ID GCKR_HUMAN Reviewed; 625 AA. AC Q14397; A1L4C2; B4DPQ2; Q53RY6; Q99522; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 6. DT 27-MAR-2024, entry version 174. DE RecName: Full=Glucokinase regulatory protein {ECO:0000303|PubMed:8589523}; DE Short=GKRP {ECO:0000303|PubMed:23621087}; DE Short=Glucokinase regulator {ECO:0000303|PubMed:9570959}; GN Name=GCKR {ECO:0000303|PubMed:8589523, ECO:0000312|HGNC:HGNC:4196}; 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 / MRNA]. RC TISSUE=Hepatoblastoma; RX PubMed=8589523; DOI=10.1007/bf00356171; RA Warner J.P., Leek J.P., Intody S., Markham A.F., Bonthron D.T.; RT "Human glucokinase regulatory protein (GCKR): cDNA and genomic cloning, RT complete primary structure, and chromosomal localization."; RL Mamm. Genome 6:532-536(1995). RN [2] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION TO 393 AND RP 560, AND TISSUE SPECIFICITY. RX PubMed=9570959; DOI=10.1006/geno.1997.5195; RA Hayward B.E., Dunlop N., Intody S., Leek J.P., Markham A.F., Warner J.P., RA Bonthron D.T.; RT "Organization of the human glucokinase regulator gene GCKR."; RL Genomics 49:137-142(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-77; SER-256; LEU-446 RP AND GLN-540. RG NIEHS SNPs program; RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-446. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [7] RP SUBCELLULAR LOCATION, AND SUBUNIT. 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 [8] RP INVOLVEMENT IN FGQTL5, VARIANT LEU-446, AND ASSOCIATION WITH LOWER RISK FOR RP DIABETES TYPE 2. RX PubMed=18556336; DOI=10.2337/db07-1807; RA Vaxillaire M., Cavalcanti-Proenca C., Dechaume A., Tichet J., Marre M., RA Balkau B., Froguel P.; RT "The common P446L polymorphism in GCKR inversely modulates fasting glucose RT and triglyceride levels and reduces type 2 diabetes risk in the DESIR RT prospective general French population."; RL Diabetes 57:2253-2257(2008). RN [9] RP TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT LEU-446. RX PubMed=19643913; DOI=10.1093/hmg/ddp357; RA Beer N.L., Tribble N.D., McCulloch L.J., Roos C., Johnson P.R., RA Orho-Melander M., Gloyn A.L.; RT "The P446L variant in GCKR associated with fasting plasma glucose and RT triglyceride levels exerts its effect through increased glucokinase RT activity in liver."; RL Hum. Mol. Genet. 18:4081-4088(2009). RN [10] RP FUNCTION, INTERACTION WITH GCK, AND MUTAGENESIS OF ASP-413 AND RP 463-LEU--PHE-465. RX PubMed=23733961; DOI=10.1073/pnas.1300457110; RA Choi J.M., Seo M.H., Kyeong H.H., Kim E., Kim H.S.; RT "Molecular basis for the role of glucokinase regulatory protein as the RT allosteric switch for glucokinase."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10171-10176(2013). RN [11] {ECO:0007744|PDB:4BB9, ECO:0007744|PDB:4BBA} RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) IN COMPLEX WITH RP BETA-D-FRUCTOSE-1-PHOSPHATE, FUNCTION, INTERACTION WITH GCK, AND RP MUTAGENESIS OF 326-LYS-LYS-327 AND 450-LYS-LYS-451. RX PubMed=23621087; DOI=10.1021/bi4000782; RA Pautsch A., Stadler N., Lohle A., Rist W., Berg A., Glocker L., Nar H., RA Reinert D., Lenter M., Heckel A., Schnapp G., Kauschke S.G.; RT "Crystal structure of glucokinase regulatory protein."; RL Biochemistry 52:3523-3531(2013). RN [12] RP VARIANT LEU-446, INVOLVEMENT IN FGQTL5, AND ASSOCIATION WITH HIGH PLASMA RP TRIGLYCERIDE LEVELS. RX PubMed=18678614; DOI=10.2337/db08-0516; RA Orho-Melander M., Melander O., Guiducci C., Perez-Martinez P., Corella D., RA Roos C., Tewhey R., Rieder M.J., Hall J., Abecasis G., Tai E.S., Welch C., RA Arnett D.K., Lyssenko V., Lindholm E., Saxena R., de Bakker P.I., Burtt N., RA Voight B.F., Hirschhorn J.N., Tucker K.L., Hedner T., Tuomi T., Isomaa B., RA Eriksson K.F., Taskinen M.R., Wahlstrand B., Hughes T.E., Parnell L.D., RA Lai C.Q., Berglund G., Peltonen L., Vartiainen E., Jousilahti P., RA Havulinna A.S., Salomaa V., Nilsson P., Groop L., Altshuler D., RA Ordovas J.M., Kathiresan S.; RT "Common missense variant in the glucokinase regulatory protein gene is RT associated with increased plasma triglyceride and C-reactive protein but RT lower fasting glucose concentrations."; RL Diabetes 57:3112-3121(2008). CC -!- FUNCTION: Regulates glucokinase (GCK) by forming an inactive complex CC with this enzyme (PubMed:23621087, PubMed:23733961). Acts by promoting CC GCK recruitment to the nucleus, possibly to provide a reserve of GCK CC that can be quickly released in the cytoplasm after a meal CC (PubMed:10456334). The affinity of GCKR for GCK is modulated by CC fructose metabolites: GCKR with bound fructose 6-phosphate has CC increased affinity for GCK, while GCKR with bound fructose 1-phosphate CC has strongly decreased affinity for GCK and does not inhibit GCK CC activity (PubMed:23621087, PubMed:23733961). CC {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:23621087, CC ECO:0000269|PubMed:23733961}. CC -!- SUBUNIT: Interacts (fructose 6-phosphate bound form) with GCK. CC {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:23621087, CC ECO:0000269|PubMed:23733961}. CC -!- INTERACTION: CC Q14397; P35557: GCK; NbExp=5; IntAct=EBI-709948, EBI-709928; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334}. Nucleus CC {ECO:0000269|PubMed:10456334}. Mitochondrion CC {ECO:0000250|UniProtKB:Q07071}. Note=Under low glucose concentrations, CC GCKR associates with GCK and the inactive complex is recruited to the CC hepatocyte nucleus. {ECO:0000269|PubMed:10456334}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14397-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14397-2; Sequence=VSP_054853, VSP_054854; CC -!- TISSUE SPECIFICITY: Found in liver and pancreas. Not detected in CC muscle, brain, heart, thymus, intestine, uterus, adipose tissue, CC kidney, adrenal, lung or spleen. {ECO:0000269|PubMed:19643913, CC ECO:0000269|PubMed:9570959}. CC -!- DOMAIN: Fructose 1-phosphate and fructose 6-phosphate compete for the CC same binding site. {ECO:0000269|PubMed:23621087}. CC -!- POLYMORPHISM: Genetic variations in GCKR define the fasting plasma CC glucose levels quantitative trait locus 5 (FGQTL5) [MIM:613463] CC (PubMed:18556336, PubMed:18678614). The normal fasting plasma glucose CC level is defined as less than 100 mg glucose per deciliter plasma (5.55 CC mmol per liter). Higher fasting plasma glucose levels predict type 2 CC diabetes in young adults and increases the risk of mortality CC (PubMed:18556336, PubMed:18678614). {ECO:0000269|PubMed:18556336, CC ECO:0000269|PubMed:18678614}. CC -!- SIMILARITY: Belongs to the GCKR family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/gckr/"; 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; Z48475; CAA88367.1; -; mRNA. DR EMBL; Y09593; CAA70779.2; -; Genomic_DNA. DR EMBL; Y09592; CAB61828.1; -; Genomic_DNA. DR EMBL; AY320034; AAP72013.1; -; Genomic_DNA. DR EMBL; AK298448; BAG60664.1; -; mRNA. DR EMBL; AC074117; AAY14850.1; -; Genomic_DNA. DR EMBL; BC130481; AAI30482.1; -; mRNA. DR EMBL; BC130483; AAI30484.1; -; mRNA. DR CCDS; CCDS1757.1; -. [Q14397-1] DR PIR; S52485; S52485. DR RefSeq; NP_001477.2; NM_001486.3. DR PDB; 4BB9; X-ray; 1.47 A; A=1-625. DR PDB; 4BBA; X-ray; 1.92 A; A=1-625. DR PDB; 4LY9; X-ray; 2.35 A; A/B=1-625. DR PDB; 4MQU; X-ray; 2.22 A; A/B=1-625. DR PDB; 4MRO; X-ray; 2.20 A; A/B=1-625. DR PDB; 4MSU; X-ray; 2.50 A; A/B=1-625. DR PDB; 4OHK; X-ray; 2.80 A; A/B=1-625. DR PDB; 4OHM; X-ray; 2.40 A; A/B=1-625. DR PDB; 4OHO; X-ray; 2.58 A; A/B=1-625. DR PDB; 4OHP; X-ray; 2.40 A; A/B=1-625. DR PDB; 4OLH; X-ray; 2.40 A; A/B=1-625. DR PDB; 4OP1; X-ray; 2.39 A; A/B=1-625. DR PDB; 4OP2; X-ray; 2.24 A; A/B=1-625. DR PDB; 4OP3; X-ray; 2.82 A; A/B=1-625. DR PDB; 4PX2; X-ray; 2.15 A; A/B=1-625. DR PDB; 4PX3; X-ray; 2.43 A; A/B=1-625. DR PDB; 4PX5; X-ray; 2.20 A; A/B=1-625. DR PDB; 4PXS; X-ray; 2.60 A; A/B=1-625. DR PDBsum; 4BB9; -. DR PDBsum; 4BBA; -. DR PDBsum; 4LY9; -. DR PDBsum; 4MQU; -. DR PDBsum; 4MRO; -. DR PDBsum; 4MSU; -. DR PDBsum; 4OHK; -. DR PDBsum; 4OHM; -. DR PDBsum; 4OHO; -. DR PDBsum; 4OHP; -. DR PDBsum; 4OLH; -. DR PDBsum; 4OP1; -. DR PDBsum; 4OP2; -. DR PDBsum; 4OP3; -. DR PDBsum; 4PX2; -. DR PDBsum; 4PX3; -. DR PDBsum; 4PX5; -. DR PDBsum; 4PXS; -. DR AlphaFoldDB; Q14397; -. DR SMR; Q14397; -. DR BioGRID; 108916; 8. DR IntAct; Q14397; 3. DR MINT; Q14397; -. DR STRING; 9606.ENSP00000264717; -. DR BindingDB; Q14397; -. DR ChEMBL; CHEMBL1075152; -. DR iPTMnet; Q14397; -. DR PhosphoSitePlus; Q14397; -. DR BioMuta; GCKR; -. DR DMDM; 327478611; -. DR jPOST; Q14397; -. DR MassIVE; Q14397; -. DR PaxDb; 9606-ENSP00000264717; -. DR PeptideAtlas; Q14397; -. DR ProteomicsDB; 4803; -. DR ProteomicsDB; 59979; -. [Q14397-1] DR DNASU; 2646; -. DR GeneID; 2646; -. DR KEGG; hsa:2646; -. DR UCSC; uc002rky.4; human. [Q14397-1] DR AGR; HGNC:4196; -. DR CTD; 2646; -. DR DisGeNET; 2646; -. DR GeneCards; GCKR; -. DR HGNC; HGNC:4196; GCKR. DR MalaCards; GCKR; -. DR MIM; 600842; gene. DR MIM; 613463; phenotype. DR neXtProt; NX_Q14397; -. DR PharmGKB; PA28611; -. DR VEuPathDB; HostDB:ENSG00000084734; -. DR eggNOG; ENOG502QS2J; Eukaryota. DR HOGENOM; CLU_1739896_0_0_1; -. DR InParanoid; Q14397; -. DR OrthoDB; 7403at2759; -. DR PhylomeDB; Q14397; -. DR TreeFam; TF329177; -. DR PathwayCommons; Q14397; -. DR Reactome; R-HSA-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein. DR Reactome; R-HSA-5619107; Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC). DR SignaLink; Q14397; -. DR BioGRID-ORCS; 2646; 9 hits in 1159 CRISPR screens. DR GenomeRNAi; 2646; -. DR Pharos; Q14397; Tchem. DR PRO; PR:Q14397; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q14397; Protein. DR Bgee; ENSG00000084734; Expressed in right lobe of liver and 98 other cell types or tissues. DR ExpressionAtlas; Q14397; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB. DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central. DR GO; GO:0019899; F:enzyme binding; IBA:GO_Central. DR GO; GO:0004857; F:enzyme inhibitor activity; IBA:GO_Central. DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:UniProtKB. DR GO; GO:0141089; F:glucose sensor activity; IDA:BHF-UCL. DR GO; GO:0019210; F:kinase inhibitor activity; IDA:BHF-UCL. DR GO; GO:1901135; P:carbohydrate derivative metabolic process; IEA:InterPro. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-KW. DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central. DR GO; GO:0033132; P:negative regulation of glucokinase activity; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; ISS:BHF-UCL. DR GO; GO:0009750; P:response to fructose; IDA:BHF-UCL. DR GO; GO:0009749; P:response to glucose; IDA:BHF-UCL. DR GO; GO:0070328; P:triglyceride homeostasis; IMP:BHF-UCL. DR GO; GO:0046415; P:urate metabolic process; IMP:BHF-UCL. DR Gene3D; 1.10.8.1080; -; 1. DR Gene3D; 3.40.50.12620; -; 1. DR InterPro; IPR005486; Glucokinase_regulatory_CS. DR InterPro; IPR040190; MURQ/GCKR. DR InterPro; IPR001347; SIS_dom. DR InterPro; IPR046348; SIS_dom_sf. DR PANTHER; PTHR10088; GLUCOKINASE REGULATORY PROTEIN; 1. DR PANTHER; PTHR10088:SF4; GLUCOKINASE REGULATORY PROTEIN; 1. DR Pfam; PF20741; GKRP-like_C; 1. DR SUPFAM; SSF53697; SIS domain; 2. DR PROSITE; PS01272; GCKR; 1. DR PROSITE; PS51464; SIS; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Carbohydrate metabolism; Cytoplasm; KW Mitochondrion; Nucleus; Reference proteome; Repeat. FT CHAIN 1..625 FT /note="Glucokinase regulatory protein" FT /id="PRO_0000214826" FT DOMAIN 90..286 FT /note="SIS 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00797" FT DOMAIN 320..499 FT /note="SIS 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00797" FT REGION 199..200 FT /note="Important for interaction with GCK" FT /evidence="ECO:0000250|UniProtKB:Q07071" FT REGION 463..465 FT /note="Essential for interaction with GCK" FT /evidence="ECO:0000269|PubMed:23733961" FT BINDING 109..110 FT /ligand="beta-D-fructose 1-phosphate" FT /ligand_id="ChEBI:CHEBI:138881" FT /evidence="ECO:0000269|PubMed:23621087, FT ECO:0007744|PDB:4BB9" FT BINDING 109..110 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q07071" FT BINDING 153 FT /ligand="beta-D-fructose 1-phosphate" FT /ligand_id="ChEBI:CHEBI:138881" FT /evidence="ECO:0000269|PubMed:23621087, FT ECO:0007744|PDB:4BB9" FT BINDING 179..181 FT /ligand="beta-D-fructose 1-phosphate" FT /ligand_id="ChEBI:CHEBI:138881" FT /evidence="ECO:0000269|PubMed:23621087, FT ECO:0007744|PDB:4BB9" FT BINDING 179..181 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q07071" FT BINDING 348 FT /ligand="beta-D-fructose 1-phosphate" FT /ligand_id="ChEBI:CHEBI:138881" FT /evidence="ECO:0000269|PubMed:23621087, FT ECO:0007744|PDB:4BB9" FT BINDING 514 FT /ligand="beta-D-fructose 1-phosphate" FT /ligand_id="ChEBI:CHEBI:138881" FT /evidence="ECO:0000269|PubMed:23621087, FT ECO:0007744|PDB:4BB9" FT BINDING 514 FT /ligand="beta-D-fructose 6-phosphate" FT /ligand_id="ChEBI:CHEBI:57634" FT /evidence="ECO:0000250|UniProtKB:Q07071" FT VAR_SEQ 144..150 FT /note="SVVASRE -> WLPGRRE (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054853" FT VAR_SEQ 151..625 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054854" FT VARIANT 77 FT /note="E -> G (in dbSNP:rs8179206)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018849" FT VARIANT 256 FT /note="G -> S (in dbSNP:rs8179212)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018850" FT VARIANT 446 FT /note="P -> L (protective factor against diabetes type 2; FT correlated with high triglyceride levels and low fasting FT plasma glucose levels; the mutant protein is less FT efficiently regulated by physiological concentrations of FT fructose-6 phosphate; dbSNP:rs1260326)" FT /evidence="ECO:0000269|PubMed:15815621, FT ECO:0000269|PubMed:18556336, ECO:0000269|PubMed:18678614, FT ECO:0000269|PubMed:19643913, ECO:0000269|Ref.3" FT /id="VAR_008906" FT VARIANT 540 FT /note="R -> Q (in dbSNP:rs8179249)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018851" FT MUTAGEN 326..327 FT /note="KK->TT: No effect on inhibition of glucokinase." FT /evidence="ECO:0000269|PubMed:23621087" FT MUTAGEN 413 FT /note="D->A: Impairs inhibition of glucokinase." FT /evidence="ECO:0000269|PubMed:23733961" FT MUTAGEN 450..451 FT /note="KK->TT: Impairs inhibition of glucokinase." FT /evidence="ECO:0000269|PubMed:23621087" FT MUTAGEN 463..465 FT /note="LLF->ALA: Abolishes interaction with GCK. Abolishes FT inhibition of GCK." FT /evidence="ECO:0000269|PubMed:23733961" FT CONFLICT 251 FT /note="P -> V (in Ref. 2; CAB61828)" FT /evidence="ECO:0000305" FT CONFLICT 393 FT /note="L -> P (in Ref. 1; CAA88367)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="H -> R (in Ref. 1; CAA88367)" FT /evidence="ECO:0000305" FT TURN 2..4 FT /evidence="ECO:0007829|PDB:4PX2" FT HELIX 5..7 FT /evidence="ECO:0007829|PDB:4PX2" FT TURN 19..22 FT /evidence="ECO:0007829|PDB:4PX2" FT HELIX 23..26 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 30..32 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 36..38 FT /evidence="ECO:0007829|PDB:4PX2" FT HELIX 41..43 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 46..58 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 77..94 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 100..107 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 108..127 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 134..138 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 143..146 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 150..154 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 156..167 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 171..178 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 185..195 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 198..200 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 201..206 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 211..213 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:4PX2" FT HELIX 226..237 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 238..240 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 258..260 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 261..283 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 289..307 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 310..325 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 330..335 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 337..353 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 359..366 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 369..371 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 375..377 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 378..380 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 383..385 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 389..395 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 397..399 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 405..411 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 416..427 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 433..440 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 447..452 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 453..455 FT /evidence="ECO:0007829|PDB:4OP2" FT STRAND 457..461 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 467..469 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 470..495 FT /evidence="ECO:0007829|PDB:4BB9" FT TURN 496..498 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 513..527 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 531..543 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 550..553 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 557..564 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 567..569 FT /evidence="ECO:0007829|PDB:4OP3" FT HELIX 570..580 FT /evidence="ECO:0007829|PDB:4BB9" FT HELIX 584..592 FT /evidence="ECO:0007829|PDB:4BB9" FT STRAND 594..596 FT /evidence="ECO:0007829|PDB:4BBA" FT HELIX 597..605 FT /evidence="ECO:0007829|PDB:4BB9" SQ SEQUENCE 625 AA; 68685 MW; DE750462AC603C80 CRC64; MPGTKRFQHV IETPEPGKWE LSGYEAAVPI TEKSNPLTQD LDKADAENIV RLLGQCDAEI FQEEGQALST YQRLYSESIL TTMVQVAGKV QEVLKEPDGG LVVLSGGGTS GRMAFLMSVS FNQLMKGLGQ KPLYTYLIAG GDRSVVASRE GTEDSALHGI EELKKVAAGK KRVIVIGISV GLSAPFVAGQ MDCCMNNTAV FLPVLVGFNP VSMARNDPIE DWSSTFRQVA ERMQKMQEKQ KAFVLNPAIG PEGLSGSSRM KGGSATKILL ETLLLAAHKT VDQGIAASQR CLLEILRTFE RAHQVTYSQS PKIATLMKSV STSLEKKGHV YLVGWQTLGI IAIMDGVECI HTFGADFRDV RGFLIGDHSD MFNQKAELTN QGPQFTFSQE DFLTSILPSL TEIDTVVFIF TLDDNLTEVQ TIVEQVKEKT NHIQALAHST VGQTLPIPLK KLFPSIISIT WPLLFFEYEG NFIQKFQREL STKWVLNTVS TGAHVLLGKI LQNHMLDLRI SNSKLFWRAL AMLQRFSGQS KARCIESLLR AIHFPQPLSD DIRAAPISCH VQVAHEKEQV IPIALLSLLF RCSITEAQAH LAAAPSVCEA VRSALAGPGQ KRTADPLEIL EPDVQ //