ID P3H1_HUMAN Reviewed; 736 AA. AC Q32P28; Q7KZR4; Q96BR8; Q96SK8; Q96SL5; Q96SN3; Q9H6K3; Q9HC86; Q9HC87; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUN-2006, sequence version 2. DT 10-JUN-2026, entry version 175. DE RecName: Full=Prolyl 3-hydroxylase 1 {ECO:0000312|HGNC:HGNC:19316}; DE EC=1.14.11.7 {ECO:0000269|PubMed:39245686}; DE AltName: Full=Growth suppressor 1 {ECO:0000303|PubMed:10951563}; DE AltName: Full=Leucine- and proline-enriched proteoglycan 1 {ECO:0000250|UniProtKB:Q9R1J8}; DE Short=Leprecan-1 {ECO:0000250|UniProtKB:Q9R1J8}; DE Flags: Precursor; GN Name=P3H1 {ECO:0000312|HGNC:HGNC:19316}; GN Synonyms=GROS1 {ECO:0000303|PubMed:10951563}, LEPRE1 GN {ECO:0000303|PubMed:17277775, ECO:0000303|PubMed:19088120}; GN ORFNames=PSEC0109; 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] (ISOFORMS 1 AND 2), AND FUNCTION. RC TISSUE=Testis; RX PubMed=10951563; DOI=10.1038/sj.onc.1203696; RA Kaul S.C., Sugihara T., Yoshida A., Nomura H., Wadhwa R.; RT "Gros1, a potential growth suppressor on chromosome 1: its identity to RT basement membrane-associated proteoglycan, leprecan."; RL Oncogene 19:3576-3583(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Epithelium, and Teratocarcinoma; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Teratocarcinoma; RX PubMed=16303743; DOI=10.1093/dnares/12.2.117; RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y., RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., RA Isogai T.; RT "Signal sequence and keyword trap in silico for selection of full-length RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA RT libraries."; RL DNA Res. 12:117-126(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 336-736 (ISOFORM 1). RC TISSUE=Duodenum, and Testis; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 347-736 (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP INVOLVEMENT IN OI8. RX PubMed=17277775; DOI=10.1038/ng1968; RA Cabral W.A., Chang W., Barnes A.M., Weis M., Scott M.A., Leikin S., RA Makareeva E., Kuznetsova N.V., Rosenbaum K.N., Tifft C.J., Bulas D.I., RA Kozma C., Smith P.A., Eyre D.R., Marini J.C.; RT "Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone RT disorder resembling lethal/severe osteogenesis imperfecta."; RL Nat. Genet. 39:359-365(2007). RN [7] RP INVOLVEMENT IN OI8, SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING RP (ISOFORMS 1; 3 AND 4). RX PubMed=19088120; DOI=10.1136/jmg.2008.062729; RA Willaert A., Malfait F., Symoens S., Gevaert K., Kayserili H., RA Megarbane A., Mortier G., Leroy J.G., Coucke P.J., De Paepe A.; RT "Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical RT documentation and identification of the splice form responsible for prolyl RT 3-hydroxylation."; RL J. Med. Genet. 46:233-241(2009). RN [8] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-540. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [9] 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 [10] 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 [11] {ECO:0007744|PDB:8K0E, ECO:0007744|PDB:8K0F, ECO:0007744|PDB:8K0I, ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, ECO:0007744|PDB:8KC9} RP STRUCTURE BY ELECTRON MICROSCOPY (3.17 ANGSTROMS) IN COMPLEX WITH RP 2-OXOGLUTARATE AND FE(3+) AND IN COMPLEX WITH PPIB; CRTAP AND COLLAGEN RP ANALOG, GLYCOSYLATION AT ASN-316 AND ASN-540, DISULFIDE BONDS, SUBUNIT, RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-76; ASP-106; ARG-121; RP ASP-263; HIS-587; ASP-589; HIS-659 AND ARG-669, AND CHARACTERIZATION OF RP VARIANT LEU-675. RX PubMed=39245686; DOI=10.1038/s41467-024-52321-6; RA Li W., Peng J., Yao D., Rao B., Xia Y., Wang Q., Li S., Cao M., Shen Y., RA Ma P., Liao R., Qin A., Zhao J., Cao Y.; RT "The structural basis for the collagen processing by human P3H1/CRTAP/PPIB RT ternary complex."; RL Nat. Commun. 15:7844-7844(2024). RN [12] RP VARIANTS OI8 GLU-363 AND LEU-675, VARIANTS TRP-501 AND ILE-549, AND RP INVOLVEMENT IN OI8. RX PubMed=26634552; DOI=10.4238/2015.december.1.36; RA Barbirato C., Trancozo M., Almeida M.G., Almeida L.S., Santos T.O., RA Duarte J.C., Reboucas M.R., Sipolatti V., Nunes V.R., Paula F.; RT "Mutational characterization of the P3H1/CRTAP/CypB complex in recessive RT osteogenesis imperfecta."; RL Genet. Mol. Res. 14:15848-15858(2015). CC -!- FUNCTION: Has prolyl 3-hydroxylase activity and catalyzes the post- CC translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences CC in pro-collagen chains, a critical step for the formation of mature CC collagen trimers (PubMed:39245686). May be involved in the secretory CC pathway of cells. Has growth suppressive activity in fibroblasts. CC {ECO:0000269|PubMed:10951563, ECO:0000269|PubMed:39245686}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-prolyl-[collagen] + 2-oxoglutarate + O2 = trans-3-hydroxy-L- CC prolyl-[collagen] + succinate + CO2; Xref=Rhea:RHEA:22872, Rhea:RHEA- CC COMP:11676, Rhea:RHEA-COMP:11678, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:50342, ChEBI:CHEBI:85428; EC=1.14.11.7; CC Evidence={ECO:0000269|PubMed:39245686}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22873; CC Evidence={ECO:0000305|PubMed:39245686}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC Evidence={ECO:0000269|PubMed:39245686}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC Evidence={ECO:0000250|UniProtKB:Q8IVL5}; CC -!- SUBUNIT: Forms a ternary complex with PPIB (CYPB) and CRTAP, known as CC the PCP complex, in a 1:1:1 stoichiometric ratio; this complex binds CC unfolded collagen (PubMed:39245686). Two PCP complexes can further CC associate to form a higher-order assembly composed of two ternary units CC (PubMed:39245686). {ECO:0000269|PubMed:39245686}. CC -!- INTERACTION: CC Q32P28; O75718: CRTAP; NbExp=3; IntAct=EBI-396328, EBI-2515576; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Endoplasmic reticulum CC {ECO:0000269|PubMed:19088120}. CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000250|UniProtKB:Q9R1J8}. Note=Secreted into the CC extracellular matrix as a chondroitin sulfate proteoglycan (CSPG). CC {ECO:0000250|UniProtKB:Q9R1J8}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=GROS1-L, LEPREa, P3H1a; CC IsoId=Q32P28-1; Sequence=Displayed; CC Name=2; Synonyms=GROS1-S; CC IsoId=Q32P28-2; Sequence=VSP_019346, VSP_019347; CC Name=3; Synonyms=LEPREc; CC IsoId=Q32P28-3; Sequence=VSP_019348; CC Name=4; Synonyms=LEPREb, P3H1b; CC IsoId=Q32P28-4; Sequence=VSP_054864; CC -!- PTM: O-glycosylated; chondroitin sulfate. CC {ECO:0000250|UniProtKB:Q9R1J8}. CC -!- DISEASE: Osteogenesis imperfecta 8 (OI8) [MIM:610915]: A form of CC osteogenesis imperfecta, a disorder of bone formation characterized by CC low bone mass, bone fragility and susceptibility to fractures after CC minimal trauma. Disease severity ranges from very mild forms without CC fractures to intrauterine fractures and perinatal lethality. CC Extraskeletal manifestations, which affect a variable number of CC patients, are dentinogenesis imperfecta, hearing loss, and blue CC sclerae. OI8 is characterized by disproportionate short stature, CC shortening of the long bones, white sclerae, a round face and a short CC barrel-shaped chest. {ECO:0000269|PubMed:17277775, CC ECO:0000269|PubMed:19088120, ECO:0000269|PubMed:26634552}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. A splice site mutation leading to the absence of isoform 1 has CC been reported in 2 OI8 patients. Isoform 1 is the only form predicted CC to be located in the endoplasmic reticulum, which the appropriate CC location for the catalysis of collagen hydroxylation. These patients CC show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120). CC {ECO:0000269|PubMed:19088120}. CC -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15256.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Osteogenesis imperfecta variant database; Note=The CC P3H1 gene homepage; CC URL="https://www.LOVD.nl/P3H1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF097431; AAG31018.1; -; mRNA. DR EMBL; AF097432; AAG31019.1; -; mRNA. DR EMBL; AK025841; BAB15256.1; ALT_INIT; mRNA. DR EMBL; AK027648; BAB55264.1; -; mRNA. DR EMBL; AK027680; BAB55291.1; -; mRNA. DR EMBL; AK027697; BAB55305.1; -; mRNA. DR EMBL; AK075418; BAC11608.1; -; mRNA. DR EMBL; BC015309; AAH15309.3; -; mRNA. DR EMBL; BC108311; AAI08312.1; -; mRNA. DR EMBL; BT007039; AAP35688.1; -; mRNA. DR CCDS; CCDS472.2; -. [Q32P28-1] DR CCDS; CCDS53307.1; -. [Q32P28-4] DR CCDS; CCDS57986.1; -. [Q32P28-3] DR RefSeq; NP_001139761.1; NM_001146289.2. [Q32P28-4] DR RefSeq; NP_001230175.1; NM_001243246.2. [Q32P28-3] DR RefSeq; NP_071751.3; NM_022356.3. [Q32P28-1] DR PDB; 8K0E; EM; 3.65 A; A=1-736. DR PDB; 8K0F; EM; 3.37 A; A=1-736. DR PDB; 8K0I; EM; 3.62 A; A/a=1-736. DR PDB; 8K0M; EM; 3.17 A; A=1-736. DR PDB; 8K17; EM; 3.18 A; A=1-736. DR PDB; 8KC9; EM; 3.75 A; A=1-736. DR PDBsum; 8K0E; -. DR PDBsum; 8K0F; -. DR PDBsum; 8K0I; -. DR PDBsum; 8K0M; -. DR PDBsum; 8K17; -. DR PDBsum; 8KC9; -. DR AlphaFoldDB; Q32P28; -. DR EMDB; EMD-36762; -. DR EMDB; EMD-36763; -. DR EMDB; EMD-36765; -. DR EMDB; EMD-36774; -. DR EMDB; EMD-36787; -. DR EMDB; EMD-37097; -. DR SMR; Q32P28; -. DR BioGRID; 122098; 214. DR FunCoup; Q32P28; 968. DR IntAct; Q32P28; 136. DR MINT; Q32P28; -. DR NDEx; IQUERY-CP-P3H1; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000236040; -. DR DrugBank; DB00126; Ascorbic acid. DR DrugBank; DB00172; Proline. DR DrugBank; DB00139; Succinic acid. DR GlyConnect; Q32P28; 10 N-Linked glycans (2 sites). DR GlyCosmos; Q32P28; 4 sites, 11 glycans. DR GlyGen; Q32P28; 7 sites, 21 N-linked glycans (3 sites), 2 O-linked glycans (2 sites). DR iPTMnet; Q32P28; -. DR MetOSite; Q32P28; -. DR PhosphoSitePlus; Q32P28; -. DR SwissPalm; Q32P28; -. DR BioMuta; P3H1; -. DR DMDM; 109892809; -. DR jPOST; Q32P28; -. DR MassIVE; Q32P28; -. DR PaxDb; 9606-ENSP00000236040; -. DR PeptideAtlas; Q32P28; -. DR ProteomicsDB; 61620; -. [Q32P28-1] DR ProteomicsDB; 61621; -. [Q32P28-2] DR ProteomicsDB; 61622; -. [Q32P28-3] DR Pumba; Q32P28; -. DR Antibodypedia; 32239; 311 antibodies from 23 providers. DR DNASU; 64175; -. DR Ensembl; ENST00000236040.8; ENSP00000236040.4; ENSG00000117385.17. [Q32P28-3] DR Ensembl; ENST00000296388.10; ENSP00000296388.5; ENSG00000117385.17. [Q32P28-1] DR Ensembl; ENST00000397054.7; ENSP00000380245.3; ENSG00000117385.17. [Q32P28-4] DR GeneID; 64175; -. DR KEGG; hsa:64175; -. DR MANE-Select; ENST00000296388.10; ENSP00000296388.5; NM_022356.4; NP_071751.3. DR UCSC; uc001chv.3; human. [Q32P28-1] DR AGR; HGNC:19316; -. DR ClinPGx; PA134930599; -. DR CTD; 64175; -. DR DisGeNET; 64175; -. DR GeneCards; P3H1; -. DR HGNC; HGNC:19316; P3H1. DR HPA; ENSG00000117385; Low tissue specificity. DR MalaCards; P3H1; -. DR MIM; 610339; gene. DR MIM; 610915; phenotype. DR OpenTargets; ENSG00000117385; -. DR Orphanet; 216804; Osteogenesis imperfecta type 2. DR Orphanet; 216812; Osteogenesis imperfecta type 3. DR VEuPathDB; HostDB:ENSG00000117385; -. DR eggNOG; KOG4459; Eukaryota. DR GeneTree; ENSGT00940000158725; -. DR HOGENOM; CLU_017820_0_0_1; -. DR InParanoid; Q32P28; -. DR OMA; HTPSEMF; -. DR OrthoDB; 8517835at2759; -. DR PAN-GO; Q32P28; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q32P28; -. DR BioCyc; MetaCyc:HS04122-MONOMER; -. DR BRENDA; 1.14.11.28; 2681. DR BRENDA; 1.14.11.7; 2681. DR PathwayCommons; Q32P28; -. DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes. DR SignaLink; Q32P28; -. DR Agora; ENSG00000117385; -. DR BioGRID-ORCS; 64175; 21 hits in 1162 CRISPR screens. DR ChiTaRS; P3H1; human. DR GenomeRNAi; 64175; -. DR Pharos; Q32P28; Tbio. DR PRO; PR:Q32P28; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q32P28; protein. DR Bgee; ENSG00000117385; Expressed in stromal cell of endometrium and 157 other cell types or tissues. DR ExpressionAtlas; Q32P28; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB. 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:0019797; F:procollagen-proline 3-dioxygenase activity; ISS:UniProtKB. DR GO; GO:0060348; P:bone development; IMP:UniProtKB. DR GO; GO:0032963; P:collagen metabolic process; ISS:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; NAS:UniProtKB. DR GO; GO:1901874; P:negative regulation of post-translational protein modification; IMP:UniProtKB. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:ARUK-UCL. DR GO; GO:0006457; P:protein folding; IMP:UniProtKB. DR GO; GO:0018126; P:protein hydroxylation; IMP:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB. DR GO; GO:0050708; P:regulation of protein secretion; IMP:UniProtKB. DR FunFam; 2.60.120.620:FF:000003; Prolyl 3-hydroxylase 2; 1. DR Gene3D; 2.60.120.620; q2cbj1_9rhob like domain; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 2. DR InterPro; IPR056585; Leprecan_dom. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase_dom. DR InterPro; IPR039575; P3H. DR InterPro; IPR006620; Pro_4_hyd_alph. DR InterPro; IPR044862; Pro_4_hyd_alph_FE2OG_OXY. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR PANTHER; PTHR14049; LEPRECAN 1; 1. DR PANTHER; PTHR14049:SF5; PROLYL 3-HYDROXYLASE 1; 1. DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1. DR Pfam; PF23557; TPR_leprecan; 1. DR SMART; SM00702; P4Hc; 1. DR SUPFAM; SSF48452; TPR-like; 1. DR PROSITE; PS00014; ER_TARGET; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Dioxygenase; KW Disease variant; Disulfide bond; Dwarfism; Endoplasmic reticulum; KW Extracellular matrix; Glycoprotein; Iron; Metal-binding; KW Osteogenesis imperfecta; Oxidoreductase; Proteoglycan; KW Proteomics identification; Reference proteome; Repeat; Secreted; Signal; KW TPR repeat; Vitamin C. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..736 FT /note="Prolyl 3-hydroxylase 1" FT /id="PRO_0000240352" FT REPEAT 35..68 FT /note="TPR 1" FT REPEAT 143..176 FT /note="TPR 2" FT REPEAT 205..238 FT /note="TPR 3" FT REPEAT 301..334 FT /note="TPR 4" FT DOMAIN 564..678 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT REGION 699..736 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 401..439 FT /evidence="ECO:0000255" FT MOTIF 733..736 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138" FT BINDING 569 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0M" FT BINDING 587 FT /ligand="Fe(3+)" FT /ligand_id="ChEBI:CHEBI:29034" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17" FT BINDING 589 FT /ligand="Fe(3+)" FT /ligand_id="ChEBI:CHEBI:29034" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0E, ECO:0007744|PDB:8K0F, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, FT ECO:0007744|PDB:8KC9" FT BINDING 659 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0M" FT BINDING 659 FT /ligand="Fe(3+)" FT /ligand_id="ChEBI:CHEBI:29034" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0E, ECO:0007744|PDB:8K0F, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, FT ECO:0007744|PDB:8KC9" FT BINDING 669 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0M" FT CARBOHYD 316 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0F, ECO:0007744|PDB:8K0I, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, FT ECO:0007744|PDB:8KC9" FT CARBOHYD 467 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 540 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:39245686, ECO:0007744|PDB:8K0F, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, FT ECO:0007744|PDB:8KC9" FT DISULFID 75..123 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0E, ECO:0007744|PDB:8K0F, FT ECO:0007744|PDB:8K0M, ECO:0007744|PDB:8K17, FT ECO:0007744|PDB:8KC9" FT DISULFID 79..119 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0F, ECO:0007744|PDB:8K0M, FT ECO:0007744|PDB:8KC9" FT DISULFID 242..282 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0E, ECO:0007744|PDB:8KC9" FT DISULFID 246..278 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0I, ECO:0007744|PDB:8KC9" FT DISULFID 483..645 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0M" FT DISULFID 591..600 FT /evidence="ECO:0000269|PubMed:39245686, FT ECO:0007744|PDB:8K0F, ECO:0007744|PDB:8K0M, FT ECO:0007744|PDB:8K17" FT VAR_SEQ 361..363 FT /note="SAK -> QGT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10951563" FT /id="VSP_019346" FT VAR_SEQ 364..736 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10951563" FT /id="VSP_019347" FT VAR_SEQ 686..736 FT /note="DRVQADDLVKMLFSPEEMDLSQEQPLDAQQGPPEPAQESLSGSESKPKDEL FT -> VRAARAGESSWCCGDPFPERPWFAFLFPKSHCQWLRHERSTWDTSSNALSLWSHCL FT VLPGPAVNGIQVGKEVKTGSDAEFLVPSLGPTSAVLFQRVGPAGKEMSLGPLRNLPCPL FT GSSS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019348" FT VAR_SEQ 686..736 FT /note="DRVQADDLVKMLFSPEEMDLSQEQPLDAQQGPPEPAQESLSGSESKPKDEL FT -> VRAARAGQGAGR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054864" FT VARIANT 349 FT /note="G -> R (in dbSNP:rs6700677)" FT /id="VAR_033252" FT VARIANT 363 FT /note="K -> E (in OI8; uncertain significance; FT dbSNP:rs146476495)" FT /evidence="ECO:0000269|PubMed:26634552" FT /id="VAR_091504" FT VARIANT 501 FT /note="R -> W (in dbSNP:rs115108794)" FT /evidence="ECO:0000269|PubMed:26634552" FT /id="VAR_091505" FT VARIANT 506 FT /note="P -> R (in dbSNP:rs3738501)" FT /id="VAR_033253" FT VARIANT 549 FT /note="M -> I (in dbSNP:rs11581921)" FT /evidence="ECO:0000269|PubMed:26634552" FT /id="VAR_033254" FT VARIANT 644 FT /note="Q -> K (in dbSNP:rs3738497)" FT /id="VAR_050442" FT VARIANT 675 FT /note="W -> L (in OI8; likely pathogenic; loss of catalytic FT activity; dbSNP:rs1226770904)" FT /evidence="ECO:0000269|PubMed:26634552, FT ECO:0000269|PubMed:39245686" FT /id="VAR_091506" FT MUTAGEN 76 FT /note="R->A,D: Decreased interaction with CRTAP." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 106 FT /note="D->A,R: Decreased interaction with CRTAP." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 121 FT /note="R->A,D: Decreased interaction with CRTAP." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 263 FT /note="D->A,K: Decreased interaction with CRTAP." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 587 FT /note="H->A: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 589 FT /note="D->A: Severely decreased catalytic activity." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 659 FT /note="H->A: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:39245686" FT MUTAGEN 669 FT /note="R->H: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:39245686" FT CONFLICT 102 FT /note="A -> G (in Ref. 1; AAG31018/AAG31019)" FT /evidence="ECO:0000305" FT CONFLICT 321 FT /note="V -> G (in Ref. 1; AAG31018/AAG31019)" FT /evidence="ECO:0000305" FT CONFLICT 396 FT /note="E -> G (in Ref. 2; BAB55264)" FT /evidence="ECO:0000305" FT CONFLICT 469 FT /note="S -> Y (in Ref. 1; AAG31019)" FT /evidence="ECO:0000305" FT CONFLICT 605 FT /note="P -> L (in Ref. 2; BAB15256)" FT /evidence="ECO:0000305" FT CONFLICT 711 FT /note="L -> M (in Ref. 2; BAB55291)" FT /evidence="ECO:0000305" FT HELIX 32..34 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 35..48 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 51..82 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 84..86 FT /evidence="ECO:0007829|PDB:8K17" FT HELIX 92..94 FT /evidence="ECO:0007829|PDB:8K0F" FT HELIX 100..124 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 128..130 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 134..141 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 144..156 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 159..172 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 177..188 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 189..191 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 194..196 FT /evidence="ECO:0007829|PDB:8K0F" FT STRAND 200..202 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 204..217 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 222..224 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 225..243 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 254..259 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 264..280 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 281..287 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 292..294 FT /evidence="ECO:0007829|PDB:8K17" FT HELIX 299..314 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 318..328 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 336..347 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 350..355 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 360..383 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 396..398 FT /evidence="ECO:0007829|PDB:8K17" FT HELIX 401..427 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 443..445 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 454..456 FT /evidence="ECO:0007829|PDB:8K17" FT STRAND 458..461 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 463..467 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 468..475 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 480..492 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 512..516 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 518..527 FT /evidence="ECO:0007829|PDB:8K0M" FT HELIX 532..552 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 560..570 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 583..587 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 589..594 FT /evidence="ECO:0007829|PDB:8K0M" FT TURN 595..598 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 599..601 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 612..617 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 622..624 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 627..630 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 637..641 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 648..652 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 659..661 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 664..678 FT /evidence="ECO:0007829|PDB:8K0M" FT STRAND 680..682 FT /evidence="ECO:0007829|PDB:8K0F" FT HELIX 686..698 FT /evidence="ECO:0007829|PDB:8K0M" SQ SEQUENCE 736 AA; 83394 MW; EA1909828FAE685E CRC64; MAVRALKLLT TLLAVVAAAS QAEVESEAGW GMVTPDLLFA EGTAAYARGD WPGVVLSMER ALRSRAALRA LRLRCRTQCA ADFPWELDPD WSPSPAQASG AAALRDLSFF GGLLRRAACL RRCLGPPAAH SLSEEMELEF RKRSPYNYLQ VAYFKINKLE KAVAAAHTFF VGNPEHMEMQ QNLDYYQTMS GVKEADFKDL ETQPHMQEFR LGVRLYSEEQ PQEAVPHLEA ALQEYFVAYE ECRALCEGPY DYDGYNYLEY NADLFQAITD HYIQVLNCKQ NCVTELASHP SREKPFEDFL PSHYNYLQFA YYNIGNYTQA VECAKTYLLF FPNDEVMNQN LAYYAAMLGE EHTRSIGPRE SAKEYRQRSL LEKELLFFAY DVFGIPFVDP DSWTPEEVIP KRLQEKQKSE RETAVRISQE IGNLMKEIET LVEEKTKESL DVSRLTREGG PLLYEGISLT MNSKLLNGSQ RVVMDGVISD HECQELQRLT NVAATSGDGY RGQTSPHTPN EKFYGVTVFK ALKLGQEGKV PLQSAHLYYN VTEKVRRIME SYFRLDTPLY FSYSHLVCRT AIEEVQAERK DDSHPVHVDN CILNAETLVC VKEPPAYTFR DYSAILYLNG DFDGGNFYFT ELDAKTVTAE VQPQCGRAVG FSSGTENPHG VKAVTRGQRC AIALWFTLDP RHSERDRVQA DDLVKMLFSP EEMDLSQEQP LDAQQGPPEP AQESLSGSES KPKDEL //