UniProtKB - P00189 (CP11A_BOVIN)
Cholesterol side-chain cleavage enzyme, mitochondrial
CYP11A1
Functioni
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones (PubMed:11412116).
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:11412116).
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:11412116).
1 PublicationCatalytic activityi
- cholesterol + 6 H+ + 3 O2 + 6 reduced [adrenodoxin] = 4-methylpentanal + 4 H2O + 6 oxidized [adrenodoxin] + pregnenolone1 PublicationEC:1.14.15.61 PublicationThis reaction proceeds in the forward1 Publication direction.
- cholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 22R-hydroxycholesterol + H2O + 2 oxidized [adrenodoxin]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 22R-hydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2 oxidized [adrenodoxin]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (20R,22R)-20,22-dihydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 4-methylpentanal + 2 H2O + 2 oxidized [adrenodoxin] + pregnenolone1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
: C21-steroid hormone metabolism Pathwayi
This protein is involved in the pathway C21-steroid hormone metabolism, which is part of Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway C21-steroid hormone metabolism and in Lipid metabolism.
Pathwayi: cholesterol metabolism
This protein is involved in the pathway cholesterol metabolism, which is part of Steroid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway cholesterol metabolism and in Steroid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 461 | Iron (heme axial ligand)Combined sources1 Publication | 1 |
GO - Molecular functioni
- cholesterol monooxygenase (side-chain-cleaving) activity Source: UniProtKB
- heme binding Source: UniProtKB
- iron ion binding Source: InterPro
GO - Biological processi
- C21-steroid hormone biosynthetic process Source: UniProtKB
- cholesterol metabolic process Source: UniProtKB
- vitamin D metabolic process Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Steroidogenesis, Sterol metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.14.15.6, 908 |
SABIO-RKi | P00189 |
UniPathwayi | UPA00229 UPA00296 |
Names & Taxonomyi
Protein namesi | Recommended name: Cholesterol side-chain cleavage enzyme, mitochondrial1 Publication (EC:1.14.15.61 Publication)Alternative name(s): CYPXIA1 Cholesterol desmolase Cytochrome P450 11A1 Cytochrome P450(scc) |
Gene namesi | Name:CYP11A1 |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane By similarity; Peripheral membrane protein Curated
Note: Localizes to the matrix side of the mitochondrion inner membrane.By similarity
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 233 | F → A: Impairs the hydroxylase activity toward cholesterol; increases the electron leakage from the electron transfer chain. 1 Publication | 1 | |
Mutagenesisi | 233 | F → K: Markedly reduces the hydroxylase activity toward cholesterol. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL4813 |
DrugCentrali | P00189 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 39 | Mitochondrion2 PublicationsAdd BLAST | 39 | |
ChainiPRO_0000003582 | 40 – 520 | Cholesterol side-chain cleavage enzyme, mitochondrialAdd BLAST | 481 |
Proteomic databases
PaxDbi | P00189 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Interacts with FDX1/adrenodoxin.
By similarityProtein-protein interaction databases
STRINGi | 9913.ENSBTAP00000009106 |
Chemistry databases
BindingDBi | P00189 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | P00189 |
SMRi | P00189 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0159, Eukaryota |
InParanoidi | P00189 |
OrthoDBi | 561463at2759 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR033283, CYP11A1 IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
PANTHERi | PTHR24279:SF3, PTHR24279:SF3, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MLARGLPLRS ALVKACPPIL STVGEGWGHH RVGTGEGAGI STKTPRPYSE
60 70 80 90 100
IPSPGDNGWL NLYHFWREKG SQRIHFRHIE NFQKYGPIYR EKLGNLESVY
110 120 130 140 150
IIHPEDVAHL FKFEGSYPER YDIPPWLAYH RYYQKPIGVL FKKSGTWKKD
160 170 180 190 200
RVVLNTEVMA PEAIKNFIPL LNPVSQDFVS LLHKRIKQQG SGKFVGDIKE
210 220 230 240 250
DLFHFAFESI TNVMFGERLG MLEETVNPEA QKFIDAVYKM FHTSVPLLNV
260 270 280 290 300
PPELYRLFRT KTWRDHVAAW DTIFNKAEKY TEIFYQDLRR KTEFRNYPGI
310 320 330 340 350
LYCLLKSEKM LLEDVKANIT EMLAGGVNTT SMTLQWHLYE MARSLNVQEM
360 370 380 390 400
LREEVLNARR QAEGDISKML QMVPLLKASI KETLRLHPIS VTLQRYPESD
410 420 430 440 450
LVLQDYLIPA KTLVQVAIYA MGRDPAFFSS PDKFDPTRWL SKDKDLIHFR
460 470 480 490 500
NLGFGWGVRQ CVGRRIAELE MTLFLIHILE NFKVEMQHIG DVDTIFNLIL
510 520
TPDKPIFLVF RPFNQDPPQA
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 22 | T → S in AAA30681 (PubMed:2154474).Curated | 1 | |
Sequence conflicti | 57 | N → D AA sequence (PubMed:3518802).Curated | 1 | |
Sequence conflicti | 106 | D → N AA sequence (PubMed:3518802).Curated | 1 | |
Sequence conflicti | 197 | D → N AA sequence (PubMed:3518802).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | K02130 mRNA Translation: AAA30488.1 J05245 Genomic DNA Translation: AAA30681.1 |
PIRi | A00189, O4BOM |
RefSeqi | NP_788817.1, NM_176644.2 |
Genome annotation databases
GeneIDi | 338048 |
KEGGi | bta:338048 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | K02130 mRNA Translation: AAA30488.1 J05245 Genomic DNA Translation: AAA30681.1 |
PIRi | A00189, O4BOM |
RefSeqi | NP_788817.1, NM_176644.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3MZS | X-ray | 2.50 | A/B/C/D | 41-520 | [»] | |
AlphaFoldDBi | P00189 | |||||
SMRi | P00189 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
STRINGi | 9913.ENSBTAP00000009106 |
Chemistry databases
BindingDBi | P00189 |
ChEMBLi | CHEMBL4813 |
DrugCentrali | P00189 |
Proteomic databases
PaxDbi | P00189 |
Genome annotation databases
GeneIDi | 338048 |
KEGGi | bta:338048 |
Organism-specific databases
CTDi | 1583 |
Phylogenomic databases
eggNOGi | KOG0159, Eukaryota |
InParanoidi | P00189 |
OrthoDBi | 561463at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00229 UPA00296 |
BRENDAi | 1.14.15.6, 908 |
SABIO-RKi | P00189 |
Miscellaneous databases
PROi | PR:P00189 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR033283, CYP11A1 IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
PANTHERi | PTHR24279:SF3, PTHR24279:SF3, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CP11A_BOVIN | |
Accessioni | P00189Primary (citable) accession number: P00189 Secondary accession number(s): Q28152 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | July 21, 1986 | |
Last modified: | May 25, 2022 | |
This is version 151 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families