ID CP19A_RAT Reviewed; 508 AA. AC P22443; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1991, sequence version 1. DT 02-SEP-2026, entry version 150. DE RecName: Full=Aromatase; 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 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=Ovary; RX PubMed=2157976; DOI=10.1210/mend-4-1-3; RA Hickey G.J., Krasnow J.S., Beattie W.G., Richards J.S.; RT "Aromatase cytochrome P450 in rat ovarian granulosa cells before and after RT luteinization: adenosine 3',5'-monophosphate-dependent and independent RT regulation. Cloning and sequencing of rat aromatase cDNA and 5' genomic RT DNA."; RL Mol. Endocrinol. 4:3-12(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2340950; DOI=10.1016/0303-7207(90)90056-e; RA Lephart E.D., Peterson K.G., Noble J.F., George F.W., McPhaul M.J.; RT "The structure of cDNA clones encoding the aromatase P-450 isolated from a RT rat Leydig cell tumor line demonstrates differential processing of RT aromatase mRNA in rat ovary and a neoplastic cell line."; RL Mol. Cell. Endocrinol. 70:31-40(1990). CC -!- FUNCTION: Catalyzes the formation of aromatic C18 estrogens from C19 CC androgens. CC -!- CATALYTIC ACTIVITY: CC Reaction=testosterone + 3 reduced [NADPH--hemoprotein reductase] + 3 O2 CC = 17beta-estradiol + formate + 3 oxidized [NADPH--hemoprotein CC reductase] + 4 H2O + 4 H(+); 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 -!- CATALYTIC ACTIVITY: CC Reaction=androst-4-ene-3,17-dione + 3 reduced [NADPH--hemoprotein CC reductase] + 3 O2 = estrone + formate + 3 oxidized CC [NADPH--hemoprotein reductase] + 4 H2O + 4 H(+); CC Xref=Rhea:RHEA:38195, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16422, ChEBI:CHEBI:17263, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.14; CC Evidence={ECO:0000250|UniProtKB:P11511}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250}; CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein. 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; M33986; AAA41044.1; -; mRNA. DR PIR; A36121; A36121. DR AlphaFoldDB; P22443; -. DR SMR; P22443; -. DR FunCoup; P22443; 15. DR STRING; 10116.ENSRNOP00000000212; -. DR BindingDB; P22443; -. DR ChEMBL; CHEMBL3859; -. DR DrugCentral; P22443; -. DR PhosphoSitePlus; P22443; -. DR PaxDb; 10116-ENSRNOP00000000212; -. DR AGR; RGD:2457; -. DR RGD; 2457; Cyp19a1. DR eggNOG; KOG0157; Eukaryota. DR InParanoid; P22443; -. DR PhylomeDB; P22443; -. DR Reactome; R-RNO-193144; Estrogen biosynthesis. DR Reactome; R-RNO-211976; Endogenous sterols. DR PRO; PR:P22443; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0043679; C:axon terminus; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD. DR GO; GO:0043195; C:terminal bouton; IDA:RGD. DR GO; GO:0070330; F:aromatase activity; IDA:RGD. DR GO; GO:0101021; F:estrogen 2-hydroxylase activity; ISO:RGD. DR GO; GO:0020037; F:heme binding; ISO:RGD. 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:RGD. DR GO; GO:0008395; F:steroid hydroxylase activity; ISO:RGD. DR GO; GO:0030325; P:adrenal gland development; IEP:RGD. DR GO; GO:0006710; P:androgen catabolic process; ISO:RGD. DR GO; GO:0008209; P:androgen metabolic process; IMP:RGD. DR GO; GO:0008206; P:bile acid metabolic process; IEP:RGD. DR GO; GO:0060348; P:bone development; IEP:RGD. DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:RGD. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD. DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD. DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD. DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD. DR GO; GO:0071464; P:cellular response to hydrostatic pressure; IEP:RGD. DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:RGD. DR GO; GO:0030540; P:female genitalia development; ISO:RGD. DR GO; GO:0008585; P:female gonad development; ISO:RGD. DR GO; GO:0030851; P:granulocyte differentiation; IEP:RGD. DR GO; GO:0021766; P:hippocampus development; IEP:RGD. DR GO; GO:0021854; P:hypothalamus development; IEP:RGD. DR GO; GO:0001553; P:luteinization; IEP:RGD. DR GO; GO:0008584; P:male gonad development; IEP:RGD. DR GO; GO:0030879; P:mammary gland development; ISO:RGD. DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:RGD. DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; ISO:RGD. DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; ISO:RGD. DR GO; GO:0018963; P:phthalate metabolic process; IEP:RGD. DR GO; GO:2000866; P:positive regulation of estradiol secretion; ISO:RGD. DR GO; GO:0060736; P:prostate gland growth; ISO:RGD. DR GO; GO:0050803; P:regulation of synapse structure or activity; IMP:RGD. DR GO; GO:1904612; P:response to 2,3,7,8-tetrachlorodibenzodioxine; IEP:RGD. DR GO; GO:0010164; P:response to cesium ion; IEP:RGD. DR GO; GO:0032355; P:response to estradiol; IEP:RGD. DR GO; GO:0043627; P:response to estrogen; IEP:RGD. DR GO; GO:0009635; P:response to herbicide; IEP:RGD. DR GO; GO:0010212; P:response to ionizing radiation; IEP:RGD. DR GO; GO:0010038; P:response to metal ion; IEP:RGD. DR GO; GO:0033574; P:response to testosterone; IEP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0061370; P:testosterone biosynthetic process; ISO:RGD. DR GO; GO:0060065; P:uterus development; ISO:RGD. DR CDD; cd20616; CYP19A1; 1. DR FunFam; 1.10.630.10:FF:000032; Cytochrome P450 aromatase; 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 InterPro; IPR050196; Cytochrome_P450_Monoox. 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. PE 2: Evidence at transcript level; KW Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Monooxygenase; KW Oxidoreductase; Reference proteome. FT CHAIN 1..508 FT /note="Aromatase" FT /id="PRO_0000051962" 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 CONFLICT 3..4 FT /note="LE -> FQ (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 10 FT /note="H -> Q (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 88 FT /note="W -> C (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 101 FT /note="S -> L (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 123..129 FT /note="QCIGMHE -> VVHGHAR (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 188 FT /note="V -> L (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 210 FT /note="E -> G (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 328..331 FT /note="VETA -> WKQ (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 342 FT /note="D -> A (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 364..369 FT /note="LRYQPV -> CGISPF (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 422 FT /note="V -> L (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 425 FT /note="R -> T (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 449 FT /note="V -> I (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 466 FT /note="R -> K (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 493..497 FT /note="RHIFN -> SPRNS (in Ref. 2; no nucleotide entry)" FT /evidence="ECO:0000305" SQ SEQUENCE 508 AA; 58412 MW; C0ADFB0FD80AB352 CRC64; MFLEMLNPMH YNVTIMVPET VPVSAMPLLL IMGLLLLIRN CESSSSIPGP GYCLGIGPLI SHGRFLWMGI GSACNYYNKM YGEFMRVWIS GEETLIISKS SSMVHVMKHS NYISRFGSKR GLQCIGMHEN GIIFNNNPSL WRTVRPFFMK ALTGPGLIRM VEVCVESIKQ HLDRLGDVTD NSGYVDVVTL MRHIMLDTSN TLFLGIPLDE SSIVKKIQGY FNAWQALLIK PNIFFKISWL YRKYERSVKD LKDEIEILVE KKRQKVSSAE KLEDCMDFAT DLIFAERRGD LTKENVNQCI LEMLIAAPDT MSVTLYVMLL LIAEYPEVET AILKEIHTVV GDRDIRIGDV QNLKVVENFI NESLRYQPVV DLVMRRALED DVIDGYPVKK GTNIILNIGR MHRLEYFPKP NEFTLENFEK NVPYRYFQPF GFGPRSCAGK YIAMVMMKVV LVTLLKRFHV KTLQKRCIEN MPKNNDLSLH LDEDSPIVEI IFRHIFNTPF LQCLYISL //