TH tyrosine hydroxylase [Homo sapiens (human)] - Gene

Summary

Official Symbol: THprovided by HGNC
Official Full Name: tyrosine hydroxylaseprovided by HGNC
Primary source: HGNC:HGNC:11782
See related: Ensembl:ENSG00000180176 MIM:191290; AllianceGenome:HGNC:11782
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TYH; DYT14; DYT5b
Summary: 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]
Expression: Restricted expression toward adrenal (RPKM 42.8) See more
Orthologs: mouse all
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Genomic context

Location:: 11p15.5

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (2163929..2171815, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (2253295..2261192, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (2185159..2193045, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.
Title: Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.
Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.
Title: Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.
[Clinical and genetic analysis of tyrosine hydroxylase deficiency of six cases].
Title: [Clinical and genetic analysis of tyrosine hydroxylase deficiency of six cases].
[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].
Title: [Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].
Aging accentuates decrease in tyrosine hydroxylase immunoreactivity associated with the increase in the motor impairment in a model of reserpine-induced parkinsonism.
Title: Aging accentuates decrease in tyrosine hydroxylase immunoreactivity associated with the increase in the motor impairment in a model of reserpine-induced parkinsonism.
Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens.
Title: Expression Quantitative Trait Locus rs6356 Is Associated with Susceptibility to Heroin Addiction by Potentially Influencing TH Gene Expression in the Hippocampus and Nucleus Accumbens.
Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas.
Title: Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas.
Tyrosine hydroxylase activity is regulated through the modification of the 176th cysteine residue.
Title: Tyrosine hydroxylase activity is regulated through the modification of the 176th cysteine residue.
Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.
Title: Structural mechanism for tyrosine hydroxylase inhibition by dopamine and reactivation by Ser40 phosphorylation.
Post-translational and post-transcriptional mechanisms of activity regulation of tyrosine hydroxylase in the central nervous system - the effect of physical exercise", trans "Post-translacyjne i post-transkrypcyjne mechanizmy regulacji aktywnosci hydroksylazy tyrozynowej w osrodkowym ukladzie nerwowym-wplyw wysilku fizycznego.
Title: [Post-translational and post-transcriptional mechanisms of activity regulation of tyrosine hydroxylase in the central nervous system – the effect of physical exercise].

Submit: New GeneRIF Correction See all GeneRIFs (163)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal recessive DOPA responsive dystonia MedGen: C2673535 OMIM: 605407 GeneReviews: Tyrosine Hydroxylase Deficiency	Compare labs

EBI GWAS Catalog

Description
A possible mechanism behind autoimmune disorders discovered by genome-wide linkage and association analysis in celiac disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan for variants associated with early-onset prostate cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of seven new prostate cancer susceptibility loci through a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in african americans provides insights into the genetic architecture of type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	In vivo injection of HIV-1 Tat into the striatum of rats caused a loss of tyrosine hydroxylase positive neurons, which may contribute to the explanation of the pathogenesis of the motorial abnormalities often reported in HIV-1 seropositive individuals	PubMed
	tat	Treatment of dopaminergic rat PC12 cells with HIV-1 Tat downregulates the expression of tyrosine hydroxylase (TH) by upregulating the expression of the inducible cAMP early repressor which in turn abrogates the transcription activity of the TH promoter	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

ECD08746 (e-PCR)
- UniSTS:289794

GDB:212652 (e-PCR)
- UniSTS:156170

TH (e-PCR)
- UniSTS:33037

ECD04129 (e-PCR)
- UniSTS:285208

REN117108 (e-PCR)
- UniSTS:441903

ECD12135 (e-PCR)
- UniSTS:293168

GDB:197838 (e-PCR)
- UniSTS:155958

REN117118 (e-PCR)
- UniSTS:441913

ECD01847 (e-PCR)
- UniSTS:282948

ECD00576 (e-PCR)
- UniSTS:281686

GDB:197908 (e-PCR)
- UniSTS:155999

RH76200 (e-PCR)
- UniSTS:86886

ECD00347 (e-PCR)
- UniSTS:281458

NoName (e-PCR)
- UniSTS:481400

ECD09396 (e-PCR)
- UniSTS:290439

ECD08379 (e-PCR)
- UniSTS:289427

ECD00907 (e-PCR)
- UniSTS:282016

GDB:179880 (e-PCR)
- UniSTS:155057

ECD22045 (e-PCR)
- UniSTS:303036

GDB:180306 (e-PCR)
- UniSTS:155073

ECD01213 (e-PCR)
- UniSTS:282320

HUMTH01 (e-PCR)
- UniSTS:240639

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables iron ion binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables monooxygenase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tyrosine 3-monooxygenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables tyrosine 3-monooxygenase activity	IDA Inferred from Direct Assay more info	PubMed
enables tyrosine 3-monooxygenase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within animal organ morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in animal organ morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in aromatic amino acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in catecholamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in dopamine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in dopamine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in dopamine biosynthetic process from tyrosine	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within dopamine biosynthetic process from tyrosine	IEA Inferred from Electronic Annotation more info
involved_in dopamine biosynthetic process from tyrosine	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within eating behavior	IEA Inferred from Electronic Annotation more info
involved_in embryonic camera-type eye morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in embryonic camera-type eye morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in epinephrine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in eye photoreceptor cell development	IEA Inferred from Electronic Annotation more info
involved_in eye photoreceptor cell development	ISS Inferred from Sequence or Structural Similarity more info
involved_in heart development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within heart development	IEA Inferred from Electronic Annotation more info
involved_in heart development	ISS Inferred from Sequence or Structural Similarity more info
involved_in heart morphogenesis	NAS Non-traceable Author Statement more info	PubMed
involved_in hyaloid vascular plexus regression	IEA Inferred from Electronic Annotation more info
involved_in hyaloid vascular plexus regression	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within learning	IEA Inferred from Electronic Annotation more info
involved_in learning	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in locomotory behavior	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within mating behavior	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within memory	IEA Inferred from Electronic Annotation more info
involved_in memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in norepinephrine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in pigmentation	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within regulation of heart contraction	IEA Inferred from Electronic Annotation more info
involved_in regulation of heart contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to ethanol	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to ethanol	IDA Inferred from Direct Assay more info	PubMed
involved_in response to hypoxia	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within synaptic transmission, dopaminergic	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission, dopaminergic	ISS Inferred from Sequence or Structural Similarity more info
involved_in visual perception	IEA Inferred from Electronic Annotation more info
involved_in visual perception	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cell projection	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in melanosome membrane	IDA Inferred from Direct Assay more info	PubMed
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuron projection	IEA Inferred from Electronic Annotation more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
is_active_in perikaryon	IBA Inferred from Biological aspect of Ancestor more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perikaryon	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in smooth endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: tyrosine 3-monooxygenase

Names: dystonia 14; tyrosine 3-hydroxylase

NP_000351.2

EC 1.14.16.2

NP_954986.2

EC 1.14.16.2

NP_954987.2

EC 1.14.16.2

XP_011518637.1

EC 1.14.16.2

XP_054225745.1

EC 1.14.16.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008128.1 RefSeqGene

Range

4991..12877

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000360.4 → NP_000351.2 tyrosine 3-monooxygenase isoform b

See identical proteins and their annotated locations for NP_000351.2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses a different donor splice site at the first coding exon and is missing an adjacent in-frame coding exon compared to transcript variant 1, resulting in an isoform (b) missing a 31 aa segment compared to isoform a.

Source sequence(s)

AA447751, AC132217, BM718799, X05290

Consensus CDS

CCDS7730.1

UniProtKB/Swiss-Prot

P07101

Related

ENSP00000325951.4, ENST00000352909.8

Conserved Domains (4) summary

TIGR01269
Location:38 → 494

Tyr_3_monoox; tyrosine 3-monooxygenase, tetrameric

cd04930
Location:38 → 159

ACT_TH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH)

pfam00351
Location:164 → 494

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase

pfam12549
Location:2 → 26

TOH_N; Tyrosine hydroxylase N terminal
NM_199292.3 → NP_954986.2 tyrosine 3-monooxygenase isoform a

See identical proteins and their annotated locations for NP_954986.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AC132217, BM718799, M17589, M24790

Consensus CDS

CCDS7731.1

UniProtKB/Swiss-Prot

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

Related

ENSP00000370571.1, ENST00000381178.5

Conserved Domains (4) summary

TIGR01269
Location:69 → 525

Tyr_3_monoox; tyrosine 3-monooxygenase, tetrameric

cd04930
Location:69 → 190

ACT_TH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH)

pfam00351
Location:195 → 525

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase

pfam12549
Location:2 → 26

TOH_N; Tyrosine hydroxylase N terminal
NM_199293.3 → NP_954987.2 tyrosine 3-monooxygenase isoform c

See identical proteins and their annotated locations for NP_954987.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses a different donor splice site at the first coding exon compared to transcript variant 1, resulting in an isoform (c) missing a 4 aa segment compared to isoform a.

Source sequence(s)

AA447751, AC132217, BM718799, M24790, Y00414

Consensus CDS

CCDS31338.1

UniProtKB/Swiss-Prot

P07101

UniProtKB/TrEMBL

P78428

Related

ENSP00000370567.1, ENST00000381175.5

Conserved Domains (4) summary

TIGR01269
Location:65 → 521

Tyr_3_monoox; tyrosine 3-monooxygenase, tetrameric

cd04930
Location:65 → 186

ACT_TH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH)

pfam00351
Location:191 → 521

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase

pfam12549
Location:2 → 26

TOH_N; Tyrosine hydroxylase N terminal

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

2163929..2171815 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011520335.3 → XP_011518637.1 tyrosine 3-monooxygenase isoform X1

See identical proteins and their annotated locations for XP_011518637.1

UniProtKB/Swiss-Prot

P07101

Conserved Domains (4) summary

TIGR01269
Location:42 → 498

Tyr_3_monoox; tyrosine 3-monooxygenase, tetrameric

cd04930
Location:42 → 163

ACT_TH; ACT domain of the nonheme iron-dependent aromatic amino acid hydroxylase, tyrosine hydroxylases (TH)

pfam00351
Location:168 → 498

Biopterin_H; Biopterin-dependent aromatic amino acid hydroxylase

pfam12549
Location:2 → 26

TOH_N; Tyrosine hydroxylase N terminal