PLOD1_HUMAN
ID PLOD1_HUMAN Reviewed; 727 AA.
AC Q02809; B4DR87; Q96AV9; Q9H132;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1;
DE EC=1.14.11.4 {ECO:0000269|PubMed:10686424, ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:8621606};
DE AltName: Full=Lysyl hydroxylase 1;
DE Short=LH1;
DE Flags: Precursor;
GN Name=PLOD1; Synonyms=LLH, PLOD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 19-28 AND
RP 332-34, AND VARIANT THR-99.
RC TISSUE=Placenta;
RX PubMed=1577494; DOI=10.1016/0888-7543(92)90202-4;
RA Hautala T., Byers M.G., Eddy R.L., Shows T.B., Kivirikko K.I., Myllylae R.;
RT "Cloning of human lysyl hydroxylase: complete cDNA-derived amino acid
RT sequence and assignment of the gene (PLOD) to chromosome 1p36.3-p36.2.";
RL Genomics 13:62-69(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7713497; DOI=10.1006/geno.1994.1654;
RA Heikkinen J., Hautala T., Kivirikko K.I., Myllylae R.;
RT "Structure and expression of the human lysyl hydroxylase gene (PLOD):
RT introns 9 and 16 contain Alu sequences at the sites of recombination in
RT Ehlers-Danlos syndrome type VI patients.";
RL Genomics 24:464-471(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS THR-99 AND
RP SER-120.
RC TISSUE=Skin;
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 [6]
RP MUTAGENESIS OF HIS-656; ASP-658; HIS-706 AND HIS-708, CATALYTIC ACTIVITY,
RP FUNCTION, AND COFACTOR.
RX PubMed=8621606; DOI=10.1074/jbc.271.16.9398;
RA Pirskanen A., Kaimio A.M., Myllylae R., Kivirikko K.I.;
RT "Site-directed mutagenesis of human lysyl hydroxylase expressed in insect
RT cells. Identification of histidine residues and an aspartic acid residue
RT critical for catalytic activity.";
RL J. Biol. Chem. 271:9398-9402(1996).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP VARIANTS EDSKSCL1 GLU-532 DEL AND ARG-678.
RX PubMed=8163671; DOI=10.1172/jci117155;
RA Ha V.T., Marshall M.K., Elsas L.J., Pinnell S.R., Yeowell H.N.;
RT "A patient with Ehlers-Danlos syndrome type VI is a compound heterozygote
RT for mutations in the lysyl hydroxylase gene.";
RL J. Clin. Invest. 93:1716-1721(1994).
RN [11]
RP VARIANT EDSKSCL1 CYS-612.
RX PubMed=9617436; DOI=10.1007/s004030050287;
RA Brinckmann J., Acil Y., Feshchenko S., Katzer E., Brenner R., Kulozik A.,
RA Kugler S.;
RT "Ehlers-Danlos syndrome type VI: lysyl hydroxylase deficiency due to a
RT novel point mutation (W612C).";
RL Arch. Dermatol. Res. 290:181-186(1998).
RN [12]
RP VARIANT EDSKSCL1 367-ASP--GLN-371 DEL, MUTAGENESIS OF CYS-369, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RX PubMed=10686424; DOI=10.1016/s0945-053x(99)00055-4;
RA Yeowell H.N., Allen J.D., Walker L.C., Overstreet M.A., Murad S.,
RA Thai S.F.;
RT "Deletion of cysteine 369 in lysyl hydroxylase 1 eliminates enzyme activity
RT and causes Ehlers-Danlos syndrome type VI.";
RL Matrix Biol. 19:37-46(2000).
RN [13]
RP INVOLVEMENT IN EDSKSCL1.
RX PubMed=15666309; DOI=10.1002/ajmg.a.30529;
RA Giunta C., Randolph A., Al-Gazali L.I., Brunner H.G., Kraenzlin M.E.,
RA Steinmann B.;
RT "Nevo syndrome is allelic to the kyphoscoliotic type of the Ehlers-Danlos
RT syndrome (EDS VIA).";
RL Am. J. Med. Genet. A 133:158-164(2005).
RN [14]
RP VARIANT EDSKSCL1 GLY-446, CHARACTERIZATION OF VARIANT EDSKSCL1 GLY-446,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=15854030; DOI=10.1111/j.0022-202x.2005.23727.x;
RA Walker L.C., Overstreet M.A., Siddiqui A., De Paepe A., Ceylaner G.,
RA Malfait F., Symoens S., Atsawasuwan P., Yamauchi M., Ceylaner S.,
RA Bank R.A., Yeowell H.N.;
RT "A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl
RT hydroxylase activity in an Ehlers-Danlos VIA patient.";
RL J. Invest. Dermatol. 124:914-918(2005).
RN [15]
RP VARIANTS EDSKSCL1 THR-667 AND ARG-706.
RX PubMed=15979919; DOI=10.1016/j.ymgme.2005.04.014;
RA Giunta C., Randolph A., Steinmann B.;
RT "Mutation analysis of the PLOD1 gene: an efficient multistep approach to
RT the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos
RT syndrome (EDS VIA).";
RL Mol. Genet. Metab. 86:269-276(2005).
RN [16]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-123.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Part of a complex composed of PLOD1, P3H3 and P3H4 that
CC catalyzes hydroxylation of lysine residues in collagen alpha chains and
CC is required for normal assembly and cross-linkling of collagen fibrils
CC (By similarity). Forms hydroxylysine residues in -Xaa-Lys-
CC Gly- sequences in collagens (PubMed:8621606, PubMed:10686424,
CC PubMed:15854030). These hydroxylysines serve as sites of attachment for
CC carbohydrate units and are essential for the stability of the
CC intermolecular collagen cross-links (Probable).
CC {ECO:0000250|UniProtKB:Q9R0E2, ECO:0000269|PubMed:10686424,
CC ECO:0000269|PubMed:15854030, ECO:0000269|PubMed:8621606, ECO:0000305}.
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:0000269|PubMed:10686424, ECO:0000269|PubMed:15854030,
CC ECO:0000269|PubMed:8621606};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:8621606};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000269|PubMed:8621606};
CC -!- SUBUNIT: Homodimer (By similarity). Identified in a complex with P3H3
CC and P3H4 (By similarity). {ECO:0000250|UniProtKB:P24802,
CC ECO:0000250|UniProtKB:Q9R0E2}.
CC -!- INTERACTION:
CC Q02809; P55795: HNRNPH2; NbExp=2; IntAct=EBI-357174, EBI-352823;
CC -!- SUBCELLULAR LOCATION: Rough endoplasmic reticulum membrane; Peripheral
CC membrane protein; Lumenal side.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q02809-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02809-2; Sequence=VSP_056300;
CC -!- DISEASE: Ehlers-Danlos syndrome, kyphoscoliotic type, 1 (EDSKSCL1)
CC [MIM:225400]: A form of Ehlers-Danlos syndrome, a group of connective
CC tissue disorders characterized by skin hyperextensibility, articular
CC hypermobility, and tissue fragility. EDSKSCL1 is an autosomal recessive
CC form characterized by severe muscle hypotonia at birth, generalized
CC joint laxity, scoliosis at birth, and scleral fragility and rupture of
CC the ocular globe. {ECO:0000269|PubMed:10686424,
CC ECO:0000269|PubMed:15666309, ECO:0000269|PubMed:15854030,
CC ECO:0000269|PubMed:15979919, ECO:0000269|PubMed:8163671,
CC ECO:0000269|PubMed:9617436}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; L06419; AAA60116.1; -; mRNA.
DR EMBL; AF490527; AAM12752.1; -; Genomic_DNA.
DR EMBL; AF490514; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490515; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490516; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490517; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490518; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490519; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490520; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490521; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490522; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490523; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490524; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490525; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AF490526; AAM12752.1; JOINED; Genomic_DNA.
DR EMBL; AK299150; BAG61199.1; -; mRNA.
DR EMBL; AK316285; BAH14656.1; -; mRNA.
DR EMBL; AL096840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016657; AAH16657.1; -; mRNA.
DR CCDS; CCDS142.1; -. [Q02809-1]
DR PIR; A38206; A38206.
DR RefSeq; NP_000293.2; NM_000302.3. [Q02809-1]
DR RefSeq; NP_001303249.1; NM_001316320.1. [Q02809-2]
DR AlphaFoldDB; Q02809; -.
DR SMR; Q02809; -.
DR BioGRID; 111366; 222.
DR IntAct; Q02809; 93.
DR MINT; Q02809; -.
DR STRING; 9606.ENSP00000196061; -.
DR DrugBank; DB00126; Ascorbic acid.
DR DrugCentral; Q02809; -.
DR GlyConnect; 1633; 21 N-Linked glycans (3 sites).
DR GlyGen; Q02809; 5 sites, 21 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q02809; -.
DR PhosphoSitePlus; Q02809; -.
DR SwissPalm; Q02809; -.
DR BioMuta; PLOD1; -.
DR DMDM; 78099790; -.
DR CPTAC; CPTAC-1500; -.
DR CPTAC; CPTAC-2232; -.
DR CPTAC; CPTAC-566; -.
DR CPTAC; CPTAC-567; -.
DR EPD; Q02809; -.
DR jPOST; Q02809; -.
DR MassIVE; Q02809; -.
DR MaxQB; Q02809; -.
DR PaxDb; Q02809; -.
DR PeptideAtlas; Q02809; -.
DR PRIDE; Q02809; -.
DR ProteomicsDB; 4934; -.
DR ProteomicsDB; 58126; -. [Q02809-1]
DR Antibodypedia; 28331; 144 antibodies from 25 providers.
DR DNASU; 5351; -.
DR Ensembl; ENST00000196061.5; ENSP00000196061.4; ENSG00000083444.17. [Q02809-1]
DR GeneID; 5351; -.
DR KEGG; hsa:5351; -.
DR MANE-Select; ENST00000196061.5; ENSP00000196061.4; NM_000302.4; NP_000293.2.
DR UCSC; uc001atm.4; human. [Q02809-1]
DR CTD; 5351; -.
DR DisGeNET; 5351; -.
DR GeneCards; PLOD1; -.
DR GeneReviews; PLOD1; -.
DR HGNC; HGNC:9081; PLOD1.
DR HPA; ENSG00000083444; Low tissue specificity.
DR MalaCards; PLOD1; -.
DR MIM; 153454; gene.
DR MIM; 225400; phenotype.
DR neXtProt; NX_Q02809; -.
DR OpenTargets; ENSG00000083444; -.
DR Orphanet; 1900; Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency.
DR PharmGKB; PA33411; -.
DR VEuPathDB; HostDB:ENSG00000083444; -.
DR eggNOG; KOG1971; Eukaryota.
DR GeneTree; ENSGT01030000234558; -.
DR HOGENOM; CLU_022320_1_0_1; -.
DR InParanoid; Q02809; -.
DR OMA; CTYYFSM; -.
DR OrthoDB; 194164at2759; -.
DR PhylomeDB; Q02809; -.
DR TreeFam; TF313826; -.
DR BioCyc; MetaCyc:HS01440-MON; -.
DR PathwayCommons; Q02809; -.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR SignaLink; Q02809; -.
DR SIGNOR; Q02809; -.
DR BioGRID-ORCS; 5351; 19 hits in 1079 CRISPR screens.
DR ChiTaRS; PLOD1; human.
DR GenomeRNAi; 5351; -.
DR Pharos; Q02809; Tbio.
DR PRO; PR:Q02809; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q02809; protein.
DR Bgee; ENSG00000083444; Expressed in stromal cell of endometrium and 198 other tissues.
DR ExpressionAtlas; Q02809; baseline and differential.
DR Genevisible; Q02809; HS.
DR GO; GO:1902494; C:catalytic complex; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030867; C:rough endoplasmic reticulum membrane; 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:0008475; F:procollagen-lysine 5-dioxygenase activity; IDA:CAFA.
DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB.
DR GO; GO:0017185; P:peptidyl-lysine hydroxylation; IDA:UniProtKB.
DR GO; GO:0001666; P:response to hypoxia; IEP:UniProtKB.
DR InterPro; IPR044861; IPNS-like_FE2OG_OXY.
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 Pfam; PF03171; 2OG-FeII_Oxy; 1.
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 Alternative splicing; Dioxygenase; Direct protein sequencing;
KW Disease variant; Ehlers-Danlos syndrome; Endoplasmic reticulum;
KW Glycoprotein; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Reference proteome; Signal; Vitamin C.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:1577494"
FT CHAIN 19..727
FT /note="Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1"
FT /id="PRO_0000024678"
FT DOMAIN 636..727
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT ACT_SITE 718
FT /evidence="ECO:0000255"
FT BINDING 656
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305|PubMed:8621606"
FT BINDING 658
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305|PubMed:8621606"
FT BINDING 708
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000305|PubMed:8621606"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT CARBOHYD 686
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 25
FT /note="E -> EAPCCQEGLRAGGSGSLHLGRDFTVLAGARGSPSPSVSSIPRFWIPG
FT S (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056300"
FT VARIANT 67
FT /note="E -> D (in dbSNP:rs7551068)"
FT /id="VAR_032754"
FT VARIANT 84
FT /note="A -> T (in dbSNP:rs34878020)"
FT /id="VAR_032755"
FT VARIANT 99
FT /note="A -> T (in dbSNP:rs7551175)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1577494"
FT /id="VAR_014220"
FT VARIANT 120
FT /note="A -> S (in dbSNP:rs2273285)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032756"
FT VARIANT 123
FT /note="Q -> H (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035479"
FT VARIANT 367..371
FT /note="Missing (in EDSKSCL1)"
FT /evidence="ECO:0000269|PubMed:10686424"
FT /id="VAR_009269"
FT VARIANT 446
FT /note="W -> G (in EDSKSCL1; loss of enzyme activity)"
FT /evidence="ECO:0000269|PubMed:15854030"
FT /id="VAR_023466"
FT VARIANT 532
FT /note="Missing (in EDSKSCL1; dbSNP:rs797044446)"
FT /evidence="ECO:0000269|PubMed:8163671"
FT /id="VAR_006354"
FT VARIANT 612
FT /note="W -> C (in EDSKSCL1; dbSNP:rs121913553)"
FT /evidence="ECO:0000269|PubMed:9617436"
FT /id="VAR_006355"
FT VARIANT 667
FT /note="A -> T (in EDSKSCL1; dbSNP:rs199730384)"
FT /evidence="ECO:0000269|PubMed:15979919"
FT /id="VAR_023467"
FT VARIANT 678
FT /note="G -> R (in EDSKSCL1; dbSNP:rs121913551)"
FT /evidence="ECO:0000269|PubMed:8163671"
FT /id="VAR_006356"
FT VARIANT 706
FT /note="H -> R (in EDSKSCL1)"
FT /evidence="ECO:0000269|PubMed:15979919"
FT /id="VAR_023468"
FT MUTAGEN 369
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10686424"
FT MUTAGEN 656
FT /note="H->S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:8621606"
FT MUTAGEN 658
FT /note="D->A: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:8621606"
FT MUTAGEN 706
FT /note="H->S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:8621606"
FT MUTAGEN 708
FT /note="H->S: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:8621606"
SQ SEQUENCE 727 AA; 83550 MW; 6C3E0C11B15D598C CRC64;
MRPLLLLALL GWLLLAEAKG DAKPEDNLLV LTVATKETEG FRRFKRSAQF FNYKIQALGL
GEDWNVEKGT SAGGGQKVRL LKKALEKHAD KEDLVILFAD SYDVLFASGP RELLKKFRQA
RSQVVFSAEE LIYPDRRLET KYPVVSDGKR FLGSGGFIGY APNLSKLVAE WEGQDSDSDQ
LFYTKIFLDP EKREQINITL DHRCRIFQNL DGALDEVVLK FEMGHVRARN LAYDTLPVLI
HGNGPTKLQL NYLGNYIPRF WTFETGCTVC DEGLRSLKGI GDEALPTVLV GVFIEQPTPF
VSLFFQRLLR LHYPQKHMRL FIHNHEQHHK AQVEEFLAQH GSEYQSVKLV GPEVRMANAD
ARNMGADLCR QDRSCTYYFS VDADVALTEP NSLRLLIQQN KNVIAPLMTR HGRLWSNFWG
ALSADGYYAR SEDYVDIVQG RRVGVWNVPY ISNIYLIKGS ALRGELQSSD LFHHSKLDPD
MAFCANIRQQ DVFMFLTNRH TLGHLLSLDS YRTTHLHNDL WEVFSNPEDW KEKYIHQNYT
KALAGKLVET PCPDVYWFPI FTEVACDELV EEMEHFGQWS LGNNKDNRIQ GGYENVPTID
IHMNQIGFER EWHKFLLEYI APMTEKLYPG YYTRAQFDLA FVVRYKPDEQ PSLMPHHDAS
TFTINIALNR VGVDYEGGGC RFLRYNCSIR APRKGWTLMH PGRLTHYHEG LPTTRGTRYI
AVSFVDP
