ID G6PC2_HUMAN Reviewed; 355 AA. AC Q9NQR9; E9PAX2; Q6AHZ0; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 24-JAN-2024, entry version 153. 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 Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, AND TISSUE RP SPECIFICITY. RX PubMed=11297555; DOI=10.1074/jbc.m101549200; RA Martin C.C., Bischof L.J., Bergman B., Hornbuckle L.A., Hilliker C., RA Frigeri C., Wahl D., Svitek C.A., Wong R., Goldman J.K., Oeser J.K., RA Lepretre F., Froguel P., O'Brien R.M., Hutton J.C.; RT "Cloning and characterization of the human and rat islet-specific glucose- RT 6-phosphatase catalytic subunit-related protein (IGRP) genes."; RL J. Biol. Chem. 276:25197-25207(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Pancreas; RA Melton D., Brown J., Kenty G., Permutt A., Lee C., Kaestner K., RA Lemishka I., Scearce M., Brestelli J., Gradwohl G., Clifton S., Hillier L., RA Marra M., Pape D., Wylie T., Martin J., Blistain A., Schmitt A., RA Theising B., Ritter E., Ronko I., Bennett J., Cardenas M., Gibbons M., RA McCann R., Cole R., Tsagareishvili R., Williams T., Jackson Y., Bowers Y.; RT "Endocrine pancreas consortium."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Retina; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cerebellum; 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 [7] RP SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF ASN-50; ASN-92 AND ASN-287, RP AND GLYCOSYLATION AT ASN-92. RX PubMed=15044018; DOI=10.1016/s0014-5793(04)00223-6; RA Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y.; RT "The islet-specific glucose-6-phosphatase-related protein, implicated in RT diabetes, is a glycoprotein embedded in the endoplasmic reticulum RT membrane."; RL FEBS Lett. 562:160-164(2004). RN [8] RP CATALYTIC ACTIVITY. 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 ALTERNATIVE SPLICING. RX PubMed=16520917; DOI=10.1007/s00125-006-0185-8; RA Dogra R.S., Vaidyanathan P., Prabakar K.R., Marshall K.E., Hutton J.C., RA Pugliese A.; RT "Alternative splicing of G6PC2, the gene coding for the islet-specific RT glucose-6-phosphatase catalytic subunit-related protein (IGRP), results in RT differential expression in human thymus and spleen compared with RT pancreas."; RL Diabetologia 49:953-957(2006). RN [10] RP INVOLVEMENT IN FGQTL1. RX PubMed=18451265; DOI=10.1126/science.1156849; RA Bouatia-Naji N., Rocheleau G., Van Lommel L., Lemaire K., Schuit F., RA Cavalcanti-Proenca C., Marchand M., Hartikainen A.-L., Sovio U., RA De Graeve F., Rung J., Vaxillaire M., Tichet J., Marre M., Balkau B., RA Weill J., Elliott P., Jarvelin M.-R., Meyre D., Polychronakos C., Dina C., RA Sladek R., Froguel P.; RT "A polymorphism within the G6PC2 gene is associated with fasting plasma RT glucose levels."; RL Science 320:1085-1088(2008). 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 -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.45 mM for glucose-6-phosphate (at pH 6.5); CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:15044018}; Multi-pass membrane protein CC {ECO:0000269|PubMed:15044018}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9NQR9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NQR9-2; Sequence=VSP_033648, VSP_033649; CC Name=3; CC IsoId=Q9NQR9-3; Sequence=VSP_046180, VSP_046181; CC -!- TISSUE SPECIFICITY: Specifically expressed in pancreas and also CC detected to a lower extent in testis. Expressed by most islet cells in CC the pancreas (at protein level). {ECO:0000269|PubMed:11297555}. CC -!- PTM: N-glycosylated; the non-glycosylated form is more unstable and is CC degraded through the proteasome. {ECO:0000269|PubMed:15044018}. CC -!- POLYMORPHISM: Genetic variations in G6PC2 define the fasting plasma CC glucose levels quantitative trait locus 1 (FGQTL1) [MIM:612108]. The CC normal fasting plasma glucose level in the plasma is defined as less CC than 100 mg per deciliter (5.55 mmol per liter). Higher fasting plasma CC glucose levels predict type 2 diabetes in young adults and increases CC the risk of mortality. CC -!- SIMILARITY: Belongs to the glucose-6-phosphatase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF283835; AAF82810.1; -; Genomic_DNA. DR EMBL; BQ777188; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CR627438; CAH10524.1; -; mRNA. DR EMBL; AC069137; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471058; EAX11291.1; -; Genomic_DNA. DR EMBL; BC104778; AAI04779.1; -; mRNA. DR EMBL; BC113376; AAI13377.1; -; mRNA. DR CCDS; CCDS2230.1; -. [Q9NQR9-1] DR CCDS; CCDS46443.1; -. [Q9NQR9-3] DR RefSeq; NP_001075155.1; NM_001081686.1. [Q9NQR9-3] DR RefSeq; NP_066999.1; NM_021176.2. [Q9NQR9-1] DR AlphaFoldDB; Q9NQR9; -. DR SMR; Q9NQR9; -. DR BioGRID; 121777; 1. DR STRING; 9606.ENSP00000364512; -. DR DEPOD; G6PC2; -. DR GlyCosmos; Q9NQR9; 1 site, No reported glycans. DR GlyGen; Q9NQR9; 1 site. DR iPTMnet; Q9NQR9; -. DR PhosphoSitePlus; Q9NQR9; -. DR BioMuta; G6PC2; -. DR DMDM; 74725272; -. DR PaxDb; 9606-ENSP00000364512; -. DR Antibodypedia; 53147; 94 antibodies from 13 providers. DR DNASU; 57818; -. DR Ensembl; ENST00000282075.5; ENSP00000282075.4; ENSG00000152254.11. [Q9NQR9-2] DR Ensembl; ENST00000375363.8; ENSP00000364512.3; ENSG00000152254.11. [Q9NQR9-1] DR Ensembl; ENST00000429379.2; ENSP00000396939.2; ENSG00000152254.11. [Q9NQR9-3] DR Ensembl; ENST00000612807.1; ENSP00000481098.1; ENSG00000278373.4. [Q9NQR9-3] DR Ensembl; ENST00000617403.1; ENSP00000483899.1; ENSG00000278373.4. [Q9NQR9-2] DR Ensembl; ENST00000622133.4; ENSP00000482583.1; ENSG00000278373.4. [Q9NQR9-1] DR GeneID; 57818; -. DR KEGG; hsa:57818; -. DR MANE-Select; ENST00000375363.8; ENSP00000364512.3; NM_021176.3; NP_066999.1. DR UCSC; uc002uem.4; human. [Q9NQR9-1] DR AGR; HGNC:28906; -. DR CTD; 57818; -. DR DisGeNET; 57818; -. DR GeneCards; G6PC2; -. DR HGNC; HGNC:28906; G6PC2. DR HPA; ENSG00000152254; Group enriched (pancreas, retina). DR MIM; 608058; gene. DR MIM; 612108; phenotype. DR neXtProt; NX_Q9NQR9; -. DR OpenTargets; ENSG00000152254; -. DR PharmGKB; PA134944773; -. DR VEuPathDB; HostDB:ENSG00000152254; -. DR eggNOG; ENOG502QS9B; Eukaryota. DR GeneTree; ENSGT00950000183150; -. DR HOGENOM; CLU_052517_0_0_1; -. DR InParanoid; Q9NQR9; -. DR OMA; EEHLFYV; -. DR OrthoDB; 4030642at2759; -. DR PhylomeDB; Q9NQR9; -. DR TreeFam; TF324388; -. DR BioCyc; MetaCyc:HS14422-MONOMER; -. DR BRENDA; 3.1.3.9; 2681. DR PathwayCommons; Q9NQR9; -. DR Reactome; R-HSA-70263; Gluconeogenesis. DR SABIO-RK; Q9NQR9; -. DR SIGNOR; Q9NQR9; -. DR UniPathway; UPA00138; -. DR BioGRID-ORCS; 57818; 13 hits in 1165 CRISPR screens. DR GeneWiki; G6PC2; -. DR GenomeRNAi; 57818; -. DR Pharos; Q9NQR9; Tbio. DR PRO; PR:Q9NQR9; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9NQR9; Protein. DR Bgee; ENSG00000152254; Expressed in islet of Langerhans and 47 other cell types or tissues. DR ExpressionAtlas; Q9NQR9; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0004346; F:glucose-6-phosphatase activity; EXP:Reactome. 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; IMP:BHF-UCL. DR GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL. DR CDD; cd03381; PAP2_glucose_6_phosphatase; 1. DR Gene3D; 1.20.144.10; Phosphatidic acid phosphatase type 2/haloperoxidase; 1. DR InterPro; IPR016275; Glucose-6-phosphatase. DR InterPro; IPR036938; P_Acid_Pase_2/haloperoxi_sf. DR InterPro; IPR000326; P_Acid_Pase_2/haloperoxidase. DR PANTHER; PTHR12591; GLUCOSE-6-PHOSPHATASE; 1. DR PANTHER; PTHR12591:SF1; GLUCOSE-6-PHOSPHATASE 2; 1. DR Pfam; PF01569; PAP2; 1. DR PIRSF; PIRSF000905; Glucose-6-phosphatase; 1. DR SMART; SM00014; acidPPc; 1. DR SUPFAM; SSF48317; Acid phosphatase/Vanadium-dependent haloperoxidase; 1. DR Genevisible; Q9NQR9; HS. 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_0000334509" 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..261 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 262..282 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 283..293 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 294..314 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 315..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:0000269|PubMed:15044018" FT VAR_SEQ 74..102 FT /note="ILFGHRPYWWVQETQIYPNHSSPCLEQFP -> KSIWPCNGRILCLVCHGNR FT CPEPHCLWDG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_033648" FT VAR_SEQ 103..355 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_033649" FT VAR_SEQ 148..154 FT /note="LTWSFLW -> HAGGRGL (in isoform 3)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_046180" FT VAR_SEQ 155..355 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_046181" FT VARIANT 171 FT /note="I -> V (in dbSNP:rs2232322)" FT /id="VAR_043372" FT VARIANT 207 FT /note="Y -> S (in dbSNP:rs2232323)" FT /id="VAR_043373" FT VARIANT 219 FT /note="V -> L (in dbSNP:rs492594)" FT /id="VAR_043374" FT VARIANT 324 FT /note="S -> P (in dbSNP:rs2232326)" FT /id="VAR_043375" FT VARIANT 340 FT /note="P -> L (in dbSNP:rs2232327)" FT /id="VAR_043376" FT VARIANT 342 FT /note="S -> C (in dbSNP:rs2232328)" FT /id="VAR_043377" FT MUTAGEN 50 FT /note="N->A: No effect on N-glycosylation." FT /evidence="ECO:0000269|PubMed:15044018" FT MUTAGEN 92 FT /note="N->A: Loss of N-glycosylation." FT /evidence="ECO:0000269|PubMed:15044018" FT MUTAGEN 287 FT /note="N->A: No effect on N-glycosylation." FT /evidence="ECO:0000269|PubMed:15044018" SQ SEQUENCE 355 AA; 40580 MW; D642C37496B6C4EB CRC64; MDFLHRNGVL IIQHLQKDYR AYYTFLNFMS NVGDPRNIFF IYFPLCFQFN QTVGTKMIWV AVIGDWLNLI FKWILFGHRP YWWVQETQIY PNHSSPCLEQ FPTTCETGPG SPSGHAMGAS CVWYVMVTAA LSHTVCGMDK FSITLHRLTW SFLWSVFWLI QISVCISRVF IATHFPHQVI LGVIGGMLVA EAFEHTPGIQ TASLGTYLKT NLFLFLFAVG FYLLLRVLNI DLLWSVPIAK KWCANPDWIH IDTTPFAGLV RNLGVLFGLG FAINSEMFLL SCRGGNNYTL SFRLLCALTS LTILQLYHFL QIPTHEEHLF YVLSFCKSAS IPLTVVAFIP YSVHMLMKQS GKKSQ //