Reviewed, UniProtKB/Swiss-Prot P11511 (CP19A_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	CYP19A1
Synonyms:	ARO1, CYAR, CYP19

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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.

General annotation (Comments)

Function	Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group.
Subcellular location	Membrane; Peripheral membrane protein.
Tissue specificity	Brain, placenta and gonads. Ref.10 Ref.12 Ref.13 Ref.15
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. Ref.17 Ref.18 Ref.19
Sequence similarities	Belongs to the cytochrome P450 family.

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 Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW steroid biosynthetic process Ref.3 Inferred from Experiment. Source: Reactome
Cellular component	endoplasmic reticulum Inferred from direct assay. Source: LIFEdb extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.3 Traceable author statement. Source: ProtInc
Molecular function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Ref.3 Traceable author statement. Source: UniProtKB heme binding Inferred from electronic annotation. Source: InterPro oxygen binding Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 503

502

Cytochrome P450 19A1

PRO_0000051955

Sites

Metal binding

437

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

162

1

Phosphothreonine Ref.16

Natural variations

Natural variant

39

1

W → R: dbSNP rs2236722. Ref.8

VAR_023428

Natural variant

201

1

T → M: dbSNP rs28757184. Ref.8 Ref.9

VAR_023429

Natural variant

264

1

R → C: dbSNP rs700519. Ref.8 Ref.3 Ref.11

VAR_018406

Natural variant

365

1

R → Q in AROD; 0.4% of wild-type activity. Ref.19

VAR_016962

Natural variant

375

1

R → C in AROD. Ref.18

VAR_016963

Natural variant

375

1

R → L

VAR_054152

Natural variant

435

1

R → C in AROD; 1.1% of wild-type activity. Ref.17

VAR_016964

Natural variant

437

1

C → Y in AROD; complete loss of activity. Ref.17

VAR_016965

Experimental info

Sequence conflict

496

1

N → S in AAA35557. Ref.1

Sequence conflict

496

1

N → S in CAA31929. Ref.1

Secondary structure

1

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503

Helix Strand Turn

Details...

Beta strand

59 – 61

3

Helix

64 – 67

4

Helix

71 – 80

10

Beta strand

82 – 88

7

Beta strand

91 – 96

6

Helix

99 – 106

8

Helix

118 – 123

6

Turn

126 – 129

4

Beta strand

130 – 132

3

Helix

138 – 151

14

Beta strand

155 – 158

4

Helix

161 – 178

18

Turn

179 – 181

3

Helix

187 – 203

17

Helix

210 – 224

15

Turn

233 – 235

3

Helix

238 – 263

26

Helix

271 – 283

13

Helix

292 – 305

14

Helix

308 – 323

16

Helix

325 – 338

14

Helix

348 – 351

4

Helix

353 – 365

13

Beta strand

380 – 382

3

Beta strand

385 – 387

3

Beta strand

392 – 394

3

Beta strand

399 – 401

3

Turn

403 – 405

3

Helix

414 – 417

4

Beta strand

418 – 420

3

Helix

439 – 456

18

Beta strand

457 – 462

6

Beta strand

483 – 486

4

Beta strand

489 – 493

5

Sequences

	Sequence		Length	Mass (Da)
	P11511-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 9BD9B28651D9A69A	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

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 program Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-39; MET-201 AND CYS-264.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-201. Tissue: Placenta.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed: 18987736] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-375.
+	Additional computationally mapped references.

Web resources

Wikipedia

Aromatase entry

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22246 mRNA. Translation: AAA35557.1.
X13589 mRNA. Translation: CAA31929.1.
M18856 mRNA. Translation: AAA35556.1.
J04127 mRNA. Translation: AAA52132.1.
Y07508 mRNA. Translation: CAA68807.1.
M30804 , M30796, M30797, M30798, M30800, M30801, M30802, M30803 Genomic DNA. Translation: AAA35728.1.
AY957953 Genomic DNA. Translation: AAX44046.1.
BC107785 mRNA. Translation: AAI07786.1.
M28420 mRNA. Translation: AAA52141.1.

IPI

IPI00465065.

PIR

O4HU19. A34451.

RefSeq

NP_000094.2.
NP_112503.1.

UniGene

Hs.260074

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TQA	model	-	A	53-495	[»]
3EQM	X-ray	2.90	A	1-503	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P11511.

PTM databases

PhosphoSite

P11511.

Proteomic databases

PRIDE

P11511.

Genome annotation databases

Ensembl

ENST00000260433; ENSP00000260433; ENSG00000137869; Homo sapiens. [Genome view]
ENST00000396402; ENSP00000379683; ENSG00000137869; Homo sapiens. [Genome view]
ENST00000396404; ENSP00000379685; ENSG00000137869; Homo sapiens. [Genome view]

GeneID

1588.

KEGG

hsa:1588.

UCSC

uc001zyz.2. human.

Organism-specific databases

CTD

1588.

GeneCards

GC15M049288.

H-InvDB

HIX0026807.

HGNC

HGNC:2594. CYP19A1.

HPA

CAB000355.

MIM

107910. gene+phenotype.
139300. phenotype.

Orphanet

91. Aromatase deficiency.
178345. Aromatase excess syndrome.

PharmGKB

PA27091.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06854.

HOGENOM

HBG713559.

HOVERGEN

P11511.

InParanoid

P11511.

OMA

TRENVNQ.

OrthoDB

EOG9F20P2.

PhylomeDB

P11511.

Enzyme and pathway databases

BRENDA

1.14.14.1. 247.

Reactome

REACT_13433. Biological oxidations.
REACT_15314. Hormone biosynthesis.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

P11511.

Bgee

P11511.

CleanEx

HS_CYP19A1.

Genevestigator

P11511.

GermOnline

ENSG00000137869. Homo sapiens.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

PANTHER

PTHR19383. Cyt_P450. 1 hit.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR00385. P450.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00357. Aminoglutethimide.
DB01217. Anastrozole.
DB00286. Conjugated Estrogens.
DB01406. Danazol.
DB00255. Diethylstilbestrol.
DB00990. Exemestane.
DB01006. Letrozole.
DB00894. Testolactone.
DB00624. Testosterone.

NextBio

6526.

SOURCE

Search...

Entry information

Entry name

CP19A_HUMAN

Accession

Primary (citable) accession number: P11511
Secondary accession number(s): Q16731, Q3B764, Q58FA0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	January 23, 2007
Last modified:	February 9, 2010
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.