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Database: UniProt/SWISS-PROT
Entry: HXK4_HUMAN
LinkDB: HXK4_HUMAN
Original site: HXK4_HUMAN 
ID   HXK4_HUMAN              Reviewed;         465 AA.
AC   P35557; A4D2J2; A4D2J3; Q05810;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   05-DEC-2018, entry version 201.
DE   RecName: Full=Glucokinase;
DE            EC=2.7.1.2 {ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19146401, ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:8325892};
DE   AltName: Full=Hexokinase type IV;
DE            Short=HK IV;
DE   AltName: Full=Hexokinase-4;
DE            Short=HK4;
DE   AltName: Full=Hexokinase-D;
GN   Name=GCK;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1354840; DOI=10.1210/mend.6.7.1354840;
RA   Tanizawa Y., Matsutani A., Chiu K.C., Permutt M.A.;
RT   "Human glucokinase gene: isolation, structural characterization, and
RT   identification of a microsatellite repeat polymorphism.";
RL   Mol. Endocrinol. 6:1070-1081(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-107.
RX   PubMed=1871135; DOI=10.1073/pnas.88.16.7294;
RA   Tanizawa Y., Koranyi L.I., Welling C.M., Permutt M.A.;
RT   "Human liver glucokinase gene: cloning and sequence determination of
RT   two alternatively spliced cDNAs.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:7294-7297(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Pancreas;
RX   PubMed=1511800;
RA   Nishi S., Stoffel M., Xiang K.S., Shows T.B., Bell G.I., Takeda J.;
RT   "Human pancreatic beta-cell glucokinase: cDNA sequence and
RT   localization of the polymorphic gene to chromosome 7, band p13.";
RL   Diabetologia 35:743-747(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Pancreas;
RX   PubMed=1612194; DOI=10.2337/diab.41.7.807;
RA   Koranyi L.I., Tanizawa Y., Welling C.M., Rabin D.U., Permutt M.A.;
RT   "Human islet glucokinase gene. Isolation and sequence analysis of
RT   full-length cDNA.";
RL   Diabetes 41:807-811(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MODY2 MET-228 AND
RP   ARG-261.
RC   TISSUE=Placenta;
RX   PubMed=1502186; DOI=10.1073/pnas.89.16.7698;
RA   Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S.,
RA   Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M.,
RA   Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.;
RT   "Human glucokinase gene: isolation, characterization, and
RT   identification of two missense mutations linked to early-onset non-
RT   insulin-dependent (type 2) diabetes mellitus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992).
RN   [6]
RP   ERRATUM.
RA   Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S.,
RA   Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M.,
RA   Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.;
RL   Proc. Natl. Acad. Sci. U.S.A. 89:10562-10562(1992).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-107, AND VARIANT MODY2
RP   ARG-261.
RX   PubMed=1464666; DOI=10.1210/jcem.75.6.1464666;
RA   Sakura H., Eto K., Kadowaki H., Simokawa K., Ueno H., Koda N.,
RA   Fukushima Y., Akanuma Y., Yazaki Y., Kadowaki T.;
RT   "Structure of the human glucokinase gene and identification of a
RT   missense mutation in a Japanese patient with early-onset non-insulin-
RT   dependent diabetes mellitus.";
RL   J. Clin. Endocrinol. Metab. 75:1571-1573(1992).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Liver;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA   Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA   Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA   Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA   Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA   Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA   Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA   Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA   Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA   Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA   Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA   Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA   Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA   Mural R.J., Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [12]
RP   ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX   PubMed=10456334; DOI=10.1016/S0014-5793(99)00971-0;
RA   de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E.,
RA   Guinovart J.J., Ferrer J.C.;
RT   "Glucokinase regulatory protein is essential for the proper
RT   subcellular localisation of liver glucokinase.";
RL   FEBS Lett. 456:332-338(1999).
RN   [13]
RP   FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-64; MET-197;
RP   ILE-211 AND SER-453.
RX   PubMed=19146401; DOI=10.1021/bi802142q;
RA   Pal P., Miller B.G.;
RT   "Activating mutations in the human glucokinase gene revealed by
RT   genetic selection.";
RL   Biochemistry 48:814-816(2009).
RN   [14]
RP   INTERACTION WITH MIDN, AND SUBCELLULAR LOCATION.
RX   PubMed=24187134; DOI=10.1074/jbc.M113.526632;
RA   Hofmeister-Brix A., Kollmann K., Langer S., Schultz J., Lenzen S.,
RA   Baltrusch S.;
RT   "Identification of the ubiquitin-like domain of midnolin as a new
RT   glucokinase interaction partner.";
RL   J. Biol. Chem. 288:35824-35839(2013).
RN   [15]
RP   3D-STRUCTURE MODELING.
RX   PubMed=8194664; DOI=10.2337/diab.43.6.784;
RA   St Charles R., Harrison R.W., Bell G.I., Pilkis S.J., Weber I.T.;
RT   "Molecular model of human beta-cell glucokinase built by analogy to
RT   the crystal structure of yeast hexokinase B.";
RL   Diabetes 43:784-791(1994).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 16-465 OF APOPROTEIN AND IN
RP   COMPLEX WITH GLUCOSE, SUBUNIT, AND ACTIVITY REGULATION.
RX   PubMed=15016359; DOI=10.1016/j.str.2004.02.005;
RA   Kamata K., Mitsuya M., Nishimura T., Eiki J., Nagata Y.;
RT   "Structural basis for allosteric regulation of the monomeric
RT   allosteric enzyme human glucokinase.";
RL   Structure 12:429-438(2004).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-465 IN COMPLEX WITH
RP   SYNTHETIC ALLOSTERIC ACTIVATOR.
RX   PubMed=19362831; DOI=10.1016/j.bmcl.2009.03.137;
RA   Mitsuya M., Kamata K., Bamba M., Watanabe H., Sasaki Y., Sasaki K.,
RA   Ohyama S., Hosaka H., Nagata Y., Eiki J., Nishimura T.;
RT   "Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide
RT   derivatives as GK activators.";
RL   Bioorg. Med. Chem. Lett. 19:2718-2721(2009).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 3-465 IN COMPLEX WITH RAT
RP   GKRP.
RX   PubMed=23957911; DOI=10.1021/bi400838t;
RA   Beck T., Miller B.G.;
RT   "Structural basis for regulation of human glucokinase by glucokinase
RT   regulatory protein.";
RL   Biochemistry 52:6232-6239(2013).
RN   [19]
RP   INVOLVEMENT IN NIDDM, AND VARIANT NIDDM 186-ARG--GLN-465 DEL.
RX   PubMed=1360036;
RA   Katagiri H., Asano T., Ishihara H., Inukai K., Anai M., Miyazaki J.,
RA   Tsukuda K., Kikuchi M., Yazaki Y., Oka Y.;
RT   "Nonsense mutation of glucokinase gene in late-onset non-insulin-
RT   dependent diabetes mellitus.";
RL   Lancet 340:1316-1317(1992).
RN   [20]
RP   VARIANT MODY2 ARG-299.
RX   PubMed=1303265; DOI=10.1038/ng1092-153;
RA   Stoffel M., Patel P., Lo Y.-M.D., Hattersley A.T., Lucassen A.M.,
RA   Page R., Bell J.I., Bell G.I., Turner R.C., Wainscoat J.S.;
RT   "Missense glucokinase mutation in maturity-onset diabetes of the young
RT   and mutation screening in late-onset diabetes.";
RL   Nat. Genet. 2:153-156(1992).
RN   [21]
RP   VARIANT THR-11.
RX   PubMed=8454109; DOI=10.2337/diab.42.4.579;
RA   Chiu K.C., Tanizawa Y., Permutt M.A.;
RT   "Glucokinase gene variants in the common form of NIDDM.";
RL   Diabetes 42:579-582(1993).
RN   [22]
RP   VARIANT MODY2 PRO-131.
RX   PubMed=8495817; DOI=10.2337/diab.42.6.937;
RA   Stoffel M., Bell K.L., Blackburn C.L., Powell K.L., Seo T.S.,
RA   Takeda J., Vionnet N., Xiang K.-S., Gidh-Jain M., Pilkis S.J.,
RA   Ober C., Bell G.I.;
RT   "Identification of glucokinase mutations in subjects with gestational
RT   diabetes mellitus.";
RL   Diabetes 42:937-940(1993).
RN   [23]
RP   VARIANT ASN-4, VARIANTS MODY2 LYS-70; PRO-131; THR-188; ARG-257 AND
RP   GLU-414, MUTAGENESIS OF GLU-177; GLU-256 AND LYS-414, CATALYTIC
RP   ACTIVITY, AND FUNCTION.
RX   PubMed=8325892;
RA   Takeda J., Gidh-Jain M., Xu L.Z., Froguel P., Velho G., Vaxillaire M.,
RA   Cohen D., Shimada F., Makino H., Nishi S., Stoffel M., Vionnet N.,
RA   St Charles R., Harrison R.W., Weber I.T., Bell G.I., Pilkis S.J.;
RT   "Structure/function studies of human beta-cell glucokinase. Enzymatic
RT   properties of a sequence polymorphism, mutations associated with
RT   diabetes, and other site-directed mutants.";
RL   J. Biol. Chem. 268:15200-15204(1993).
RN   [24]
RP   CHARACTERIZATION OF VARIANTS MODY2.
RX   PubMed=8446612; DOI=10.1073/pnas.90.5.1932;
RA   Gidh-Jain M., Takeda J., Xu L.Z., Lange A.J., Vionnet N., Stoffel M.,
RA   Froguel P., Velho G., Sun D., Cohen D., Patel P., Lo Y.-M.D.,
RA   Hattersley A.T., Luthman H., Wedell A., St Charles R., Harrison R.W.,
RA   Weber I.T., Bell G.I., Pilkis S.J.;
RT   "Glucokinase mutations associated with non-insulin-dependent (type 2)
RT   diabetes mellitus have decreased enzymatic activity: implications for
RT   structure/function relationships.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:1932-1936(1993).
RN   [25]
RP   VARIANTS MODY2 TRP-36; MET-209 AND GLU-261.
RX   PubMed=8168652; DOI=10.2337/diab.43.5.730;
RA   Hager J., Blanche H., Sun F., Vionnet N., Vaxillaire M., Poller W.,
RA   Cohen D., Czernichow P., Velho G., Robert J.-J., Cohen N., Froguel P.;
RT   "Six mutations in the glucokinase gene identified in MODY by using a
RT   nonradioactive sensitive screening technique.";
RL   Diabetes 43:730-733(1994).
RN   [26]
RP   VARIANTS MODY2.
RX   PubMed=9049484; DOI=10.1007/s001250050666;
RA   Velho G., Blanche H., Vaxillaire M., Bellanne-Chantelot C.,
RA   Pardini V.C., Timsit J., Passa P., Deschamps I., Robert J.-J.,
RA   Weber I.T., Marotta D., Pilkis S.J., Lipkind G.M., Bell G.I.,
RA   Froguel P.;
RT   "Identification of 14 new glucokinase mutations and description of the
RT   clinical profile of 42 MODY-2 families.";
RL   Diabetologia 40:217-224(1997).
RN   [27]
RP   VARIANTS MODY2 SER-80; LYS-221 AND CYS-227.
RX   PubMed=10694920;
RX   DOI=10.1002/(SICI)1098-1004(1998)12:2<136::AID-HUMU13>3.3.CO;2-M;
RA   Guazzini B., Gaffi D., Mainieri D., Multari G., Cordera R.,
RA   Bertolini S., Pozza G., Meschi F., Barbetti F.;
RT   "Three novel missense mutations in the glucokinase gene (G80S; E221K;
RT   G227C) in Italian subjects with maturity-onset diabetes of the young
RT   (MODY).";
RL   Hum. Mutat. 12:136-136(1998).
RN   [28]
RP   VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384
RP   AND CYS-392.
RX   PubMed=9662401; DOI=10.1038/953;
RA   Hattersley A.T., Beards F., Ballantyne E., Appleton M., Harvey R.,
RA   Ellard S.;
RT   "Mutations in the glucokinase gene of the fetus result in reduced
RT   birth weight.";
RL   Nat. Genet. 19:268-270(1998).
RN   [29]
RP   VARIANT HHF3 MET-455.
RX   PubMed=9435328; DOI=10.1056/NEJM199801223380404;
RA   Glaser B., Kesavan P., Heyman M., Davis E., Cuesta A., Buchs A.,
RA   Stanley C.A., Thornton P.S., Permutt M.A., Matschinsky F.M.,
RA   Herold K.C.;
RT   "Familial hyperinsulinism caused by an activating glucokinase
RT   mutation.";
RL   N. Engl. J. Med. 338:226-230(1998).
RN   [30]
RP   VARIANTS MODY2 THR-110; ASP-119 AND VAL-385.
RX   PubMed=10588527; DOI=10.1046/j.1464-5491.1999.00188.x;
RA   Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C.,
RA   So W.-Y., Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S.,
RA   Critchley J.A.J.H., Bell G.I., Chan J.C.N.;
RT   "Molecular genetics of diabetes mellitus in Chinese subjects:
RT   identification of mutations in glucokinase and hepatocyte nuclear
RT   factor-1alpha genes in patients with early-onset type 2 diabetes
RT   mellitus/MODY.";
RL   Diabet. Med. 16:956-963(1999).
RN   [31]
RP   VARIANT MODY2 PRO-164.
RX   PubMed=11106831; DOI=10.1016/S0168-8227(00)00191-1;
RA   Nam J.H., Lee H.C., Kim Y.H., Cha B.S., Song Y.D., Lim S.K., Kim K.R.,
RA   Huh K.B.;
RT   "Identification of glucokinase mutation in subjects with post-renal
RT   transplantation diabetes mellitus.";
RL   Diabetes Res. Clin. Pract. 50:169-176(2000).
RN   [32]
RP   INVOLVEMENT IN PNDM, INVOLVEMENT IN MODY2, VARIANTS MODY2 LYS-210 AND
RP   MET-228, AND VARIANTS PNDM LYS-210 AND MET-228.
RX   PubMed=11372010; DOI=10.1056/NEJM200105243442104;
RA   Njoelstad P.R., Soevik O., Cuesta-Munoz A., Bjoerkhaug L., Massa O.,
RA   Barbetti F., Undlien D.E., Shiota C., Magnuson M.A., Molven A.,
RA   Matschinsky F.M., Bell G.I.;
RT   "Neonatal diabetes mellitus due to complete glucokinase deficiency.";
RL   N. Engl. J. Med. 344:1588-1592(2001).
RN   [33]
RP   VARIANT HHF3 VAL-456, CHARACTERIZATION OF VARIANT HHF3 VAL-456,
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=11916951;
RA   Christesen H.B., Jacobsen B.B., Odili S., Buettger C.,
RA   Cuesta-Munoz A., Hansen T., Brusgaard K., Massa O., Magnuson M.A.,
RA   Shiota C., Matschinsky F.M., Barbetti F.;
RT   "The second activating glucokinase mutation (A456V): implications for
RT   glucose homeostasis and diabetes therapy.";
RL   Diabetes 51:1240-1246(2002).
RN   [34]
RP   VARIANT HHF3 ILE-65, AND CHARACTERIZATION OF VARIANT HHF3 ILE-65.
RX   PubMed=12941786;
RA   Gloyn A.L., Noordam K., Willemsen M.A., Ellard S., Lam W.W.,
RA   Campbell I.W., Midgley P., Shiota C., Buettger C., Magnuson M.A.,
RA   Matschinsky F.M., Hattersley A.T.;
RT   "Insights into the biochemical and genetic basis of glucokinase
RT   activation from naturally occurring hypoglycemia mutations.";
RL   Diabetes 52:2433-2440(2003).
RN   [35]
RP   VARIANT HHF3 CYS-214, CHARACTERIZATION OF VARIANT HHF3 CYS-214,
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=15277402;
RA   Cuesta-Munoz A.L., Huopio H., Otonkoski T., Gomez-Zumaquero J.M.,
RA   Naentoe-Salonen K., Rahier J., Lopez-Enriquez S., Garcia-Gimeno M.A.,
RA   Sanz P., Soriguer F.C., Laakso M.;
RT   "Severe persistent hyperinsulinemic hypoglycemia due to a de novo
RT   glucokinase mutation.";
RL   Diabetes 53:2164-2168(2004).
RN   [36]
RP   VARIANTS MODY2 TRP-36; TYR-129; LEU-152; VAL-188; TRP-191; ARG-202;
RP   SER-223; MET-226; HIS-231; PHE-315; THR-378; PHE-434; TRP-441 AND
RP   GLN-447.
RX   PubMed=16965331; DOI=10.1111/j.1399-0004.2006.00686.x;
RA   Vits L., Beckers D., Craen M., de Beaufort C., Vanfleteren E.,
RA   Dahan K., Nollet A., Vanhaverbeke G., Imschoot S.V., Bourguignon J.P.,
RA   Beauloye V., Storm K., Massa G., Giri M., Nobels F., De Schepper J.,
RA   Rooman R., Van den Bruel A., Mathieu C., Wuyts W.;
RT   "Identification of novel and recurrent glucokinase mutations in
RT   Belgian and Luxembourg maturity onset diabetes of the young
RT   patients.";
RL   Clin. Genet. 70:355-359(2006).
RN   [37]
RP   CHARACTERIZATION OF VARIANTS HHF3 ILE-65; CYS-214; MET-455 AND
RP   VAL-456, MUTAGENESIS OF TYR-214 AND TYR-215, FUNCTION, AND CATALYTIC
RP   ACTIVITY.
RX   PubMed=17082186; DOI=10.1074/jbc.M607987200;
RA   Heredia V.V., Carlson T.J., Garcia E., Sun S.;
RT   "Biochemical basis of glucokinase activation and the regulation by
RT   glucokinase regulatory protein in naturally occurring mutations.";
RL   J. Biol. Chem. 281:40201-40207(2006).
RN   [38]
RP   VARIANTS MODY2 GLU-16; ASN-19; PRO-20; TRP-36; SER-43; SER-44;
RP   61-TYR--GLN-465 DEL; SER-61; LYS-70; ARG-72; PRO-77; GLU-78; ASP-80;
RP   ILE-82; HIS-108; PRO-116; LEU-182; 186-ARG--GLN-465 DEL; TYR-187;
RP   TRP-191; LEU-200; THR-202; MET-206; MET-209; SER-223; ARG-224;
RP   SER-227; MET-228; ARG-233; 234-TYR--GLN-465 DEL; GLY-252; ALA-255;
RP   LYS-256; ARG-261; LYS-265; LYS-298; TRP-308; HIS-377; VAL-379;
RP   LEU-383; 399-GLU--GLN-465 DEL; PHE-411; PRO-416; GLU-420 AND TRP-441.
RX   PubMed=17573900; DOI=10.1111/j.1365-2265.2007.02921.x;
RG   Spanish MODY Group;
RA   Estalella I., Rica I., Perez de Nanclares G., Bilbao J.R.,
RA   Vazquez J.A., San Pedro J.I., Busturia M.A., Castano L.;
RT   "Mutations in GCK and HNF-1alpha explain the majority of cases with
RT   clinical diagnosis of MODY in Spain.";
RL   Clin. Endocrinol. (Oxf.) 67:538-546(2007).
RN   [39]
RP   CHARACTERIZATION OF VARIANTS MODY2 SER-61; LEU-182; ARG-233; LYS-265;
RP   VAL-379 AND GLU-420, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=18322640; DOI=10.1007/s10038-008-0271-5;
RA   Estalella I., Garcia-Gimeno M.A., Marina A., Castano L., Sanz P.;
RT   "Biochemical characterization of novel glucokinase mutations isolated
RT   from Spanish maturity-onset diabetes of the young (MODY2) patients.";
RL   J. Hum. Genet. 53:460-466(2008).
RN   [40]
RP   VARIANT MODY2 TRP-441, CHARACTERIZATION OF VARIANT MODY2 TRP-441,
RP   VARIANT HHF3 LYS-442, AND CHARACTERIZATION OF VARIANT HHF3 LYS-442.
RX   PubMed=19884385; DOI=10.1210/me.2009-0094;
RA   Barbetti F., Cobo-Vuilleumier N., Dionisi-Vici C., Toni S.,
RA   Ciampalini P., Massa O., Rodriguez-Bada P., Colombo C., Lenzi L.,
RA   Garcia-Gimeno M.A., Bermudez-Silva F.J., Rodriguez de Fonseca F.,
RA   Banin P., Aledo J.C., Baixeras E., Sanz P., Cuesta-Munoz A.L.;
RT   "Opposite clinical phenotypes of glucokinase disease: Description of a
RT   novel activating mutation and contiguous inactivating mutations in
RT   human glucokinase (GCK) gene.";
RL   Mol. Endocrinol. 23:1983-1989(2009).
RN   [41]
RP   VARIANT HHF3 LEU-91, AND CHARACTERIZATION OF VARIANT HHF3 LEU-91.
RX   PubMed=20375417; DOI=10.1056/NEJMc0909845;
RA   Kassem S., Bhandari S., Rodriguez-Bada P., Motaghedi R., Heyman M.,
RA   Garcia-Gimeno M.A., Cobo-Vuilleumier N., Sanz P., Maclaren N.K.,
RA   Rahier J., Glaser B., Cuesta-Munoz A.L.;
RT   "Large islets, beta-cell proliferation, and a glucokinase mutation.";
RL   N. Engl. J. Med. 362:1348-1350(2010).
RN   [42]
RP   ERRATUM.
RA   Kassem S., Bhandari S., Rodriguez-Bada P., Motaghedi R., Heyman M.,
RA   Garcia-Gimeno M.A., Cobo-Vuilleumier N., Sanz P., Maclaren N.K.,
RA   Rahier J., Glaser B., Cuesta-Munoz A.L.;
RL   N. Engl. J. Med. 363:2178-2178(2010).
RN   [43]
RP   VARIANT PRO-342.
RX   PubMed=21604084; DOI=10.1007/s00125-011-2194-5;
RA   Steele A.M., Tribble N.D., Caswell R., Wensley K.J., Hattersley A.T.,
RA   Gloyn A.L., Ellard S.;
RT   "The previously reported T342P GCK missense variant is not a
RT   pathogenic mutation causing MODY.";
RL   Diabetologia 54:2202-2205(2011).
RN   [44]
RP   VARIANTS MODY2 HIS-43; ASP-68; ASN-217; MET-225; LYS-248; ARG-261 AND
RP   ARG-261, AND CHARACTERIZATION OF VARIANTS MODY2 HIS-43; ASP-68;
RP   ASN-217; MET-225; LYS-248; ARG-261 AND ARG-261.
RX   PubMed=22611063; DOI=10.2337/dc11-2420;
RA   Beer N.L., Osbak K.K., van de Bunt M., Tribble N.D., Steele A.M.,
RA   Wensley K.J., Edghill E.L., Colcough K., Barrett A., Valentinova L.,
RA   Rundle J.K., Raimondo A., Grimsby J., Ellard S., Gloyn A.L.;
RT   "Insights into the pathogenicity of rare missense GCK variants from
RT   the identification and functional characterization of compound
RT   heterozygous and double mutations inherited in cis.";
RL   Diabetes Care 35:1482-1484(2012).
RN   [45]
RP   VARIANTS PNDM LYS-40; CYS-43; ASP-50; ARG-72; THR-151; PRO-164;
RP   ALA-168; ARG-169; ARG-261; THR-393; LEU-397; LEU-441 AND THR-449,
RP   CHARACTERIZATION OF VARIANTS PNDM LYS-40; CYS-43; ASP-50; ARG-72;
RP   ALA-168; ARG-261; THR-393; LEU-397; LEU-441 AND THR-449, VARIANTS
RP   MODY2 ASN-160 AND MET-226, CHARACTERIZATION OF VARIANT MODY2 ASN-160
RP   AND MET-226, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=25015100; DOI=10.1093/hmg/ddu360;
RG   International NDM Consortium;
RA   Raimondo A., Chakera A.J., Thomsen S.K., Colclough K., Barrett A.,
RA   De Franco E., Chatelas A., Demirbilek H., Akcay T., Alawneh H.,
RA   Flanagan S.E., Van De Bunt M., Hattersley A.T., Gloyn A.L., Ellard S.;
RT   "Phenotypic severity of homozygous GCK mutations causing neonatal or
RT   childhood-onset diabetes is primarily mediated through effects on
RT   protein stability.";
RL   Hum. Mol. Genet. 23:6432-6440(2014).
RN   [46]
RP   VARIANTS HHF3 ILE-65; LEU-91; CYS-99 AND LYS-442, AND CHARACTERIZATION
RP   OF VARIANT HHF3 CYS-99.
RX   PubMed=28247534; DOI=10.1111/cen.13318;
RG   Spanish Congenital Hyperinsulinism Group;
RA   Martinez R., Gutierrez-Nogues A., Fernandez-Ramos C., Velayos T.,
RA   Vela A., Navas M.A., Castano L.;
RT   "Heterogeneity in phenotype of hyperinsulinism caused by activating
RT   glucokinase mutations: a novel mutation and its functional
RT   characterization.";
RL   Clin. Endocrinol. (Oxf.) 86:778-783(2017).
CC   -!- FUNCTION: Catalyzes the initial step in utilization of glucose by
CC       the beta-cell and liver at physiological glucose concentration.
CC       Glucokinase has a high Km for glucose, and so it is effective only
CC       when glucose is abundant. The role of GCK is to provide G6P for
CC       the synthesis of glycogen. Pancreatic glucokinase plays an
CC       important role in modulating insulin secretion. Hepatic
CC       glucokinase helps to facilitate the uptake and conversion of
CC       glucose by acting as an insulin-sensitive determinant of hepatic
CC       glucose usage. {ECO:0000269|PubMed:11916951,
CC       ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186,
CC       ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19146401,
CC       ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:8325892}.
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;
CC         EC=2.7.1.2; Evidence={ECO:0000269|PubMed:11916951,
CC         ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186,
CC         ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19146401,
CC         ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:8325892};
CC   -!- ACTIVITY REGULATION: The use of alternative promoters apparently
CC       enables the type IV hexokinase gene to be regulated by insulin in
CC       the liver and glucose in the beta cell. This may constitute an
CC       important feedback loop for maintaining glucose homeostasis.
CC       Subject to allosteric regulation. Low glucose and high fructose-6-
CC       phosphate triggers association with the inhibitor GKRP followed by
CC       sequestration in the nucleus. {ECO:0000269|PubMed:10456334,
CC       ECO:0000269|PubMed:15016359}.
CC   -!- SUBUNIT: Monomer (PubMed:15016359, PubMed:19362831,
CC       PubMed:23957911). Interacts with MIDN; the interaction occurs
CC       preferentially at low glucose levels and results in inhibition of
CC       GCK activity (PubMed:24187134). {ECO:0000269|PubMed:15016359,
CC       ECO:0000269|PubMed:19362831, ECO:0000269|PubMed:23957911,
CC       ECO:0000269|PubMed:24187134}.
CC   -!- INTERACTION:
CC       Q14397:GCKR; NbExp=2; IntAct=EBI-709928, EBI-709948;
CC       P16118:PFKFB1; NbExp=2; IntAct=EBI-709928, EBI-709807;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334,
CC       ECO:0000269|PubMed:24187134}. Nucleus
CC       {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:24187134}.
CC       Note=Under low glucose concentrations, GCK associates with GKRP
CC       and the inactive complex is recruited to the hepatocyte nucleus.
CC       {ECO:0000269|PubMed:10456334}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P35557-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P35557-2; Sequence=VSP_002074;
CC       Name=3;
CC         IsoId=P35557-3; Sequence=VSP_002075;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is expressed in pancreas. Isoform 2
CC       and isoform 3 is expressed in liver.
CC   -!- DISEASE: Maturity-onset diabetes of the young 2 (MODY2)
CC       [MIM:125851]: A form of diabetes that is characterized by an
CC       autosomal dominant mode of inheritance, onset in childhood or
CC       early adulthood (usually before 25 years of age), a primary defect
CC       in insulin secretion and frequent insulin-independence at the
CC       beginning of the disease. {ECO:0000269|PubMed:10588527,
CC       ECO:0000269|PubMed:10694920, ECO:0000269|PubMed:11106831,
CC       ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:1303265,
CC       ECO:0000269|PubMed:1464666, ECO:0000269|PubMed:1502186,
CC       ECO:0000269|PubMed:16965331, ECO:0000269|PubMed:17573900,
CC       ECO:0000269|PubMed:18322640, ECO:0000269|PubMed:19884385,
CC       ECO:0000269|PubMed:22611063, ECO:0000269|PubMed:25015100,
CC       ECO:0000269|PubMed:8168652, ECO:0000269|PubMed:8325892,
CC       ECO:0000269|PubMed:8446612, ECO:0000269|PubMed:8495817,
CC       ECO:0000269|PubMed:9049484, ECO:0000269|PubMed:9662401}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Familial hyperinsulinemic hypoglycemia 3 (HHF3)
CC       [MIM:602485]: Most common cause of persistent hypoglycemia in
CC       infancy. Unless early and aggressive intervention is undertaken,
CC       brain damage from recurrent episodes of hypoglycemia may occur.
CC       {ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:12941786,
CC       ECO:0000269|PubMed:15277402, ECO:0000269|PubMed:17082186,
CC       ECO:0000269|PubMed:19884385, ECO:0000269|PubMed:20375417,
CC       ECO:0000269|PubMed:28247534, ECO:0000269|PubMed:9435328}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM)
CC       [MIM:125853]: A multifactorial disorder of glucose homeostasis
CC       caused by a lack of sensitivity to the body's own insulin.
CC       Affected individuals usually have an obese body habitus and
CC       manifestations of a metabolic syndrome characterized by diabetes,
CC       insulin resistance, hypertension and hypertriglyceridemia. The
CC       disease results in long-term complications that affect the eyes,
CC       kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:1360036}.
CC       Note=Disease susceptibility is associated with variations
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Diabetes mellitus, permanent neonatal (PNDM)
CC       [MIM:606176]: A rare form of diabetes distinct from childhood-
CC       onset autoimmune diabetes mellitus type 1. It is characterized by
CC       insulin-requiring hyperglycemia that is diagnosed within the first
CC       months of life. Permanent neonatal diabetes requires lifelong
CC       therapy. {ECO:0000269|PubMed:11372010,
CC       ECO:0000269|PubMed:25015100}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
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}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Glucokinase entry;
CC       URL="https://en.wikipedia.org/wiki/Glucokinase";
DR   EMBL; M88011; AAA51824.1; -; mRNA.
DR   EMBL; M69051; AAB59563.1; ALT_SEQ; mRNA.
DR   EMBL; M90298; AAA67541.1; ALT_TERM; Genomic_DNA.
DR   EMBL; M90298; AAA67542.1; ALT_TERM; Genomic_DNA.
DR   EMBL; M90299; AAA52562.1; -; mRNA.
DR   EMBL; AF041022; AAB97680.1; -; Genomic_DNA.
DR   EMBL; AF041012; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041015; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041016; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041017; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041018; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041019; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041020; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041021; AAB97680.1; JOINED; Genomic_DNA.
DR   EMBL; AF041022; AAB97681.1; -; Genomic_DNA.
DR   EMBL; AF041013; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041015; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041016; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041017; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041018; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041019; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041020; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041021; AAB97681.1; JOINED; Genomic_DNA.
DR   EMBL; AF041022; AAB97682.1; -; Genomic_DNA.
DR   EMBL; AF041014; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041015; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041016; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041017; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041018; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041019; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041020; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AF041021; AAB97682.1; JOINED; Genomic_DNA.
DR   EMBL; AK122876; BAG53774.1; -; mRNA.
DR   EMBL; CH236960; EAL23765.1; -; Genomic_DNA.
DR   EMBL; CH236960; EAL23766.1; -; Genomic_DNA.
DR   EMBL; CH471128; EAW61114.1; -; Genomic_DNA.
DR   EMBL; CH471128; EAW61116.1; -; Genomic_DNA.
DR   EMBL; BC001890; AAH01890.1; -; mRNA.
DR   CCDS; CCDS5479.1; -. [P35557-1]
DR   CCDS; CCDS5480.1; -. [P35557-2]
DR   CCDS; CCDS5481.1; -. [P35557-3]
DR   PIR; A46157; A46157.
DR   PIR; B46157; B46157.
DR   PIR; C46157; C46157.
DR   RefSeq; NP_000153.1; NM_000162.3. [P35557-1]
DR   RefSeq; NP_277042.1; NM_033507.1. [P35557-2]
DR   RefSeq; NP_277043.1; NM_033508.1. [P35557-3]
DR   UniGene; Hs.1270; -.
DR   PDB; 1GLK; Model; -; A=1-465.
DR   PDB; 1V4S; X-ray; 2.30 A; A=16-465.
DR   PDB; 1V4T; X-ray; 3.40 A; A=16-465.
DR   PDB; 3A0I; X-ray; 2.20 A; X=16-465.
DR   PDB; 3F9M; X-ray; 1.50 A; A=12-465.
DR   PDB; 3FGU; X-ray; 2.15 A; A=12-465.
DR   PDB; 3FR0; X-ray; 2.70 A; A=16-465.
DR   PDB; 3GOI; X-ray; 2.52 A; A=16-465.
DR   PDB; 3H1V; X-ray; 2.11 A; X=16-465.
DR   PDB; 3ID8; X-ray; 2.40 A; A=12-465.
DR   PDB; 3IDH; X-ray; 2.14 A; A=12-465.
DR   PDB; 3IMX; X-ray; 2.00 A; A=16-465.
DR   PDB; 3QIC; X-ray; 2.20 A; A=12-465.
DR   PDB; 3S41; X-ray; 2.18 A; A=12-465.
DR   PDB; 3VEV; X-ray; 1.80 A; A=12-465.
DR   PDB; 3VEY; X-ray; 2.25 A; A=16-465.
DR   PDB; 3VF6; X-ray; 1.86 A; A=12-465.
DR   PDB; 4DCH; X-ray; 1.79 A; A=1-465.
DR   PDB; 4DHY; X-ray; 2.38 A; A=12-465.
DR   PDB; 4ISE; X-ray; 1.78 A; A=16-465.
DR   PDB; 4ISF; X-ray; 2.09 A; A=16-465.
DR   PDB; 4ISG; X-ray; 2.64 A; A=16-465.
DR   PDB; 4IWV; X-ray; 2.10 A; A=16-465.
DR   PDB; 4IXC; X-ray; 2.00 A; A=16-465.
DR   PDB; 4L3Q; X-ray; 2.70 A; A=16-465.
DR   PDB; 4LC9; X-ray; 3.40 A; B=3-465.
DR   PDB; 4MLE; X-ray; 2.60 A; A=16-465.
DR   PDB; 4MLH; X-ray; 2.90 A; A=16-465.
DR   PDB; 4NO7; X-ray; 1.70 A; A=12-465.
DR   PDB; 4RCH; X-ray; 2.30 A; A=16-465.
DR   PDB; 5V4W; X-ray; 2.39 A; A=16-465.
DR   PDB; 5V4X; X-ray; 2.08 A; A=16-465.
DR   PDBsum; 1GLK; -.
DR   PDBsum; 1V4S; -.
DR   PDBsum; 1V4T; -.
DR   PDBsum; 3A0I; -.
DR   PDBsum; 3F9M; -.
DR   PDBsum; 3FGU; -.
DR   PDBsum; 3FR0; -.
DR   PDBsum; 3GOI; -.
DR   PDBsum; 3H1V; -.
DR   PDBsum; 3ID8; -.
DR   PDBsum; 3IDH; -.
DR   PDBsum; 3IMX; -.
DR   PDBsum; 3QIC; -.
DR   PDBsum; 3S41; -.
DR   PDBsum; 3VEV; -.
DR   PDBsum; 3VEY; -.
DR   PDBsum; 3VF6; -.
DR   PDBsum; 4DCH; -.
DR   PDBsum; 4DHY; -.
DR   PDBsum; 4ISE; -.
DR   PDBsum; 4ISF; -.
DR   PDBsum; 4ISG; -.
DR   PDBsum; 4IWV; -.
DR   PDBsum; 4IXC; -.
DR   PDBsum; 4L3Q; -.
DR   PDBsum; 4LC9; -.
DR   PDBsum; 4MLE; -.
DR   PDBsum; 4MLH; -.
DR   PDBsum; 4NO7; -.
DR   PDBsum; 4RCH; -.
DR   PDBsum; 5V4W; -.
DR   PDBsum; 5V4X; -.
DR   ProteinModelPortal; P35557; -.
DR   SMR; P35557; -.
DR   BioGrid; 108915; 10.
DR   IntAct; P35557; 6.
DR   STRING; 9606.ENSP00000223366; -.
DR   BindingDB; P35557; -.
DR   ChEMBL; CHEMBL3820; -.
DR   DrugBank; DB02379; Beta-D-Glucose.
DR   GuidetoPHARMACOLOGY; 2798; -.
DR   iPTMnet; P35557; -.
DR   PhosphoSitePlus; P35557; -.
DR   BioMuta; GCK; -.
DR   DMDM; 547696; -.
DR   PaxDb; P35557; -.
DR   PeptideAtlas; P35557; -.
DR   PRIDE; P35557; -.
DR   ProteomicsDB; 55084; -.
DR   ProteomicsDB; 55085; -. [P35557-2]
DR   ProteomicsDB; 55086; -. [P35557-3]
DR   DNASU; 2645; -.
DR   Ensembl; ENST00000345378; ENSP00000223366; ENSG00000106633. [P35557-2]
DR   Ensembl; ENST00000395796; ENSP00000379142; ENSG00000106633. [P35557-3]
DR   Ensembl; ENST00000403799; ENSP00000384247; ENSG00000106633. [P35557-1]
DR   Ensembl; ENST00000616242; ENSP00000482149; ENSG00000106633. [P35557-3]
DR   GeneID; 2645; -.
DR   KEGG; hsa:2645; -.
DR   UCSC; uc003tkj.2; human. [P35557-1]
DR   CTD; 2645; -.
DR   DisGeNET; 2645; -.
DR   EuPathDB; HostDB:ENSG00000106633.15; -.
DR   GeneCards; GCK; -.
DR   GeneReviews; GCK; -.
DR   HGNC; HGNC:4195; GCK.
DR   HPA; HPA007034; -.
DR   HPA; HPA007093; -.
DR   MalaCards; GCK; -.
DR   MIM; 125851; phenotype.
DR   MIM; 125853; phenotype.
DR   MIM; 138079; gene.
DR   MIM; 602485; phenotype.
DR   MIM; 606176; phenotype.
DR   MIM; 606391; phenotype.
DR   neXtProt; NX_P35557; -.
DR   OpenTargets; ENSG00000106633; -.
DR   Orphanet; 79299; Hyperinsulinism due to glucokinase deficiency.
DR   Orphanet; 552; MODY.
DR   Orphanet; 99885; Permanent neonatal diabetes mellitus.
DR   PharmGKB; PA28610; -.
DR   eggNOG; KOG1369; Eukaryota.
DR   eggNOG; COG5026; LUCA.
DR   GeneTree; ENSGT00940000153555; -.
DR   HOGENOM; HOG000162670; -.
DR   HOVERGEN; HBG000142; -.
DR   InParanoid; P35557; -.
DR   KO; K12407; -.
DR   OMA; ASHYVNP; -.
DR   OrthoDB; EOG091G08MD; -.
DR   PhylomeDB; P35557; -.
DR   TreeFam; TF314238; -.
DR   BioCyc; MetaCyc:HS02935-MONOMER; -.
DR   BRENDA; 2.7.1.1; 2681.
DR   BRENDA; 2.7.1.2; 2681.
DR   Reactome; R-HSA-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR   Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR   Reactome; R-HSA-5619073; Defective GCK causes maturity-onset diabetes of the young 2 (MODY2).
DR   Reactome; R-HSA-5619107; Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC).
DR   Reactome; R-HSA-70171; Glycolysis.
DR   SABIO-RK; P35557; -.
DR   SIGNOR; P35557; -.
DR   ChiTaRS; GCK; human.
DR   EvolutionaryTrace; P35557; -.
DR   GeneWiki; Glucokinase; -.
DR   GenomeRNAi; 2645; -.
DR   PRO; PR:P35557; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   Bgee; ENSG00000106633; Expressed in 96 organ(s), highest expression level in liver.
DR   CleanEx; HS_GCK; -.
DR   ExpressionAtlas; P35557; baseline and differential.
DR   Genevisible; P35557; HS.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR   GO; GO:0008865; F:fructokinase activity; IBA:GO_Central.
DR   GO; GO:0004340; F:glucokinase activity; IDA:UniProtKB.
DR   GO; GO:0005536; F:glucose binding; IDA:UniProtKB.
DR   GO; GO:0019158; F:mannokinase activity; IBA:GO_Central.
DR   GO; GO:0070509; P:calcium ion import; IEA:Ensembl.
DR   GO; GO:0061621; P:canonical glycolysis; TAS:Reactome.
DR   GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; ISS:BHF-UCL.
DR   GO; GO:0044320; P:cellular response to leptin stimulus; ISS:BHF-UCL.
DR   GO; GO:0051594; P:detection of glucose; IMP:UniProtKB.
DR   GO; GO:0051156; P:glucose 6-phosphate metabolic process; IMP:UniProtKB.
DR   GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR   GO; GO:0006096; P:glycolytic process; IBA:GO_Central.
DR   GO; GO:0006739; P:NADP metabolic process; IEA:Ensembl.
DR   GO; GO:0045721; P:negative regulation of gluconeogenesis; IMP:UniProtKB.
DR   GO; GO:0045725; P:positive regulation of glycogen biosynthetic process; IMP:UniProtKB.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IMP:UniProtKB.
DR   GO; GO:0006110; P:regulation of glycolytic process; TAS:Reactome.
DR   GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
DR   GO; GO:0043266; P:regulation of potassium ion transport; IEA:Ensembl.
DR   InterPro; IPR039073; GCK_chordate.
DR   InterPro; IPR001312; Hexokinase.
DR   InterPro; IPR019807; Hexokinase_BS.
DR   InterPro; IPR022673; Hexokinase_C.
DR   InterPro; IPR022672; Hexokinase_N.
DR   PANTHER; PTHR19443; PTHR19443; 1.
DR   PANTHER; PTHR19443:SF3; PTHR19443:SF3; 1.
DR   Pfam; PF00349; Hexokinase_1; 1.
DR   Pfam; PF03727; Hexokinase_2; 1.
DR   PROSITE; PS00378; HEXOKINASE_1; 1.
DR   PROSITE; PS51748; HEXOKINASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding;
KW   Complete proteome; Cytoplasm; Diabetes mellitus; Disease mutation;
KW   Glycolysis; Kinase; Nucleotide-binding; Nucleus; Polymorphism;
KW   Reference proteome; Transferase.
FT   CHAIN         1    465       Glucokinase.
FT                                /FTId=PRO_0000197593.
FT   DOMAIN       10    454       Hexokinase. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01084}.
FT   NP_BIND      78     83       ATP. {ECO:0000250}.
FT   NP_BIND     295    296       ATP. {ECO:0000250}.
FT   NP_BIND     332    336       ATP. {ECO:0000250}.
FT   NP_BIND     411    415       ATP. {ECO:0000250}.
FT   REGION       67    203       Hexokinase small subdomain.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      151    152       Substrate binding.
FT   REGION      168    169       Substrate binding.
FT   REGION      204    443       Hexokinase large subdomain.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01084}.
FT   REGION      204    205       Substrate binding.
FT   BINDING     104    104       ATP. {ECO:0000255}.
FT   BINDING     228    228       ATP. {ECO:0000250}.
FT   BINDING     231    231       Substrate.
FT   BINDING     256    256       Substrate.
FT   BINDING     290    290       Substrate.
FT   VAR_SEQ       1     15       MLDDRARMEAAKKEK -> MAMDVTRSQAQTALTL (in
FT                                isoform 2).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_002074.
FT   VAR_SEQ       1     15       MLDDRARMEAAKKEK -> MPRPRSQLPQPNSQ (in
FT                                isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_002075.
FT   VARIANT       4      4       D -> N (in dbSNP:rs202091228).
FT                                {ECO:0000269|PubMed:8325892}.
FT                                /FTId=VAR_003692.
FT   VARIANT      11     11       A -> T (in dbSNP:rs116093166).
FT                                {ECO:0000269|PubMed:8454109}.
FT                                /FTId=VAR_010583.
FT   VARIANT      16     16       V -> E (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079430.
FT   VARIANT      19     19       I -> N (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079431.
FT   VARIANT      20     20       L -> P (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079432.
FT   VARIANT      36     36       R -> W (in MODY2; dbSNP:rs762263694).
FT                                {ECO:0000269|PubMed:16965331,
FT                                ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:8168652}.
FT                                /FTId=VAR_010584.
FT   VARIANT      40     40       E -> K (in PNDM; decreased stability;
FT                                decreased glucokinase activity; decreased
FT                                affinity for glucose; dbSNP:rs794727236).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079433.
FT   VARIANT      43     43       R -> C (in PNDM; decreased stability;
FT                                decreased glucokinase activity; no effect
FT                                on affinity for glucose;
FT                                dbSNP:rs1486280029).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079434.
FT   VARIANT      43     43       R -> H (in MODY2; unknown pathological
FT                                significance; no change in glucokinase
FT                                activity; dbSNP:rs764232985).
FT                                {ECO:0000269|PubMed:22611063}.
FT                                /FTId=VAR_075220.
FT   VARIANT      43     43       R -> S (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079435.
FT   VARIANT      44     44       G -> S (in MODY2; dbSNP:rs267601516).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079436.
FT   VARIANT      50     50       H -> D (in PNDM; loss of stability; loss
FT                                of glucokinase activity; decreased
FT                                affinity for glucose).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079437.
FT   VARIANT      53     53       A -> S (in MODY2).
FT                                /FTId=VAR_010585.
FT   VARIANT      61    465       Missing (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079438.
FT   VARIANT      61     61       Y -> S (in MODY2; decreased glucokinase
FT                                activity; decreased affinity for glucose;
FT                                increased affinity for ATP).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079439.
FT   VARIANT      65     65       T -> I (in HHF3; increased glucokinase
FT                                activity based on measure of catalytic
FT                                efficiency; increased affinity for
FT                                glucose; loss of inhibition by GKRP;
FT                                unchanged affinity for ATP).
FT                                {ECO:0000269|PubMed:12941786,
FT                                ECO:0000269|PubMed:17082186,
FT                                ECO:0000269|PubMed:28247534}.
FT                                /FTId=VAR_078243.
FT   VARIANT      68     68       G -> D (in MODY2; unknown pathological
FT                                significance; mildly increases
FT                                glucokinase activity; dbSNP:rs373418736).
FT                                {ECO:0000269|PubMed:22611063}.
FT                                /FTId=VAR_075221.
FT   VARIANT      70     70       E -> K (in MODY2; decreased affinity for
FT                                glucose). {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:8325892}.
FT                                /FTId=VAR_003693.
FT   VARIANT      72     72       G -> R (in MODY2 and PNDM; decreased
FT                                stability; no effect on glucokinase
FT                                activity; no effect on affinity for
FT                                glucose; dbSNP:rs193922289).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079440.
FT   VARIANT      77     77       L -> P (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079441.
FT   VARIANT      78     78       D -> E (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079442.
FT   VARIANT      80     80       G -> A (in MODY2).
FT                                /FTId=VAR_003694.
FT   VARIANT      80     80       G -> D (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079443.
FT   VARIANT      80     80       G -> S (in MODY2).
FT                                {ECO:0000269|PubMed:10694920}.
FT                                /FTId=VAR_003695.
FT   VARIANT      82     82       T -> I (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079444.
FT   VARIANT      91     91       V -> L (in HHF3; increased glucokinase
FT                                activity; increased affinity for
FT                                glucose). {ECO:0000269|PubMed:20375417,
FT                                ECO:0000269|PubMed:28247534}.
FT                                /FTId=VAR_078244.
FT   VARIANT      99     99       W -> C (in HHF3; increased glucokinase
FT                                activity; increased affinity for glucose;
FT                                increased affinity for ATP).
FT                                {ECO:0000269|PubMed:28247534}.
FT                                /FTId=VAR_078245.
FT   VARIANT     107    107       M -> T. {ECO:0000269|PubMed:1464666,
FT                                ECO:0000269|PubMed:1871135}.
FT                                /FTId=VAR_003696.
FT   VARIANT     108    108       Y -> H (in MODY2).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010586.
FT   VARIANT     110    110       I -> T (in MODY2; dbSNP:rs1338970607).
FT                                {ECO:0000269|PubMed:10588527}.
FT                                /FTId=VAR_012352.
FT   VARIANT     116    116       T -> P (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079445.
FT   VARIANT     119    119       A -> D (in MODY2; dbSNP:rs1176659689).
FT                                {ECO:0000269|PubMed:10588527}.
FT                                /FTId=VAR_012353.
FT   VARIANT     129    129       C -> Y (in MODY2).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078246.
FT   VARIANT     131    131       S -> P (in MODY2; decreased affinity for
FT                                glucose; dbSNP:rs104894010).
FT                                {ECO:0000269|PubMed:8325892,
FT                                ECO:0000269|PubMed:8495817}.
FT                                /FTId=VAR_003697.
FT   VARIANT     137    137       H -> R (in MODY2).
FT                                /FTId=VAR_010587.
FT   VARIANT     150    150       F -> S (in MODY2; dbSNP:rs193922297).
FT                                {ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010588.
FT   VARIANT     151    151       S -> T (in PNDM).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079446.
FT   VARIANT     152    152       F -> L (in MODY2; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078247.
FT   VARIANT     160    160       D -> N (in MODY2; no effect on stability;
FT                                decreased glucokinase activity; decreased
FT                                affinity for glucose).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079447.
FT   VARIANT     164    164       L -> P (in MODY2 and PNDM).
FT                                {ECO:0000269|PubMed:11106831,
FT                                ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_012350.
FT   VARIANT     168    168       T -> A (in PNDM; decreased glucokinase
FT                                activity; decreased affinity for
FT                                glucose). {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079448.
FT   VARIANT     168    168       T -> P (in MODY2).
FT                                /FTId=VAR_010589.
FT   VARIANT     169    169       K -> R (in PNDM).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079449.
FT   VARIANT     175    175       G -> R (in MODY2; dbSNP:rs587780344).
FT                                /FTId=VAR_003698.
FT   VARIANT     182    182       V -> L (in MODY2; decreased glucokinase
FT                                activity; decreased affinity for glucose;
FT                                increased affinity for ATP).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079450.
FT   VARIANT     182    182       V -> M (in MODY2; dbSNP:rs587780345).
FT                                /FTId=VAR_003699.
FT   VARIANT     186    465       Missing (in MODY2 and NIDDM).
FT                                {ECO:0000269|PubMed:1360036,
FT                                ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079451.
FT   VARIANT     187    187       D -> Y (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079452.
FT   VARIANT     188    188       A -> T (in MODY2; decreased affinity for
FT                                glucose; dbSNP:rs751279776).
FT                                {ECO:0000269|PubMed:8325892}.
FT                                /FTId=VAR_003700.
FT   VARIANT     188    188       A -> V (in MODY2; dbSNP:rs193922307).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078248.
FT   VARIANT     191    191       R -> W (in MODY2; dbSNP:rs1085307455).
FT                                {ECO:0000269|PubMed:16965331,
FT                                ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_078249.
FT   VARIANT     200    200       V -> L (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079453.
FT   VARIANT     202    202       M -> R (in MODY2).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078250.
FT   VARIANT     202    202       M -> T (in MODY2; dbSNP:rs193922311).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079454.
FT   VARIANT     203    203       V -> A (in MODY2).
FT                                /FTId=VAR_003701.
FT   VARIANT     206    206       T -> M (in MODY2; dbSNP:rs1441649062).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079455.
FT   VARIANT     209    209       T -> M (in MODY2).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:8168652}.
FT                                /FTId=VAR_010590.
FT   VARIANT     210    210       M -> K (in MODY2 and PNDM;
FT                                dbSNP:rs80356654).
FT                                {ECO:0000269|PubMed:11372010}.
FT                                /FTId=VAR_012351.
FT   VARIANT     210    210       M -> T (in MODY2).
FT                                /FTId=VAR_010591.
FT   VARIANT     213    213       C -> R (in MODY2).
FT                                /FTId=VAR_010592.
FT   VARIANT     214    214       Y -> C (in HHF3; increased glucokinase
FT                                activity based on measure of catalytic
FT                                efficiency; increased affinity for
FT                                glucose; decreased inhibition by GKRP;
FT                                dbSNP:rs104894015).
FT                                {ECO:0000269|PubMed:15277402,
FT                                ECO:0000269|PubMed:17082186}.
FT                                /FTId=VAR_079456.
FT   VARIANT     217    217       D -> N (in MODY2; associated in cis with
FT                                R-261 in some patients; mildly increased
FT                                glucokinase activity; loss of glucokinase
FT                                activity when associated with R-261;
FT                                dbSNP:rs147065275).
FT                                {ECO:0000269|PubMed:22611063}.
FT                                /FTId=VAR_075222.
FT   VARIANT     221    221       E -> K (in MODY2; dbSNP:rs193922317).
FT                                {ECO:0000269|PubMed:10694920}.
FT                                /FTId=VAR_003702.
FT   VARIANT     223    223       G -> S (in MODY2).
FT                                {ECO:0000269|PubMed:16965331,
FT                                ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_078251.
FT   VARIANT     224    224       M -> R (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079457.
FT   VARIANT     225    225       I -> M (in MODY2; associated in cis with
FT                                K-248; highly decreased glucokinase
FT                                activity; loss of glucokinase activity
FT                                when associated with K-248).
FT                                {ECO:0000269|PubMed:22611063}.
FT                                /FTId=VAR_075223.
FT   VARIANT     226    226       V -> M (in MODY2; no effect on stability;
FT                                decreased glucokinase activity; decreased
FT                                affinity for glucose; dbSNP:rs148311934).
FT                                {ECO:0000269|PubMed:16965331,
FT                                ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_003703.
FT   VARIANT     227    227       G -> C (in MODY2).
FT                                {ECO:0000269|PubMed:10694920}.
FT                                /FTId=VAR_003704.
FT   VARIANT     227    227       G -> S (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079458.
FT   VARIANT     228    228       T -> M (in MODY2 and PNDM;
FT                                dbSNP:rs80356655).
FT                                {ECO:0000269|PubMed:11372010,
FT                                ECO:0000269|PubMed:1502186,
FT                                ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_003705.
FT   VARIANT     231    231       N -> H (in MODY2; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078252.
FT   VARIANT     233    233       C -> R (in MODY2; loss of glucokinase
FT                                activity; loss of affinity for glucose;
FT                                loss of affinity for ATP).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079459.
FT   VARIANT     234    465       Missing (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079460.
FT   VARIANT     248    248       E -> K (in MODY2; associated in cis with
FT                                M-225; highly decreased glucokinase
FT                                activity; loss of glucokinase activity
FT                                when associated with M-225;
FT                                dbSNP:rs759421263).
FT                                {ECO:0000269|PubMed:22611063}.
FT                                /FTId=VAR_075224.
FT   VARIANT     252    252       C -> G (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079461.
FT   VARIANT     255    255       T -> A (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079462.
FT   VARIANT     256    256       E -> K (in MODY2; dbSNP:rs769268803).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_003706.
FT   VARIANT     257    257       W -> R (in MODY2; almost complete loss of
FT                                glucokinase activity).
FT                                {ECO:0000269|PubMed:8325892}.
FT                                /FTId=VAR_003707.
FT   VARIANT     259    259       A -> T (in MODY2; dbSNP:rs1375656631).
FT                                {ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010593.
FT   VARIANT     261    261       G -> E (in MODY2).
FT                                {ECO:0000269|PubMed:8168652}.
FT                                /FTId=VAR_010594.
FT   VARIANT     261    261       G -> R (in MODY2 and PNDM; associated in
FT                                cis with N-217 in some patients; highly
FT                                decreased glucokinase activity; loss of
FT                                glucokinase activity when associated with
FT                                N-217; decreased affinity for glucose;
FT                                dbSNP:rs104894008).
FT                                {ECO:0000269|PubMed:1464666,
FT                                ECO:0000269|PubMed:1502186,
FT                                ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:22611063,
FT                                ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_003708.
FT   VARIANT     265    265       E -> K (in MODY2; decreased glucokinase
FT                                activity; decreased affinity for glucose;
FT                                no effect on affinity for ATP).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079463.
FT   VARIANT     279    279       E -> Q (in MODY2; dbSNP:rs104894005).
FT                                /FTId=VAR_003709.
FT   VARIANT     298    298       M -> K (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079464.
FT   VARIANT     299    299       G -> R (in MODY2; dbSNP:rs104894009).
FT                                {ECO:0000269|PubMed:1303265,
FT                                ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_003710.
FT   VARIANT     300    300       E -> K (in MODY2; dbSNP:rs1255911887).
FT                                /FTId=VAR_003712.
FT   VARIANT     300    300       E -> Q (in MODY2).
FT                                /FTId=VAR_003711.
FT   VARIANT     308    308       R -> W (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079465.
FT   VARIANT     309    309       L -> P (in MODY2).
FT                                /FTId=VAR_003713.
FT   VARIANT     315    315       L -> F (in MODY2; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078253.
FT   VARIANT     336    336       S -> L (in MODY2).
FT                                /FTId=VAR_010595.
FT   VARIANT     342    342       T -> P (in dbSNP:rs1000236360).
FT                                {ECO:0000269|PubMed:21604084}.
FT                                /FTId=VAR_066615.
FT   VARIANT     367    367       V -> M (in MODY2; dbSNP:rs1057521092).
FT                                /FTId=VAR_010596.
FT   VARIANT     377    377       R -> H (in MODY2; dbSNP:rs193922264).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079466.
FT   VARIANT     378    378       A -> T (in MODY2; dbSNP:rs104894016).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078254.
FT   VARIANT     379    379       A -> V (in MODY2; decreased glucokinase
FT                                activity; decreased affinity for glucose;
FT                                decreased affinity for ATP).
FT                                {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079467.
FT   VARIANT     382    382       C -> Y (in MODY2).
FT                                {ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010597.
FT   VARIANT     383    383       S -> L (in MODY2; dbSNP:rs777870079).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079468.
FT   VARIANT     384    384       A -> T (in MODY2; dbSNP:rs1376620210).
FT                                {ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010598.
FT   VARIANT     385    385       G -> V (in MODY2).
FT                                {ECO:0000269|PubMed:10588527}.
FT                                /FTId=VAR_012354.
FT   VARIANT     392    392       R -> C (in MODY2; dbSNP:rs1167124132).
FT                                {ECO:0000269|PubMed:9662401}.
FT                                /FTId=VAR_010599.
FT   VARIANT     393    393       M -> T (in PNDM; decreased stability;
FT                                increased glucokinase activity; no effect
FT                                on affinity for glucose).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079469.
FT   VARIANT     397    397       R -> L (in PNDM; decreased stability;
FT                                increased glucokinase activity; no effect
FT                                on affinity for glucose;
FT                                dbSNP:rs193929375).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079470.
FT   VARIANT     399    465       Missing (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079471.
FT   VARIANT     411    411       S -> F (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079472.
FT   VARIANT     414    414       K -> E (in MODY2; decreased affinity for
FT                                glucose; dbSNP:rs193922272).
FT                                {ECO:0000269|PubMed:8325892}.
FT                                /FTId=VAR_003714.
FT   VARIANT     416    416       H -> P (in MODY2).
FT                                {ECO:0000269|PubMed:17573900}.
FT                                /FTId=VAR_079473.
FT   VARIANT     420    420       K -> E (in MODY2; no effect on
FT                                glucokinase activity; decreased affinity
FT                                for glucose; no effect on affinity for
FT                                ATP). {ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:18322640}.
FT                                /FTId=VAR_079474.
FT   VARIANT     434    434       C -> F (in MODY2; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078255.
FT   VARIANT     441    441       S -> L (in PNDM; decreased stability;
FT                                decreased glucokinase activity; no effect
FT                                on affinity for glucose;
FT                                dbSNP:rs1286804191).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079475.
FT   VARIANT     441    441       S -> W (in MODY2; decreased affinity for
FT                                glucose). {ECO:0000269|PubMed:16965331,
FT                                ECO:0000269|PubMed:17573900,
FT                                ECO:0000269|PubMed:19884385}.
FT                                /FTId=VAR_078256.
FT   VARIANT     442    442       E -> K (in HHF3; increased affinity for
FT                                glucose; dbSNP:rs758737171).
FT                                {ECO:0000269|PubMed:19884385,
FT                                ECO:0000269|PubMed:28247534}.
FT                                /FTId=VAR_078257.
FT   VARIANT     447    447       R -> Q (in MODY2; dbSNP:rs1131691416).
FT                                {ECO:0000269|PubMed:16965331}.
FT                                /FTId=VAR_078258.
FT   VARIANT     449    449       A -> T (in PNDM; decreased stability;
FT                                increased glucokinase activity; increased
FT                                affinity for glucose; dbSNP:rs193922282).
FT                                {ECO:0000269|PubMed:25015100}.
FT                                /FTId=VAR_079476.
FT   VARIANT     455    455       V -> M (in HHF3; increased glucokinase
FT                                activity based on measure of catalytic
FT                                efficiency; increased affinity for
FT                                glucose; decreased inhibition by GKRP; no
FT                                effect on affinity for ATP;
FT                                dbSNP:rs104894012).
FT                                {ECO:0000269|PubMed:17082186,
FT                                ECO:0000269|PubMed:9435328}.
FT                                /FTId=VAR_003715.
FT   VARIANT     456    456       A -> V (in HHF3; increased glucokinase
FT                                activity based on measure of catalytic
FT                                efficiency; increased affinity for
FT                                glucose; loss of inhibition by GKRP; no
FT                                effect on affinity for ATP;
FT                                dbSNP:rs104894014).
FT                                {ECO:0000269|PubMed:11916951,
FT                                ECO:0000269|PubMed:17082186}.
FT                                /FTId=VAR_079477.
FT   MUTAGEN      64     64       S->P: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose.
FT                                {ECO:0000269|PubMed:19146401}.
FT   MUTAGEN     177    177       E->K: Small change in glucokinase
FT                                activity. {ECO:0000269|PubMed:8325892}.
FT   MUTAGEN     197    197       M->V: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose.
FT                                {ECO:0000269|PubMed:19146401}.
FT   MUTAGEN     211    211       I->F: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose.
FT                                {ECO:0000269|PubMed:19146401}.
FT   MUTAGEN     214    214       Y->A: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose. No effect
FT                                on affinity for ATP.
FT                                {ECO:0000269|PubMed:17082186}.
FT   MUTAGEN     215    215       Y->A: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose. Loss of
FT                                inhibition by GKRP. No effect on affinity
FT                                for ATP. {ECO:0000269|PubMed:17082186}.
FT   MUTAGEN     256    256       E->A: Inactive enzyme with no glucokinase
FT                                activity. {ECO:0000269|PubMed:8325892}.
FT   MUTAGEN     414    414       K->A: Small change in glucokinase
FT                                activity. {ECO:0000269|PubMed:8325892}.
FT   MUTAGEN     453    453       S->A: Increased glucokinase activity
FT                                based on measure of catalytic efficiency.
FT                                Increased affinity for glucose.
FT                                {ECO:0000269|PubMed:19146401}.
FT   HELIX        12     20       {ECO:0000244|PDB:3F9M}.
FT   HELIX        21     23       {ECO:0000244|PDB:3F9M}.
FT   HELIX        27     45       {ECO:0000244|PDB:3F9M}.
FT   TURN         47     52       {ECO:0000244|PDB:3F9M}.
FT   STRAND       58     65       {ECO:0000244|PDB:3F9M}.
FT   TURN         66     68       {ECO:0000244|PDB:4LC9}.
FT   STRAND       72     92       {ECO:0000244|PDB:3F9M}.
FT   STRAND       95     97       {ECO:0000244|PDB:3H1V}.
FT   STRAND       99    109       {ECO:0000244|PDB:3F9M}.
FT   HELIX       112    115       {ECO:0000244|PDB:3F9M}.
FT   STRAND      116    118       {ECO:0000244|PDB:3F9M}.
FT   HELIX       119    136       {ECO:0000244|PDB:3F9M}.
FT   STRAND      140    142       {ECO:0000244|PDB:3F9M}.
FT   STRAND      145    150       {ECO:0000244|PDB:3F9M}.
FT   STRAND      154    158       {ECO:0000244|PDB:3F9M}.
FT   STRAND      161    164       {ECO:0000244|PDB:3F9M}.
FT   HELIX       181    192       {ECO:0000244|PDB:3F9M}.
FT   STRAND      198    203       {ECO:0000244|PDB:3F9M}.
FT   HELIX       205    214       {ECO:0000244|PDB:3F9M}.
FT   STRAND      220    237       {ECO:0000244|PDB:3F9M}.
FT   HELIX       238    240       {ECO:0000244|PDB:3F9M}.
FT   STRAND      248    254       {ECO:0000244|PDB:3F9M}.
FT   HELIX       257    259       {ECO:0000244|PDB:3F9M}.
FT   TURN        260    263       {ECO:0000244|PDB:3F9M}.
FT   STRAND      264    266       {ECO:0000244|PDB:4MLH}.
FT   HELIX       267    269       {ECO:0000244|PDB:3F9M}.
FT   HELIX       272    280       {ECO:0000244|PDB:3F9M}.
FT   STRAND      281    283       {ECO:0000244|PDB:3F9M}.
FT   HELIX       288    291       {ECO:0000244|PDB:3F9M}.
FT   HELIX       295    311       {ECO:0000244|PDB:3F9M}.
FT   HELIX       316    318       {ECO:0000244|PDB:3F9M}.
FT   TURN        322    325       {ECO:0000244|PDB:3F9M}.
FT   HELIX       332    339       {ECO:0000244|PDB:3F9M}.
FT   STRAND      340    342       {ECO:0000244|PDB:3QIC}.
FT   STRAND      343    345       {ECO:0000244|PDB:4ISE}.
FT   HELIX       346    354       {ECO:0000244|PDB:3F9M}.
FT   HELIX       361    396       {ECO:0000244|PDB:3F9M}.
FT   STRAND      400    409       {ECO:0000244|PDB:3F9M}.
FT   HELIX       411    415       {ECO:0000244|PDB:3F9M}.
FT   STRAND      416    418       {ECO:0000244|PDB:3VEV}.
FT   HELIX       419    430       {ECO:0000244|PDB:3F9M}.
FT   STRAND      434    440       {ECO:0000244|PDB:3F9M}.
FT   HELIX       444    456       {ECO:0000244|PDB:3F9M}.
FT   TURN        457    459       {ECO:0000244|PDB:3H1V}.
SQ   SEQUENCE   465 AA;  52191 MW;  094D4A2F78096724 CRC64;
     MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT
     YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE
     MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN
     VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN
     VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE
     LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS
     TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK
     ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ
//
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