ID   P3H3_HUMAN              Reviewed;         736 AA.
AC   Q8IVL6; Q13512; Q15740; Q66K32; Q6NX61; Q7L2T1;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   27-MAR-2024, entry version 169.
DE   RecName: Full=Prolyl 3-hydroxylase 3 {ECO:0000312|HGNC:HGNC:19318};
DE            EC=1.14.11.7;
DE   AltName: Full=Leprecan-like protein 2 {ECO:0000303|PubMed:15063763};
DE   AltName: Full=Protein B {ECO:0000303|PubMed:8723724};
DE   Flags: Precursor;
GN   Name=P3H3 {ECO:0000312|HGNC:HGNC:19318};
GN   Synonyms=LEPREL2 {ECO:0000303|PubMed:15063763};
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 [GENOMIC DNA / MRNA] (ISOFORM 2), TISSUE SPECIFICITY,
RP   AND VARIANT ALA-301.
RC   TISSUE=Fibrosarcoma;
RX   PubMed=8723724; DOI=10.1101/gr.6.4.314;
RA   Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA   Malley T., Gibbs R.A.;
RT   "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at
RT   human chromosome 12p13.";
RL   Genome Res. 6:314-326(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA   Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT   "Large-scale sequencing in human chromosome 12p13: experimental and
RT   computational gene structure determination.";
RL   Genome Res. 7:268-280(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 54-736 (ISOFORM 1), AND VARIANT
RP   THR-685.
RC   TISSUE=Eye, and Uterus;
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   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   [6]
RP   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       Required for normal hydroxylation of lysine residues in type I collagen
CC       chains in skin, bone, tendon, aorta and cornea. Required for normal
CC       skin stability via its role in hydroxylation of lysine residues in
CC       collagen alpha chains and in collagen fibril assembly. Apparently not
CC       required for normal prolyl 3-hydroxylation on collagen chains, possibly
CC       because it functions redundantly with other prolyl 3-hydroxylases.
CC       {ECO:0000250|UniProtKB:Q8CG70}.
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:0000250|UniProtKB:Q8CG70}.
CC   -!- INTERACTION:
CC       Q8IVL6-2; P22607: FGFR3; NbExp=3; IntAct=EBI-12149899, EBI-348399;
CC       Q8IVL6-2; P42858: HTT; NbExp=6; IntAct=EBI-12149899, EBI-466029;
CC       Q8IVL6-2; Q15323: KRT31; NbExp=3; IntAct=EBI-12149899, EBI-948001;
CC       Q8IVL6-2; Q8IUG1: KRTAP1-3; NbExp=3; IntAct=EBI-12149899, EBI-11749135;
CC       Q8IVL6-2; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-12149899, EBI-11953334;
CC       Q8IVL6-2; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-12149899, EBI-1044640;
CC       Q8IVL6-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-12149899, EBI-748974;
CC       Q8IVL6-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-12149899, EBI-5235340;
CC       Q8IVL6-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-12149899, EBI-741480;
CC       Q8IVL6-2; Q9Y649; NbExp=3; IntAct=EBI-12149899, EBI-25900580;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000255|PROSITE-
CC       ProRule:PRU10138}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8IVL6-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8IVL6-2; Sequence=VSP_019352;
CC   -!- TISSUE SPECIFICITY: Detected in fetal cartilage (at protein level)
CC       (PubMed:28115524). Weak expression in heart, lung, ovary and skeletal
CC       muscle (PubMed:8723724). {ECO:0000269|PubMed:28115524,
CC       ECO:0000269|PubMed:8723724}.
CC   -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
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DR   EMBL; U47924; AAB51312.1; -; Genomic_DNA.
DR   EMBL; U47926; AAC50464.1; -; mRNA.
DR   EMBL; AJ430349; CAD23037.1; -; mRNA.
DR   EMBL; BC017217; AAH17217.2; -; mRNA.
DR   EMBL; BC067251; AAH67251.1; -; mRNA.
DR   EMBL; BC080630; AAH80630.1; -; mRNA.
DR   CCDS; CCDS61027.1; -. [Q8IVL6-1]
DR   RefSeq; NP_055077.2; NM_014262.4. [Q8IVL6-1]
DR   AlphaFoldDB; Q8IVL6; -.
DR   BioGRID; 115790; 164.
DR   IntAct; Q8IVL6; 32.
DR   STRING; 9606.ENSP00000478600; -.
DR   DrugBank; DB00126; Ascorbic acid.
DR   DrugBank; DB00172; Proline.
DR   DrugBank; DB00139; Succinic acid.
DR   GlyCosmos; Q8IVL6; 2 sites, No reported glycans.
DR   GlyGen; Q8IVL6; 3 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q8IVL6; -.
DR   PhosphoSitePlus; Q8IVL6; -.
DR   BioMuta; P3H3; -.
DR   DMDM; 74714366; -.
DR   EPD; Q8IVL6; -.
DR   jPOST; Q8IVL6; -.
DR   MassIVE; Q8IVL6; -.
DR   MaxQB; Q8IVL6; -.
DR   PaxDb; 9606-ENSP00000478600; -.
DR   PeptideAtlas; Q8IVL6; -.
DR   ProteomicsDB; 70738; -. [Q8IVL6-1]
DR   ProteomicsDB; 70739; -. [Q8IVL6-2]
DR   Pumba; Q8IVL6; -.
DR   Antibodypedia; 21590; 135 antibodies from 20 providers.
DR   DNASU; 10536; -.
DR   Ensembl; ENST00000290510.10; ENSP00000478600.1; ENSG00000110811.20. [Q8IVL6-1]
DR   GeneID; 10536; -.
DR   KEGG; hsa:10536; -.
DR   MANE-Select; ENST00000290510.10; ENSP00000478600.1; NM_014262.5; NP_055077.2.
DR   UCSC; uc031yrv.2; human. [Q8IVL6-1]
DR   AGR; HGNC:19318; -.
DR   CTD; 10536; -.
DR   DisGeNET; 10536; -.
DR   GeneCards; P3H3; -.
DR   HGNC; HGNC:19318; P3H3.
DR   HPA; ENSG00000110811; Low tissue specificity.
DR   MIM; 610342; gene.
DR   neXtProt; NX_Q8IVL6; -.
DR   OpenTargets; ENSG00000110811; -.
DR   PharmGKB; PA134890414; -.
DR   VEuPathDB; HostDB:ENSG00000110811; -.
DR   eggNOG; KOG4459; Eukaryota.
DR   GeneTree; ENSGT00940000159164; -.
DR   HOGENOM; CLU_017820_0_0_1; -.
DR   InParanoid; Q8IVL6; -.
DR   OMA; KQCWREP; -.
DR   OrthoDB; 5398065at2759; -.
DR   PhylomeDB; Q8IVL6; -.
DR   BRENDA; 1.14.11.28; 2681.
DR   BRENDA; 1.14.11.7; 2681.
DR   PathwayCommons; Q8IVL6; -.
DR   Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR   SignaLink; Q8IVL6; -.
DR   BioGRID-ORCS; 10536; 10 hits in 719 CRISPR screens.
DR   ChiTaRS; P3H3; human.
DR   GeneWiki; LEPREL2; -.
DR   GenomeRNAi; 10536; -.
DR   Pharos; Q8IVL6; Tbio.
DR   PRO; PR:Q8IVL6; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; Q8IVL6; Protein.
DR   Bgee; ENSG00000110811; Expressed in stromal cell of endometrium and 105 other cell types or tissues.
DR   GO; GO:1902494; C:catalytic complex; ISS: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; ISS:UniProtKB.
DR   GO; GO:0032963; P:collagen metabolic process; IBA:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR   GO; GO:0017185; P:peptidyl-lysine hydroxylation; ISS:UniProtKB.
DR   Gene3D; 2.60.120.620; q2cbj1_9rhob like domain; 1.
DR   Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR   InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
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:SF14; PROLYL 3-HYDROXYLASE 3; 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.
DR   Genevisible; Q8IVL6; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Coiled coil; Dioxygenase; Endoplasmic reticulum;
KW   Glycoprotein; Iron; Metal-binding; Oxidoreductase; Reference proteome;
KW   Repeat; Signal; TPR repeat; Vitamin C.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..736
FT                   /note="Prolyl 3-hydroxylase 3"
FT                   /id="PRO_0000240360"
FT   REPEAT          37..70
FT                   /note="TPR 1"
FT   REPEAT          154..187
FT                   /note="TPR 2"
FT   REPEAT          216..249
FT                   /note="TPR 3"
FT   REPEAT          316..349
FT                   /note="TPR 4"
FT   DOMAIN          561..675
FT                   /note="Fe2OG dioxygenase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT   REGION          253..275
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          689..736
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          681..709
FT                   /evidence="ECO:0000255"
FT   MOTIF           733..736
FT                   /note="Prevents secretion from ER"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT   COMPBIAS        692..707
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        708..736
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        666
FT                   /evidence="ECO:0000250"
FT   BINDING         584
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT   BINDING         586
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT   BINDING         656
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        462
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..185
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:8723724"
FT                   /id="VSP_019352"
FT   VARIANT         301
FT                   /note="T -> A (in dbSNP:rs10744716)"
FT                   /evidence="ECO:0000269|PubMed:8723724"
FT                   /id="VAR_050443"
FT   VARIANT         304
FT                   /note="R -> C (in dbSNP:rs35359746)"
FT                   /id="VAR_050444"
FT   VARIANT         385
FT                   /note="G -> E (in dbSNP:rs1047771)"
FT                   /id="VAR_050445"
FT   VARIANT         685
FT                   /note="I -> T (in dbSNP:rs1129649)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_050446"
FT   VARIANT         705
FT                   /note="M -> T (in dbSNP:rs3213431)"
FT                   /id="VAR_050447"
FT   CONFLICT        79..82
FT                   /note="ASCA -> RTRG (in Ref. 4; AAH67251)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   736 AA;  81837 MW;  82526D30C9788369 CRC64;
     MLRLLRPLLL LLLLPPPGSP EPPGLTQLSP GAPPQAPDLL YADGLRAYAA GAWAPAVALL
     REALRSQAAL GRVRLDCGAS CAADPGAALP AVLLGAPEPD SGPGPTQGSW ERQLLRAALR
     RADCLTQCAA RRLGPGGAAR LRVGSALRDA FRRREPYNYL QRAYYQLKKL DLAAAAAHTF
     FVANPMHLQM REDMAKYRRM SGVRPQSFRD LETPPHWAAY DTGLELLGRQ EAGLALPRLE
     EALQGSLAQM ESCRADCEGP EEQQGAEEEE DGAASQGGLY EAIAGHWIQV LQCRQRCVGE
     TATRPGRSFP VPDFLPNQLR RLHEAHAQVG NLSQAIENVL SVLLFYPEDE AAKRALNQYQ
     AQLGEPRPGL GPREDIQRFI LRSLGEKRQL YYAMEHLGTS FKDPDPWTPA ALIPEALREK
     LREDQEKRPW DHEPVKPKPL TYWKDVLLLE GVTLTQDSRQ LNGSERAVLD GLLTPAECGV
     LLQLAKDAAG AGARSGYRGR RSPHTPHERF EGLTVLKAAQ LARAGTVGSQ GAKLLLEVSE
     RVRTLTQAYF SPERPLHLSF THLVCRSAIE GEQEQRMDLS HPVHADNCVL DPDTGECWRE
     PPAYTYRDYS GLLYLNDDFQ GGDLFFTEPN ALTVTARVRP RCGRLVAFSS GVENPHGVWA
     VTRGRRCALA LWHTWAPEHR EQEWIEAKEL LQESQEEEEE EEEEMPSKDP SPEPPSRRHQ
     RVQDKTGRAP RVREEL
//