CP27B_HUMAN
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 03-AUG-2022, entry version 196.
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; O15528; -.
DR PeptideAtlas; O15528; -.
DR PRIDE; O15528; -.
DR ProteomicsDB; 48734; -.
DR TopDownProteomics; O15528; -.
DR Antibodypedia; 55993; 139 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 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; AWDLFAR; -.
DR OrthoDB; 574756at2759; -.
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 SignaLink; O15528; -.
DR SIGNOR; O15528; -.
DR UniPathway; UPA00954; -.
DR BioGRID-ORCS; 1594; 51 hits in 1069 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 106 other tissues.
DR ExpressionAtlas; O15528; baseline and differential.
DR Genevisible; O15528; HS.
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:0034341; P:response to interferon-gamma; IDA:BHF-UCL.
DR GO; GO:0032496; P:response to lipopolysaccharide; 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 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 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
