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 27-MAR-2024, entry version 233. 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 T2D, AND VARIANT T2D 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 VARIANTS MODY2 ARG-175; MET-182; ALA-203; GLN-300; LYS-300 AND PRO-309. RX PubMed=8433729; DOI=10.1056/nejm199303113281005; RA Froguel P., Zouali H., Vionnet N., Velho G., Vaxillaire M., Sun F., RA Lesage S., Stoffel M., Takeda J., Passa P.; RT "Familial hyperglycemia due to mutations in glucokinase. Definition of a RT subtype of diabetes mellitus."; RL N. Engl. J. Med. 328:697-702(1993). RN [28] RP CHARACTERIZATION OF VARIANTS MODY2, AND VARIANT MODY2 GLN-279. 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 [29] 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 [30] 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 [31] 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-humu11>3.0.co;2-0; 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 [32] 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 [33] 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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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:8433729, CC ECO:0000269|PubMed:8446612, ECO:0000269|PubMed:8495817, CC ECO:0000269|PubMed:8878425, ECO:0000269|PubMed:9049484, CC ECO:0000269|PubMed:9662401}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Hyperinsulinemic hypoglycemia, familial, 3 (HHF3) CC [MIM:602485]: A form of hyperinsulinemic hypoglycemia, a clinically and CC genetically heterogeneous disorder characterized by inappropriate CC insulin secretion from the pancreatic beta-cells in the presence of low CC blood glucose levels. HHF3 clinical features include loss of CC consciousness due to hypoglycemia, hypoglycemic coma, mental CC retardation due to repeated episodes of hypoglycemia, and seizures. CC HHF3 inheritance is autosomal dominant. {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: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial CC disorder of glucose homeostasis caused by a lack of sensitivity to the CC body's own insulin. Affected individuals usually have an obese body CC habitus and manifestations of a metabolic syndrome characterized by CC diabetes, insulin resistance, hypertension and hypertriglyceridemia. CC The 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 variants affecting the CC 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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; 18. 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; 9606-ENSP00000223366; -. DR PeptideAtlas; P35557; -. DR ProteomicsDB; 55084; -. [P35557-1] DR ProteomicsDB; 55085; -. [P35557-2] DR ProteomicsDB; 55086; -. [P35557-3] DR Antibodypedia; 2045; 618 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 AGR; HGNC:4195; -. 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; Congenital glucokinase-related hyperinsulinism. 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; 5481886at2759; -. DR PhylomeDB; P35557; -. DR TreeFam; TF314238; -. DR BioCyc; MetaCyc:HS02935-MONOMER; -. 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; 15 hits in 1186 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 100 other cell types or tissues. DR ExpressionAtlas; P35557; baseline and differential. 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:0141089; F:glucose sensor activity; ISS:BHF-UCL. 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: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:0051156; P:glucose 6-phosphate metabolic process; IMP:UniProtKB. DR GO; GO:0006007; P:glucose catabolic 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:0001678; P:intracellular glucose homeostasis; 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 GO; GO:0009749; P:response to glucose; ISS:BHF-UCL. DR CDD; cd00012; NBD_sugar-kinase_HSP70_actin; 1. DR Gene3D; 3.30.420.40; -; 1. DR Gene3D; 3.40.367.20; -; 1. DR InterPro; IPR043129; ATPase_NBD. DR InterPro; IPR001312; Hexokinase. DR InterPro; IPR019807; Hexokinase_BS. DR InterPro; IPR022673; Hexokinase_C. DR InterPro; IPR022672; Hexokinase_N. DR PANTHER; PTHR19443; HEXOKINASE; 1. DR PANTHER; PTHR19443:SF3; HEXOKINASE-4; 1. DR Pfam; PF00349; Hexokinase_1; 1. DR Pfam; PF03727; Hexokinase_2; 1. DR PRINTS; PR00475; HEXOKINASE. DR SUPFAM; SSF53067; Actin-like ATPase domain; 2. DR PROSITE; PS00378; HEXOKINASE_1; 1. DR PROSITE; PS51748; HEXOKINASE_2; 1. DR Genevisible; P35557; HS. 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; uncertain significance; no change FT 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; uncertain significance; mildly FT 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; dbSNP:rs2096281827)" 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; uncertain significance; FT dbSNP:rs2096280050)" 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; dbSNP:rs2096278847)" 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 /evidence="ECO:0000269|PubMed:8433729" 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 /evidence="ECO:0000269|PubMed:8433729" FT /id="VAR_003699" FT VARIANT 186..465 FT /note="Missing (in MODY2 and T2D)" 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 /evidence="ECO:0000269|PubMed:8433729" 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; benign; 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; uncertain 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; pathogenic; highly FT decreased glucokinase activity; decreased affinity for FT 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 /evidence="ECO:0000269|PubMed:8446612" 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 /evidence="ECO:0000269|PubMed:8433729" FT /id="VAR_003712" FT VARIANT 300 FT /note="E -> Q (in MODY2)" FT /evidence="ECO:0000269|PubMed:8433729" 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 /evidence="ECO:0000269|PubMed:8433729" FT /id="VAR_003713" FT VARIANT 315 FT /note="L -> F (in MODY2; uncertain 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 dbSNP:rs2096271425)" 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; uncertain 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 //