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Protein

D-glucuronyl C5-epimerase

Gene

Glce

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts D-glucuronic acid residues adjacent to N-sulfate sugar residues to L-iduronic acid residues, both in maturing heparan sulfate (HS) and heparin chains. This is important for further modifications that determine the specificity of interactions between these glycosaminoglycans and proteins.4 Publications

Catalytic activityi

Epimerization of D-glucuronate in heparosan-N-sulfate to L-iduronate.2 Publications

Pathwayi: heparan sulfate biosynthesis

This protein is involved in the pathway heparan sulfate biosynthesis, which is part of Glycan metabolism.
View all proteins of this organism that are known to be involved in the pathway heparan sulfate biosynthesis and in Glycan metabolism.

Pathwayi: heparin biosynthesis

This protein is involved in the pathway heparin biosynthesis, which is part of Glycan metabolism.
View all proteins of this organism that are known to be involved in the pathway heparin biosynthesis and in Glycan metabolism.

GO - Molecular functioni

GO - Biological processi

  • heparan sulfate proteoglycan biosynthetic process Source: UniProtKB
  • heparin biosynthetic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Enzyme and pathway databases

BRENDAi5.1.3.17. 3474.
UniPathwayiUPA00756.
UPA00862.

Names & Taxonomyi

Protein namesi
Recommended name:
D-glucuronyl C5-epimerase (EC:5.1.3.172 Publications)
Alternative name(s):
Heparan sulfate C5-epimerase
Short name:
Hsepi
Heparin sulfate C5-epimerase
Heparin/heparan sulfate:glucuronic acid C5-epimerase
Heparosan-N-sulfate-glucuronate 5-epimerase
Gene namesi
Name:Glce
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:2136405. Glce.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1111CytoplasmicSequence analysisAdd
BLAST
Transmembranei12 – 2918Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini30 – 618589LumenalSequence analysisAdd
BLAST

GO - Cellular componenti

  • Golgi apparatus Source: UniProtKB
  • Golgi membrane Source: Reactome
  • integral component of membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Perinatal lethality. Pups die shortly after birth, apparently from respiratory failure. Mice show immature lung structure, lack kidneys, have abnormally small thymus and spleen, defects in inguinal lymph node development and in blood vessel formation proximal to the inguinal lymph nodes, and display important skeletal deficiencies. Mutant mice have heparan and heparin chains that are deficient in iduronic acid residues, and that therefore have altered O-sulfation patterns.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 618618D-glucuronyl C5-epimerasePRO_0000192646Add
BLAST

Proteomic databases

EPDiQ9EPS3.
MaxQBiQ9EPS3.
PaxDbiQ9EPS3.
PRIDEiQ9EPS3.

PTM databases

iPTMnetiQ9EPS3.
PhosphoSiteiQ9EPS3.

Expressioni

Tissue specificityi

Widely expressed with highest levels in lung and lowest levels in spleen.1 Publication

Gene expression databases

BgeeiQ9EPS3.
CleanExiMM_GLCE.
ExpressionAtlasiQ9EPS3. baseline and differential.
GenevisibleiQ9EPS3. MM.

Interactioni

Subunit structurei

Interacts with HS2ST1.1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034785.

Structurei

3D structure databases

ProteinModelPortaliQ9EPS3.
SMRiQ9EPS3. Positions 101-618.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the D-glucuronyl C5-epimerase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3760. Eukaryota.
ENOG410XQJ3. LUCA.
GeneTreeiENSGT00390000006043.
HOGENOMiHOG000230542.
HOVERGENiHBG031576.
InParanoidiQ9EPS3.
KOiK01793.
OMAiWDYHATH.
OrthoDBiEOG71K62J.
TreeFamiTF105869.

Family and domain databases

InterProiIPR010598. C5-epim.
[Graphical view]
PfamiPF06662. C5-epim_C. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9EPS3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCLAARVNY KTLIIICALF TLVTVLLWNK CSSDKAIQFP RHLSSGFRVD
60 70 80 90 100
GLEKRSAASE SNHYANHIAK QQSEEAFPQE QQKAPPVVGG FNSNGGSKVL
110 120 130 140 150
GLKYEEIDCL INDEHTIKGR REGNEVFLPF TWVEKYFDVY GKVVQYDGYD
160 170 180 190 200
RFEFSHSYSK VYAQRSPYHP DGVFMSFEGY NVEVRDRVKC ISGVEGVPLS
210 220 230 240 250
TQWGPQGYFY PIQIAQYGLS HYSKNLTEKP PHIEVYETAE DRDRNIRPNE
260 270 280 290 300
WTVPKGCFMA SVADKSRSTN VKQFIAPETS EGVSLQLGNT KDFIISFDLK
310 320 330 340 350
LLTNGSVSVV LETTEKNQLF TVHYVSNTQL IAFRDRDIYY GIGPRTSWST
360 370 380 390 400
VTRDLVTDLR KGVGLSNTKA VKPTKIMPKK VVRLIAKGKG FLDNITISTT
410 420 430 440 450
AHMAAFFAAS DWLVRNQDEK GGWPIMVTRK LGEGFKSLEP GWYSAMAQGQ
460 470 480 490 500
AISTLVRAYL LTKDYVFLSS ALRATAPYKF PSEQHGVKAV FMNKHDWYEE
510 520 530 540 550
YPTTPSSFVL NGFMYSLIGL YDLKETAGET LGKEARSLYE RGMESLKAML
560 570 580 590 600
PLYDTGSGTI YDLRHFMLGI APNLARWDYH TTHINQLQLL STIDESPIFK
610
EFVKRWKSYL KGSRAKHN
Length:618
Mass (Da):70,089
Last modified:July 27, 2011 - v2
Checksum:iBF962A24459A446A
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti537 – 5371S → P in AAG42004 (PubMed:11279150).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330049 mRNA. Translation: AAK26246.1.
AF325532 mRNA. Translation: AAG42004.1.
CH466522 Genomic DNA. Translation: EDL26018.1.
BC094587 mRNA. Translation: AAH94587.1.
CCDSiCCDS23262.1.
RefSeqiNP_201577.3. NM_033320.4.
XP_006511634.1. XM_006511571.1.
XP_006511635.1. XM_006511572.1.
UniGeneiMm.24411.
Mm.447195.

Genome annotation databases

EnsembliENSMUST00000034785; ENSMUSP00000034785; ENSMUSG00000032252.
ENSMUST00000185675; ENSMUSP00000139949; ENSMUSG00000032252.
GeneIDi93683.
KEGGimmu:93683.
UCSCiuc009qac.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF330049 mRNA. Translation: AAK26246.1.
AF325532 mRNA. Translation: AAG42004.1.
CH466522 Genomic DNA. Translation: EDL26018.1.
BC094587 mRNA. Translation: AAH94587.1.
CCDSiCCDS23262.1.
RefSeqiNP_201577.3. NM_033320.4.
XP_006511634.1. XM_006511571.1.
XP_006511635.1. XM_006511572.1.
UniGeneiMm.24411.
Mm.447195.

3D structure databases

ProteinModelPortaliQ9EPS3.
SMRiQ9EPS3. Positions 101-618.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000034785.

PTM databases

iPTMnetiQ9EPS3.
PhosphoSiteiQ9EPS3.

Proteomic databases

EPDiQ9EPS3.
MaxQBiQ9EPS3.
PaxDbiQ9EPS3.
PRIDEiQ9EPS3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034785; ENSMUSP00000034785; ENSMUSG00000032252.
ENSMUST00000185675; ENSMUSP00000139949; ENSMUSG00000032252.
GeneIDi93683.
KEGGimmu:93683.
UCSCiuc009qac.1. mouse.

Organism-specific databases

CTDi26035.
MGIiMGI:2136405. Glce.

Phylogenomic databases

eggNOGiKOG3760. Eukaryota.
ENOG410XQJ3. LUCA.
GeneTreeiENSGT00390000006043.
HOGENOMiHOG000230542.
HOVERGENiHBG031576.
InParanoidiQ9EPS3.
KOiK01793.
OMAiWDYHATH.
OrthoDBiEOG71K62J.
TreeFamiTF105869.

Enzyme and pathway databases

UniPathwayiUPA00756.
UPA00862.
BRENDAi5.1.3.17. 3474.

Miscellaneous databases

ChiTaRSiGlce. mouse.
NextBioi351404.
PROiQ9EPS3.
SOURCEiSearch...

Gene expression databases

BgeeiQ9EPS3.
CleanExiMM_GLCE.
ExpressionAtlasiQ9EPS3. baseline and differential.
GenevisibleiQ9EPS3. MM.

Family and domain databases

InterProiIPR010598. C5-epim.
[Graphical view]
PfamiPF06662. C5-epim_C. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Characterization of the D-glucuronyl C5-epimerase involved in the biosynthesis of heparin and heparan sulfate."
    Li J.-P., Gong F., El Darwish K., Jalkanen M., Lindahl U.
    J. Biol. Chem. 276:20069-20077(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION.
    Strain: BALB/cJ.
    Tissue: Liver and Mast cell.
  2. "Cloning, Golgi localization, and enzyme activity of the full-length heparin/heparan sulfate-glucuronic acid C5-epimerase."
    Crawford B.E., Olson S.K., Esko J.D., Pinhal M.A.S.
    J. Biol. Chem. 276:21538-21543(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Mast cell.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  5. "Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase and 2-O-sulfotransferase interact in vivo."
    Pinhal M.A.S., Smith B., Olson S., Aikawa J., Kimata K., Esko J.D.
    Proc. Natl. Acad. Sci. U.S.A. 98:12984-12989(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HS2ST1.
  6. "Targeted disruption of a murine glucuronyl C5-epimerase gene results in heparan sulfate lacking L-iduronic acid and in neonatal lethality."
    Li J.P., Gong F., Hagner-McWhirter A., Forsberg E., Abrink M., Kisilevsky R., Zhang X., Lindahl U.
    J. Biol. Chem. 278:28363-28366(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  7. "Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast cells."
    Feyerabend T.B., Li J.P., Lindahl U., Rodewald H.R.
    Nat. Chem. Biol. 2:195-196(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  8. "Impaired lymphoid organ development in mice lacking the heparan sulfate modifying enzyme glucuronyl C5-epimerase."
    Reijmers R.M., Vondenhoff M.F., Roozendaal R., Kuil A., Li J.P., Spaargaren M., Pals S.T., Mebius R.E.
    J. Immunol. 184:3656-3664(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.

Entry informationi

Entry nameiGLCE_MOUSE
AccessioniPrimary (citable) accession number: Q9EPS3
Secondary accession number(s): Q505E6, Q99MM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: July 27, 2011
Last modified: March 16, 2016
This is version 107 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.