P4HA1_MOUSE
ID P4HA1_MOUSE Reviewed; 534 AA.
AC Q60715; Q3TEB7; Q80T05; Q91VJ7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Prolyl 4-hydroxylase subunit alpha-1;
DE Short=4-PH alpha-1;
DE EC=1.14.11.2 {ECO:0000269|PubMed:7753822};
DE AltName: Full=Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-1;
DE Flags: Precursor;
GN Name=P4ha1;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, Head, and Thymus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-534 (ISOFORM 2), FUNCTION, COFACTOR,
RP SUBUNIT, ACTIVITY REGULATION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND TISSUE SPECIFICITY.
RX PubMed=7753822; DOI=10.1073/pnas.92.10.4427;
RA Helaakoski T., Annunen P., Vuori K., Macneil I.A., Pihlajaniemi T.,
RA Kivirikko K.I.;
RT "Cloning, baculovirus expression, and characterization of a second mouse
RT prolyl 4-hydroxylase alpha-subunit isoform: formation of an alpha 2 beta 2
RT tetramer with the protein disulfide-isomerase/beta subunit.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4427-4431(1995).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
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).
CC -!- FUNCTION: Catalyzes the post-translational formation of 4-
CC hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other
CC proteins. {ECO:0000269|PubMed:7753822}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-prolyl-[collagen] + O2 = CO2 + succinate +
CC trans-4-hydroxy-L-prolyl-[collagen]; Xref=Rhea:RHEA:18945, Rhea:RHEA-
CC COMP:11676, Rhea:RHEA-COMP:11680, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:50342, ChEBI:CHEBI:61965; EC=1.14.11.2;
CC Evidence={ECO:0000269|PubMed:7753822};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18946;
CC Evidence={ECO:0000305|PubMed:7753822};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000305|PubMed:7753822};
CC Note=Binds 1 Fe(2+) ion per subunit.;
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000305|PubMed:7753822};
CC -!- ACTIVITY REGULATION: Inhibited by poly(L-proline).
CC {ECO:0000269|PubMed:7753822}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=22 uM for 2-oxoglutarate {ECO:0000269|PubMed:7753822};
CC -!- SUBUNIT: Heterotetramer of two alpha-1 chains and two beta chains
CC (P4HB)(the beta chain is the multi-functional PDI), where P4HB plays
CC the role of a structural subunit; this tetramer catalyzes the formation
CC of 4-hydroxyproline in collagen. {ECO:0000269|PubMed:7753822}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60715-1; Sequence=Displayed;
CC Name=2; Synonyms=alpha(I) {ECO:0000303|PubMed:7753822};
CC IsoId=Q60715-2; Sequence=VSP_004505;
CC -!- TISSUE SPECIFICITY: Expressed at least in brain, heart and lung.
CC {ECO:0000269|PubMed:7753822}.
CC -!- SIMILARITY: Belongs to the P4HA family. {ECO:0000305}.
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DR EMBL; AK045008; BAC32183.1; -; mRNA.
DR EMBL; AK160798; BAE36020.1; -; mRNA.
DR EMBL; AK169726; BAE41331.1; -; mRNA.
DR EMBL; BC009654; AAH09654.1; -; mRNA.
DR EMBL; U16162; AAC52197.1; -; mRNA.
DR CCDS; CCDS23863.1; -. [Q60715-1]
DR CCDS; CCDS83698.1; -. [Q60715-2]
DR PIR; I49134; I49134.
DR RefSeq; NP_001303300.1; NM_001316371.1. [Q60715-2]
DR RefSeq; NP_035160.1; NM_011030.2. [Q60715-1]
DR AlphaFoldDB; Q60715; -.
DR SMR; Q60715; -.
DR BioGRID; 202006; 11.
DR IntAct; Q60715; 3.
DR MINT; Q60715; -.
DR STRING; 10090.ENSMUSP00000009789; -.
DR GlyGen; Q60715; 2 sites.
DR iPTMnet; Q60715; -.
DR PhosphoSitePlus; Q60715; -.
DR SwissPalm; Q60715; -.
DR EPD; Q60715; -.
DR jPOST; Q60715; -.
DR MaxQB; Q60715; -.
DR PaxDb; Q60715; -.
DR PeptideAtlas; Q60715; -.
DR PRIDE; Q60715; -.
DR ProteomicsDB; 287752; -. [Q60715-1]
DR ProteomicsDB; 287753; -. [Q60715-2]
DR Antibodypedia; 2000; 264 antibodies from 33 providers.
DR DNASU; 18451; -.
DR Ensembl; ENSMUST00000009789; ENSMUSP00000009789; ENSMUSG00000019916. [Q60715-1]
DR Ensembl; ENSMUST00000105466; ENSMUSP00000101106; ENSMUSG00000019916. [Q60715-2]
DR GeneID; 18451; -.
DR KEGG; mmu:18451; -.
DR UCSC; uc007fdo.2; mouse. [Q60715-1]
DR UCSC; uc007fdp.2; mouse. [Q60715-2]
DR CTD; 5033; -.
DR MGI; MGI:97463; P4ha1.
DR VEuPathDB; HostDB:ENSMUSG00000019916; -.
DR eggNOG; KOG1591; Eukaryota.
DR GeneTree; ENSGT00940000156635; -.
DR InParanoid; Q60715; -.
DR OMA; NLTQYRN; -.
DR PhylomeDB; Q60715; -.
DR TreeFam; TF313393; -.
DR BRENDA; 1.14.11.2; 3474.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR BioGRID-ORCS; 18451; 2 hits in 77 CRISPR screens.
DR ChiTaRS; P4ha1; mouse.
DR PRO; PR:Q60715; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q60715; protein.
DR Bgee; ENSMUSG00000019916; Expressed in vault of skull and 269 other tissues.
DR ExpressionAtlas; Q60715; baseline and differential.
DR Genevisible; Q60715; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0016222; C:procollagen-proline 4-dioxygenase complex; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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:0004656; F:procollagen-proline 4-dioxygenase activity; IDA:MGI.
DR GO; GO:0030199; P:collagen fibril organization; IMP:MGI.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:MGI.
DR Gene3D; 1.25.40.10; -; 1.
DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase.
DR InterPro; IPR045054; P4HA-like.
DR InterPro; IPR006620; Pro_4_hyd_alph.
DR InterPro; IPR044862; Pro_4_hyd_alph_FE2OG_OXY.
DR InterPro; IPR013547; Pro_4_hyd_alph_N.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR PANTHER; PTHR10869; PTHR10869; 1.
DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1.
DR Pfam; PF08336; P4Ha_N; 1.
DR SMART; SM00702; P4Hc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR PROSITE; PS51471; FE2OG_OXY; 1.
DR PROSITE; PS50005; TPR; 1.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Dioxygenase; Endoplasmic reticulum; Glycoprotein;
KW Iron; Metal-binding; Oxidoreductase; Reference proteome; Signal;
KW TPR repeat; Vitamin C.
FT SIGNAL 1..17
FT /evidence="ECO:0000250"
FT CHAIN 18..534
FT /note="Prolyl 4-hydroxylase subunit alpha-1"
FT /id="PRO_0000022724"
FT REPEAT 205..238
FT /note="TPR"
FT DOMAIN 411..519
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 429
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 431
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 500
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 510
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 361..380
FT /note="RRATISNPVTGALETVHYRI -> SRATVHDPETGKLTTAQYRV (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:7753822"
FT /id="VSP_004505"
FT CONFLICT 69
FT /note="T -> R (in Ref. 3; AAC52197)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="T -> N (in Ref. 3; AAC52197)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="D -> Y (in Ref. 3; AAC52197)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 534 AA; 60910 MW; 81F6C61019E79460 CRC64;
MIWVVLMMAI LLPQSLAHPG FFTSIGQMTD LIHNEKDLVT SLKDYIKAEE DKLEQIKKWA
EKLDRLTSTA TKDPEGFVGH PVNAFKLMKR LNTEWSELEN LILKDMSDGF ISNLTIQRQY
FPNDEDQVGA AKALFRLQDT YNLDTNTISK GNLPGVQHKS FLTAEDCFEL GKVAYTEADY
YHTELWMEQA LTQLEEGELS TVDKVSVLDY LSYAVYQQGD LDKALLLTKK LLELDPEHQR
ANGNLVYFEY IMSKEKDANK SASGDQSDQK TAPKKKGIAV DYLPERQKYE MLCRGEGIKM
TPRRQKRLFC RYHDGNRNPK FILAPAKQED EWDKPRIIRF HDIISDAEIE IVKDLAKPRL
RRATISNPVT GALETVHYRI SKSAWLSGYE DPVVSRINMR IQDLTGLDVS TAEELQVANY
GVGGQYEPHF DFARKDEPDA FRELGTGNRI ATWLFYMSDV SAGGATVFPE VGASVWPKKG
TAVFWYNLFA SGEGDYSTRH AACPVLVGNK WVSNKWLHER GQEFRRPCTL SELE
