Human Gene TH (ENST00000352909.8) from GENCODE V44
  Description: Homo sapiens tyrosine hydroxylase (TH), transcript variant 2, mRNA. (from RefSeq NM_000360)
RefSeq Summary (NM_000360): 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].
Gencode Transcript: ENST00000352909.8
Gencode Gene: ENSG00000180176.15
Transcript (Including UTRs)
   Position: hg38 chr11:2,163,929-2,171,815 Size: 7,887 Total Exon Count: 13 Strand: -
Coding Region
   Position: hg38 chr11:2,164,233-2,171,786 Size: 7,554 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:2,163,929-2,171,815)mRNA (may differ from genome)Protein (497 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: TY3H_HUMAN
DESCRIPTION: RecName: Full=Tyrosine 3-monooxygenase; EC=1.14.16.2; AltName: Full=Tyrosine 3-hydroxylase; Short=TH;
FUNCTION: Plays an important role in the physiology of adrenergic neurons.
CATALYTIC ACTIVITY: L-tyrosine + tetrahydrobiopterin + O(2) = L- dopa + 4a-hydroxytetrahydrobiopterin.
COFACTOR: Fe(2+) ion.
ENZYME REGULATION: Phosphorylation leads to an increase in the catalytic activity.
PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine from L-tyrosine: step 1/2.
TISSUE SPECIFICITY: Mainly expressed in the brain and adrenal glands.
DISEASE: Defects in TH are the cause of Segawa syndrome autosomal recessive (ARSEGS) [MIM:605407]. A form of DOPA-responsive dystonia presenting in infancy or early childhood. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. Some cases present with parkinsonian symptoms in infancy. Unlike all other forms of dystonia, it is an eminently treatable condition, due to a favorable response to L-DOPA.
DISEASE: Note=May play a role in the pathogenesis of Parkinson disease (PD). A genome-wide copy number variation analysis has identified a 34 kilobase deletion over the TH gene in a PD patient but not in any controls.
SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TH";
WEB RESOURCE: Name=Wikipedia; Note=Tyrosine hydroxylase entry; URL="http://en.wikipedia.org/wiki/Tyrosine_hydroxylase";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: TH
Diseases sorted by gene-association score: segawa syndrome, recessive* (1570), tyrosine hydroxylase deficiency* (519), tyrosine hydroxylase-deficient dopa-responsive dystonia* (500), synucleinopathy (16), perry syndrome (13), placental insufficiency (13), gangliocytoma (12), delusional disorder (12), bipolar disorder (10), leber congenital amaurosis 6 (10), hereditary dystonia (10), dystonia (10), tendinosis (10), multiple system atrophy (10), hyperphenylalaninemia, bh4-deficient, b (10), sudden infant death syndrome (10), pure autonomic failure (9), autoimmune polyendocrine syndrome type 1 (9), parkinson disease, late-onset (8), supratentorial primitive neuroectodermal tumor (8), hypoganglionosis (8), mood disorder (8), opiate dependence (7), dementia, lewy body (7), stiff-person syndrome (7), central hypoventilation syndrome, congenital (7), phenylketonuria (7), pheochromocytoma (7), rett syndrome (7), early-onset schizophrenia (6), neonatal hypoxic and ischemic brain injury (6), kidney sarcoma (6), toxic encephalopathy (6), kidney clear cell sarcoma (5), movement disease (5), tetrahydrobiopterin deficiency (5), rhabdomyosarcoma 2, alveolar (5), dystonia, dopa-responsive, with or without hyperphenylalaninemia (5), supranuclear palsy, progressive (5), autonomic nervous system neoplasm (5), dystonia-1, torsion (4), peripheral nervous system neoplasm (4), hyperphenylalaninemia (4), parkinson disease 15, autosomal recessive (4), dystonia-11, myoclonic (3), schizophrenia (2), attention deficit-hyperactivity disorder (2), nervous system disease (2), neuroblastoma (1), west syndrome (1), central nervous system disease (1), leigh syndrome (1), amyotrophic lateral sclerosis 1 (0)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 34.92 RPKM in Brain - Substantia nigra
Total median expression: 58.08 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -4.0029-0.138 Picture PostScript Text
3' UTR -111.50304-0.367 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001273 - ArAA_hydroxylase
IPR018301 - ArAA_hydroxylase_Fe/CU_BS
IPR019774 - Aromatic-AA_hydroxylase_C
IPR005962 - Tyr_3_mOase
IPR019773 - Tyrosine_3-monooxygenase-like
IPR021164 - Tyrosine_hydroxylase_CS

Pfam Domains:
PF00351 - Biopterin-dependent aromatic amino acid hydroxylase
PF12549 - Tyrosine hydroxylase N terminal

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2XSN - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P07101
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein SequenceProtein Sequence   
AlignmentAlignmentAlignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004497 monooxygenase activity
GO:0004511 tyrosine 3-monooxygenase activity
GO:0005506 iron ion binding
GO:0005515 protein binding
GO:0008198 ferrous iron binding
GO:0008199 ferric iron binding
GO:0016491 oxidoreductase activity
GO:0016597 amino acid binding
GO:0016714 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
GO:0019825 oxygen binding
GO:0019899 enzyme binding
GO:0019904 protein domain specific binding
GO:0034617 tetrahydrobiopterin binding
GO:0035240 dopamine binding
GO:0046872 metal ion binding

Biological Process:
GO:0001666 response to hypoxia
GO:0001963 synaptic transmission, dopaminergic
GO:0001975 response to amphetamine
GO:0003007 heart morphogenesis
GO:0006585 dopamine biosynthetic process from tyrosine
GO:0006631 fatty acid metabolic process
GO:0006665 sphingolipid metabolic process
GO:0007507 heart development
GO:0007601 visual perception
GO:0007605 sensory perception of sound
GO:0007612 learning
GO:0007613 memory
GO:0007617 mating behavior
GO:0007626 locomotory behavior
GO:0008016 regulation of heart contraction
GO:0009072 aromatic amino acid family metabolic process
GO:0009414 response to water deprivation
GO:0009416 response to light stimulus
GO:0009635 response to herbicide
GO:0009651 response to salt stress
GO:0009653 anatomical structure morphogenesis
GO:0009887 animal organ morphogenesis
GO:0010038 response to metal ion
GO:0010043 response to zinc ion
GO:0010259 multicellular organism aging
GO:0014070 response to organic cyclic compound
GO:0014823 response to activity
GO:0015842 aminergic neurotransmitter loading into synaptic vesicle
GO:0016137 glycoside metabolic process
GO:0017085 response to insecticide
GO:0018963 phthalate metabolic process
GO:0021987 cerebral cortex development
GO:0031667 response to nutrient levels
GO:0032355 response to estradiol
GO:0032496 response to lipopolysaccharide
GO:0033076 isoquinoline alkaloid metabolic process
GO:0035094 response to nicotine
GO:0035176 social behavior
GO:0035690 cellular response to drug
GO:0035900 response to isolation stress
GO:0035902 response to immobilization stress
GO:0042136 neurotransmitter biosynthetic process
GO:0042214 terpene metabolic process
GO:0042416 dopamine biosynthetic process
GO:0042418 epinephrine biosynthetic process
GO:0042421 norepinephrine biosynthetic process
GO:0042423 catecholamine biosynthetic process
GO:0042462 eye photoreceptor cell development
GO:0042493 response to drug
GO:0042745 circadian sleep/wake cycle
GO:0042755 eating behavior
GO:0043434 response to peptide hormone
GO:0043473 pigmentation
GO:0045471 response to ethanol
GO:0045472 response to ether
GO:0046684 response to pyrethroid
GO:0048545 response to steroid hormone
GO:0048596 embryonic camera-type eye morphogenesis
GO:0050890 cognition
GO:0051412 response to corticosterone
GO:0051602 response to electrical stimulus
GO:0052314 phytoalexin metabolic process
GO:0055114 oxidation-reduction process
GO:0070848 response to growth factor
GO:0071287 cellular response to manganese ion
GO:0071312 cellular response to alkaloid
GO:0071316 cellular response to nicotine
GO:0071333 cellular response to glucose stimulus
GO:0071363 cellular response to growth factor stimulus

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005790 smooth endoplasmic reticulum
GO:0005829 cytosol
GO:0008021 synaptic vesicle
GO:0009898 cytoplasmic side of plasma membrane
GO:0030424 axon
GO:0030425 dendrite
GO:0030659 cytoplasmic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0033162 melanosome membrane
GO:0043005 neuron projection
GO:0043025 neuronal cell body
GO:0043195 terminal bouton
GO:0043204 perikaryon


-  Descriptions from all associated GenBank mRNAs
  M17589 - Human tyrosine hydroxylase type 4 mRNA, complete cds.
DQ677336 - Homo sapiens tyrosine hydroxylase isoform D1b,2,8,9 (TH) mRNA, complete cds, alternatively spliced.
DQ677337 - Homo sapiens tyrosine hydroxylase isoform D2,8,9 (TH) mRNA, complete cds, alternatively spliced.
Y00414 - Human mRNA for tyrosine hydroxylase type 3.
X05290 - Human mRNA for tyrosine hydroxylase (HTH-1).
JD423906 - Sequence 404930 from Patent EP1572962.
JD135202 - Sequence 116226 from Patent EP1572962.
JD255619 - Sequence 236643 from Patent EP1572962.
JD227300 - Sequence 208324 from Patent EP1572962.
JD233009 - Sequence 214033 from Patent EP1572962.
JD125196 - Sequence 106220 from Patent EP1572962.
JD227182 - Sequence 208206 from Patent EP1572962.
JD545925 - Sequence 526949 from Patent EP1572962.
BC143611 - Homo sapiens tyrosine hydroxylase, mRNA (cDNA clone MGC:177141 IMAGE:9052124), complete cds.
BC104967 - Homo sapiens tyrosine hydroxylase, mRNA (cDNA clone MGC:132627 IMAGE:8143970), complete cds.
BC143614 - Homo sapiens tyrosine hydroxylase, mRNA (cDNA clone MGC:177144 IMAGE:9052127), complete cds.
JD452354 - Sequence 433378 from Patent EP1572962.
JD146497 - Sequence 127521 from Patent EP1572962.
KJ897670 - Synthetic construct Homo sapiens clone ccsbBroadEn_07064 TH gene, encodes complete protein.
KR712162 - Synthetic construct Homo sapiens clone CCSBHm_00036334 TH (TH) mRNA, encodes complete protein.
KR712163 - Synthetic construct Homo sapiens clone CCSBHm_00036336 TH (TH) mRNA, encodes complete protein.
KR712164 - Synthetic construct Homo sapiens clone CCSBHm_00036341 TH (TH) mRNA, encodes complete protein.
KR712165 - Synthetic construct Homo sapiens clone CCSBHm_00036345 TH (TH) mRNA, encodes complete protein.
AB591012 - Synthetic construct DNA, clone: pFN21AE1963, Homo sapiens TH gene for tyrosine hydroxylase, without stop codon, in Flexi system.
AY144494 - Homo sapiens putative tyrosine hydroxylase variant mRNA, partial cds; alternatively spliced.
AY144495 - Homo sapiens truncated tyrosine hydroxylase mRNA, partial cds; alternatively spliced.
M24790 - Homo sapiens tyrosine hydroxylase (TH) alternatively spliced isoform mRNA, 5' end.
M20912 - Human tyrosine hydroxylase (HTH-2) protein mRNA, 5' end.
M20911 - Human tyrosine hydroxylase (HTH-1) protein mRNA, 5' end.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00350 - Tyrosine metabolism
hsa01100 - Metabolic pathways
hsa05012 - Parkinson's disease

BioCyc Knowledge Library
PWY66-301 - catecholamine biosynthesis

Reactome (by CSHL, EBI, and GO)

Protein P07101 (Reactome details) participates in the following event(s):

R-HSA-209823 Tyrosine is hydroxylated to dopa
R-HSA-209905 Catecholamine biosynthesis
R-HSA-209776 Amine-derived hormones
R-HSA-71291 Metabolism of nitrogenous molecules
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: B7ZL70, ENST00000352909.1, ENST00000352909.2, ENST00000352909.3, ENST00000352909.4, ENST00000352909.5, ENST00000352909.6, ENST00000352909.7, NM_000360, P07101, Q15585, Q15588, Q15589, TY3H_HUMAN, TYH, uc001lvr.1, uc001lvr.2, uc001lvr.3, uc001lvr.4, uc001lvr.5
UCSC ID: ENST00000352909.8
RefSeq Accession: NM_000360
Protein: P07101 (aka TY3H_HUMAN)
CCDS: CCDS7730.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene TH:
dystonia-ov (Hereditary Dystonia Overview)
thdrd (Tyrosine Hydroxylase Deficiency)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.