CP19A_CANLF
ID CP19A_CANLF Reviewed; 503 AA.
AC Q5QQX7;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Aromatase {ECO:0000303|Ref.1};
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 Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RA Pappas I.S.;
RT "Cloning, expression and characterization of dog aromatase gene.";
RL Submitted (NOV-2004) 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}.
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; AJ854107; CAH69600.1; -; mRNA.
DR RefSeq; NP_001008715.1; NM_001008715.1.
DR AlphaFoldDB; Q5QQX7; -.
DR SMR; Q5QQX7; -.
DR STRING; 9615.ENSCAFP00000022607; -.
DR PaxDb; Q5QQX7; -.
DR PRIDE; Q5QQX7; -.
DR GeneID; 494003; -.
DR KEGG; cfa:494003; -.
DR CTD; 1588; -.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; Q5QQX7; -.
DR Proteomes; UP000002254; 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_0000051952"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 51..71
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
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"
SQ SEQUENCE 503 AA; 58084 MW; 27F4C3CF75E978A8 CRC64;
MLLEMLNPMH YNITSMMPEV MPVATMPILL LTGFLLLVWN YEDTSSIPGP GYCMGIGPLI
SHCRFLWMGI GSACNYYNKM YGEFMRVWIC GEETLIISKS SSMFHIMKHS HYSSRFGSKL
GLQCIGMHEN GIIFNNNPTL WKAIRPFFTK ALSGPGLVRM VTVCVGSIIT HLDRLEEVSN
ELGYVDVLTL MRRIMLDTSN ILFLGIPLDE SAIVVKIQGY FDAWQALLLK PDIFFKISWL
YKKYEKSVKD LKDAMEILIE EKRHRISTAE KLEDHMDFAT ELIFAEKRGD LTRENVNQCI
LEMLIAAPDT MSVSVFFMLF LIAKHPKVEE SIMKEIQAVV GERDIRIDDM QKLKVVENFI
YESMRYQPVV NLVMRKALQD DIIDGYLVKK GTNIILNIGR MHRLEFFPKP NEFTLENFAK
NVPYRYFQPF GFGPRSCAGK YIAMVMMKVV LVTLLRRFHV QTLQGECIEN MQKKYGLSLH
PDETNNLLEM VFVPRNSEKC LER
