CP27A_MOUSE
ID CP27A_MOUSE Reviewed; 533 AA.
AC Q9DBG1;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Sterol 26-hydroxylase, mitochondrial {ECO:0000250|UniProtKB:P17177};
DE EC=1.14.15.15 {ECO:0000250|UniProtKB:P17177, ECO:0000250|UniProtKB:Q02318};
DE AltName: Full=5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase {ECO:0000250|UniProtKB:Q02318};
DE AltName: Full=Cytochrome P-450C27/25;
DE AltName: Full=Cytochrome P450 27;
DE AltName: Full=Sterol 27-hydroxylase {ECO:0000250|UniProtKB:Q02318};
DE AltName: Full=Vitamin D(3) 25-hydroxylase {ECO:0000250|UniProtKB:Q02318};
DE Flags: Precursor;
GN Name=Cyp27a1 {ECO:0000312|MGI:MGI:88594};
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-142; LYS-232; LYS-285; LYS-296;
RP LYS-375; LYS-512 AND LYS-523, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=28190002; DOI=10.1074/jbc.m116.774760;
RA Mast N., Anderson K.W., Lin J.B., Li Y., Turko I.V., Tatsuoka C.,
RA Bjorkhem I., Pikuleva I.A.;
RT "Cytochrome P450 27A1 Deficiency and Regional Differences in Brain Sterol
RT Metabolism Cause Preferential Cholestanol Accumulation in the Cerebellum.";
RL J. Biol. Chem. 292:4913-4924(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase that catalyzes regio- and
CC stereospecific hydroxylation of cholesterol and its derivatives.
CC Hydroxylates (with R stereochemistry) the terminal methyl group of
CC cholesterol side-chain in a three step reaction to yield at first a C26
CC alcohol, then a C26 aldehyde and finally a C26 acid. Regulates
CC cholesterol homeostasis by catalyzing the conversion of excess
CC cholesterol to bile acids via both the 'neutral' (classic) and the
CC 'acid' (alternative) pathways. May also regulate cholesterol
CC homeostasis via generation of active oxysterols, which act as ligands
CC for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of
CC genes involved in lipid metabolism (By similarity). Plays a role in
CC cholestanol metabolism in the cerebellum (PubMed:28190002). Similarly
CC to cholesterol, hydroxylates cholestanol and may facilitate sterol
CC diffusion through the blood-brain barrier to the systemic circulation
CC for further degradation. Also hydroxylates retinal 7-ketocholesterol, a
CC noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and
CC may play a role in its elimination from the retinal pigment epithelium.
CC May play a redundant role in vitamin D biosynthesis. Catalyzes 25-
CC hydroxylation of vitamin D3 that is required for its conversion to a
CC functionally active form (By similarity).
CC {ECO:0000250|UniProtKB:Q02318, ECO:0000269|PubMed:28190002}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha,12alpha-triol + 5 H(+) + 3 O2 +
CC 6 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-trihydroxy-
CC 5beta-cholestan-26-oate + 4 H2O + 6 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:34631, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16496, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:58734; EC=1.14.15.15;
CC Evidence={ECO:0000250|UniProtKB:P17177,
CC ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34632;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholestanol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-
CC 26-hydroxycholestanol + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:53812, 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:86570,
CC ChEBI:CHEBI:137688; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53813;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3beta-hydroxycholest-5-en-7-one-26-al + H(+) + O2 + 2
CC reduced [adrenodoxin] = (25R)-3beta-hydroxycholest-5-en-7-one-26-oate
CC + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:47380, Rhea:RHEA-
CC COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:87677, ChEBI:CHEBI:87678;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47381;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3beta,26-dihydroxycholest-5-en-7-one + 2 H(+) + O2 + 2
CC reduced [adrenodoxin] = (25R)-3beta-hydroxycholest-5-en-7-one-26-al +
CC 2 H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:47376, Rhea:RHEA-
CC COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:87653, ChEBI:CHEBI:87677;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47377;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-oxocholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] =
CC (25R)-3beta,26-dihydroxycholest-5-en-7-one + H2O + 2 oxidized
CC [adrenodoxin]; Xref=Rhea:RHEA:47344, 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:64294,
CC ChEBI:CHEBI:87653; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47345;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=calciol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = calcidiol +
CC H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46588, Rhea:RHEA-
CC COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17933, ChEBI:CHEBI:28940,
CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46589;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-5beta-cholestane-3alpha,7alpha,12alpha,26-tetrol + 2
CC H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-
CC trihydroxy-5beta-cholestan-26-al + 2 H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:40231, 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:48939,
CC ChEBI:CHEBI:48940; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40232;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-
CC cholest-5-ene-3beta,26-diol + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:46400, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:76591; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46401;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3beta,4beta-dihydroxycholest-5-en-26-al + H(+) + O2 + 2
CC reduced [adrenodoxin] = (25R)-3beta,4beta-dihydroxycholest-5-en-26-
CC oate + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46436,
CC Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:86115, ChEBI:CHEBI:86116;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46437;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-4beta,26-dihydroxycholesterol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (25R)-3beta,4beta-dihydroxycholest-5-en-26-al + 2 H2O
CC + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46432, Rhea:RHEA-
CC COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:86113, ChEBI:CHEBI:86115;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46433;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4beta-hydroxycholesterol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (25R)-4beta,26-dihydroxycholesterol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:46428, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:85778, ChEBI:CHEBI:86113;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46429;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3beta-hydroxy-5-cholesten-26-al + H(+) + O2 + 2 reduced
CC [adrenodoxin] = (25R)-3beta-hydroxy-5-cholestenoate + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:45236, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:86096, ChEBI:CHEBI:86098;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45237;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-cholest-5-ene-3beta,26-diol + 2 H(+) + O2 + 2 reduced
CC [adrenodoxin] = (25R)-3beta-hydroxy-5-cholesten-26-al + 2 H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:46092, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:76591, ChEBI:CHEBI:86096;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46093;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-al +
CC H(+) + O2 + 2 reduced [adrenodoxin] = (25R)-3alpha,7alpha,12alpha-
CC trihydroxy-5beta-cholestan-26-oate + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:34627, 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:48940,
CC ChEBI:CHEBI:58734; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34628;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha,12alpha-triol + 2 H(+) + O2 + 2
CC reduced [adrenodoxin] = (25R)-5beta-cholestane-
CC 3alpha,7alpha,12alpha,26-tetrol + H2O + 2 oxidized [adrenodoxin];
CC Xref=Rhea:RHEA:14373, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16496, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:48939; Evidence={ECO:0000250|UniProtKB:Q02318};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14374;
CC Evidence={ECO:0000250|UniProtKB:Q02318};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P17177};
CC -!- PATHWAY: Hormone biosynthesis; cholecalciferol biosynthesis.
CC {ECO:0000250|UniProtKB:Q02318}.
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000250|UniProtKB:Q02318}.
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q02318}.
CC -!- SUBUNIT: Interacts with HSP70; this interaction is required for initial
CC targeting to mitochondria. {ECO:0000250|UniProtKB:P17178}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P17178}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P17178}. Note=Post-translationally targeted to
CC mitochondria. All three of the receptor proteins in the TOM complex,
CC TOMM70, TOMM20 and TOMM22 are required for the translocation across the
CC mitochondrial outer membrane. After translocation into the matrix,
CC associates with the inner membrane as a membrane extrinsic protein.
CC {ECO:0000250|UniProtKB:P17178}.
CC -!- TISSUE SPECIFICITY: Expressed in the gray and white matter of
CC cerebellum (at protein level). {ECO:0000269|PubMed:28190002}.
CC -!- PTM: Acetylation of Lys-125 and Lys-285 is observed in liver
CC mitochondria from fasted mice but not from fed mice.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show cholestanol accumulation in the
CC cerebellum. {ECO:0000269|PubMed:28190002}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AK004977; BAB23713.1; -; mRNA.
DR EMBL; BC055028; AAH55028.1; -; mRNA.
DR CCDS; CCDS15054.1; -.
DR RefSeq; NP_077226.2; NM_024264.5.
DR AlphaFoldDB; Q9DBG1; -.
DR SMR; Q9DBG1; -.
DR BioGRID; 222345; 10.
DR STRING; 10090.ENSMUSP00000027356; -.
DR iPTMnet; Q9DBG1; -.
DR PhosphoSitePlus; Q9DBG1; -.
DR SwissPalm; Q9DBG1; -.
DR jPOST; Q9DBG1; -.
DR MaxQB; Q9DBG1; -.
DR PaxDb; Q9DBG1; -.
DR PeptideAtlas; Q9DBG1; -.
DR PRIDE; Q9DBG1; -.
DR ProteomicsDB; 283810; -.
DR Antibodypedia; 34289; 304 antibodies from 34 providers.
DR DNASU; 104086; -.
DR Ensembl; ENSMUST00000027356; ENSMUSP00000027356; ENSMUSG00000026170.
DR GeneID; 104086; -.
DR KEGG; mmu:104086; -.
DR UCSC; uc007bna.1; mouse.
DR CTD; 1593; -.
DR MGI; MGI:88594; Cyp27a1.
DR VEuPathDB; HostDB:ENSMUSG00000026170; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00950000182905; -.
DR HOGENOM; CLU_001570_28_3_1; -.
DR InParanoid; Q9DBG1; -.
DR OMA; QVSDMAH; -.
DR OrthoDB; 871849at2759; -.
DR PhylomeDB; Q9DBG1; -.
DR TreeFam; TF105094; -.
DR BRENDA; 1.14.15.15; 3474.
DR Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-MMU-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA00955; -.
DR UniPathway; UPA01058; -.
DR BioGRID-ORCS; 104086; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9DBG1; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9DBG1; protein.
DR Bgee; ENSMUSG00000026170; Expressed in left lobe of liver and 197 other tissues.
DR Genevisible; Q9DBG1; MM.
DR GO; GO:0005740; C:mitochondrial envelope; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0047103; F:3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity; IEA:UniProtKB-EC.
DR GO; GO:0047748; F:cholestanetetraol 26-dehydrogenase activity; IEA:RHEA.
DR GO; GO:0047749; F:cholestanetriol 26-monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0031073; F:cholesterol 26-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0008123; F:cholesterol 7-alpha-monooxygenase activity; ISS:UniProtKB.
DR GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0030343; F:vitamin D3 25-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; ISS:UniProtKB.
DR GO; GO:0036378; P:calcitriol biosynthetic process from calciol; ISS:UniProtKB.
DR GO; GO:0006707; P:cholesterol catabolic process; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol 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 Acetylation; Cholesterol metabolism; Heme; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol metabolism; Transit peptide.
FT TRANSIT 1..32
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 33..533
FT /note="Sterol 26-hydroxylase, mitochondrial"
FT /id="PRO_0000003619"
FT REGION 34..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..400
FT /note="Sterol-binding"
FT /evidence="ECO:0000255"
FT BINDING 479
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 MOD_RES 142
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 285
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 296
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 512
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 523
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
SQ SEQUENCE 533 AA; 60720 MW; A7F808CA505EF4E6 CRC64;
MAAWSRTRLR WTLLDPRVVG RGLCPQGARA KATIPAALQA QESTEGPGTG QDRPRLRSPA
ELPGTGTLQF LFQLFLQGYV LHLPDLQVLN KTKYGPMWTT SFGTYTNVNL ASAPLLEQVM
RQEGKYPIRD HMDQWKDHRD HKGLTYGIFI AQGEQWYHLR QALKQRLLKP DEAALYTDAL
NEVISDFITR LDQVRAESES GDQVPDMAHL LYHLALEAIT YILFEKRIGC LKPSIPEDTA
AFIRSVAIMF QNSVYITFLP KWTRPLLPFW KRYLNGWDNI FSFGKKLIDE KVQELKAQLQ
ETGPDGVRVS GYLHFLLTNE LLSTQETIGT FPELLLAGVD TTSNTLTWAL YHLSKSPEIQ
EALHKEVTGV VPFGKVPQHK DFAHMPLLKA VIKETLRLYP VVPTNSRIIT EKETEINGFL
FPKNTQFVLC HYVVSRDPSV FPEPNSFQPH RWLRKKEADN PGILHPFGSV PFGYGVRSCL
GRRIAELEMQ LMLSRLVQKY EIALAPGMGE VKTVSRIVLV PSKKVRLHFL QRQ
