G6PC2_MOUSE
ID G6PC2_MOUSE Reviewed; 355 AA.
AC Q9Z186; A2AUN2; Q2M2M7;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Glucose-6-phosphatase 2;
DE Short=G-6-Pase 2;
DE Short=G6Pase 2;
DE EC=3.1.3.9;
DE AltName: Full=Islet-specific glucose-6-phosphatase catalytic subunit-related protein;
GN Name=G6pc2; Synonyms=Igrp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, GLYCOSYLATION,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Pancreatic islet;
RX PubMed=10078553; DOI=10.2337/diabetes.48.3.531;
RA Arden S.D., Zahn T., Steegers S., Webb S., Bergman B., O'Brien R.M.,
RA Hutton J.C.;
RT "Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase
RT catalytic subunit-related protein.";
RL Diabetes 48:531-542(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10078554; DOI=10.2337/diabetes.48.3.543;
RA Ebert D.H., Bischof L.J., Streeper R.S., Chapman S.C., Svitek C.A.,
RA Goldman J.K., Mathews C.E., Leiter E.H., Hutton J.C., O'Brien R.M.;
RT "Structure and promoter activity of an islet-specific glucose-6-phosphatase
RT catalytic subunit-related gene.";
RL Diabetes 48:543-551(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=12878201; DOI=10.1016/s0006-291x(03)01242-7;
RA Goh B.-H., Efendic S., Khan A., Portwood N.;
RT "Evidence for the expression of both the hydrolase and translocase
RT components of hepatic glucose-6-phosphatase in murine pancreatic islets.";
RL Biochem. Biophys. Res. Commun. 307:935-941(2003).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION AS AN AUTOANTIGEN.
RX PubMed=12815107; DOI=10.1073/pnas.0932778100;
RA Lieberman S.M., Evans A.M., Han B., Takaki T., Vinnitskaya Y.,
RA Caldwell J.A., Serreze D.V., Shabanowitz J., Hunt D.F., Nathenson S.G.,
RA Santamaria P., DiLorenzo T.P.;
RT "Identification of the beta cell antigen targeted by a prevalent population
RT of pathogenic CD8+ T cells in autoimmune diabetes.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8384-8388(2003).
RN [8]
RP CATALYTIC ACTIVITY, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=14722102; DOI=10.1074/jbc.m307756200;
RA Petrolonis A.J., Yang Q., Tummino P.J., Fish S.M., Prack A.E., Jain S.,
RA Parsons T.F., Li P., Dales N.A., Ge L., Langston S.P., Schuller A.G.P.,
RA An W.F., Tartaglia L.A., Chen H., Hong S.-B.;
RT "Enzymatic characterization of the pancreatic islet-specific glucose-6-
RT phosphatase-related protein (IGRP).";
RL J. Biol. Chem. 279:13976-13983(2004).
RN [9]
RP IDENTIFICATION AS AN AUTOANTIGEN.
RX PubMed=15843527; DOI=10.4049/jimmunol.174.9.5306;
RA Mukherjee R., Wagar D., Stephens T.A., Lee-Chan E., Singh B.;
RT "Identification of CD4+ T cell-specific epitopes of islet-specific glucose-
RT 6-phosphatase catalytic subunit-related protein: a novel beta cell
RT autoantigen in type 1 diabetes.";
RL J. Immunol. 174:5306-5315(2005).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=17265032; DOI=10.1007/s00125-006-0564-1;
RA Wang Y., Martin C.C., Oeser J.K., Sarkar S., McGuinness O.P., Hutton J.C.,
RA O'Brien R.M.;
RT "Deletion of the gene encoding the islet-specific glucose-6-phosphatase
RT catalytic subunit-related protein autoantigen results in a mild metabolic
RT phenotype.";
RL Diabetologia 50:774-778(2007).
CC -!- FUNCTION: May hydrolyze glucose-6-phosphate to glucose in the
CC endoplasmic reticulum. May be responsible for glucose production
CC through glycogenolysis and gluconeogenesis (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + H2O = D-glucose + phosphate;
CC Xref=Rhea:RHEA:16689, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:61548; EC=3.1.3.9;
CC Evidence={ECO:0000269|PubMed:14722102};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Z186-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z186-2; Sequence=VSP_033650, VSP_033651;
CC -!- TISSUE SPECIFICITY: Specifically expressed in pancreatic islet cells,
CC in particular those of beta-cell origin. Not detected in testis,
CC kidney, muscle, liver, lung, spleen, brain, pituitary, gastric fundus
CC or heart. {ECO:0000269|PubMed:10078553, ECO:0000269|PubMed:12878201,
CC ECO:0000269|PubMed:14722102}.
CC -!- DEVELOPMENTAL STAGE: Initial onset of expression in the pancreas is at
CC 12 dpc and prominent expression is detected at 14 dpc.
CC {ECO:0000269|PubMed:10078553}.
CC -!- INDUCTION: Up-regulated in islet cells cultured in hyperglycemic
CC concentrations of glucose. {ECO:0000269|PubMed:14722102}.
CC -!- PTM: N-glycosylated; the non-glycosylated form is more unstable and is
CC degraded through the proteasome. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are no overt anatomical or behavioral
CC phenotype but display a mild metabolic phenotype. Upon fasting those
CC mice exhibit a significant decrease in blood glucose and
CC triacylglycerol compared to wild-type mice.
CC {ECO:0000269|PubMed:17265032}.
CC -!- MISCELLANEOUS: G6pc2 is an autoantigen which is the natural target of a
CC prevalent T-cell population causing insulin-dependent diabetes mellitus
CC through destruction of pancreatic beta cells.
CC -!- SIMILARITY: Belongs to the glucose-6-phosphatase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI11906.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR EMBL; Z47787; CAA87708.1; -; mRNA.
DR EMBL; AF118766; AAD28562.1; -; Genomic_DNA.
DR EMBL; AF118762; AAD28562.1; JOINED; Genomic_DNA.
DR EMBL; AF118763; AAD28562.1; JOINED; Genomic_DNA.
DR EMBL; AF118764; AAD28562.1; JOINED; Genomic_DNA.
DR EMBL; AF118765; AAD28562.1; JOINED; Genomic_DNA.
DR EMBL; AK148465; BAE28569.1; -; mRNA.
DR EMBL; AL929170; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC111905; AAI11906.1; ALT_SEQ; mRNA.
DR CCDS; CCDS16089.1; -. [Q9Z186-1]
DR CCDS; CCDS71066.1; -. [Q9Z186-2]
DR RefSeq; NP_001276785.1; NM_001289856.1.
DR RefSeq; NP_001276786.1; NM_001289857.1. [Q9Z186-2]
DR RefSeq; NP_067306.1; NM_021331.4. [Q9Z186-1]
DR AlphaFoldDB; Q9Z186; -.
DR BioGRID; 199788; 1.
DR STRING; 10090.ENSMUSP00000005364; -.
DR GlyGen; Q9Z186; 1 site.
DR PhosphoSitePlus; Q9Z186; -.
DR PaxDb; Q9Z186; -.
DR PRIDE; Q9Z186; -.
DR ProteomicsDB; 271626; -. [Q9Z186-1]
DR ProteomicsDB; 271627; -. [Q9Z186-2]
DR Antibodypedia; 53147; 75 antibodies from 12 providers.
DR DNASU; 14378; -.
DR Ensembl; ENSMUST00000005364; ENSMUSP00000005364; ENSMUSG00000005232. [Q9Z186-1]
DR Ensembl; ENSMUST00000112317; ENSMUSP00000107936; ENSMUSG00000005232. [Q9Z186-2]
DR GeneID; 14378; -.
DR KEGG; mmu:14378; -.
DR UCSC; uc008jxy.2; mouse. [Q9Z186-1]
DR UCSC; uc008jxz.2; mouse. [Q9Z186-2]
DR CTD; 57818; -.
DR MGI; MGI:1277193; G6pc2.
DR VEuPathDB; HostDB:ENSMUSG00000005232; -.
DR eggNOG; ENOG502QS9B; Eukaryota.
DR GeneTree; ENSGT00950000183150; -.
DR HOGENOM; CLU_052517_0_0_1; -.
DR InParanoid; Q9Z186; -.
DR OMA; PKAKKWC; -.
DR OrthoDB; 743717at2759; -.
DR PhylomeDB; Q9Z186; -.
DR TreeFam; TF324388; -.
DR BRENDA; 3.1.3.9; 3474.
DR Reactome; R-MMU-70263; Gluconeogenesis.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 14378; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9Z186; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9Z186; protein.
DR Bgee; ENSMUSG00000005232; Expressed in islet of Langerhans and 68 other tissues.
DR Genevisible; Q9Z186; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; IBA:GO_Central.
DR GO; GO:0042593; P:glucose homeostasis; ISO:MGI.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI.
DR InterPro; IPR016275; Glucose-6-phosphatase.
DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf.
DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase.
DR Pfam; PF01569; PAP2; 1.
DR PIRSF; PIRSF000905; Glucose-6-phosphatase; 1.
DR SMART; SM00014; acidPPc; 1.
DR SUPFAM; SSF48317; SSF48317; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Gluconeogenesis; Glycoprotein;
KW Hydrolase; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..355
FT /note="Glucose-6-phosphatase 2"
FT /id="PRO_0000334510"
FT TOPO_DOM 1..24
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..56
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 57..77
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 78..115
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 137..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..211
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 233..252
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 253..273
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 274..290
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..307
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..318
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOTIF 352..355
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255"
FT ACT_SITE 115
FT /note="Proton donor"
FT /evidence="ECO:0000255"
FT ACT_SITE 174
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 168
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT CARBOHYD 92
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 148..154
FT /note="LTWSFLW -> DASSRGL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033650"
FT VAR_SEQ 155..355
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_033651"
SQ SEQUENCE 355 AA; 40681 MW; C814C27DE44E306A CRC64;
MDFLHRSGVL IIHHLQEDYR TYYGFLNFMS NVGDPRNIFS IYFPLWFQLN QNVGTKMIWV
AVIGDWFNLI FKWILFGHRP YWWIQETEIY PNHSSPCLEQ FPTTCETGPG SPSGHAMGSS
CVWYVMVTAA LSYTISRMEE SSVTLHRLTW SFLWSVFWLI QISVCISRVF IATHFPHQVI
LGVIGGMLVA EAFEHTPGVH MASLSVYLKT NVFLFLFALG FYLLLRLFGI DLLWSVPIAK
KWCANPDWIH IDSTPFAGLV RNLGVLFGLG FAINSEMFLR SCQGENGTKP SFRLLCALTS
LTTMQLYRFI KIPTHAEPLF YLLSFCKSAS IPLMVVALIP YCVHMLMRPG DKKTK
