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
//
