CP19A_CAPHI
ID CP19A_CAPHI Reviewed; 503 AA.
AC Q6YI21;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Aromatase {ECO:0000303|PubMed:15226009};
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 Capra hircus (Goat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Capra.
OX NCBI_TaxID=9925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=15226009; DOI=10.1016/j.theriogenology.2003.11.009;
RA Bobes R.J., Miranda C., Perez-Martinez M., Luu-The V., Romano M.C.;
RT "Isolation and characterization of goat ovarian aromatase cDNA: assessment
RT of the activity using an intact cell system and placental expression.";
RL Theriogenology 62:532-543(2004).
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; AY148883; AAN23836.1; -; mRNA.
DR RefSeq; NP_001272676.1; NM_001285747.1.
DR RefSeq; XP_013822500.2; XM_013967046.2.
DR AlphaFoldDB; Q6YI21; -.
DR SMR; Q6YI21; -.
DR STRING; 9925.ENSCHIP00000020521; -.
DR Ensembl; ENSCHIT00000028356; ENSCHIP00000020521; ENSCHIG00000019108.
DR GeneID; 100861413; -.
DR KEGG; chx:100861413; -.
DR CTD; 1588; -.
DR VGNC; VGNC:103466; CYP19A1.
DR GeneTree; ENSGT00840000129915; -.
DR OMA; VRPFFMK; -.
DR OrthoDB; 1247045at2759; -.
DR Proteomes; UP000291000; Chromosome 10.
DR Bgee; ENSCHIG00000019108; Expressed in ovary.
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_0000051953"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
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; 57970 MW; FA9FC7510691B3D8 CRC64;
MLLEVLNPRH YNVTSMVSEV VPIASIAILL LTGFLLLVWN YEDTSSIPGP SYFLGIGPLI
SHCRFLWMGI GSACNYYNKM YGEFMRVWVC GEETLIISKS SSMFHVMKHS HYISRFGSKL
GLQFIGMHEK GIIFNNNPAL WKAVRPFFTK ALSGPGLVRM VTICADSITK HLDRLEEVCN
DLGYVDVLTL MRRIMLDTSN ILFLGIPLDE SAIVVKIQGY FDAWQALLLK PDIFFKISWL
CRKYEKSVKD LKDAMEILIE EKRHRISTAE KLEDCIDFAT ELIFAEKRGE LTKENVNQCI
LEMLIAAPDT MSVSVFFMLF LIAKHPQVEE AMMREIQTVV GERDIRIDDM QKLKVVENFI
NESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNLGR MHRLEFFPKP NEFTLENFAK
NVPYRYFQPF GFGPRACAGK YIAMVMMKVI LVTLLRRFHV QTLQGRCVEK MQKKNDLSLH
PDETSDRLEM IFIPRNSDKC LEC
