CP19A_BOVIN
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 03-AUG-2022, entry version 125.
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 [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 -!- 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; P46194; -.
DR PRIDE; P46194; -.
DR GeneID; 281740; -.
DR KEGG; bta:281740; -.
DR CTD; 1588; -.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; P46194; -.
DR OrthoDB; 1247045at2759; -.
DR Proteomes; UP000009136; Unplaced.
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:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
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_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
