Reviewed, UniProtKB/Swiss-Prot Q9Z186 (G6PC2_MOUSE)

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	355 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 By similarity.
Tissue specificity	Specifically expressed in pancreatic islet cells, in particular those of beta-cell origin. Not detected in testis, kidney, muscle, liver, lung, spleen, brain, pituitary, gastric fundus or heart. Ref.8 Ref.1 Ref.6
Developmental stage	Initial onset of expression in the pancreas is at E12 and prominent expression is detected at E14. Ref.1
Induction	Up-regulated in islet cells cultured in hyperglycemic concentrations of glucose. Ref.8
Post-translational modification	N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome By similarity.
Disruption phenotype	Mice are no overt anatomical or behavioral phenotype but display a mild metabolic phenotype. Upon fasting those mice exhibit a significant decrease in blood glucose and triacylglycerol compared to wild type mice. Ref.10
Miscellaneous	G6pc2 is an autoantigen which is the natural target of a prevalent T-cell population causing insulin-dependent diabetes mellitus through destruction of pancreatic beta cells.
Sequence similarities	Belongs to the glucose-6-phosphatase family.
Sequence caution	The sequence AAI11906.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

Ontologies

Keywords
Biological process	Gluconeogenesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	gluconeogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	glucose-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: Q9Z186-1)

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: Q9Z186-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 355	355	Glucose-6-phosphatase 2		PRO_0000334510
Regions
	Topological domain	1 – 24	24	Lumenal Potential
	Transmembrane	25 – 45	21	Potential
	Topological domain	46 – 56	11	Cytoplasmic Potential
	Transmembrane	57 – 77	21	Potential
	Topological domain	78 – 115	38	Lumenal Potential
	Transmembrane	116 – 136	21	Potential
	Topological domain	137 – 146	10	Cytoplasmic Potential
	Transmembrane	147 – 167	21	Potential
	Topological domain	168	1	Lumenal Potential
	Transmembrane	169 – 189	21	Potential
	Topological domain	190 – 211	22	Cytoplasmic Potential
	Transmembrane	212 – 232	21	Potential
	Topological domain	233 – 252	20	Lumenal Potential
	Transmembrane	253 – 273	21	Potential
	Topological domain	274 – 290	17	Cytoplasmic Potential
	Transmembrane	291 – 307	17	Potential
	Topological domain	308 – 318	11	Lumenal Potential
	Transmembrane	319 – 339	21	Potential
	Topological domain	340 – 355	16	Cytoplasmic Potential
	Motif	352 – 355	4	Prevents secretion from ER Potential
Sites
	Active site	115	1	Proton donor Potential
	Active site	174	1	Nucleophile By similarity
	Binding site	79	1	Substrate Potential
	Binding site	168	1	Substrate Potential
Amino acid modifications
	Glycosylation	92	1	N-linked (GlcNAc...) By similarity
Natural variations
	Alternative sequence	148 – 154	7	LTWSFLW → DASSRGL in isoform 2.		VSP_033650
	Alternative sequence	155 – 355	201	Missing in isoform 2.		VSP_033651

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: C814C27DE44E306A	FASTA	355	40,681
	10 20 30 40 50 60 MDFLHRSGVL IIHHLQEDYR TYYGFLNFMS NVGDPRNIFS IYFPLWFQLN QNVGTKMIWV 70 80 90 100 110 120 AVIGDWFNLI FKWILFGHRP YWWIQETEIY PNHSSPCLEQ FPTTCETGPG SPSGHAMGSS 130 140 150 160 170 180 CVWYVMVTAA LSYTISRMEE SSVTLHRLTW SFLWSVFWLI QISVCISRVF IATHFPHQVI 190 200 210 220 230 240 LGVIGGMLVA EAFEHTPGVH MASLSVYLKT NVFLFLFALG FYLLLRLFGI DLLWSVPIAK 250 260 270 280 290 300 KWCANPDWIH IDSTPFAGLV RNLGVLFGLG FAINSEMFLR SCQGENGTKP SFRLLCALTS 310 320 330 340 350 LTTMQLYRFI KIPTHAEPLF YLLSFCKSAS IPLMVVALIP YCVHMLMRPG DKKTK
	Isoform 2. Checksum: 3B97B3DEE219A09C	FASTA	154	17,894
	10 20 30 40 50 60 MDFLHRSGVL IIHHLQEDYR TYYGFLNFMS NVGDPRNIFS IYFPLWFQLN QNVGTKMIWV 70 80 90 100 110 120 AVIGDWFNLI FKWILFGHRP YWWIQETEIY PNHSSPCLEQ FPTTCETGPG SPSGHAMGSS 130 140 150 CVWYVMVTAA LSYTISRMEE SSVTLHRDAS SRGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a pancreatic islet-specific glucose-6-phosphatase catalytic subunit-related protein." Arden S.D., Zahn T., Steegers S., Webb S., Bergman B., O'Brien R.M., Hutton J.C. Diabetes 48:531-542(1999) [PubMed: 10078553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, GLYCOSYLATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE. Tissue: Pancreatic islet.
[2]	"Structure and promoter activity of an islet-specific glucose-6-phosphatase catalytic subunit-related gene." Ebert D.H., Bischof L.J., Streeper R.S., Chapman S.C., Svitek C.A., Goldman J.K., Mathews C.E., Leiter E.H., Hutton J.C., O'Brien R.M. Diabetes 48:543-551(1999) [PubMed: 10078554] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Pancreas.
[4]	The mouse genome sequencing consortium Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[5]	"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 2).
[6]	"Evidence for the expression of both the hydrolase and translocase components of hepatic glucose-6-phosphatase in murine pancreatic islets." Goh B.-H., Efendic S., Khan A., Portwood N. Biochem. Biophys. Res. Commun. 307:935-941(2003) [PubMed: 12878201] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes." Lieberman S.M., Evans A.M., Han B., Takaki T., Vinnitskaya Y., Caldwell J.A., Serreze D.V., Shabanowitz J., Hunt D.F., Nathenson S.G., Santamaria P., DiLorenzo T.P. Proc. Natl. Acad. Sci. U.S.A. 100:8384-8388(2003) [PubMed: 12815107] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION AS AN AUTOANTIGEN.
[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: 14722102] [Abstract] Cited for: CATALYTIC ACTIVITY, INDUCTION, TISSUE SPECIFICITY.
[9]	"Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6-phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in type 1 diabetes." Mukherjee R., Wagar D., Stephens T.A., Lee-Chan E., Singh B. J. Immunol. 174:5306-5315(2005) [PubMed: 15843527] [Abstract] Cited for: IDENTIFICATION AS AN AUTOANTIGEN.
[10]	"Deletion of the gene encoding the islet-specific glucose-6-phosphatase catalytic subunit-related protein autoantigen results in a mild metabolic phenotype." Wang Y., Martin C.C., Oeser J.K., Sarkar S., McGuinness O.P., Hutton J.C., O'Brien R.M. Diabetologia 50:774-778(2007) [PubMed: 17265032] [Abstract] Cited for: DISRUPTION PHENOTYPE.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z47787 mRNA. Translation: CAA87708.1. AF118766 , AF118762, AF118763, AF118764, AF118765 Genomic DNA. Translation: AAD28562.1. AK148465 mRNA. Translation: BAE28569.1. AL929170 Genomic DNA. Translation: CAM24718.1. AL929170 Genomic DNA. Translation: CAM24719.1. BC111905 mRNA. Translation: AAI11906.1. Sequence problems.
IPI	IPI00129645. IPI00756928.
RefSeq	NP_067306.1.
UniGene	Mm.140768
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000005232. Mus musculus. [Contig view]
GeneID	14378.
KEGG	mmu:14378.
Organism-specific databases
MGI	MGI:1277193. G6pc2.
Phylogenomic databases
HOGENOM	Q9Z186.
HOVERGEN	Q9Z186.
OMA	Q9Z186. HQVILGV.
Gene expression databases
ArrayExpress	Q9Z186.
Bgee	Q9Z186.
Family and domain databases
InterPro	IPR016275. Glucose-6-phosphatase. IPR000326. P_Acid_Pase_2/haloperoxidase. [Graphical view]
Pfam	PF01569. PAP2. 1 hit. [Graphical view]
PIRSF	PIRSF000905. Glucose-6-phosphatase. 1 hit.
SMART	SM00014. acidPPc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	285885.
SOURCE	Search...

Entry information

Entry name

G6PC2_MOUSE

Accession

Primary (citable) accession number: Q9Z186
Secondary accession number(s): A2AUN2, Q2M2M7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	May 1, 1999
Last modified:	June 16, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)