CP2DP_PIG
ID CP2DP_PIG Reviewed; 500 AA.
AC O46658;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Vitamin D(3) 25-hydroxylase;
DE EC=1.14.14.24;
DE AltName: Full=CYPIID25;
DE AltName: Full=Cytochrome P450 2D25;
GN Name=CYP2D25;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-57; 249-273 AND
RP 408-430.
RC TISSUE=Liver;
RX PubMed=9425298; DOI=10.1006/bbrc.1997.7551;
RA Postlind H., Axen E., Bergman T., Wikvall K.;
RT "Cloning, structure, and expression of a cDNA encoding vitamin D3 25-
RT hydroxylase.";
RL Biochem. Biophys. Res. Commun. 241:491-497(1997).
RN [2]
RP PROTEIN SEQUENCE OF 2-22, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Kidney;
RX PubMed=2169238; DOI=10.1042/bj2700345;
RA Bergman T., Postlind H.;
RT "Characterization of pig kidney microsomal cytochrome P-450 catalysing 25-
RT hydroxylation of vitamin D3 and C27 steroids.";
RL Biochem. J. 270:345-350(1990).
RN [3]
RP PROTEIN SEQUENCE OF 2-17, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=1445236; DOI=10.1042/bj2870725;
RA Axen E., Bergman T., Wikvall K.;
RT "Purification and characterization of a vitamin D3 25-hydroxylase from pig
RT liver microsomes.";
RL Biochem. J. 287:725-731(1992).
CC -!- FUNCTION: Catalyzes the 25-hydroxylation of vitamin D(3) (calciol),
CC 1alpha-hydroxyvitamin D(3) (alphacalcidiol) and some C27 steroids. In
CC addition the enzyme catalyzes the hydroxylation of positions 11 and 12
CC of dodecanoate. {ECO:0000269|PubMed:1445236,
CC ECO:0000269|PubMed:2169238}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calciol + O2 + reduced [NADPH--hemoprotein reductase] =
CC calcidiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:32903, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17933, ChEBI:CHEBI:28940, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.24;
CC Evidence={ECO:0000269|PubMed:1445236, ECO:0000269|PubMed:2169238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alfacalcidol + O2 + reduced [NADPH--hemoprotein reductase] =
CC calcitriol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49272, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17823, ChEBI:CHEBI:31186, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:1445236,
CC ECO:0000269|PubMed:2169238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 12-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:38947, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:36204, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:1445236,
CC ECO:0000269|PubMed:2169238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoate + O2 + reduced [NADPH--hemoprotein reductase] =
CC 11-hydroxydodecanoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39751, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18262, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:76628; Evidence={ECO:0000269|PubMed:1445236,
CC ECO:0000269|PubMed:2169238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 5beta-cholestane-3alpha,7alpha,25-triol +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:67384, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28047, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:169972; Evidence={ECO:0000269|PubMed:1445236,
CC ECO:0000269|PubMed:2169238};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha,12alpha-triol + O2 + reduced
CC [NADPH--hemoprotein reductase] = 5beta-cholestane-
CC 3alpha,7alpha,12alpha,25-tetrol + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:67396, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16496, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:169973;
CC Evidence={ECO:0000269|PubMed:1445236, ECO:0000269|PubMed:2169238};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Found in liver and kidney.
CC {ECO:0000269|PubMed:9425298}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 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; Y16417; CAA76205.1; -; mRNA.
DR PIR; JC5819; JC5819.
DR RefSeq; NP_999559.1; NM_214394.1.
DR AlphaFoldDB; O46658; -.
DR SMR; O46658; -.
DR STRING; 9823.ENSSSCP00000000051; -.
DR PaxDb; O46658; -.
DR PeptideAtlas; O46658; -.
DR GeneID; 397687; -.
DR KEGG; ssc:397687; -.
DR CTD; 1565; -.
DR eggNOG; KOG0156; Eukaryota.
DR InParanoid; O46658; -.
DR OrthoDB; 702827at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0047103; F:3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0047749; F:cholestanetriol 26-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IEA:InterPro.
DR GO; GO:0030343; F:vitamin D3 25-hydroxylase activity; IEA:RHEA.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:1445236,
FT ECO:0000269|PubMed:9425298"
FT CHAIN 2..500
FT /note="Vitamin D(3) 25-hydroxylase"
FT /id="PRO_0000051745"
FT BINDING 446
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
SQ SEQUENCE 500 AA; 56512 MW; F1C878A02C44503D CRC64;
MGLLTGDLLG ILALAMVIFL LLVDLMHRRS RWAPRYPPGP MPLPGLGNLL QVNFQDPRLS
FIQLRRRFGD VFSLQQIWRP VVVLNGLAAV REALVSHSHE TSDRPPVFIL EHLGYGPRSE
GVILARYGKA WREQRRFSVS TLRNFGLGKK SLEEWVTQEA SCLCAAFADQ AGRPFSPNNL
LNKAVSNVIA SLTFARRFEY NDPRMLKLLD LVLEGLKEEV GLMRQVLEAM PVLRHIPGLC
AKLFPRQKAF LVMIDELITE HKMTRDLAQP PRDLTDAFLD EMKEAKGNPE SSFNDENLRL
VVAHLFSAGM ITTSTTLAWA LLLMILHPDV QRRVQQEIDE VIGHVRQPEI KDQALMPFTL
AVLHEVQRFG DIVPLGVAHM TSCDIEVQGF LIPKGTTLIT NLTSVLKDET VWKKPFRFYP
EHFLDAQGRF TKQEAFMPFS AGRRSCLGEP LARMELFLFF TTLLQAFSFS VPTGQPCPSD
HGVFAFLLFP SPYQLCAVPR
