P3H3_HUMAN
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 03-AUG-2022, entry version 160.
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}.
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; 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; 161.
DR IntAct; Q8IVL6; 32.
DR STRING; 9606.ENSP00000478600; -.
DR DrugBank; DB00126; Ascorbic acid.
DR DrugBank; DB00172; Proline.
DR DrugBank; DB00139; Succinic acid.
DR GlyGen; Q8IVL6; 2 sites.
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; Q8IVL6; -.
DR PeptideAtlas; Q8IVL6; -.
DR PRIDE; Q8IVL6; -.
DR ProteomicsDB; 70738; -. [Q8IVL6-1]
DR ProteomicsDB; 70739; -. [Q8IVL6-2]
DR Antibodypedia; 21590; 120 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 CTD; 10536; -.
DR DisGeNET; 10536; -.
DR GeneCards; P3H3; -.
DR HGNC; HGNC:19318; P3H3.
DR HPA; ENSG00000110811; Tissue enhanced (endometrium).
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; KLYRDME; -.
DR OrthoDB; 660619at2759; -.
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 660 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 104 other tissues.
DR Genevisible; Q8IVL6; HS.
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; 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 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
