GLCEB_DANRE
ID GLCEB_DANRE Reviewed; 586 AA.
AC F1QR43; B3DID7; Q6TS32;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=D-glucuronyl C5-epimerase B {ECO:0000303|PubMed:16156897};
DE EC=5.1.3.17 {ECO:0000269|PubMed:25568314, ECO:0000305|PubMed:16156897};
GN Name=glceb {ECO:0000303|PubMed:16156897,
GN ECO:0000312|ZFIN:ZDB-GENE-040630-8};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2] {ECO:0000312|EMBL:AAI63091.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|EMBL:AAQ90467.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2-586, FUNCTION, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=16156897; DOI=10.1186/1471-213x-5-19;
RA Ghiselli G., Farber S.A.;
RT "D-glucuronyl C5-epimerase acts in dorso-ventral axis formation in
RT zebrafish.";
RL BMC Dev. Biol. 5:19-19(2005).
RN [4] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=17195182; DOI=10.1002/dvdy.21051;
RA Cadwallader A.B., Yost H.J.;
RT "Combinatorial expression patterns of heparan sulfate sulfotransferases in
RT zebrafish: III. 2-O-sulfotransferase and C5-epimerases.";
RL Dev. Dyn. 236:581-586(2007).
RN [5] {ECO:0007744|PDB:4PW2, ECO:0007744|PDB:4PXQ}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN APO FORM AND IN COMPLEX WITH
RP HEPARIN HEXASACCHARIDE, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP PATHWAY, SUBUNIT, AND MUTAGENESIS OF TYR-150; ARG-155; ARG-157; TYR-178;
RP TYR-180; ARG-397; TYR-469; TYR-483; TYR-529; ARG-532; ARG-544; TYR-547;
RP HIS-585 AND ASN-586.
RX PubMed=25568314; DOI=10.1074/jbc.m114.602201;
RA Qin Y., Ke J., Gu X., Fang J., Wang W., Cong Q., Li J., Tan J.,
RA Brunzelle J.S., Zhang C., Jiang Y., Melcher K., Li J.P., Xu H.E., Ding K.;
RT "Structural and functional study of D-glucuronyl C5-epimerase.";
RL J. Biol. Chem. 290:4620-4630(2015).
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 (PubMed:16156897, PubMed:25568314).
CC Plays a role in dorso-ventral axis specification during early
CC development, together with glcea, where it may potentiate signaling via
CC the BMP pathway (PubMed:16156897). {ECO:0000269|PubMed:16156897,
CC ECO:0000269|PubMed:25568314}.
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:25568314, ECO:0000305|PubMed:16156897};
CC -!- ACTIVITY REGULATION: Inhibited by O-sulfated heparin, which is produced
CC by a downstream step in the heparin biosynthesis pathway.
CC {ECO:0000269|PubMed:25568314}.
CC -!- PATHWAY: Glycan metabolism; heparan sulfate biosynthesis.
CC {ECO:0000305|PubMed:16156897, ECO:0000305|PubMed:25568314}.
CC -!- PATHWAY: Glycan metabolism; heparin biosynthesis.
CC {ECO:0000305|PubMed:16156897, ECO:0000305|PubMed:25568314}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25568314}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9EPS3}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9EPS3}.
CC -!- DEVELOPMENTAL STAGE: Detected from 0.5 to 48 hours post-fertilization
CC (hpf) (PubMed:16156897). At 24-36 hpf, expressed in adaxial mesoderm,
CC somites, notochord, floorplate, hypochord, tail bud, eye,
CC telencephalon, diencephalon, midbrain, hindbrain and otic vesicle
CC (PubMed:17195182). {ECO:0000269|PubMed:16156897,
CC ECO:0000269|PubMed:17195182}.
CC -!- DISRUPTION PHENOTYPE: Double morpholino knockdown of both glcea and
CC glceb results in dorsalized embryos, with reduced ventral tail fin,
CC kinked tail and an enlarged heart cavity. In severe cases there is
CC significant shortening of the body and tail coiling. Epimerase activity
CC is reduced. Expression of the dorsalizing factor chordin is expanded,
CC whereas expression of bmp2b is reduced, notably in the tail. Expression
CC of gata1 in blood islets is also reduced.
CC {ECO:0000269|PubMed:16156897}.
CC -!- SIMILARITY: Belongs to the D-glucuronyl C5-epimerase family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-2 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI63091.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI63093.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; BX914196; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC163091; AAI63091.1; ALT_INIT; mRNA.
DR EMBL; BC163093; AAI63093.1; ALT_INIT; mRNA.
DR EMBL; AY388517; AAQ90467.1; -; mRNA.
DR RefSeq; NP_998014.1; NM_212849.1.
DR RefSeq; XP_005168896.1; XM_005168839.2.
DR PDB; 4PW2; X-ray; 1.90 A; A=1-585.
DR PDB; 4PXQ; X-ray; 2.20 A; A/B=1-585.
DR PDBsum; 4PW2; -.
DR PDBsum; 4PXQ; -.
DR AlphaFoldDB; F1QR43; -.
DR SMR; F1QR43; -.
DR STRING; 7955.ENSDARP00000090760; -.
DR PaxDb; F1QR43; -.
DR Ensembl; ENSDART00000099988; ENSDARP00000090760; ENSDARG00000068981.
DR Ensembl; ENSDART00000193436; ENSDARP00000151285; ENSDARG00000068981.
DR GeneID; 100007670; -.
DR KEGG; dre:100007670; -.
DR CTD; 100007670; -.
DR ZFIN; ZDB-GENE-040630-8; glceb.
DR eggNOG; KOG3760; Eukaryota.
DR GeneTree; ENSGT00390000006043; -.
DR InParanoid; F1QR43; -.
DR OMA; RGVFMYF; -.
DR OrthoDB; 561819at2759; -.
DR PhylomeDB; F1QR43; -.
DR TreeFam; TF105869; -.
DR BRENDA; 5.1.3.17; 928.
DR UniPathway; UPA00756; -.
DR UniPathway; UPA00862; -.
DR PRO; PR:F1QR43; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 7.
DR Bgee; ENSDARG00000068981; Expressed in early embryo and 29 other tissues.
DR ExpressionAtlas; F1QR43; baseline.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
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:0047464; F:heparosan-N-sulfate-glucuronate 5-epimerase activity; IDA:ZFIN.
DR GO; GO:0042802; F:identical protein binding; IPI:ZFIN.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0015012; P:heparan sulfate proteoglycan biosynthetic process; IBA:GO_Central.
DR GO; GO:0030210; P:heparin biosynthetic process; IEA:UniProtKB-UniPathway.
DR DisProt; DP02883; -.
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 3D-structure; Calcium; Golgi apparatus; Isomerase; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix.
FT CHAIN 1..586
FT /note="D-glucuronyl C5-epimerase B"
FT /id="PRO_0000442920"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 9..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..586
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 40..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 42..68
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 150
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 155..157
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 183
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 210
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
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 361
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O94923"
FT BINDING 398..401
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 483
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 532
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 544..550
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT BINDING 568
FT /ligand="substrate"
FT /evidence="ECO:0007744|PDB:4PXQ"
FT SITE 150
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:25568314"
FT SITE 157
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:25568314"
FT SITE 529
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:25568314"
FT SITE 547
FT /note="Critical for catalysis"
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 150
FT /note="Y->F: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 155
FT /note="R->A: Moderately reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 157
FT /note="R->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 178
FT /note="Y->F: Moderately reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 180
FT /note="Y->F: Moderately reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 397
FT /note="R->A: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 469
FT /note="Y->A,F: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 483
FT /note="Y->F: Moderately reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 529
FT /note="Y->A,F: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 532
FT /note="R->A: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 544
FT /note="R->A: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 547
FT /note="Y->A,F: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 585
FT /note="H->A: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT MUTAGEN 586
FT /note="N->A: Significantly reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:25568314"
FT CONFLICT 8
FT /note="R -> G (in Ref. 3; AAQ90467)"
FT /evidence="ECO:0000305"
FT CONFLICT 43
FT /note="R -> Q (in Ref. 3; AAQ90467)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="Q -> E (in Ref. 3; AAQ90467)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="T -> R (in Ref. 3; AAQ90467)"
FT /evidence="ECO:0000305"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:4PW2"
FT TURN 82..84
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 100..107
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:4PW2"
FT TURN 163..165
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4PXQ"
FT HELIX 181..197
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:4PXQ"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:4PXQ"
FT STRAND 226..230
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 235..237
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 251..259
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 262..272
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 274..286
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 288..295
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 317..322
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 323..331
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 346..367
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 370..384
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 413..430
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 433..441
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 442..447
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 450..452
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 456..459
FT /evidence="ECO:0007829|PDB:4PW2"
FT TURN 460..462
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 463..466
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 478..499
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 501..517
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 518..521
FT /evidence="ECO:0007829|PDB:4PW2"
FT STRAND 524..531
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 532..536
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 545..561
FT /evidence="ECO:0007829|PDB:4PW2"
FT HELIX 565..577
FT /evidence="ECO:0007829|PDB:4PW2"
FT TURN 578..580
FT /evidence="ECO:0007829|PDB:4PW2"
SQ SEQUENCE 586 AA; 66256 MW; 3F4FE54C344B30E4 CRC64;
MMRCLAARVH YKTLIVICAL LSLLTVLLWN KCTSEKALRF LPRHPQPPPS PKIDSHPQQP
QPPEPPPVVG GVRYEEIDCL INDDATIKGR REGSEVYMPF SWMEKYFEVY GKVVQYDGYD
RFEFSHSYSK VYAQREQYHP NGVFMSFEGY NVEVRDRVKC ISGVEGVPLS TQWGPQGYFY
AIQIAQYGLS HYSKNLTERP PHVEVYDTAE ERDSRSSAWT VPKGCSLTRV YDKTRATSVR
QFSAPENSEG VSLPLGNTKD FIISFDLKFT SNGSVSVILE TTEKGPPFVI HYVTTTQLIL
LKDRDITYGI GPRTTWTTVT RDLLTDLRKG IGLSNTKAVK ATKTMPRRVV KLVVHGTGTI
DNITISTTSH MAAFYAASDW LVRNQDERGG WPIMVTRKLG EGFRALEPGW YSAMAQGQAM
STLVRAYLMT KDDTYLKAAL RATGPFKLPS EQHGVKAVFM NKYDWYEEYP TIPSSFVLNG
FIYSLIGLFD LAQTAGEKLG RDAGQLYSKG MESLKVMLPL YDTGSGTIYD LRHFILGTAP
NLARWDYHTT HINQLQLLGT IDNSPIFRDS VKRWKSYLKG GRAKHN
