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Q9NQR9 (G6PC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glucose-6-phosphatase 2

Short name=G-6-Pase 2
Short name=G6Pase 2
EC=3.1.3.9
Alternative name(s):
Islet-specific glucose-6-phosphatase catalytic subunit-related protein
Gene names
Name:G6PC2
Synonyms:IGRP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length355 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis By similarity.

Catalytic activity

D-glucose 6-phosphate + H2O = D-glucose + phosphate. Ref.8

Pathway

Carbohydrate biosynthesis; gluconeogenesis.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7.

Tissue specificity

Specifically expressed in pancreas and also detected to a lower extent in testis. Expressed by most islet cells in the pancreas (at protein level). Ref.1

Post-translational modification

N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome. Ref.7

Polymorphism

Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 1 (FGQTL1) [MIM:612108]. The normal fasting plasma glucose level in the plasma is defined as less than 100 mg per deciliter (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 glucose-6-phosphatase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.45 mM for glucose-6-phosphate (at pH 6.5)

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NQR9-1)

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.
Isoform 2 (identifier: Q9NQR9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     74-102: ILFGHRPYWWVQETQIYPNHSSPCLEQFP → KSIWPCNGRILCLVCHGNRCPEPHCLWDG
     103-355: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9NQR9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     148-154: LTWSFLW → HAGGRGL
     155-355: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 355355Glucose-6-phosphatase 2
PRO_0000334509

Regions

Topological domain1 – 2424Lumenal Potential
Transmembrane25 – 4521Helical; Potential
Topological domain46 – 5611Cytoplasmic Potential
Transmembrane57 – 7721Helical; Potential
Topological domain78 – 11538Lumenal Potential
Transmembrane116 – 13621Helical; Potential
Topological domain137 – 14610Cytoplasmic Potential
Transmembrane147 – 16721Helical; Potential
Topological domain1681Lumenal Potential
Transmembrane169 – 18921Helical; Potential
Topological domain190 – 21122Cytoplasmic Potential
Transmembrane212 – 23221Helical; Potential
Topological domain233 – 26129Lumenal Potential
Transmembrane262 – 28221Helical; Potential
Topological domain283 – 29311Cytoplasmic Potential
Transmembrane294 – 31421Helical; Potential
Topological domain315 – 3184Lumenal Potential
Transmembrane319 – 33921Helical; Potential
Topological domain340 – 35516Cytoplasmic Potential
Motif352 – 3554Prevents secretion from ER Potential

Sites

Active site1151Proton donor Potential
Active site1741Nucleophile By similarity
Binding site791Substrate Potential
Binding site1681Substrate Potential

Amino acid modifications

Glycosylation921N-linked (GlcNAc...) Ref.7

Natural variations

Alternative sequence74 – 10229ILFGH…LEQFP → KSIWPCNGRILCLVCHGNRC PEPHCLWDG in isoform 2.
VSP_033648
Alternative sequence103 – 355253Missing in isoform 2.
VSP_033649
Alternative sequence148 – 1547LTWSFLW → HAGGRGL in isoform 3.
VSP_046180
Alternative sequence155 – 355201Missing in isoform 3.
VSP_046181
Natural variant1711I → V.
Corresponds to variant rs2232322 [ dbSNP | Ensembl ].
VAR_043372
Natural variant2071Y → S.
Corresponds to variant rs2232323 [ dbSNP | Ensembl ].
VAR_043373
Natural variant2191V → L.
Corresponds to variant rs492594 [ dbSNP | Ensembl ].
VAR_043374
Natural variant3241S → P.
Corresponds to variant rs2232326 [ dbSNP | Ensembl ].
VAR_043375
Natural variant3401P → L.
Corresponds to variant rs2232327 [ dbSNP | Ensembl ].
VAR_043376
Natural variant3421S → C.
Corresponds to variant rs2232328 [ dbSNP | Ensembl ].
VAR_043377

Experimental info

Mutagenesis501N → A: No effect on N-glycosylation. Ref.7
Mutagenesis921N → A: Loss of N-glycosylation. Ref.7
Mutagenesis2871N → A: No effect on N-glycosylation. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: D642C37496B6C4EB

FASTA35540,580
        10         20         30         40         50         60 
MDFLHRNGVL IIQHLQKDYR AYYTFLNFMS NVGDPRNIFF IYFPLCFQFN QTVGTKMIWV 

        70         80         90        100        110        120 
AVIGDWLNLI FKWILFGHRP YWWVQETQIY PNHSSPCLEQ FPTTCETGPG SPSGHAMGAS 

       130        140        150        160        170        180 
CVWYVMVTAA LSHTVCGMDK FSITLHRLTW SFLWSVFWLI QISVCISRVF IATHFPHQVI 

       190        200        210        220        230        240 
LGVIGGMLVA EAFEHTPGIQ TASLGTYLKT NLFLFLFAVG FYLLLRVLNI DLLWSVPIAK 

       250        260        270        280        290        300 
KWCANPDWIH IDTTPFAGLV RNLGVLFGLG FAINSEMFLL SCRGGNNYTL SFRLLCALTS 

       310        320        330        340        350 
LTILQLYHFL QIPTHEEHLF YVLSFCKSAS IPLTVVAFIP YSVHMLMKQS GKKSQ 

« Hide

Isoform 2 [UniParc].

Checksum: 45E36A48F44C0C93
Show »

FASTA10212,160
Isoform 3 [UniParc].

Checksum: 7203B17AA6D4CF40
Show »

FASTA15417,757

References

« Hide 'large scale' references
[1]"Cloning and characterization of the human and rat islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) genes."
Martin C.C., Bischof L.J., Bergman B., Hornbuckle L.A., Hilliker C., Frigeri C., Wahl D., Svitek C.A., Wong R., Goldman J.K., Oeser J.K., Lepretre F., Froguel P., O'Brien R.M., Hutton J.C.
J. Biol. Chem. 276:25197-25207(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, TISSUE SPECIFICITY.
[2]"Endocrine pancreas consortium."
Melton D., Brown J., Kenty G., Permutt A., Lee C., Kaestner K., Lemishka I., Scearce M., Brestelli J., Gradwohl G., Clifton S., Hillier L., Marra M., Pape D., Wylie T., Martin J., Blistain A., Schmitt A. expand/collapse author list , Theising B., Ritter E., Ronko I., Bennett J., Cardenas M., Gibbons M., McCann R., Cole R., Tsagareishvili R., Williams T., Jackson Y., Bowers Y.
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Pancreas.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Retina.
[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. expand/collapse author list , 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].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 1).
Tissue: Cerebellum.
[7]"The islet-specific glucose-6-phosphatase-related protein, implicated in diabetes, is a glycoprotein embedded in the endoplasmic reticulum membrane."
Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y.
FEBS Lett. 562:160-164(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF ASN-50; ASN-92 AND ASN-287, GLYCOSYLATION AT ASN-92.
[8]"Enzymatic characterization of the pancreatic islet-specific glucose-6-phosphatase-related protein (IGRP)."
Petrolonis A.J., Yang Q., Tummino P.J., Fish S.M., Prack A.E., Jain S., Parsons T.F., Li P., Dales N.A., Ge L., Langston S.P., Schuller A.G.P., An W.F., Tartaglia L.A., Chen H., Hong S.-B.
J. Biol. Chem. 279:13976-13983(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[9]"Alternative splicing of G6PC2, the gene coding for the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), results in differential expression in human thymus and spleen compared with pancreas."
Dogra R.S., Vaidyanathan P., Prabakar K.R., Marshall K.E., Hutton J.C., Pugliese A.
Diabetologia 49:953-957(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[10]"A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels."
Bouatia-Naji N., Rocheleau G., Van Lommel L., Lemaire K., Schuit F., Cavalcanti-Proenca C., Marchand M., Hartikainen A.-L., Sovio U., De Graeve F., Rung J., Vaxillaire M., Tichet J., Marre M., Balkau B., Weill J., Elliott P., Jarvelin M.-R. expand/collapse author list , Meyre D., Polychronakos C., Dina C., Sladek R., Froguel P.
Science 320:1085-1088(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN FGQTL1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF283835 Genomic DNA. Translation: AAF82810.1.
BQ777188 mRNA. No translation available.
CR627438 mRNA. Translation: CAH10524.1.
AC069137 Genomic DNA. No translation available.
CH471058 Genomic DNA. Translation: EAX11291.1.
BC104778 mRNA. Translation: AAI04779.1.
BC113376 mRNA. Translation: AAI13377.1.
CCDSCCDS2230.1. [Q9NQR9-1]
CCDS46443.1. [Q9NQR9-3]
RefSeqNP_001075155.1. NM_001081686.1. [Q9NQR9-3]
NP_066999.1. NM_021176.2. [Q9NQR9-1]
UniGeneHs.283963.

3D structure databases

ProteinModelPortalQ9NQR9.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000364512.

Polymorphism databases

DMDM74725272.

Proteomic databases

PaxDbQ9NQR9.
PRIDEQ9NQR9.

Protocols and materials databases

DNASU57818.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000282075; ENSP00000282075; ENSG00000152254. [Q9NQR9-2]
ENST00000375363; ENSP00000364512; ENSG00000152254. [Q9NQR9-1]
ENST00000429379; ENSP00000396939; ENSG00000152254. [Q9NQR9-3]
ENST00000571993; ENSP00000460909; ENSG00000262563. [Q9NQR9-2]
ENST00000572378; ENSP00000459575; ENSG00000262563. [Q9NQR9-3]
ENST00000573192; ENSP00000461775; ENSG00000262563. [Q9NQR9-1]
GeneID57818.
KEGGhsa:57818.
UCSCuc002uem.3. human. [Q9NQR9-1]
uc002uen.3. human.

Organism-specific databases

CTD57818.
GeneCardsGC02P169757.
HGNCHGNC:28906. G6PC2.
MIM608058. gene.
612108. phenotype.
neXtProtNX_Q9NQR9.
PharmGKBPA134944773.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82628.
HOGENOMHOG000264239.
HOVERGENHBG003560.
InParanoidQ9NQR9.
KOK01084.
OMALIQISVC.
PhylomeDBQ9NQR9.
TreeFamTF324388.

Enzyme and pathway databases

BioCycMetaCyc:HS14422-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.
SABIO-RKQ9NQR9.
UniPathwayUPA00138.

Gene expression databases

ArrayExpressQ9NQR9.
BgeeQ9NQR9.
CleanExHS_G6PC2.
GenevestigatorQ9NQR9.

Family and domain databases

Gene3D1.20.144.10. 1 hit.
InterProIPR016275. Glucose-6-phosphatase.
IPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view]
PfamPF01569. PAP2. 1 hit.
[Graphical view]
PIRSFPIRSF000905. Glucose-6-phosphatase. 1 hit.
SMARTSM00014. acidPPc. 1 hit.
[Graphical view]
SUPFAMSSF48317. SSF48317. 1 hit.
ProtoNetSearch...

Other

GeneWikiG6PC2.
GenomeRNAi57818.
NextBio64766.
PROQ9NQR9.
SOURCESearch...

Entry information

Entry nameG6PC2_HUMAN
AccessionPrimary (citable) accession number: Q9NQR9
Secondary accession number(s): E9PAX2, Q6AHZ0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM