UniProtKB - P17177 (CP27A_RABIT)
Sterol 26-hydroxylase, mitochondrial
CYP27A1
Functioni
Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid (By similarity).
Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways (PubMed:2722778).
May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism. Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (By similarity).
By similarity1 PublicationCatalytic activityi
- 5β-cholestane-3α,7α,12α-triol + 5 H+ + 3 O2 + 6 reduced [adrenodoxin] = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 4 H2O + 6 oxidized [adrenodoxin]1 PublicationEC:1.14.15.151 PublicationThis reaction proceeds in the forwardCurated direction.
- cholestanol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-26-hydroxycholestanol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3β-hydroxycholest-5-en-7-one-26-al + H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β-hydroxycholest-5-en-7-one-26-oate + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3β,26-dihydroxycholest-5-en-7-one + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β-hydroxycholest-5-en-7-one-26-al + 2 H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- 7-oxocholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β,26-dihydroxycholest-5-en-7-one + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- calciol + 2 H+ + O2 + 2 reduced [adrenodoxin] = calcidiol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-5β-cholestane-3α,7α,12α,26-tetrol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + 2 H2O + 2 oxidized [adrenodoxin]1 PublicationThis reaction proceeds in the forwardCurated direction.
- cholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-cholest-5-ene-3β,26-diol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3β,4β-dihydroxycholest-5-en-26-al + H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β,4β-dihydroxycholest-5-en-26-oate + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-4β,26-dihydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β,4β-dihydroxycholest-5-en-26-al + 2 H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- 4β-hydroxycholesterol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-4β,26-dihydroxycholesterol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3β-hydroxy-5-cholesten-26-al + H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β-hydroxy-5-cholestenoate + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-cholest-5-ene-3β,26-diol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3β-hydroxy-5-cholesten-26-al + 2 H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
- (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + H+ + O2 + 2 reduced [adrenodoxin] = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + H2O + 2 oxidized [adrenodoxin]1 PublicationThis reaction proceeds in the forwardCurated direction.
- 5β-cholestane-3α,7α,12α-triol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (25R)-5β-cholestane-3α,7α,12α,26-tetrol + H2O + 2 oxidized [adrenodoxin]By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
: cholecalciferol biosynthesis Pathwayi
This protein is involved in the pathway cholecalciferol biosynthesis, which is part of Hormone biosynthesis.By similarityView all proteins of this organism that are known to be involved in the pathway cholecalciferol biosynthesis and in Hormone biosynthesis.
Pathwayi: cholesterol degradation
This protein is involved in the pathway cholesterol degradation, which is part of Steroid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway cholesterol degradation and in Steroid metabolism.
Pathwayi: bile acid biosynthesis
This protein is involved in the pathway bile acid biosynthesis, which is part of Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway bile acid biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 480 | Iron (heme axial ligand) | 1 |
GO - Molecular functioni
- 3-alpha,7-alpha,12-alpha-trihydroxycholestan-26-al 26-oxidoreductase activity Source: UniProtKB-EC
- cholestanetetraol 26-dehydrogenase activity Source: RHEA
- cholestanetriol 26-monooxygenase activity Source: UniProtKB
- cholesterol 26-hydroxylase activity Source: UniProtKB
- cholesterol 7-alpha-monooxygenase activity Source: UniProtKB
- cholesterol monooxygenase (side-chain-cleaving) activity Source: UniProtKB
- heme binding Source: UniProtKB
- Hsp70 protein binding Source: UniProtKB
- iron ion binding Source: InterPro
- vitamin D3 25-hydroxylase activity Source: UniProtKB
GO - Biological processi
- bile acid biosynthetic process Source: UniProtKB
- C21-steroid hormone biosynthetic process Source: UniProtKB
- calcitriol biosynthetic process from calciol Source: UniProtKB
- cholesterol catabolic process Source: UniProtKB
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
UniPathwayi | UPA00221 UPA00955 UPA01058 |
Names & Taxonomyi
Protein namesi | Recommended name: Sterol 26-hydroxylase, mitochondrial1 Publication (EC:1.14.15.151 Publication)Alternative name(s): 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 26-hydroxylase1 Publication Cytochrome P-450C27/25 Cytochrome P450 27 Sterol 27-hydroxylaseBy similarity Vitamin D(3) 25-hydroxylaseBy similarity |
Gene namesi | Name:CYP27A1 Synonyms:CYP27 |
Organismi | Oryctolagus cuniculus (Rabbit) |
Taxonomic identifieri | 9986 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus |
Proteomesi |
|
Subcellular locationi
Mitochondrion
- Mitochondrion inner membrane By similarity; Peripheral membrane protein By similarity
Note: Post-translationally targeted to mitochondria. All three of the receptor proteins in the TOM complex, TOMM70, TOMM20 and TOMM22 are required for the translocation across the mitochondrial outer membrane. After translocation into the matrix, associates with the inner membrane as a membrane extrinsic protein.By similarity
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 36 | Mitochondrion1 PublicationAdd BLAST | 36 | |
ChainiPRO_0000003620 | 37 – 535 | Sterol 26-hydroxylase, mitochondrialAdd BLAST | 499 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 286 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 524 | N6-acetyllysineBy similarity | 1 |
Keywords - PTMi
AcetylationExpressioni
Tissue specificityi
Interactioni
Subunit structurei
Interacts with HSP70; this interaction is required for initial targeting to mitochondria.
By similarityGO - Molecular functioni
- Hsp70 protein binding Source: UniProtKB
Protein-protein interaction databases
STRINGi | 9986.ENSOCUP00000002930 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 387 – 401 | Sterol-bindingSequence analysisAdd BLAST | 15 |
Sequence similaritiesi
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG0159, Eukaryota |
InParanoidi | P17177 |
OMAi | SNTMTWA |
OrthoDBi | 871849at2759 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
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
MAALGCARLR WALLGPRVAG CGLCPQGARA KAAIPTALPA DEAAQAPGAG
60 70 80 90 100
PGDRRRRRSL EELPRLGQLR FFYQAFVQGY LLHLHKLQVL NKARYGPMWV
110 120 130 140 150
SYLGPQLFVN LASAPLVETV MRQEGKYPVR NDMQLWKEHR DHQDLAYGVF
160 170 180 190 200
TTDGHDWYQL RQALNQRLLK PAEAALYTDA LNEVIDSFVV RLDQLRAESA
210 220 230 240 250
SGDQVPDMAD LLYHFALEAI CYILFEKRIG CLEASIPKDT ENFIRSVGLM
260 270 280 290 300
FQNSVYVTFL PKWTRPLLPF WKRYLDGWDT IFSFGKNLID QKLQEVVAQL
310 320 330 340 350
QSAGSDGVQV SGYLHSLLTS GQLSPREALG SLPELLLAGV DTTSNTLTWA
360 370 380 390 400
LYHLSKNPEI QAALRKEVVG VVAAGQVPQH KDFAHMPLLK AVLKETLRLY
410 420 430 440 450
PVIPANSRII VDKEIEVGGF LFPKNTQFVF CHYVTSRDPS TFSEPDTFWP
460 470 480 490 500
YRWLRKGQPE TSKTQHPFGS VPFGYGVRAC LGRRIAELEM QLLLARLIQR
510 520 530
YELMLAPETG EVQSVARIVL VPNKKVGLRF LPTQR
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04717 mRNA Translation: AAA31225.1 |
PIRi | A33813 |
RefSeqi | NP_001177359.1, NM_001190430.1 |
Genome annotation databases
GeneIDi | 100348736 |
KEGGi | ocu:100348736 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | J04717 mRNA Translation: AAA31225.1 |
PIRi | A33813 |
RefSeqi | NP_001177359.1, NM_001190430.1 |
3D structure databases
SMRi | P17177 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9986.ENSOCUP00000002930 |
Genome annotation databases
GeneIDi | 100348736 |
KEGGi | ocu:100348736 |
Organism-specific databases
CTDi | 1593 |
Phylogenomic databases
eggNOGi | KOG0159, Eukaryota |
InParanoidi | P17177 |
OMAi | SNTMTWA |
OrthoDBi | 871849at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00221 UPA00955 UPA01058 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR036396, Cyt_P450_sf |
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 | CP27A_RABIT | |
Accessioni | P17177Primary (citable) accession number: P17177 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | August 1, 1990 | |
Last modified: | February 23, 2022 | |
This is version 120 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
Direct protein sequencing, Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families