GCKR_MOUSE
ID GCKR_MOUSE Reviewed; 587 AA.
AC Q91X44;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Glucokinase regulatory protein {ECO:0000303|PubMed:10713097};
DE Short=GKRP {ECO:0000303|PubMed:10713097};
DE Short=Glucokinase regulator {ECO:0000250|UniProtKB:Q14397};
GN Name=Gckr {ECO:0000312|MGI:MGI:1096345};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GCK, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10713097; DOI=10.1074/jbc.275.11.7826;
RA Grimsby J., Coffey J.W., Dvorozniak M.T., Magram J., Li G.,
RA Matschinsky F.M., Shiota C., Kaur S., Magnuson M.A., Grippo J.F.;
RT "Characterization of glucokinase regulatory protein-deficient mice.";
RL J. Biol. Chem. 275:7826-7831(2000).
CC -!- FUNCTION: Regulates glucokinase (GCK) by forming an inactive complex
CC with this enzyme (PubMed:10713097). Acts by promoting GCK recruitment
CC to the nucleus, possibly to provide a reserve of GCK that can be
CC quickly released in the cytoplasm after a meal (PubMed:10713097). The
CC affinity of GCKR for GCK is modulated by fructose metabolites: GCKR
CC with bound fructose 6-phosphate has increased affinity for GCK, while
CC GCKR with bound fructose 1-phosphate has strongly decreased affinity
CC for GCK and does not inhibit GCK activity (By similarity).
CC {ECO:0000250|UniProtKB:Q14397, ECO:0000269|PubMed:10713097}.
CC -!- SUBUNIT: Interacts (fructose 6-phosphate bound form) with GCK.
CC {ECO:0000269|PubMed:10713097}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14397}. Nucleus
CC {ECO:0000269|PubMed:10713097}. 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:0000250|UniProtKB:Q14397}.
CC -!- DOMAIN: Fructose 1-phosphate and fructose 6-phosphate compete for the
CC same binding site. {ECO:0000250|UniProtKB:Q14397}.
CC -!- DISRUPTION PHENOTYPE: Mice appear normal and are fertile
CC (PubMed:10713097). Their body weights do not differ significantly from
CC the body weights of wild-type animals up to 60 weeks of age
CC (PubMed:10713097). Mice however show a substantial decrease in hepatic
CC glucokinase (Gck) expression and enzymatic activity, with no change in
CC basal blood glucose levels (PubMed:10713097). However, following a
CC glucose tolerance test, mice show impaired glucose clearance, possibly
CC because they cannot recruit sufficient glucokinase due to the absence
CC of a nuclear reserve (PubMed:10713097). {ECO:0000269|PubMed:10713097}.
CC -!- SIMILARITY: Belongs to the GCKR family. {ECO:0000305}.
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DR EMBL; BC012412; AAH12412.1; -; mRNA.
DR CCDS; CCDS19182.1; -.
DR RefSeq; NP_659158.1; NM_144909.1.
DR AlphaFoldDB; Q91X44; -.
DR SMR; Q91X44; -.
DR BioGRID; 231083; 1.
DR STRING; 10090.ENSMUSP00000072084; -.
DR BindingDB; Q91X44; -.
DR ChEMBL; CHEMBL3232700; -.
DR iPTMnet; Q91X44; -.
DR PhosphoSitePlus; Q91X44; -.
DR SwissPalm; Q91X44; -.
DR jPOST; Q91X44; -.
DR MaxQB; Q91X44; -.
DR PaxDb; Q91X44; -.
DR PeptideAtlas; Q91X44; -.
DR PRIDE; Q91X44; -.
DR ProteomicsDB; 268857; -.
DR Antibodypedia; 28588; 391 antibodies from 28 providers.
DR DNASU; 231103; -.
DR Ensembl; ENSMUST00000072228; ENSMUSP00000072084; ENSMUSG00000059434.
DR GeneID; 231103; -.
DR KEGG; mmu:231103; -.
DR UCSC; uc008wyf.1; mouse.
DR CTD; 2646; -.
DR MGI; MGI:1096345; Gckr.
DR VEuPathDB; HostDB:ENSMUSG00000059434; -.
DR eggNOG; ENOG502QS2J; Eukaryota.
DR GeneTree; ENSGT00390000005345; -.
DR InParanoid; Q91X44; -.
DR PhylomeDB; Q91X44; -.
DR TreeFam; TF329177; -.
DR Reactome; R-MMU-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR BioGRID-ORCS; 231103; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q91X44; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q91X44; protein.
DR Bgee; ENSMUSG00000059434; Expressed in left lobe of liver and 45 other tissues.
DR ExpressionAtlas; Q91X44; baseline and differential.
DR Genevisible; Q91X44; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0030246; F:carbohydrate binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0004857; F:enzyme inhibitor activity; ISO:MGI.
DR GO; GO:0070095; F:fructose-6-phosphate binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
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:0001678; P:cellular glucose homeostasis; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR GO; GO:0033132; P:negative regulation of glucokinase activity; IMP:MGI.
DR GO; GO:1903300; P:negative regulation of hexokinase activity; ISO:MGI.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; IMP:BHF-UCL.
DR GO; GO:0006606; P:protein import into nucleus; IMP:MGI.
DR GO; GO:0034504; P:protein localization to nucleus; IMP:MGI.
DR GO; GO:0009750; P:response to fructose; ISO:MGI.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:MGI.
DR GO; GO:0046415; P:urate metabolic process; ISO:MGI.
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 Carbohydrate metabolism; Cytoplasm; Mitochondrion; Nucleus;
KW Reference proteome; Repeat.
FT CHAIN 1..587
FT /note="Glucokinase regulatory protein"
FT /id="PRO_0000248832"
FT DOMAIN 90..286
FT /note="SIS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00797"
FT DOMAIN 320..476
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:0000250|UniProtKB:Q14397"
FT BINDING 109..110
FT /ligand="beta-D-fructose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:138881"
FT /evidence="ECO:0000250|UniProtKB:Q14397"
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:0000250|UniProtKB:Q14397"
FT BINDING 179..181
FT /ligand="beta-D-fructose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:138881"
FT /evidence="ECO:0000250|UniProtKB:Q14397"
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:0000250|UniProtKB:Q14397"
SQ SEQUENCE 587 AA; 64679 MW; 54319C68A136952A CRC64;
MPSTKRYQHV IETPEPGEWE LSGYEAAVPI TEKSNPLTRN LDKADAEKIV QLLGQCDAEI
FQEEGQIMPT YQRLYSESVL TTMLQVAGKV QEVLKEPDGG LVVLSGGGTS GRMAFLMSVS
FNQLMKGLGQ KPLYTYLIAG GDRSVVASRE RTEDSALHGI EELKKVAAGK KRVVVIGISV
GLSAPFVAGQ MDYCMDNTAV FLPVLVGFNP VSMARNDPIE DWRSTFRQVA ERMQKMQEKQ
EAFVLNPAIG PEGLSGSSRM KGGSATKILL ETLLLAAHKT VDQGVVSSQR CLLEILRTFE
RAHQVTYSQS SKIATLTKQV GISLEKKGHV HLVGWQTLGI IAIMDGVECI HTFGADFRDI
RGFLIGDHND MFNQKDELSN QGPQFTFSQD DFLTSVLPSL TEIDTVVFIF TLDDNLAEVQ
ALAERVREKS WNIQALVHST VGQSLPAPLK KLFPSLISIT WPLLFFDYEG SYVQKFQREL
STKWVLNTRF SGQSKARCIE SLLQVIHFPQ PLSNDVRAAP ISCHVQVAHE KEKVIPTALL
SLLLRCSITE AKERLAAASS VCEVVRSALS GPGQKRSIQA FGDPVVP
