ID   CP19A_BOVIN             Reviewed;         503 AA.
AC   P46194; Q29445; Q29453;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   29-AUG-2001, sequence version 3.
DT   08-NOV-2023, entry version 131.
DE   RecName: Full=Aromatase {ECO:0000303|PubMed:8404644};
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=CYP19;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Ovary;
RX   PubMed=8404644; DOI=10.1210/endo.133.5.8404644;
RA   Hinshelwood M.M., Corbin C.J., Tsang P.C., Simpson E.R.;
RT   "Isolation and characterization of a complementary deoxyribonucleic acid
RT   insert encoding bovine aromatase cytochrome P450.";
RL   Endocrinology 133:1971-1977(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Placenta;
RX   PubMed=7890178; DOI=10.1016/0378-1119(94)00753-f;
RA   Vanselow J., Furbass R.;
RT   "Novel aromatase transcripts from bovine placenta contain repeated sequence
RT   motifs.";
RL   Gene 154:281-286(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9202222; DOI=10.1210/endo.138.7.5257;
RA   Furbass R., Kalbe C., Vanselow J.;
RT   "Tissue-specific expression of the bovine aromatase-encoding gene uses
RT   multiple transcriptional start sites and alternative first exons.";
RL   Endocrinology 138:2813-2819(1997).
RN   [4]
RP   SEQUENCE REVISION TO 443.
RA   Furbass R.;
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
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}; Multi-pass membrane protein
CC       {ECO:0000305}. Microsome membrane {ECO:0000250|UniProtKB:P11511};
CC       Multi-pass membrane protein {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR   EMBL; U18447; AAA62244.1; -; mRNA.
DR   EMBL; Z32741; CAA83651.1; -; mRNA.
DR   EMBL; Z69242; CAC12940.1; -; Genomic_DNA.
DR   EMBL; Z69243; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69244; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69245; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69246; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69247; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69248; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69249; CAC12940.1; JOINED; Genomic_DNA.
DR   EMBL; Z69250; CAC12940.1; JOINED; Genomic_DNA.
DR   PIR; I46015; I46015.
DR   RefSeq; NP_776730.1; NM_174305.1.
DR   AlphaFoldDB; P46194; -.
DR   SMR; P46194; -.
DR   STRING; 9913.ENSBTAP00000019823; -.
DR   PaxDb; 9913-ENSBTAP00000019823; -.
DR   GeneID; 281740; -.
DR   KEGG; bta:281740; -.
DR   CTD; 1588; -.
DR   eggNOG; KOG0157; Eukaryota.
DR   InParanoid; P46194; -.
DR   OrthoDB; 5385594at2759; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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:0008585; P:female gonad development; IBA:GO_Central.
DR   GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0032355; P:response to estradiol; IBA:GO_Central.
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.
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_0000051950"
FT   TRANSMEM        19..39
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        53..73
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"
FT   CONFLICT        216
FT                   /note="K -> N (in Ref. 1; AAA62244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        260
FT                   /note="E -> A (in Ref. 1; AAA62244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        436
FT                   /note="A -> G (in Ref. 1; AAA62244)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        443
FT                   /note="T -> A (in Ref. 1; AAA62244)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   503 AA;  58090 MW;  47C70292D21AFF97 CRC64;
     MLLEVLNPRH YNVTSMVSEV VPIASIAILL LTGFLLLVWN YEDTSSIPGP SYFLGIGPLI
     SHCRFLWMGI GSACNYYNKM YGEFMRVWVC GEETLIISKS SSMFHVMKHS HYISRFGSKL
     GLQFIGMHEK GIIFNNNPAL WKAVRPFFTK ALSGPGLVRM VTICADSITK HLDRLEEVCN
     DLGYVDVLTL MRRIMLDTSN MLFLGIPLDE SAIVVKIQGY FDAWQALLLK PDIFFKISWL
     CRKYEKSVKD LKDAMEILIE EKRHRISTAE KLEDSIDFAT ELIFAEKRGE LTRENVNQCI
     LEMLIAAPDT MSVSVFFMLF LIAKHPQVEE AIIREIQTVV GERDIRIDDM QKLKVVENFI
     NESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNLGR MHRLEFFPKP NEFTLENFAK
     NVPYRYFQPF GFGPRACAGK YITMVMMKVV LVTLLRRFHV QTLQGRCVEK MQKKNDLSLH
     PDETRDRLEM IFTPRNSDKC LER
//