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Reviewed, UniProtKB/Swiss-Prot Q9NQR9 (G6PC2_HUMAN)

Last modified July 7, 2009. Version 51. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length355 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.6

Pathway

Carbohydrate biosynthesis; gluconeogenesis.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Ref.5

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.5

Involvement in disease

Genetic variation in G6PC2 is associated with fasting plasma glucose levels quantitative trait locus type 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. Ref.8

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)

Ontologies

Keywords
   Biological processGluconeogenesis
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
   Molecular functionHydrolase
   PTMGlycoprotein
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processgluconeogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionglucose-6-phosphatase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 355355Glucose-6-phosphatase 2
PRO_0000334509

Regions

Topological domain1 – 2424Lumenal Potential
Transmembrane25 – 4521 Potential
Topological domain46 – 5611Cytoplasmic Potential
Transmembrane57 – 7721 Potential
Topological domain78 – 11538Lumenal Potential
Transmembrane116 – 13621 Potential
Topological domain137 – 14610Cytoplasmic Potential
Transmembrane147 – 16721 Potential
Topological domain1681Lumenal Potential
Transmembrane169 – 18921 Potential
Topological domain190 – 21122Cytoplasmic Potential
Transmembrane212 – 23221 Potential
Topological domain233 – 26129Lumenal Potential
Transmembrane262 – 28221 Potential
Topological domain283 – 29311Cytoplasmic Potential
Transmembrane294 – 31421 Potential
Topological domain315 – 3184Lumenal Potential
Transmembrane319 – 33921 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.5

Natural variations

Alternative sequence74 – 10229ILFGH…LEQFP → KSIWPCNGRILCLVCHGNRC PEPHCLWDG in isoform 2.
VSP_033648
Alternative sequence103 – 355253Missing in isoform 2.
VSP_033649
Natural variant1711I → V: dbSNP rs2232322.
VAR_043372
Natural variant2071Y → S: dbSNP rs2232323.
VAR_043373
Natural variant2191V → L: dbSNP rs492594.
VAR_043374
Natural variant3241S → P: dbSNP rs2232326.
VAR_043375
Natural variant3401P → L: dbSNP rs2232327.
VAR_043376
Natural variant3421S → C: dbSNP rs2232328.
VAR_043377

Experimental info

Mutagenesis501N → A: No effect on N-glycosylation. Ref.5
Mutagenesis921N → A: Loss of N-glycosylation. Ref.5
Mutagenesis2871N → A: No effect on N-glycosylation. Ref.5

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.

Checksum: 45E36A48F44C0C93
Show »

FASTA10212,160

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: 11297555] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, TISSUE SPECIFICITY.
[2]"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., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Retina.
[3]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].
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Cerebellum.
[5]"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: 15044018] [Abstract]
Cited for: SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF ASN-50; ASN-92 AND ASN-287, GLYCOSYLATION AT ASN-92.
[6]"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: 14722102] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[7]"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: 16520917] [Abstract]
Cited for: ALTERNATIVE SPLICING.
[8]"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: 18451265] [Abstract]
Cited for: INVOLVEMENT IN FGQTL1.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF283835 Genomic DNA. Translation: AAF82810.1.
CR627438 mRNA. Translation: CAH10524.1.
CH471058 Genomic DNA. Translation: EAX11291.1.
BC104778 mRNA. Translation: AAI04779.1.
BC113376 mRNA. Translation: AAI13377.1.
IPIIPI00028155.
IPI00465025.
RefSeqNP_001075155.1.
NP_066999.1.
UniGeneHs.283963

3D structure databases

ModBaseSearch...

Proteomic databases

PRIDEQ9NQR9.

Genome annotation databases

EnsemblENSG00000152254. Homo sapiens. [Contig view]
GeneID57818.
KEGGhsa:57818.
UCSCuc002uem.1. human.

Organism-specific databases

GeneCardsGC02P169466.
HGNCHGNC:28906. G6PC2.
MIM608058. gene.
612108. phenotype.
PharmGKBPA134944773.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ9NQR9.
HOVERGENQ9NQR9.
OMAQ9NQR9. HQVILGV.

Gene expression databases

ArrayExpressQ9NQR9.
BgeeQ9NQR9.
CleanExHS_G6PC2.

Family and domain databases

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]
ProtoNetSearch...

Other Resources

NextBio64766.
SOURCESearch...

Entry information

Entry nameG6PC2_HUMAN
AccessionPrimary (citable) accession number: Q9NQR9
Secondary accession number(s): Q6AHZ0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: October 1, 2000
Last modified: July 7, 2009
This is version 51 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 2

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents