CP27B_MOUSE
ID CP27B_MOUSE Reviewed; 507 AA.
AC O35084;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial;
DE EC=1.14.15.18 {ECO:0000269|PubMed:10092858};
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, Cyp40;
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].
RC TISSUE=Kidney;
RX PubMed=9295274; DOI=10.1126/science.277.5333.1827;
RA Takeyama K., Kitanaka S., Sato T., Kobori M., Yanagisawa J., Kato S.;
RT "25-hydroxyvitamin D3 1alpha-hydroxylase and vitamin D synthesis.";
RL Science 277:1827-1830(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=129;
RA Kimmel-Jehan C., DeLuca H.F.;
RT "Cloning of the mouse 25-hydroxyvitamin D3 1-alpha hydroxylase gene.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=11149489; DOI=10.1359/jbmr.2001.16.1.46;
RA Panda D.K., Al-Kawas S., Seldin M.F., Hendy G.N., Goltzman D.;
RT "25-hydroxyvitamin D 1alpha-hydroxylase: structure of the mouse gene,
RT chromosomal assignment, and developmental expression.";
RL J. Bone Miner. Res. 16:46-56(2001).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10092858; DOI=10.1046/j.1432-1327.1999.00096.x;
RA Sakaki T., Sawada N., Takeyama K., Kato S., Inouye K.;
RT "Enzymatic properties of mouse 25-hydroxyvitamin D3 1 alpha-hydroxylase
RT expressed in Escherichia coli.";
RL Eur. J. Biochem. 259:731-738(1999).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP GLN-65 AND SER-408, AND COFACTOR.
RX PubMed=15972816; DOI=10.1074/jbc.m505244200;
RA Yamamoto K., Uchida E., Urushino N., Sakaki T., Kagawa N., Sawada N.,
RA Kamakura M., Kato S., Inouye K., Yamada S.;
RT "Identification of the amino acid residue of CYP27B1 responsible for
RT binding of 25-hydroxyvitamin D3 whose mutation causes vitamin D-dependent
RT rickets type 1.";
RL J. Biol. Chem. 280:30511-30516(2005).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in vitamin D
CC metabolism and in calcium and phosphorus homeostasis. Catalyzes the
CC rate-limiting step in the activation of vitamin D in the kidney, namely
CC the hydroxylation of 25-hydroxyvitamin D3/calcidiol at the C1-alpha
CC position to form the hormonally active form of vitamin D3, 1alpha,25-
CC dihydroxyvitamin D3/calcitriol that acts via the vitamin D receptor
CC (VDR) (PubMed:15972816, PubMed:10092858). Has 1-alpha-hydroxylase
CC activity on vitamin D intermediates of the CYP24A1-mediated
CC inactivation pathway. Converts 24R,25-dihydroxyvitamin D3/secalciferol
CC to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand of VDR. Also
CC active on 25-hydroxyvitamin D2 (By similarity). Mechanistically, uses
CC molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via FDXR/adrenodoxin reductase and FDX1/adrenodoxin
CC (PubMed:15972816, PubMed:10092858). {ECO:0000250|UniProtKB:O15528,
CC ECO:0000269|PubMed:10092858, ECO:0000269|PubMed:15972816}.
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:0000269|PubMed:10092858, ECO:0000269|PubMed:15972816};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20574;
CC Evidence={ECO:0000305|PubMed:15972816};
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:0000269|PubMed:10092858};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49065;
CC Evidence={ECO:0000305|PubMed:10092858};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=25-hydroxy-24-oxocalciol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (1S)-1,25-dihydroxy-24-oxocalciol + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:49068, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:47805,
CC ChEBI:CHEBI:47812; Evidence={ECO:0000250|UniProtKB:O15528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49069;
CC Evidence={ECO:0000250|UniProtKB:O15528};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=25-hydroxyvitamin D2 + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC 1alpha,25-dihydroxyvitamin D2 + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:49048, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:86319,
CC ChEBI:CHEBI:86320; Evidence={ECO:0000250|UniProtKB:O15528};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49049;
CC Evidence={ECO:0000250|UniProtKB:O15528};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:15972816};
CC -!- ACTIVITY REGULATION: Activated by cardiolipin and dioleoyl
CC phosphatidylethanolamine (DOPE), phospholipids found in the inner
CC mitochondrial membrane. Inhibited by high substrate concentration.
CC {ECO:0000250|UniProtKB:O15528}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.7 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:10092858};
CC KM=1.3 uM for 24,25-dihydroxyvitamin D3
CC {ECO:0000269|PubMed:10092858};
CC KM=0.28 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:15972816};
CC Vmax=9.5 pmol/min/mg enzyme with 25-hydroxyvitamin D3 as substrate
CC {ECO:0000269|PubMed:10092858};
CC Vmax=16.7 pmol/min/mg enzyme with 24,25-dihydroxyvitamin D3 as
CC substrate {ECO:0000269|PubMed:10092858};
CC -!- PATHWAY: Hormone biosynthesis; vitamin D biosynthesis.
CC {ECO:0000250|UniProtKB:O15528}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane.
CC -!- TISSUE SPECIFICITY: Kidney.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA22434.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB006034; BAA22434.1; ALT_INIT; mRNA.
DR EMBL; AF235021; AAK15024.1; -; Genomic_DNA.
DR EMBL; AF286219; AAG44889.1; -; Genomic_DNA.
DR CCDS; CCDS24224.2; -.
DR RefSeq; NP_034139.2; NM_010009.2.
DR AlphaFoldDB; O35084; -.
DR SMR; O35084; -.
DR BioGRID; 199031; 6.
DR STRING; 10090.ENSMUSP00000130005; -.
DR BindingDB; O35084; -.
DR ChEMBL; CHEMBL3329080; -.
DR DrugCentral; O35084; -.
DR SwissLipids; SLP:000001485; -.
DR iPTMnet; O35084; -.
DR PhosphoSitePlus; O35084; -.
DR PaxDb; O35084; -.
DR PRIDE; O35084; -.
DR ProteomicsDB; 283811; -.
DR Antibodypedia; 55993; 139 antibodies from 24 providers.
DR DNASU; 13115; -.
DR Ensembl; ENSMUST00000165764; ENSMUSP00000130005; ENSMUSG00000006724.
DR GeneID; 13115; -.
DR KEGG; mmu:13115; -.
DR UCSC; uc007hhs.2; mouse.
DR CTD; 1594; -.
DR MGI; MGI:1098274; Cyp27b1.
DR VEuPathDB; HostDB:ENSMUSG00000006724; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00950000182905; -.
DR HOGENOM; CLU_001570_28_3_1; -.
DR InParanoid; O35084; -.
DR OMA; SRDPTQF; -.
DR OrthoDB; 574756at2759; -.
DR PhylomeDB; O35084; -.
DR TreeFam; TF105094; -.
DR BRENDA; 1.14.15.18; 3474.
DR Reactome; R-MMU-196791; Vitamin D (calciferol) metabolism.
DR Reactome; R-MMU-211916; Vitamins.
DR UniPathway; UPA00954; -.
DR BioGRID-ORCS; 13115; 1 hit in 75 CRISPR screens.
DR PRO; PR:O35084; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; O35084; protein.
DR Bgee; ENSMUSG00000006724; Expressed in right kidney and 31 other tissues.
DR ExpressionAtlas; O35084; baseline and differential.
DR Genevisible; O35084; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004498; F:calcidiol 1-monooxygenase activity; IDA:UniProtKB.
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:MGI.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0036378; P:calcitriol biosynthetic process from calciol; IDA:UniProtKB.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:MGI.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0070314; P:G1 to G0 transition; ISO:MGI.
DR GO; GO:1900155; P:negative regulation of bone trabecula formation; ISO:MGI.
DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0030279; P:negative regulation of ossification; ISO:MGI.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISO:MGI.
DR GO; GO:2000830; P:positive regulation of parathyroid hormone secretion; ISO:MGI.
DR GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; ISO:MGI.
DR GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; ISO:MGI.
DR GO; GO:0030500; P:regulation of bone mineralization; ISO:MGI.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR GO; GO:0046688; P:response to copper ion; ISO:MGI.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; ISO:MGI.
DR GO; GO:0034341; P:response to interferon-gamma; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0034695; P:response to prostaglandin E; ISO:MGI.
DR GO; GO:0033280; P:response to vitamin D; IDA:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0042369; P:vitamin D catabolic process; IDA:BHF-UCL.
DR GO; GO:0042359; P:vitamin D metabolic process; ISO:MGI.
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; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein 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 ?..507
FT /note="25-hydroxyvitamin D-1 alpha hydroxylase,
FT mitochondrial"
FT /id="PRO_0000003623"
FT BINDING 454
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 MUTAGEN 65
FT /note="Q->E: Impaired 1-alpha hydroxylase activity toward
FT 25-hydroxyvitamin D3. Impaired heme binding."
FT /evidence="ECO:0000269|PubMed:15972816"
FT MUTAGEN 408
FT /note="S->A,V,I: Impaired 1-alpha hydroxylase activity
FT toward 25-hydroxyvitamin D3."
FT /evidence="ECO:0000269|PubMed:15972816"
SQ SEQUENCE 507 AA; 56225 MW; 0669B4478C461B83 CRC64;
MTQAVKLASR VFHRIHLPLQ LDASLGSRGS ESVLRSLSDI PGPSTLSFLA ELFCKGGLSR
LHELQVHGAA RYGPIWSGSF GTLRTVYVAD PTLVEQLLRQ ESHCPERCSF SSWAEHRRRH
QRACGLLTAD GEEWQRLRSL LAPLLLRPQA AAGYAGTLDN VVRDLVRRLR RQRGRGSGLP
GLVLDVAGEF YKFGLESIGA VLLGSRLGCL EAEVPPDTET FIHAVGSVFV STLLTMAMPN
WLHHLIPGPW ARLCRDWDQM FAFAQRHVEL REGEAAMRNQ GKPEEDMPSG HHLTHFLFRE
KVSVQSIVGN VTELLLAGVD TVSNTLSWTL YELSRHPDVQ TALHSEITAG TRGSCAHPHG
TALSQLPLLK AVIKEVLRLY PVVPGNSRVP DRDIRVGNYV IPQDTLVSLC HYATSRDPTQ
FPDPNSFNPA RWLGEGPTPH PFASLPFGFG KRSCIGRRLA ELELQMALSQ ILTHFEVLPE
PGALPIKPMT RTVLVPERSI NLQFVDR
