P3H2_MOUSE
ID P3H2_MOUSE Reviewed; 703 AA.
AC Q8CG71; Q8C673;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Prolyl 3-hydroxylase 2 {ECO:0000312|MGI:MGI:2146663};
DE EC=1.14.11.7 {ECO:0000305|PubMed:25645914};
DE AltName: Full=Leprecan-like protein 1 {ECO:0000303|PubMed:15063763};
DE Flags: Precursor;
GN Name=P3h2 {ECO:0000312|MGI:MGI:2146663};
GN Synonyms=Leprel1 {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 [LARGE SCALE MRNA] OF 295-703.
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=18487197; DOI=10.1074/jbc.m802973200;
RA Tiainen P., Pasanen A., Sormunen R., Myllyharju J.;
RT "Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an
RT enzyme modifying the basement membrane collagen IV.";
RL J. Biol. Chem. 283:19432-19439(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
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 [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=24368846; DOI=10.1073/pnas.1307597111;
RA Pokidysheva E., Boudko S., Vranka J., Zientek K., Maddox K., Moser M.,
RA Faessler R., Ware J., Baechinger H.P.;
RT "Biological role of prolyl 3-hydroxylation in type IV collagen.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:161-166(2014).
RN [6]
RP DISRUPTION PHENOTYPE, FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RX PubMed=25645914; DOI=10.1074/jbc.m114.634915;
RA Hudson D.M., Joeng K.S., Werther R., Rajagopal A., Weis M., Lee B.H.,
RA Eyre D.R.;
RT "Post-translationally abnormal collagens of prolyl 3-hydroxylase-2 null
RT mice offer a pathobiological mechanism for the high myopia linked to human
RT LEPREL1 mutations.";
RL J. Biol. Chem. 290:8613-8622(2015).
CC -!- FUNCTION: Prolyl 3-hydroxylase that catalyzes the post-translational
CC formation of 3-hydroxyproline on collagens (PubMed:24368846,
CC PubMed:25645914). Contributes to proline 3-hydroxylation of collagen
CC COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens
CC capsule (PubMed:25645914). Has high activity with the type IV collagen
CC COL4A1, and lower activity with COL1A1. Catalyzes hydroxylation of the
CC first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline. Has
CC no activity on substrates that have proline instead of 4-hydroxyproline
CC in the third position (By similarity). {ECO:0000250|UniProtKB:Q8IVL5,
CC ECO:0000269|PubMed:24368846, ECO:0000269|PubMed:25645914}.
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 Evidence={ECO:0000305|PubMed:25645914};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q8IVL5};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000250|UniProtKB:Q8IVL5};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q8IVL5, ECO:0000255|PROSITE-ProRule:PRU10138}.
CC Sarcoplasmic reticulum {ECO:0000250|UniProtKB:Q8IVL5}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q8IVL5}.
CC -!- TISSUE SPECIFICITY: Detected in kidney (PubMed:25645914). Detected on
CC kidney tubular cells, pancreas acinar cells, Schwann cells of the
CC peripheral nerve in the pinna, and in tunica adventitia, the smooth
CC muscle layer of the aortic wall (at protein level) (PubMed:18487197).
CC Detected in lung, skeletal muscle and kidney (PubMed:18487197).
CC Detected in kidney glomeruli and in prehypertrophic regions of long
CC bone from neonates (PubMed:25645914). In the eye, detected in the
CC epithelial layer of the cornea and at lower levels in the sclera at the
CC posterior end of the eye (PubMed:25645914).
CC {ECO:0000269|PubMed:18487197, ECO:0000269|PubMed:25645914}.
CC -!- DISRUPTION PHENOTYPE: Contradictory results have been described and may
CC be due to differences in the methods used for gene disruption
CC (PubMed:24368846, PubMed:25645914). No visible phenotype, but decreased
CC 3-hydroxyproline formation in collagen COL4A1 and COL1A1
CC (PubMed:25645914). Full embryonic lethality; the vast majority die
CC before 8.5 dpc (PubMed:24368846). The embryos appear normal, but are
CC surrounded by maternal platelet aggregates and blood clots that form at
CC about 6.5 dpc, resulting in embryonic death (PubMed:24368846). Maternal
CC platelet aggregation is triggered by interaction between maternal Gp6
CC and embryonic type IV collagen that lacks 3-hydroxyproline
CC (PubMed:24368846). Likewise, pregnant females deficient for Gp6 and
CC P3h2 that bear embryos deficient in P3h2 and heterozygous for Gp6 do
CC not produce any live offspring (PubMed:24368846). In contrast, mutant
CC mice deficient in Gp6 and P3h2 are born at the expected Mendelian rate
CC and have no visible phenotype (PubMed:24368846).
CC {ECO:0000269|PubMed:24368846, ECO:0000269|PubMed:25645914}.
CC -!- SIMILARITY: Belongs to the leprecan family. {ECO:0000305}.
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DR EMBL; AJ430350; CAD23038.1; -; mRNA.
DR EMBL; AK076434; BAC36342.1; -; mRNA.
DR CCDS; CCDS28086.1; -.
DR RefSeq; NP_775555.1; NM_173379.2.
DR AlphaFoldDB; Q8CG71; -.
DR BioGRID; 229159; 1.
DR IntAct; Q8CG71; 1.
DR STRING; 10090.ENSMUSP00000038056; -.
DR GlyGen; Q8CG71; 2 sites.
DR iPTMnet; Q8CG71; -.
DR PhosphoSitePlus; Q8CG71; -.
DR MaxQB; Q8CG71; -.
DR PaxDb; Q8CG71; -.
DR PeptideAtlas; Q8CG71; -.
DR PRIDE; Q8CG71; -.
DR ProteomicsDB; 294304; -.
DR Antibodypedia; 1998; 118 antibodies from 20 providers.
DR DNASU; 210530; -.
DR Ensembl; ENSMUST00000039990; ENSMUSP00000038056; ENSMUSG00000038168.
DR GeneID; 210530; -.
DR KEGG; mmu:210530; -.
DR UCSC; uc007yuy.1; mouse.
DR CTD; 55214; -.
DR MGI; MGI:2146663; P3h2.
DR VEuPathDB; HostDB:ENSMUSG00000038168; -.
DR eggNOG; KOG4459; Eukaryota.
DR GeneTree; ENSGT00940000159593; -.
DR HOGENOM; CLU_017820_0_0_1; -.
DR InParanoid; Q8CG71; -.
DR OMA; AKPHMED; -.
DR OrthoDB; 660619at2759; -.
DR PhylomeDB; Q8CG71; -.
DR TreeFam; TF320837; -.
DR BRENDA; 1.14.11.7; 3474.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR BioGRID-ORCS; 210530; 1 hit in 73 CRISPR screens.
DR ChiTaRS; P3h2; mouse.
DR PRO; PR:Q8CG71; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q8CG71; protein.
DR Bgee; ENSMUSG00000038168; Expressed in right kidney and 160 other tissues.
DR Genevisible; Q8CG71; MM.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; 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:0019797; F:procollagen-proline 3-dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0032963; P:collagen metabolic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0019511; P:peptidyl-proline hydroxylation; ISS:UniProtKB.
DR Gene3D; 1.25.40.10; -; 2.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR039575; P3H.
DR InterPro; IPR039838; P3H2.
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:SF1; PTHR14049:SF1; 1.
DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1.
DR SMART; SM00702; P4Hc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
PE 1: Evidence at protein level;
KW Dioxygenase; Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Iron;
KW Metal-binding; Oxidoreductase; Reference proteome; Repeat;
KW Sarcoplasmic reticulum; Signal; TPR repeat; Vitamin C.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..703
FT /note="Prolyl 3-hydroxylase 2"
FT /id="PRO_0000240357"
FT REPEAT 42..75
FT /note="TPR 1"
FT REPEAT 144..177
FT /note="TPR 2"
FT REPEAT 205..238
FT /note="TPR 3"
FT REPEAT 301..334
FT /note="TPR 4"
FT DOMAIN 552..666
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT REGION 17..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 700..703
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10138"
FT ACT_SITE 657
FT /evidence="ECO:0000250"
FT BINDING 575
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 577
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT BINDING 647
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 497
FT /note="P -> A (in Ref. 2; BAC36342)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 703 AA; 80154 MW; 1F42F9B9938573E4 CRC64;
MRESTWVSLL LLLLLPTPQR GGPQDGRRSP EPEPERGPLQ PFDLLYASGV AAYYSGDYER
AVRDLEAALS SHRRLRDIRT RCARHCAARR PLAPPGAGPG AELPFFRAVL ERARCSRSCQ
SQRLGGPASR HRVSEDVRSD FQRRVPYNYL QRAYIKLNQL EKAMEAAHTF FMANPEHMEM
QQDLEDYKAT ARVEAPLLDR EAKPHLESYN AGVKHYEADD FESAIKYFEQ ALREYFNEDM
ECRALCEGPQ RFEEYEYLGY KGGLYEAIAD HYMQVLVCQH ECVRELATRP GRLSPIENFL
PLHYDYLQFA YYRVGEYVKA LECAKAYLMF HPDNEDVLDN VDFYESLLDD STDPASIEAR
EDLTAFVKRH KLEAELIKLA AEGLGFSYAE PNYWISYGGR QDENRVPSGV NMDGAEVHGL
SMGKKSPPKI GRDLREGGPL LYENITFVYN SEQLNGTQRV LLDNVLSQEQ CRELHSVANG
IMLVGDGYRG KTSPHTPNEK FEGATVLKAL KFGYEGRVPL KSARLFYDIS EKARKIVESY
FMLNSTLYFS YTHMVCRTAL SGQQDRRNDL SHPIHADNCL LDPEANECWK EPPAYTFRDY
SALLYMNDDF DGGEFIFTEM DAKTVTASIK PKCGRMISFS SGGENPHGVK AVTRGQRCAV
ALWFTLDPLY RELERIQADE VIAILDQEQR GKHGLNINPK DEL
