Q9BUM1 (G6PC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glucose-6-phosphatase 3
Short name=G-6-Pase 3
Short name=G6Pase 3
EC=3.1.3.9

Alternative name(s):
Glucose-6-phosphatase beta
Short name=G6Pase-beta
Ubiquitous glucose-6-phosphatase catalytic subunit-related protein

Gene names

Name:	G6PC3
Synonyms:	UGRP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function. Ref.3 Ref.4 Ref.5
Catalytic activity	D-glucose 6-phosphate + H2O = D-glucose + phosphate. Ref.4
Enzyme regulation	Inhibited by vanadate. Ref.5
Pathway	Carbohydrate biosynthesis; gluconeogenesis.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.5.
Tissue specificity	Ubiquitously expressed. Highly expressed in skeletal muscle, at intermediate levels in heart, brain, placenta, kidney, colon, thymus, spleen and pancreas. Also detected in testis, prostate, ovary, liver, lung, small intestine and peripheral blood lymphocytes. Ref.3 Ref.4 Ref.7
Involvement in disease	Defects in G6PC3 are the cause of neutropenia severe congenital autosomal recessive type 4 (SCN4) [MIM:612541]. Autosomal recessive SCN constitutes a primary immunodeficiency syndrome associated with increased apoptosis in myeloid cells. Individuals show a paucity of mature neutrophils in peripheral blood and bone marrow and develop life-threatening bacterial infections. SCN4 is a severe congenital neutropenia syndrome associated with cardiac and urogenital malformations. Ref.8 Ref.10 Ref.11 Defects in G6PC3 are the cause of Dursun syndrome (DURSS) [MIM:612541]. A disease characterized by pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, intermittent neutropenia, lymphopenia, monocytosis and anemia. Ref.9
Sequence similarities	Belongs to the glucose-6-phosphatase family.
Caution	According to Ref.3, it has no hydrolytic activity.
Biophysicochemical properties	Kinetic parameters: 8 times less active compared to G6PC under the same experimental conditions. KM=1.0 mM for glucose-6-phosphate (at pH 5.5) Ref.4 Ref.5 KM=2.0 mM for glucose-6-phosphate (at pH 6.5)

Ontologies

Keywords
Biological process	Gluconeogenesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	gluconeogenesis Inferred from electronic annotation. Source: UniProtKB-KW 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 346	346	Glucose-6-phosphatase 3		PRO_0000334512
Regions
	Topological domain	1 – 24	24	Lumenal Potential
	Transmembrane	25 – 45	21	Helical; Potential
	Topological domain	46 – 54	9	Cytoplasmic Potential
	Transmembrane	55 – 75	21	Helical; Potential
	Topological domain	76 – 114	39	Lumenal Potential
	Transmembrane	115 – 135	21	Helical; Potential
	Topological domain	136 – 146	11	Cytoplasmic Potential
	Transmembrane	147 – 164	18	Helical; Potential
	Topological domain	165 – 169	5	Lumenal Potential
	Transmembrane	170 – 186	17	Helical; Potential
	Topological domain	187 – 197	11	Cytoplasmic Potential
	Transmembrane	198 – 218	21	Helical; Potential
	Topological domain	219 – 254	36	Lumenal Potential
	Transmembrane	255 – 273	19	Helical; Potential
	Topological domain	274 – 283	10	Cytoplasmic Potential
	Transmembrane	284 – 304	21	Helical; Potential
	Topological domain	305 – 307	3	Lumenal Potential
	Transmembrane	308 – 328	21	Helical; Potential
	Topological domain	329 – 346	18	Cytoplasmic Potential
Sites
	Active site	114	1	Proton donor Potential
	Active site	167	1	Nucleophile Ref.6
	Binding site	79	1	Substrate Potential
	Binding site	161	1	Substrate Potential
Natural variations
	Natural variant	116	1	M → K in SCN4; the patient also carries mutation Thr-166 in ELANE. Ref.11		VAR_064508
	Natural variant	116	1	M → V in DURSS. Ref.9		VAR_064509
	Natural variant	185	1	L → P in SCN4. Ref.8		VAR_055156
	Natural variant	189	1	R → Q in SCN4. Ref.11		VAR_064510
	Natural variant	216	1	T → I. Corresponds to variant rs34406052 [ dbSNP | Ensembl ].		VAR_043378
	Natural variant	253	1	R → H in SCN4; the mutant protein has no phosphatase activity in vitro; electron microscopic studies show enlarged rough endoplasmic reticulum consistent with increased stress. Ref.8		VAR_055157
	Natural variant	260	1	G → R in SCN4; loss of function. Ref.10 Ref.11		VAR_064511
	Natural variant	262	1	G → R in SCN4. Ref.8		VAR_055158
Experimental info
	Mutagenesis	79	1	R → A: Loss of catalytic activity. Ref.5
	Mutagenesis	114	1	H → A: Loss of catalytic activity. Ref.5
	Mutagenesis	167	1	H → A: Loss of catalytic activity. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9BUM1 [UniParc]. Last modified March 1, 2004. Version 2. Checksum: 55C1F322E59C8439	FASTA	346	38,735
	10 20 30 40 50 60 MESTLGAGIV IAEALQNQLA WLENVWLWIT FLGDPKILFL FYFPAAYYAS RRVGIAVLWI 70 80 90 100 110 120 SLITEWLNLI FKWFLFGDRP FWWVHESGYY SQAPAQVHQF PSSCETGPGS PSGHCMITGA 130 140 150 160 170 180 ALWPIMTALS SQVATRARSR WVRVMPSLAY CTFLLAVGLS RIFILAHFPH QVLAGLITGA 190 200 210 220 230 240 VLGWLMTPRV PMERELSFYG LTALALMLGT SLIYWTLFTL GLDLSWSISL AFKWCERPEW 250 260 270 280 290 300 IHVDSRPFAS LSRDSGAALG LGIALHSPCY AQVRRAQLGN GQKIACLVLA MGLLGPLDWL 310 320 330 340 GHPPQISLFY IFNFLKYTLW PCLVLALVPW AVHMFSAQEA PPIHSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	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].
[2]	"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]. Tissue: Eye and Skin.
[3]	"Identification and characterization of a human cDNA and gene encoding a ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein." Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I., Hutton J.C., O'Brien R.M. J. Mol. Endocrinol. 29:205-222(2002) [PubMed: 12370122] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[4]	"Identification and characterisation of a new human glucose-6-phosphatase isoform." Guionie O., Clottes E., Stafford K., Burchell A. FEBS Lett. 551:159-164(2003) [PubMed: 12965222] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
[5]	"A glucose-6-phosphate hydrolase, widely expressed outside the liver, can explain age-dependent resolution of hypoglycemia in glycogen storage disease type Ia." Shieh J.-J., Pan C.-J., Mansfield B.C., Chou J.Y. J. Biol. Chem. 278:47098-47103(2003) [PubMed: 13129915] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-79; HIS-114 AND HIS-167.
[6]	"Histidine 167 is the phosphate acceptor in glucose-6-phosphatase-beta forming a phosphohistidine enzyme intermediate during catalysis." Ghosh A., Shieh J.-J., Pan C.-J., Chou J.Y. J. Biol. Chem. 279:12479-12483(2004) [PubMed: 14718531] [Abstract] Cited for: TOPOLOGY, ACTIVE SITE.
[7]	"Identification and characterization of a cDNA and the gene encoding the mouse ubiquitously expressed glucose-6-phosphatase catalytic subunit-related protein." Boustead J.N., Martin C.C., Oeser J.K., Svitek C.A., Hunter S.I., Hutton J.C., O'Brien R.M. J. Mol. Endocrinol. 32:33-53(2004) [PubMed: 14765991] [Abstract] Cited for: TISSUE SPECIFICITY.
[8]	"A syndrome with congenital neutropenia and mutations in G6PC3." Boztug K., Appaswamy G., Ashikov A., Schaeffer A.A., Salzer U., Diestelhorst J., Germeshausen M., Brandes G., Lee-Gossler J., Noyan F., Gatzke A.-K., Minkov M., Greil J., Kratz C., Petropoulou T., Pellier I., Bellanne-Chantelot C., Rezaei N. , Moenkemoeller K., Irani-Hakimeh N., Bakker H., Gerardy-Schahn R., Zeidler C., Grimbacher B., Welte K., Klein C. N. Engl. J. Med. 360:32-43(2009) [PubMed: 19118303] [Abstract] Cited for: VARIANTS SCN4 PRO-185; HIS-253 AND ARG-262, CHARACTERIZATION OF VARIANT SCN4 HIS-253.
[9]	"Mutations in the G6PC3 gene cause Dursun syndrome." Banka S., Newman W.G., Ozgul R.K., Dursun A. Am. J. Med. Genet. A 152:2609-2611(2010) [PubMed: 20799326] [Abstract] Cited for: VARIANT DURSS VAL-116.
[10]	"Severe congenital neutropenia resulting from G6PC3 deficiency with increased neutrophil CXCR4 expression and myelokathexis." McDermott D.H., De Ravin S.S., Jun H.S., Liu Q., Priel D.A., Noel P., Takemoto C.M., Ojode T., Paul S.M., Dunsmore K.P., Hilligoss D., Marquesen M., Ulrick J., Kuhns D.B., Chou J.Y., Malech H.L., Murphy P.M. Blood 116:2793-2802(2010) [PubMed: 20616219] [Abstract] Cited for: VARIANT SCN4 ARG-260, CHARACTERIZATION OF VARIANT SCN4 ARG-260.
[11]	"Digenic mutations in severe congenital neutropenia." Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M., Welte K. Haematologica 95:1207-1210(2010) [PubMed: 20220065] [Abstract] Cited for: VARIANTS SCN4 LYS-116; GLN-189 AND ARG-260.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	CH471178 Genomic DNA. Translation: EAW51638.1. BC002494 mRNA. Translation: AAH02494.2. BC021574 mRNA. Translation: AAH21574.1.
IPI	IPI00031052.
RefSeq	NP_612396.1. NM_138387.3.
UniGene	Hs.294005.
3D structure databases
ProteinModelPortal	Q9BUM1.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9BUM1.
Polymorphism databases
DMDM	74733234.
Proteomic databases
PeptideAtlas	Q9BUM1.
PRIDE	Q9BUM1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000269097; ENSP00000269097; ENSG00000141349.
GeneID	92579.
KEGG	hsa:92579.
NMPDR	fig|9606.3.peg.13854.
UCSC	uc002iex.1. human.
Organism-specific databases
CTD	92579.
GeneCards	GC17P042148.
H-InvDB	HIX0013874.
HGNC	HGNC:24861. G6PC3.
MIM	611045. gene. 612541. phenotype.
neXtProt	NX_Q9BUM1.
Orphanet	486. Autosomal dominant severe congenital neutropenia. 178503. Dursun syndrome.
PharmGKB	PA134968446.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06462.
GeneTree	ENSGT00510000046465.
HOGENOM	HBG443930.
HOVERGEN	HBG003560.
InParanoid	Q9BUM1.
OMA	TFLGDPK.
OrthoDB	EOG441QCC.
PhylomeDB	Q9BUM1.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules. REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	Q9BUM1.
Bgee	Q9BUM1.
CleanEx	HS_G6PC3.
Genevestigator	Q9BUM1.
Family and domain databases
InterPro	IPR016275. Glucose-6-phosphatase. IPR016118. P_Acid_Pase/Cl_peroxidase_N. IPR000326. P_Acid_Pase_2/haloperoxidase. [Graphical view]
Gene3D	G3DSA:1.20.144.10. P_Acid_Pase/Cl_peroxidase_N. 1 hit.
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
NextBio	77803.
SOURCE	Search...

Entry information

Entry name

G6PC3_HUMAN

Accession

Primary (citable) accession number: Q9BUM1
Secondary accession number(s): Q8WU15

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	March 1, 2004
Last modified:	January 25, 2012
This is version 87 of the entry and version 2 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.