ID   CP27B_HUMAN             Reviewed;         508 AA.
AC   O15528; B2RC61; Q548T3;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 205.
DE   RecName: Full=25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial;
DE            EC=1.14.15.18 {ECO:0000269|PubMed:10518789};
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=CYP1ALPHA, CYP27B;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX   PubMed=9428799; DOI=10.1089/dna.1997.16.1499;
RA   Fu G.K., Portale A.P., Miller W.L.;
RT   "Complete structure of the human gene for the vitamin D 1alpha-hydroxylase,
RT   P450c1alpha.";
RL   DNA Cell Biol. 16:1499-1507(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Kidney;
RX   PubMed=9344864; DOI=10.1006/bbrc.1997.7508;
RA   Monkawa T., Yoshida T., Wakino S., Shinki T., Anazawa H., Deluca H.F.,
RA   Suda T., Hayashi M., Saruta T.;
RT   "Molecular cloning of cDNA and genomic DNA for human 25-hydroxyvitamin D3 1
RT   alpha-hydroxylase.";
RL   Biochem. Biophys. Res. Commun. 239:527-533(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9415400; DOI=10.1210/mend.11.13.0035;
RA   Fu G.K., Lin D., Zhang Y.H., Bikle D.D., Shackleton C.H., Miller W.L.,
RA   Portale A.A.;
RT   "Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations
RT   causing vitamin D-dependent rickets type 1.";
RL   Mol. Endocrinol. 11:1961-1970(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=12496369;
RA   Huang D.C., Papavasiliou V., Rhim J.S., Horst R.L., Kremer R.;
RT   "Targeted disruption of the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in
RT   ras-transformed keratinocytes demonstrates that locally produced 1alpha,25-
RT   dihydroxyvitamin D3 suppresses growth and induces differentiation in an
RT   autocrine fashion.";
RL   Mol. Cancer Res. 1:56-67(2002).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Huang D.C., Papavasiliou J., Rhim J., Kremer R.;
RT   "Targeted disruption of the 25-hydroxyvitamin D3 1 a-hydroxylase gene in a
RT   Ras-transformed human keratinocyte cell line: evidence for an autocrine
RT   growth regulatory function of 1 alpha, 25-dihydroxyvitamin D3 in vitro and
RT   in vivo.";
RL   Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-166.
RG   NIEHS SNPs program;
RL   Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [10]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=10518789; DOI=10.1046/j.1432-1327.1999.00794.x;
RA   Sawada N., Sakaki T., Kitanaka S., Takeyama K., Kato S., Inouye K.;
RT   "Enzymatic properties of human 25-hydroxyvitamin D3 1alpha-hydroxylase
RT   coexpression with adrenodoxin and NADPH-adrenodoxin reductase in
RT   Escherichia coli.";
RL   Eur. J. Biochem. 265:950-956(1999).
RN   [11]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=22862690; DOI=10.1111/j.1742-4658.2012.08736.x;
RA   Tang E.K.Y., Tieu E.W., Tuckey R.C.;
RT   "Expression of human CYP27B1 in Escherichia coli and characterization in
RT   phospholipid vesicles.";
RL   FEBS J. 279:3749-3761(2012).
RN   [12]
RP   VARIANTS VDDR1A HIS-107; GLU-125; PRO-335 AND SER-382, FUNCTION, CATALYTIC
RP   ACTIVITY, TISSUE SPECIFICITY, AND PATHWAY.
RX   PubMed=9486994; DOI=10.1056/nejm199803053381004;
RA   Kitanaka S., Takeyama K., Murayama A., Sato T., Okumura K., Nogami M.,
RA   Hasegawa Y., Niimi H., Yanagisawa J., Tanaka T., Kato S.;
RT   "Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene
RT   in patients with pseudovitamin D-deficiency rickets.";
RL   N. Engl. J. Med. 338:653-661(1998).
RN   [13]
RP   VARIANTS VDDR1A HIS-65; LYS-189; HIS-389; ILE-409; PRO-429; CYS-453 AND
RP   ARG-497.
RX   PubMed=9837822; DOI=10.1086/302156;
RA   Wang J.T., Lin C.-J., Burridge S.M., Fu G.K., Labuda M., Portale A.A.,
RA   Miller W.L.;
RT   "Genetics of vitamin D 1-alpha-hydroxylase deficiency in 17 families.";
RL   Am. J. Hum. Genet. 63:1694-1702(1998).
RN   [14]
RP   VARIANTS VDDR1A TYR-323 AND GLY-478.
RX   PubMed=10320521; DOI=10.1359/jbmr.1999.14.5.730;
RA   Smith S.J., Rucka A.K., Berry J.L., Davies M., Mylchreest S.,
RA   Paterson C.R., Heath D.A., Tassabehji M., Read A.P., Mee A.P., Mawer E.B.;
RT   "Novel mutations in the 1alpha-hydroxylase (P450c1) gene in three families
RT   with pseudovitamin D-deficiency rickets resulting in loss of functional
RT   enzyme activity in blood-derived macrophages.";
RL   J. Bone Miner. Res. 14:730-739(1999).
RN   [15]
RP   VARIANTS VDDR1A ARG-321 AND CYS-389, FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=10566658; DOI=10.1210/jcem.84.11.6131;
RA   Kitanaka S., Murayama A., Sakaki T., Inouye K., Seino Y., Fukumoto S.,
RA   Shima M., Yukizane S., Takayanagi M., Niimi H., Takeyama K., Kato S.;
RT   "No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product
RT   in pseudovitamin D deficiency rickets, including that with mild clinical
RT   manifestation.";
RL   J. Clin. Endocrinol. Metab. 84:4111-4117(1999).
RN   [16]
RP   VARIANTS VDDR1A GLY-189; PHE-343; GLY-389; HIS-389 AND ILE-409, FUNCTION,
RP   AND CATALYTIC ACTIVITY.
RX   PubMed=12050193; DOI=10.1210/jcem.87.6.8534;
RA   Wang X., Zhang M.Y., Miller W.L., Portale A.A.;
RT   "Novel gene mutations in patients with 1alpha-hydroxylase deficiency that
RT   confer partial enzyme activity in vitro.";
RL   J. Clin. Endocrinol. Metab. 87:2424-2430(2002).
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 C1alpha-
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:10518789, PubMed:9486994, PubMed:22862690,
CC       PubMed:10566658, PubMed:12050193). Has 1alpha-hydroxylase activity on
CC       vitamin D intermediates of the CYP24A1-mediated inactivation pathway
CC       (PubMed:10518789, PubMed:22862690). Converts 24R,25-dihydroxyvitamin
CC       D3/secalciferol to 1-alpha,24,25-trihydroxyvitamin D3, an active ligand
CC       of VDR. Also active on 25-hydroxyvitamin D2 (PubMed:10518789).
CC       Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC       substrate, and reducing the second into a water molecule, with two
CC       electrons provided by NADPH via FDXR/adrenodoxin reductase and
CC       FDX1/adrenodoxin (PubMed:22862690). {ECO:0000269|PubMed:10518789,
CC       ECO:0000269|PubMed:10566658, ECO:0000269|PubMed:12050193,
CC       ECO:0000269|PubMed:22862690, ECO:0000269|PubMed:9486994}.
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:10518789, ECO:0000269|PubMed:10566658,
CC         ECO:0000269|PubMed:12050193, ECO:0000269|PubMed:22862690,
CC         ECO:0000269|PubMed:9486994};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20574;
CC         Evidence={ECO:0000305|PubMed:22862690};
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:10518789};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49065;
CC         Evidence={ECO:0000305|PubMed:10518789};
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:0000269|PubMed:22862690};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49069;
CC         Evidence={ECO:0000305|PubMed:22862690};
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:0000269|PubMed:22862690};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49049;
CC         Evidence={ECO:0000305|PubMed:22862690};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000250|UniProtKB:O35084};
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:0000269|PubMed:22862690}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.7 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:10518789};
CC         KM=1.1 uM for 24,25-dihydroxyvitamin D3
CC         {ECO:0000269|PubMed:10518789};
CC         KM=0.9 uM for 25-hydroxyvitamin D3 {ECO:0000269|PubMed:22862690};
CC         Vmax=3.9 pmol/min/mg enzyme toward 25-hydroxyvitamin D3
CC         {ECO:0000269|PubMed:10518789};
CC         Vmax=3.2 pmol/min/mg enzyme toward 24,25-dihydroxyvitamin D3
CC         {ECO:0000269|PubMed:10518789};
CC         Vmax=1.3 nmol/min/mg enzyme toward 25-hydroxyvitamin D3
CC         {ECO:0000269|PubMed:22862690};
CC   -!- PATHWAY: Hormone biosynthesis; vitamin D biosynthesis.
CC       {ECO:0000269|PubMed:9486994}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion membrane.
CC   -!- TISSUE SPECIFICITY: Kidney. {ECO:0000269|PubMed:9428799,
CC       ECO:0000269|PubMed:9486994}.
CC   -!- DISEASE: Rickets vitamin D-dependent 1A (VDDR1A) [MIM:264700]: A
CC       disorder caused by a selective deficiency of the active form of vitamin
CC       D (1,25-dihydroxyvitamin D3) and resulting in defective bone
CC       mineralization and clinical features of rickets.
CC       {ECO:0000269|PubMed:10320521, ECO:0000269|PubMed:10566658,
CC       ECO:0000269|PubMed:12050193, ECO:0000269|PubMed:9486994,
CC       ECO:0000269|PubMed:9837822}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/cyp27b1/";
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DR   EMBL; AF027152; AAC51854.1; -; Genomic_DNA.
DR   EMBL; AB005038; BAA23416.1; -; mRNA.
DR   EMBL; AB005989; BAA22656.1; -; mRNA.
DR   EMBL; AB005990; BAA22657.1; -; Genomic_DNA.
DR   EMBL; AB006987; BAA23418.1; -; Genomic_DNA.
DR   EMBL; AF020192; AAC51853.1; -; mRNA.
DR   EMBL; AF256213; AAG00416.1; -; Genomic_DNA.
DR   EMBL; AF246895; AAF64299.1; -; mRNA.
DR   EMBL; AY288916; AAP31972.1; -; Genomic_DNA.
DR   EMBL; AK314953; BAG37458.1; -; mRNA.
DR   EMBL; CH471054; EAW97067.1; -; Genomic_DNA.
DR   EMBL; BC136386; AAI36387.1; -; mRNA.
DR   CCDS; CCDS8954.1; -.
DR   PIR; JC5713; JC5713.
DR   RefSeq; NP_000776.1; NM_000785.3.
DR   AlphaFoldDB; O15528; -.
DR   SMR; O15528; -.
DR   BioGRID; 107966; 12.
DR   IntAct; O15528; 1.
DR   STRING; 9606.ENSP00000228606; -.
DR   BindingDB; O15528; -.
DR   ChEMBL; CHEMBL5993; -.
DR   DrugBank; DB01436; Alfacalcidol.
DR   DrugBank; DB00146; Calcifediol.
DR   DrugBank; DB01285; Corticotropin.
DR   DrugBank; DB00153; Ergocalciferol.
DR   DrugBank; DB11094; Vitamin D.
DR   DrugCentral; O15528; -.
DR   GuidetoPHARMACOLOGY; 1370; -.
DR   SwissLipids; SLP:000001478; -.
DR   PhosphoSitePlus; O15528; -.
DR   BioMuta; CYP27B1; -.
DR   EPD; O15528; -.
DR   MassIVE; O15528; -.
DR   PaxDb; 9606-ENSP00000228606; -.
DR   PeptideAtlas; O15528; -.
DR   ProteomicsDB; 48734; -.
DR   TopDownProteomics; O15528; -.
DR   Antibodypedia; 55993; 174 antibodies from 24 providers.
DR   DNASU; 1594; -.
DR   Ensembl; ENST00000228606.9; ENSP00000228606.4; ENSG00000111012.10.
DR   GeneID; 1594; -.
DR   KEGG; hsa:1594; -.
DR   MANE-Select; ENST00000228606.9; ENSP00000228606.4; NM_000785.4; NP_000776.1.
DR   UCSC; uc001spz.2; human.
DR   AGR; HGNC:2606; -.
DR   CTD; 1594; -.
DR   DisGeNET; 1594; -.
DR   GeneCards; CYP27B1; -.
DR   HGNC; HGNC:2606; CYP27B1.
DR   HPA; ENSG00000111012; Tissue enhanced (kidney, thyroid gland).
DR   MalaCards; CYP27B1; -.
DR   MIM; 264700; phenotype.
DR   MIM; 609506; gene.
DR   neXtProt; NX_O15528; -.
DR   OpenTargets; ENSG00000111012; -.
DR   Orphanet; 289157; Hypocalcemic vitamin D-dependent rickets.
DR   PharmGKB; PA27099; -.
DR   VEuPathDB; HostDB:ENSG00000111012; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   GeneTree; ENSGT00950000182905; -.
DR   HOGENOM; CLU_001570_28_3_1; -.
DR   InParanoid; O15528; -.
DR   OMA; KPWKTFC; -.
DR   OrthoDB; 2658719at2759; -.
DR   PhylomeDB; O15528; -.
DR   TreeFam; TF105094; -.
DR   BRENDA; 1.14.15.18; 2681.
DR   PathwayCommons; O15528; -.
DR   Reactome; R-HSA-196791; Vitamin D (calciferol) metabolism.
DR   Reactome; R-HSA-211916; Vitamins.
DR   Reactome; R-HSA-5579014; Defective CYP27B1 causes VDDR1A.
DR   SABIO-RK; O15528; -.
DR   SignaLink; O15528; -.
DR   SIGNOR; O15528; -.
DR   UniPathway; UPA00954; -.
DR   BioGRID-ORCS; 1594; 64 hits in 1148 CRISPR screens.
DR   GeneWiki; 25-Hydroxyvitamin_D3_1-alpha-hydroxylase; -.
DR   GenomeRNAi; 1594; -.
DR   Pharos; O15528; Tchem.
DR   PRO; PR:O15528; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   RNAct; O15528; Protein.
DR   Bgee; ENSG00000111012; Expressed in nephron tubule and 107 other cell types or tissues.
DR   ExpressionAtlas; O15528; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; ISS:BHF-UCL.
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; IDA:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; IEP:BHF-UCL.
DR   GO; GO:0036378; P:calcitriol biosynthetic process from calciol; IDA:UniProtKB.
DR   GO; GO:0055074; P:calcium ion homeostasis; IMP:BHF-UCL.
DR   GO; GO:0006816; P:calcium ion transport; ISS:BHF-UCL.
DR   GO; GO:0046697; P:decidualization; IEP:BHF-UCL.
DR   GO; GO:0070314; P:G1 to G0 transition; IMP:BHF-UCL.
DR   GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL.
DR   GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:BHF-UCL.
DR   GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; IDA:BHF-UCL.
DR   GO; GO:0070564; P:positive regulation of vitamin D receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0030500; P:regulation of bone mineralization; IMP:BHF-UCL.
DR   GO; GO:0043627; P:response to estrogen; IEP:BHF-UCL.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IDA:BHF-UCL.
DR   GO; GO:0034341; P:response to type II interferon; IDA:BHF-UCL.
DR   GO; GO:0033280; P:response to vitamin D; IDA:BHF-UCL.
DR   GO; GO:0042369; P:vitamin D catabolic process; IBA:GO_Central.
DR   GO; GO:0042359; P:vitamin D metabolic process; IDA:BHF-UCL.
DR   GO; GO:0006766; P:vitamin metabolic process; TAS:Reactome.
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.
DR   Genevisible; O15528; HS.
PE   1: Evidence at protein level;
KW   Disease variant; Heme; Iron; Lipid metabolism; Membrane; Metal-binding;
KW   Mitochondrion; Monooxygenase; Oxidoreductase; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..?
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255"
FT   CHAIN           ?..508
FT                   /note="25-hydroxyvitamin D-1 alpha hydroxylase,
FT                   mitochondrial"
FT                   /id="PRO_0000003622"
FT   BINDING         455
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   VARIANT         65
FT                   /note="Q -> H (in VDDR1A; dbSNP:rs868704228)"
FT                   /evidence="ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016969"
FT   VARIANT         107
FT                   /note="R -> H (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs28934604)"
FT                   /evidence="ECO:0000269|PubMed:9486994"
FT                   /id="VAR_016952"
FT   VARIANT         125
FT                   /note="G -> E (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs28934605)"
FT                   /evidence="ECO:0000269|PubMed:9486994"
FT                   /id="VAR_016953"
FT   VARIANT         166
FT                   /note="V -> L (in dbSNP:rs8176344)"
FT                   /evidence="ECO:0000269|Ref.6"
FT                   /id="VAR_018841"
FT   VARIANT         189
FT                   /note="E -> G (in VDDR1A; 22% of wild-type activity;
FT                   dbSNP:rs118204012)"
FT                   /evidence="ECO:0000269|PubMed:12050193"
FT                   /id="VAR_016954"
FT   VARIANT         189
FT                   /note="E -> K (in VDDR1A; 11% of wild-type activity)"
FT                   /evidence="ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016967"
FT   VARIANT         321
FT                   /note="T -> R (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs118204007)"
FT                   /evidence="ECO:0000269|PubMed:10566658"
FT                   /id="VAR_016955"
FT   VARIANT         323
FT                   /note="S -> Y (in VDDR1A)"
FT                   /evidence="ECO:0000269|PubMed:10320521"
FT                   /id="VAR_016970"
FT   VARIANT         335
FT                   /note="R -> P (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs28934606)"
FT                   /evidence="ECO:0000269|PubMed:9486994"
FT                   /id="VAR_016956"
FT   VARIANT         343
FT                   /note="L -> F (in VDDR1A; 2.3% of wild-type activity;
FT                   dbSNP:rs118204011)"
FT                   /evidence="ECO:0000269|PubMed:12050193"
FT                   /id="VAR_016957"
FT   VARIANT         382
FT                   /note="P -> S (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs28934607)"
FT                   /evidence="ECO:0000269|PubMed:9486994"
FT                   /id="VAR_016958"
FT   VARIANT         389
FT                   /note="R -> C (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs118204010)"
FT                   /evidence="ECO:0000269|PubMed:10566658"
FT                   /id="VAR_016968"
FT   VARIANT         389
FT                   /note="R -> G (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs118204010)"
FT                   /evidence="ECO:0000269|PubMed:12050193"
FT                   /id="VAR_016960"
FT   VARIANT         389
FT                   /note="R -> H (in VDDR1A; complete loss of activity;
FT                   dbSNP:rs118204009)"
FT                   /evidence="ECO:0000269|PubMed:12050193,
FT                   ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016959"
FT   VARIANT         409
FT                   /note="T -> I (in VDDR1A; dbSNP:rs118204008)"
FT                   /evidence="ECO:0000269|PubMed:12050193,
FT                   ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016961"
FT   VARIANT         429
FT                   /note="R -> P (in VDDR1A; dbSNP:rs568165874)"
FT                   /evidence="ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016971"
FT   VARIANT         453
FT                   /note="R -> C (in VDDR1A; dbSNP:rs767480544)"
FT                   /evidence="ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016972"
FT   VARIANT         478
FT                   /note="V -> G (in VDDR1A)"
FT                   /evidence="ECO:0000269|PubMed:10320521"
FT                   /id="VAR_016973"
FT   VARIANT         497
FT                   /note="P -> R (in VDDR1A; dbSNP:rs1161799032)"
FT                   /evidence="ECO:0000269|PubMed:9837822"
FT                   /id="VAR_016974"
FT   CONFLICT        320
FT                   /note="D -> N (in Ref. 7; BAG37458)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   508 AA;  56504 MW;  7F0611EFAD1B5C1C CRC64;
     MTQTLKYASR VFHRVRWAPE LGASLGYREY HSARRSLADI PGPSTPSFLA ELFCKGGLSR
     LHELQVQGAA HFGPVWLASF GTVRTVYVAA PALVEELLRQ EGPRPERCSF SPWTEHRRCR
     QRACGLLTAE GEEWQRLRSL LAPLLLRPQA AARYAGTLNN VVCDLVRRLR RQRGRGTGPP
     ALVRDVAGEF YKFGLEGIAA VLLGSRLGCL EAQVPPDTET FIRAVGSVFV STLLTMAMPH
     WLRHLVPGPW GRLCRDWDQM FAFAQRHVER REAEAAMRNG GQPEKDLESG AHLTHFLFRE
     ELPAQSILGN VTELLLAGVD TVSNTLSWAL YELSRHPEVQ TALHSEITAA LSPGSSAYPS
     ATVLSQLPLL KAVVKEVLRL YPVVPGNSRV PDKDIHVGDY IIPKNTLVTL CHYATSRDPA
     QFPEPNSFRP ARWLGEGPTP HPFASLPFGF GKRSCMGRRL AELELQMALA QILTHFEVQP
     EPGAAPVRPK TRTVLVPERS INLQFLDR
//