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Database: UniProt
Entry: P05108
LinkDB: P05108
Original site: P05108 
ID   CP11A_HUMAN             Reviewed;         521 AA.
AC   P05108; A8K8D5; B3KPU8; G3XAD7; Q15081; Q16805; Q8N1A7;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 2.
DT   29-SEP-2021, entry version 216.
DE   RecName: Full=Cholesterol side-chain cleavage enzyme, mitochondrial {ECO:0000303|PubMed:3024157};
DE            EC=1.14.15.6 {ECO:0000269|PubMed:21636783};
DE   AltName: Full=CYPXIA1;
DE   AltName: Full=Cholesterol desmolase;
DE   AltName: Full=Cytochrome P450 11A1;
DE   AltName: Full=Cytochrome P450(scc);
DE   Flags: Precursor;
GN   Name=CYP11A1 {ECO:0000303|PubMed:21636783, ECO:0000312|HGNC:HGNC:2590};
GN   Synonyms=CYP11A;
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 [MRNA] (ISOFORM 1).
RX   PubMed=3024157; DOI=10.1073/pnas.83.23.8962;
RA   Chung B.-C., Matteson K.J., Voutilainen R., Mohandas T.K., Miller W.L.;
RT   "Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning,
RT   assignment of the gene to chromosome 15, and expression in the placenta.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:8962-8966(1986).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=3038854; DOI=10.1093/oxfordjournals.jbchem.a121955;
RA   Morohashi K., Sogawa K., Omura T., Fujii-Kuriyama Y.;
RT   "Gene structure of human cytochrome P-450(SCC), cholesterol desmolase.";
RL   J. Biochem. 101:879-887(1987).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Placenta, and Testis;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
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   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
RA   Chung B.-C.;
RL   Submitted (JAN-1989) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   PROTEIN SEQUENCE OF 51-54, AND INDUCTION.
RC   TISSUE=Choriocarcinoma;
RX   PubMed=1849407; DOI=10.1042/bj2740813;
RA   Hu M.C., Guo I.C., Lin J.H., Chung B.-C.;
RT   "Regulated expression of cytochrome P-450scc (cholesterol-side-chain
RT   cleavage enzyme) in cultured cell lines detected by antibody against
RT   bacterially expressed human protein.";
RL   Biochem. J. 274:813-817(1991).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 283-521 (ISOFORM 1).
RX   PubMed=2419119; DOI=10.1210/endo-118-4-1296;
RA   Matteson K.J., Chung B.-C., Urdea M.S., Miller W.L.;
RT   "Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency
RT   causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc
RT   oligodeoxyribonucleotide probes.";
RL   Endocrinology 118:1296-1305(1986).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 41-521 IN COMPLEXES WITH FDX1;
RP   HEME AND CHOLESTEROL, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, AND
RP   INTERACTION WITH FDX1.
RX   PubMed=21636783; DOI=10.1073/pnas.1019441108;
RA   Strushkevich N., MacKenzie F., Cherkesova T., Grabovec I., Usanov S.,
RA   Park H.W.;
RT   "Structural basis for pregnenolone biosynthesis by the mitochondrial
RT   monooxygenase system.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:10139-10143(2011).
RN   [11]
RP   VARIANT LYS-314.
RX   PubMed=10391209; DOI=10.1038/10290;
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RT   "Characterization of single-nucleotide polymorphisms in coding regions of
RT   human genes.";
RL   Nat. Genet. 22:231-238(1999).
RN   [12]
RP   ERRATUM OF PUBMED:10391209.
RA   Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N.,
RA   Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L.,
RA   Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q.,
RA   Lander E.S.;
RL   Nat. Genet. 23:373-373(1999).
RN   [13]
RP   VARIANT AICSR GLY-ASP-271 INS.
RX   PubMed=11502818; DOI=10.1210/jcem.86.8.7748;
RA   Tajima T., Fujieda K., Kouda N., Nakae J., Miller W.L.;
RT   "Heterozygous mutation in the cholesterol side chain cleavage enzyme
RT   (P450scc) gene in a patient with 46,XY sex reversal and adrenal
RT   insufficiency.";
RL   J. Clin. Endocrinol. Metab. 86:3820-3825(2001).
RN   [14]
RP   VARIANTS AICSR VAL-189 AND TRP-353.
RX   PubMed=12161514; DOI=10.1210/jcem.87.8.8763;
RA   Katsumata N., Ohtake M., Hojo T., Ogawa E., Hara T., Sato N., Tanaka T.;
RT   "Compound heterozygous mutations in the cholesterol side-chain cleavage
RT   enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans.";
RL   J. Clin. Endocrinol. Metab. 87:3808-3813(2002).
RN   [15]
RP   VARIANT AICSR VAL-359, AND CHARACTERIZATION OF VARIANT AICSR VAL-359.
RX   PubMed=16705068; DOI=10.1210/jc.2005-2230;
RA   al Kandari H., Katsumata N., Alexander S., Rasoul M.A.;
RT   "Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in
RT   46, XY patient with adrenal insufficiency, complete sex reversal, and
RT   agenesis of corpus callosum.";
RL   J. Clin. Endocrinol. Metab. 91:2821-2826(2006).
RN   [16]
RP   VARIANTS AICSR TRP-141 AND GLU-415, AND CHARACTERIZATION OF VARIANTS AICSR
RP   TRP-141 AND GLU-415.
RX   PubMed=18182448; DOI=10.1210/jc.2007-2330;
RA   Kim C.J., Lin L., Huang N., Quigley C.A., Avruskin T.W., Achermann J.C.,
RA   Miller W.L.;
RT   "Severe combined adrenal and gonadal deficiency caused by novel mutations
RT   in the cholesterol side chain cleavage enzyme, P450scc.";
RL   J. Clin. Endocrinol. Metab. 93:696-702(2008).
RN   [17]
RP   VARIANT AICSR PRO-222, AND CHARACTERIZATION OF VARIANT AICSR PRO-222.
RX   PubMed=19116240; DOI=10.1210/jc.2008-1118;
RA   Rubtsov P., Karmanov M., Sverdlova P., Spirin P., Tiulpakov A.;
RT   "A novel homozygous mutation in CYP11A1 gene is associated with late-onset
RT   adrenal insufficiency and hypospadias in a 46,XY patient.";
RL   J. Clin. Endocrinol. Metab. 94:936-939(2009).
CC   -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the side-chain
CC       hydroxylation and cleavage of cholesterol to pregnenolone, the
CC       precursor of most steroid hormones (PubMed:21636783). Catalyzes three
CC       sequential oxidation reactions of cholesterol, namely the hydroxylation
CC       at C22 followed with the hydroxylation at C20 to yield 20R,22R-
CC       hydroxycholesterol that is further cleaved between C20 and C22 to yield
CC       the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783).
CC       Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC       substrate and reducing the second into a water molecule. Two electrons
CC       are provided by NADPH via a two-protein mitochondrial transfer system
CC       comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and
CC       nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin)
CC       (PubMed:21636783). {ECO:0000269|PubMed:21636783}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholesterol + 6 H(+) + 3 O2 + 6 reduced [adrenodoxin] = 4-
CC         methylpentanal + 4 H2O + 6 oxidized [adrenodoxin] + pregnenolone;
CC         Xref=Rhea:RHEA:35739, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:16113, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998,
CC         ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; EC=1.14.15.6;
CC         Evidence={ECO:0000269|PubMed:21636783};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35740;
CC         Evidence={ECO:0000305|PubMed:21636783};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=cholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 22R-
CC         hydroxycholesterol + H2O + 2 oxidized [adrenodoxin];
CC         Xref=Rhea:RHEA:34335, 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:67237; Evidence={ECO:0000269|PubMed:21636783};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34336;
CC         Evidence={ECO:0000305|PubMed:21636783};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=22R-hydroxycholesterol + 2 H(+) + O2 + 2 reduced [adrenodoxin]
CC         = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2 oxidized
CC         [adrenodoxin]; Xref=Rhea:RHEA:34339, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC         COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC         ChEBI:CHEBI:67237; Evidence={ECO:0000269|PubMed:21636783};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34340;
CC         Evidence={ECO:0000305|PubMed:21636783};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(20R,22R)-20,22-dihydroxycholesterol + 2 H(+) + O2 + 2 reduced
CC         [adrenodoxin] = 4-methylpentanal + 2 H2O + 2 oxidized [adrenodoxin] +
CC         pregnenolone; Xref=Rhea:RHEA:34343, Rhea:RHEA-COMP:9998, Rhea:RHEA-
CC         COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:17998,
CC         ChEBI:CHEBI:33737, ChEBI:CHEBI:33738;
CC         Evidence={ECO:0000269|PubMed:21636783};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34344;
CC         Evidence={ECO:0000305|PubMed:21636783};
CC   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413;
CC         Evidence={ECO:0000269|PubMed:21636783};
CC   -!- PATHWAY: Lipid metabolism; C21-steroid hormone metabolism.
CC       {ECO:0000269|PubMed:21636783}.
CC   -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC       {ECO:0000269|PubMed:21636783}.
CC   -!- SUBUNIT: Interacts with FDX1/adrenodoxin.
CC       {ECO:0000269|PubMed:21636783}.
CC   -!- INTERACTION:
CC       P05108; Q9NZ94-2: NLGN3; NbExp=3; IntAct=EBI-7183136, EBI-16423037;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC       {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC       {ECO:0000305}. Note=Localizes to the matrix side of the mitochondrion
CC       inner membrane. {ECO:0000250|UniProtKB:P14137}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P05108-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P05108-2; Sequence=VSP_045695;
CC   -!- INDUCTION: By 8-bromo cyclic AMP. {ECO:0000269|PubMed:1849407}.
CC   -!- DISEASE: Adrenal insufficiency, congenital, with 46,XY sex reversal
CC       (AICSR) [MIM:613743]: A rare disorder that can present as acute adrenal
CC       insufficiency in infancy or childhood. ACTH and plasma renin activity
CC       are elevated and adrenal steroids are inappropriately low or absent;
CC       the 46,XY patients have female external genitalia, sometimes with
CC       clitoromegaly. The phenotypic spectrum ranges from prematurity,
CC       complete underandrogenization, and severe early-onset adrenal failure
CC       to term birth with clitoromegaly and later-onset adrenal failure.
CC       Patients with congenital adrenal insufficiency do not manifest the
CC       massive adrenal enlargement typical of congenital lipoid adrenal
CC       hyperplasia. {ECO:0000269|PubMed:11502818, ECO:0000269|PubMed:12161514,
CC       ECO:0000269|PubMed:16705068, ECO:0000269|PubMed:18182448,
CC       ECO:0000269|PubMed:19116240}. 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}.
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DR   EMBL; M14565; AAA52162.1; -; mRNA.
DR   EMBL; X05367; CAA28965.1; -; Genomic_DNA.
DR   EMBL; X05368; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05369; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05370; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05371; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05372; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05373; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; X05374; CAA28965.1; JOINED; Genomic_DNA.
DR   EMBL; AK056794; BAG51810.1; -; mRNA.
DR   EMBL; AK292300; BAF84989.1; -; mRNA.
DR   EMBL; AC090826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471136; EAW99341.1; -; Genomic_DNA.
DR   EMBL; CH471136; EAW99342.1; -; Genomic_DNA.
DR   EMBL; BC032329; AAH32329.1; -; mRNA.
DR   EMBL; X14257; CAA32471.1; -; Genomic_DNA.
DR   EMBL; M28253; AAA36404.1; -; mRNA.
DR   CCDS; CCDS32291.1; -. [P05108-1]
DR   CCDS; CCDS45303.1; -. [P05108-2]
DR   PIR; A25922; A25922.
DR   RefSeq; NP_000772.2; NM_000781.2. [P05108-1]
DR   RefSeq; NP_001093243.1; NM_001099773.1. [P05108-2]
DR   PDB; 3N9Y; X-ray; 2.10 A; A/B=41-521.
DR   PDB; 3N9Z; X-ray; 2.17 A; A/B=41-521.
DR   PDB; 3NA0; X-ray; 2.50 A; A/B=44-514.
DR   PDB; 3NA1; X-ray; 2.25 A; A/B=41-521.
DR   PDBsum; 3N9Y; -.
DR   PDBsum; 3N9Z; -.
DR   PDBsum; 3NA0; -.
DR   PDBsum; 3NA1; -.
DR   SMR; P05108; -.
DR   BioGRID; 107955; 5.
DR   IntAct; P05108; 5.
DR   MINT; P05108; -.
DR   STRING; 9606.ENSP00000268053; -.
DR   BindingDB; P05108; -.
DR   ChEMBL; CHEMBL2033; -.
DR   DrugBank; DB00357; Aminoglutethimide.
DR   DrugBank; DB00169; Cholecalciferol.
DR   DrugBank; DB01396; Digitoxin.
DR   DrugBank; DB00390; Digoxin.
DR   DrugBank; DB00153; Ergocalciferol.
DR   DrugBank; DB01437; Glutethimide.
DR   DrugBank; DB02901; Stanolone.
DR   DrugBank; DB00624; Testosterone.
DR   DrugBank; DB13943; Testosterone cypionate.
DR   DrugBank; DB13944; Testosterone enanthate.
DR   DrugBank; DB13946; Testosterone undecanoate.
DR   DrugCentral; P05108; -.
DR   GuidetoPHARMACOLOGY; 1358; -.
DR   SwissLipids; SLP:000001196; -.
DR   iPTMnet; P05108; -.
DR   PhosphoSitePlus; P05108; -.
DR   BioMuta; CYP11A1; -.
DR   DMDM; 143811381; -.
DR   MassIVE; P05108; -.
DR   PaxDb; P05108; -.
DR   PeptideAtlas; P05108; -.
DR   PRIDE; P05108; -.
DR   ProteomicsDB; 33720; -.
DR   ProteomicsDB; 51794; -. [P05108-1]
DR   Antibodypedia; 3076; 438 antibodies.
DR   DNASU; 1583; -.
DR   Ensembl; ENST00000268053; ENSP00000268053; ENSG00000140459. [P05108-1]
DR   Ensembl; ENST00000358632; ENSP00000351455; ENSG00000140459. [P05108-2]
DR   Ensembl; ENST00000672385; ENSP00000500767; ENSG00000288362. [P05108-1]
DR   Ensembl; ENST00000672913; ENSP00000499849; ENSG00000288362. [P05108-2]
DR   GeneID; 1583; -.
DR   KEGG; hsa:1583; -.
DR   UCSC; uc002axs.3; human. [P05108-1]
DR   CTD; 1583; -.
DR   DisGeNET; 1583; -.
DR   GeneCards; CYP11A1; -.
DR   HGNC; HGNC:2590; CYP11A1.
DR   HPA; ENSG00000140459; Group enriched (adrenal gland, placenta).
DR   MalaCards; CYP11A1; -.
DR   MIM; 118485; gene.
DR   MIM; 613743; phenotype.
DR   neXtProt; NX_P05108; -.
DR   OpenTargets; ENSG00000140459; -.
DR   Orphanet; 168558; 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency.
DR   Orphanet; 289548; Inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency.
DR   PharmGKB; PA27089; -.
DR   VEuPathDB; HostDB:ENSG00000140459; -.
DR   eggNOG; KOG0159; Eukaryota.
DR   GeneTree; ENSGT00940000158575; -.
DR   HOGENOM; CLU_001570_28_4_1; -.
DR   InParanoid; P05108; -.
DR   OMA; YHFWREK; -.
DR   PhylomeDB; P05108; -.
DR   TreeFam; TF105094; -.
DR   BioCyc; MetaCyc:HS06719-MONOMER; -.
DR   BRENDA; 1.14.15.6; 2681.
DR   PathwayCommons; P05108; -.
DR   Reactome; R-HSA-196108; Pregnenolone biosynthesis.
DR   Reactome; R-HSA-211976; Endogenous sterols.
DR   Reactome; R-HSA-5579026; Defective CYP11A1 causes AICSR.
DR   SABIO-RK; P05108; -.
DR   SIGNOR; P05108; -.
DR   UniPathway; UPA00229; -.
DR   UniPathway; UPA00296; -.
DR   BioGRID-ORCS; 1583; 7 hits in 1009 CRISPR screens.
DR   ChiTaRS; CYP11A1; human.
DR   EvolutionaryTrace; P05108; -.
DR   GeneWiki; Cholesterol_side-chain_cleavage_enzyme; -.
DR   GenomeRNAi; 1583; -.
DR   Pharos; P05108; Tclin.
DR   PRO; PR:P05108; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; P05108; protein.
DR   Bgee; ENSG00000140459; Expressed in right adrenal gland and 116 other tissues.
DR   ExpressionAtlas; P05108; baseline and differential.
DR   Genevisible; P05108; HS.
DR   GO; GO:0005743; C:mitochondrial inner membrane; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR   GO; GO:0008386; F:cholesterol monooxygenase (side-chain-cleaving) activity; IDA:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central.
DR   GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR   GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central.
DR   GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR   GO; GO:0042359; P:vitamin D metabolic process; ISS:UniProtKB.
DR   Gene3D; 1.10.630.10; -; 1.
DR   InterPro; IPR033283; CYP11A1.
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:SF3; PTHR24279:SF3; 1.
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   3D-structure; Alternative splicing; Cholesterol metabolism;
KW   Direct protein sequencing; Disease variant; 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   Steroidogenesis; Sterol metabolism; Transit peptide.
FT   TRANSIT         1..39
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P00189"
FT   CHAIN           40..521
FT                   /note="Cholesterol side-chain cleavage enzyme,
FT                   mitochondrial"
FT                   /id="PRO_0000003585"
FT   METAL           462
FT                   /note="Iron (heme axial ligand)"
FT                   /evidence="ECO:0000269|PubMed:21636783,
FT                   ECO:0007744|PDB:3N9Y, ECO:0007744|PDB:3N9Z,
FT                   ECO:0007744|PDB:3NA0, ECO:0007744|PDB:3NA1"
FT   VAR_SEQ         1..158
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045695"
FT   VARIANT         141
FT                   /note="L -> W (in AICSR; reduced activity;
FT                   dbSNP:rs121912813)"
FT                   /evidence="ECO:0000269|PubMed:18182448"
FT                   /id="VAR_065241"
FT   VARIANT         189
FT                   /note="A -> V (in AICSR; no loss of activity;
FT                   dbSNP:rs121912811)"
FT                   /evidence="ECO:0000269|PubMed:12161514"
FT                   /id="VAR_016949"
FT   VARIANT         222
FT                   /note="L -> P (in AICSR; markedly reduced activity;
FT                   dbSNP:rs387906601)"
FT                   /evidence="ECO:0000269|PubMed:19116240"
FT                   /id="VAR_065242"
FT   VARIANT         271
FT                   /note="D -> DGD (in AICSR; complete loss of activity)"
FT                   /evidence="ECO:0000269|PubMed:11502818"
FT                   /id="VAR_016950"
FT   VARIANT         314
FT                   /note="E -> K (in dbSNP:rs6161)"
FT                   /evidence="ECO:0000269|PubMed:10391209"
FT                   /id="VAR_013944"
FT   VARIANT         353
FT                   /note="R -> W (in AICSR; loss of activity;
FT                   dbSNP:rs72547508)"
FT                   /evidence="ECO:0000269|PubMed:12161514"
FT                   /id="VAR_016951"
FT   VARIANT         359
FT                   /note="A -> V (in AICSR; markedly reduced activity;
FT                   dbSNP:rs121912812)"
FT                   /evidence="ECO:0000269|PubMed:16705068"
FT                   /id="VAR_065243"
FT   VARIANT         415
FT                   /note="V -> E (in AICSR; complete loss of activity;
FT                   dbSNP:rs121912814)"
FT                   /evidence="ECO:0000269|PubMed:18182448"
FT                   /id="VAR_065244"
FT   CONFLICT        16
FT                   /note="C -> Y (in Ref. 1; AAA52162)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        274
FT                   /note="F -> L (in Ref. 2; CAA28965)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        283
FT                   /note="N -> H (in Ref. 9; AAA36404)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        301
FT                   /note="I -> M (in Ref. 1; AAA52162 and 9; AAA36404)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        505
FT                   /note="K -> E (in Ref. 3; BAG51810)"
FT                   /evidence="ECO:0000305"
FT   HELIX           48..50
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           58..68
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           71..73
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           74..85
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          87..93
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          96..101
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           104..112
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           124..132
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           139..141
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           144..158
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           161..164
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           167..189
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          190..196
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           199..215
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          223..225
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           228..244
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           245..247
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           252..258
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           260..291
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           301..307
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           313..328
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           330..344
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           346..362
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   TURN            363..365
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           367..370
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           375..387
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          390..397
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          402..404
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          407..409
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          414..418
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           419..423
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   TURN            426..428
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          429..431
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           437..440
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   TURN            449..451
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           458..460
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   HELIX           465..482
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          483..486
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          495..505
FT                   /evidence="ECO:0007829|PDB:3N9Y"
FT   STRAND          509..513
FT                   /evidence="ECO:0007829|PDB:3N9Y"
SQ   SEQUENCE   521 AA;  60102 MW;  AB0501E7A5665D8B CRC64;
     MLAKGLPPRS VLVKGCQTFL SAPREGLGRL RVPTGEGAGI STRSPRPFNE IPSPGDNGWL
     NLYHFWRETG THKVHLHHVQ NFQKYGPIYR EKLGNVESVY VIDPEDVALL FKSEGPNPER
     FLIPPWVAYH QYYQRPIGVL LKKSAAWKKD RVALNQEVMA PEATKNFLPL LDAVSRDFVS
     VLHRRIKKAG SGNYSGDISD DLFRFAFESI TNVIFGERQG MLEEVVNPEA QRFIDAIYQM
     FHTSVPMLNL PPDLFRLFRT KTWKDHVAAW DVIFSKADIY TQNFYWELRQ KGSVHHDYRG
     ILYRLLGDSK MSFEDIKANV TEMLAGGVDT TSMTLQWHLY EMARNLKVQD MLRAEVLAAR
     HQAQGDMATM LQLVPLLKAS IKETLRLHPI SVTLQRYLVN DLVLRDYMIP AKTLVQVAIY
     ALGREPTFFF DPENFDPTRW LSKDKNITYF RNLGFGWGVR QCLGRRIAEL EMTIFLINML
     ENFRVEIQHL SDVGTTFNLI LMPEKPISFT FWPFNQEATQ Q
//
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