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Protein

Glucokinase regulatory protein

Gene

GCKR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • carbohydrate binding Source: InterPro
  • fructose-6-phosphate binding Source: UniProtKB

GO - Biological processi

  • carbohydrate metabolic process Source: UniProtKB-KW
  • negative regulation of glucokinase activity Source: UniProtKB
  • protein import into nucleus, translocation Source: BHF-UCL
  • regulation of glucose transport Source: Reactome
  • response to fructose Source: BHF-UCL
  • triglyceride homeostasis Source: BHF-UCL
  • urate metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Carbohydrate metabolism

Enzyme and pathway databases

BioCyciZFISH:ENSG00000084734-MONOMER.
ReactomeiR-HSA-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-HSA-5619107. Defective TRP 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

HGNCiHGNC:4196. GCKR.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
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.

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.
CleanExiHS_GCKR.
ExpressionAtlasiQ14397. baseline and differential.

Organism-specific databases

HPAiCAB034098.

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. 5 interactors.
IntActiQ14397. 2 interactors.
STRINGi9606.ENSP00000264717.

Chemistry databases

BindingDBiQ14397.

Structurei

Secondary structure

1625
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni2 – 4Combined sources3
Helixi5 – 7Combined sources3
Turni19 – 22Combined sources4
Helixi23 – 26Combined sources4
Helixi30 – 32Combined sources3
Helixi36 – 38Combined sources3
Helixi41 – 43Combined sources3
Helixi46 – 58Combined sources13
Helixi59 – 61Combined sources3
Helixi77 – 94Combined sources18
Beta strandi100 – 107Combined sources8
Helixi108 – 127Combined sources20
Beta strandi134 – 138Combined sources5
Helixi143 – 146Combined sources4
Helixi150 – 154Combined sources5
Helixi156 – 167Combined sources12
Beta strandi171 – 178Combined sources8
Helixi185 – 195Combined sources11
Turni198 – 200Combined sources3
Beta strandi201 – 206Combined sources6
Helixi211 – 213Combined sources3
Beta strandi222 – 224Combined sources3
Helixi226 – 237Combined sources12
Turni238 – 240Combined sources3
Beta strandi243 – 245Combined sources3
Turni258 – 260Combined sources3
Helixi261 – 283Combined sources23
Helixi289 – 307Combined sources19
Helixi310 – 325Combined sources16
Beta strandi330 – 335Combined sources6
Helixi337 – 353Combined sources17
Beta strandi359 – 366Combined sources8
Turni369 – 371Combined sources3
Helixi375 – 377Combined sources3
Turni378 – 380Combined sources3
Helixi383 – 385Combined sources3
Helixi389 – 395Combined sources7
Helixi397 – 399Combined sources3
Beta strandi405 – 411Combined sources7
Helixi416 – 427Combined sources12
Beta strandi433 – 440Combined sources8
Helixi447 – 452Combined sources6
Beta strandi453 – 455Combined sources3
Beta strandi457 – 461Combined sources5
Turni467 – 469Combined sources3
Helixi470 – 495Combined sources26
Turni496 – 498Combined sources3
Helixi513 – 527Combined sources15
Helixi531 – 543Combined sources13
Helixi550 – 553Combined sources4
Helixi557 – 564Combined sources8
Beta strandi567 – 569Combined sources3
Helixi570 – 580Combined sources11
Helixi584 – 592Combined sources9
Beta strandi594 – 596Combined sources3
Helixi597 – 605Combined sources9

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...

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
Contains 2 SIS domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IHMK. Eukaryota.
ENOG4111GRB. LUCA.
GeneTreeiENSGT00390000005345.
HOGENOMiHOG000031501.
HOVERGENiHBG005818.
InParanoidiQ14397.
PhylomeDBiQ14397.
TreeFamiTF329177.

Family and domain databases

InterProiIPR005486. Glucokinase_regulatory_CS.
IPR001347. SIS.
[Graphical view]
PROSITEiPS01272. GCKR. 1 hit.
PS51464. SIS. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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 → G.1 PublicationCorresponds to variant rs8179206dbSNPEnsembl.1
Natural variantiVAR_018850256G → S.1 PublicationCorresponds to variant rs8179212dbSNPEnsembl.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 rs1260326dbSNPEnsembl.1
Natural variantiVAR_018851540R → Q.1 PublicationCorresponds to variant rs8179249dbSNPEnsembl.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

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. 5 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.

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.
GeneCardsiGCKR.
H-InvDBHIX0030026.
HGNCiHGNC:4196. GCKR.
HPAiCAB034098.
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

BioCyciZFISH:ENSG00000084734-MONOMER.
ReactomeiR-HSA-170822. Regulation of Glucokinase by Glucokinase Regulatory Protein.
R-HSA-5619107. Defective TRP may confer susceptibility towards thyroid papillary carcinoma (TPC).

Miscellaneous databases

GenomeRNAii2646.
PROiQ14397.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000084734.
CleanExiHS_GCKR.
ExpressionAtlasiQ14397. baseline and differential.

Family and domain databases

InterProiIPR005486. Glucokinase_regulatory_CS.
IPR001347. SIS.
[Graphical view]
PROSITEiPS01272. GCKR. 1 hit.
PS51464. SIS. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGCKR_HUMAN
AccessioniPrimary (citable) accession number: Q14397
Secondary accession number(s): A1L4C2
, B4DPQ2, Q53RY6, Q99522
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: April 5, 2011
Last modified: November 2, 2016
This is version 136 of the entry and version 6 of the sequence. [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. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.