GLCE_MOUSE
ID GLCE_MOUSE Reviewed; 618 AA.
AC Q9EPS3; Q505E6; Q99MM0;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=D-glucuronyl C5-epimerase;
DE EC=5.1.3.17 {ECO:0000269|PubMed:11279150, ECO:0000269|PubMed:16532012};
DE AltName: Full=Heparan sulfate C5-epimerase;
DE Short=Hsepi;
DE AltName: Full=Heparin sulfate C5-epimerase;
DE AltName: Full=Heparin/heparan sulfate:glucuronic acid C5-epimerase;
DE AltName: Full=Heparosan-N-sulfate-glucuronate 5-epimerase;
GN Name=Glce;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAG42004.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, FUNCTION, AND PATHWAY.
RC STRAIN=BALB/cJ; TISSUE=Liver, and Mast cell;
RX PubMed=11274177; DOI=10.1074/jbc.m011783200;
RA Li J.-P., Gong F., El Darwish K., Jalkanen M., Lindahl U.;
RT "Characterization of the D-glucuronyl C5-epimerase involved in the
RT biosynthesis of heparin and heparan sulfate.";
RL J. Biol. Chem. 276:20069-20077(2001).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, PATHWAY, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Mast cell;
RX PubMed=11279150; DOI=10.1074/jbc.m100880200;
RA Crawford B.E., Olson S.K., Esko J.D., Pinhal M.A.S.;
RT "Cloning, Golgi localization, and enzyme activity of the full-length
RT heparin/heparan sulfate-glucuronic acid C5-epimerase.";
RL J. Biol. Chem. 276:21538-21543(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH HS2ST1.
RX PubMed=11687650; DOI=10.1073/pnas.241175798;
RA Pinhal M.A.S., Smith B., Olson S., Aikawa J., Kimata K., Esko J.D.;
RT "Enzyme interactions in heparan sulfate biosynthesis: uronosyl 5-epimerase
RT and 2-O-sulfotransferase interact in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12984-12989(2001).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=12788935; DOI=10.1074/jbc.c300219200;
RA Li J.P., Gong F., Hagner-McWhirter A., Forsberg E., Abrink M.,
RA Kisilevsky R., Zhang X., Lindahl U.;
RT "Targeted disruption of a murine glucuronyl C5-epimerase gene results in
RT heparan sulfate lacking L-iduronic acid and in neonatal lethality.";
RL J. Biol. Chem. 278:28363-28366(2003).
RN [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16532012; DOI=10.1038/nchembio777;
RA Feyerabend T.B., Li J.P., Lindahl U., Rodewald H.R.;
RT "Heparan sulfate C5-epimerase is essential for heparin biosynthesis in mast
RT cells.";
RL Nat. Chem. Biol. 2:195-196(2006).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20208005; DOI=10.4049/jimmunol.0902200;
RA Reijmers R.M., Vondenhoff M.F., Roozendaal R., Kuil A., Li J.P.,
RA Spaargaren M., Pals S.T., Mebius R.E.;
RT "Impaired lymphoid organ development in mice lacking the heparan sulfate
RT modifying enzyme glucuronyl C5-epimerase.";
RL J. Immunol. 184:3656-3664(2010).
CC -!- FUNCTION: Converts D-glucuronic acid residues adjacent to N-sulfate
CC sugar residues to L-iduronic acid residues, both in maturing heparan
CC sulfate (HS) and heparin chains. This is important for further
CC modifications that determine the specificity of interactions between
CC these glycosaminoglycans and proteins. {ECO:0000269|PubMed:11274177,
CC ECO:0000269|PubMed:11279150, ECO:0000269|PubMed:16532012,
CC ECO:0000269|PubMed:20208005}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[heparosan-N-sulfate](n) = [heparan-N-sulfate](n);
CC Xref=Rhea:RHEA:20197, Rhea:RHEA-COMP:9556, Rhea:RHEA-COMP:9557,
CC ChEBI:CHEBI:58041, ChEBI:CHEBI:58287; EC=5.1.3.17;
CC Evidence={ECO:0000269|PubMed:11279150, ECO:0000269|PubMed:16532012};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000305|PubMed:11274177, ECO:0000305|PubMed:11279150}.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC {ECO:0000305|PubMed:11274177, ECO:0000305|PubMed:11279150}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with HS2ST1
CC (PubMed:11687650). {ECO:0000250|UniProtKB:F1QR43,
CC ECO:0000269|PubMed:11687650}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:11279150}; Single-pass type II membrane protein
CC {ECO:0000269|PubMed:11279150}.
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in lung and
CC lowest levels in spleen. {ECO:0000269|PubMed:11274177}.
CC -!- DISRUPTION PHENOTYPE: Perinatal lethality. Pups die shortly after
CC birth, apparently from respiratory failure. Mice show immature lung
CC structure, lack kidneys, have abnormally small thymus and spleen,
CC defects in inguinal lymph node development and in blood vessel
CC formation proximal to the inguinal lymph nodes, and display important
CC skeletal deficiencies. Mutant mice have heparan and heparin chains that
CC are deficient in iduronic acid residues, and that therefore have
CC altered O-sulfation patterns. {ECO:0000269|PubMed:12788935,
CC ECO:0000269|PubMed:20208005}.
CC -!- SIMILARITY: Belongs to the D-glucuronyl C5-epimerase family.
CC {ECO:0000305}.
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DR EMBL; AF330049; AAK26246.1; -; mRNA.
DR EMBL; AF325532; AAG42004.1; -; mRNA.
DR EMBL; CH466522; EDL26018.1; -; Genomic_DNA.
DR EMBL; BC094587; AAH94587.1; -; mRNA.
DR CCDS; CCDS23262.1; -.
DR RefSeq; NP_201577.3; NM_033320.4.
DR RefSeq; XP_006511634.1; XM_006511571.2.
DR RefSeq; XP_006511635.1; XM_006511572.2.
DR AlphaFoldDB; Q9EPS3; -.
DR SMR; Q9EPS3; -.
DR BioGRID; 220233; 2.
DR STRING; 10090.ENSMUSP00000139949; -.
DR GlyConnect; 2253; 2 N-Linked glycans (1 site).
DR GlyGen; Q9EPS3; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q9EPS3; -.
DR PhosphoSitePlus; Q9EPS3; -.
DR SwissPalm; Q9EPS3; -.
DR EPD; Q9EPS3; -.
DR jPOST; Q9EPS3; -.
DR MaxQB; Q9EPS3; -.
DR PaxDb; Q9EPS3; -.
DR PeptideAtlas; Q9EPS3; -.
DR PRIDE; Q9EPS3; -.
DR ProteomicsDB; 271227; -.
DR Antibodypedia; 26368; 67 antibodies from 13 providers.
DR DNASU; 93683; -.
DR Ensembl; ENSMUST00000034785; ENSMUSP00000034785; ENSMUSG00000032252.
DR Ensembl; ENSMUST00000185675; ENSMUSP00000139949; ENSMUSG00000032252.
DR GeneID; 93683; -.
DR KEGG; mmu:93683; -.
DR UCSC; uc009qac.1; mouse.
DR CTD; 26035; -.
DR MGI; MGI:2136405; Glce.
DR VEuPathDB; HostDB:ENSMUSG00000032252; -.
DR eggNOG; KOG3760; Eukaryota.
DR GeneTree; ENSGT00390000006043; -.
DR HOGENOM; CLU_028636_0_0_1; -.
DR InParanoid; Q9EPS3; -.
DR OMA; RGVFMYF; -.
DR OrthoDB; 561819at2759; -.
DR PhylomeDB; Q9EPS3; -.
DR TreeFam; TF105869; -.
DR BRENDA; 5.1.3.17; 3474.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR BioGRID-ORCS; 93683; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Glce; mouse.
DR PRO; PR:Q9EPS3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9EPS3; protein.
DR Bgee; ENSMUSG00000032252; Expressed in saccule of membranous labyrinth and 259 other tissues.
DR ExpressionAtlas; Q9EPS3; baseline and differential.
DR Genevisible; Q9EPS3; MM.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0047464; F:heparosan-N-sulfate-glucuronate 5-epimerase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0016857; F:racemase and epimerase activity, acting on carbohydrates and derivatives; IDA:UniProtKB.
DR GO; GO:0050379; F:UDP-glucuronate 5'-epimerase activity; TAS:Reactome.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030210; P:heparin biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR010598; C5-epim_C.
DR InterPro; IPR039721; C5-epimerase.
DR PANTHER; PTHR13174; PTHR13174; 1.
DR Pfam; PF06662; C5-epim_C; 1.
PE 1: Evidence at protein level;
KW Calcium; Golgi apparatus; Isomerase; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..618
FT /note="D-glucuronyl C5-epimerase"
FT /id="PRO_0000192646"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..618
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 180
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 185..187
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 210
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 216
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 238
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 240
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 269
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 430..433
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 500..501
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 511
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 515
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 561
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 564
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 573..582
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT SITE 180
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 187
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 561
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 579
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT CONFLICT 537
FT /note="S -> P (in Ref. 2; AAG42004)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 70089 MW; BF962A24459A446A CRC64;
MRCLAARVNY KTLIIICALF TLVTVLLWNK CSSDKAIQFP RHLSSGFRVD GLEKRSAASE
SNHYANHIAK QQSEEAFPQE QQKAPPVVGG FNSNGGSKVL GLKYEEIDCL INDEHTIKGR
REGNEVFLPF TWVEKYFDVY GKVVQYDGYD RFEFSHSYSK VYAQRSPYHP DGVFMSFEGY
NVEVRDRVKC ISGVEGVPLS TQWGPQGYFY PIQIAQYGLS HYSKNLTEKP PHIEVYETAE
DRDRNIRPNE WTVPKGCFMA SVADKSRSTN VKQFIAPETS EGVSLQLGNT KDFIISFDLK
LLTNGSVSVV LETTEKNQLF TVHYVSNTQL IAFRDRDIYY GIGPRTSWST VTRDLVTDLR
KGVGLSNTKA VKPTKIMPKK VVRLIAKGKG FLDNITISTT AHMAAFFAAS DWLVRNQDEK
GGWPIMVTRK LGEGFKSLEP GWYSAMAQGQ AISTLVRAYL LTKDYVFLSS ALRATAPYKF
PSEQHGVKAV FMNKHDWYEE YPTTPSSFVL NGFMYSLIGL YDLKETAGET LGKEARSLYE
RGMESLKAML PLYDTGSGTI YDLRHFMLGI APNLARWDYH TTHINQLQLL STIDESPIFK
EFVKRWKSYL KGSRAKHN
