HXK1_HUMAN
ID HXK1_HUMAN Reviewed; 917 AA.
AC P19367; E9PCK0; O43443; O43444; O75574; Q5VTC3; Q96HC8; Q9NNZ4; Q9NNZ5;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 244.
DE RecName: Full=Hexokinase-1 {ECO:0000305};
DE EC=2.7.1.1 {ECO:0000269|PubMed:1637300};
DE AltName: Full=Brain form hexokinase {ECO:0000303|PubMed:8706938};
DE AltName: Full=Hexokinase type I {ECO:0000303|PubMed:9531504};
DE Short=HK I {ECO:0000303|PubMed:9531504};
DE AltName: Full=Hexokinase-A {ECO:0000250|UniProtKB:P05708};
GN Name=HK1 {ECO:0000312|HGNC:HGNC:4922};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-776.
RX PubMed=3207429; DOI=10.1016/s0006-291x(88)80964-1;
RA Nishi S., Seino S., Bell G.I.;
RT "Human hexokinase: sequences of amino- and carboxyl-terminal halves are
RT homologous.";
RL Biochem. Biophys. Res. Commun. 157:937-943(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RX PubMed=9531504; DOI=10.1042/bj3310607;
RA Ruzzo A., Andreoni F., Magnani M.;
RT "Structure of the human hexokinase type I gene and nucleotide sequence of
RT the 5' flanking region.";
RL Biochem. J. 331:607-613(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-126 (ISOFORM 4), AND ALTERNATIVE SPLICING.
RX PubMed=10978502; DOI=10.1016/s0167-4781(00)00147-0;
RA Andreoni F., Ruzzo A., Magnani M.;
RT "Structure of the 5' region of the human hexokinase type I (HKI) gene and
RT identification of an additional testis-specific HKI mRNA.";
RL Biochim. Biophys. Acta 1493:19-26(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-20 (ISOFORM 2).
RA Murakami K., Piomelli S.;
RT "The erythrocyte-specific hexokinase isozyme (HKR) and the common
RT hexokinase isozyme (HKI) are produced from a single gene by alternate
RT promoters.";
RL Blood 90:272-272(1998).
RN [7]
RP PROTEIN SEQUENCE OF 1-20; 31-42; 382-396 AND 900-910, ACETYLATION AT MET-1,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RA Bienvenut W.V., Waridel P., Quadroni M.;
RL Submitted (MAR-2009) to UniProtKB.
RN [8]
RP PROTEIN SEQUENCE OF 11-31 AND 103-120, AND SUBCELLULAR LOCATION.
RC TISSUE=Placenta;
RX PubMed=1985912; DOI=10.1016/s0021-9258(18)52464-9;
RA Magnani M., Serafini G., Bianchi M., Casabianca A., Stocchi V.;
RT "Human hexokinase type I microheterogeneity is due to different amino-
RT terminal sequences.";
RL J. Biol. Chem. 266:502-505(1991).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 287-917, FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, AND VARIANT MET-776.
RC TISSUE=Placenta;
RX PubMed=1637300; DOI=10.1042/bj2850193;
RA Magnani M., Bianchi M., Casabianca A., Stocchi V., Daniele A., Altruda F.,
RA Ferrone M., Silengo L.;
RT "A recombinant human 'mini'-hexokinase is catalytically active and
RT regulated by hexose 6-phosphates.";
RL Biochem. J. 285:193-199(1992).
RN [10]
RP ALTERNATIVE SPLICING.
RX PubMed=9028305;
RA Murakami K., Piomelli S.;
RT "Identification of the cDNA for human red blood cell-specific hexokinase
RT isozyme.";
RL Blood 89:762-766(1997).
RN [11]
RP CRYSTALLIZATION.
RX PubMed=8706938; DOI=10.1016/0014-5793(96)00688-6;
RA Aleshin A.E., Zeng C., Fromm H.J., Honatko R.B.;
RT "Crystallization and preliminary X-ray analysis of human brain
RT hexokinase.";
RL FEBS Lett. 391:9-10(1996).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP INVOLVEMENT IN HMSNR.
RX PubMed=19536174; DOI=10.1038/ejhg.2009.99;
RA Hantke J., Chandler D., King R., Wanders R.J., Angelicheva D., Tournev I.,
RA McNamara E., Kwa M., Guergueltcheva V., Kaneva R., Baas F., Kalaydjieva L.;
RT "A mutation in an alternative untranslated exon of hexokinase 1 associated
RT with hereditary motor and sensory neuropathy -- Russe (HMSNR).";
RL Eur. J. Hum. Genet. 17:1606-1614(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP INTERACTION WITH ATF2 AND VDAC1.
RX PubMed=22304920; DOI=10.1016/j.cell.2012.01.016;
RA Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L., Ideker T.,
RA Ronai Z.A.;
RT "PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while
RT blocking its apoptotic function at mitochondria.";
RL Cell 148:543-555(2012).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION.
RX PubMed=27374331; DOI=10.1016/j.cell.2016.05.076;
RA Wolf A.J., Reyes C.N., Liang W., Becker C., Shimada K., Wheeler M.L.,
RA Cho H.C., Popescu N.I., Coggeshall K.M., Arditi M., Underhill D.M.;
RT "Hexokinase is an innate immune receptor for the detection of bacterial
RT peptidoglycan.";
RL Cell 166:624-636(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 16-914 IN COMPLEX WITH GLUCOSE AND
RP GLUCOSE-6-PHOSPHATE, SUBUNIT, AND DOMAIN.
RX PubMed=9493266; DOI=10.1016/s0969-2126(98)00006-9;
RA Aleshin A.E., Zeng C., Bourenkov G.P., Bartunik H.D., Fromm H.J.,
RA Honzatko R.B.;
RT "The mechanism of regulation of hexokinase: new insights from the crystal
RT structure of recombinant human brain hexokinase complexed with glucose and
RT glucose-6-phosphate.";
RL Structure 6:39-50(1998).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 16-914, AND DOMAIN.
RX PubMed=9735292; DOI=10.1006/jmbi.1998.2017;
RA Aleshin A.E., Zeng C., Bartunik H.D., Fromm H.J., Honzatko R.B.;
RT "Regulation of hexokinase I: crystal structure of recombinant human brain
RT hexokinase complexed with glucose and phosphate.";
RL J. Mol. Biol. 282:345-357(1998).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH AMP-PNP AND
RP MAGNESIUM, SUBUNIT, AND DOMAIN.
RX PubMed=10574795; DOI=10.1016/s0969-2126(00)80032-5;
RA Rosano C., Sabini E., Rizzi M., Deriu D., Murshudov G., Bianchi M.,
RA Serafini G., Magnani M., Bolognesi M.;
RT "Binding of non-catalytic ATP to human hexokinase I highlights the
RT structural components for enzyme-membrane association control.";
RL Structure 7:1427-1437(1999).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH GLUCOSE;
RP GLUCOSE-6-PHOSPHATE AND ADP.
RX PubMed=10686099; DOI=10.1006/jmbi.1999.3494;
RA Aleshin A.E., Kirby C., Liu X., Bourenkov G.P., Bartunik H.D., Fromm H.J.,
RA Honzatko R.B.;
RT "Crystal structures of mutant monomeric hexokinase I reveal multiple ADP
RT binding sites and conformational changes relevant to allosteric
RT regulation.";
RL J. Mol. Biol. 296:1001-1015(2000).
RN [22]
RP VARIANT HK DEFICIENCY SER-529.
RX PubMed=7655856; DOI=10.1006/bcmd.1995.0002;
RA Bianchi M., Magnani M.;
RT "Hexokinase mutations that produce nonspherocytic hemolytic anemia.";
RL Blood Cells Mol. Dis. 21:2-8(1995).
RN [23]
RP VARIANT HK DEFICIENCY SER-680.
RX PubMed=12393545; DOI=10.1182/blood-2002-06-1851;
RA van Wijk R., Rijksen G., Huizinga E.G., Nieuwenhuis H.K., van Solinge W.W.;
RT "HK Utrecht: missense mutation in the active site of human hexokinase
RT associated with hexokinase deficiency and severe nonspherocytic hemolytic
RT anemia.";
RL Blood 101:345-347(2003).
RN [24]
RP INVOLVEMENT IN RP79, AND VARIANT RP79 LYS-847.
RX PubMed=25190649; DOI=10.1167/iovs.14-15419;
RA Sullivan L.S., Koboldt D.C., Bowne S.J., Lang S., Blanton S.H., Cadena E.,
RA Avery C.E., Lewis R.A., Webb-Jones K., Wheaton D.H., Birch D.G., Coussa R.,
RA Ren H., Lopez I., Chakarova C., Koenekoop R.K., Garcia C.A., Fulton R.S.,
RA Wilson R.K., Weinstock G.M., Daiger S.P.;
RT "A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.";
RL Invest. Ophthalmol. Vis. Sci. 55:7147-7158(2014).
RN [25]
RP INVOLVEMENT IN RP79, VARIANT RP79 LYS-847, CHARACTERIZATION OF VARIANT RP79
RP LYS-847, AND FUNCTION.
RX PubMed=25316723; DOI=10.1167/iovs.14-15520;
RA Wang F., Wang Y., Zhang B., Zhao L., Lyubasyuk V., Wang K., Xu M., Li Y.,
RA Wu F., Wen C., Bernstein P.S., Lin D., Zhu S., Wang H., Zhang K., Chen R.;
RT "A missense mutation in HK1 leads to autosomal dominant retinitis
RT pigmentosa.";
RL Invest. Ophthalmol. Vis. Sci. 55:7159-7164(2014).
RN [26]
RP INVOLVEMENT IN NEDVIBA, VARIANTS NEDVIBA GLU-414; GLU-418; LEU-445 AND
RP MET-457, AND CHARACTERIZATION OF VARIANTS NEDVIBA GLU-418 AND LEU-445.
RX PubMed=30778173; DOI=10.1038/s41431-019-0366-9;
RA Okur V., Cho M.T., van Wijk R., van Oirschot B., Picker J., Coury S.A.,
RA Grange D., Manwaring L., Krantz I., Muraresku C.C., Hulick P.J., May H.,
RA Pierce E., Place E., Bujakowska K., Telegrafi A., Douglas G.,
RA Monaghan K.G., Begtrup A., Wilson A., Retterer K., Anyane-Yeboa K.,
RA Chung W.K.;
RT "De novo variants in HK1 associated with neurodevelopmental abnormalities
RT and visual impairment.";
RL Eur. J. Hum. Genet. 27:1081-1089(2019).
CC -!- FUNCTION: Catalyzes the phosphorylation of various hexoses, such as D-
CC glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to
CC hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate,
CC D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-
CC phosphate, respectively) (PubMed:1637300, PubMed:25316723,
CC PubMed:27374331). Does not phosphorylate N-acetyl-D-glucosamine
CC (PubMed:27374331). Mediates the initial step of glycolysis by
CC catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By
CC similarity). Involved in innate immunity and inflammation by acting as
CC a pattern recognition receptor for bacterial peptidoglycan
CC (PubMed:27374331). When released in the cytosol, N-acetyl-D-glucosamine
CC component of bacterial peptidoglycan inhibits the hexokinase activity
CC of HK1 and causes its dissociation from mitochondrial outer membrane,
CC thereby activating the NLRP3 inflammasome (PubMed:27374331).
CC {ECO:0000250|UniProtKB:P05708, ECO:0000269|PubMed:1637300,
CC ECO:0000269|PubMed:25316723, ECO:0000269|PubMed:27374331}.
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:0000269|PubMed:1637300, ECO:0000269|PubMed:27374331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:1637300, ECO:0000269|PubMed:27374331};
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:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000250|UniProtKB:P05708};
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:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000250|UniProtKB:P05708};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-mannose = ADP + D-mannose 6-phosphate + H(+);
CC Xref=Rhea:RHEA:11028, ChEBI:CHEBI:4208, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58735, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000250|UniProtKB:P05708};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029;
CC Evidence={ECO:0000250|UniProtKB:P05708};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + D-glucosamine = ADP + D-glucosamine 6-phosphate + H(+);
CC Xref=Rhea:RHEA:10948, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:58723, ChEBI:CHEBI:58725, ChEBI:CHEBI:456216; EC=2.7.1.1;
CC Evidence={ECO:0000269|PubMed:27374331};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10949;
CC Evidence={ECO:0000269|PubMed:27374331};
CC -!- ACTIVITY REGULATION: Hexokinase is an allosteric enzyme inhibited by
CC its product D-glucose 6-phosphate (PubMed:1637300). Hexokinase activity
CC is inhibited by N-acetyl-D-glucosamine (PubMed:27374331).
CC {ECO:0000269|PubMed:1637300, ECO:0000269|PubMed:27374331}.
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:1637300, ECO:0000305|PubMed:27374331}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000250|UniProtKB:P05708}.
CC -!- SUBUNIT: Monomer (PubMed:10686099). Interacts with RABL2/RABL2A; binds
CC preferentially to GTP-bound RABL2 (By similarity). Interacts with VDAC1
CC (PubMed:22304920). The HK1-VDAC1 complex interacts with ATF2
CC (PubMed:22304920). Interacts (via N-terminal spermatogenic cell-
CC specific region) with PFKM (via C-terminus) (By similarity).
CC {ECO:0000250|UniProtKB:P17710, ECO:0000269|PubMed:10686099,
CC ECO:0000269|PubMed:22304920}.
CC -!- INTERACTION:
CC P19367; P12931: SRC; NbExp=2; IntAct=EBI-713162, EBI-621482;
CC P19367; P21796: VDAC1; NbExp=2; IntAct=EBI-713162, EBI-354158;
CC P19367; P05480: Src; Xeno; NbExp=8; IntAct=EBI-713162, EBI-298680;
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:1985912, ECO:0000269|PubMed:27374331}; Peripheral
CC membrane protein {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:27374331}. Note=The mitochondrial-binding peptide
CC (MBP) region promotes association with the mitochondrial outer membrane
CC (Probable). Dissociates from the mitochondrial outer membrane following
CC inhibition by N-acetyl-D-glucosamine, leading to relocation to the
CC cytosol (PubMed:27374331). {ECO:0000269|PubMed:27374331,
CC ECO:0000305|PubMed:1985912}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Common;
CC IsoId=P19367-1; Sequence=Displayed;
CC Name=2; Synonyms=Erythrocyte, R;
CC IsoId=P19367-2; Sequence=VSP_002071;
CC Name=3; Synonyms=TA, TB;
CC IsoId=P19367-3; Sequence=VSP_002072;
CC Name=4; Synonyms=TD;
CC IsoId=P19367-4; Sequence=VSP_002073;
CC -!- TISSUE SPECIFICITY: Isoform 2: Erythrocyte specific (Ref.6). Isoform 3:
CC Testis-specific (PubMed:10978502). Isoform 4: Testis-specific
CC (PubMed:10978502). {ECO:0000269|PubMed:10978502, ECO:0000269|Ref.6}.
CC -!- DOMAIN: The N- and C-terminal halves of this hexokinase contain a
CC hexokinase domain (PubMed:9493266, PubMed:9735292, PubMed:10574795).
CC The catalytic activity is associated with the C-terminus while
CC regulatory function is associated with the N-terminus (PubMed:9493266,
CC PubMed:9735292, PubMed:10574795). Each domain can bind a single D-
CC glucose and D-glucose 6-phosphate molecule (PubMed:9493266).
CC {ECO:0000269|PubMed:10574795, ECO:0000269|PubMed:9493266,
CC ECO:0000269|PubMed:9735292}.
CC -!- DISEASE: Hexokinase deficiency (HK deficiency) [MIM:235700]: Rare
CC autosomal recessive disease with nonspherocytic hemolytic anemia as the
CC predominant clinical feature. {ECO:0000269|PubMed:12393545,
CC ECO:0000269|PubMed:7655856}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neuropathy, hereditary motor and sensory, Russe type (HMSNR)
CC [MIM:605285]: An autosomal recessive progressive complex peripheral
CC neuropathy characterized by onset in the first decade of distal lower
CC limb weakness and muscle atrophy resulting in walking difficulties.
CC Distal impairment of the upper limbs usually occurs later, as does
CC proximal lower limb weakness. There is distal sensory impairment, with
CC pes cavus and areflexia. Laboratory studies suggest that it is a
CC myelinopathy resulting in reduced nerve conduction velocities in the
CC demyelinating range as well as a length-dependent axonopathy.
CC {ECO:0000269|PubMed:19536174}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Retinitis pigmentosa 79 (RP79) [MIM:617460]: A form of
CC retinitis pigmentosa, a retinal dystrophy belonging to the group of
CC pigmentary retinopathies. Retinitis pigmentosa is characterized by
CC retinal pigment deposits visible on fundus examination and primary loss
CC of rod photoreceptor cells followed by secondary loss of cone
CC photoreceptors. Patients typically have night vision blindness and loss
CC of midperipheral visual field. As their condition progresses, they lose
CC their far peripheral visual field and eventually central vision as
CC well. RP79 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:25190649, ECO:0000269|PubMed:25316723}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Neurodevelopmental disorder with visual defects and brain
CC anomalies (NEDVIBA) [MIM:618547]: A disorder characterized by global
CC developmental delay, speech delay, intellectual disability, structural
CC brain abnormalities, and visual impairments including retinitis
CC pigmentosa and optic atrophy. {ECO:0000269|PubMed:30778173}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the hexokinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01084, ECO:0000305}.
CC -!- CAUTION: Hexokinase is known to act as a monomer (PubMed:10686099). It
CC however homodimerizes at elevated protein concentrations used for
CC crystallizations (PubMed:9493266, PubMed:10574795).
CC {ECO:0000269|PubMed:10574795, ECO:0000269|PubMed:10686099,
CC ECO:0000269|PubMed:9493266}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Hexokinase entry;
CC URL="https://en.wikipedia.org/wiki/Hexokinase";
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DR EMBL; M75126; AAA52646.1; -; mRNA.
DR EMBL; AF016365; AAC15862.1; -; Genomic_DNA.
DR EMBL; AF016349; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016351; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016352; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016353; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016354; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016355; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016356; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016357; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016358; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016359; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016360; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016361; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016362; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016363; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016364; AAC15862.1; JOINED; Genomic_DNA.
DR EMBL; AF016365; AAC15863.1; -; Genomic_DNA.
DR EMBL; AF016349; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016351; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016352; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016353; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016354; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016355; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016356; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016357; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016358; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016359; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016360; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016361; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016362; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016363; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016364; AAC15863.1; JOINED; Genomic_DNA.
DR EMBL; AF016365; AAF82319.1; -; Genomic_DNA.
DR EMBL; AF163910; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF163911; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016351; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016352; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016353; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016354; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016355; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016356; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016357; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016358; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016359; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016360; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016361; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016362; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016363; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016364; AAF82319.1; JOINED; Genomic_DNA.
DR EMBL; AF016365; AAF82320.1; -; Genomic_DNA.
DR EMBL; AF163912; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016351; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016352; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016353; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016354; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016355; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016356; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016357; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016358; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016359; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016360; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016361; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016362; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016363; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AF016364; AAF82320.1; JOINED; Genomic_DNA.
DR EMBL; AC016821; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL596223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL672126; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008730; AAH08730.1; -; mRNA.
DR EMBL; AF073786; AAC25424.1; -; mRNA.
DR EMBL; AF029306; AAC00172.1; -; Genomic_DNA.
DR EMBL; X66957; CAA47379.1; -; mRNA.
DR CCDS; CCDS7289.1; -. [P19367-3]
DR CCDS; CCDS7291.1; -. [P19367-2]
DR CCDS; CCDS7292.1; -. [P19367-1]
DR PIR; A31869; A31869.
DR RefSeq; NP_000179.2; NM_000188.2. [P19367-1]
DR RefSeq; NP_001309293.1; NM_001322364.1. [P19367-3]
DR RefSeq; NP_277031.1; NM_033496.2. [P19367-2]
DR RefSeq; NP_277032.1; NM_033497.2. [P19367-3]
DR RefSeq; NP_277033.1; NM_033498.2. [P19367-3]
DR RefSeq; NP_277035.2; NM_033500.2. [P19367-4]
DR RefSeq; XP_011538034.1; XM_011539732.1. [P19367-4]
DR PDB; 1CZA; X-ray; 1.90 A; N=1-917.
DR PDB; 1DGK; X-ray; 2.80 A; N=1-917.
DR PDB; 1HKB; X-ray; 2.80 A; A/B=1-917.
DR PDB; 1HKC; X-ray; 2.80 A; A=1-917.
DR PDB; 1QHA; X-ray; 2.25 A; A/B=1-917.
DR PDB; 4F9O; X-ray; 2.65 A; A/B=1-914.
DR PDB; 4FOE; X-ray; 2.70 A; A/B=1-917.
DR PDB; 4FOI; X-ray; 2.40 A; A/B=1-917.
DR PDB; 4FPA; X-ray; 2.48 A; A/B=1-917.
DR PDB; 4FPB; X-ray; 3.00 A; A/B=1-917.
DR PDBsum; 1CZA; -.
DR PDBsum; 1DGK; -.
DR PDBsum; 1HKB; -.
DR PDBsum; 1HKC; -.
DR PDBsum; 1QHA; -.
DR PDBsum; 4F9O; -.
DR PDBsum; 4FOE; -.
DR PDBsum; 4FOI; -.
DR PDBsum; 4FPA; -.
DR PDBsum; 4FPB; -.
DR AlphaFoldDB; P19367; -.
DR SMR; P19367; -.
DR BioGRID; 109345; 192.
DR CORUM; P19367; -.
DR DIP; DIP-56245N; -.
DR IntAct; P19367; 65.
DR MINT; P19367; -.
DR STRING; 9606.ENSP00000402103; -.
DR BindingDB; P19367; -.
DR ChEMBL; CHEMBL2688; -.
DR DrugBank; DB02007; alpha-D-glucose 6-phosphate.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB01914; D-glucose.
DR DrugBank; DB09341; Dextrose, unspecified form.
DR DrugBank; DB09502; Fludeoxyglucose (18F).
DR DrugBank; DB06266; Lonidamine.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR CarbonylDB; P19367; -.
DR GlyGen; P19367; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P19367; -.
DR MetOSite; P19367; -.
DR PhosphoSitePlus; P19367; -.
DR SwissPalm; P19367; -.
DR BioMuta; HK1; -.
DR DMDM; 116242516; -.
DR CPTAC; CPTAC-80; -.
DR CPTAC; CPTAC-81; -.
DR EPD; P19367; -.
DR jPOST; P19367; -.
DR MassIVE; P19367; -.
DR MaxQB; P19367; -.
DR PaxDb; P19367; -.
DR PeptideAtlas; P19367; -.
DR PRIDE; P19367; -.
DR ProteomicsDB; 53648; -. [P19367-1]
DR ProteomicsDB; 53649; -. [P19367-2]
DR ProteomicsDB; 53650; -. [P19367-3]
DR ProteomicsDB; 53651; -. [P19367-4]
DR Antibodypedia; 2057; 862 antibodies from 42 providers.
DR DNASU; 3098; -.
DR Ensembl; ENST00000298649.8; ENSP00000298649.3; ENSG00000156515.24. [P19367-2]
DR Ensembl; ENST00000359426.7; ENSP00000352398.6; ENSG00000156515.24. [P19367-1]
DR Ensembl; ENST00000360289.6; ENSP00000353433.2; ENSG00000156515.24. [P19367-4]
DR Ensembl; ENST00000436817.6; ENSP00000415949.2; ENSG00000156515.24. [P19367-3]
DR Ensembl; ENST00000448642.6; ENSP00000402103.3; ENSG00000156515.24. [P19367-3]
DR Ensembl; ENST00000643399.2; ENSP00000494664.1; ENSG00000156515.24. [P19367-3]
DR GeneID; 3098; -.
DR KEGG; hsa:3098; -.
DR MANE-Select; ENST00000359426.7; ENSP00000352398.6; NM_000188.3; NP_000179.2.
DR UCSC; uc001jpg.5; human. [P19367-1]
DR CTD; 3098; -.
DR DisGeNET; 3098; -.
DR GeneCards; HK1; -.
DR HGNC; HGNC:4922; HK1.
DR HPA; ENSG00000156515; Low tissue specificity.
DR MalaCards; HK1; -.
DR MIM; 142600; gene.
DR MIM; 235700; phenotype.
DR MIM; 605285; phenotype.
DR MIM; 617460; phenotype.
DR MIM; 618547; phenotype.
DR neXtProt; NX_P19367; -.
DR OpenTargets; ENSG00000156515; -.
DR Orphanet; 99953; Charcot-Marie-Tooth disease type 4G.
DR Orphanet; 90031; Non-spherocytic hemolytic anemia due to hexokinase deficiency.
DR PharmGKB; PA29300; -.
DR VEuPathDB; HostDB:ENSG00000156515; -.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR HOGENOM; CLU_014393_1_0_1; -.
DR InParanoid; P19367; -.
DR OMA; DKYLYTM; -.
DR OrthoDB; 1153545at2759; -.
DR PhylomeDB; P19367; -.
DR TreeFam; TF314238; -.
DR BioCyc; MetaCyc:HS08136-MON; -.
DR BRENDA; 2.7.1.1; 2681.
DR PathwayCommons; P19367; -.
DR Reactome; R-HSA-5619056; Defective HK1 causes hexokinase deficiency (HK deficiency).
DR Reactome; R-HSA-70171; Glycolysis.
DR SABIO-RK; P19367; -.
DR SignaLink; P19367; -.
DR SIGNOR; P19367; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR BioGRID-ORCS; 3098; 14 hits in 1090 CRISPR screens.
DR ChiTaRS; HK1; human.
DR EvolutionaryTrace; P19367; -.
DR GenomeRNAi; 3098; -.
DR Pharos; P19367; Tchem.
DR PRO; PR:P19367; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P19367; protein.
DR Bgee; ENSG00000156515; Expressed in cerebellar vermis and 203 other tissues.
DR ExpressionAtlas; P19367; baseline and differential.
DR Genevisible; P19367; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008865; F:fructokinase activity; ISS:UniProtKB.
DR GO; GO:0004340; F:glucokinase activity; ISS:UniProtKB.
DR GO; GO:0047931; F:glucosamine kinase activity; IEA:RHEA.
DR GO; GO:0005536; F:glucose binding; IEA:InterPro.
DR GO; GO:0004396; F:hexokinase activity; IMP:CAFA.
DR GO; GO:0019158; F:mannokinase activity; ISS:UniProtKB.
DR GO; GO:0042834; F:peptidoglycan binding; IDA:CAFA.
DR GO; GO:0061621; P:canonical glycolysis; TAS:Reactome.
DR GO; GO:0046835; P:carbohydrate phosphorylation; IMP:CAFA.
DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR GO; GO:0072655; P:establishment of protein localization to mitochondrion; IMP:ParkinsonsUK-UCL.
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:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0072656; P:maintenance of protein location in mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006013; P:mannose metabolic process; ISS:UniProtKB.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IEA:Ensembl.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IEA:Ensembl.
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; 2.
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 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW ATP-binding; Charcot-Marie-Tooth disease; Cytoplasm;
KW Direct protein sequencing; Disease variant; Glycolysis; Immunity;
KW Inflammatory response; Innate immunity; Intellectual disability; Kinase;
KW Membrane; Mitochondrion; Mitochondrion outer membrane; Neurodegeneration;
KW Neuropathy; Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Retinitis pigmentosa; Transferase.
FT CHAIN 1..917
FT /note="Hexokinase-1"
FT /id="PRO_0000197585"
FT DOMAIN 16..458
FT /note="Hexokinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT DOMAIN 464..906
FT /note="Hexokinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 1..10
FT /note="Mitochondrial-binding peptide (MBP)"
FT /evidence="ECO:0000305|PubMed:1985912"
FT REGION 73..207
FT /note="Hexokinase small subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 208..447
FT /note="Hexokinase large subdomain 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 521..655
FT /note="Hexokinase small subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 656..895
FT /note="Hexokinase large subdomain 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 30
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1QHA"
FT BINDING 84..91
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA"
FT BINDING 84..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKC"
FT BINDING 155
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0000269|PubMed:9493266, ECO:0000269|PubMed:9735292,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA"
FT BINDING 172..173
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 208..209
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 209
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA"
FT BINDING 232
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 235
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 260
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 291..294
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1HKC, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0007744|PDB:1QHA"
FT BINDING 413..415
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 425..426
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1DGK, ECO:0007744|PDB:1QHA"
FT BINDING 449
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 532..537
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0007744|PDB:1DGK"
FT BINDING 532..536
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0007744|PDB:1CZA,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA"
FT BINDING 603..604
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0000269|PubMed:9493266, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 620..621
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 656..657
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 657
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA"
FT BINDING 680
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKC"
FT BINDING 680
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 682..683
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 708
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 742
FT /ligand="D-glucose"
FT /ligand_id="ChEBI:CHEBI:4167"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKB, ECO:0007744|PDB:1QHA,
FT ECO:0007744|PDB:4F9O, ECO:0007744|PDB:4FOE,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT BINDING 747..748
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0007744|PDB:1DGK"
FT BINDING 784..788
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0007744|PDB:1DGK"
FT BINDING 861..863
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOE, ECO:0007744|PDB:4FOI,
FT ECO:0007744|PDB:4FPA, ECO:0007744|PDB:4FPB"
FT BINDING 863..867
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10686099,
FT ECO:0000269|PubMed:9735292, ECO:0007744|PDB:1DGK,
FT ECO:0007744|PDB:1HKC"
FT BINDING 897
FT /ligand="D-glucose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:61548"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:10574795,
FT ECO:0000269|PubMed:10686099, ECO:0000269|PubMed:9493266,
FT ECO:0007744|PDB:1CZA, ECO:0007744|PDB:1HKB,
FT ECO:0007744|PDB:1QHA, ECO:0007744|PDB:4F9O,
FT ECO:0007744|PDB:4FOI, ECO:0007744|PDB:4FPA,
FT ECO:0007744|PDB:4FPB"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:25944712"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P05708"
FT VAR_SEQ 1..21
FT /note="MIAAQLLAYYFTELKDDQVKK -> MDCEHSLSLPCRGAEAWEIG (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_002071"
FT VAR_SEQ 1..21
FT /note="MIAAQLLAYYFTELKDDQVKK -> MGQICQRESATAAEKPKLHLLAESE
FT (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002072"
FT VAR_SEQ 1..21
FT /note="MIAAQLLAYYFTELKDDQVKK -> MAKRALHDF (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10978502"
FT /id="VSP_002073"
FT VARIANT 414
FT /note="G -> E (in NEDVIBA; dbSNP:rs1064795154)"
FT /evidence="ECO:0000269|PubMed:30778173"
FT /id="VAR_083222"
FT VARIANT 418
FT /note="K -> E (in NEDVIBA; no effect on the affinity for
FT glucose or ATP; no effect on thermal stability;
FT dbSNP:rs1564557037)"
FT /evidence="ECO:0000269|PubMed:30778173"
FT /id="VAR_083223"
FT VARIANT 445
FT /note="S -> L (in NEDVIBA; no effect on the affinity for
FT glucose or ATP; no effect on thermal stability;
FT dbSNP:rs1064794848)"
FT /evidence="ECO:0000269|PubMed:30778173"
FT /id="VAR_083224"
FT VARIANT 457
FT /note="T -> M (in NEDVIBA; dbSNP:rs1057517928)"
FT /evidence="ECO:0000269|PubMed:30778173"
FT /id="VAR_083225"
FT VARIANT 529
FT /note="L -> S (in HK deficiency; dbSNP:rs137853249)"
FT /evidence="ECO:0000269|PubMed:7655856"
FT /id="VAR_009878"
FT VARIANT 680
FT /note="T -> S (in HK deficiency; HK Utrecht;
FT dbSNP:rs398122379)"
FT /evidence="ECO:0000269|PubMed:12393545"
FT /id="VAR_023780"
FT VARIANT 776
FT /note="L -> M (in dbSNP:rs1054203)"
FT /evidence="ECO:0000269|PubMed:1637300,
FT ECO:0000269|PubMed:3207429"
FT /id="VAR_023781"
FT VARIANT 847
FT /note="E -> K (in RP79; unknown pathological significance;
FT no effect on hexokinase activity; no effect on protein
FT abundance; dbSNP:rs777849213)"
FT /evidence="ECO:0000269|PubMed:25190649,
FT ECO:0000269|PubMed:25316723"
FT /id="VAR_078923"
FT CONFLICT 730
FT /note="D -> N (in Ref. 1; AAA52646 and 9; CAA47379)"
FT /evidence="ECO:0000305"
FT HELIX 17..25
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 33..51
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 78..100
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 103..112
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 123..141
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:4FOI"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:4FPB"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:4FPB"
FT HELIX 185..196
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 224..241
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 252..258
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 264..273
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 276..283
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 285..287
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 294..297
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 299..315
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 326..329
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 336..342
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 348..358
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 365..401
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 404..413
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 415..419
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 423..434
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 438..444
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 449..475
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 481..499
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 526..546
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:1QHA"
FT STRAND 552..560
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 564..567
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:4F9O"
FT HELIX 571..589
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 597..602
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 606..610
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 613..616
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 633..644
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 650..655
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 657..666
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 672..689
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 690..692
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 700..706
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 709..711
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 712..715
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 717..721
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 724..731
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 734..737
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 742..744
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 747..749
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 750..763
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 768..770
FT /evidence="ECO:0007829|PDB:1CZA"
FT TURN 774..777
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 784..790
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 797..807
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 813..848
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 852..861
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 863..867
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 871..882
FT /evidence="ECO:0007829|PDB:1CZA"
FT STRAND 886..892
FT /evidence="ECO:0007829|PDB:1CZA"
FT HELIX 898..912
FT /evidence="ECO:0007829|PDB:1CZA"
SQ SEQUENCE 917 AA; 102486 MW; F29A6837531C0594 CRC64;
MIAAQLLAYY FTELKDDQVK KIDKYLYAMR LSDETLIDIM TRFRKEMKNG LSRDFNPTAT
VKMLPTFVRS IPDGSEKGDF IALDLGGSSF RILRVQVNHE KNQNVHMESE VYDTPENIVH
GSGSQLFDHV AECLGDFMEK RKIKDKKLPV GFTFSFPCQQ SKIDEAILIT WTKRFKASGV
EGADVVKLLN KAIKKRGDYD ANIVAVVNDT VGTMMTCGYD DQHCEVGLII GTGTNACYME
ELRHIDLVEG DEGRMCINTE WGAFGDDGSL EDIRTEFDRE IDRGSLNPGK QLFEKMVSGM
YLGELVRLIL VKMAKEGLLF EGRITPELLT RGKFNTSDVS AIEKNKEGLH NAKEILTRLG
VEPSDDDCVS VQHVCTIVSF RSANLVAATL GAILNRLRDN KGTPRLRTTV GVDGSLYKTH
PQYSRRFHKT LRRLVPDSDV RFLLSESGSG KGAAMVTAVA YRLAEQHRQI EETLAHFHLT
KDMLLEVKKR MRAEMELGLR KQTHNNAVVK MLPSFVRRTP DGTENGDFLA LDLGGTNFRV
LLVKIRSGKK RTVEMHNKIY AIPIEIMQGT GEELFDHIVS CISDFLDYMG IKGPRMPLGF
TFSFPCQQTS LDAGILITWT KGFKATDCVG HDVVTLLRDA IKRREEFDLD VVAVVNDTVG
TMMTCAYEEP TCEVGLIVGT GSNACYMEEM KNVEMVEGDQ GQMCINMEWG AFGDNGCLDD
IRTHYDRLVD EYSLNAGKQR YEKMISGMYL GEIVRNILID FTKKGFLFRG QISETLKTRG
IFETKFLSQI ESDRLALLQV RAILQQLGLN STCDDSILVK TVCGVVSRRA AQLCGAGMAA
VVDKIRENRG LDRLNVTVGV DGTLYKLHPH FSRIMHQTVK ELSPKCNVSF LLSEDGSGKG
AALITAVGVR LRTEASS
