ID   CP27B_RAT               Reviewed;         501 AA.
AC   O35132; O35076;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 2.
DT   24-JAN-2024, entry version 132.
DE   RecName: Full=25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial;
DE            EC=1.14.15.18 {ECO:0000250|UniProtKB:O35084};
DE   AltName: Full=25-OHD-1 alpha-hydroxylase;
DE   AltName: Full=25-hydroxyvitamin D(3) 1-alpha-hydroxylase;
DE            Short=VD3 1A hydroxylase;
DE   AltName: Full=Calcidiol 1-monooxygenase;
DE   AltName: Full=Cytochrome P450 subfamily XXVIIB polypeptide 1;
DE   AltName: Full=Cytochrome P450C1 alpha;
DE   AltName: Full=Cytochrome P450VD1-alpha;
DE   AltName: Full=Cytochrome p450 27B1;
DE   Flags: Precursor;
GN   Name=Cyp27b1; Synonyms=Cyp27b;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RX   PubMed=9333115; DOI=10.1359/jbmr.1997.12.10.1552;
RA   St Arnaud R., Messerlian S., Moir J.M., Omdahl J.L., Glorieux F.H.;
RT   "The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin
RT   D-deficiency rickets (PDDR) disease locus.";
RL   J. Bone Miner. Res. 12:1552-1559(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   PubMed=9371776; DOI=10.1073/pnas.94.24.12920;
RA   Shinki T., Shimada H., Wakino S., Anazawa H., Hayashi M., Saruta T.,
RA   Deluca H.F., Suda T.;
RT   "Cloning and expression of rat 25-hydroxyvitamin D3-1alpha-hydroxylase
RT   cDNA.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:12920-12925(1997).
CC   -!- FUNCTION: Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D3)
CC       to 1-alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)(2)D3), and of 24,25-
CC       dihydroxyvitamin D3 (24,25(OH)(2)D3) to 1-alpha,24,25-trihydroxyvitamin
CC       D3 (1alpha,24,25(OH)(3)D3). Is also active with 25-hydroxy-24-oxo-
CC       vitamin D3. Plays an important role in normal bone growth, calcium
CC       metabolism, and tissue differentiation. {ECO:0000250|UniProtKB:O35084}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=calcidiol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = calcitriol
CC         + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:20573, Rhea:RHEA-
CC         COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:17823, ChEBI:CHEBI:17933,
CC         ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.18;
CC         Evidence={ECO:0000250|UniProtKB:O35084};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 H(+) + O2 + 2 reduced [adrenodoxin] + secalciferol =
CC         calcitetrol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:49064,
CC         Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:28818,
CC         ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47799;
CC         EC=1.14.15.18; Evidence={ECO:0000250|UniProtKB:O35084};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC   -!- PATHWAY: Hormone biosynthesis; cholecalciferol biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion membrane.
CC   -!- TISSUE SPECIFICITY: Kidney.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; AF000139; AAB86461.1; -; mRNA.
DR   EMBL; AB001992; BAA23271.1; -; mRNA.
DR   RefSeq; NP_446215.1; NM_053763.1.
DR   AlphaFoldDB; O35132; -.
DR   SMR; O35132; -.
DR   BioGRID; 250405; 1.
DR   STRING; 10116.ENSRNOP00000064023; -.
DR   PhosphoSitePlus; O35132; -.
DR   PaxDb; 10116-ENSRNOP00000064023; -.
DR   Ensembl; ENSRNOT00065026720; ENSRNOP00065020967; ENSRNOG00065016075.
DR   GeneID; 114700; -.
DR   KEGG; rno:114700; -.
DR   AGR; RGD:69192; -.
DR   CTD; 1594; -.
DR   RGD; 69192; Cyp27b1.
DR   eggNOG; KOG0159; Eukaryota.
DR   InParanoid; O35132; -.
DR   OrthoDB; 2658719at2759; -.
DR   PhylomeDB; O35132; -.
DR   BioCyc; MetaCyc:MONOMER-14354; -.
DR   Reactome; R-RNO-196791; Vitamin D (calciferol) metabolism.
DR   Reactome; R-RNO-211916; Vitamins.
DR   SABIO-RK; O35132; -.
DR   UniPathway; UPA00955; -.
DR   PRO; PR:O35132; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR   GO; GO:0004498; F:calcidiol 1-monooxygenase activity; IDA:BHF-UCL.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0062185; F:secalciferol 1-monooxygenase activity; ISO:RGD.
DR   GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR   GO; GO:0036378; P:calcitriol biosynthetic process from calciol; ISO:RGD.
DR   GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR   GO; GO:0006816; P:calcium ion transport; ISO:RGD.
DR   GO; GO:0046697; P:decidualization; ISO:RGD.
DR   GO; GO:0070314; P:G1 to G0 transition; ISO:RGD.
DR   GO; GO:0007595; P:lactation; IEP:RGD.
DR   GO; GO:1900155; P:negative regulation of bone trabecula formation; IMP:RGD.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR   GO; GO:0030279; P:negative regulation of ossification; IMP:RGD.
DR   GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:RGD.
DR   GO; GO:2000830; P:positive regulation of parathyroid hormone secretion; IMP:RGD.
DR   GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; ISO:RGD.
DR   GO; GO:0030500; P:regulation of bone mineralization; ISO:RGD.
DR   GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR   GO; GO:0051591; P:response to cAMP; IDA:RGD.
DR   GO; GO:0046688; P:response to copper ion; IDA:RGD.
DR   GO; GO:0043627; P:response to estrogen; ISO:RGD.
DR   GO; GO:0032868; P:response to insulin; IDA:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR   GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR   GO; GO:0034695; P:response to prostaglandin E; IDA:RGD.
DR   GO; GO:0034341; P:response to type II interferon; ISO:RGD.
DR   GO; GO:0033280; P:response to vitamin D; IDA:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IDA:RGD.
DR   GO; GO:0042369; P:vitamin D catabolic process; IDA:BHF-UCL.
DR   GO; GO:0042359; P:vitamin D metabolic process; IDA:RGD.
DR   CDD; cd20648; CYP27B1; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 1.
DR   InterPro; IPR001128; Cyt_P450.
DR   InterPro; IPR017972; Cyt_P450_CS.
DR   InterPro; IPR002401; Cyt_P450_E_grp-I.
DR   InterPro; IPR036396; Cyt_P450_sf.
DR   PANTHER; PTHR24279; -; 1.
DR   PANTHER; PTHR24279:SF118; CYTOCHROME P450 FAMILY 27 SUBFAMILY A MEMBER 1; 1.
DR   Pfam; PF00067; p450; 1.
DR   PRINTS; PR00463; EP450I.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   PROSITE; PS00086; CYTOCHROME_P450; 1.
PE   2: Evidence at transcript level;
KW   Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW   Monooxygenase; Oxidoreductase; Reference proteome; Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..501
FT                   /note="25-hydroxyvitamin D-1 alpha hydroxylase,
FT                   mitochondrial"
FT                   /id="PRO_0000003624"
FT   BINDING         448
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"
FT   CONFLICT        13
FT                   /note="H -> D (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        55
FT                   /note="H -> D (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        103..112
FT                   /note="FSSWSEHRRR -> SHLGQSTVAS (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        119
FT                   /note="L -> W (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        129..144
FT                   /note="RLRSLLAPLLLRPQAA -> EAPKSPGPASPPTSSS (in Ref. 1;
FT                   AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        201
FT                   /note="G -> R (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251
FT                   /note="D -> N (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        288
FT                   /note="H -> D (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        305
FT                   /note="T -> R (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        372..374
FT                   /note="RLY -> MLD (in Ref. 1; AAB86461)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   501 AA;  55369 MW;  B0A85286A219EA0E CRC64;
     MTQAVKLASR VFHRVQLPSQ LGSDSVLRSL SDIPGPSTPS FLAELFCKGG LSRLHELQVH
     GAARYGPIWS GSFGTLRTVY VADPALVEQL LRQESHCPER CSFSSWSEHR RRHQRACGLL
     TADGEEWQRL RSLLAPLLLR PQAAAGYAGT LDSVVSDLVR RLRRQRGRGS GLPDLVLDVA
     GEFYKFGLEG IGAVLLGSRL GCLEAEVPPD TETFIEAVGS VFVSTLLTMA MPSWLHRLIP
     GPWARLCRDW DQMFAFAQKH VEQREGEAAV RNQGKPEEDL PTGHHLTHFL FREKVSVQSI
     VGNVTELLLA GVDTVSNTLS WALYELSRHP EVQSALHSEI TGAVNPGSYA HLQATALSQL
     PLLKAVIKEV LRLYPVVPGN SRVPDRDICV GNYVIPQDTL VSLCHYATSR DPAQFREPNS
     FNPARWLGEG PAPHPFASLP FGFGKRSCIG RRLAELELQM ALAQILTHFE VLPEPGALPV
     KPMTRTVLVP ERSIHLQFVD R
//