COMT: Polycystic Ovarian Syndrome Database

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COMT

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

COMT

Aliases

HEL-S-98n

Entrez Gene ID

1312

Gene Name

Catechol-O-methyltransferase

Chromosomal Location

22q11.21

HGNC ID

HGNC:2228

Summary

Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. [provided by RefSeq, Sep 2008]

RefSeq DNA

NG_011526.1

RefSeq mRNA

NM_000754.4, NM_007310.3, NM_001135161.2, NM_001135162.2, NM_001362828.2, NM_000754.3

e!Ensembl

Gene	ENSG00000093010
Transcript	ENST00000361682, ENST00000403184, ENST00000403710, ENST00000407537, ENST00000412786, ENST00000207636, ENST00000406520, ENST00000449653, ENST00000428707
Protein	ENSP00000354511, ENSP00000383966, ENSP00000385917, ENSP00000384654, ENSP00000403958, ENSP00000207636, ENSP00000385150, ENSP00000416778, ENSP00000387695

Gene Ontology (GO)

Show/Hide all(13 )

GO ID	Ontology	Function	Evidence	Reference
GO:0032502	Biological process	Developmental process	IBA	21873635
GO:0042417	Biological process	Dopamine metabolic process	IBA	21873635
GO:0042424	Biological process	Catecholamine catabolic process	IBA	21873635
GO:0042424	Biological process	Catecholamine catabolic process	IDA	15645182, 21846718
GO:0016020	Cellular component	Membrane	HDA	19946888
GO:0016020	Cellular component	Membrane	IBA	21873635
GO:0030424	Cellular component	Axon	IBA	21873635
GO:0030425	Cellular component	Dendrite	IBA	21873635
GO:0070062	Cellular component	Extracellular exosome	HDA	19056867, 23533145
GO:0005515	Molecular function	Protein binding	IPI	16189514, 19060904
GO:0008171	Molecular function	O-methyltransferase activity	TAS	1707278
GO:0016206	Molecular function	Catechol O-methyltransferase activity	IBA	21873635
GO:0016206	Molecular function	Catechol O-methyltransferase activity	IDA	15645182, 21846718

Protein Information

Protein Name

Catechol O-methyltransferase, catechol-O-methyltransferase isoform, epididymis secretory sperm binding protein Li 98n, testicular tissue protein Li 42

Function

Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol

Refseq Proteins

NP_000745.1, NP_009294.1, NP_001128633.1, NP_001128634.1, NP_001349757.1

UniProt

P21964

PDB

3A7E, 3BWM, 3BWY, 4PYI, 4PYJ, 4PYK, 4XUC, 4XUD, 4XUE, 5LSA

Pfam

Pfam Accession	Pfam ID
PF01596	Methyltransf_3

Pathways
	KEGG	Reactome
	Steroid hormone biosynthesis Tyrosine metabolism Metabolic pathways Dopaminergic synapse	Methylation Enzymatic degradation of dopamine by COMT Enzymatic degradation of Dopamine by monoamine oxidase

Interactions

STRING	MINT	IntAct
ENSP00000414303		P23560

View interactions

Associated Diseases

Show/Hide all(4 )

Disease group	Disease Name	References
Endocrine System Diseases
	Conotruncal Anomaly Face Syndrome	8886163
	Shprintzen syndrome	8886163
	DiGeorge Syndrome	8886163
	PCOS	17535988
Musculoskeletal Diseases
Musculoskeletal Diseases	Temporomandibular Joint Disorders	25218601
Neoplasms
	Breast Cancer	16077979, 9407957, 15455371
	Liver Cancer	15341023
	Pheochromocytoma	22569243
	Prostate cancer	17013881
Psychiatric/Brain disorders
	Mental Depression	24751310, 23351565, 24555772, 23706899, 25766270, 6846043, 11772685, 16483362, 12815746, 25037115, 24679392, 25011686, 25106036, 24661160
	Attention Deficit Disorder	10490706
	Mental disorders	16780746
	Memory Disorders	28195063
	Bipolar Disorder	25766270, 23421957, 22777684, 23861766, 25744938, 11772685
	Mood Disorders	21438144, 23351565, 23928267, 25766270, 22745815, 17079080, 15584875
	Minimal Brain Dysfunction	10490706
	Schizophrenia	20561508, 17123785, 16234811, 18583979, 28195063
	Drug induced paranoia	21656904
	Psychosis	18092319, 18407467, 20591499, 20493536, 17706335
	Manic Disorder	11772685
	Autistic Disorder	16917939
	Behavior Disorders	16780746
	Anhedonia	19025226
	Cognition Disorders	17123785
	Diagnosis, Psychiatric	16780746
	Eating Disorders	29879886, 19447357

References

PMID: 17535988

Lower levels of urinary 2-hydroxyestrogens in polycystic ovary syndrome.

Salih Sana, Xu Xia, Veenstra Timothy D, Duleba Antoni J, Fouad Hala, Nagamani Manubai, Al-Hendy Ayman

Department of Obstetrics and Gynecology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0587, USA.

J Clin Endocrinol Metab. 2007 Aug;92(8):3285-91. doi: 10.1210/jc.2006-2719. Epub

Abstract

CONTEXT: Women with polycystic ovary syndrome (PCOS) have anovulation due to arrested follicular maturation. The substrate (2-hydroxyestrogen) and product (2-methoxyestrogen) of catechol-O-methyl transferase (COMT) have been shown to modulate proliferation and angiogenesis of granulosa cells.
OBJECTIVE: The objective of the study was to evaluate COMT ovarian expression as well as the production of estrogen metabolites (2-hydroxyestrogen and 2-methoxyestrogen) in subjects with PCOS. DESIGN: Immunohistochemistry was used to assess COMT expression in ovarian tissues. Urinary levels of 10 different estrogens and estrogen metabolites were measured using enzyme-labeled immunoassays and/or liquid chromatography with tandem mass spectrometry. SETTING: The study was conducted at a tertiary university referral center. PATIENTS AND OTHER PARTICIPANTS: Ovarian tissues were obtained from six control subjects and six subjects with PCOS. Fasting first-void urinary samples were collected from 49 subjects with PCOS and 36 healthy control subjects. MAIN OUTCOME MEASURE(S): COMT protein expression in ovarian tissues was measured. Urinary levels of 2-hydroxyestrogen and 2-methoxyestrogen levels in PCOS patients were also measured.
RESULTS: Whereas immunohistochemistry showed that COMT was expressed in ovaries from control and PCOS subjects, its expression was significantly higher in ovaries from subjects with PCOS, in both the follicular structures and ovarian stroma. The urinary 2-hydroxyestrogen level was significantly lower in subjects with PCOS, compared with normal controls (P = 0.009). Additionally, urinary 2-hydroxyestrogen levels negatively correlated with serum insulin levels in subjects with PCOS (r = -0.333, P =0 .031).
CONCLUSIONS: Urinary 2-hydroxyestrogen is decreased in subjects with PCOS, which could be due in part to increased ovarian expression of COMT. Further studies are needed to ascertain the role of estrogen metabolism in PCOS before this information can be used in clinical settings.

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