Cholesterol side-chain cleavage enzyme, mitochondrial
Details
- Name
- Cholesterol side-chain cleavage enzyme, mitochondrial
- Kind
- protein
- Synonyms
- 1.14.15.6
- Cholesterol desmolase
- CYP11A
- CYPXIA1
- Cytochrome P450 11A1
- Cytochrome P450(scc)
- Gene Name
- CYP11A1
- UniProtKB Entry
- P05108Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0006815|Cholesterol side-chain cleavage enzyme, mitochondrial MLAKGLPPRSVLVKGCQTFLSAPREGLGRLRVPTGEGAGISTRSPRPFNEIPSPGDNGWL NLYHFWRETGTHKVHLHHVQNFQKYGPIYREKLGNVESVYVIDPEDVALLFKSEGPNPER FLIPPWVAYHQYYQRPIGVLLKKSAAWKKDRVALNQEVMAPEATKNFLPLLDAVSRDFVS VLHRRIKKAGSGNYSGDISDDLFRFAFESITNVIFGERQGMLEEVVNPEAQRFIDAIYQM FHTSVPMLNLPPDLFRLFRTKTWKDHVAAWDVIFSKADIYTQNFYWELRQKGSVHHDYRG ILYRLLGDSKMSFEDIKANVTEMLAGGVDTTSMTLQWHLYEMARNLKVQDMLRAEVLAAR HQAQGDMATMLQLVPLLKASIKETLRLHPISVTLQRYLVNDLVLRDYMIPAKTLVQVAIY ALGREPTFFFDPENFDPTRWLSKDKNITYFRNLGFGWGVRQCLGRRIAELEMTIFLINML ENFRVEIQHLSDVGTTFNLILMPEKPISFTFWPFNQEATQQ
- Number of residues
- 521
- Molecular Weight
- 60101.87
- Theoretical pI
- 9.18
- GO Classification
- Not Available
- General Function
- A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:21636783). Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal (PubMed:21636783). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:21636783)
- Specific Function
- cholesterol monooxygenase (side-chain-cleaving) activity
- Pfam Domain Function
- p450 (PF00067)
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Mitochondrion inner membrane
- Gene sequence
>lcl|BSEQ0012463|Cholesterol side-chain cleavage enzyme, mitochondrial (CYP11A1) ATGCTGGCCAAGGGTCTTCCCCCACGCTCAGTCCTGGTCAAAGGCTGCCAGACCTTTCTG AGTGCCCCCAGGGAGGGGCTGGGGCGTCTCAGGGTGCCCACTGGCGAGGGAGCTGGCATC TCCACCCGCAGTCCTCGCCCCTTCAATGAGATCCCCTCTCCTGGTGACAATGGCTGGCTA AACCTGTACCATTTCTGGAGGGAGACGGGCACACACAAAGTCCACCTTCACCATGTCCAG AATTTCCAGAAGTATGGCCCGATTTACAGGGAGAAGCTCGGCAACGTGGAGTCGGTTTAT GTCATCGACCCTGAAGATGTGGCCCTTCTCTTTAAGTCCGAGGGCCCCAACCCAGAACGA TTCCTCATCCCGCCCTGGGTCGCCTATCACCAGTATTACCAGAGACCCATAGGAGTCCTG TTGAAGAAGTCGGCAGCCTGGAAGAAAGACCGGGTGGCCCTGAACCAGGAGGTGATGGCT CCAGAGGCCACCAAGAACTTTTTGCCCCTGTTGGATGCAGTGTCTCGGGACTTCGTCAGT GTCCTGCACAGGCGCATCAAGAAGGCGGGCTCCGGAAATTACTCGGGGGACATCAGTGAT GACCTGTTCCGCTTTGCCTTTGAGTCCATCACTAACGTCATTTTTGGGGAGCGCCAGGGG ATGCTGGAGGAAGTAGTGAACCCCGAGGCCCAGCGATTCATTGATGCCATCTACCAGATG TTCCACACCAGCGTCCCCATGCTCAACCTTCCCCCAGACCTGTTCCGTCTGTTCAGGACC AAGACCTGGAAGGACCATGTGGCTGCATGGGACGTGATTTTCAGTAAAGCTGACATATAC ACCCAGAACTTCTACTGGGAATTGAGACAGAAAGGAAGTGTTCACCACGATTACCGTGGC ATCCTCTACAGACTCCTGGGAGACAGCAAGATGTCCTTCGAGGACATCAAGGCCAACGTC ACAGAGATGCTGGCAGGAGGGGTGGACACGACGTCCATGACCCTGCAGTGGCACTTGTAT GAGATGGCACGCAACCTGAAGGTGCAGGATATGCTGCGGGCAGAGGTCTTGGCTGCGCGG CACCAGGCCCAGGGAGACATGGCCACGATGCTACAGCTGGTCCCCCTCCTCAAAGCCAGC ATCAAGGAGACACTAAGACTTCACCCCATCTCCGTGACCCTGCAGAGATATCTTGTAAAT GACTTGGTTCTTCGAGATTACATGATTCCTGCCAAGACACTGGTGCAAGTGGCCATCTAT GCTCTGGGCCGAGAGCCCACCTTCTTCTTCGACCCGGAAAATTTTGACCCAACCCGATGG CTGAGCAAAGACAAGAACATCACCTACTTCCGGAACTTGGGCTTTGGCTGGGGTGTGCGG CAGTGTCTGGGACGGCGGATCGCTGAGCTAGAGATGACCATCTTCCTCATCAATATGCTG GAGAACTTCAGAGTTGAAATCCAACACCTCAGCGATGTGGGCACCACATTCAACCTCATT CTGATGCCTGAAAAGCCCATCTCCTTCACCTTCTGGCCCTTTAACCAGGAAGCAACCCAG CAGTGA
- Chromosome Location
- 15
- Locus
- 15q24.1
- External Identifiers
Resource Link UniProtKB ID P05108 UniProtKB Entry Name CP11A_HUMAN GenBank Protein ID 181376 GenBank Gene ID M14565 GeneCard ID CYP11A1 HGNC ID HGNC:2590 PDB ID(s) 3N9Y, 3N9Z, 3NA0, 3NA1 KEGG ID hsa:1583 IUPHAR/Guide To Pharmacology ID 1358 NCBI Gene ID 1583 - General References
- Chung BC, Matteson KJ, Voutilainen R, Mohandas TK, Miller WL: Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8962-6. [Article]
- Morohashi K, Sogawa K, Omura T, Fujii-Kuriyama Y: Gene structure of human cytochrome P-450(SCC), cholesterol desmolase. J Biochem. 1987 Apr;101(4):879-87. [Article]
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- Hu MC, Guo IC, Lin JH, Chung BC: Regulated expression of cytochrome P-450scc (cholesterol-side-chain cleavage enzyme) in cultured cell lines detected by antibody against bacterially expressed human protein. Biochem J. 1991 Mar 15;274 ( Pt 3):813-7. [Article]
- Matteson KJ, Chung BC, Urdea MS, Miller WL: Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes. Endocrinology. 1986 Apr;118(4):1296-305. [Article]
- Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S, Park HW: Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10139-43. doi: 10.1073/pnas.1019441108. Epub 2011 Jun 2. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Cholecalciferol approved, nutraceutical unknown enzyme substrate Details Digoxin approved unknown enzyme inhibitor Details Testosterone approved, investigational unknown enzyme inhibitor Details Digitoxin approved, investigational unknown enzyme inhibitor Details Aminoglutethimide approved, investigational yes target inhibitor Details Stanolone illicit, investigational unknown enzyme substrate Details Glutethimide approved, illicit unknown enzyme inhibitor Details Testosterone cypionate approved unknown enzyme inhibitor Details Testosterone enanthate approved unknown enzyme inhibitor Details Testosterone undecanoate approved, investigational unknown enzyme inhibitor Details Ergocalciferol approved, nutraceutical no enzyme substrate Details Levoketoconazole approved, investigational yes target inhibitor Details