQ SKIDEAVLIT WTKRFKASGV
     EGADVVKLLN KAIKKRGDYD ANIVAVVNDT VGTMMTCGYD DQQCEVGLII GTGTNACYME
     ELRHIDLVEG DEGRMCINTE WGAFGDDGSL EDIRTEFDRE LDRGSLNPGK QLFEKMVSGM
     YMGELVRLIL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKDKEGIQ NAKEILTRLG
     VEPSDVDCVS VQHICTIVSF RSANLVAATL GAILNRLRDN KGTPRLRTTV GVDGSLYKMH
     PQYSRRFHKT LRRLVPDSDV RFLLSESGTG KGAAMVTAVA YRLAEQHRQI EETLAHFRLS
     KQTLMEVKKR LRTEMEMGLR KETNSKATVK MLPSFVRSIP DGTEHGDFLA LDLGGTNFRV
     LLVKIRSGKK RTVEMHNKIY SIPLEIMQGT GDELFDHIVS CISDFLDYMG IKGPRMPLGF
     TFSFPCHQTN LDCGILISWT KGFKATDCEG HDVASLLRDA VKRREEFDLD VVAVVNDTVG
     TMMTCAYEEP TCEIGLIVGT GTNACYMEEM KNVEMVEGNQ GQMCINMEWG AFGDNGCLDD
     IRTDFDKVVD EYSLNSGKQR FEKMISGMYL GEIVRNILID FTKKGFLFRG QISEPLKTRG
     IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSKRA AQLCGAGMAA
     VVEKIRENRG LDHLNVTVGV DGTLYKLHPH FSRIMHQTVK ELSPKCTVSF LLSEDGSGKG
     AALITAVGVR LRGDPSIA
//
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