CP19A_RAT
ID CP19A_RAT Reviewed; 508 AA.
AC P22443;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Aromatase;
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=Arom, Cyp19;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Ovary;
RX PubMed=2157976; DOI=10.1210/mend-4-1-3;
RA Hickey G.J., Krasnow J.S., Beattie W.G., Richards J.S.;
RT "Aromatase cytochrome P450 in rat ovarian granulosa cells before and after
RT luteinization: adenosine 3',5'-monophosphate-dependent and independent
RT regulation. Cloning and sequencing of rat aromatase cDNA and 5' genomic
RT DNA.";
RL Mol. Endocrinol. 4:3-12(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2340950; DOI=10.1016/0303-7207(90)90056-e;
RA Lephart E.D., Peterson K.G., Noble J.F., George F.W., McPhaul M.J.;
RT "The structure of cDNA clones encoding the aromatase P-450 isolated from a
RT rat Leydig cell tumor line demonstrates differential processing of
RT aromatase mRNA in rat ovary and a neoplastic cell line.";
RL Mol. Cell. Endocrinol. 70:31-40(1990).
CC -!- FUNCTION: Catalyzes the formation of aromatic C18 estrogens from C19
CC androgens.
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 -!- 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 -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; M33986; AAA41044.1; -; mRNA.
DR PIR; A36121; A36121.
DR AlphaFoldDB; P22443; -.
DR SMR; P22443; -.
DR STRING; 10116.ENSRNOP00000000212; -.
DR BindingDB; P22443; -.
DR ChEMBL; CHEMBL3859; -.
DR DrugCentral; P22443; -.
DR PhosphoSitePlus; P22443; -.
DR PaxDb; P22443; -.
DR RGD; 2457; Cyp19a1.
DR eggNOG; KOG0157; Eukaryota.
DR InParanoid; P22443; -.
DR PhylomeDB; P22443; -.
DR Reactome; R-RNO-193144; Estrogen biosynthesis.
DR Reactome; R-RNO-211976; Endogenous sterols.
DR PRO; PR:P22443; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0070330; F:aromatase activity; IDA:RGD.
DR GO; GO:0020037; F:heme binding; ISO:RGD.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016712; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen; IDA:RGD.
DR GO; GO:0030325; P:adrenal gland development; IEP:RGD.
DR GO; GO:0006710; P:androgen catabolic process; ISO:RGD.
DR GO; GO:0008209; P:androgen metabolic process; IMP:RGD.
DR GO; GO:0008206; P:bile acid metabolic process; IEP:RGD.
DR GO; GO:0018879; P:biphenyl metabolic process; IEP:RGD.
DR GO; GO:0060348; P:bone development; IEP:RGD.
DR GO; GO:0008207; P:C21-steroid hormone metabolic process; IDA:RGD.
DR GO; GO:0097720; P:calcineurin-mediated signaling; IMP:RGD.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0071371; P:cellular response to gonadotropin stimulus; IEP:RGD.
DR GO; GO:0071464; P:cellular response to hydrostatic pressure; IEP:RGD.
DR GO; GO:0018894; P:dibenzo-p-dioxin metabolic process; IEP:RGD.
DR GO; GO:0006703; P:estrogen biosynthetic process; IDA:RGD.
DR GO; GO:0030540; P:female genitalia development; ISO:RGD.
DR GO; GO:0008585; P:female gonad development; ISO:RGD.
DR GO; GO:0030851; P:granulocyte differentiation; IEP:RGD.
DR GO; GO:0021766; P:hippocampus development; IEP:RGD.
DR GO; GO:0021854; P:hypothalamus development; IEP:RGD.
DR GO; GO:0001553; P:luteinization; IEP:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0030186; P:melatonin metabolic process; IEP:RGD.
DR GO; GO:0045779; P:negative regulation of bone resorption; IMP:RGD.
DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; ISO:RGD.
DR GO; GO:0010760; P:negative regulation of macrophage chemotaxis; ISO:RGD.
DR GO; GO:0018963; P:phthalate metabolic process; IEP:RGD.
DR GO; GO:2000866; P:positive regulation of estradiol secretion; ISO:RGD.
DR GO; GO:0060736; P:prostate gland growth; ISO:RGD.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IMP:RGD.
DR GO; GO:0010164; P:response to cesium ion; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0043627; P:response to estrogen; IEP:RGD.
DR GO; GO:0009635; P:response to herbicide; IEP:RGD.
DR GO; GO:0010212; P:response to ionizing radiation; IEP:RGD.
DR GO; GO:0010038; P:response to metal ion; IEP:RGD.
DR GO; GO:0043278; P:response to morphine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0061370; P:testosterone biosynthetic process; ISO:RGD.
DR GO; GO:0060065; P:uterus development; ISO:RGD.
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 Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..508
FT /note="Aromatase"
FT /id="PRO_0000051962"
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 CONFLICT 3..4
FT /note="LE -> FQ (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 10
FT /note="H -> Q (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="W -> C (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="S -> L (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 123..129
FT /note="QCIGMHE -> VVHGHAR (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="V -> L (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="E -> G (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 328..331
FT /note="VETA -> WKQ (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 342
FT /note="D -> A (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 364..369
FT /note="LRYQPV -> CGISPF (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="V -> L (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 425
FT /note="R -> T (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="V -> I (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 466
FT /note="R -> K (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 493..497
FT /note="RHIFN -> SPRNS (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 508 AA; 58412 MW; C0ADFB0FD80AB352 CRC64;
MFLEMLNPMH YNVTIMVPET VPVSAMPLLL IMGLLLLIRN CESSSSIPGP GYCLGIGPLI
SHGRFLWMGI GSACNYYNKM YGEFMRVWIS GEETLIISKS SSMVHVMKHS NYISRFGSKR
GLQCIGMHEN GIIFNNNPSL WRTVRPFFMK ALTGPGLIRM VEVCVESIKQ HLDRLGDVTD
NSGYVDVVTL MRHIMLDTSN TLFLGIPLDE SSIVKKIQGY FNAWQALLIK PNIFFKISWL
YRKYERSVKD LKDEIEILVE KKRQKVSSAE KLEDCMDFAT DLIFAERRGD LTKENVNQCI
LEMLIAAPDT MSVTLYVMLL LIAEYPEVET AILKEIHTVV GDRDIRIGDV QNLKVVENFI
NESLRYQPVV DLVMRRALED DVIDGYPVKK GTNIILNIGR MHRLEYFPKP NEFTLENFEK
NVPYRYFQPF GFGPRSCAGK YIAMVMMKVV LVTLLKRFHV KTLQKRCIEN MPKNNDLSLH
LDEDSPIVEI IFRHIFNTPF LQCLYISL
