CP11A_HUMAN
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 03-AUG-2022, entry version 219.
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
CC [adrenodoxin] = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2
CC oxidized [adrenodoxin]; Xref=Rhea:RHEA:34339, Rhea:RHEA-COMP:9998,
CC Rhea:RHEA-COMP:9999, ChEBI:CHEBI:1294, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:33737,
CC ChEBI:CHEBI:33738, ChEBI:CHEBI:67237;
CC 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 AlphaFoldDB; P05108; -.
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; 440 antibodies from 32 providers.
DR DNASU; 1583; -.
DR Ensembl; ENST00000268053.11; ENSP00000268053.6; ENSG00000140459.18. [P05108-1]
DR Ensembl; ENST00000358632.8; ENSP00000351455.4; ENSG00000140459.18. [P05108-2]
DR Ensembl; ENST00000672385.1; ENSP00000500767.1; ENSG00000288362.1. [P05108-1]
DR Ensembl; ENST00000672913.1; ENSP00000499849.1; ENSG00000288362.1. [P05108-2]
DR GeneID; 1583; -.
DR KEGG; hsa:1583; -.
DR MANE-Select; ENST00000268053.11; ENSP00000268053.6; NM_000781.3; NP_000772.2.
DR UCSC; uc002axs.3; human. [P05108-1]
DR CTD; 1583; -.
DR DisGeNET; 1583; -.
DR GeneCards; CYP11A1; -.
DR HGNC; HGNC:2590; CYP11A1.
DR HPA; ENSG00000140459; Tissue enriched (adrenal).
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; MPDKPIF; -.
DR PhylomeDB; P05108; -.
DR TreeFam; TF105094; -.
DR BioCyc; MetaCyc:HS06719-MON; -.
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 SignaLink; P05108; -.
DR SIGNOR; P05108; -.
DR UniPathway; UPA00229; -.
DR UniPathway; UPA00296; -.
DR BioGRID-ORCS; 1583; 16 hits in 1072 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 adrenal tissue and 97 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 BINDING 462
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: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
