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 03-AUG-2022, entry version 224.
DE RecName: Full=Hexokinase-4 {ECO:0000305};
DE Short=HK4 {ECO:0000305};
DE EC=2.7.1.1 {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=Glucokinase {ECO:0000303|PubMed:1354840};
DE AltName: Full=Hexokinase type IV {ECO:0000250|UniProtKB:P17712};
DE Short=HK IV {ECO:0000250|UniProtKB:P17712};
DE AltName: Full=Hexokinase-D {ECO:0000250|UniProtKB:P17712};
GN Name=GCK {ECO:0000303|PubMed:17573900, ECO:0000312|HGNC:HGNC:4195};
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 [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 two
RT 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; DOI=10.1007/bf00429094;
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 localization of
RT 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 full-
RT length cDNA.";
RL Diabetes 41:807-811(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MODY2 MET-228 AND 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., Velho G.,
RA Sun F., Iris F., Passa P., Cohen D., Bell G.I.;
RT "Human glucokinase gene: isolation, characterization, and identification of
RT two missense mutations linked to early-onset non-insulin-dependent (type 2)
RT diabetes mellitus.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992).
RN [6]
RP ERRATUM OF PUBMED:1502186.
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., Velho G.,
RA 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 missense
RT mutation in a Japanese patient with early-onset non-insulin-dependent
RT 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., 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., Mural R.J.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7742312; DOI=10.1021/bi00018a011;
RA Xu L.Z., Weber I.T., Harrison R.W., Gidh-Jain M., Pilkis S.J.;
RT "Sugar specificity of human beta-cell glucokinase: correlation of molecular
RT models with kinetic measurements.";
RL Biochemistry 34:6083-6092(1995).
RN [13]
RP INVOLVEMENT IN MODY2, AND FUNCTION.
RX PubMed=8878425; DOI=10.1172/jci118974;
RA Velho G., Petersen K.F., Perseghin G., Hwang J.H., Rothman D.L.,
RA Pueyo M.E., Cline G.W., Froguel P., Shulman G.I.;
RT "Impaired hepatic glycogen synthesis in glucokinase-deficient (MODY-2)
RT subjects.";
RL J. Clin. Invest. 98:1755-1761(1996).
RN [14]
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., Guinovart J.J.,
RA Ferrer J.C.;
RT "Glucokinase regulatory protein is essential for the proper subcellular
RT localisation of liver glucokinase.";
RL FEBS Lett. 456:332-338(1999).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-64; MET-197; ILE-211
RP 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 genetic
RT selection.";
RL Biochemistry 48:814-816(2009).
RN [16]
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 [17]
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 the
RT crystal structure of yeast hexokinase B.";
RL Diabetes 43:784-791(1994).
RN [18]
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 allosteric
RT enzyme human glucokinase.";
RL Structure 12:429-438(2004).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-465 IN COMPLEX WITH SYNTHETIC
RP 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 derivatives as
RT GK activators.";
RL Bioorg. Med. Chem. Lett. 19:2718-2721(2009).
RN [20] {ECO:0007744|PDB:3F9M, ECO:0007744|PDB:3FGU, ECO:0007744|PDB:3ID8, ECO:0007744|PDB:3IDH, ECO:0007744|PDB:4NO7}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 12-465 IN COMPLEX WITH ATP ANALOG
RP AND GLUCOSE.
RX PubMed=22101819; DOI=10.1107/s0907444911036729;
RA Petit P., Antoine M., Ferry G., Boutin J.A., Lagarde A., Gluais L.,
RA Vincentelli R., Vuillard L.;
RT "The active conformation of human glucokinase is not altered by allosteric
RT activators.";
RL Acta Crystallogr. D 67:929-935(2011).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 3-465 IN COMPLEX WITH RAT GCKR.
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 [22]
RP INVOLVEMENT IN NIDDM, AND VARIANT NIDDM 186-ARG--GLN-465 DEL.
RX PubMed=1360036; DOI=10.1016/0140-6736(92)92494-z;
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-dependent
RT diabetes mellitus.";
RL Lancet 340:1316-1317(1992).
RN [23]
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., Page R.,
RA Bell J.I., Bell G.I., Turner R.C., Wainscoat J.S.;
RT "Missense glucokinase mutation in maturity-onset diabetes of the young and
RT mutation screening in late-onset diabetes.";
RL Nat. Genet. 2:153-156(1992).
RN [24]
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 [25]
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., Takeda J.,
RA Vionnet N., Xiang K.-S., Gidh-Jain M., Pilkis S.J., Ober C., Bell G.I.;
RT "Identification of glucokinase mutations in subjects with gestational
RT diabetes mellitus.";
RL Diabetes 42:937-940(1993).
RN [26]
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 ACTIVITY,
RP AND FUNCTION.
RX PubMed=8325892; DOI=10.1016/s0021-9258(18)82456-5;
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 diabetes,
RT and other site-directed mutants.";
RL J. Biol. Chem. 268:15200-15204(1993).
RN [27]
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 [28]
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 [29]
RP VARIANTS MODY2 SER-53; ALA-80; ARG-137; PRO-168; 186-ARG--GLN-465 DEL;
RP THR-210; ARG-213; MET-226; 248-GLU--GLN-465 DEL; ARG-261; LEU-336;
RP 360-SER--GLN-465 DEL AND MET-367.
RX PubMed=9049484; DOI=10.1007/s001250050666;
RA Velho G., Blanche H., Vaxillaire M., Bellanne-Chantelot C., Pardini V.C.,
RA Timsit J., Passa P., Deschamps I., Robert J.-J., Weber I.T., Marotta D.,
RA Pilkis S.J., Lipkind G.M., Bell G.I., 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 [30]
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>3.0.co;2-v;
RA Guazzini B., Gaffi D., Mainieri D., Multari G., Cordera R., Bertolini S.,
RA 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 [31]
RP VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384 AND
RP 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 birth
RT weight.";
RL Nat. Genet. 19:268-270(1998).
RN [32]
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., Herold K.C.;
RT "Familial hyperinsulinism caused by an activating glucokinase mutation.";
RL N. Engl. J. Med. 338:226-230(1998).
RN [33]
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., So W.-Y.,
RA Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., Critchley J.A.J.H.,
RA 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 factor-
RT 1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY.";
RL Diabet. Med. 16:956-963(1999).
RN [34]
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 [35]
RP INVOLVEMENT IN PNDM1, INVOLVEMENT IN MODY2, VARIANTS MODY2 LYS-210 AND
RP MET-228, AND VARIANTS PNDM1 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 [36]
RP VARIANT HHF3 VAL-456, CHARACTERIZATION OF VARIANT HHF3 VAL-456, FUNCTION,
RP AND CATALYTIC ACTIVITY.
RX PubMed=11916951; DOI=10.2337/diabetes.51.4.1240;
RA Christesen H.B., Jacobsen B.B., Odili S., Buettger C., Cuesta-Munoz A.,
RA Hansen T., Brusgaard K., Massa O., Magnuson M.A., Shiota C.,
RA 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 [37]
RP VARIANT HHF3 ILE-65, AND CHARACTERIZATION OF VARIANT HHF3 ILE-65.
RX PubMed=12941786; DOI=10.2337/diabetes.52.9.2433;
RA Gloyn A.L., Noordam K., Willemsen M.A., Ellard S., Lam W.W., Campbell I.W.,
RA Midgley P., Shiota C., Buettger C., Magnuson M.A., Matschinsky F.M.,
RA Hattersley A.T.;
RT "Insights into the biochemical and genetic basis of glucokinase activation
RT from naturally occurring hypoglycemia mutations.";
RL Diabetes 52:2433-2440(2003).
RN [38]
RP VARIANT HHF3 CYS-214, CHARACTERIZATION OF VARIANT HHF3 CYS-214, FUNCTION,
RP AND CATALYTIC ACTIVITY.
RX PubMed=15277402; DOI=10.2337/diabetes.53.8.2164;
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 [39]
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 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., Dahan K.,
RA Nollet A., Vanhaverbeke G., Imschoot S.V., Bourguignon J.P., Beauloye V.,
RA Storm K., Massa G., Giri M., Nobels F., De Schepper J., Rooman R.,
RA Van den Bruel A., Mathieu C., Wuyts W.;
RT "Identification of novel and recurrent glucokinase mutations in Belgian and
RT Luxembourg maturity onset diabetes of the young patients.";
RL Clin. Genet. 70:355-359(2006).
RN [40]
RP CHARACTERIZATION OF VARIANTS HHF3 ILE-65; CYS-214; MET-455 AND VAL-456,
RP MUTAGENESIS OF TYR-214 AND TYR-215, FUNCTION, AND CATALYTIC 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 [41]
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; TRP-191;
RP LEU-200; THR-202; MET-206; MET-209; SER-223; ARG-224; SER-227; MET-228;
RP ARG-233; 234-TYR--GLN-465 DEL; GLY-252; ALA-255; LYS-256; ARG-261; LYS-265;
RP LYS-298; TRP-308; HIS-377; VAL-379; LEU-383; 399-GLU--GLN-465 DEL; PHE-411;
RP 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., Vazquez J.A.,
RA 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 [42]
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 from
RT Spanish maturity-onset diabetes of the young (MODY2) patients.";
RL J. Hum. Genet. 53:460-466(2008).
RN [43]
RP VARIANT MODY2 TRP-441, CHARACTERIZATION OF VARIANT MODY2 TRP-441, VARIANT
RP 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., Ciampalini P.,
RA Massa O., Rodriguez-Bada P., Colombo C., Lenzi L., Garcia-Gimeno M.A.,
RA Bermudez-Silva F.J., Rodriguez de Fonseca F., Banin P., Aledo J.C.,
RA 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 human
RT glucokinase (GCK) gene.";
RL Mol. Endocrinol. 23:1983-1989(2009).
RN [44]
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., Rahier J.,
RA 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 [45]
RP ERRATUM OF PUBMED:20375417.
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., Rahier J.,
RA Glaser B., Cuesta-Munoz A.L.;
RL N. Engl. J. Med. 363:2178-2178(2010).
RN [46]
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 pathogenic
RT mutation causing MODY.";
RL Diabetologia 54:2202-2205(2011).
RN [47]
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; ASN-217;
RP 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 the
RT identification and functional characterization of compound heterozygous and
RT double mutations inherited in cis.";
RL Diabetes Care 35:1482-1484(2012).
RN [48]
RP VARIANTS PNDM1 LYS-40; CYS-43; ASP-50; ARG-72; THR-151; PRO-164; ALA-168;
RP ARG-169; ARG-261; THR-393; LEU-397; LEU-441 AND THR-449, CHARACTERIZATION
RP OF VARIANTS PNDM1 LYS-40; CYS-43; ASP-50; ARG-72; ALA-168; ARG-261;
RP THR-393; LEU-397; LEU-441 AND THR-449, VARIANTS MODY2 ASN-160 AND MET-226,
RP CHARACTERIZATION OF VARIANT MODY2 ASN-160 AND MET-226, FUNCTION, AND
RP 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 protein
RT stability.";
RL Hum. Mol. Genet. 23:6432-6440(2014).
RN [49]
RP VARIANTS HHF3 ILE-65; LEU-91; CYS-99 AND LYS-442, AND CHARACTERIZATION OF
RP 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., Vela A.,
RA 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 phosphorylation of hexose, such as D-glucose,
CC D-fructose and D-mannose, to hexose 6-phosphate (D-glucose 6-phosphate,
CC D-fructose 6-phosphate and D-mannose 6-phosphate, respectively)
CC (PubMed:7742312, PubMed:11916951, PubMed:15277402, PubMed:17082186,
CC PubMed:18322640, PubMed:19146401, PubMed:25015100, PubMed:8325892).
CC Compared to other hexokinases, has a weak affinity for D-glucose, and
CC is effective only when glucose is abundant (By similarity). Mainly
CC expressed in pancreatic beta cells and the liver and constitutes a
CC rate-limiting step in glucose metabolism in these tissues
CC (PubMed:18322640, PubMed:25015100, PubMed:8325892, PubMed:11916951,
CC PubMed:15277402). Since insulin secretion parallels glucose metabolism
CC and the low glucose affinity of GCK ensures that it can change its
CC enzymatic activity within the physiological range of glucose
CC concentrations, GCK acts as a glucose sensor in the pancreatic beta
CC cell (By similarity). In pancreas, plays an important role in
CC modulating insulin secretion (By similarity). In liver, helps to
CC facilitate the uptake and conversion of glucose by acting as an
CC insulin-sensitive determinant of hepatic glucose usage (By similarity).
CC Required to provide D-glucose 6-phosphate for the synthesis of glycogen
CC (PubMed:8878425). Mediates the initial step of glycolysis by catalyzing
CC phosphorylation of D-glucose to D-glucose 6-phosphate (PubMed:7742312).
CC {ECO:0000250|UniProtKB:P17712, ECO:0000250|UniProtKB:P52792,
CC ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:15277402,
CC ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:18322640,
CC ECO:0000269|PubMed:19146401, ECO:0000269|PubMed:25015100,
CC ECO:0000269|PubMed:7742312, ECO:0000269|PubMed:8325892,
CC ECO:0000269|PubMed:8878425}.
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:11916951, ECO:0000269|PubMed:15277402,
CC ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:18322640,
CC ECO:0000269|PubMed:19146401, ECO:0000269|PubMed:25015100,
CC ECO:0000269|PubMed:8325892};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22741;
CC Evidence={ECO:0000269|PubMed:11916951, ECO:0000269|PubMed:15277402,
CC ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:18322640,
CC ECO:0000269|PubMed:19146401, ECO:0000269|PubMed:25015100,
CC ECO:0000269|PubMed:8325892};
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:0000269|PubMed:7742312};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16126;
CC Evidence={ECO:0000269|PubMed:7742312};
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:0000269|PubMed:7742312};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17826;
CC Evidence={ECO:0000269|PubMed:7742312};
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:0000269|PubMed:7742312};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11029;
CC Evidence={ECO:0000269|PubMed:7742312};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation
CC (PubMed:15016359). Low glucose and high fructose-6-phosphate triggers
CC association with the inhibitor GCKR followed by sequestration in the
CC nucleus (PubMed:10456334). {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:15016359}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=6.03 mM for glucose (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:7742312};
CC KM=4.35 mM for mannose (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:7742312};
CC KM=18 mM for 2-deoxyglucose (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:7742312};
CC KM=240 mM for fructose (at 30 degrees Celsius and pH 7.5)
CC {ECO:0000269|PubMed:7742312};
CC KM=61 mM for glucosamine (at 30 degrees Celsius and pH 9)
CC {ECO:0000269|PubMed:7742312};
CC KM=4.5 mM for ATP (at pH 7) {ECO:0000269|PubMed:7742312};
CC Note=kcat is 66.4 sec(-1) with glucose as substrate (at 30 degrees
CC Celsius and pH 7.5) (PubMed:7742312). kcat is 56.4 sec(-1) with
CC mannose as substrate (at 30 degrees Celsius and pH 7.5)
CC (PubMed:7742312). kcat is 56.4 sec(-1) with 2-deoxyglucose as
CC substrate (at 30 degrees Celsius and pH 7.5) (PubMed:7742312). kcat
CC is 116.9 sec(-1) with fructose as substrate (at 30 degrees Celsius
CC and pH 7.5) (PubMed:7742312). kcat is 19.9 sec(-1) with glucosamine
CC as substrate (at 30 degrees Celsius and pH 9) (PubMed:7742312).
CC {ECO:0000269|PubMed:7742312};
CC pH dependence:
CC Optimum pH is 6-8 with glucose as substrate (PubMed:7742312). Optimum
CC pH is 9-10 with glucosamine as substrate (PubMed:7742312).
CC {ECO:0000269|PubMed:7742312};
CC -!- PATHWAY: Carbohydrate metabolism; hexose metabolism.
CC {ECO:0000305|PubMed:7742312}.
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 1/4.
CC {ECO:0000305|PubMed:7742312}.
CC -!- SUBUNIT: Monomer (PubMed:15016359, PubMed:19362831, PubMed:23957911).
CC Interacts with MIDN; the interaction occurs preferentially at low
CC glucose levels and results in inhibition of hexokinase activity
CC (PubMed:24187134). Interacts with GCKR; leading to sequestration in the
CC nucleus (PubMed:10456334). {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:15016359, ECO:0000269|PubMed:19362831,
CC ECO:0000269|PubMed:23957911, ECO:0000269|PubMed:24187134}.
CC -!- INTERACTION:
CC P35557; Q14397: GCKR; NbExp=5; IntAct=EBI-709928, EBI-709948;
CC P35557; P16118: PFKFB1; NbExp=2; IntAct=EBI-709928, EBI-709807;
CC P35557; A6NLX3: SPDYE4; NbExp=3; IntAct=EBI-709928, EBI-12047907;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:24187134}. Nucleus {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:24187134}. Mitochondrion
CC {ECO:0000250|UniProtKB:P17712}. Note=Under low glucose concentrations,
CC GCK associates with GCKR and the inactive complex is recruited to the
CC hepatocyte nucleus. {ECO:0000269|PubMed:10456334}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=A number of isoforms are produced by alternative promoter
CC usage. The use of alternative promoters apparently enables the type
CC IV hexokinase gene to be regulated by insulin in the liver and
CC glucose in the beta cell. This may constitute an important feedback
CC loop for maintaining glucose homeostasis.
CC {ECO:0000305|PubMed:1871135};
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 -!- DISEASE: Maturity-onset diabetes of the young 2 (MODY2) [MIM:125851]: A
CC form of diabetes that is characterized by an autosomal dominant mode of
CC inheritance, onset in childhood or early adulthood (usually before 25
CC years of age), a primary defect in insulin secretion and frequent
CC insulin-independence at the beginning of the disease.
CC {ECO:0000269|PubMed:10588527, ECO:0000269|PubMed:10694920,
CC ECO:0000269|PubMed:11106831, ECO:0000269|PubMed:11372010,
CC ECO:0000269|PubMed:1303265, ECO:0000269|PubMed:1464666,
CC ECO:0000269|PubMed:1502186, ECO:0000269|PubMed:16965331,
CC ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:18322640,
CC ECO:0000269|PubMed:19884385, ECO:0000269|PubMed:22611063,
CC ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:8168652,
CC ECO:0000269|PubMed:8325892, ECO:0000269|PubMed:8446612,
CC ECO:0000269|PubMed:8495817, ECO:0000269|PubMed:8878425,
CC ECO:0000269|PubMed:9049484, ECO:0000269|PubMed:9662401}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Familial hyperinsulinemic hypoglycemia 3 (HHF3) [MIM:602485]:
CC Most common cause of persistent hypoglycemia in infancy. Unless early
CC and aggressive intervention is undertaken, brain damage from recurrent
CC episodes of hypoglycemia may occur. {ECO:0000269|PubMed:11916951,
CC ECO:0000269|PubMed:12941786, ECO:0000269|PubMed:15277402,
CC ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:19884385,
CC ECO:0000269|PubMed:20375417, ECO:0000269|PubMed:28247534,
CC ECO:0000269|PubMed:9435328}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:1360036}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, permanent neonatal, 1 (PNDM1) [MIM:606176]:
CC An autosomal recessive form of permanent neonatal diabetes mellitus, a
CC type of diabetes characterized by onset of persistent hyperglycemia
CC within the first six months of life. Initial clinical manifestations
CC include intrauterine growth retardation, hyperglycemia, glycosuria,
CC osmotic polyuria, severe dehydration, and failure to thrive.
CC {ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:25015100}. 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 -!- SEQUENCE CAUTION:
CC Sequence=AAA67541.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAA67542.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glucokinase entry;
CC URL="https://en.wikipedia.org/wiki/Glucokinase";
CC ---------------------------------------------------------------------------
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DR EMBL; M88011; AAA51824.1; -; mRNA.
DR EMBL; M69051; AAB59563.1; ALT_SEQ; mRNA.
DR EMBL; M90298; AAA67541.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M90298; AAA67542.1; ALT_SEQ; 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 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 PDB; 6E0E; X-ray; 2.70 A; A=16-461.
DR PDB; 6E0I; X-ray; 1.90 A; A=1-458.
DR PDB; 7T78; X-ray; 2.40 A; A/B=16-465.
DR PDB; 7T79; X-ray; 2.40 A; A/B=16-465.
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 PDBsum; 6E0E; -.
DR PDBsum; 6E0I; -.
DR PDBsum; 7T78; -.
DR PDBsum; 7T79; -.
DR AlphaFoldDB; P35557; -.
DR SMR; P35557; -.
DR BioGRID; 108915; 15.
DR IntAct; P35557; 6.
DR STRING; 9606.ENSP00000223366; -.
DR BindingDB; P35557; -.
DR ChEMBL; CHEMBL3820; -.
DR DrugBank; DB08118; 2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide.
DR DrugBank; DB08210; 2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE.
DR DrugBank; DB07358; 2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide.
DR DrugBank; DB07359; 3-[(4-fluorophenyl)sulfanyl]-N-(4-methyl-1,3-thiazol-2-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamide.
DR DrugBank; DB02379; Beta-D-Glucose.
DR DrugBank; DB01914; D-glucose.
DR DrugBank; DB09341; Dextrose, unspecified form.
DR DrugBank; DB09344; Invert sugar.
DR GuidetoPHARMACOLOGY; 2798; -.
DR iPTMnet; P35557; -.
DR PhosphoSitePlus; P35557; -.
DR BioMuta; GCK; -.
DR DMDM; 547696; -.
DR jPOST; P35557; -.
DR MassIVE; P35557; -.
DR PaxDb; P35557; -.
DR PeptideAtlas; P35557; -.
DR PRIDE; P35557; -.
DR ProteomicsDB; 55084; -. [P35557-1]
DR ProteomicsDB; 55085; -. [P35557-2]
DR ProteomicsDB; 55086; -. [P35557-3]
DR Antibodypedia; 2045; 539 antibodies from 35 providers.
DR DNASU; 2645; -.
DR Ensembl; ENST00000345378.7; ENSP00000223366.2; ENSG00000106633.18. [P35557-2]
DR Ensembl; ENST00000403799.8; ENSP00000384247.3; ENSG00000106633.18. [P35557-1]
DR GeneID; 2645; -.
DR KEGG; hsa:2645; -.
DR MANE-Select; ENST00000403799.8; ENSP00000384247.3; NM_000162.5; NP_000153.1.
DR UCSC; uc003tkj.2; human. [P35557-1]
DR CTD; 2645; -.
DR DisGeNET; 2645; -.
DR GeneCards; GCK; -.
DR GeneReviews; GCK; -.
DR HGNC; HGNC:4195; GCK.
DR HPA; ENSG00000106633; Tissue enhanced (brain, liver, pituitary gland).
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; 99885; Isolated permanent neonatal diabetes mellitus.
DR Orphanet; 552; MODY.
DR PharmGKB; PA28610; -.
DR VEuPathDB; HostDB:ENSG00000106633; -.
DR eggNOG; KOG1369; Eukaryota.
DR GeneTree; ENSGT00950000182787; -.
DR HOGENOM; CLU_014393_5_3_1; -.
DR InParanoid; P35557; -.
DR OrthoDB; 1153545at2759; -.
DR PhylomeDB; P35557; -.
DR TreeFam; TF314238; -.
DR BioCyc; MetaCyc:HS02935-MON; -.
DR BRENDA; 2.7.1.1; 2681.
DR PathwayCommons; P35557; -.
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 Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR SABIO-RK; P35557; -.
DR SignaLink; P35557; -.
DR SIGNOR; P35557; -.
DR UniPathway; UPA00109; UER00180.
DR UniPathway; UPA00242; -.
DR BioGRID-ORCS; 2645; 14 hits in 1106 CRISPR screens.
DR ChiTaRS; GCK; human.
DR EvolutionaryTrace; P35557; -.
DR GeneWiki; Glucokinase; -.
DR GenomeRNAi; 2645; -.
DR Pharos; P35557; Tchem.
DR PRO; PR:P35557; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P35557; protein.
DR Bgee; ENSG00000106633; Expressed in pituitary gland and 98 other tissues.
DR ExpressionAtlas; P35557; baseline and differential.
DR Genevisible; P35557; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
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:0046835; P:carbohydrate phosphorylation; IBA:GO_Central.
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:0006006; P:glucose metabolic process; IBA:GO_Central.
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; NAS:BHF-UCL.
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; IPR043129; ATPase_NBD.
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 SUPFAM; SSF53067; SSF53067; 2.
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 Cytoplasm; Diabetes mellitus; Disease variant; Glycolysis; Kinase;
KW Mitochondrion; Nucleotide-binding; Nucleus; Reference proteome;
KW Transferase.
FT CHAIN 1..465
FT /note="Hexokinase-4"
FT /id="PRO_0000197593"
FT DOMAIN 10..454
FT /note="Hexokinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 67..203
FT /note="Hexokinase small subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT REGION 204..443
FT /note="Hexokinase large subdomain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01084"
FT BINDING 78..83
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P19367"
FT BINDING 151..152
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 168..169
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 204..205
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22101819,
FT ECO:0007744|PDB:3FGU, ECO:0007744|PDB:3ID8"
FT BINDING 231
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 256
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 290
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15016359"
FT BINDING 295..296
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22101819,
FT ECO:0007744|PDB:3FGU, ECO:0007744|PDB:3ID8"
FT BINDING 332..336
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22101819,
FT ECO:0007744|PDB:3FGU, ECO:0007744|PDB:3ID8"
FT BINDING 411..415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:22101819,
FT ECO:0007744|PDB:3FGU, ECO:0007744|PDB:3ID8"
FT VAR_SEQ 1..15
FT /note="MLDDRARMEAAKKEK -> MAMDVTRSQAQTALTL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_002074"
FT VAR_SEQ 1..15
FT /note="MLDDRARMEAAKKEK -> MPRPRSQLPQPNSQ (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_002075"
FT VARIANT 4
FT /note="D -> N (in dbSNP:rs202091228)"
FT /evidence="ECO:0000269|PubMed:8325892"
FT /id="VAR_003692"
FT VARIANT 11
FT /note="A -> T (in dbSNP:rs116093166)"
FT /evidence="ECO:0000269|PubMed:8454109"
FT /id="VAR_010583"
FT VARIANT 16
FT /note="V -> E (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079430"
FT VARIANT 19
FT /note="I -> N (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079431"
FT VARIANT 20
FT /note="L -> P (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079432"
FT VARIANT 36
FT /note="R -> W (in MODY2; dbSNP:rs762263694)"
FT /evidence="ECO:0000269|PubMed:16965331,
FT ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:8168652"
FT /id="VAR_010584"
FT VARIANT 40
FT /note="E -> K (in PNDM1; decreased stability; decreased
FT glucokinase activity; decreased affinity for glucose;
FT dbSNP:rs794727236)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079433"
FT VARIANT 43
FT /note="R -> C (in PNDM1; decreased stability; decreased
FT glucokinase activity; no effect on affinity for glucose;
FT dbSNP:rs1486280029)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079434"
FT VARIANT 43
FT /note="R -> H (in MODY2; unknown pathological significance;
FT no change in glucokinase activity; dbSNP:rs764232985)"
FT /evidence="ECO:0000269|PubMed:22611063"
FT /id="VAR_075220"
FT VARIANT 43
FT /note="R -> S (in MODY2; dbSNP:rs1486280029)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079435"
FT VARIANT 44
FT /note="G -> S (in MODY2; dbSNP:rs267601516)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079436"
FT VARIANT 50
FT /note="H -> D (in PNDM1; loss of stability; loss of
FT glucokinase activity; decreased affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079437"
FT VARIANT 53
FT /note="A -> S (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010585"
FT VARIANT 61..465
FT /note="Missing (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079438"
FT VARIANT 61
FT /note="Y -> S (in MODY2; decreased glucokinase activity;
FT decreased affinity for glucose; increased affinity for
FT ATP)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079439"
FT VARIANT 65
FT /note="T -> I (in HHF3; increased glucokinase activity
FT based on measure of catalytic efficiency; increased
FT affinity for glucose; loss of inhibition by GCKR; unchanged
FT affinity for ATP)"
FT /evidence="ECO:0000269|PubMed:12941786,
FT ECO:0000269|PubMed:17082186, ECO:0000269|PubMed:28247534"
FT /id="VAR_078243"
FT VARIANT 68
FT /note="G -> D (in MODY2; unknown pathological significance;
FT mildly increases glucokinase activity; dbSNP:rs373418736)"
FT /evidence="ECO:0000269|PubMed:22611063"
FT /id="VAR_075221"
FT VARIANT 70
FT /note="E -> K (in MODY2; decreased affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:8325892"
FT /id="VAR_003693"
FT VARIANT 72
FT /note="G -> R (in MODY2 and PNDM1; decreased stability; no
FT effect on glucokinase activity; no effect on affinity for
FT glucose; dbSNP:rs193922289)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:25015100"
FT /id="VAR_079440"
FT VARIANT 77
FT /note="L -> P (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079441"
FT VARIANT 78
FT /note="D -> E (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079442"
FT VARIANT 80
FT /note="G -> A (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_003694"
FT VARIANT 80
FT /note="G -> D (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079443"
FT VARIANT 80
FT /note="G -> S (in MODY2; dbSNP:rs1554335761)"
FT /evidence="ECO:0000269|PubMed:10694920"
FT /id="VAR_003695"
FT VARIANT 82
FT /note="T -> I (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079444"
FT VARIANT 91
FT /note="V -> L (in HHF3; increased glucokinase activity;
FT increased affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:20375417,
FT ECO:0000269|PubMed:28247534"
FT /id="VAR_078244"
FT VARIANT 99
FT /note="W -> C (in HHF3; increased glucokinase activity;
FT increased affinity for glucose; increased affinity for
FT ATP)"
FT /evidence="ECO:0000269|PubMed:28247534"
FT /id="VAR_078245"
FT VARIANT 107
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:1464666,
FT ECO:0000269|PubMed:1871135"
FT /id="VAR_003696"
FT VARIANT 108
FT /note="Y -> H (in MODY2; dbSNP:rs193922292)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:9662401"
FT /id="VAR_010586"
FT VARIANT 110
FT /note="I -> T (in MODY2; dbSNP:rs1338970607)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012352"
FT VARIANT 116
FT /note="T -> P (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079445"
FT VARIANT 119
FT /note="A -> D (in MODY2; dbSNP:rs1176659689)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012353"
FT VARIANT 129
FT /note="C -> Y (in MODY2)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078246"
FT VARIANT 131
FT /note="S -> P (in MODY2; decreased affinity for glucose;
FT dbSNP:rs104894010)"
FT /evidence="ECO:0000269|PubMed:8325892,
FT ECO:0000269|PubMed:8495817"
FT /id="VAR_003697"
FT VARIANT 137
FT /note="H -> R (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010587"
FT VARIANT 150
FT /note="F -> S (in MODY2; dbSNP:rs193922297)"
FT /evidence="ECO:0000269|PubMed:9662401"
FT /id="VAR_010588"
FT VARIANT 151
FT /note="S -> T (in PNDM1)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079446"
FT VARIANT 152
FT /note="F -> L (in MODY2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078247"
FT VARIANT 160
FT /note="D -> N (in MODY2; decreased glucokinase activity;
FT decreased affinity for glucose; dbSNP:rs1554335566)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079447"
FT VARIANT 164
FT /note="L -> P (in MODY2 and PNDM1)"
FT /evidence="ECO:0000269|PubMed:11106831,
FT ECO:0000269|PubMed:25015100"
FT /id="VAR_012350"
FT VARIANT 168
FT /note="T -> A (in PNDM1; decreased glucokinase activity;
FT decreased affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079448"
FT VARIANT 168
FT /note="T -> P (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010589"
FT VARIANT 169
FT /note="K -> R (in PNDM1)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079449"
FT VARIANT 175
FT /note="G -> R (in MODY2; dbSNP:rs587780344)"
FT /id="VAR_003698"
FT VARIANT 182
FT /note="V -> L (in MODY2; decreased glucokinase activity;
FT decreased affinity for glucose; increased affinity for
FT ATP)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079450"
FT VARIANT 182
FT /note="V -> M (in MODY2; dbSNP:rs587780345)"
FT /id="VAR_003699"
FT VARIANT 186..465
FT /note="Missing (in MODY2 and NIDDM)"
FT /evidence="ECO:0000269|PubMed:1360036,
FT ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:9049484"
FT /id="VAR_079451"
FT VARIANT 187
FT /note="D -> Y (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079452"
FT VARIANT 188
FT /note="A -> T (in MODY2; decreased affinity for glucose;
FT dbSNP:rs751279776)"
FT /evidence="ECO:0000269|PubMed:8325892"
FT /id="VAR_003700"
FT VARIANT 188
FT /note="A -> V (in MODY2; dbSNP:rs193922307)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078248"
FT VARIANT 191
FT /note="R -> W (in MODY2; dbSNP:rs1085307455)"
FT /evidence="ECO:0000269|PubMed:16965331,
FT ECO:0000269|PubMed:17573900"
FT /id="VAR_078249"
FT VARIANT 200
FT /note="V -> L (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079453"
FT VARIANT 202
FT /note="M -> R (in MODY2)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078250"
FT VARIANT 202
FT /note="M -> T (in MODY2; dbSNP:rs193922311)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079454"
FT VARIANT 203
FT /note="V -> A (in MODY2; dbSNP:rs1562717053)"
FT /id="VAR_003701"
FT VARIANT 206
FT /note="T -> M (in MODY2; dbSNP:rs1441649062)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079455"
FT VARIANT 209
FT /note="T -> M (in MODY2; dbSNP:rs1583599303)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:8168652"
FT /id="VAR_010590"
FT VARIANT 210
FT /note="M -> K (in MODY2 and PNDM1; dbSNP:rs80356654)"
FT /evidence="ECO:0000269|PubMed:11372010"
FT /id="VAR_012351"
FT VARIANT 210
FT /note="M -> T (in MODY2; dbSNP:rs80356654)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010591"
FT VARIANT 213
FT /note="C -> R (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010592"
FT VARIANT 214
FT /note="Y -> C (in HHF3; increased glucokinase activity
FT based on measure of catalytic efficiency; increased
FT affinity for glucose; decreased inhibition by GCKR;
FT dbSNP:rs104894015)"
FT /evidence="ECO:0000269|PubMed:15277402,
FT ECO:0000269|PubMed:17082186"
FT /id="VAR_079456"
FT VARIANT 217
FT /note="D -> N (in MODY2; associated in cis with R-261 in
FT some patients; mildly increased glucokinase activity; loss
FT of glucokinase activity when associated with R-261;
FT dbSNP:rs147065275)"
FT /evidence="ECO:0000269|PubMed:22611063"
FT /id="VAR_075222"
FT VARIANT 221
FT /note="E -> K (in MODY2; dbSNP:rs193922317)"
FT /evidence="ECO:0000269|PubMed:10694920"
FT /id="VAR_003702"
FT VARIANT 223
FT /note="G -> S (in MODY2; dbSNP:rs1360415315)"
FT /evidence="ECO:0000269|PubMed:16965331,
FT ECO:0000269|PubMed:17573900"
FT /id="VAR_078251"
FT VARIANT 224
FT /note="M -> R (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079457"
FT VARIANT 225
FT /note="I -> M (in MODY2; associated in cis with K-248;
FT highly decreased glucokinase activity; loss of glucokinase
FT activity when associated with K-248; dbSNP:rs772754004)"
FT /evidence="ECO:0000269|PubMed:22611063"
FT /id="VAR_075223"
FT VARIANT 226
FT /note="V -> M (in MODY2; no effect on stability; decreased
FT glucokinase activity; decreased affinity for glucose;
FT dbSNP:rs148311934)"
FT /evidence="ECO:0000269|PubMed:16965331,
FT ECO:0000269|PubMed:25015100, ECO:0000269|PubMed:9049484"
FT /id="VAR_003703"
FT VARIANT 227
FT /note="G -> C (in MODY2)"
FT /evidence="ECO:0000269|PubMed:10694920"
FT /id="VAR_003704"
FT VARIANT 227
FT /note="G -> S (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079458"
FT VARIANT 228
FT /note="T -> M (in MODY2 and PNDM1; dbSNP:rs80356655)"
FT /evidence="ECO:0000269|PubMed:11372010,
FT ECO:0000269|PubMed:1502186, ECO:0000269|PubMed:17573900"
FT /id="VAR_003705"
FT VARIANT 231
FT /note="N -> H (in MODY2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078252"
FT VARIANT 233
FT /note="C -> R (in MODY2; loss of glucokinase activity; loss
FT of affinity for glucose; loss of affinity for ATP)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079459"
FT VARIANT 234..465
FT /note="Missing (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079460"
FT VARIANT 248..465
FT /note="Missing (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_081975"
FT VARIANT 248
FT /note="E -> K (in MODY2; associated in cis with M-225;
FT highly decreased glucokinase activity; loss of glucokinase
FT activity when associated with M-225; dbSNP:rs759421263)"
FT /evidence="ECO:0000269|PubMed:22611063"
FT /id="VAR_075224"
FT VARIANT 252
FT /note="C -> G (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079461"
FT VARIANT 255
FT /note="T -> A (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079462"
FT VARIANT 256
FT /note="E -> K (in MODY2; dbSNP:rs769268803)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_003706"
FT VARIANT 257
FT /note="W -> R (in MODY2; almost complete loss of
FT glucokinase activity; dbSNP:rs1554335135)"
FT /evidence="ECO:0000269|PubMed:8325892"
FT /id="VAR_003707"
FT VARIANT 259
FT /note="A -> T (in MODY2; dbSNP:rs1375656631)"
FT /evidence="ECO:0000269|PubMed:9662401"
FT /id="VAR_010593"
FT VARIANT 261
FT /note="G -> E (in MODY2)"
FT /evidence="ECO:0000269|PubMed:8168652"
FT /id="VAR_010594"
FT VARIANT 261
FT /note="G -> R (in MODY2 and PNDM1; associated in cis with
FT N-217 in some patients; highly decreased glucokinase
FT activity; loss of glucokinase activity when associated with
FT N-217; decreased affinity for glucose; dbSNP:rs104894008)"
FT /evidence="ECO:0000269|PubMed:1464666,
FT ECO:0000269|PubMed:1502186, ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:22611063, ECO:0000269|PubMed:25015100,
FT ECO:0000269|PubMed:9049484"
FT /id="VAR_003708"
FT VARIANT 265
FT /note="E -> K (in MODY2; decreased glucokinase activity;
FT decreased affinity for glucose; no effect on affinity for
FT ATP; dbSNP:rs104894011)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079463"
FT VARIANT 279
FT /note="E -> Q (in MODY2; dbSNP:rs104894005)"
FT /id="VAR_003709"
FT VARIANT 298
FT /note="M -> K (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079464"
FT VARIANT 299
FT /note="G -> R (in MODY2; dbSNP:rs104894009)"
FT /evidence="ECO:0000269|PubMed:1303265,
FT ECO:0000269|PubMed:9662401"
FT /id="VAR_003710"
FT VARIANT 300
FT /note="E -> K (in MODY2; dbSNP:rs1255911887)"
FT /id="VAR_003712"
FT VARIANT 300
FT /note="E -> Q (in MODY2)"
FT /id="VAR_003711"
FT VARIANT 308
FT /note="R -> W (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079465"
FT VARIANT 309
FT /note="L -> P (in MODY2)"
FT /id="VAR_003713"
FT VARIANT 315
FT /note="L -> F (in MODY2; unknown pathological significance;
FT dbSNP:rs1583594350)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078253"
FT VARIANT 336
FT /note="S -> L (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010595"
FT VARIANT 342
FT /note="T -> P (in dbSNP:rs1000236360)"
FT /evidence="ECO:0000269|PubMed:21604084"
FT /id="VAR_066615"
FT VARIANT 360..465
FT /note="Missing (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_081976"
FT VARIANT 367
FT /note="V -> M (in MODY2; dbSNP:rs1057521092)"
FT /evidence="ECO:0000269|PubMed:9049484"
FT /id="VAR_010596"
FT VARIANT 377
FT /note="R -> H (in MODY2; dbSNP:rs193922264)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079466"
FT VARIANT 378
FT /note="A -> T (in MODY2; dbSNP:rs104894016)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078254"
FT VARIANT 379
FT /note="A -> V (in MODY2; decreased glucokinase activity;
FT decreased affinity for glucose; decreased affinity for ATP;
FT dbSNP:rs193922265)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079467"
FT VARIANT 382
FT /note="C -> Y (in MODY2)"
FT /evidence="ECO:0000269|PubMed:9662401"
FT /id="VAR_010597"
FT VARIANT 383
FT /note="S -> L (in MODY2; dbSNP:rs777870079)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079468"
FT VARIANT 384
FT /note="A -> T (in MODY2; dbSNP:rs1376620210)"
FT /evidence="ECO:0000269|PubMed:9662401"
FT /id="VAR_010598"
FT VARIANT 385
FT /note="G -> V (in MODY2)"
FT /evidence="ECO:0000269|PubMed:10588527"
FT /id="VAR_012354"
FT VARIANT 392
FT /note="R -> C (in MODY2; dbSNP:rs1167124132)"
FT /evidence="ECO:0000269|PubMed:9662401"
FT /id="VAR_010599"
FT VARIANT 393
FT /note="M -> T (in PNDM1; decreased stability; increased
FT glucokinase activity; no effect on affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079469"
FT VARIANT 397
FT /note="R -> L (in PNDM1; decreased stability; increased
FT glucokinase activity; no effect on affinity for glucose;
FT dbSNP:rs193929375)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079470"
FT VARIANT 399..465
FT /note="Missing (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079471"
FT VARIANT 411
FT /note="S -> F (in MODY2)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079472"
FT VARIANT 414
FT /note="K -> E (in MODY2; decreased affinity for glucose;
FT dbSNP:rs193922272)"
FT /evidence="ECO:0000269|PubMed:8325892"
FT /id="VAR_003714"
FT VARIANT 416
FT /note="H -> P (in MODY2; dbSNP:rs1583591303)"
FT /evidence="ECO:0000269|PubMed:17573900"
FT /id="VAR_079473"
FT VARIANT 420
FT /note="K -> E (in MODY2; no effect on glucokinase activity;
FT decreased affinity for glucose; no effect on affinity for
FT ATP)"
FT /evidence="ECO:0000269|PubMed:17573900,
FT ECO:0000269|PubMed:18322640"
FT /id="VAR_079474"
FT VARIANT 434
FT /note="C -> F (in MODY2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078255"
FT VARIANT 441
FT /note="S -> L (in PNDM1; decreased stability; decreased
FT glucokinase activity; no effect on affinity for glucose;
FT dbSNP:rs1286804191)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079475"
FT VARIANT 441
FT /note="S -> W (in MODY2; decreased affinity for glucose)"
FT /evidence="ECO:0000269|PubMed:16965331,
FT ECO:0000269|PubMed:17573900, ECO:0000269|PubMed:19884385"
FT /id="VAR_078256"
FT VARIANT 442
FT /note="E -> K (in HHF3; increased affinity for glucose;
FT dbSNP:rs758737171)"
FT /evidence="ECO:0000269|PubMed:19884385,
FT ECO:0000269|PubMed:28247534"
FT /id="VAR_078257"
FT VARIANT 447
FT /note="R -> Q (in MODY2; dbSNP:rs1131691416)"
FT /evidence="ECO:0000269|PubMed:16965331"
FT /id="VAR_078258"
FT VARIANT 449
FT /note="A -> T (in PNDM1; decreased stability; increased
FT glucokinase activity; increased affinity for glucose;
FT dbSNP:rs193922282)"
FT /evidence="ECO:0000269|PubMed:25015100"
FT /id="VAR_079476"
FT VARIANT 455
FT /note="V -> M (in HHF3; increased glucokinase activity
FT based on measure of catalytic efficiency; increased
FT affinity for glucose; decreased inhibition by GCKR; no
FT effect on affinity for ATP; dbSNP:rs104894012)"
FT /evidence="ECO:0000269|PubMed:17082186,
FT ECO:0000269|PubMed:9435328"
FT /id="VAR_003715"
FT VARIANT 456
FT /note="A -> V (in HHF3; increased glucokinase activity
FT based on measure of catalytic efficiency; increased
FT affinity for glucose; loss of inhibition by GCKR; no effect
FT on affinity for ATP; dbSNP:rs104894014)"
FT /evidence="ECO:0000269|PubMed:11916951,
FT ECO:0000269|PubMed:17082186"
FT /id="VAR_079477"
FT MUTAGEN 64
FT /note="S->P: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose."
FT /evidence="ECO:0000269|PubMed:19146401"
FT MUTAGEN 177
FT /note="E->K: Small change in glucokinase activity."
FT /evidence="ECO:0000269|PubMed:8325892"
FT MUTAGEN 197
FT /note="M->V: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose."
FT /evidence="ECO:0000269|PubMed:19146401"
FT MUTAGEN 211
FT /note="I->F: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose."
FT /evidence="ECO:0000269|PubMed:19146401"
FT MUTAGEN 214
FT /note="Y->A: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose. No effect on affinity for ATP."
FT /evidence="ECO:0000269|PubMed:17082186"
FT MUTAGEN 215
FT /note="Y->A: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose. Loss of inhibition by GCKR. No effect on affinity
FT for ATP."
FT /evidence="ECO:0000269|PubMed:17082186"
FT MUTAGEN 256
FT /note="E->A: Inactive enzyme with no glucokinase activity."
FT /evidence="ECO:0000269|PubMed:8325892"
FT MUTAGEN 414
FT /note="K->A: Small change in glucokinase activity."
FT /evidence="ECO:0000269|PubMed:8325892"
FT MUTAGEN 453
FT /note="S->A: Increased glucokinase activity based on
FT measure of catalytic efficiency. Increased affinity for
FT glucose."
FT /evidence="ECO:0000269|PubMed:19146401"
FT HELIX 12..20
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 27..45
FT /evidence="ECO:0007829|PDB:3F9M"
FT TURN 47..52
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 58..65
FT /evidence="ECO:0007829|PDB:3F9M"
FT TURN 66..68
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 72..92
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:3H1V"
FT STRAND 99..109
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 119..136
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 140..142
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 145..150
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 181..192
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 205..214
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 220..237
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 248..254
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:3F9M"
FT TURN 260..263
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:4MLH"
FT HELIX 267..269
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 272..280
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 288..291
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 295..311
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:3F9M"
FT TURN 322..325
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 332..339
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:3QIC"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:4ISE"
FT HELIX 346..354
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 361..396
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 400..409
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 411..415
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:3VEV"
FT HELIX 419..430
FT /evidence="ECO:0007829|PDB:3F9M"
FT STRAND 434..440
FT /evidence="ECO:0007829|PDB:3F9M"
FT HELIX 444..456
FT /evidence="ECO:0007829|PDB:3F9M"
FT TURN 457..459
FT /evidence="ECO:0007829|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
