CP7B1_RAT
ID CP7B1_RAT Reviewed; 414 AA.
AC Q63688;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=25-hydroxycholesterol 7-alpha-hydroxylase;
DE EC=1.14.14.29 {ECO:0000269|PubMed:12759897};
DE AltName: Full=Cytochrome P450 7B1;
DE AltName: Full=Hippocampal transcript 1 protein;
DE Short=HCT-1;
DE AltName: Full=Oxysterol 7-alpha-hydroxylase;
DE Flags: Fragment;
GN Name=Cyp7b1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hippocampus;
RX PubMed=8530364; DOI=10.1074/jbc.270.50.29739;
RA Stapleton G., Steel M., Richardson M., Mason J.O., Rose K.A., Morris R.G.,
RA Lathe R.;
RT "A novel cytochrome P450 expressed primarily in brain.";
RL J. Biol. Chem. 270:29739-29745(1995).
RN [2]
RP CATALYTIC ACTIVITY, AND CHARACTERIZATION.
RX PubMed=12759897; DOI=10.1053/meta.2003.50106;
RA Ren S., Marques D., Redford K., Hylemon P.B., Gil G., Vlahcevic Z.R.,
RA Pandak W.M.;
RT "Regulation of oxysterol 7alpha-hydroxylase (CYP7B1) in the rat.";
RL Metabolism 52:636-642(2003).
CC -!- FUNCTION: Oxysterol 7alpha-hydroxylase that mediates formation of 7-
CC alpha,25-dihydroxycholesterol (7-alpha,25-OHC) from 25-
CC hydroxycholesterol. Plays a key role in cell positioning and movement
CC in lymphoid tissues: 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC)
CC acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a
CC chemotactic receptor for a number of lymphoid cells.
CC {ECO:0000250|UniProtKB:Q60991}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=25-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 7alpha,25-dihydroxycholesterol + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:24308, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:37623,
CC ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.29; Evidence={ECO:0000269|PubMed:12759897};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-cholest-5-ene-3beta,26-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = (25R)-cholest-5-en-3beta,7alpha,26-triol +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:19041, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76591,
CC ChEBI:CHEBI:76592; EC=1.14.14.29;
CC Evidence={ECO:0000269|PubMed:12759897};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain; also expressed in liver
CC and kidney.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; U36992; AAA92616.1; -; mRNA.
DR RefSeq; NP_062011.1; NM_019138.1.
DR AlphaFoldDB; Q63688; -.
DR SMR; Q63688; -.
DR STRING; 10116.ENSRNOP00000013116; -.
DR PhosphoSitePlus; Q63688; -.
DR PaxDb; Q63688; -.
DR PRIDE; Q63688; -.
DR GeneID; 25429; -.
DR KEGG; rno:25429; -.
DR UCSC; RGD:2483; rat.
DR CTD; 9420; -.
DR RGD; 2483; Cyp7b1.
DR eggNOG; KOG0684; Eukaryota.
DR InParanoid; Q63688; -.
DR OrthoDB; 614788at2759; -.
DR PhylomeDB; Q63688; -.
DR Reactome; R-RNO-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-RNO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-RNO-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR UniPathway; UPA00221; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033783; F:25-hydroxycholesterol 7alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0047092; F:27-hydroxycholesterol 7-alpha-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0008396; F:oxysterol 7-alpha-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0035754; P:B cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; TAS:RGD.
DR GO; GO:0007623; P:circadian rhythm; IDA:RGD.
DR GO; GO:0007613; P:memory; IDA:RGD.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; ISO:RGD.
DR GO; GO:0051591; P:response to cAMP; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN <1..414
FT /note="25-hydroxycholesterol 7-alpha-hydroxylase"
FT /id="PRO_0000051908"
FT BINDING 354
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250"
FT NON_TER 1
SQ SEQUENCE 414 AA; 48227 MW; F2111BF6A1575BD2 CRC64;
ALEYQYVMKN PKQLSFEKFS RRLSAKAFSV KKLLTNDDLS NDIHRGYLLL QGKSLDGLLE
TMIQEVKEIF ESRLLKLTDW NTARVFDFCS SLVFEITFTT IYGKILAANK KQIISELRDD
FLKFDDHFPY LVSDIPIQLL RNAEFMQKKI IKCLTPEKVA QMQRRSEIVQ ERQEMLKKYY
GHEEFEIGAH HLGLLWASLA NTIPAMFWAM YYLLQHPEAM EVLRDEIDSF LQSTGQKKGP
GISVHFTREQ LDSLVCLESA ILEVLRLCSY SSIIREVQED MDFSSESRSY RLRKGDFVAV
FPPMIHNDPE VFDAPKDFRF DRFVEDGKKK TTFFKGGKKL KSYIIPFGLG TSKCPGRYFA
INEMKLLVII LLTYFDLEVI DTKPIGLNHS RMFLGIQHPD SDISFRYKAK SWRS
