Tclin TH Tyrosine 3-monooxygenase

Protein Summary

Description

Plays an important role in the physiology of adrenergic neurons. The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P07101
• B7ZL70
• B7ZL73
• Q0PWM2
• Q0PWM3
• Q15585
• Q15588
• Q15589
• Q2M3B4

Gene Name

• TH

Ensembl ID

• ENST00000333684
• ENSP00000328814
• ENSG00000180176
• ENST00000352909
• ENSP00000325951
• ENST00000381175
• ENSP00000370567
• ENST00000381178
• ENSP00000370571

Symbol

• TYH
• TYH
• DYT14
• DYT5b

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
chemical	1
kinase	0.99
molecular function	0.95
biological term	0.94

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2464.45   (req: < 5)

Gene RIFs: 143   (req: <= 3)

Antibodies: 1508   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2464.45   (req: >= 5)

Gene RIFs: 143   (req: > 3)

Antibodies: 1508   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 67

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 3

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (1)

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1 – 1 of 1

metirosine

THTclin Enzyme

INHIBITOR :

Active Ligands (3)

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1 – 3 of 3

N-propylapomorphine

THTclin Enzyme

pKi : 9

(S)-2-amino-3-(4-hydroxy-3-iodophenyl)propanoic acid

THTclin Enzyme

pIC50 : 6.14

CHEMBL330274

THTclin Enzyme

pIC50 : 6

Protein-Protein Interactions (275)

Explore Interacting Targets

1 – 10 of 275

• See Interactions on String-DB

KDM3B

Tbio

Family:  Epigenetic

Novelty:  0.05322289

p_int:  0.99999982

p_ni:  1.79e-7

p_wrong:  1e-9

Score:  0.188

Data Source:  BioPlex,STRINGDB

NFIC

Tbio

Family:  TF

Novelty:  0.00438636

p_int:  0.999999396

p_ni:  3.71e-7

p_wrong:  2.32e-7

Score:  0.281

Data Source:  BioPlex,STRINGDB

RELL1

Tbio

Novelty:  0.28949625

p_int:  0.999990475

p_ni:  0.000009336

p_wrong:  1.89e-7

Score:  0.19

Data Source:  BioPlex,STRINGDB

DNAJC12

Tbio

Novelty:  0.05214775

p_int:  0.999989971

p_ni:  0.000010029

Score:  0.186

Data Source:  BioPlex,STRINGDB

ZBTB34

Tdark

Family:  TF

Novelty:  0.5693361

p_int:  0.999969092

p_ni:  8.32e-7

p_wrong:  0.000030075

Score:  0.199

Data Source:  BioPlex,STRINGDB

MTFR2

Tbio

Novelty:  0.20272025

p_int:  0.999933769

p_ni:  0.00006621

p_wrong:  2.1e-8

Score:  0.187

Data Source:  BioPlex,STRINGDB

MAP3K7

Tchem

Family:  Kinase

Novelty:  0.00540177

p_int:  0.999518484

p_ni:  0.000481515

Score:  0.169

Data Source:  BioPlex,STRINGDB

TAOK2

Tchem

Family:  Kinase

Novelty:  0.0232708

p_int:  0.994501834

p_ni:  0.005444694

p_wrong:  0.000053472

Score:  0.188

Data Source:  BioPlex,STRINGDB

TAB1

Tchem

Family:  Kinase

Novelty:  0.00721424

p_int:  0.909738913

p_ni:  0.090261085

p_wrong:  2e-9

Score:  0.172

Data Source:  BioPlex,STRINGDB

DDC

Tclin

Family:  Enzyme

Novelty:  0.0012284

Score:  0.994

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (34)

Reactome (4)

KEGG (9)

PathwayCommons (9)

UniProt (1)

WikiPathways (11)

Catecholamine biosynthesis (R-HSA-209905)

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1 – 4 of 4

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Catecholamine biosynthesis	4 targets	R-HSA-209905
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of amine-derived hormones	18 targets	R-HSA-209776
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291

Name	Explore in Pharos	Explore in Source
Catecholamine biosynthesis	4 targets	R-HSA-209905
Metabolism	2112 targets	R-HSA-1430728
Metabolism of amine-derived hormones	18 targets	R-HSA-209776
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (81)

Functions (9)

Components (14)

Processes (58)

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10

1 – 9 of 9

GO Term	Evidence	Assigned by
tyrosine 3-monooxygenase activity	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	ParkinsonsUK-UCL
amino acid binding	Inferred from Electronic Annotation (IEA)	Ensembl
dopamine binding	Inferred from Electronic Annotation (IEA)	Ensembl
ferric iron binding	Inferred from Electronic Annotation (IEA)	Ensembl
ferrous iron binding	Inferred from Electronic Annotation (IEA)	Ensembl
oxygen binding	Inferred from Electronic Annotation (IEA)	Ensembl
protein domain specific binding	Inferred from Electronic Annotation (IEA)	Ensembl
tetrahydrobiopterin binding	Inferred from Electronic Annotation (IEA)	Ensembl

Disease Associations ()

No disease associations found

GWAS Traits (29)

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1 – 5 of 29

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
IGF-1 measurement	EFO_0004627	1	8	8		99.2
type II diabetes mellitus	EFO_0001360	12	12	2	1.2	99.1
type I diabetes mellitus	EFO_0001359	6	6	2	1.6	99.1
prostate carcinoma	EFO_0001663	6	4	0	1.2	94.1
glomerular filtration rate	EFO_0005208	5	6	6	7	91.9

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
IGF-1 measurement	EFO_0004627	8		99.2
type II diabetes mellitus	EFO_0001360	2	1.2	99.1
type I diabetes mellitus	EFO_0001359	2	1.6	99.1
prostate carcinoma	EFO_0001663	0	1.2	94.1
glomerular filtration rate	EFO_0005208	6	7	91.9

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Catecholamine biosynthesis
Complete proteome
Disease mutation
Dystonia
Iron
Metal-binding
Monooxygenase
Neurotransmitter biosynthesis

GWAS Trait Find Similar Targets

No Header	No Header
allergic rhinitis
birth weight
BMI-adjusted hip circumference
body height
body mass index
cervical carcinoma
corneal topography
creatinine measurement
Eczema
ferritin measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
liver/biliary system phenotype
mortality/aging
nervous system phenotype
respiratory system phenotype
vision/eye phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tyrosine hydroxylase	VGNC:988	450955
Macaque	tyrosine hydroxylase		721137
Mouse	tyrosine hydroxylase	MGI:98735	21823
Rat	tyrosine hydroxylase	RGD:3853	25085
Dog	tyrosine hydroxylase	VGNC:47322	403444

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tyrosine hydroxylase
Macaque	tyrosine hydroxylase
Mouse	tyrosine hydroxylase
Rat	tyrosine hydroxylase
Dog	tyrosine hydroxylase

Publication Statistics

PubMed Score 2464.45

PubMed score by year

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PubTator Score 1083.25

PubTator score by year

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Related Publications

Text Mined References (218)

GeneRif Annotations (143)

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PMID	Year	Title