UniProtKB - Q14397 (GCKR_HUMAN)
Protein
Glucokinase regulatory protein
Gene
GCKR
Organism
Homo sapiens (Human)
Status
Functioni
Regulates glucokinase (GCK) by forming an inactive complex with this enzyme (PubMed:23621087, PubMed:23733961). Acts by promoting GCK recruitment to the nucleus, possibly to provide a reserve of GCK that can be quickly released in the cytoplasm after a meal (PubMed:10456334). The affinity of GCKR for GCK is modulated by fructose metabolites: GCKR with bound fructose 6-phosphate has increased affinity for GCK, while GCKR with bound fructose 1-phosphate has strongly decreased affinity for GCK and does not inhibit GCK activity (PubMed:23621087, PubMed:23733961).3 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 153 | Beta-D-fructose 1-phosphateCombined sources1 Publication | 1 | |
Binding sitei | 348 | Beta-D-fructose 1-phosphateCombined sources1 Publication | 1 | |
Binding sitei | 514 | Beta-D-fructose 1-phosphateCombined sources1 Publication | 1 | |
Binding sitei | 514 | Beta-D-fructose 6-phosphateBy similarity | 1 |
GO - Molecular functioni
- carbohydrate binding Source: GO_Central
- enzyme binding Source: GO_Central
- enzyme inhibitor activity Source: GO_Central
- fructose-6-phosphate binding Source: UniProtKB
GO - Biological processi
- carbohydrate derivative metabolic process Source: InterPro
- carbohydrate metabolic process Source: UniProtKB-KW
- glucose homeostasis Source: GO_Central
- negative regulation of glucokinase activity Source: UniProtKB
- protein import into nucleus Source: BHF-UCL
- regulation of glycolytic process Source: Reactome
- response to fructose Source: BHF-UCL
- triglyceride homeostasis Source: BHF-UCL
- urate metabolic process Source: BHF-UCL
Keywordsi
Biological process | Carbohydrate metabolism |
Enzyme and pathway databases
PathwayCommonsi | Q14397 |
Reactomei | R-HSA-170822, Regulation of Glucokinase by Glucokinase Regulatory Protein R-HSA-5619107, Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) |
Names & Taxonomyi
Protein namesi | Recommended name: Glucokinase regulatory protein1 PublicationShort name: GKRP1 Publication Short name: Glucokinase regulator1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4196, GCKR |
MIMi | 600842, gene |
neXtProti | NX_Q14397 |
VEuPathDBi | HostDB:ENSG00000084734.8 |
Subcellular locationi
Mitochondrion
- Mitochondrion By similarity
Nucleus
- Nucleus 1 Publication
Other locations
- Cytoplasm 1 Publication
Note: Under low glucose concentrations, GCKR associates with GCK and the inactive complex is recruited to the hepatocyte nucleus.1 Publication
Cytosol
- cytosol Source: GO_Central
Mitochondrion
- mitochondrion Source: GO_Central
Nucleus
- nucleoplasm Source: UniProtKB
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Mitochondrion, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 326 – 327 | KK → TT: No effect on inhibition of glucokinase. 1 Publication | 2 | |
Mutagenesisi | 413 | D → A: Impairs inhibition of glucokinase. 1 Publication | 1 | |
Mutagenesisi | 450 – 451 | KK → TT: Impairs inhibition of glucokinase. 1 Publication | 2 | |
Mutagenesisi | 463 – 465 | LLF → ALA: Abolishes interaction with GCK. Abolishes inhibition of GCK. 1 Publication | 3 |
Organism-specific databases
DisGeNETi | 2646 |
MalaCardsi | GCKR |
MIMi | 613463, phenotype |
OpenTargetsi | ENSG00000084734 |
PharmGKBi | PA28611 |
Miscellaneous databases
Pharosi | Q14397, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1075152 |
Genetic variation databases
BioMutai | GCKR |
DMDMi | 327478611 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000214826 | 1 – 625 | Glucokinase regulatory proteinAdd BLAST | 625 |
Proteomic databases
jPOSTi | Q14397 |
MassIVEi | Q14397 |
PaxDbi | Q14397 |
PeptideAtlasi | Q14397 |
PRIDEi | Q14397 |
ProteomicsDBi | 4803 59979 [Q14397-1] |
PTM databases
iPTMneti | Q14397 |
PhosphoSitePlusi | Q14397 |
Expressioni
Tissue specificityi
Found in liver and pancreas. Not detected in muscle, brain, heart, thymus, intestine, uterus, adipose tissue, kidney, adrenal, lung or spleen.2 Publications
Gene expression databases
Bgeei | ENSG00000084734, Expressed in right lobe of liver and 112 other tissues |
ExpressionAtlasi | Q14397, baseline and differential |
Interactioni
Subunit structurei
Interacts (fructose 6-phosphate bound form) with GCK.
3 PublicationsBinary interactionsi
Q14397
With | #Exp. | IntAct |
---|---|---|
GCK [P35557] | 5 | EBI-709948,EBI-709928 |
GO - Molecular functioni
- enzyme binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 108916, 6 interactors |
IntActi | Q14397, 2 interactors |
STRINGi | 9606.ENSP00000264717 |
Chemistry databases
BindingDBi | Q14397 |
Miscellaneous databases
RNActi | Q14397, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q14397 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 90 – 286 | SIS 1PROSITE-ProRule annotationAdd BLAST | 197 | |
Domaini | 320 – 499 | SIS 2PROSITE-ProRule annotationAdd BLAST | 180 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 109 – 110 | Beta-D-fructose 1-phosphate bindingCombined sources1 Publication | 2 | |
Regioni | 109 – 110 | Beta-D-fructose 6-phosphate bindingBy similarity | 2 | |
Regioni | 179 – 181 | Beta-D-fructose 1-phosphate bindingCombined sources1 Publication | 3 | |
Regioni | 179 – 181 | Beta-D-fructose 6-phosphate bindingBy similarity | 3 | |
Regioni | 199 – 200 | Important for interaction with GCKBy similarity | 2 | |
Regioni | 463 – 465 | Essential for interaction with GCK1 Publication | 3 |
Domaini
Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.1 Publication
Sequence similaritiesi
Belongs to the GCKR family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | ENOG502QS2J, Eukaryota |
GeneTreei | ENSGT00390000005345 |
HOGENOMi | CLU_1739896_0_0_1 |
InParanoidi | Q14397 |
OrthoDBi | 858819at2759 |
PhylomeDBi | Q14397 |
TreeFami | TF329177 |
Family and domain databases
InterProi | View protein in InterPro IPR005486, Glucokinase_regulatory_CS IPR040190, MURQ/GCKR IPR001347, SIS |
PANTHERi | PTHR10088, PTHR10088, 2 hits |
PROSITEi | View protein in PROSITE PS01272, GCKR, 1 hit PS51464, SIS, 2 hits |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q14397-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPGTKRFQHV IETPEPGKWE LSGYEAAVPI TEKSNPLTQD LDKADAENIV
60 70 80 90 100
RLLGQCDAEI FQEEGQALST YQRLYSESIL TTMVQVAGKV QEVLKEPDGG
110 120 130 140 150
LVVLSGGGTS GRMAFLMSVS FNQLMKGLGQ KPLYTYLIAG GDRSVVASRE
160 170 180 190 200
GTEDSALHGI EELKKVAAGK KRVIVIGISV GLSAPFVAGQ MDCCMNNTAV
210 220 230 240 250
FLPVLVGFNP VSMARNDPIE DWSSTFRQVA ERMQKMQEKQ KAFVLNPAIG
260 270 280 290 300
PEGLSGSSRM KGGSATKILL ETLLLAAHKT VDQGIAASQR CLLEILRTFE
310 320 330 340 350
RAHQVTYSQS PKIATLMKSV STSLEKKGHV YLVGWQTLGI IAIMDGVECI
360 370 380 390 400
HTFGADFRDV RGFLIGDHSD MFNQKAELTN QGPQFTFSQE DFLTSILPSL
410 420 430 440 450
TEIDTVVFIF TLDDNLTEVQ TIVEQVKEKT NHIQALAHST VGQTLPIPLK
460 470 480 490 500
KLFPSIISIT WPLLFFEYEG NFIQKFQREL STKWVLNTVS TGAHVLLGKI
510 520 530 540 550
LQNHMLDLRI SNSKLFWRAL AMLQRFSGQS KARCIESLLR AIHFPQPLSD
560 570 580 590 600
DIRAAPISCH VQVAHEKEQV IPIALLSLLF RCSITEAQAH LAAAPSVCEA
610 620
VRSALAGPGQ KRTADPLEIL EPDVQ
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0C4DFN2 | A0A0C4DFN2_HUMAN | Glucokinase (Hexokinase 4) regulato... | GCKR hCG_21226 | 625 | Annotation score: | ||
H7C1B4 | H7C1B4_HUMAN | Glucokinase regulatory protein | GCKR | 227 | Annotation score: | ||
H7C4D3 | H7C4D3_HUMAN | Glucokinase regulatory protein | GCKR | 189 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 251 | P → V in CAB61828 (PubMed:9570959).Curated | 1 | |
Sequence conflicti | 393 | L → P in CAA88367 (PubMed:8589523).Curated | 1 | |
Sequence conflicti | 560 | H → R in CAA88367 (PubMed:8589523).Curated | 1 |
Polymorphismi
Genetic variations in GCKR define the fasting plasma glucose levels quantitative trait locus 5 (FGQTL5) [MIMi:613463] (PubMed:18556336, PubMed:18678614). The normal fasting plasma glucose level is defined as less than 100 mg glucose per deciliter plasma (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality (PubMed:18556336, PubMed:18678614).2 Publications
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018849 | 77 | E → G1 PublicationCorresponds to variant dbSNP:rs8179206EnsemblClinVar. | 1 | |
Natural variantiVAR_018850 | 256 | G → S1 PublicationCorresponds to variant dbSNP:rs8179212Ensembl. | 1 | |
Natural variantiVAR_008906 | 446 | P → L Associated with high triglyceride levels and low fasting plasma glucose levels; associated with a reduced risk for type 2 diabetes; the mutant protein is less efficiently regulated by physiological concentrations of fructose-6 phosphate. 5 PublicationsCorresponds to variant dbSNP:rs1260326Ensembl. | 1 | |
Natural variantiVAR_018851 | 540 | R → Q1 PublicationCorresponds to variant dbSNP:rs8179249Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_054853 | 144 – 150 | SVVASRE → WLPGRRE in isoform 2. 1 Publication | 7 | |
Alternative sequenceiVSP_054854 | 151 – 625 | Missing in isoform 2. 1 PublicationAdd BLAST | 475 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z48475 mRNA Translation: CAA88367.1 Y09593 Genomic DNA Translation: CAA70779.2 Y09592 Genomic DNA Translation: CAB61828.1 AY320034 Genomic DNA Translation: AAP72013.1 AK298448 mRNA Translation: BAG60664.1 AC074117 Genomic DNA Translation: AAY14850.1 BC130481 mRNA Translation: AAI30482.1 BC130483 mRNA Translation: AAI30484.1 |
CCDSi | CCDS1757.1 [Q14397-1] |
PIRi | S52485 |
RefSeqi | NP_001477.2, NM_001486.3 |
Genome annotation databases
Ensembli | ENST00000417872; ENSP00000398303; ENSG00000084734 [Q14397-2] |
GeneIDi | 2646 |
KEGGi | hsa:2646 |
UCSCi | uc002rky.4, human [Q14397-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Z48475 mRNA Translation: CAA88367.1 Y09593 Genomic DNA Translation: CAA70779.2 Y09592 Genomic DNA Translation: CAB61828.1 AY320034 Genomic DNA Translation: AAP72013.1 AK298448 mRNA Translation: BAG60664.1 AC074117 Genomic DNA Translation: AAY14850.1 BC130481 mRNA Translation: AAI30482.1 BC130483 mRNA Translation: AAI30484.1 |
CCDSi | CCDS1757.1 [Q14397-1] |
PIRi | S52485 |
RefSeqi | NP_001477.2, NM_001486.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4BB9 | X-ray | 1.47 | A | 1-625 | [»] | |
4BBA | X-ray | 1.92 | A | 1-625 | [»] | |
4LY9 | X-ray | 2.35 | A/B | 1-625 | [»] | |
4MQU | X-ray | 2.22 | A/B | 1-625 | [»] | |
4MRO | X-ray | 2.20 | A/B | 1-625 | [»] | |
4MSU | X-ray | 2.50 | A/B | 1-625 | [»] | |
4OHK | X-ray | 2.80 | A/B | 1-625 | [»] | |
4OHM | X-ray | 2.40 | A/B | 1-625 | [»] | |
4OHO | X-ray | 2.58 | A/B | 1-625 | [»] | |
4OHP | X-ray | 2.40 | A/B | 1-625 | [»] | |
4OLH | X-ray | 2.40 | A/B | 1-625 | [»] | |
4OP1 | X-ray | 2.39 | A/B | 1-625 | [»] | |
4OP2 | X-ray | 2.24 | A/B | 1-625 | [»] | |
4OP3 | X-ray | 2.82 | A/B | 1-625 | [»] | |
4PX2 | X-ray | 2.15 | A/B | 1-625 | [»] | |
4PX3 | X-ray | 2.43 | A/B | 1-625 | [»] | |
4PX5 | X-ray | 2.20 | A/B | 1-625 | [»] | |
4PXS | X-ray | 2.60 | A/B | 1-625 | [»] | |
SMRi | Q14397 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108916, 6 interactors |
IntActi | Q14397, 2 interactors |
STRINGi | 9606.ENSP00000264717 |
Chemistry databases
BindingDBi | Q14397 |
ChEMBLi | CHEMBL1075152 |
PTM databases
iPTMneti | Q14397 |
PhosphoSitePlusi | Q14397 |
Genetic variation databases
BioMutai | GCKR |
DMDMi | 327478611 |
Proteomic databases
jPOSTi | Q14397 |
MassIVEi | Q14397 |
PaxDbi | Q14397 |
PeptideAtlasi | Q14397 |
PRIDEi | Q14397 |
ProteomicsDBi | 4803 59979 [Q14397-1] |
Protocols and materials databases
DNASUi | 2646 |
Genome annotation databases
Ensembli | ENST00000417872; ENSP00000398303; ENSG00000084734 [Q14397-2] |
GeneIDi | 2646 |
KEGGi | hsa:2646 |
UCSCi | uc002rky.4, human [Q14397-1] |
Organism-specific databases
CTDi | 2646 |
DisGeNETi | 2646 |
GeneCardsi | GCKR |
HGNCi | HGNC:4196, GCKR |
MalaCardsi | GCKR |
MIMi | 600842, gene 613463, phenotype |
neXtProti | NX_Q14397 |
OpenTargetsi | ENSG00000084734 |
PharmGKBi | PA28611 |
VEuPathDBi | HostDB:ENSG00000084734.8 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QS2J, Eukaryota |
GeneTreei | ENSGT00390000005345 |
HOGENOMi | CLU_1739896_0_0_1 |
InParanoidi | Q14397 |
OrthoDBi | 858819at2759 |
PhylomeDBi | Q14397 |
TreeFami | TF329177 |
Enzyme and pathway databases
PathwayCommonsi | Q14397 |
Reactomei | R-HSA-170822, Regulation of Glucokinase by Glucokinase Regulatory Protein R-HSA-5619107, Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC) |
Miscellaneous databases
BioGRID-ORCSi | 2646, 4 hits in 882 CRISPR screens |
GenomeRNAii | 2646 |
Pharosi | Q14397, Tchem |
PROi | PR:Q14397 |
RNActi | Q14397, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000084734, Expressed in right lobe of liver and 112 other tissues |
ExpressionAtlasi | Q14397, baseline and differential |
Family and domain databases
InterProi | View protein in InterPro IPR005486, Glucokinase_regulatory_CS IPR040190, MURQ/GCKR IPR001347, SIS |
PANTHERi | PTHR10088, PTHR10088, 2 hits |
PROSITEi | View protein in PROSITE PS01272, GCKR, 1 hit PS51464, SIS, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | GCKR_HUMAN | |
Accessioni | Q14397Primary (citable) accession number: Q14397 Secondary accession number(s): A1L4C2 Q99522 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | April 5, 2011 | |
Last modified: | February 10, 2021 | |
This is version 162 of the entry and version 6 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM