Reviewed, UniProtKB/Swiss-Prot Q9NQR9 (G6PC2_HUMAN)

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

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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.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 process	Gluconeogenesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome
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: 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 355	355	Glucose-6-phosphatase 2		PRO_0000334509
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 – 261	29	Lumenal Potential
	Transmembrane	262 – 282	21	Potential
	Topological domain	283 – 293	11	Cytoplasmic Potential
	Transmembrane	294 – 314	21	Potential
	Topological domain	315 – 318	4	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...) Ref.5
Natural variations
	Alternative sequence	74 – 102	29	ILFGH…LEQFP → KSIWPCNGRILCLVCHGNRC PEPHCLWDG in isoform 2.		VSP_033648
	Alternative sequence	103 – 355	253	Missing in isoform 2.		VSP_033649
	Natural variant	171	1	I → V: dbSNP rs2232322.		VAR_043372
	Natural variant	207	1	Y → S: dbSNP rs2232323.		VAR_043373
	Natural variant	219	1	V → L: dbSNP rs492594.		VAR_043374
	Natural variant	324	1	S → P: dbSNP rs2232326.		VAR_043375
	Natural variant	340	1	P → L: dbSNP rs2232327.		VAR_043376
	Natural variant	342	1	S → C: dbSNP rs2232328.		VAR_043377
Experimental info
	Mutagenesis	50	1	N → A: No effect on N-glycosylation. Ref.5
	Mutagenesis	92	1	N → A: Loss of N-glycosylation. Ref.5
	Mutagenesis	287	1	N → A: No effect on N-glycosylation. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: D642C37496B6C4EB	FASTA	355	40,580
	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
	Isoform 2. Checksum: 45E36A48F44C0C93	FASTA	102	12,160
	10 20 30 40 50 60 MDFLHRNGVL IIQHLQKDYR AYYTFLNFMS NVGDPRNIFF IYFPLCFQFN QTVGTKMIWV 70 80 90 100 AVIGDWLNLI FKWKSIWPCN GRILCLVCHG NRCPEPHCLW DG

References

	« Hide 'large scale' referencesShow '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. , 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. , 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
EMBLGenBankDDBJ	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.
IPI	IPI00028155. IPI00465025.
RefSeq	NP_001075155.1. NP_066999.1.
UniGene	Hs.283963
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	Q9NQR9.
Genome annotation databases
Ensembl	ENSG00000152254. Homo sapiens. [Contig view]
GeneID	57818.
KEGG	hsa:57818.
UCSC	uc002uem.1. human.
Organism-specific databases
GeneCards	GC02P169466.
HGNC	HGNC:28906. G6PC2.
MIM	608058. gene. 612108. phenotype.
PharmGKB	PA134944773.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9NQR9.
HOVERGEN	Q9NQR9.
OMA	Q9NQR9. HQVILGV.
Gene expression databases
ArrayExpress	Q9NQR9.
Bgee	Q9NQR9.
CleanEx	HS_G6PC2.
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	64766.
SOURCE	Search...

Entry information

Entry name

G6PC2_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)