UniProtKB - P14137 (CP11A_RAT)
Protein
Cholesterol side-chain cleavage enzyme, mitochondrial
Gene
Cyp11a1
Organism
Rattus norvegicus (Rat)
Status
Functioni
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. 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. 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).By similarity
Catalytic activityi
- cholesterol + 6 H+ + 3 O2 + 6 reduced [adrenodoxin] = 4-methylpentanal + 4 H2O + 6 oxidized [adrenodoxin] + pregnenoloneBy similarityEC:1.14.15.6By similarityThis reaction proceeds in the forwardBy similarity direction.
- cholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 22R-hydroxycholesterol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- 22R-hydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (20R,22R)-20,22-dihydroxycholesterol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (20R,22R)-20,22-dihydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 4-methylpentanal + 2 H2O + 2 oxidized [adrenodoxin] + pregnenoloneBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
hemeBy similarity
: C21-steroid hormone metabolism Pathwayi
This protein is involved in the pathway C21-steroid hormone metabolism, which is part of Lipid metabolism.By similarityView 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.By similarityView 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 | 459 | Iron (heme axial ligand)By similarity | 1 |
GO - Molecular functioni
- cholesterol binding Source: RGD
- cholesterol monooxygenase (side-chain-cleaving) activity Source: RGD
- heme binding Source: UniProtKB
- iron ion binding Source: InterPro
GO - Biological processi
- biphenyl metabolic process Source: RGD
- C21-steroid hormone biosynthetic process Source: RGD
- cellular response to antibiotic Source: RGD
- cellular response to cadmium ion Source: RGD
- cellular response to cAMP Source: RGD
- cellular response to fibroblast growth factor stimulus Source: RGD
- cellular response to follicle-stimulating hormone stimulus Source: RGD
- cellular response to gonadotropin stimulus Source: RGD
- cellular response to interleukin-1 Source: RGD
- cellular response to lipopolysaccharide Source: RGD
- cellular response to peptide hormone stimulus Source: RGD
- cellular response to transforming growth factor beta stimulus Source: RGD
- cellular response to tumor necrosis factor Source: RGD
- cerebellum development Source: RGD
- cholesterol metabolic process Source: UniProtKB
- cortisol metabolic process Source: GO_Central
- dibenzo-p-dioxin metabolic process Source: RGD
- glucocorticoid biosynthetic process Source: GO_Central
- granulosa cell differentiation Source: RGD
- hippocampus development Source: RGD
- Leydig cell differentiation Source: RGD
- male gonad development Source: RGD
- maternal process involved in female pregnancy Source: RGD
- mating behavior Source: RGD
- organic acid metabolic process Source: RGD
- phenol-containing compound metabolic process Source: RGD
- phthalate metabolic process Source: RGD
- response to alkaloid Source: RGD
- response to amino acid Source: RGD
- response to antibiotic Source: RGD
- response to cadmium ion Source: RGD
- response to cAMP Source: RGD
- response to corticosterone Source: RGD
- response to drug Source: RGD
- response to estrogen Source: RGD
- response to fungicide Source: RGD
- response to gamma radiation Source: RGD
- response to genistein Source: RGD
- response to gonadotropin Source: RGD
- response to hydrogen peroxide Source: RGD
- response to insecticide Source: RGD
- response to ionizing radiation Source: RGD
- response to L-ascorbic acid Source: RGD
- response to nutrient Source: RGD
- response to organic cyclic compound Source: RGD
- response to organic substance Source: RGD
- response to peptide hormone Source: RGD
- response to salt stress Source: RGD
- response to steroid hormone Source: RGD
- response to vitamin E Source: RGD
- Schwann cell differentiation Source: RGD
- steroid biosynthetic process Source: RGD
- testosterone biosynthetic process Source: RGD
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
Reactomei | R-RNO-196108, Pregnenolone biosynthesis R-RNO-211976, Endogenous sterols |
SABIO-RKi | P14137 |
UniPathwayi | UPA00229 UPA00296 |
Names & Taxonomyi
Protein namesi | Recommended name: Cholesterol side-chain cleavage enzyme, mitochondrial1 Publication (EC:1.14.15.6By similarity)Alternative name(s): CYPXIA1 Cholesterol desmolase Cytochrome P450 11A1 Cytochrome P450(scc) |
Gene namesi | |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 69325, Cyp11a1 |
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane 3 Publications; Peripheral membrane protein Curated
Note: Localizes to the matrix side of the mitochondrion inner membrane.1 Publication
Mitochondrion
- mitochondrial crista Source: RGD
- mitochondrial inner membrane Source: RGD
- mitochondrion Source: UniProtKB
Other locations
- perikaryon Source: RGD
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 36 | MitochondrionBy similarityAdd BLAST | 36 | |
ChainiPRO_0000003590 | 37 – 526 | Cholesterol side-chain cleavage enzyme, mitochondrialAdd BLAST | 490 |
Proteomic databases
PaxDbi | P14137 |
PTM databases
iPTMneti | P14137 |
PhosphoSitePlusi | P14137 |
Expressioni
Tissue specificityi
Expressed in the kidney where it localizes to the distal convoluted tubule and the thick ascending limb of the loop of Henle (at protein level) (PubMed:21075169). In the ovary, highly expressed in interstitial cells (at protein level) (PubMed:3948785). Also expressed in adrenal gland and testis (PubMed:3123325).3 Publications
Inductioni
Induced by FSH or pregnant mare's serum gonadotropin in ovaries of estrogen-treated immature rats in vivo.
Gene expression databases
Genevisiblei | P14137, RN |
Interactioni
Subunit structurei
Interacts with FDX1/adrenodoxin.
By similarityProtein-protein interaction databases
STRINGi | 10116.ENSRNOP00000010831 |
Chemistry databases
BindingDBi | P14137 |
Family & Domainsi
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0159, Eukaryota |
HOGENOMi | CLU_001570_28_4_1 |
InParanoidi | P14137 |
OrthoDBi | 561463at2759 |
PhylomeDBi | P14137 |
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 |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P14137-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MLAKGLCLRS VLVKSCQPFL SPVWQGPGLA TGNGAGISST NSPRSFNEIP
60 70 80 90 100
SPGDNGWINL YHFLRENGTH RIHYHHMQNF QKYGPIYREK LGNMESVYIL
110 120 130 140 150
DPKDAATLFS CEGPNPERYL VPPWVAYHQY YQRPIGVLFK SSDAWRKDRI
160 170 180 190 200
VLNQEVMAPD SIKNFVPLLE GVAQDFIKVL HRRIKQQNSG KFSGDISDDL
210 220 230 240 250
FRFAFESITS VVFGERLGML EEIVDPESQR FIDAVYQMFH TSVPMLNMPP
260 270 280 290 300
DLFRLFRTKT WKDHAAAWDV IFSKADEYTQ NFYWDLRQKR DFSKYPGVLY
310 320 330 340 350
SLLGGNKLPF KNIQANITEM LAGGVDTTSM TLQWNLYEMA HNLKVQEMLR
360 370 380 390 400
AEVLAARRQA QGDMAKMVQL VPLLKASIKE TLRLHPISVT LQRYIVNDLV
410 420 430 440 450
LRNYKIPAKT LVQVASYAMG RESSFFPNPN KFDPTRWLEK SQNTTHFRYL
460 470 480 490 500
GFGWGVRQCL GRRIAELEMT IFLINVLENF RIEVQSIRDV GTKFNLILMP
510 520
EKPIFFNFQP LKQDLGSTMP RKGDTV
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A0H2UHG1 | A0A0H2UHG1_RAT | Cholesterol side-chain cleavage enz... | Cyp11a1 | 490 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05156 mRNA Translation: AAA40989.1 M63133 , M63125, M63126, M63127, M63128, M63129, M63130, M63131, M63132 Genomic DNA Translation: AAA40958.1 BC089100 mRNA Translation: AAH89100.1 M22615 mRNA Translation: AAA62267.1 |
PIRi | A34164 |
RefSeqi | NP_058982.1, NM_017286.3 |
Genome annotation databases
GeneIDi | 29680 |
KEGGi | rno:29680 |
UCSCi | RGD:69325, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J05156 mRNA Translation: AAA40989.1 M63133 , M63125, M63126, M63127, M63128, M63129, M63130, M63131, M63132 Genomic DNA Translation: AAA40958.1 BC089100 mRNA Translation: AAH89100.1 M22615 mRNA Translation: AAA62267.1 |
PIRi | A34164 |
RefSeqi | NP_058982.1, NM_017286.3 |
3D structure databases
SMRi | P14137 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000010831 |
Chemistry databases
BindingDBi | P14137 |
ChEMBLi | CHEMBL5246 |
DrugCentrali | P14137 |
PTM databases
iPTMneti | P14137 |
PhosphoSitePlusi | P14137 |
Proteomic databases
PaxDbi | P14137 |
Genome annotation databases
GeneIDi | 29680 |
KEGGi | rno:29680 |
UCSCi | RGD:69325, rat |
Organism-specific databases
CTDi | 1583 |
RGDi | 69325, Cyp11a1 |
Phylogenomic databases
eggNOGi | KOG0159, Eukaryota |
HOGENOMi | CLU_001570_28_4_1 |
InParanoidi | P14137 |
OrthoDBi | 561463at2759 |
PhylomeDBi | P14137 |
Enzyme and pathway databases
UniPathwayi | UPA00229 UPA00296 |
Reactomei | R-RNO-196108, Pregnenolone biosynthesis R-RNO-211976, Endogenous sterols |
SABIO-RKi | P14137 |
Miscellaneous databases
PROi | PR:P14137 |
Gene expression databases
Genevisiblei | P14137, RN |
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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CP11A_RAT | |
Accessioni | P14137Primary (citable) accession number: P14137 Secondary accession number(s): Q5FWY8, Q6LDR9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 1, 1990 |
Last sequence update: | January 1, 1990 | |
Last modified: | December 2, 2020 | |
This is version 155 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
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families