CP39A_MOUSE
ID CP39A_MOUSE Reviewed; 470 AA.
AC Q9JKJ9;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=24-hydroxycholesterol 7-alpha-hydroxylase;
DE EC=1.14.14.26 {ECO:0000269|PubMed:10748047};
DE AltName: Full=Cytochrome P450 39A1;
DE Short=mCYP39A1;
DE AltName: Full=Oxysterol 7-alpha-hydroxylase;
GN Name=Cyp39a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=10748047; DOI=10.1074/jbc.m001810200;
RA Li-Hawkins J., Lund E.G., Bronson A.D., Russell D.W.;
RT "Expression cloning of an oxysterol 7alpha-hydroxylase selective for 24-
RT hydroxycholesterol.";
RL J. Biol. Chem. 275:16543-16549(2000).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in neural
CC cholesterol clearance through bile acid synthesis. Catalyzes 7-alpha
CC hydroxylation of (24S)-hydroxycholesterol, a neural oxysterol that is
CC metabolized to bile acids in the liver (PubMed:10748047).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-
CC ferrihemoprotein reductase) (PubMed:10748047).
CC {ECO:0000269|PubMed:10748047}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (24S)-7alpha-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46124,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:37640, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.26; Evidence={ECO:0000269|PubMed:10748047};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q16850};
CC -!- PATHWAY: Steroid metabolism; cholesterol degradation.
CC {ECO:0000250|UniProtKB:Q9NYL5}.
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:Q9NYL5}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q64654}; Multi-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q64654};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver specific. Hepatic expression is sexually
CC dimorphic (female > male).
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF237981; AAF63328.1; -; mRNA.
DR CCDS; CCDS28799.1; -.
DR RefSeq; NP_061375.1; NM_018887.4.
DR AlphaFoldDB; Q9JKJ9; -.
DR SMR; Q9JKJ9; -.
DR STRING; 10090.ENSMUSP00000130073; -.
DR SwissLipids; SLP:000001228; -.
DR iPTMnet; Q9JKJ9; -.
DR PhosphoSitePlus; Q9JKJ9; -.
DR SwissPalm; Q9JKJ9; -.
DR jPOST; Q9JKJ9; -.
DR MaxQB; Q9JKJ9; -.
DR PaxDb; Q9JKJ9; -.
DR PRIDE; Q9JKJ9; -.
DR ProteomicsDB; 283619; -.
DR Antibodypedia; 30714; 253 antibodies from 28 providers.
DR DNASU; 56050; -.
DR Ensembl; ENSMUST00000170988; ENSMUSP00000130073; ENSMUSG00000023963.
DR GeneID; 56050; -.
DR KEGG; mmu:56050; -.
DR UCSC; uc008cpn.2; mouse.
DR CTD; 51302; -.
DR MGI; MGI:1927096; Cyp39a1.
DR VEuPathDB; HostDB:ENSMUSG00000023963; -.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153141; -.
DR HOGENOM; CLU_558065_0_0_1; -.
DR InParanoid; Q9JKJ9; -.
DR OMA; RPPCIKG; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; Q9JKJ9; -.
DR TreeFam; TF105090; -.
DR BRENDA; 1.14.14.26; 3474.
DR Reactome; R-MMU-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR UniPathway; UPA00221; -.
DR UniPathway; UPA01058; -.
DR BioGRID-ORCS; 56050; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Cyp39a1; mouse.
DR PRO; PR:Q9JKJ9; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9JKJ9; protein.
DR Bgee; ENSMUSG00000023963; Expressed in sciatic nerve and 195 other tissues.
DR ExpressionAtlas; Q9JKJ9; baseline and differential.
DR Genevisible; Q9JKJ9; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:UniProtKB.
DR GO; GO:0033782; F:24-hydroxycholesterol 7alpha-hydroxylase 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; IDA:UniProtKB.
DR GO; GO:0008387; F:steroid 7-alpha-hydroxylase activity; IDA:MGI.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0006699; P:bile acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030573; P:bile acid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006707; P:cholesterol catabolic process; IDA:MGI.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0007586; P:digestion; TAS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR024204; Cyt_P450_CYP7A1-type.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Bile acid catabolism; Endoplasmic reticulum; Heme; Iron; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase;
KW Oxidoreductase; Reference proteome; Steroid metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..470
FT /note="24-hydroxycholesterol 7-alpha-hydroxylase"
FT /id="PRO_0000051993"
FT TRANSMEM 3..23
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 415
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|UniProtKB:Q16850"
SQ SEQUENCE 470 AA; 53575 MW; 9F08D3D936C26270 CRC64;
MGIMELFSPI AIAVLGSCVL FLFSRLKNLL GPPCIQGWIP WIGAGLEFGK APLEFIEKAR
IKYGPVFTIF AMGNRMTFVS EEEGINVLLK SEHVDFESAV QSPVYHTAWI PKNVFSALHE
RLYALMKGKM GTFNTHHFTG PLTEELHEQL EGLGTHGTMD LNDFVRYLLY PATLNTLFKK
GLFLTDKRTI KEFYQQFKTY DEGFEYGSQL PEWLLRNWSK SKRWLLALFE KNIGNIKAHG
SAGHSGTLLQ AILEVVETET RQYSPNYGLV VLWAALANAP PIAFWTLGYI LSHPDIHRTV
LESISSVFGT AGKDKIKVSE DDLKKLLIIK WCILESVRLR APGVITRKVV KPVKILNHTV
PSGDLLMLSP FWLHRNPKYF PEPESFKPER WKEANLDKYI FLDYFMAFGG GKFQCPGRWF
ALLEIQLCII LVLYKYECSL LDPLPKQSSR HLVGVPQPAG KCRIEYKQRA
