P4HA2_MOUSE
ID P4HA2_MOUSE Reviewed; 537 AA.
AC Q60716; Q8VBU4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Prolyl 4-hydroxylase subunit alpha-2;
DE Short=4-PH alpha-2;
DE EC=1.14.11.2 {ECO:0000269|PubMed:7753822};
DE AltName: Full=Procollagen-proline,2-oxoglutarate-4-dioxygenase subunit alpha-2;
DE Flags: Precursor;
GN Name=P4ha2;
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] (ISOFORM IIB), FUNCTION, ACTIVITY REGULATION,
RP SUBUNIT, COFACTOR, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP INTERACTION WITH P4HB, 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 [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS IIA AND IIB).
RX PubMed=11606192; DOI=10.1046/j.0014-2956.2001.02464.x;
RA Nokelainen M., Nissi R., Kukkola L., Helaakoski T., Myllyharju J.;
RT "Characterization of the human and mouse genes for the alpha subunit of
RT type II prolyl 4-hydroxylase. Identification of a previously unknown
RT alternatively spliced exon and its expression in various tissues.";
RL Eur. J. Biochem. 268:5300-5309(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IIA).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and 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 [5]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-482, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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 Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000305|PubMed:7753822};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000305|PubMed:7753822};
CC -!- ACTIVITY REGULATION: Inhibited by poly(L-proline) only at very high
CC concentrations. {ECO:0000269|PubMed:7753822}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12 uM for 2-oxoglutarate {ECO:0000269|PubMed:7753822};
CC -!- SUBUNIT: Heterotetramer of two alpha-2 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=IIb; Synonyms=alpha(II) {ECO:0000303|PubMed:7753822};
CC IsoId=Q60716-1; Sequence=Displayed;
CC Name=IIa;
CC IsoId=Q60716-2; Sequence=VSP_004507;
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; U16163; AAC52198.1; -; mRNA.
DR EMBL; AJ314858; CAC85690.1; -; Genomic_DNA.
DR EMBL; AJ314858; CAC85691.1; -; Genomic_DNA.
DR EMBL; BC018411; AAH18411.1; -; mRNA.
DR CCDS; CCDS24691.1; -. [Q60716-1]
DR CCDS; CCDS48797.1; -. [Q60716-2]
DR PIR; I49135; I49135.
DR RefSeq; NP_001129548.1; NM_001136076.2. [Q60716-2]
DR RefSeq; NP_035161.2; NM_011031.2.
DR AlphaFoldDB; Q60716; -.
DR SMR; Q60716; -.
DR BioGRID; 202007; 3.
DR CORUM; Q60716; -.
DR IntAct; Q60716; 1.
DR STRING; 10090.ENSMUSP00000019050; -.
DR GlyConnect; 2612; 1 N-Linked glycan (1 site).
DR GlyGen; Q60716; 2 sites, 1 N-linked glycan (1 site).
DR PhosphoSitePlus; Q60716; -.
DR EPD; Q60716; -.
DR jPOST; Q60716; -.
DR MaxQB; Q60716; -.
DR PaxDb; Q60716; -.
DR PeptideAtlas; Q60716; -.
DR PRIDE; Q60716; -.
DR ProteomicsDB; 294230; -. [Q60716-1]
DR ProteomicsDB; 294231; -. [Q60716-2]
DR Antibodypedia; 35136; 145 antibodies from 25 providers.
DR DNASU; 18452; -.
DR Ensembl; ENSMUST00000093107; ENSMUSP00000091749; ENSMUSG00000018906. [Q60716-2]
DR Ensembl; ENSMUST00000174616; ENSMUSP00000133275; ENSMUSG00000018906. [Q60716-2]
DR GeneID; 18452; -.
DR KEGG; mmu:18452; -.
DR CTD; 8974; -.
DR MGI; MGI:894286; P4ha2.
DR VEuPathDB; HostDB:ENSMUSG00000018906; -.
DR eggNOG; KOG1591; Eukaryota.
DR GeneTree; ENSGT00940000157695; -.
DR InParanoid; Q60716; -.
DR OrthoDB; 391515at2759; -.
DR PhylomeDB; Q60716; -.
DR Reactome; R-MMU-1650814; Collagen biosynthesis and modifying enzymes.
DR BioGRID-ORCS; 18452; 1 hit in 74 CRISPR screens.
DR PRO; PR:Q60716; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60716; protein.
DR Bgee; ENSMUSG00000018906; Expressed in molar tooth and 232 other tissues.
DR ExpressionAtlas; Q60716; baseline and differential.
DR Genevisible; Q60716; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0016222; C:procollagen-proline 4-dioxygenase complex; IDA: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: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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..537
FT /note="Prolyl 4-hydroxylase subunit alpha-2"
FT /id="PRO_0000022727"
FT REPEAT 209..242
FT /note="TPR"
FT DOMAIN 414..522
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 432
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 434
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 503
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 513
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT MOD_RES 482
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 438..453
FT /note="SDDEDAFKRLGTGNRV -> RPFDSGLKTEGNRL (in isoform IIa)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_004507"
SQ SEQUENCE 537 AA; 61002 MW; C47D976C75E82518 CRC64;
MKLQVLVLVL LMSWFGVLSW VQAEFFTSIG HMTDLIYAEK DLVQSLKEYI LVEEAKLAKI
KSWASKMEAL TSRSAADPEG YLAHPVNAYK LVKRLNTDWP ALGDLVLQDA SAGFVANLSV
QRQFFPTDED ESGAARALMR LQDTYKLDPD TISRGELPGT KYQAMLSVDD CFGLGRSAYN
EGDYYHTVLW MEQVLKQLDA GEEATVTKSL VLDYLSYAVF QLGDLHRAVE LTRRLLSLDP
SHERAGGNLR YFERLLEEER GKSLSNQTDA GLATQENLYE RPTDYLPERD VYESLCRGEG
VKLTPRRQKK LFCRYHHGNR VPQLLIAPFK EEDEWDSPHI VRYYDVMSDE EIERIKEIAK
PKLARATVRD PKTGVLTVAS YRVSKSSWLE EDDDPVVARV NRRMQHITGL TVKTAELLQV
ANYGMGGQYE PHFDFSRSDD EDAFKRLGTG NRVATFLNYM SDVEAGGATV FPDLGAAIWP
KKGTAVFWYN LLRSGEGDYR TRHAACPVLV GCKWVSNKWF HERGQEFLRP CGTTEVD
