GCKR_HUMAN
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 03-AUG-2022, entry version 168.
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/";
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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; 7.
DR IntAct; Q14397; 2.
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; Q14397; -.
DR PeptideAtlas; Q14397; -.
DR PRIDE; Q14397; -.
DR ProteomicsDB; 4803; -.
DR ProteomicsDB; 59979; -. [Q14397-1]
DR DNASU; 2646; -.
DR Ensembl; ENST00000417872.5; ENSP00000398303.1; ENSG00000084734.9. [Q14397-2]
DR GeneID; 2646; -.
DR KEGG; hsa:2646; -.
DR UCSC; uc002rky.4; human. [Q14397-1]
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 OpenTargets; ENSG00000084734; -.
DR PharmGKB; PA28611; -.
DR VEuPathDB; HostDB:ENSG00000084734; -.
DR eggNOG; ENOG502QS2J; Eukaryota.
DR GeneTree; ENSGT00390000005345; -.
DR HOGENOM; CLU_1739896_0_0_1; -.
DR InParanoid; Q14397; -.
DR OrthoDB; 858819at2759; -.
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 1079 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 96 other 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; IBA:GO_Central.
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: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:0070328; P:triglyceride homeostasis; IMP:BHF-UCL.
DR GO; GO:0046415; P:urate metabolic process; IMP:BHF-UCL.
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; PTHR10088; 2.
DR SUPFAM; SSF53697; SSF53697; 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 (associated with high triglyceride levels and
FT low fasting plasma glucose levels; associated with a
FT reduced risk for type 2 diabetes; the mutant protein is
FT less efficiently regulated by physiological concentrations
FT of 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
