GCKR_RAT
ID GCKR_RAT Reviewed; 627 AA.
AC Q07071;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Glucokinase regulatory protein {ECO:0000303|PubMed:7682971};
DE Short=Glucokinase regulator {ECO:0000250|UniProtKB:Q14397};
GN Name=Gckr {ECO:0000312|RGD:2671};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=7682971; DOI=10.1016/0014-5793(93)80089-d;
RA Detheux M., Vandekerckhove J., van Schaftingen E.;
RT "Cloning and sequencing of rat liver cDNAs encoding the regulatory protein
RT of glucokinase.";
RL FEBS Lett. 321:111-115(1993).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=8112473; DOI=10.1016/0014-5793(94)80437-0;
RA Detheux M., Vandekerckhove J., van Schaftingen E.;
RT "Cloning and sequencing of rat liver cDNAs encoding the regulatory protein
RT of glucokinase.";
RL FEBS Lett. 339:312-312(1994).
RN [3]
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 [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10518020; DOI=10.1016/s0014-5793(99)01249-1;
RA Fernandez-Novell J.M., Castel S., Bellido D., Ferrer J.C., Vilaro S.,
RA Guinovart J.J.;
RT "Intracellular distribution of hepatic glucokinase and glucokinase
RT regulatory protein during the fasted to refed transition in rats.";
RL FEBS Lett. 459:211-214(1999).
RN [5]
RP 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 [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GCK.
RX PubMed=10601273; DOI=10.1074/jbc.274.52.37125;
RA Shiota C., Coffey J., Grimsby J., Grippo J.F., Magnuson M.A.;
RT "Nuclear import of hepatic glucokinase depends upon glucokinase regulatory
RT protein, whereas export is due to a nuclear export signal sequence in
RT glucokinase.";
RL J. Biol. Chem. 274:37125-37130(1999).
RN [7]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GCK.
RX PubMed=16542652; DOI=10.1016/j.febslet.2006.03.009;
RA Arden C., Baltrusch S., Agius L.;
RT "Glucokinase regulatory protein is associated with mitochondria in
RT hepatocytes.";
RL FEBS Lett. 580:2065-2070(2006).
RN [8] {ECO:0007744|PDB:4LC9}
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH HUMAN GCK AND
RP BETA-D-FRUCTOSE-6-PHOSPHATE, FUNCTION, FRUCTOSE-6-PHOSPHATE BINDING SITES,
RP AND SUBUNIT.
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).
CC -!- FUNCTION: Regulates glucokinase (GCK) by forming an inactive complex
CC with this enzyme (PubMed:23957911). 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:10456334). 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 (PubMed:23957911).
CC {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:23957911}.
CC -!- SUBUNIT: Interacts (fructose 6-phosphate bound form) with GCK.
CC {ECO:0000269|PubMed:10601273, ECO:0000269|PubMed:23957911}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10456334,
CC ECO:0000269|PubMed:10518020, ECO:0000269|PubMed:16542652}. Nucleus
CC {ECO:0000269|PubMed:10456334, ECO:0000269|PubMed:10601273}.
CC Mitochondrion {ECO:0000269|PubMed:16542652}. Note=Under low glucose
CC concentrations, GCKR associates with GCK and the inactive complex is
CC recruited to the hepatocyte nucleus. {ECO:0000269|PubMed:10456334}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level)
CC (PubMed:7682971, PubMed:10518020). Not detected in muscle, brain,
CC heart, testis, intestine or spleen (PubMed:10518020).
CC {ECO:0000269|PubMed:10518020, ECO:0000269|PubMed:7682971}.
CC -!- DOMAIN: Fructose 1-phosphate and fructose 6-phosphate compete for the
CC same binding site. {ECO:0000269|PubMed:23957911}.
CC -!- SIMILARITY: Belongs to the GCKR family. {ECO:0000305}.
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; X68497; CAA48511.1; -; mRNA.
DR EMBL; BC081843; AAH81843.1; -; mRNA.
DR PIR; S41745; S41745.
DR RefSeq; NP_037252.1; NM_013120.2.
DR PDB; 4LC9; X-ray; 3.40 A; A=1-627.
DR PDBsum; 4LC9; -.
DR AlphaFoldDB; Q07071; -.
DR SMR; Q07071; -.
DR IntAct; Q07071; 3.
DR MINT; Q07071; -.
DR STRING; 10116.ENSRNOP00000064260; -.
DR BindingDB; Q07071; -.
DR ChEMBL; CHEMBL3124733; -.
DR iPTMnet; Q07071; -.
DR PhosphoSitePlus; Q07071; -.
DR PaxDb; Q07071; -.
DR PRIDE; Q07071; -.
DR Ensembl; ENSRNOT00000073228; ENSRNOP00000064260; ENSRNOG00000048874.
DR GeneID; 25658; -.
DR KEGG; rno:25658; -.
DR CTD; 2646; -.
DR RGD; 2671; Gckr.
DR eggNOG; ENOG502QS2J; Eukaryota.
DR GeneTree; ENSGT00390000005345; -.
DR HOGENOM; CLU_031122_0_0_1; -.
DR InParanoid; Q07071; -.
DR OMA; ANSKLFW; -.
DR OrthoDB; 858819at2759; -.
DR PhylomeDB; Q07071; -.
DR Reactome; R-RNO-170822; Regulation of Glucokinase by Glucokinase Regulatory Protein.
DR SABIO-RK; Q07071; -.
DR PRO; PR:Q07071; -.
DR Proteomes; UP000002494; Chromosome 6.
DR Bgee; ENSRNOG00000048874; Expressed in liver and 11 other tissues.
DR Genevisible; Q07071; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0030246; F:carbohydrate binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; IMP:RGD.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:RGD.
DR GO; GO:0070095; F:fructose-6-phosphate binding; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:1901135; P:carbohydrate derivative metabolic process; IEA:InterPro.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISO:RGD.
DR GO; GO:0051594; P:detection of glucose; NAS:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IBA:GO_Central.
DR GO; GO:0006006; P:glucose metabolic process; TAS:RGD.
DR GO; GO:0033132; P:negative regulation of glucokinase activity; IDA:BHF-UCL.
DR GO; GO:1903300; P:negative regulation of hexokinase activity; IDA:RGD.
DR GO; GO:0033133; P:positive regulation of glucokinase activity; ISO:RGD.
DR GO; GO:0006606; P:protein import into nucleus; IDA:BHF-UCL.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:RGD.
DR GO; GO:0009750; P:response to fructose; IDA:BHF-UCL.
DR GO; GO:0070328; P:triglyceride homeostasis; ISO:RGD.
DR GO; GO:0046415; P:urate metabolic process; ISO:RGD.
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; 1.
DR SUPFAM; SSF53697; SSF53697; 2.
DR PROSITE; PS01272; GCKR; 1.
DR PROSITE; PS51464; SIS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Cytoplasm;
KW Direct protein sequencing; Mitochondrion; Nucleus; Reference proteome;
KW Repeat.
FT CHAIN 1..627
FT /note="Glucokinase regulatory protein"
FT /id="PRO_0000214827"
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:0000269|PubMed:10601273"
FT REGION 463..465
FT /note="Essential for interaction with GCK"
FT /evidence="ECO:0000269|PubMed:10601273"
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:0000269|PubMed:23957911,
FT ECO:0007744|PDB:4LC9"
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:0000269|PubMed:23957911,
FT ECO:0007744|PDB:4LC9"
FT BINDING 348
FT /ligand="beta-D-fructose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:138881"
FT /evidence="ECO:0000250|UniProtKB:Q14397"
FT BINDING 514
FT /ligand="beta-D-fructose 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:138881"
FT /evidence="ECO:0000250|UniProtKB:Q14397"
FT BINDING 514
FT /ligand="beta-D-fructose 6-phosphate"
FT /ligand_id="ChEBI:CHEBI:57634"
FT /evidence="ECO:0000269|PubMed:23957911,
FT ECO:0007744|PDB:4LC9"
FT TURN 23..25
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 30..32
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 39..43
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 46..58
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 77..95
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 100..107
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 108..127
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 134..138
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 143..146
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 150..154
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 156..167
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 171..178
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 198..200
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 261..280
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 289..307
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 310..325
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 330..335
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 337..352
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 360..365
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 405..411
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 416..425
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 433..440
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 447..452
FT /evidence="ECO:0007829|PDB:4LC9"
FT STRAND 457..461
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 470..495
FT /evidence="ECO:0007829|PDB:4LC9"
FT TURN 496..498
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 513..527
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 531..543
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 550..553
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 557..564
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 570..579
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 584..592
FT /evidence="ECO:0007829|PDB:4LC9"
FT HELIX 597..604
FT /evidence="ECO:0007829|PDB:4LC9"
SQ SEQUENCE 627 AA; 68917 MW; 2C330146A0289928 CRC64;
MPGTKRYQHV IETPEPGEWE LSGYEAAVPI TEKSNPLTRN LDKADAEKIV KLLGQCDAEI
FQEEGQIVPT YQRLYSESVL TTMLQVAGKV QEVLKEPDGG LVVLSGGGTS GRMAFLMSVS
FNQLMKGLGQ KPLYTYLIAG GDRSVVASRE QTEDSALHGI EELKKVAAGK KRVVVIGISV
GLSAPFVAGQ MDYCMDNTAV FLPVLVGFNP VSMARNDPIE DWRSTFRQVA ERMQKMQEKQ
EAFVLNPAIG PEGLSGSSRM KGGGATKILL ETLLLAAHKT VDQGVVSSQR CLLEILRTFE
RAHQVTYSQS SKIATLMKQV GISLEKKGRV HLVGWQTLGI IAIMDGVECI HTFGADFQDI
RGFLIGDHSD MFNQKDELTN QGPQFTFSQD DFLTSILPSL TETDTVVFIF TLDDNLTEVQ
ALAERVREKC QNIQALVHST VGQSLPAPLK KLFPSLISIT WPLLFFDYEG TYVQKFQREL
STKWVLNTVS TGAHVLLGKI LQNHMLDLRI ANSKLFWRAL AMLQRFSGQS KARCIESLLQ
AIHFPQPLSD DVRAAPISCH VQVAHEKEKV IPTALLSLLL RCSISEAKAR LSAASSVCEV
VRSALSGPGQ KRSTQALEDP PACGTLN
