UniProtKB - Q60991 (CP7B1_MOUSE)
Protein
Cytochrome P450 7B1
Gene
Cyp7b1
Organism
Mus musculus (Mouse)
Status
Functioni
A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a preference for 7-alpha position. Usually metabolizes steroids carrying a hydroxy group at position 3, functioning as a 3-hydroxy steroid 7-alpha hydroxylase (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Hydroxylates oxysterols, including 25-hydroxycholesterol and (25R)-cholest-5-ene-3beta,26-diol toward 7-alpha hydroxy derivatives, which may be transported to the liver and converted to bile acids (PubMed:9295351, PubMed:9144166, PubMed:10748047, PubMed:11067870). Via its product 7-alpha,25-dihydroxycholesterol, a ligand for the chemotactic G protein-coupled receptor GPR183/EBI2, regulates B cell migration in germinal centers of lymphoid organs, thus guiding efficient maturation of plasma B cells and overall antigen-specific humoral immune response (PubMed:22999953). 7-alpha hydroxylates neurosteroids, including 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) and pregnenolone, both involved in hippocampus-associated memory and learning (PubMed:9144166). Metabolizes androstanoids toward 6- or 7-alpha hydroxy derivatives (By similarity).By similarity5 Publications
Catalytic activityi
- 25-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = 7α,25-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]4 PublicationsEC:1.14.14.294 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (25R)-cholest-5-ene-3β,26-diol + O2 + reduced [NADPH—hemoprotein reductase] = (25R)-cholest-5-en-3β,7α,26-triol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]3 PublicationsEC:1.14.14.293 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (24S)-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (24S)-7α-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationEC:1.14.14.261 PublicationThis reaction proceeds in the forward1 Publication direction.
- (24S)-25-epoxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (24S,25)-epoxy-7α-hydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 22R-hydroxycholesterol + O2 + reduced [NADPH—hemoprotein reductase] = (22R,7α)-dihydroxycholesterol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- androst-5-en-3β,17β-diol + O2 + reduced [NADPH—hemoprotein reductase] = androst-5-en-3β,7α,17β-triol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardBy similarity direction.
- 5α-androstane-3β,17β-diol + O2 + reduced [NADPH—hemoprotein reductase] = 5α-androstane-3β,6α,17β-triol + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardBy similarity direction.
- 3β-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH—hemoprotein reductase] = 3β,7α-dihydroxyandrost-5-en-17-one + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 3β-hydroxy-5α-androstan-17-one + O2 + reduced [NADPH—hemoprotein reductase] = 3β,7α-dihydroxy-5α-androstan-17-one + H+ + H2O + oxidized [NADPH—hemoprotein reductase]By similarityThis reaction proceeds in the forwardBy similarity direction.
- O2 + pregnenolone + reduced [NADPH—hemoprotein reductase] = 7α-hydroxypregnenolone + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
hemeBy similarity
Activity regulationi
Inhibited by drugs voriconazole and metyrapone.By similarity
Kineticsi
- KM=13.6 µM for 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone)1 Publication
- KM=4 µM for pregnenolone1 Publication
: bile acid biosynthesis Pathwayi
This protein is involved in the pathway bile acid biosynthesis, which is part of Lipid metabolism.4 PublicationsView all proteins of this organism that are known to be involved in the pathway bile acid biosynthesis and in Lipid metabolism.
Pathwayi: Steroid hormone biosynthesis
This protein is involved in Steroid hormone biosynthesis.1 PublicationView all proteins of this organism that are known to be involved in Steroid hormone biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 447 | Iron (heme axial ligand)By similarity | 1 |
GO - Molecular functioni
- 25-hydroxycholesterol 7alpha-hydroxylase activity Source: UniProtKB-EC
- 27-hydroxycholesterol 7-alpha-monooxygenase activity Source: UniProtKB-EC
- heme binding Source: InterPro
- iron ion binding Source: InterPro
- oxysterol 7-alpha-hydroxylase activity Source: UniProtKB
- steroid hydroxylase activity Source: GO_Central
GO - Biological processi
- B cell chemotaxis Source: UniProtKB
- bile acid biosynthetic process Source: UniProtKB
- cholesterol homeostasis Source: GO_Central
- cholesterol metabolic process Source: UniProtKB-KW
- circadian rhythm Source: MGI
- digestion Source: UniProtKB
- memory Source: MGI
- negative regulation of intracellular estrogen receptor signaling pathway Source: MGI
- positive regulation of epithelial cell proliferation Source: MGI
- prostate gland epithelium morphogenesis Source: MGI
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
BRENDAi | 1.14.13.100, 3474 |
Reactomei | R-MMU-192105, Synthesis of bile acids and bile salts R-MMU-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-MMU-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-MMU-211976, Endogenous sterols |
UniPathwayi | UPA00221 |
Chemistry databases
SwissLipidsi | SLP:000001208 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome P450 7B1Alternative name(s): 24-hydroxycholesterol 7-alpha-hydroxylase1 Publication (EC:1.14.14.261 Publication) 25/26-hydroxycholesterol 7-alpha-hydroxylase1 Publication (EC:1.14.14.291 Publication) 3-hydroxysteroid 7-alpha hydroxylase Hippocampal transcript 1 protein1 Publication Short name: HCT-11 Publication Oxysterol 7-alpha-hydroxylase1 Publication |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104978, Cyp7b1 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Curated
- Microsome membrane By similarity; Multi-pass membrane protein Curated
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Other locations
- integral component of membrane Source: UniProtKB-KW
- intracellular membrane-bounded organelle Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 14 – 34 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 178 – 198 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 287 – 307 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, MicrosomePathology & Biotechi
Disruption phenotypei
Knockout mice exhibit impaired generation of plasma cells and overall deficient antigen-specific humoral immune response.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000051907 | 1 – 507 | Cytochrome P450 7B1Add BLAST | 507 |
Proteomic databases
jPOSTi | Q60991 |
MaxQBi | Q60991 |
PaxDbi | Q60991 |
PeptideAtlasi | Q60991 |
PRIDEi | Q60991 |
PTM databases
iPTMneti | Q60991 |
PhosphoSitePlusi | Q60991 |
SwissPalmi | Q60991 |
Expressioni
Tissue specificityi
Highly expressed in brain structures including the corpus callosum, the anterior commissure and fornix (PubMed:8530364). The hippocampal expression is particularly prominent in the dentate gyrus (PubMed:8530364). Expressed in liver and kidney. The hepatic expression is sexually dimorphic, predominantly detected in male liver while barely detectable in females (PubMed:8530364). Expressed in lymph nodes and spleens, in both lymphoid and stromal compartments (PubMed:22999953). Higher expression is detected in fibroblastic reticular cells, a type of stromal cells in the lymph nodes (PubMed:22999953). Also expressed at high levels in the outer follicle and at the B cell-T cell boundary of splenic germinal centers (PubMed:22999953). Expressed in dendritic cells (DCs) subpopulations being most abundant in CD8-positive DCs (PubMed:22999953).2 Publications
Gene expression databases
Bgeei | ENSMUSG00000039519, Expressed in liver and 269 other tissues |
Genevisiblei | Q60991, MM |
Interactioni
Protein-protein interaction databases
BioGRIDi | 199039, 1 interactor |
STRINGi | 10090.ENSMUSP00000037487 |
Miscellaneous databases
RNActi | Q60991, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00940000153141 |
HOGENOMi | CLU_018012_1_2_1 |
InParanoidi | Q60991 |
OMAi | LKYFLMP |
OrthoDBi | 614788at2759 |
TreeFami | TF105090 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR024204, Cyt_P450_CYP7A1-type IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PIRSFi | PIRSF000047, Cytochrome_CYPVIIA1, 1 hit |
PRINTSi | PR00465, EP450IV |
SUPFAMi | SSF48264, SSF48264, 1 hit |
i Sequence
Sequence statusi: Complete.
Q60991-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MQGATTLDAA SPGPLALLGL LFAATLLLSA LFLLTRRTRR PREPPLIKGW
60 70 80 90 100
LPYLGMALKF FKDPLTFLKT LQRQHGDTFT VFLVGKYITF VLNPFQYQYV
110 120 130 140 150
TKNPKQLSFQ KFSSRLSAKA FSVKKLLTDD DLNEDVHRAY LLLQGKPLDA
160 170 180 190 200
LLETMIQEVK ELFESQLLKI TDWNTERIFA FCGSLVFEIT FATLYGKILA
210 220 230 240 250
GNKKQIISEL RDDFFKFDDM FPYLVSDIPI QLLRNEESMQ KKIIKCLTSE
260 270 280 290 300
KVAQMQGQSK IVQERQDLLK RYYRHDDPEI GAHHLGFLWA SLANTIPAMF
310 320 330 340 350
WAMYYILRHP EAMEALRDEI DSFLQSTGQK KGPGISVHFT REQLDSLVCL
360 370 380 390 400
ESTILEVLRL CSYSSIIREV QEDMNLSLES KSFSLRKGDF VALFPPLIHN
410 420 430 440 450
DPEIFDAPKE FRFDRFIEDG KKKSTFFKGG KKLKTYVMPF GLGTSKCPGR
460 470 480 490 500
YFAVNEMKLL LIMLLTYFDL EIIDRKPIGL NHSRMFLGIQ HPDSAVSFRY
KAKSWRS
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 265 | R → S in AAA92615 (PubMed:8530364).Curated | 1 | |
Sequence conflicti | 278 | P → S in AAA92615 (PubMed:8530364).Curated | 1 | |
Sequence conflicti | 432 | K → R in AAA92615 (PubMed:8530364).Curated | 1 | |
Sequence conflicti | 463 | M → E in AAA92615 (PubMed:8530364).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U36993 mRNA Translation: AAA92615.1 AK013034 mRNA Translation: BAB28613.1 |
CCDSi | CCDS17254.1 |
RefSeqi | NP_031851.3, NM_007825.4 XP_006535446.1, XM_006535383.3 |
Genome annotation databases
Ensembli | ENSMUST00000035625; ENSMUSP00000037487; ENSMUSG00000039519 |
GeneIDi | 13123 |
KEGGi | mmu:13123 |
UCSCi | uc008orm.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U36993 mRNA Translation: AAA92615.1 AK013034 mRNA Translation: BAB28613.1 |
CCDSi | CCDS17254.1 |
RefSeqi | NP_031851.3, NM_007825.4 XP_006535446.1, XM_006535383.3 |
3D structure databases
SMRi | Q60991 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 199039, 1 interactor |
STRINGi | 10090.ENSMUSP00000037487 |
Chemistry databases
SwissLipidsi | SLP:000001208 |
PTM databases
iPTMneti | Q60991 |
PhosphoSitePlusi | Q60991 |
SwissPalmi | Q60991 |
Proteomic databases
jPOSTi | Q60991 |
MaxQBi | Q60991 |
PaxDbi | Q60991 |
PeptideAtlasi | Q60991 |
PRIDEi | Q60991 |
Protocols and materials databases
Antibodypediai | 3058, 285 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000035625; ENSMUSP00000037487; ENSMUSG00000039519 |
GeneIDi | 13123 |
KEGGi | mmu:13123 |
UCSCi | uc008orm.2, mouse |
Organism-specific databases
CTDi | 9420 |
MGIi | MGI:104978, Cyp7b1 |
Phylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00940000153141 |
HOGENOMi | CLU_018012_1_2_1 |
InParanoidi | Q60991 |
OMAi | LKYFLMP |
OrthoDBi | 614788at2759 |
TreeFami | TF105090 |
Enzyme and pathway databases
UniPathwayi | UPA00221 |
BRENDAi | 1.14.13.100, 3474 |
Reactomei | R-MMU-192105, Synthesis of bile acids and bile salts R-MMU-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-MMU-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-MMU-211976, Endogenous sterols |
Miscellaneous databases
BioGRID-ORCSi | 13123, 2 hits in 17 CRISPR screens |
ChiTaRSi | Cyp7b1, mouse |
PROi | PR:Q60991 |
RNActi | Q60991, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000039519, Expressed in liver and 269 other tissues |
Genevisiblei | Q60991, MM |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR024204, Cyt_P450_CYP7A1-type IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PIRSFi | PIRSF000047, Cytochrome_CYPVIIA1, 1 hit |
PRINTSi | PR00465, EP450IV |
SUPFAMi | SSF48264, SSF48264, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CP7B1_MOUSE | |
Accessioni | Q60991Primary (citable) accession number: Q60991 Secondary accession number(s): Q9CZ39 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 15, 1999 |
Last sequence update: | July 27, 2011 | |
Last modified: | December 2, 2020 | |
This is version 154 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families