ID   CP19A_HORSE             Reviewed;         503 AA.
AC   O46512; O46513;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1998, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Aromatase {ECO:0000303|PubMed:12591609};
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 17-alpha;
DE   AltName: Full=Cytochrome P450 19A1;
DE   AltName: Full=Estrogen synthase;
GN   Name=CYP19A1; Synonyms=CYP19;
OS   Equus caballus (Horse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX   NCBI_TaxID=9796;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (CLONE A1 AND CLONE A17).
RC   TISSUE=Follicular cell;
RX   PubMed=10465286; DOI=10.1210/endo.140.9.6951;
RA   Boerboom D., Kerban A., Sirois J.;
RT   "Dual regulation of promoter II- and promoter 1f-derived cytochrome P450
RT   aromatase transcripts in equine granulosa cells during human chorionic
RT   gonadotropin-induced ovulation: a novel model for the study of aromatase
RT   promoter switching.";
RL   Endocrinology 140:4133-4141(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Testis;
RX   PubMed=12591609; DOI=10.1016/s0167-4781(02)00621-8;
RA   Seralini G.E., Tomilin A., Auvray P., Nativelle-Serpentini C.,
RA   Sourdaine P., Moslemi S.;
RT   "Molecular characterization and expression of equine testicular cytochrome
RT   P450 aromatase.";
RL   Biochim. Biophys. Acta 1625:229-238(2003).
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   -!- TISSUE SPECIFICITY: Expressed in placenta. Highly expressed in
CC       follicles (0 hour:hCG), followed by a drop (12-24 hour:hCG) and by an
CC       increase (30-39 hour:hCG). Highly expressed in corpora lutea. Also
CC       expressed in granulosa cell layer. Not expressed in theca interna.
CC   -!- DOMAIN: Contains a I helix thought to serve as the substrate-binding
CC       pocket.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC   -!- CAUTION: Clone A1 form may be a splice variant or an artifact.
CC       {ECO:0000305}.
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DR   EMBL; AF031520; AAC04698.1; -; mRNA.
DR   EMBL; AF031521; AAC04699.1; -; mRNA.
DR   EMBL; AJ012610; CAB38442.1; -; mRNA.
DR   RefSeq; NP_001075274.1; NM_001081805.2.
DR   RefSeq; XP_005602644.1; XM_005602587.2.
DR   RefSeq; XP_005602645.1; XM_005602588.2.
DR   AlphaFoldDB; O46512; -.
DR   SMR; O46512; -.
DR   STRING; 9796.ENSECAP00000047527; -.
DR   PaxDb; 9796-ENSECAP00000047527; -.
DR   Ensembl; ENSECAT00000070733.2; ENSECAP00000048342.2; ENSECAG00000020474.4.
DR   GeneID; 100009712; -.
DR   KEGG; ecb:100009712; -.
DR   CTD; 1588; -.
DR   VGNC; VGNC:50557; CYP19A1.
DR   GeneTree; ENSGT00840000129915; -.
DR   HOGENOM; CLU_041874_0_0_1; -.
DR   InParanoid; O46512; -.
DR   OrthoDB; 5385594at2759; -.
DR   TreeFam; TF352039; -.
DR   Proteomes; UP000002281; Chromosome 1.
DR   Bgee; ENSECAG00000020474; Expressed in chorionic villus and 13 other cell types or tissues.
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_0000051954"
FT   TRANSMEM        19..39
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        51..71
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          294..324
FT                   /note="Substrate-binding pocket"
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        342..347
FT                   /note="ERDLKN -> RNLSNK (in Ref. 1; clone A1)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        348..503
FT                   /note="Missing (in Ref. 1; clone A1)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   503 AA;  57825 MW;  878E2CB040B5AECE CRC64;
     MILEMLNPMH YNLTSMVPEV MPVATLPILL LTGFLFFVWN HEETSSIPGP GYCMGIGPLI
     SHLRFLWMGL GSACNYYNKM YGEFVRVWIS GEETLVISKS SSTFHIMKHD HYSSRFGSTF
     GLQYMGMHEN GVIFNNNPAV WKALRPFFVK ALSGPSLARM VTVCVESVNN HLDRLDEVTN
     ALGHVNVLTL MRRTMLDASN TLFLRIPLDE KNIVLKIQGY FDAWQALLIK PNIFFKISWL
     SRKHQKSIKE LRDAVGILAE EKRHRIFTAE KLEDHVDFAT DLILAEKRGE LTKENVNQCI
     LEMMIAAPDT LSVTVFFMLC LIAQHPKVEE ALMKEIQTVL GERDLKNDDM QKLKVMENFI
     NESMRYQPVV DIVMRKALED DVIDGYPVKK GTNIILNIGR MHKLEFFPKP NEFTLENFEK
     NVPYRYFQPF GFGPRSCAGK FIAMVMMKVM LVSLLRRFHV KTLQGNCLEN MQKTNDLALH
     PDESRSLPAM IFTPRNSEKC LEH
//