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Protein

Glucokinase regulatory protein

Gene

GCKR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Inhibits glucokinase (GCK) by forming an inactive complex with this enzyme. 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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei153Fructose 1-phosphate1
Binding sitei348Fructose 1-phosphate1
Binding sitei514Fructose 1-phosphate/Fructose 6-phosphate1

GO - Molecular functioni

  • fructose-6-phosphate binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCarbohydrate metabolism

Enzyme and pathway databases

ReactomeiR-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 protein
Short name:
GKRP
Short name:
Glucokinase regulator
Gene namesi
Name:GCKR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000084734.8
HGNCiHGNC:4196 GCKR
MIMi600842 gene
neXtProtiNX_Q14397

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi326 – 327KK → TT: No effect on inhibition of glucokinase. 1 Publication2
Mutagenesisi413D → A: Impairs inhibition of glucokinase. 1 Publication1
Mutagenesisi450 – 451KK → TT: Impairs inhibition of glucokinase. 1 Publication2
Mutagenesisi463 – 465LLF → ALA: Abolishes interaction with GCK. Abolishes inhibition of GCK. 1 Publication3

Organism-specific databases

DisGeNETi2646
MalaCardsiGCKR
MIMi613463 phenotype
OpenTargetsiENSG00000084734
PharmGKBiPA28611

Chemistry databases

ChEMBLiCHEMBL1075152

Polymorphism and mutation databases

BioMutaiGCKR
DMDMi327478611

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002148261 – 625Glucokinase regulatory proteinAdd BLAST625

Proteomic databases

EPDiQ14397
PaxDbiQ14397
PeptideAtlasiQ14397
PRIDEiQ14397
ProteomicsDBi59979

PTM databases

iPTMnetiQ14397
PhosphoSitePlusiQ14397

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

BgeeiENSG00000084734 Expressed in 84 organ(s), highest expression level in right lobe of liver
CleanExiHS_GCKR
ExpressionAtlasiQ14397 baseline and differential

Organism-specific databases

HPAiHPA064305

Interactioni

Subunit structurei

Interacts (fructose 6-phosphate bound form) with GCK.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GCKP355572EBI-709948,EBI-709928

Protein-protein interaction databases

BioGridi108916, 6 interactors
IntActiQ14397, 2 interactors
STRINGi9606.ENSP00000264717

Chemistry databases

BindingDBiQ14397

Structurei

Secondary structure

1625
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ14397
SMRiQ14397
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini90 – 286SIS 1PROSITE-ProRule annotationAdd BLAST197
Domaini320 – 499SIS 2PROSITE-ProRule annotationAdd BLAST180

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni109 – 110Fructose 1-phosphate/Fructose 6-phosphate binding2
Regioni179 – 181Fructose 1-phosphate/Fructose 6-phosphate binding3
Regioni199 – 200Important for interaction with GCKBy similarity2
Regioni463 – 465Essential for interaction with GCK3

Domaini

Fructose 1-phosphate and fructose 6-phosphate compete for the same binding site.

Sequence similaritiesi

Belongs to the GCKR family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IHMK Eukaryota
ENOG4111GRB LUCA
GeneTreeiENSGT00390000005345
HOGENOMiHOG000031501
HOVERGENiHBG005818
InParanoidiQ14397
PhylomeDBiQ14397
TreeFamiTF329177

Family and domain databases

InterProiView protein in InterPro
IPR005486 Glucokinase_regulatory_CS
IPR001347 SIS
PROSITEiView protein in PROSITE
PS01272 GCKR, 1 hit
PS51464 SIS, 2 hits

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This 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 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:625
Mass (Da):68,685
Last modified:April 5, 2011 - v6
Checksum:iDE750462AC603C80
GO
Isoform 2 (identifier: Q14397-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     144-150: SVVASRE → WLPGRRE
     151-625: Missing.

Note: No experimental confirmation available.
Show »
Length:150
Mass (Da):16,477
Checksum:iB958AFB4A930F3B1
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DFN2A0A0C4DFN2_HUMAN
Glucokinase (Hexokinase 4) regulato...
GCKR hCG_21226
625Annotation score:
H7C1B4H7C1B4_HUMAN
Glucokinase regulatory protein
GCKR
227Annotation score:
H7C4D3H7C4D3_HUMAN
Glucokinase regulatory protein
GCKR
189Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti251P → V in CAB61828 (PubMed:9570959).Curated1
Sequence conflicti393L → P in CAA88367 (PubMed:8589523).Curated1
Sequence conflicti560H → R in CAA88367 (PubMed:8589523).Curated1

Polymorphismi

Genetic variations in GCKR define the fasting plasma glucose levels quantitative trait locus 5 (FGQTL5) [MIMi:613463]. 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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01884977E → G1 PublicationCorresponds to variant dbSNP:rs8179206EnsemblClinVar.1
Natural variantiVAR_018850256G → S1 PublicationCorresponds to variant dbSNP:rs8179212Ensembl.1
Natural variantiVAR_008906446P → 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_018851540R → Q1 PublicationCorresponds to variant dbSNP:rs8179249Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_054853144 – 150SVVASRE → WLPGRRE in isoform 2. 1 Publication7
Alternative sequenceiVSP_054854151 – 625Missing in isoform 2. 1 PublicationAdd BLAST475

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
CCDSiCCDS1757.1 [Q14397-1]
PIRiS52485
RefSeqiNP_001477.2, NM_001486.3
UniGeneiHs.89771

Genome annotation databases

EnsembliENST00000417872; ENSP00000398303; ENSG00000084734 [Q14397-2]
GeneIDi2646
KEGGihsa:2646
UCSCiuc002rky.4 human [Q14397-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS1757.1 [Q14397-1]
PIRiS52485
RefSeqiNP_001477.2, NM_001486.3
UniGeneiHs.89771

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BB9X-ray1.47A1-625[»]
4BBAX-ray1.92A1-625[»]
4LY9X-ray2.35A/B1-625[»]
4MQUX-ray2.22A/B1-625[»]
4MROX-ray2.20A/B1-625[»]
4MSUX-ray2.50A/B1-625[»]
4OHKX-ray2.80A/B1-625[»]
4OHMX-ray2.40A/B1-625[»]
4OHOX-ray2.58A/B1-625[»]
4OHPX-ray2.40A/B1-625[»]
4OLHX-ray2.40A/B1-625[»]
4OP1X-ray2.39A/B1-625[»]
4OP2X-ray2.24A/B1-625[»]
4OP3X-ray2.82A/B1-625[»]
4PX2X-ray2.15A/B1-625[»]
4PX3X-ray2.43A/B1-625[»]
4PX5X-ray2.20A/B1-625[»]
4PXSX-ray2.60A/B1-625[»]
ProteinModelPortaliQ14397
SMRiQ14397
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108916, 6 interactors
IntActiQ14397, 2 interactors
STRINGi9606.ENSP00000264717

Chemistry databases

BindingDBiQ14397
ChEMBLiCHEMBL1075152

PTM databases

iPTMnetiQ14397
PhosphoSitePlusiQ14397

Polymorphism and mutation databases

BioMutaiGCKR
DMDMi327478611

Proteomic databases

EPDiQ14397
PaxDbiQ14397
PeptideAtlasiQ14397
PRIDEiQ14397
ProteomicsDBi59979

Protocols and materials databases

DNASUi2646
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000417872; ENSP00000398303; ENSG00000084734 [Q14397-2]
GeneIDi2646
KEGGihsa:2646
UCSCiuc002rky.4 human [Q14397-1]

Organism-specific databases

CTDi2646
DisGeNETi2646
EuPathDBiHostDB:ENSG00000084734.8
GeneCardsiGCKR
H-InvDBiHIX0030026
HGNCiHGNC:4196 GCKR
HPAiHPA064305
MalaCardsiGCKR
MIMi600842 gene
613463 phenotype
neXtProtiNX_Q14397
OpenTargetsiENSG00000084734
PharmGKBiPA28611
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IHMK Eukaryota
ENOG4111GRB LUCA
GeneTreeiENSGT00390000005345
HOGENOMiHOG000031501
HOVERGENiHBG005818
InParanoidiQ14397
PhylomeDBiQ14397
TreeFamiTF329177

Enzyme and pathway databases

ReactomeiR-HSA-170822 Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-5619107 Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)

Miscellaneous databases

ChiTaRSiGCKR human
GenomeRNAii2646
PROiPR:Q14397
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000084734 Expressed in 84 organ(s), highest expression level in right lobe of liver
CleanExiHS_GCKR
ExpressionAtlasiQ14397 baseline and differential

Family and domain databases

InterProiView protein in InterPro
IPR005486 Glucokinase_regulatory_CS
IPR001347 SIS
PROSITEiView protein in PROSITE
PS01272 GCKR, 1 hit
PS51464 SIS, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiGCKR_HUMAN
AccessioniPrimary (citable) accession number: Q14397
Secondary accession number(s): A1L4C2
, B4DPQ2, Q53RY6, Q99522
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 5, 2011
Last modified: September 12, 2018
This is version 146 of the entry and version 6 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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