Q14397 (GCKR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucokinase regulatory protein
Short name=Glucokinase regulator

Gene names

Name:

GCKR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	625 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits glucokinase by forming an inactive complex with this enzyme.
Tissue specificity	Found in liver and pancreas. Not detected in muscle, brain, heart, thymus, intestine, uterus, adipose tissue, kidney, adrenal, lung or spleen. Ref.2 Ref.7
Polymorphism	Genetic variations in GCKR define the fasting plasma glucose levels quantitative trait locus 5 (FGQTL5) [MIM: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.
Sequence similarities	Belongs to the GCKR family. Contains 2 SIS domains.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Domain	Repeat
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome cellular glucose homeostasis Inferred from electronic annotation. Source: Compara glucose transport Traceable author statement. Source: Reactome negative regulation of glucokinase activity Inferred from direct assay PubMed 14627435. Source: BHF-UCL positive regulation of glucokinase activity Inferred from electronic annotation. Source: Compara protein import into nucleus, translocation Inferred from sequence or structural similarity. Source: BHF-UCL regulation of glucose transport Traceable author statement. Source: Reactome response to fructose stimulus Inferred from direct assay PubMed 14627435. Source: BHF-UCL transmembrane transport Traceable author statement. Source: Reactome triglyceride homeostasis Inferred from mutant phenotype PubMed 19526250PubMed 20668700. Source: BHF-UCL urate metabolic process Inferred from mutant phenotype PubMed 19503597. Source: BHF-UCL
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	carbohydrate binding Inferred from electronic annotation. Source: Compara enzyme inhibitor activity Inferred from electronic annotation. Source: Compara fructose-6-phosphate binding Inferred from direct assay PubMed 14627435. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GCK	P35557	2	EBI-709948,EBI-709928

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 625	624	Glucokinase regulatory protein		PRO_0000214826
Regions
	Domain	90 – 286	197	SIS 1
	Domain	320 – 499	180	SIS 2
Natural variations
	Natural variant	77	1	E → G. Ref.3 Corresponds to variant rs8179206 [ dbSNP | Ensembl ].		VAR_018849
	Natural variant	256	1	G → S. Ref.3 Corresponds to variant rs8179212 [ dbSNP | Ensembl ].		VAR_018850
	Natural variant	446	1	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. Ref.3 Ref.4 Ref.6 Ref.7 Ref.8 Corresponds to variant rs1260326 [ dbSNP | Ensembl ].		VAR_008906
	Natural variant	540	1	R → Q. Ref.3 Corresponds to variant rs8179249 [ dbSNP | Ensembl ].		VAR_018851
Experimental info
	Sequence conflict	251	1	P → V in CAB61828. Ref.2
	Sequence conflict	393	1	L → P in CAA88367. Ref.1
	Sequence conflict	560	1	H → R in CAA88367. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q14397 [UniParc]. Last modified April 5, 2011. Version 6. Checksum: DE750462AC603C80	FASTA	625	68,685
	10 20 30 40 50 60 MPGTKRFQHV IETPEPGKWE LSGYEAAVPI TEKSNPLTQD LDKADAENIV RLLGQCDAEI 70 80 90 100 110 120 FQEEGQALST YQRLYSESIL TTMVQVAGKV QEVLKEPDGG LVVLSGGGTS GRMAFLMSVS 130 140 150 160 170 180 FNQLMKGLGQ KPLYTYLIAG GDRSVVASRE GTEDSALHGI EELKKVAAGK KRVIVIGISV 190 200 210 220 230 240 GLSAPFVAGQ MDCCMNNTAV FLPVLVGFNP VSMARNDPIE DWSSTFRQVA ERMQKMQEKQ 250 260 270 280 290 300 KAFVLNPAIG PEGLSGSSRM KGGSATKILL ETLLLAAHKT VDQGIAASQR CLLEILRTFE 310 320 330 340 350 360 RAHQVTYSQS PKIATLMKSV STSLEKKGHV YLVGWQTLGI IAIMDGVECI HTFGADFRDV 370 380 390 400 410 420 RGFLIGDHSD MFNQKAELTN QGPQFTFSQE DFLTSILPSL TEIDTVVFIF TLDDNLTEVQ 430 440 450 460 470 480 TIVEQVKEKT NHIQALAHST VGQTLPIPLK KLFPSIISIT WPLLFFEYEG NFIQKFQREL 490 500 510 520 530 540 STKWVLNTVS TGAHVLLGKI LQNHMLDLRI SNSKLFWRAL AMLQRFSGQS KARCIESLLR 550 560 570 580 590 600 AIHFPQPLSD DIRAAPISCH VQVAHEKEQV IPIALLSLLF RCSITEAQAH LAAAPSVCEA 610 620 VRSALAGPGQ KRTADPLEIL EPDVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human glucokinase regulatory protein (GCKR): cDNA and genomic cloning, complete primary structure, and chromosomal localization." Warner J.P., Leek J.P., Intody S., Markham A.F., Bonthron D.T. Mamm. Genome 6:532-536(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Tissue: Hepatoblastoma.
[2]	"Organization of the human glucokinase regulator gene GCKR." Hayward B.E., Dunlop N., Intody S., Leek J.P., Markham A.F., Warner J.P., Bonthron D.T. Genomics 49:137-142(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION TO 393 AND 560, TISSUE SPECIFICITY.
[3]	NIEHS SNPs program Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-77; SER-256; LEU-446 AND GLN-540.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LEU-446.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population." Vaxillaire M., Cavalcanti-Proenca C., Dechaume A., Tichet J., Marre M., Balkau B., Froguel P. Diabetes 57:2253-2257(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FGQTL5, VARIANT LEU-446, ASSOCIATION WITH LOWER RISK FOR DIABETES TYPE 2.
[7]	"The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver." Beer N.L., Tribble N.D., McCulloch L.J., Roos C., Johnson P.R., Orho-Melander M., Gloyn A.L. Hum. Mol. Genet. 18:4081-4088(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, CHARACTERIZATION OF VARIANT LEU-446.
[8]	"Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations." Orho-Melander M., Melander O., Guiducci C., Perez-Martinez P., Corella D., Roos C., Tewhey R., Rieder M.J., Hall J., Abecasis G., Tai E.S., Welch C., Arnett D.K., Lyssenko V., Lindholm E., Saxena R., de Bakker P.I., Burtt N. , Voight B.F., Hirschhorn J.N., Tucker K.L., Hedner T., Tuomi T., Isomaa B., Eriksson K.F., Taskinen M.R., Wahlstrand B., Hughes T.E., Parnell L.D., Lai C.Q., Berglund G., Peltonen L., Vartiainen E., Jousilahti P., Havulinna A.S., Salomaa V., Nilsson P., Groop L., Altshuler D., Ordovas J.M., Kathiresan S. Diabetes 57:3112-3121(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-446, INVOLVEMENT IN FGQTL5, ASSOCIATION WITH HIGH PLASMA TRIGLYCERIDE LEVELS.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z48475 mRNA. Translation: CAA88367.1. Y09593 Genomic DNA. Translation: CAA70779.2. Y09592 Genomic DNA. Translation: CAB61828.1. AY320034 Genomic DNA. Translation: AAP72013.1. AC074117 Genomic DNA. Translation: AAY14850.1. BC130481 mRNA. Translation: AAI30482.1. BC130483 mRNA. Translation: AAI30484.1.
IPI	IPI00030293.
PIR	S52485.
RefSeq	NP_001477.2. NM_001486.3.
UniGene	Hs.89771.
3D structure databases
ProteinModelPortal	Q14397.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q14397. 2 interactions.
STRING	9606.ENSP00000264717.
PTM databases
PhosphoSite	Q14397.
Polymorphism databases
DMDM	296439503.
Proteomic databases
PaxDb	Q14397.
PRIDE	Q14397.
Protocols and materials databases
DNASU	2646.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264717; ENSP00000264717; ENSG00000084734.
GeneID	2646.
KEGG	hsa:2646.
UCSC	uc002rky.3. human.
Organism-specific databases
CTD	2646.
GeneCards	GC02P027720.
H-InvDB	HIX0030026.
HGNC	HGNC:4196. GCKR.
MIM	600842. gene. 613463. phenotype.
neXtProt	NX_Q14397.
PharmGKB	PA28611.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2103.
HOGENOM	HOG000031501.
HOVERGEN	HBG005818.
InParanoid	Q14397.
OrthoDB	EOG4HT8S5.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q14397.
Bgee	Q14397.
CleanEx	HS_GCKR.
Genevestigator	Q14397.
GermOnline	ENSG00000084734. Homo sapiens.
Family and domain databases
InterPro	IPR005486. Glucokinase_regulatory_CS. IPR001347. SIS. [Graphical view]
PROSITE	PS01272. GCKR. 1 hit. PS51464. SIS. 2 hits. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL1075152.
GenomeRNAi	2646.
NextBio	10442.
SOURCE	Search...

Entry information

Entry name

GCKR_HUMAN

Accession

Primary (citable) accession number: Q14397
Secondary accession number(s): A1L4C2, Q53RY6, Q99522

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	April 5, 2011
Last modified:	April 3, 2013
This is version 101 of the entry and version 6 of the sequence. [Complete history]

Entry status

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.