PLOD_CAEEL
ID PLOD_CAEEL Reviewed; 730 AA.
AC Q20679;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Multifunctional procollagen lysine hydroxylase and glycosyltransferase;
DE AltName: Full=Lethal protein 268;
DE Includes:
DE RecName: Full=Procollagen-lysine,2-oxoglutarate 5-dioxygenase;
DE EC=1.14.11.4 {ECO:0000250|UniProtKB:O60568};
DE AltName: Full=Lysyl hydroxylase;
DE Short=LH;
DE Includes:
DE RecName: Full=Procollagen glycosyltransferase;
DE EC=2.4.1.50 {ECO:0000250|UniProtKB:O60568};
DE EC=2.4.1.66 {ECO:0000269|PubMed:11896059};
DE AltName: Full=Galactosylhydroxylysine-glucosyltransferase;
DE AltName: Full=Procollagen galactosyltransferase;
DE AltName: Full=Procollagen glucosyltransferase;
DE Flags: Precursor;
GN Name=let-268; ORFNames=F52H3.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-668 AND GLY-682.
RC STRAIN=Bristol N2;
RX PubMed=11071784; DOI=10.1006/dbio.2000.9897;
RA Norman K.R., Moerman D.G.;
RT "The let-268 locus of Caenorhabditis elegans encodes a procollagen lysyl
RT hydroxylase that is essential for type IV collagen secretion.";
RL Dev. Biol. 227:690-705(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF PHE-131; CYS-132; LEU-196
RP AND ALA-453.
RX PubMed=11896059; DOI=10.1074/jbc.m201389200;
RA Wang C., Risteli M., Heikkinen J., Hussa A.K., Uitto L., Myllyla R.;
RT "Identification of amino acids important for the catalytic activity of the
RT collagen glucosyltransferase associated with the multifunctional lysyl
RT hydroxylase 3 (LH3).";
RL J. Biol. Chem. 277:18568-18573(2002).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-689, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=12754521; DOI=10.1038/nbt829;
RA Kaji H., Saito H., Yamauchi Y., Shinkawa T., Taoka M., Hirabayashi J.,
RA Kasai K., Takahashi N., Isobe T.;
RT "Lectin affinity capture, isotope-coded tagging and mass spectrometry to
RT identify N-linked glycoproteins.";
RL Nat. Biotechnol. 21:667-672(2003).
RN [5]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-689, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Bristol N2;
RX PubMed=17761667; DOI=10.1074/mcp.m600392-mcp200;
RA Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T.,
RA Taoka M., Takahashi N., Isobe T.;
RT "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis
RT elegans and suggests an atypical translocation mechanism for integral
RT membrane proteins.";
RL Mol. Cell. Proteomics 6:2100-2109(2007).
CC -!- FUNCTION: Multifunctional enzyme that catalyzes a series of post-
CC translational modifications on Lys residues in procollagen
CC (PubMed:11896059). Catalyzes the formation of hydroxylysine residues in
CC -Xaa-Lys-Gly- sequences in type IV collagens (By similarity). Transfers
CC galactose onto hydroxylysine groups, giving rise to galactosyl 5-
CC hydroxylysine (By similarity). Catalyzes the subsequent transfer of
CC glucose moieties, giving rise to 1,2-glucosylgalactosyl-5-hydroxylysine
CC residues (PubMed:11896059). Essential for normal biosynthesis and
CC secretion of type IV collagens (PubMed:11071784, PubMed:11896059).
CC Essential for normal stability of the basement membrane
CC (PubMed:11071784). {ECO:0000250|UniProtKB:O60568,
CC ECO:0000269|PubMed:11071784, ECO:0000269|PubMed:11896059}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-lysyl-[collagen] + O2 = (5R)-5-hydroxy-L-
CC lysyl-[collagen] + CO2 + succinate; Xref=Rhea:RHEA:16569, Rhea:RHEA-
CC COMP:12751, Rhea:RHEA-COMP:12752, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:133442; EC=1.14.11.4;
CC Evidence={ECO:0000250|UniProtKB:O60568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + UDP-alpha-D-galactose =
CC (5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] + H(+) +
CC UDP; Xref=Rhea:RHEA:12637, Rhea:RHEA-COMP:12752, Rhea:RHEA-
CC COMP:12753, ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:66914,
CC ChEBI:CHEBI:133442, ChEBI:CHEBI:133443; EC=2.4.1.50;
CC Evidence={ECO:0000250|UniProtKB:O60568};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-O-(beta-D-galactosyl)-5-hydroxy-L-lysyl-[collagen] +
CC UDP-alpha-D-glucose = (5R)-5-O-[alpha-D-glucosyl-(1->2)-beta-D-
CC galactosyl]-5-hydroxy-L-lysyl-[collagen] + H(+) + UDP;
CC Xref=Rhea:RHEA:12576, Rhea:RHEA-COMP:12753, Rhea:RHEA-COMP:12754,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885,
CC ChEBI:CHEBI:133443, ChEBI:CHEBI:133452; EC=2.4.1.66;
CC Evidence={ECO:0000269|PubMed:11896059};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:O60568};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000250|UniProtKB:O60568};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:O60568};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O60568}.
CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum
CC {ECO:0000250|UniProtKB:O60568}. Endoplasmic reticulum lumen
CC {ECO:0000305|PubMed:11071784}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9R0E1}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9R0E1}; Lumenal side
CC {ECO:0000250|UniProtKB:Q9R0E1}. Secreted
CC {ECO:0000250|UniProtKB:O60568}. Secreted, extracellular space
CC {ECO:0000250|UniProtKB:Q9R0E1}. Note=The majority of the secreted
CC protein is associated with the extracellular matrix.
CC {ECO:0000250|UniProtKB:Q9R0E1}.
CC -!- DOMAIN: The N-terminal domain mediates glycosyltransferase activity.
CC {ECO:0000250|UniProtKB:O60568}.
CC -!- DOMAIN: The C-terminal domain that mediates lysyl hydroxylase activity
CC is also important for homodimerization. {ECO:0000250|UniProtKB:O60568}.
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DR EMBL; Z66512; CAA91321.1; -; Genomic_DNA.
DR PIR; T22517; T22517.
DR RefSeq; NP_496170.1; NM_063769.3.
DR AlphaFoldDB; Q20679; -.
DR SMR; Q20679; -.
DR BioGRID; 39884; 1.
DR STRING; 6239.F52H3.1.1; -.
DR iPTMnet; Q20679; -.
DR EPD; Q20679; -.
DR PaxDb; Q20679; -.
DR PeptideAtlas; Q20679; -.
DR EnsemblMetazoa; F52H3.1.1; F52H3.1.1; WBGene00002497.
DR EnsemblMetazoa; F52H3.1.2; F52H3.1.2; WBGene00002497.
DR EnsemblMetazoa; F52H3.1.3; F52H3.1.3; WBGene00002497.
DR EnsemblMetazoa; F52H3.1.4; F52H3.1.4; WBGene00002497.
DR UCSC; F52H3.1.1; c. elegans.
DR WormBase; F52H3.1; CE03397; WBGene00002497; let-268.
DR eggNOG; KOG1971; Eukaryota.
DR GeneTree; ENSGT01030000234558; -.
DR HOGENOM; CLU_022320_1_0_1; -.
DR InParanoid; Q20679; -.
DR OMA; CTYYFSM; -.
DR OrthoDB; 194164at2759; -.
DR PhylomeDB; Q20679; -.
DR Reactome; R-CEL-1650814; Collagen biosynthesis and modifying enzymes.
DR PRO; PR:Q20679; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00002497; Expressed in embryo and 3 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0050211; F:procollagen galactosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0033823; F:procollagen glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008475; F:procollagen-lysine 5-dioxygenase activity; IBA:GO_Central.
DR GO; GO:0003980; F:UDP-glucose:glycoprotein glucosyltransferase activity; IDA:WormBase.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:WormBase.
DR GO; GO:0017185; P:peptidyl-lysine hydroxylation; IBA:GO_Central.
DR GO; GO:0006486; P:protein glycosylation; IDA:WormBase.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR006620; Pro_4_hyd_alph.
DR InterPro; IPR001006; Procol_lys_dOase.
DR SMART; SM00702; P4Hc; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
DR PROSITE; PS01325; LYS_HYDROXYLASE; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Glycosyltransferase; Iron; Manganese; Membrane; Metal-binding;
KW Multifunctional enzyme; Oxidoreductase; Reference proteome; Secreted;
KW Signal; Transferase; Vitamin C.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..730
FT /note="Multifunctional procollagen lysine hydroxylase and
FT glycosyltransferase"
FT /id="PRO_0000024689"
FT DOMAIN 639..730
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 20..280
FT /note="Required for glycosyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT REGION 281..507
FT /note="Accessory region"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT REGION 664..707
FT /note="Important for dimerization"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 30..32
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 98..100
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 98
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 101
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 242
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 245..248
FT /ligand="UDP"
FT /ligand_id="ChEBI:CHEBI:58223"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 590
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 648
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT BINDING 659
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 661
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 711
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 721
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT CARBOHYD 689
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754521,
FT ECO:0000269|PubMed:17761667"
FT DISULFID 268..271
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT DISULFID 554..690
FT /evidence="ECO:0000250|UniProtKB:O60568"
FT MUTAGEN 131
FT /note="F->I: Nearly abolishes glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:11896059"
FT MUTAGEN 132
FT /note="C->I: Loss of glucosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11896059"
FT MUTAGEN 196
FT /note="L->I: Strongly reduced glucosyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:11896059"
FT MUTAGEN 453
FT /note="A->I: Loss of glucosyltransferase activity."
FT /evidence="ECO:0000269|PubMed:11896059"
FT MUTAGEN 668
FT /note="D->R: In let-268(mn189); lethal effect."
FT /evidence="ECO:0000269|PubMed:11071784"
FT MUTAGEN 682
FT /note="G->D: In let-268(mn198); lethal effect."
FT /evidence="ECO:0000269|PubMed:11071784"
SQ SEQUENCE 730 AA; 84425 MW; 884F3EFE1A0A86FF CRC64;
MRVLPFLLPL IPVLLATTIT DLPELVVVTV ATENTDGLKR LLESAKAFDI NIEVLGLGEK
WNGGDTRIEQ GGGQKIRILS DWIEKYKDAS DTMIMFVDAY DVVFNADSTT ILRKFFEHYS
EKRLLFGAEP FCWPDQSLAP EYPIVEFGKR FLNSGLFMGY GPEMHKILKL KSVEDKDDDQ
LYYTMIYLDE KLRKELNMDL DSMSKIFQNL NGVIEDVELQ FKEDGTPEAY NAAYNTKPLI
VHGNGPSKSH LNYLGNYLGN RWNSQLGCRT CGLEVKESEE VPLIALNLFI SKPIPFIEEV
LQKIAEFDYP KEKIALYIYN NQPFSIKNIQ DFLQKHGKSY YTKRVINGVT EIGDREARNE
AIEWNKARNV EFAFLMDGDA YFSEPKVIKD LIQYSKTYDV GIIAPMIGQP GKLFTNFWGA
IAANGYYARS EDYMAIVKGN RVGYWNVPFI TSAVLFNKEK LEAMKDAYSY NKNLDPDMSM
CKFARDNGHF LYIDNEKYYG FLIVSDEYAE TVTEGKWHPE MWQIFENREL WEARYIHPGY
HKIMEPEHVV DQACPDVYDF PLMSERFCEE LIEEMEGFGR WSDGSNNDKR LAGGYENVPT
RDIHMNQVGF ERQWLYFMDT YVRPVQEKTF IGYYHQPVES NMMFVVRYKP EEQPSLRPHH
DASTFSIDIA LNKKGRDYEG GGVRYIRYNC TVPADEVGYA MMFPGRLTHL HEGLATTKGT
RYIMVSFINP
