Q9NQR9 (G6PC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	355 AA.
Sequence status	Complete.
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 Ref.7.
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.7
Polymorphism	Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 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.
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 Transmembrane helix
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome gluconeogenesis Inferred from electronic annotation. Source: UniProtKB-UniPathway glucose homeostasis Inferred from mutant phenotype PubMed 20668700. Source: BHF-UCL glucose transport Traceable author statement. Source: Reactome regulation of insulin secretion Inferred from mutant phenotype PubMed 20668700. Source: BHF-UCL small molecule metabolic process Traceable author statement. Source: Reactome transmembrane transport Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome 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 3 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.

Isoform 3 (identifier: Q9NQR9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     148-154: LTWSFLW → HAGGRGL
     155-355: 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	Helical; Potential
	Topological domain	46 – 56	11	Cytoplasmic Potential
	Transmembrane	57 – 77	21	Helical; Potential
	Topological domain	78 – 115	38	Lumenal Potential
	Transmembrane	116 – 136	21	Helical; Potential
	Topological domain	137 – 146	10	Cytoplasmic Potential
	Transmembrane	147 – 167	21	Helical; Potential
	Topological domain	168	1	Lumenal Potential
	Transmembrane	169 – 189	21	Helical; Potential
	Topological domain	190 – 211	22	Cytoplasmic Potential
	Transmembrane	212 – 232	21	Helical; Potential
	Topological domain	233 – 261	29	Lumenal Potential
	Transmembrane	262 – 282	21	Helical; Potential
	Topological domain	283 – 293	11	Cytoplasmic Potential
	Transmembrane	294 – 314	21	Helical; Potential
	Topological domain	315 – 318	4	Lumenal Potential
	Transmembrane	319 – 339	21	Helical; 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.7
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
	Alternative sequence	148 – 154	7	LTWSFLW → HAGGRGL in isoform 3.		VSP_046180
	Alternative sequence	155 – 355	201	Missing in isoform 3.		VSP_046181
	Natural variant	171	1	I → V. Corresponds to variant rs2232322 [ dbSNP | Ensembl ].		VAR_043372
	Natural variant	207	1	Y → S. Corresponds to variant rs2232323 [ dbSNP | Ensembl ].		VAR_043373
	Natural variant	219	1	V → L. Corresponds to variant rs492594 [ dbSNP | Ensembl ].		VAR_043374
	Natural variant	324	1	S → P. Corresponds to variant rs2232326 [ dbSNP | Ensembl ].		VAR_043375
	Natural variant	340	1	P → L. Corresponds to variant rs2232327 [ dbSNP | Ensembl ].		VAR_043376
	Natural variant	342	1	S → C. Corresponds to variant rs2232328 [ dbSNP | Ensembl ].		VAR_043377
Experimental info
	Mutagenesis	50	1	N → A: No effect on N-glycosylation. Ref.7
	Mutagenesis	92	1	N → A: Loss of N-glycosylation. Ref.7
	Mutagenesis	287	1	N → A: No effect on N-glycosylation. Ref.7

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 [UniParc]. 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
	Isoform 3 [UniParc]. Checksum: 7203B17AA6D4CF40	FASTA	154	17,757
	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 CVWYVMVTAA LSHTVCGMDK FSITLHRHAG GRGL

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION, TISSUE SPECIFICITY.
[2]	"Endocrine pancreas consortium." Melton D., Brown J., Kenty G., Permutt A., Lee C., Kaestner K., Lemishka I., Scearce M., Brestelli J., Gradwohl G., Clifton S., Hillier L., Marra M., Pape D., Wylie T., Martin J., Blistain A., Schmitt A. , Theising B., Ritter E., Ronko I., Bennett J., Cardenas M., Gibbons M., McCann R., Cole R., Tsagareishvili R., Williams T., Jackson Y., Bowers Y. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Pancreas.
[3]	"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., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] 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]	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].
[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]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN FGQTL1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00028155. IPI00465025. IPI00830064.
RefSeq	NP_001075155.1. NM_001081686.1. NP_066999.1. NM_021176.2.
UniGene	Hs.283963.
3D structure databases
ProteinModelPortal	Q9NQR9.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000364512.
Polymorphism databases
DMDM	74725272.
Proteomic databases
PaxDb	Q9NQR9.
PRIDE	Q9NQR9.
Protocols and materials databases
DNASU	57818.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000282075; ENSP00000282075; ENSG00000152254. ENST00000375363; ENSP00000364512; ENSG00000152254. ENST00000429379; ENSP00000396939; ENSG00000152254. ENST00000571993; ENSP00000460909; ENSG00000262563. ENST00000572378; ENSP00000459575; ENSG00000262563. ENST00000573192; ENSP00000461775; ENSG00000262563.
GeneID	57818.
KEGG	hsa:57818.
UCSC	uc002uem.3. human. uc002uen.3. human.
Organism-specific databases
CTD	57818.
GeneCards	GC02P169757.
HGNC	HGNC:28906. G6PC2.
MIM	608058. gene. 612108. phenotype.
neXtProt	NX_Q9NQR9.
PharmGKB	PA134944773.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG82628.
HOGENOM	HOG000264239.
HOVERGEN	HBG003560.
InParanoid	Q9NQR9.
KO	K01084.
OMA	DWIHIDT.
OrthoDB	EOG402WSH.
PhylomeDB	Q9NQR9.
Enzyme and pathway databases
BioCyc	MetaCyc:HS14422-MONOMER.
Reactome	REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules.
UniPathway	UPA00138.
Gene expression databases
ArrayExpress	Q9NQR9.
Bgee	Q9NQR9.
CleanEx	HS_G6PC2.
Genevestigator	Q9NQR9.
Family and domain databases
Gene3D	1.20.144.10. 1 hit.
InterPro	IPR016275. Glucose-6-phosphatase. IPR016118. P_Acid_Pase/Cl_peroxidase_N. 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]
SUPFAM	SSF48317. AcPase_VanPerase. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	57818.
NextBio	64766.
SOURCE	Search...

Entry information

Entry name

G6PC2_HUMAN

Accession

Primary (citable) accession number: Q9NQR9
Secondary accession number(s): E9PAX2, Q6AHZ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	October 1, 2000
Last modified:	May 29, 2013
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.