GLCE_BOVIN
ID GLCE_BOVIN Reviewed; 617 AA.
AC O18756;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=D-glucuronyl C5-epimerase;
DE EC=5.1.3.17 {ECO:0000269|PubMed:10727403};
DE AltName: Full=Heparan sulfate C5-epimerase;
DE Short=Hsepi;
DE AltName: Full=Heparin/heparan sulfate:glucuronic acid C5-epimerase;
DE AltName: Full=Heparosan-N-sulfate-glucuronate 5-epimerase;
GN Name=GLCE;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913 {ECO:0000312|EMBL:AAB72083.2};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Lung;
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] OF 174-617, AND PROTEIN SEQUENCE OF 247-259;
RP 272-286; 420-429; 479-486 AND 546-581.
RC TISSUE=Lung;
RX PubMed=9346972; DOI=10.1074/jbc.272.44.28158;
RA Li J.-P., Hagner-McWhirter A., Kjellen L., Palgi J., Jalkanen M.,
RA Lindahl U.;
RT "Biosynthesis of heparin/heparan sulfate. cDNA cloning and expression of D-
RT glucuronyl C5-epimerase from bovine lung.";
RL J. Biol. Chem. 272:28158-28163(1997).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RC TISSUE=Liver;
RX PubMed=10727403; DOI=10.1042/bj3470069;
RA Hagner-McWhirter A., Lindahl U., Li J.-P.;
RT "Biosynthesis of heparin/heparan sulphate: mechanism of epimerization of
RT glucuronyl C-5.";
RL Biochem. J. 347:69-75(2000).
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:10727403,
CC ECO:0000269|PubMed:11274177}.
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:10727403};
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000305|PubMed:10727403}.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC {ECO:0000305|PubMed:10727403}.
CC -!- SUBUNIT: Homodimer. Interacts with HS2ST1.
CC {ECO:0000250|UniProtKB:F1QR43, ECO:0000250|UniProtKB:Q9EPS3}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9EPS3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9EPS3}.
CC -!- SIMILARITY: Belongs to the D-glucuronyl C5-epimerase family.
CC {ECO:0000305}.
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DR EMBL; AF003927; AAB72083.2; -; mRNA.
DR RefSeq; NP_776495.1; NM_174070.2.
DR RefSeq; XP_005211308.1; XM_005211251.3.
DR RefSeq; XP_005211309.1; XM_005211252.3.
DR AlphaFoldDB; O18756; -.
DR SMR; O18756; -.
DR STRING; 9913.ENSBTAP00000001844; -.
DR PaxDb; O18756; -.
DR PRIDE; O18756; -.
DR Ensembl; ENSBTAT00000001844; ENSBTAP00000001844; ENSBTAG00000001405.
DR GeneID; 281195; -.
DR KEGG; bta:281195; -.
DR CTD; 26035; -.
DR VEuPathDB; HostDB:ENSBTAG00000001405; -.
DR VGNC; VGNC:29394; GLCE.
DR eggNOG; KOG3760; Eukaryota.
DR GeneTree; ENSGT00390000006043; -.
DR HOGENOM; CLU_028636_0_0_1; -.
DR InParanoid; O18756; -.
DR OMA; RGVFMYF; -.
DR OrthoDB; 561819at2759; -.
DR TreeFam; TF105869; -.
DR BRENDA; 5.1.3.17; 908.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000001405; Expressed in omental fat pad and 110 other tissues.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
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: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; Direct protein sequencing; Golgi apparatus; Isomerase; Membrane;
KW Metal-binding; Reference proteome; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..617
FT /note="D-glucuronyl C5-epimerase"
FT /id="PRO_0000192644"
FT TOPO_DOM 1..11
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 12..28
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..617
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT BINDING 179
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 184..186
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 201
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 209
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 212
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 237
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 239
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 268
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 392
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 429..432
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 499..500
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 510
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 514
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 560
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 563
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT BINDING 572..581
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT SITE 179
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 186
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 560
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT SITE 578
FT /note="Critical for catalysis"
FT /evidence="ECO:0000250|UniProtKB:F1QR43"
FT CONFLICT 552
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 617 AA; 69985 MW; 8C0A854C24034103 CRC64;
MRCLAARVNY KTLIIICALF TLVTVLLWNK CSSDKAIQVP RHLSSGFRVD ALEKKAAASE
SNNYVNHMAK QSEEAFPQEQ QKAPPVVGGF NNNGGGRVLG LKYEEIDCLI NDEHTIKGRR
EGNEVFLPFT WVEKYFDVYG KVVQYDGYDR FEFSHSYSKV YAQRAPYHPD GVFMSFEGYN
VEVRDRVKCI SGVEGVPLST QWGPQGYFYP IQIAQYGLSH YSKNLTEKPP HIEVYETAED
RDKNSKPNDW TVPKGCFMAS VADKSRFTNV KQFIAPETSE GVSLQLGNTK DFIISFDLKF
LTNGSVSVVL ETTEKNQLFT VHYVSNTQLI AFKERDIYYG IGPRTSWSTV TRDLVTDLRK
GVGLSNTKAV KPTRIMPKKV VRLIAKGKGF LDNITISTTA HMAAFFAASD WLVRNQDEKG
GWPIMVTRKL GEGFKSLEPG WYSAMAQGQA ISTLVRAYLL TKDHIFLNSA LRATAPYKFL
SEQHGVKAVF MNKHDWYEEY PTTPSSFVLN GFMYSLIGLY DLKETAGEKL GKEARSLYER
GMESLKAMLP LYDTGSGTIY DLRHFMLGIA PNLARWDYHT THINQLQLLS TIDESPIFKE
FVKRWKSYLK GSRAKHN
