P3H3_MOUSE
ID P3H3_MOUSE Reviewed; 732 AA.
AC Q8CG70; O88836;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Prolyl 3-hydroxylase 3 {ECO:0000312|MGI:MGI:1315208};
DE EC=1.14.11.7;
DE AltName: Full=Leprecan-like protein 2 {ECO:0000303|PubMed:15063763};
DE AltName: Full=Protein B {ECO:0000250|UniProtKB:Q8IVL6};
DE Flags: Precursor;
GN Name=P3h3 {ECO:0000312|MGI:MGI:1315208};
GN Synonyms=Leprel2 {ECO:0000303|PubMed:15063763};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=15063763; DOI=10.1016/j.bbrc.2004.03.060;
RA Jaernum S., Kjellman C., Darabi A., Nilsson I., Edvardsen K., Aaman P.;
RT "LEPREL1, a novel ER and Golgi resident member of the Leprecan family.";
RL Biochem. Biophys. Res. Commun. 317:342-351(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15044469; DOI=10.1074/jbc.m312807200;
RA Vranka J.A., Sakai L.Y., Bachinger H.P.;
RT "Prolyl 3-hydroxylase 1, enzyme characterization and identification of a
RT novel family of enzymes.";
RL J. Biol. Chem. 279:23615-23621(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-732.
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 165-732.
RX PubMed=9445485;
RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J.,
RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.;
RT "Comparative sequence analysis of a gene-rich cluster at human chromosome
RT 12p13 and its syntenic region in mouse chromosome 6.";
RL Genome Res. 8:29-40(1998).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH PLOD1 AND P3H4.
RX PubMed=27119146; DOI=10.1371/journal.pgen.1006002;
RA Heard M.E., Besio R., Weis M., Rai J., Hudson D.M., Dimori M.,
RA Zimmerman S.M., Kamykowski J.A., Hogue W.R., Swain F.L., Burdine M.S.,
RA Mackintosh S.G., Tackett A.J., Suva L.J., Eyre D.R., Morello R.;
RT "Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex
RT Regulating Collagen Lysyl Hydroxylation.";
RL PLoS Genet. 12:E1006002-E1006002(2016).
RN [7]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=28115524; DOI=10.1074/jbc.m116.762245;
RA Hudson D.M., Weis M., Rai J., Joeng K.S., Dimori M., Lee B.H., Morello R.,
RA Eyre D.R.;
RT "P3h3-null and Sc65-null Mice Phenocopy the Collagen Lysine Under-
RT hydroxylation and Cross-linking Abnormality of Ehlers-Danlos Syndrome Type
RT VIA.";
RL J. Biol. Chem. 292:3877-3887(2017).
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 (PubMed:27119146). Required for normal hydroxylation of lysine residues
CC in type I collagen chains in skin, bone, tendon, aorta and cornea
CC (PubMed:28115524). Required for normal skin stability via its role in
CC hydroxylation of lysine residues in collagen alpha chains and in
CC collagen fibril assembly (PubMed:27119146, PubMed:28115524). Apparently
CC not required for normal prolyl 3-hydroxylation on collagen chains,
CC possibly because it functions redundantly with other prolyl 3-
CC hydroxylases (PubMed:28115524). {ECO:0000269|PubMed:27119146,
CC ECO:0000269|PubMed:28115524}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-prolyl-[collagen] + O2 = CO2 + succinate +
CC trans-3-hydroxy-L-prolyl-[collagen]; 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 -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; Evidence={ECO:0000250};
CC -!- SUBUNIT: Identified in a complex with PLOD1 and P3H4.
CC {ECO:0000269|PubMed:27119146}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000255|PROSITE-
CC ProRule:PRU10138}.
CC -!- TISSUE SPECIFICITY: Detected in kidney (at protein level).
CC {ECO:0000269|PubMed:28115524}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype at birth. Lysine
CC hydroxylation of skin and bone collagen alpha chains is strongly
CC reduced. In contrast, prolyl 3-hydroxylation is not affected, possibly
CC due to complementation by other family members. Dorsal skin displays
CC impaired packing of collagen fibrils, decreased skin tensile strength,
CC and increased skin fragility. Likewise, mice deficient for both P3h3
CC and P3h4 display decreased lysine hydroxylation of collagen alpha
CC chains, but normal collagen prolyl 3-hydroxylation.
CC {ECO:0000269|PubMed:28115524}.
CC -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
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; AJ441086; CAD29580.1; -; mRNA.
DR EMBL; AY463530; AAS45239.1; -; mRNA.
DR EMBL; BC003726; AAH03726.1; -; mRNA.
DR EMBL; BC016431; AAH16431.1; -; mRNA.
DR EMBL; AC002397; AAC36012.1; -; Genomic_DNA.
DR CCDS; CCDS20533.1; -.
DR RefSeq; NP_038562.2; NM_013534.4.
DR AlphaFoldDB; Q8CG70; -.
DR SMR; Q8CG70; -.
DR BioGRID; 200050; 2.
DR STRING; 10090.ENSMUSP00000023958; -.
DR GlyGen; Q8CG70; 2 sites.
DR PhosphoSitePlus; Q8CG70; -.
DR MaxQB; Q8CG70; -.
DR PaxDb; Q8CG70; -.
DR PeptideAtlas; Q8CG70; -.
DR PRIDE; Q8CG70; -.
DR ProteomicsDB; 287749; -.
DR Antibodypedia; 21590; 120 antibodies from 20 providers.
DR DNASU; 14789; -.
DR Ensembl; ENSMUST00000023958; ENSMUSP00000023958; ENSMUSG00000023191.
DR GeneID; 14789; -.
DR KEGG; mmu:14789; -.
DR UCSC; uc009dsf.1; mouse.
DR CTD; 10536; -.
DR MGI; MGI:1315208; P3h3.
DR VEuPathDB; HostDB:ENSMUSG00000023191; -.
DR eggNOG; KOG4459; Eukaryota.
DR GeneTree; ENSGT00940000159164; -.
DR HOGENOM; CLU_017820_0_0_1; -.
DR InParanoid; Q8CG70; -.
DR OMA; KLYRDME; -.
DR OrthoDB; 660619at2759; -.
DR PhylomeDB; Q8CG70; -.
DR TreeFam; TF320837; -.
DR BRENDA; 1.14.11.7; 3474.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR BioGRID-ORCS; 14789; 0 hits in 72 CRISPR screens.
DR ChiTaRS; P3h3; mouse.
DR PRO; PR:Q8CG70; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8CG70; protein.
DR Bgee; ENSMUSG00000023191; Expressed in humerus cartilage element and 205 other tissues.
DR ExpressionAtlas; Q8CG70; baseline and differential.
DR Genevisible; Q8CG70; MM.
DR GO; GO:1902494; C:catalytic complex; IMP:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0032964; P:collagen biosynthetic process; IMP:UniProtKB.
DR GO; GO:0032963; P:collagen metabolic process; IBA:GO_Central.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0017185; P:peptidyl-lysine hydroxylation; IMP:UniProtKB.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR039575; P3H.
DR InterPro; IPR039839; P3H3.
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; PTHR14049; 1.
DR PANTHER; PTHR14049:SF14; PTHR14049:SF14; 1.
DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1.
DR SMART; SM00702; P4Hc; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Dioxygenase; Endoplasmic reticulum; Glycoprotein; Iron;
KW Metal-binding; Oxidoreductase; Reference proteome; Repeat; Signal;
KW TPR repeat; Vitamin C.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..732
FT /note="Prolyl 3-hydroxylase 3"
FT /id="PRO_0000240361"
FT REPEAT 39..72
FT /note="TPR 1"
FT REPEAT 152..185
FT /note="TPR 2"
FT REPEAT 214..247
FT /note="TPR 3"
FT REPEAT 312..345
FT /note="TPR 4"
FT DOMAIN 557..671
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 15..35
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..732
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 674..703
FT /evidence="ECO:0000255"
FT MOTIF 729..732
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT COMPBIAS 15..32
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 684..701
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 702..732
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 662
FT /evidence="ECO:0000250"
FT BINDING 580
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 582
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 652
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 732 AA; 81701 MW; BD54733B60F1687A CRC64;
MLRLLRLLLL LLLPPPGSPE PPEPPGLAQL SPGSPPQAPD LLYADGLRAY SAGAWAPAVA
LLREALRSRA ALGRARQECG ASCAAEPGAA LPSQLLGAPH PVSGPGVWEP LLLRATLRRA
ECLTQCAVRR LGPGGAARLR VGSALRDAFR RREPYNYLQR AYYQLKKLDL AASAAHTFFV
ANPTHLQMRE DMAKYRRMSA IRPQSFRDLV TPLYWAAYDT GLELLEQREA ALALPQLEEA
LQGSLAHMES CRAACEGPEE HQGAEEEGEG SQGGLYEAIA GHWIRVLQCR QHCVADTATR
PGRSFPVQDF LLSQLRRLHE AYAQVGNMSQ AMENVLSVLL FYPEDEAAKK ALNQYQTQLG
EPRPDLGPRE DIQRFILRSL GEKRQLYYAM EHLGTSFKDP DSWTPEALIP KALRERLRED
QEKKPWDHQP PQQKPLAHWK DALLMEGVTL TQDAQQLNGS ERAVLDGLLT SAECGVLLQL
AKDAAQAGAR SGYRGRRSPH SPHERFEGLT VLKAAQLARA GTVGRPGAKL LLEVSERVRT
LTQAYFSPER PLHLSFTHLV CRSAIEGEQE QRMDLSHPVH ADNCVLDPDT GECWREPPAY
TYRDYSGLLY LNDDFKGGDL FFTQPNALTV TAQVRPRCGR LVAFSSGGEN PHGVWAVTRG
RRCALALWHT WAPEHSEQEW TEAKELLQEE EEEEEEEDIL SRDPSPEPPS HKLQRVQEKA
GKPRRVRVRE EL
