Skip Header

 
Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q9BUM1 (G6PC3_HUMAN)

Last modified July 7, 2009. Version 61. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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

Defects in G6PC3 are the cause of autosomal recessive severe congenital neutropenia 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.

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.)

KM=2.0 mM for glucose-6-phosphate (at pH 6.5.)

Ontologies

Keywords
   Biological processGluconeogenesis
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainTransmembrane
   Molecular functionHydrolase
   Technical termComplete proteome
Gene Ontology (GO)
   Biological processgluconeogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionglucose-6-phosphatase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 346346Glucose-6-phosphatase 3
PRO_0000334512

Regions

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

Sites

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

Natural variations

Natural variant1851L → P in SCN4.
VAR_055156
Natural variant2161T → I: dbSNP rs34406052.
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.
VAR_055157
Natural variant2621G → R in SCN4.
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
Q9BUM1-1 [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: 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. 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: 19118303] [Abstract]
Cited for: VARIANTS SCN4 PRO-185; HIS-253 AND ARG-262, CHARACTERIZATION OF VARIANT SCN4 HIS-253.

Cross-references

Sequence databases

CH471178 Genomic DNA. Translation: EAW51638.1.
BC002494 mRNA. Translation: AAH02494.2.
BC021574 mRNA. Translation: AAH21574.1.
IPIIPI00031052.
RefSeqNP_612396.1.
UniGeneHs.294005

3D structure databases

ModBaseSearch...

Proteomic databases

PeptideAtlasQ9BUM1.
PRIDEQ9BUM1.

Genome annotation databases

EnsemblENSG00000141349. Homo sapiens. [Contig view]
GeneID92579.
KEGGhsa:92579.
NMPDRfig|9606.3.peg.13854.
UCSCuc002iex.1. human.

Organism-specific databases

GeneCardsGC17P039503.
HGNCHGNC:24861. G6PC3.
MIM611045. gene.
612541. phenotype.
Orphanet42738. Neutropenia, congenital.
486. Severe congenital neutropenia.
PharmGKBPA134968446.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ9BUM1.
HOVERGENQ9BUM1.
OMAQ9BUM1. GIAVLWI.

Gene expression databases

ArrayExpressQ9BUM1.
BgeeQ9BUM1.
CleanExHS_G6PC3.

Family and domain databases

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]
ProtoNetSearch...

Other Resources

NextBio77803.
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: July 7, 2009
This is version 61 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 17

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents