Cytochrome P450 19A1 - Homo sapiens (Human)

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Names and origin

Protein names

Recommended name:
    Cytochrome P450 19A1
    EC=1.14.14.1
Alternative name(s):
    CYPXIX
    Aromatase
    Estrogen synthetase
    P-450AROM

Gene names

Name:	CYP19A1
Synonyms:	ARO1, CYAR, CYP19

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Catalytic activity	RH + reduced flavoprotein + O(2) = ROH + oxidized flavoprotein + H(2)O.
Cofactor	Heme group.
Subcellular location	Membrane; Peripheral membrane protein.
Tissue specificity	Brain, placenta and gonads.
Involvement in disease	Defects in CYP19A1 are a cause of familial gynecomastia [MIM:139300]. This is characterized by an estrogen excess due to an increased aromatase activity. Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:107910]. AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.
Sequence similarities	Belongs to the cytochrome P450 family.

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Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	steroid biosynthetic process Ref.3 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum Inferred from direct assay. Source: LIFEdb membrane fraction Ref.3 Traceable author statement. Source: ProtInc
Molecular function	electron carrier activity Ref.3 Traceable author statement. Source: UniProtKB oxygen binding Ref.3 Traceable author statement. Source: ProtInc unspecific monooxygenase activity Ref.7 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

Removed

Chain

2 – 503

502

Cytochrome P450 19A1

Sites

Metal binding

437

Iron (heme axial ligand)

Amino acid modifications

Modified residue

162

Phosphothreonine

Natural variations

Natural variant

Natural variant

Natural variant

R → C: dbSNP rs700519.

Natural variant

365

R → Q in AROD; 0.4% of wild-type activity.

Natural variant

375

R → C in AROD.

Natural variant

435

R → C in AROD; 1.1% of wild-type activity.

Natural variant

437

C → Y in AROD; complete loss of activity.

Experimental info

Sequence conflict

496

N → S in AAA35557 and CAA31929. Ref.1

Secondary structure

503

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P11511-1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: 9BD9B28651D9A69A
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FASTA

503

57,883

        10         20         30         40         50         60 
MVLEMLNPIH YNITSIVPEA MPAATMPVLL LTGLFLLVWN YEGTSSIPGP GYCMGIGPLI 

        70         80         90        100        110        120 
SHGRFLWMGI GSACNYYNRV YGEFMRVWIS GEETLIISKS SSMFHIMKHN HYSSRFGSKL 

       130        140        150        160        170        180 
GLQCIGMHEK GIIFNNNPEL WKTTRPFFMK ALSGPGLVRM VTVCAESLKT HLDRLEEVTN 

       190        200        210        220        230        240 
ESGYVDVLTL LRRVMLDTSN TLFLRIPLDE SAIVVKIQGY FDAWQALLIK PDIFFKISWL 

       250        260        270        280        290        300 
YKKYEKSVKD LKDAIEVLIA EKRRRISTEE KLEECMDFAT ELILAEKRGD LTRENVNQCI 

       310        320        330        340        350        360 
LEMLIAAPDT MSVSLFFMLF LIAKHPNVEE AIIKEIQTVI GERDIKIDDI QKLKVMENFI 

       370        380        390        400        410        420 
YESMRYQPVV DLVMRKALED DVIDGYPVKK GTNIILNIGR MHRLEFFPKP NEFTLENFAK 

       430        440        450        460        470        480 
NVPYRYFQPF GFGPRGCAGK YIAMVMMKAI LVTLLRRFHV KTLQGQCVES IQKIHDLSLH 

       490        500 
PDETKNMLEM IFTPRNSDRC LEH

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a complete cDNA encoding human aromatase: immunochemical identification and sequence analysis." Harada N. Biochem. Biophys. Res. Commun. 156:725-732(1988) [PubMed: 2973313] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15." Chen S., Besman M.J., Sparkes R.S., Zollman S., Klisak I., Mohandas T., Hall P.F., Shively J.E. DNA 7:27-38(1988) [PubMed: 3390233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells." Corbin C.J., Graham-Lorence S., McPhaul M., Mason J.I., Mendelson C.R., Simpson E.R. Proc. Natl. Acad. Sci. U.S.A. 85:8948-8952(1988) [PubMed: 2848247] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CYS-264.
[4]	"Alternative usage of different poly(A) addition signals for two major species of mRNA encoding human aromatase P-450." Toda K., Terashima M., Mitsuuchi Y., Yamasaki Y., Yokoyama Y., Nojima S., Ushiro H., Maeda T., Yamamoto Y., Sagara Y., Shizuta Y. FEBS Lett. 247:371-376(1989) [PubMed: 2541021] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[5]	"Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis." Means G.D., Mahendroo M.S., Corbin C.J., Mathis J.M., Powell F.E., Mendelson C.R., Simpson E.R. J. Biol. Chem. 264:19385-19391(1989) [PubMed: 2808431] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Expression of human placental aromatase in Saccharomyces cerevisiae." Pompon D., Liu R.Y., Besman M.J., Wang P.L., Shively J.E., Chen S. Mol. Endocrinol. 3:1477-1487(1989) [PubMed: 2691883] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[7]	"Biochemical and molecular genetic analyses on placental aromatase (P-450AROM) deficiency." Harada N., Ogawa H., Shozu M., Yamada K., Suhara K., Nishida E., Takagi Y. J. Biol. Chem. 267:4781-4785(1992) [PubMed: 1371509] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Rajkumar N., Downing T.K., Olson A.N., Nguyen C.P., Gildersleeve H., Cassidy C.M., Johnson E.J., Swanson J.E., McFarland I., Yool B., Park C., Nickerson D.A. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-39; MET-201 AND CYS-264.
[9]	"Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA." Evans C.T., Ledesma D.B., Schulz T.Z., Simpson E.R., Mendelson C.R. Proc. Natl. Acad. Sci. U.S.A. 83:6387-6391(1986) [PubMed: 3018730] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-503, TISSUE SPECIFICITY. Tissue: Placenta.
[10]	"Sequencing of cDNA inserts encoding aromatase cytochrome P-450 (P-450AROM)." Simpson E.R., Evans C.T., Corbin C.J., Powell F.E., Ledesma D.B., Mendelson C.R. Mol. Cell. Endocrinol. 52:267-272(1987) [PubMed: 3653507] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 85-503, VARIANT CYS-264.
[11]	"Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta." Mahendroo M.S., Means G.D., Mendelson C.R., Simpson E.R. J. Biol. Chem. 266:11276-11281(1991) [PubMed: 2040633] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, TISSUE SPECIFICITY.
[12]	"Tissue-specific and hormonally controlled alternative promoters regulate aromatase cytochrome P450 gene expression in human adipose tissue." Mahendroo M.S., Mendelson C.R., Simpson E.R. J. Biol. Chem. 268:19463-19470(1993) [PubMed: 7690033] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49, TISSUE SPECIFICITY, ALTERNATIVE PROMOTER USAGE.
[13]	"Amino terminal sequence analysis of human placenta aromatase." Chen S., Shively J.E., Nakajin S., Shinoda M., Hall P.F. Biochem. Biophys. Res. Commun. 135:713-719(1986) [PubMed: 3964273] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF N-TERMINUS. Tissue: Placenta.
[14]	"Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain." Honda S., Harada N., Takagi Y. Biochem. Biophys. Res. Commun. 198:1153-1160(1994) [PubMed: 8117272] [Abstract] Cited for: ALTERNATIVE PROMOTER USAGE, TISSUE SPECIFICITY.
[15]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-162, MASS SPECTROMETRY. Tissue: Epithelium.
[16]	"Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries." Ito Y., Fisher C.R., Conte F.A., Grumbach M.M., Simpson E.R. Proc. Natl. Acad. Sci. U.S.A. 90:11673-11677(1993) [PubMed: 8265607] [Abstract] Cited for: VARIANTS AROD CYS-435 AND TYR-437.
[17]	"Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens." Morishima A., Grumbach M.M., Simpson E.R., Fisher C., Qin K. J. Clin. Endocrinol. Metab. 80:3689-3698(1995) [PubMed: 8530621] [Abstract] Cited for: VARIANT AROD CYS-375.
[18]	"Effect of testosterone and estradiol in a man with aromatase deficiency." Carani C., Qin K., Simoni M., Faustini-Fustini M., Serpente S., Boyd J., Korach K.S., Simpson E.R. N. Engl. J. Med. 337:91-95(1997) [PubMed: 9211678] [Abstract] Cited for: VARIANT AROD GLN-365.
+	Additional computationally mapped references.