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 11-NOV-2015, entry version 174. DE RecName: Full=Glucokinase; DE EC=2.7.1.2; DE AltName: Full=Hexokinase type IV; DE Short=HK IV; DE AltName: Full=Hexokinase-4; DE Short=HK4; DE AltName: Full=Hexokinase-D; GN Name=GCK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1354840; DOI=10.1210/me.6.7.1070; RA Tanizawa Y., Matsutani A., Chiu K.C., Permutt M.A.; RT "Human glucokinase gene: isolation, structural characterization, and RT identification of a microsatellite repeat polymorphism."; RL Mol. Endocrinol. 6:1070-1081(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT THR-107. RX PubMed=1871135; DOI=10.1073/pnas.88.16.7294; RA Tanizawa Y., Koranyi L.I., Welling C.M., Permutt M.A.; RT "Human liver glucokinase gene: cloning and sequence determination of RT two alternatively spliced cDNAs."; RL Proc. Natl. Acad. Sci. U.S.A. 88:7294-7297(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas; RX PubMed=1511800; RA Nishi S., Stoffel M., Xiang K.S., Shows T.B., Bell G.I., Takeda J.; RT "Human pancreatic beta-cell glucokinase: cDNA sequence and RT localization of the polymorphic gene to chromosome 7, band p13."; RL Diabetologia 35:743-747(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas; RX PubMed=1612194; DOI=10.2337/diab.41.7.807; RA Koranyi L.I., Tanizawa Y., Welling C.M., Rabin D.U., Permutt M.A.; RT "Human islet glucokinase gene. Isolation and sequence analysis of RT full-length cDNA."; RL Diabetes 41:807-811(1992). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MODY2 MET-228 AND RP ARG-261. RC TISSUE=Placenta; RX PubMed=1502186; DOI=10.1073/pnas.89.16.7698; RA Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., RA Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., RA Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.; RT "Human glucokinase gene: isolation, characterization, and RT identification of two missense mutations linked to early-onset non- RT insulin-dependent (type 2) diabetes mellitus."; RL Proc. Natl. Acad. Sci. U.S.A. 89:7698-7702(1992). RN [6] RP ERRATUM. RA Stoffel M., Froguel P., Takeda J., Zouali H., Vionnet N., Nishi S., RA Weber I.T., Harrison R.W., Pilkis S.J., Lesage S., Vaxillaire M., RA Velho G., Sun F., Iris F., Passa P., Cohen D., Bell G.I.; RL Proc. Natl. Acad. Sci. U.S.A. 89:10562-10562(1992). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-107, AND VARIANT MODY2 RP ARG-261. RX PubMed=1464666; DOI=10.1210/jc.75.6.1571; RA Sakura H., Eto K., Kadowaki H., Simokawa K., Ueno H., Koda N., RA Fukushima Y., Akanuma Y., Yazaki Y., Kadowaki T.; RT "Structure of the human glucokinase gene and identification of a RT missense mutation in a Japanese patient with early-onset non-insulin- RT dependent diabetes mellitus."; RL J. Clin. Endocrinol. Metab. 75:1571-1573(1992). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP ENZYME REGULATION, AND SUBCELLULAR LOCATION. RX PubMed=10456334; DOI=10.1016/S0014-5793(99)00971-0; RA de la Iglesia N., Veiga-da-Cunha M., Van Schaftingen E., RA Guinovart J.J., Ferrer J.C.; RT "Glucokinase regulatory protein is essential for the proper RT subcellular localisation of liver glucokinase."; RL FEBS Lett. 456:332-338(1999). RN [13] RP 3D-STRUCTURE MODELING. RX PubMed=8194664; DOI=10.2337/diab.43.6.784; RA St Charles R., Harrison R.W., Bell G.I., Pilkis S.J., Weber I.T.; RT "Molecular model of human beta-cell glucokinase built by analogy to RT the crystal structure of yeast hexokinase B."; RL Diabetes 43:784-791(1994). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 16-465 OF APOPROTEIN AND IN RP COMPLEX WITH GLUCOSE, SUBUNIT, AND ENZYME REGULATION. RX PubMed=15016359; DOI=10.1016/j.str.2004.02.005; RA Kamata K., Mitsuya M., Nishimura T., Eiki J., Nagata Y.; RT "Structural basis for allosteric regulation of the monomeric RT allosteric enzyme human glucokinase."; RL Structure 12:429-438(2004). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 16-465 IN COMPLEX WITH RP SYNTHETIC ALLOSTERIC ACTIVATOR. RX PubMed=19362831; DOI=10.1016/j.bmcl.2009.03.137; RA Mitsuya M., Kamata K., Bamba M., Watanabe H., Sasaki Y., Sasaki K., RA Ohyama S., Hosaka H., Nagata Y., Eiki J., Nishimura T.; RT "Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide RT derivatives as GK activators."; RL Bioorg. Med. Chem. Lett. 19:2718-2721(2009). RN [16] RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 3-465 IN COMPLEX WITH RAT RP GKRP. RX PubMed=23957911; DOI=10.1021/bi400838t; RA Beck T., Miller B.G.; RT "Structural basis for regulation of human glucokinase by glucokinase RT regulatory protein."; RL Biochemistry 52:6232-6239(2013). RN [17] RP VARIANT MODY2 ARG-299. RX PubMed=1303265; DOI=10.1038/ng1092-153; RA Stoffel M., Patel P., Lo Y.-M.D., Hattersley A.T., Lucassen A.M., RA Page R., Bell J.I., Bell G.I., Turner R.C., Wainscoat J.S.; RT "Missense glucokinase mutation in maturity-onset diabetes of the young RT and mutation screening in late-onset diabetes."; RL Nat. Genet. 2:153-156(1992). RN [18] 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 [19] RP VARIANT MODY2 PRO-131. RX PubMed=8495817; DOI=10.2337/diab.42.6.937; RA Stoffel M., Bell K.L., Blackburn C.L., Powell K.L., Seo T.S., RA Takeda J., Vionnet N., Xiang K.-S., Gidh-Jain M., Pilkis S.J., RA Ober C., Bell G.I.; RT "Identification of glucokinase mutations in subjects with gestational RT diabetes mellitus."; RL Diabetes 42:937-940(1993). RN [20] RP VARIANT ASN-4, AND VARIANTS MODY2 LYS-70; PRO-131; THR-188; ARG-257 RP AND GLU-414. RX PubMed=8325892; RA Takeda J., Gidh-Jain M., Xu L.Z., Froguel P., Velho G., Vaxillaire M., RA Cohen D., Shimada F., Makino H., Nishi S., Stoffel M., Vionnet N., RA St Charles R., Harrison R.W., Weber I.T., Bell G.I., Pilkis S.J.; RT "Structure/function studies of human beta-cell glucokinase. Enzymatic RT properties of a sequence polymorphism, mutations associated with RT diabetes, and other site-directed mutants."; RL J. Biol. Chem. 268:15200-15204(1993). RN [21] 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 [22] 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 [23] RP VARIANTS MODY2. RX PubMed=9049484; DOI=10.1007/s001250050666; RA Velho G., Blanche H., Vaxillaire M., Bellanne-Chantelot C., RA Pardini V.C., Timsit J., Passa P., Deschamps I., Robert J.-J., RA Weber I.T., Marotta D., Pilkis S.J., Lipkind G.M., Bell G.I., RA Froguel P.; RT "Identification of 14 new glucokinase mutations and description of the RT clinical profile of 42 MODY-2 families."; RL Diabetologia 40:217-224(1997). RN [24] RP VARIANTS MODY2 SER-80; LYS-221 AND CYS-227. RX PubMed=10694920; RX DOI=10.1002/(SICI)1098-1004(1998)12:2<136::AID-HUMU13>3.3.CO;2-M; RA Guazzini B., Gaffi D., Mainieri D., Multari G., Cordera R., RA Bertolini S., Pozza G., Meschi F., Barbetti F.; RT "Three novel missense mutations in the glucokinase gene (G80S; E221K; RT G227C) in Italian subjects with maturity-onset diabetes of the young RT (MODY)."; RL Hum. Mutat. 12:136-136(1998). RN [25] RP VARIANTS MODY2 HIS-108; SER-150; THR-259; ARG-299; TYR-382; THR-384 RP AND CYS-392. RX PubMed=9662401; DOI=10.1038/953; RA Hattersley A.T., Beards F., Ballantyne E., Appleton M., Harvey R., RA Ellard S.; RT "Mutations in the glucokinase gene of the fetus result in reduced RT birth weight."; RL Nat. Genet. 19:268-270(1998). RN [26] RP VARIANT HHF3 MET-455. RX PubMed=9435328; DOI=10.1056/NEJM199801223380404; RA Glaser B., Kesavan P., Heyman M., Davis E., Cuesta A., Buchs A., RA Stanley C.A., Thornton P.S., Permutt M.A., Matschinsky F.M., RA Herold K.C.; RT "Familial hyperinsulinism caused by an activating glucokinase RT mutation."; RL N. Engl. J. Med. 338:226-230(1998). RN [27] RP VARIANTS MODY2 THR-110; ASP-119 AND VAL-385. RX PubMed=10588527; DOI=10.1046/j.1464-5491.1999.00188.x; RA Ng M.C.Y., Cockburn B.N., Lindner T.H., Yeung V.T.F., Chow C.-C., RA So W.-Y., Li J.K.Y., Lo Y.M.D., Lee Z.S.K., Cockram C.S., RA Critchley J.A.J.H., Bell G.I., Chan J.C.N.; RT "Molecular genetics of diabetes mellitus in Chinese subjects: RT identification of mutations in glucokinase and hepatocyte nuclear RT factor-1alpha genes in patients with early-onset type 2 diabetes RT mellitus/MODY."; RL Diabet. Med. 16:956-963(1999). RN [28] 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 [29] RP VARIANTS MODY2 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 [30] RP VARIANT PRO-342. RX PubMed=21604084; DOI=10.1007/s00125-011-2194-5; RA Steele A.M., Tribble N.D., Caswell R., Wensley K.J., Hattersley A.T., RA Gloyn A.L., Ellard S.; RT "The previously reported T342P GCK missense variant is not a RT pathogenic mutation causing MODY."; RL Diabetologia 54:2202-2205(2011). CC -!- FUNCTION: Catalyzes the initial step in utilization of glucose by CC the beta-cell and liver at physiological glucose concentration. CC Glucokinase has a high Km for glucose, and so it is effective only CC when glucose is abundant. The role of GCK is to provide G6P for CC the synthesis of glycogen. Pancreatic glucokinase plays an CC important role in modulating insulin secretion. Hepatic CC glucokinase helps to facilitate the uptake and conversion of CC glucose by acting as an insulin-sensitive determinant of hepatic CC glucose usage. CC -!- CATALYTIC ACTIVITY: ATP + D-glucose = ADP + D-glucose 6-phosphate. CC -!- ENZYME REGULATION: The use of alternative promoters apparently CC enables the type IV hexokinase gene to be regulated by insulin in CC the liver and glucose in the beta cell. This may constitute an CC important feedback loop for maintaining glucose homeostasis. CC Subject to allosteric regulation. Low glucose and high fructose-6- CC phosphate triggers association with the inhibitor GKRP followed by CC sequestration in the nucleus. {ECO:0000269|PubMed:10456334, CC ECO:0000269|PubMed:15016359}. CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15016359, CC ECO:0000269|PubMed:19362831, ECO:0000269|PubMed:23957911}. CC -!- INTERACTION: CC Q14397:GCKR; NbExp=2; IntAct=EBI-709928, EBI-709948; CC P16118:PFKFB1; NbExp=2; IntAct=EBI-709928, EBI-709807; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334}. CC Nucleus {ECO:0000269|PubMed:10456334}. Note=Under low glucose CC concentrations, GCK associates with GKRP and the inactive complex CC is recruited to the hepatocyte nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P35557-1; Sequence=Displayed; CC Name=2; CC IsoId=P35557-2; Sequence=VSP_002074; CC Name=3; CC IsoId=P35557-3; Sequence=VSP_002075; CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in pancreas. Isoform 2 CC and isoform 3 is expressed in liver. CC -!- DISEASE: Maturity-onset diabetes of the young 2 (MODY2) CC [MIM:125851]: A form of diabetes that is characterized by an CC autosomal dominant mode of inheritance, onset in childhood or CC early adulthood (usually before 25 years of age), a primary defect CC in insulin secretion and frequent insulin-independence at the CC beginning of the disease. {ECO:0000269|PubMed:10588527, CC ECO:0000269|PubMed:10694920, ECO:0000269|PubMed:11106831, CC ECO:0000269|PubMed:11372010, ECO:0000269|PubMed:1303265, CC ECO:0000269|PubMed:1464666, ECO:0000269|PubMed:1502186, CC ECO:0000269|PubMed:8168652, ECO:0000269|PubMed:8325892, CC ECO:0000269|PubMed:8495817, ECO:0000269|PubMed:9049484, CC ECO:0000269|PubMed:9662401}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Familial hyperinsulinemic hypoglycemia 3 (HHF3) CC [MIM:602485]: Most common cause of persistent hypoglycemia in CC infancy. Unless early and aggressive intervention is undertaken, CC brain damage from recurrent episodes of hypoglycemia may occur. CC {ECO:0000269|PubMed:9435328}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- MISCELLANEOUS: In vertebrates there are four major glucose- CC phosphorylating isoenzymes, designated hexokinase I, II, III and CC IV (glucokinase). CC -!- SIMILARITY: Belongs to the hexokinase family. CC {ECO:0000255|PROSITE-ProRule:PRU01084, ECO:0000305}. CC -!- SIMILARITY: Contains 1 hexokinase domain. {ECO:0000255|PROSITE- CC ProRule:PRU01084}. 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_TERM; Genomic_DNA. DR EMBL; M90298; AAA67542.1; ALT_TERM; Genomic_DNA. DR EMBL; M90299; AAA52562.1; -; mRNA. DR EMBL; AF041022; AAB97680.1; -; Genomic_DNA. DR EMBL; AF041012; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041015; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041016; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041017; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041018; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041019; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041020; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041021; AAB97680.1; JOINED; Genomic_DNA. DR EMBL; AF041022; AAB97681.1; -; Genomic_DNA. DR EMBL; AF041013; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041015; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041016; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041017; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041018; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041019; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041020; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041021; AAB97681.1; JOINED; Genomic_DNA. DR EMBL; AF041022; AAB97682.1; -; Genomic_DNA. DR EMBL; AF041014; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041015; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041016; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041017; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041018; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041019; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041020; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AF041021; AAB97682.1; JOINED; Genomic_DNA. DR EMBL; AK122876; BAG53774.1; -; mRNA. DR EMBL; CH236960; EAL23765.1; -; Genomic_DNA. DR EMBL; CH236960; EAL23766.1; -; Genomic_DNA. DR EMBL; CH471128; EAW61114.1; -; Genomic_DNA. DR EMBL; CH471128; EAW61116.1; -; Genomic_DNA. DR EMBL; BC001890; AAH01890.1; -; mRNA. DR CCDS; CCDS5479.1; -. [P35557-1] DR CCDS; CCDS5480.1; -. [P35557-2] DR CCDS; CCDS5481.1; -. [P35557-3] DR PIR; A46157; A46157. DR PIR; B46157; B46157. DR PIR; C46157; C46157. DR RefSeq; NP_000153.1; NM_000162.3. [P35557-1] DR RefSeq; NP_277042.1; NM_033507.1. [P35557-2] DR RefSeq; NP_277043.1; NM_033508.1. [P35557-3] DR UniGene; Hs.1270; -. DR PDB; 1GLK; Model; -; A=1-465. DR PDB; 1V4S; X-ray; 2.30 A; A=16-465. DR PDB; 1V4T; X-ray; 3.40 A; A=16-465. DR PDB; 3A0I; X-ray; 2.20 A; X=16-465. DR PDB; 3F9M; X-ray; 1.50 A; A=12-465. DR PDB; 3FGU; X-ray; 2.15 A; A=12-465. DR PDB; 3FR0; X-ray; 2.70 A; A=16-465. DR PDB; 3GOI; X-ray; 2.52 A; A=16-465. DR PDB; 3H1V; X-ray; 2.11 A; X=16-465. DR PDB; 3ID8; X-ray; 2.40 A; A=12-465. DR PDB; 3IDH; X-ray; 2.14 A; A=12-465. DR PDB; 3IMX; X-ray; 2.00 A; A=16-465. DR PDB; 3QIC; X-ray; 2.20 A; A=12-465. DR PDB; 3S41; X-ray; 2.18 A; A=12-465. DR PDB; 3VEV; X-ray; 1.80 A; A=12-465. DR PDB; 3VEY; X-ray; 2.25 A; A=16-465. DR PDB; 3VF6; X-ray; 1.86 A; A=12-465. DR PDB; 4DCH; X-ray; 1.79 A; A=1-465. DR PDB; 4DHY; X-ray; 2.38 A; A=12-465. DR PDB; 4ISE; X-ray; 1.78 A; A=16-465. DR PDB; 4ISF; X-ray; 2.09 A; A=16-465. DR PDB; 4ISG; X-ray; 2.64 A; A=16-465. DR PDB; 4IWV; X-ray; 2.10 A; A=16-465. DR PDB; 4IXC; X-ray; 2.00 A; A=16-465. DR PDB; 4L3Q; X-ray; 2.70 A; A=16-465. DR PDB; 4LC9; X-ray; 3.40 A; B=3-465. DR PDB; 4MLE; X-ray; 2.60 A; A=16-465. DR PDB; 4MLH; X-ray; 2.90 A; A=16-465. DR PDB; 4NO7; X-ray; 1.70 A; A=12-465. DR PDB; 4RCH; X-ray; 2.30 A; A=16-465. DR PDBsum; 1GLK; -. DR PDBsum; 1V4S; -. DR PDBsum; 1V4T; -. DR PDBsum; 3A0I; -. DR PDBsum; 3F9M; -. DR PDBsum; 3FGU; -. DR PDBsum; 3FR0; -. DR PDBsum; 3GOI; -. DR PDBsum; 3H1V; -. DR PDBsum; 3ID8; -. DR PDBsum; 3IDH; -. DR PDBsum; 3IMX; -. DR PDBsum; 3QIC; -. DR PDBsum; 3S41; -. DR PDBsum; 3VEV; -. DR PDBsum; 3VEY; -. DR PDBsum; 3VF6; -. DR PDBsum; 4DCH; -. DR PDBsum; 4DHY; -. DR PDBsum; 4ISE; -. DR PDBsum; 4ISF; -. DR PDBsum; 4ISG; -. DR PDBsum; 4IWV; -. DR PDBsum; 4IXC; -. DR PDBsum; 4L3Q; -. DR PDBsum; 4LC9; -. DR PDBsum; 4MLE; -. DR PDBsum; 4MLH; -. DR PDBsum; 4NO7; -. DR PDBsum; 4RCH; -. DR ProteinModelPortal; P35557; -. DR SMR; P35557; 16-460. DR BioGrid; 108915; 5. DR IntAct; P35557; 5. DR STRING; 9606.ENSP00000223366; -. DR BindingDB; P35557; -. DR ChEMBL; CHEMBL3820; -. DR GuidetoPHARMACOLOGY; 2798; -. DR PhosphoSite; P35557; -. DR BioMuta; GCK; -. DR DMDM; 547696; -. DR PaxDb; P35557; -. DR PRIDE; P35557; -. DR DNASU; 2645; -. DR Ensembl; ENST00000345378; ENSP00000223366; ENSG00000106633. [P35557-2] DR Ensembl; ENST00000395796; ENSP00000379142; ENSG00000106633. [P35557-3] DR Ensembl; ENST00000403799; ENSP00000384247; ENSG00000106633. [P35557-1] DR Ensembl; ENST00000616242; ENSP00000482149; ENSG00000106633. [P35557-3] DR GeneID; 2645; -. DR KEGG; hsa:2645; -. DR UCSC; uc003tkj.1; human. [P35557-3] DR UCSC; uc003tkk.1; human. [P35557-2] DR UCSC; uc003tkl.2; human. [P35557-1] DR CTD; 2645; -. DR GeneCards; GCK; -. DR GeneReviews; GCK; -. DR HGNC; HGNC:4195; GCK. DR HPA; HPA007034; -. DR HPA; HPA007093; -. DR MIM; 125851; phenotype. DR MIM; 138079; gene. DR MIM; 602485; phenotype. DR MIM; 606391; phenotype. DR neXtProt; NX_P35557; -. DR Orphanet; 79299; Hyperinsulinism due to glucokinase deficiency. DR Orphanet; 552; MODY. DR Orphanet; 99885; Permanent neonatal diabetes mellitus. DR PharmGKB; PA28610; -. DR eggNOG; KOG1369; Eukaryota. DR eggNOG; COG5026; LUCA. DR GeneTree; ENSGT00390000017159; -. DR HOGENOM; HOG000162670; -. DR HOVERGEN; HBG000142; -. DR InParanoid; P35557; -. DR KO; K12407; -. DR OMA; EDHQCEV; -. DR PhylomeDB; P35557; -. DR TreeFam; TF314238; -. DR BioCyc; MetaCyc:HS02935-MONOMER; -. DR BRENDA; 2.7.1.1; 2681. DR BRENDA; 2.7.1.2; 2681. DR Reactome; R-HSA-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein. DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells. DR Reactome; R-HSA-70153; Glucose transport. DR Reactome; R-HSA-70171; Glycolysis. DR SABIO-RK; P35557; -. DR ChiTaRS; GCK; human. DR EvolutionaryTrace; P35557; -. DR GeneWiki; Glucokinase; -. DR GenomeRNAi; 2645; -. DR NextBio; 10434; -. DR PRO; PR:P35557; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; P35557; -. DR CleanEx; HS_GCK; -. DR ExpressionAtlas; P35557; baseline and differential. DR Genevisible; P35557; HS. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0004340; F:glucokinase activity; IDA:UniProtKB. DR GO; GO:0005536; F:glucose binding; IDA:UniProtKB. DR GO; GO:0070509; P:calcium ion import; IEA:Ensembl. DR GO; GO:0061621; P:canonical glycolysis; TAS:Reactome. DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:Reactome. DR GO; GO:0001678; P:cellular glucose homeostasis; IBA:GO_Central. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:BHF-UCL. DR GO; GO:0044320; P:cellular response to leptin stimulus; ISS:BHF-UCL. DR GO; GO:0051594; P:detection of glucose; IMP:UniProtKB. DR GO; GO:0031018; P:endocrine pancreas development; TAS:Reactome. DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IDA:GOC. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome. DR GO; GO:0015758; P:glucose transport; TAS:Reactome. DR GO; GO:0006096; P:glycolytic process; IBA:GO_Central. DR GO; GO:0008645; P:hexose transport; TAS:Reactome. 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:0010827; P:regulation of glucose transport; TAS:Reactome. 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:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. 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 Pfam; PF00349; Hexokinase_1; 1. DR Pfam; PF03727; Hexokinase_2; 1. DR PROSITE; PS00378; HEXOKINASE_1; 1. DR PROSITE; PS51748; HEXOKINASE_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Alternative splicing; ATP-binding; KW Complete proteome; Cytoplasm; Diabetes mellitus; Disease mutation; KW Glycolysis; Kinase; Nucleotide-binding; Nucleus; Polymorphism; KW Reference proteome; Transferase. FT CHAIN 1 465 Glucokinase. FT /FTId=PRO_0000197593. FT DOMAIN 10 454 Hexokinase. {ECO:0000255|PROSITE- FT ProRule:PRU01084}. FT NP_BIND 78 83 ATP. {ECO:0000250}. FT NP_BIND 295 296 ATP. {ECO:0000250}. FT NP_BIND 332 336 ATP. {ECO:0000250}. FT NP_BIND 411 415 ATP. {ECO:0000250}. FT REGION 67 203 Hexokinase small subdomain. FT {ECO:0000255|PROSITE-ProRule:PRU01084}. FT REGION 151 152 Substrate binding. FT REGION 168 169 Substrate binding. FT REGION 204 443 Hexokinase large subdomain. FT {ECO:0000255|PROSITE-ProRule:PRU01084}. FT REGION 204 205 Substrate binding. FT BINDING 104 104 ATP. {ECO:0000255}. FT BINDING 228 228 ATP. {ECO:0000250}. FT BINDING 231 231 Substrate. FT BINDING 256 256 Substrate. FT BINDING 290 290 Substrate. FT VAR_SEQ 1 15 MLDDRARMEAAKKEK -> MAMDVTRSQAQTALTL (in FT isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_002074. FT VAR_SEQ 1 15 MLDDRARMEAAKKEK -> MPRPRSQLPQPNSQ (in FT isoform 3). {ECO:0000305}. FT /FTId=VSP_002075. FT VARIANT 4 4 D -> N. {ECO:0000269|PubMed:8325892}. FT /FTId=VAR_003692. FT VARIANT 11 11 A -> T (in dbSNP:rs116093166). FT {ECO:0000269|PubMed:8454109}. FT /FTId=VAR_010583. FT VARIANT 36 36 R -> W (in MODY2). FT {ECO:0000269|PubMed:8168652}. FT /FTId=VAR_010584. FT VARIANT 53 53 A -> S (in MODY2). FT /FTId=VAR_010585. FT VARIANT 70 70 E -> K (in MODY2; large increase in Km FT for glucose). FT {ECO:0000269|PubMed:8325892}. FT /FTId=VAR_003693. FT VARIANT 80 80 G -> A (in MODY2). FT /FTId=VAR_003694. FT VARIANT 80 80 G -> S (in MODY2). FT {ECO:0000269|PubMed:10694920}. FT /FTId=VAR_003695. FT VARIANT 107 107 M -> T. {ECO:0000269|PubMed:1464666, FT ECO:0000269|PubMed:1871135}. FT /FTId=VAR_003696. FT VARIANT 108 108 Y -> H (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010586. FT VARIANT 110 110 I -> T (in MODY2). FT {ECO:0000269|PubMed:10588527}. FT /FTId=VAR_012352. FT VARIANT 119 119 A -> D (in MODY2). FT {ECO:0000269|PubMed:10588527}. FT /FTId=VAR_012353. FT VARIANT 131 131 S -> P (in MODY2; significant increase in FT the Km and in the affinity for ATP). FT {ECO:0000269|PubMed:8325892, FT ECO:0000269|PubMed:8495817}. FT /FTId=VAR_003697. FT VARIANT 137 137 H -> R (in MODY2). FT /FTId=VAR_010587. FT VARIANT 150 150 F -> S (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010588. FT VARIANT 164 164 L -> P (in MODY2). FT {ECO:0000269|PubMed:11106831}. FT /FTId=VAR_012350. FT VARIANT 168 168 T -> P (in MODY2). FT /FTId=VAR_010589. FT VARIANT 175 175 G -> R (in MODY2). FT /FTId=VAR_003698. FT VARIANT 182 182 V -> M (in MODY2). FT /FTId=VAR_003699. FT VARIANT 188 188 A -> T (in MODY2; large increase in Km FT for glucose). FT {ECO:0000269|PubMed:8325892}. FT /FTId=VAR_003700. FT VARIANT 203 203 V -> A (in MODY2). FT /FTId=VAR_003701. FT VARIANT 209 209 T -> M (in MODY2). FT {ECO:0000269|PubMed:8168652}. FT /FTId=VAR_010590. FT VARIANT 210 210 M -> K (in MODY2). FT {ECO:0000269|PubMed:11372010}. FT /FTId=VAR_012351. FT VARIANT 210 210 M -> T (in MODY2). FT /FTId=VAR_010591. FT VARIANT 213 213 C -> R (in MODY2). FT /FTId=VAR_010592. FT VARIANT 221 221 E -> K (in MODY2). FT {ECO:0000269|PubMed:10694920}. FT /FTId=VAR_003702. FT VARIANT 226 226 V -> M (in MODY2). FT /FTId=VAR_003703. FT VARIANT 227 227 G -> C (in MODY2). FT {ECO:0000269|PubMed:10694920}. FT /FTId=VAR_003704. FT VARIANT 228 228 T -> M (in MODY2). FT {ECO:0000269|PubMed:11372010, FT ECO:0000269|PubMed:1502186}. FT /FTId=VAR_003705. FT VARIANT 256 256 E -> K (in MODY2). FT /FTId=VAR_003706. FT VARIANT 257 257 W -> R (in MODY2; almost complete loss of FT activity). {ECO:0000269|PubMed:8325892}. FT /FTId=VAR_003707. FT VARIANT 259 259 A -> T (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010593. FT VARIANT 261 261 G -> E (in MODY2). FT {ECO:0000269|PubMed:8168652}. FT /FTId=VAR_010594. FT VARIANT 261 261 G -> R (in MODY2). FT {ECO:0000269|PubMed:1464666, FT ECO:0000269|PubMed:1502186}. FT /FTId=VAR_003708. FT VARIANT 279 279 E -> Q (in MODY2; dbSNP:rs104894005). FT /FTId=VAR_003709. FT VARIANT 299 299 G -> R (in MODY2). FT {ECO:0000269|PubMed:1303265, FT ECO:0000269|PubMed:9662401}. FT /FTId=VAR_003710. FT VARIANT 300 300 E -> K (in MODY2). FT /FTId=VAR_003712. FT VARIANT 300 300 E -> Q (in MODY2). FT /FTId=VAR_003711. FT VARIANT 309 309 L -> P (in MODY2). FT /FTId=VAR_003713. FT VARIANT 336 336 S -> L (in MODY2). FT /FTId=VAR_010595. FT VARIANT 342 342 T -> P. {ECO:0000269|PubMed:21604084}. FT /FTId=VAR_066615. FT VARIANT 367 367 V -> M (in MODY2). FT /FTId=VAR_010596. FT VARIANT 382 382 C -> Y (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010597. FT VARIANT 384 384 A -> T (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010598. FT VARIANT 385 385 G -> V (in MODY2). FT {ECO:0000269|PubMed:10588527}. FT /FTId=VAR_012354. FT VARIANT 392 392 R -> C (in MODY2). FT {ECO:0000269|PubMed:9662401}. FT /FTId=VAR_010599. FT VARIANT 414 414 K -> E (in MODY2; large increase in Km FT for glucose). FT {ECO:0000269|PubMed:8325892}. FT /FTId=VAR_003714. FT VARIANT 455 455 V -> M (in HHF3). FT {ECO:0000269|PubMed:9435328}. FT /FTId=VAR_003715. FT MUTAGEN 177 177 E->K: Small change in activity. FT MUTAGEN 256 256 E->A: Inactive enzyme. FT MUTAGEN 414 414 K->A: Small change in activity. FT HELIX 12 20 {ECO:0000244|PDB:3F9M}. FT HELIX 21 23 {ECO:0000244|PDB:3F9M}. FT HELIX 27 45 {ECO:0000244|PDB:3F9M}. FT TURN 47 52 {ECO:0000244|PDB:3F9M}. FT STRAND 58 65 {ECO:0000244|PDB:3F9M}. FT TURN 66 68 {ECO:0000244|PDB:4LC9}. FT STRAND 72 92 {ECO:0000244|PDB:3F9M}. FT STRAND 95 97 {ECO:0000244|PDB:3H1V}. FT STRAND 99 109 {ECO:0000244|PDB:3F9M}. FT HELIX 112 115 {ECO:0000244|PDB:3F9M}. FT STRAND 116 118 {ECO:0000244|PDB:3F9M}. FT HELIX 119 136 {ECO:0000244|PDB:3F9M}. FT STRAND 140 142 {ECO:0000244|PDB:3F9M}. FT STRAND 145 150 {ECO:0000244|PDB:3F9M}. FT STRAND 154 158 {ECO:0000244|PDB:3F9M}. FT STRAND 161 164 {ECO:0000244|PDB:3F9M}. FT HELIX 181 192 {ECO:0000244|PDB:3F9M}. FT STRAND 198 203 {ECO:0000244|PDB:3F9M}. FT HELIX 205 214 {ECO:0000244|PDB:3F9M}. FT STRAND 220 237 {ECO:0000244|PDB:3F9M}. FT HELIX 238 240 {ECO:0000244|PDB:3F9M}. FT STRAND 248 254 {ECO:0000244|PDB:3F9M}. FT HELIX 257 259 {ECO:0000244|PDB:3F9M}. FT TURN 260 263 {ECO:0000244|PDB:3F9M}. FT STRAND 264 266 {ECO:0000244|PDB:4MLH}. FT HELIX 267 269 {ECO:0000244|PDB:3F9M}. FT HELIX 272 280 {ECO:0000244|PDB:3F9M}. FT STRAND 281 283 {ECO:0000244|PDB:3F9M}. FT HELIX 288 291 {ECO:0000244|PDB:3F9M}. FT HELIX 295 311 {ECO:0000244|PDB:3F9M}. FT HELIX 316 318 {ECO:0000244|PDB:3F9M}. FT TURN 322 325 {ECO:0000244|PDB:3F9M}. FT HELIX 332 339 {ECO:0000244|PDB:3F9M}. FT STRAND 340 342 {ECO:0000244|PDB:3QIC}. FT STRAND 343 345 {ECO:0000244|PDB:4ISE}. FT HELIX 346 354 {ECO:0000244|PDB:3F9M}. FT HELIX 361 396 {ECO:0000244|PDB:3F9M}. FT STRAND 400 409 {ECO:0000244|PDB:3F9M}. FT HELIX 411 415 {ECO:0000244|PDB:3F9M}. FT STRAND 416 418 {ECO:0000244|PDB:3VEV}. FT HELIX 419 430 {ECO:0000244|PDB:3F9M}. FT STRAND 434 440 {ECO:0000244|PDB:3F9M}. FT HELIX 444 456 {ECO:0000244|PDB:3F9M}. FT TURN 457 459 {ECO:0000244|PDB:3H1V}. SQ SEQUENCE 465 AA; 52191 MW; 094D4A2F78096724 CRC64; MLDDRARMEA AKKEKVEQIL AEFQLQEEDL KKVMRRMQKE MDRGLRLETH EEASVKMLPT YVRSTPEGSE VGDFLSLDLG GTNFRVMLVK VGEGEEGQWS VKTKHQMYSI PEDAMTGTAE MLFDYISECI SDFLDKHQMK HKKLPLGFTF SFPVRHEDID KGILLNWTKG FKASGAEGNN VVGLLRDAIK RRGDFEMDVV AMVNDTVATM ISCYYEDHQC EVGMIVGTGC NACYMEEMQN VELVEGDEGR MCVNTEWGAF GDSGELDEFL LEYDRLVDES SANPGQQLYE KLIGGKYMGE LVRLVLLRLV DENLLFHGEA SEQLRTRGAF ETRFVSQVES DTGDRKQIYN ILSTLGLRPS TTDCDIVRRA CESVSTRAAH MCSAGLAGVI NRMRESRSED VMRITVGVDG SVYKLHPSFK ERFHASVRRL TPSCEITFIE SEEGSGRGAA LVSAVACKKA CMLGQ //