CP19A_HORSE
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 03-AUG-2022, entry version 141.
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 [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}; 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; O46512; -.
DR Ensembl; ENSECAT00000022758; ENSECAP00000018821; ENSECAG00000020474.
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 OMA; VRPFFMK; -.
DR OrthoDB; 1247045at2759; -.
DR TreeFam; TF352039; -.
DR Proteomes; UP000002281; Chromosome 1.
DR Bgee; ENSECAG00000020474; Expressed in chorionic villus and 13 other tissues.
DR ExpressionAtlas; O46512; baseline.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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: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 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_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
