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 27-MAR-2024, entry version 165. 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38191, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:15740, CC ChEBI:CHEBI:16469, ChEBI:CHEBI:17347, 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:38192; CC Evidence={ECO:0000250|UniProtKB:P11511}; CC -!- CATALYTIC ACTIVITY: CC Reaction=androst-4-ene-3,17-dione + 3 O2 + 3 reduced CC [NADPH--hemoprotein reductase] = estrone + formate + 4 H(+) + 4 H2O + CC 3 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 CC [NADPH--hemoprotein reductase] = 19-oxo-androst-4-ene-3,17-dione + CC H(+) + 2 H2O + oxidized [NADPH--hemoprotein reductase]; CC Xref=Rhea:RHEA:38203, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, CC ChEBI:CHEBI:799, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:27576, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; 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 CC [NADPH--hemoprotein reductase] = estrone + formate + 2 H(+) + H2O + CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:38207, 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:15740, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; 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 CC [NADPH--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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10090-ENSMUSP00000034811; -. DR ProteomicsDB; 285256; -. DR Antibodypedia; 4371; 769 antibodies from 41 providers. DR Ensembl; ENSMUST00000034811.8; ENSMUSP00000034811.8; ENSMUSG00000032274.10. DR GeneID; 13075; -. DR KEGG; mmu:13075; -. DR UCSC; uc009pmu.1; mouse. DR AGR; MGI:88587; -. 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; PGLQCIG; -. DR OrthoDB; 5385594at2759; -. 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 81 CRISPR screens. DR PRO; PR:P28649; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; P28649; Protein. DR Bgee; ENSMUSG00000032274; Expressed in spermatocyte and 31 other cell types or tissues. DR ExpressionAtlas; P28649; baseline and differential. DR GO; GO:0043679; C:axon terminus; 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:0043025; C:neuronal cell body; 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 CDD; cd20616; CYP19A1; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24291:SF43; AROMATASE; 1. DR PANTHER; PTHR24291; CYTOCHROME P450 FAMILY 4; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P28649; MM. 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 //