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Q9BUM1 (G6PC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 108. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Neutropenia, severe congenital 4, autosomal recessive (SCN4) [MIM:612541]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.10 Ref.11

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. 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)

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 346346Glucose-6-phosphatase 3
PRO_0000334512

Regions

Topological domain1 – 2424Lumenal Potential
Transmembrane25 – 4521Helical; Potential
Topological domain46 – 549Cytoplasmic Potential
Transmembrane55 – 7521Helical; Potential
Topological domain76 – 11439Lumenal Potential
Transmembrane115 – 13521Helical; Potential
Topological domain136 – 14611Cytoplasmic Potential
Transmembrane147 – 16418Helical; Potential
Topological domain165 – 1695Lumenal Potential
Transmembrane170 – 18617Helical; Potential
Topological domain187 – 19711Cytoplasmic Potential
Transmembrane198 – 21821Helical; Potential
Topological domain219 – 25436Lumenal Potential
Transmembrane255 – 27319Helical; Potential
Topological domain274 – 28310Cytoplasmic Potential
Transmembrane284 – 30421Helical; Potential
Topological domain305 – 3073Lumenal Potential
Transmembrane308 – 32821Helical; Potential
Topological domain329 – 34618Cytoplasmic Potential

Sites

Active site1141Proton donor Potential
Active site1671Nucleophile Ref.6
Binding site791Substrate Potential
Binding site1611Substrate Potential

Natural variations

Natural variant1161M → K in SCN4; the patient also carries mutation Thr-166 in ELANE. Ref.11
VAR_064508
Natural variant1161M → V in DURSS. Ref.9
VAR_064509
Natural variant1851L → P in SCN4. Ref.8
VAR_055156
Natural variant1891R → Q in SCN4. Ref.11
Corresponds to variant rs140294222 [ dbSNP | Ensembl ].
VAR_064510
Natural variant2161T → I.
Corresponds to variant rs34406052 [ dbSNP | Ensembl ].
VAR_043378
Natural variant2531R → 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 variant2601G → R in SCN4; loss of function. Ref.10 Ref.11
VAR_064511
Natural variant2621G → R in SCN4. Ref.8
VAR_055158

Experimental info

Mutagenesis791R → A: Loss of catalytic activity. Ref.5
Mutagenesis1141H → A: Loss of catalytic activity. Ref.5
Mutagenesis1671H → A: Loss of catalytic activity. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q9BUM1 [UniParc].

Last modified March 1, 2004. Version 2.
Checksum: 55C1F322E59C8439

FASTA34638,735
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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.
RefSeqNP_612396.1. NM_138387.3.
UniGeneHs.294005.

3D structure databases

ProteinModelPortalQ9BUM1.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000269097.

PTM databases

PhosphoSiteQ9BUM1.

Polymorphism databases

DMDM74733234.

Proteomic databases

PaxDbQ9BUM1.
PeptideAtlasQ9BUM1.
PRIDEQ9BUM1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269097; ENSP00000269097; ENSG00000141349.
GeneID92579.
KEGGhsa:92579.
UCSCuc002iex.3. human.

Organism-specific databases

CTD92579.
GeneCardsGC17P042148.
H-InvDBHIX0013874.
HGNCHGNC:24861. G6PC3.
MIM611045. gene.
612541. phenotype.
neXtProtNX_Q9BUM1.
Orphanet331176. Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.
PharmGKBPA134968446.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82628.
HOGENOMHOG000264239.
HOVERGENHBG003560.
InParanoidQ9BUM1.
KOK01084.
OMAKWFLFGD.
OrthoDBEOG73NG4N.
PhylomeDBQ9BUM1.
TreeFamTF324388.

Enzyme and pathway databases

BioCycMetaCyc:HS13873-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.
SABIO-RKQ9BUM1.
UniPathwayUPA00138.

Gene expression databases

ArrayExpressQ9BUM1.
BgeeQ9BUM1.
CleanExHS_G6PC3.
GenevestigatorQ9BUM1.

Family and domain databases

Gene3D1.20.144.10. 1 hit.
InterProIPR016275. Glucose-6-phosphatase.
IPR000326. P_Acid_Pase_2/haloperoxidase.
[Graphical view]
PfamPF01569. PAP2. 1 hit.
[Graphical view]
PIRSFPIRSF000905. Glucose-6-phosphatase. 1 hit.
SMARTSM00014. acidPPc. 1 hit.
[Graphical view]
SUPFAMSSF48317. SSF48317. 1 hit.
ProtoNetSearch...

Other

ChiTaRSG6PC3. human.
GeneWikiG6PC3.
GenomeRNAi92579.
NextBio77803.
PROQ9BUM1.
SOURCESearch...

Entry information

Entry nameG6PC3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM