CP19A_MOUSE
ID CP19A_MOUSE Reviewed; 503 AA.
AC P28649;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Aromatase {ECO:0000303|PubMed:1897929};
DE EC=1.14.14.14 {ECO:0000250|UniProtKB:P11511};
DE AltName: Full=CYPXIX;
DE AltName: Full=Cytochrome P-450AROM;
DE AltName: Full=Cytochrome P450 19A1;
DE AltName: Full=Estrogen synthase;
GN Name=Cyp19a1; Synonyms=Arom, Cyp19;
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].
RC TISSUE=Ovary;
RX PubMed=1897929; DOI=10.1016/0003-9861(91)90354-l;
RA Terashima M., Toda K., Kawamoto T., Kuribayashi I., Ogawa Y., Maeda T.,
RA Shizuta Y.;
RT "Isolation of a full-length cDNA encoding mouse aromatase P450.";
RL Arch. Biochem. Biophys. 285:231-237(1991).
CC -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the conversion
CC of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and
CC testosterone to the C18 estrogens, estrone and estradiol, respectively.
CC Catalyzes three successive oxidations of C19 androgens: two
CC conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-
CC aldehyde derivatives, followed by a third oxidative aromatization step
CC that involves C1-beta hydrogen abstraction combined with cleavage of
CC the C10-C19 bond to yield a phenolic A ring and formic acid.
CC Alternatively, the third oxidative reaction yields a 19-norsteroid and
CC formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-
CC nordihydrotestosterone and may play a role in homeostasis of this
CC potent androgen. Also displays 2-hydroxylase activity toward estrone.
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). {ECO:0000250|UniProtKB:P11511}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 O2 + 3 reduced [NADPH--hemoprotein reductase] + testosterone
CC = 17beta-estradiol + formate + 4 H(+) + 4 H2O + 3 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:38191, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, ChEBI:CHEBI:16469,
CC ChEBI:CHEBI:17347, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.14; Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38192;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,17-dione + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = estrone + formate + 4 H(+) + 4 H2O + 3
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38195,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:16422, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.14;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38196;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-4-ene-3,17-dione + O2 + reduced [NADPH--hemoprotein
CC reductase] = 19-hydroxyandrost-4-ene-3,17-dione + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38199,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16422,
CC ChEBI:CHEBI:27576, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38200;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=19-hydroxyandrost-4-ene-3,17-dione + O2 + reduced [NADPH--
CC hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + H(+) + 2
CC H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38203,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:799,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:27576, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38204;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=19-oxo-androst-4-ene-3,17-dione + O2 + reduced [NADPH--
CC hemoprotein reductase] = estrone + formate + 2 H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38207, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:799, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38208;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-
CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-5alpha-androstan-3-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 17beta,19-dihydroxy-3-oxo-5alpha-
CC androstanone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:53200, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16330, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:137031; Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53201;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta,19-dihydroxy-3-oxo-5alpha-androstanone + O2 + reduced
CC [NADPH--hemoprotein reductase] = 17beta-hydroxy-3,19-dioxo-5alpha-
CC androstanone + H(+) + 2 H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53204, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:137031,
CC ChEBI:CHEBI:137032; Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53205;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=17beta-hydroxy-3,19-dioxo-5alpha-androstanone + O2 + reduced
CC [NADPH--hemoprotein reductase] = 17beta-hydroxy-3-oxo-19-nor-5alpha-
CC androst-1-ene + formate + 2 H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53276, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:137032, ChEBI:CHEBI:137110;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53277;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P11511};
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000250|UniProtKB:P11511}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P11511}; Single-pass membrane protein
CC {ECO:0000305}. Microsome membrane {ECO:0000250|UniProtKB:P11511};
CC Single-pass membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; D00659; BAA00551.1; -; mRNA.
DR CCDS; CCDS23187.1; -.
DR PIR; S13912; S13912.
DR RefSeq; NP_001335100.1; NM_001348171.1.
DR RefSeq; NP_001335101.1; NM_001348172.1.
DR RefSeq; NP_001335102.1; NM_001348173.1.
DR RefSeq; NP_031836.1; NM_007810.4.
DR AlphaFoldDB; P28649; -.
DR SMR; P28649; -.
DR BioGRID; 199000; 1.
DR IntAct; P28649; 1.
DR STRING; 10090.ENSMUSP00000034811; -.
DR iPTMnet; P28649; -.
DR PhosphoSitePlus; P28649; -.
DR PaxDb; P28649; -.
DR PRIDE; P28649; -.
DR ProteomicsDB; 285256; -.
DR Antibodypedia; 4371; 674 antibodies from 41 providers.
DR Ensembl; ENSMUST00000034811; ENSMUSP00000034811; ENSMUSG00000032274.
DR GeneID; 13075; -.
DR KEGG; mmu:13075; -.
DR UCSC; uc009pmu.1; mouse.
DR CTD; 1588; -.
DR MGI; MGI:88587; Cyp19a1.
DR VEuPathDB; HostDB:ENSMUSG00000032274; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00840000129915; -.
DR HOGENOM; CLU_041874_0_0_1; -.
DR InParanoid; P28649; -.
DR OMA; VRPFFMK; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; P28649; -.
DR TreeFam; TF352039; -.
DR BRENDA; 1.14.14.14; 3474.
DR Reactome; R-MMU-193144; Estrogen biosynthesis.
DR Reactome; R-MMU-211976; Endogenous sterols.
DR BioGRID-ORCS; 13075; 1 hit in 76 CRISPR screens.
DR PRO; PR:P28649; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P28649; protein.
DR Bgee; ENSMUSG00000032274; Expressed in spermatocyte and 31 other tissues.
DR ExpressionAtlas; P28649; baseline and differential.
DR Genevisible; P28649; MM.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0008021; C:synaptic vesicle; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0070330; F:aromatase activity; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IDA:MGI.
DR GO; GO:0006710; P:androgen catabolic process; ISO:MGI.
DR GO; GO:0008209; P:androgen metabolic process; IMP:MGI.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; ISO:MGI.
DR GO; GO:0097720; P:calcineurin-mediated signaling; ISO:MGI.
DR GO; GO:0006703; P:estrogen biosynthetic process; ISO:MGI.
DR GO; GO:0030540; P:female genitalia development; IMP:MGI.
DR GO; GO:0008585; P:female gonad development; IMP:MGI.
DR GO; GO:0030879; P:mammary gland development; IMP:MGI.
DR GO; GO:0045779; P:negative regulation of bone resorption; ISO:MGI.
DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; IMP:MGI.
DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; IMP:MGI.
DR GO; GO:2000866; P:positive regulation of estradiol secretion; ISO:MGI.
DR GO; GO:0060736; P:prostate gland growth; IMP:MGI.
DR GO; GO:0050803; P:regulation of synapse structure or activity; ISO:MGI.
DR GO; GO:0032355; P:response to estradiol; IBA:GO_Central.
DR GO; GO:0061370; P:testosterone biosynthetic process; IMP:MGI.
DR GO; GO:0060065; P:uterus development; IMP:MGI.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..503
FT /note="Aromatase"
FT /id="PRO_0000051957"
FT TRANSMEM 21..41
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 309
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 374
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 437
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"
SQ SEQUENCE 503 AA; 58015 MW; 737400389D1AEFF1 CRC64;
MFLEMLNPMQ YNVTIMVPET VTVSAMPLLL IMGLLLLIWN CESSSSIPGP GYCLGIGPLI
SHGRFLWMGI GSACNYYNKM YGEFMRVWIS GEETLIISKS SSMFHVMKHS HYISRFGSKR
GLQCIGMHEN GIIFNNNPSL WRTIRPFFMK ALTGPGLVRM VEVCVESIKQ HLDRLGEVTD
TSGYVDVLTL MRHIMLDTSN MLFLGIPLDE SAIVKKIQGY FNAWQALLIK PNIFFKISWL
YRKYERSVKD LKDEIAVLVE KKRHKVSTAE KLEDCMDFAT DLIFAERRGD LTKENVNQCI
LEMLIAAPDT MSVTLYFMLL LVAEYPEVEA AILKEIHTVV GDRDIKIEDI QNLKVVENFI
NESMRYQPVV DLVMRRALED DVIDGYPVKK GTNIILNIGR MHRLEYFPKP NEFTLENFEK
NVPYRYFQPF GFGPRGCAGK YIAMVMMKVV LVTLLRRFQV KTLQKRCIEN IPKKNDLSLH
PNEDRHLVEI IFSPRNSDKY LQQ
