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Q9NQR9

- G6PC2_HUMAN

UniProt

Q9NQR9 - G6PC2_HUMAN

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Protein
Glucose-6-phosphatase 2
Gene
G6PC2, IGRP
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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

Catalytic activityi

D-glucose 6-phosphate + H2O = D-glucose + phosphate.1 Publication

Kineticsi

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei79 – 791Substrate Reviewed prediction
Active sitei115 – 1151Proton donor Reviewed prediction
Binding sitei168 – 1681Substrate Reviewed prediction
Active sitei174 – 1741Nucleophile By similarity

GO - Molecular functioni

  1. glucose-6-phosphatase activity Source: UniProtKB-EC

GO - Biological processi

  1. carbohydrate metabolic process Source: Reactome
  2. gluconeogenesis Source: UniProtKB-UniPathway
  3. glucose homeostasis Source: BHF-UCL
  4. glucose transport Source: Reactome
  5. hexose transport Source: Reactome
  6. regulation of insulin secretion Source: BHF-UCL
  7. small molecule metabolic process Source: Reactome
  8. transmembrane transport Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Gluconeogenesis

Enzyme and pathway databases

BioCyciMetaCyc:HS14422-MONOMER.
ReactomeiREACT_212. Glucose transport.
SABIO-RKQ9NQR9.
UniPathwayiUPA00138.

Names & Taxonomyi

Protein namesi
Recommended name:
Glucose-6-phosphatase 2 (EC:3.1.3.9)
Short name:
G-6-Pase 2
Short name:
G6Pase 2
Alternative name(s):
Islet-specific glucose-6-phosphatase catalytic subunit-related protein
Gene namesi
Name:G6PC2
Synonyms:IGRP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 2

Organism-specific databases

HGNCiHGNC:28906. G6PC2.

Subcellular locationi

Endoplasmic reticulum membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2424Lumenal Reviewed prediction
Add
BLAST
Transmembranei25 – 4521Helical; Reviewed prediction
Add
BLAST
Topological domaini46 – 5611Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei57 – 7721Helical; Reviewed prediction
Add
BLAST
Topological domaini78 – 11538Lumenal Reviewed prediction
Add
BLAST
Transmembranei116 – 13621Helical; Reviewed prediction
Add
BLAST
Topological domaini137 – 14610Cytoplasmic Reviewed prediction
Transmembranei147 – 16721Helical; Reviewed prediction
Add
BLAST
Topological domaini168 – 1681Lumenal Reviewed prediction
Transmembranei169 – 18921Helical; Reviewed prediction
Add
BLAST
Topological domaini190 – 21122Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei212 – 23221Helical; Reviewed prediction
Add
BLAST
Topological domaini233 – 26129Lumenal Reviewed prediction
Add
BLAST
Transmembranei262 – 28221Helical; Reviewed prediction
Add
BLAST
Topological domaini283 – 29311Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei294 – 31421Helical; Reviewed prediction
Add
BLAST
Topological domaini315 – 3184Lumenal Reviewed prediction
Transmembranei319 – 33921Helical; Reviewed prediction
Add
BLAST
Topological domaini340 – 35516Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
  2. integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi50 – 501N → A: No effect on N-glycosylation. 1 Publication
Mutagenesisi92 – 921N → A: Loss of N-glycosylation. 1 Publication
Mutagenesisi287 – 2871N → A: No effect on N-glycosylation. 1 Publication

Organism-specific databases

MIMi612108. phenotype.
PharmGKBiPA134944773.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 355355Glucose-6-phosphatase 2
PRO_0000334509Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi92 – 921N-linked (GlcNAc...)1 Publication

Post-translational modificationi

N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9NQR9.
PRIDEiQ9NQR9.

Expressioni

Tissue specificityi

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

Gene expression databases

ArrayExpressiQ9NQR9.
BgeeiQ9NQR9.
CleanExiHS_G6PC2.
GenevestigatoriQ9NQR9.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000364512.

Structurei

3D structure databases

ProteinModelPortaliQ9NQR9.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi352 – 3554Prevents secretion from ER Reviewed prediction

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG82628.
HOGENOMiHOG000264239.
HOVERGENiHBG003560.
InParanoidiQ9NQR9.
KOiK01084.
OMAiLIQISVC.
PhylomeDBiQ9NQR9.
TreeFamiTF324388.

Family and domain databases

Gene3Di1.20.144.10. 1 hit.
InterProiIPR016275. Glucose-6-phosphatase.
IPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view]
PfamiPF01569. PAP2. 1 hit.
[Graphical view]
PIRSFiPIRSF000905. Glucose-6-phosphatase. 1 hit.
SMARTiSM00014. acidPPc. 1 hit.
[Graphical view]
SUPFAMiSSF48317. SSF48317. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NQR9-1) [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

MDFLHRNGVL IIQHLQKDYR AYYTFLNFMS NVGDPRNIFF IYFPLCFQFN    50
QTVGTKMIWV AVIGDWLNLI FKWILFGHRP YWWVQETQIY PNHSSPCLEQ 100
FPTTCETGPG SPSGHAMGAS CVWYVMVTAA LSHTVCGMDK FSITLHRLTW 150
SFLWSVFWLI QISVCISRVF IATHFPHQVI LGVIGGMLVA EAFEHTPGIQ 200
TASLGTYLKT NLFLFLFAVG FYLLLRVLNI DLLWSVPIAK KWCANPDWIH 250
IDTTPFAGLV RNLGVLFGLG FAINSEMFLL SCRGGNNYTL SFRLLCALTS 300
LTILQLYHFL QIPTHEEHLF YVLSFCKSAS IPLTVVAFIP YSVHMLMKQS 350
GKKSQ 355
Length:355
Mass (Da):40,580
Last modified:October 1, 2000 - v1
Checksum:iD642C37496B6C4EB
GO
Isoform 2 (identifier: Q9NQR9-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     74-102: ILFGHRPYWWVQETQIYPNHSSPCLEQFP → KSIWPCNGRILCLVCHGNRCPEPHCLWDG
     103-355: Missing.

Note: No experimental confirmation available.

Show »
Length:102
Mass (Da):12,160
Checksum:i45E36A48F44C0C93
GO
Isoform 3 (identifier: Q9NQR9-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     148-154: LTWSFLW → HAGGRGL
     155-355: Missing.

Note: No experimental confirmation available.

Show »
Length:154
Mass (Da):17,757
Checksum:i7203B17AA6D4CF40
GO

Polymorphismi

Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 1 (FGQTL1) [MIMi: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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti171 – 1711I → V.
Corresponds to variant rs2232322 [ dbSNP | Ensembl ].
VAR_043372
Natural varianti207 – 2071Y → S.
Corresponds to variant rs2232323 [ dbSNP | Ensembl ].
VAR_043373
Natural varianti219 – 2191V → L.
Corresponds to variant rs492594 [ dbSNP | Ensembl ].
VAR_043374
Natural varianti324 – 3241S → P.
Corresponds to variant rs2232326 [ dbSNP | Ensembl ].
VAR_043375
Natural varianti340 – 3401P → L.
Corresponds to variant rs2232327 [ dbSNP | Ensembl ].
VAR_043376
Natural varianti342 – 3421S → C.
Corresponds to variant rs2232328 [ dbSNP | Ensembl ].
VAR_043377

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei74 – 10229ILFGH…LEQFP → KSIWPCNGRILCLVCHGNRC PEPHCLWDG in isoform 2.
VSP_033648Add
BLAST
Alternative sequencei103 – 355253Missing in isoform 2.
VSP_033649Add
BLAST
Alternative sequencei148 – 1547LTWSFLW → HAGGRGL in isoform 3.
VSP_046180
Alternative sequencei155 – 355201Missing in isoform 3.
VSP_046181Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS2230.1. [Q9NQR9-1]
CCDS46443.1. [Q9NQR9-3]
RefSeqiNP_001075155.1. NM_001081686.1. [Q9NQR9-3]
NP_066999.1. NM_021176.2. [Q9NQR9-1]
UniGeneiHs.283963.

Genome annotation databases

EnsembliENST00000282075; 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]
GeneIDi57818.
KEGGihsa:57818.
UCSCiuc002uem.3. human. [Q9NQR9-1]
uc002uen.3. human.

Polymorphism databases

DMDMi74725272.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS2230.1. [Q9NQR9-1 ]
CCDS46443.1. [Q9NQR9-3 ]
RefSeqi NP_001075155.1. NM_001081686.1. [Q9NQR9-3 ]
NP_066999.1. NM_021176.2. [Q9NQR9-1 ]
UniGenei Hs.283963.

3D structure databases

ProteinModelPortali Q9NQR9.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000364512.

Polymorphism databases

DMDMi 74725272.

Proteomic databases

PaxDbi Q9NQR9.
PRIDEi Q9NQR9.

Protocols and materials databases

DNASUi 57818.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000282075 ; 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 ]
GeneIDi 57818.
KEGGi hsa:57818.
UCSCi uc002uem.3. human. [Q9NQR9-1 ]
uc002uen.3. human.

Organism-specific databases

CTDi 57818.
GeneCardsi GC02P169757.
HGNCi HGNC:28906. G6PC2.
MIMi 608058. gene.
612108. phenotype.
neXtProti NX_Q9NQR9.
PharmGKBi PA134944773.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG82628.
HOGENOMi HOG000264239.
HOVERGENi HBG003560.
InParanoidi Q9NQR9.
KOi K01084.
OMAi LIQISVC.
PhylomeDBi Q9NQR9.
TreeFami TF324388.

Enzyme and pathway databases

UniPathwayi UPA00138 .
BioCyci MetaCyc:HS14422-MONOMER.
Reactomei REACT_212. Glucose transport.
SABIO-RK Q9NQR9.

Miscellaneous databases

GeneWikii G6PC2.
GenomeRNAii 57818.
NextBioi 64766.
PROi Q9NQR9.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9NQR9.
Bgeei Q9NQR9.
CleanExi HS_G6PC2.
Genevestigatori Q9NQR9.

Family and domain databases

Gene3Di 1.20.144.10. 1 hit.
InterProi IPR016275. Glucose-6-phosphatase.
IPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view ]
Pfami PF01569. PAP2. 1 hit.
[Graphical view ]
PIRSFi PIRSF000905. Glucose-6-phosphatase. 1 hit.
SMARTi SM00014. acidPPc. 1 hit.
[Graphical view ]
SUPFAMi SSF48317. SSF48317. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
    Tissue: Pancreas.
  3. 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.
    , 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. 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. Cited for: INVOLVEMENT IN FGQTL1.

Entry informationi

Entry nameiG6PC2_HUMAN
AccessioniPrimary (citable) accession number: Q9NQR9
Secondary accession number(s): E9PAX2, Q6AHZ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: October 1, 2000
Last modified: September 3, 2014
This is version 98 of the entry and version 1 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

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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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