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Protein

Tyrosine 3-monooxygenase

Gene

TH

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in the physiology of adrenergic neurons.

Catalytic activityi

L-tyrosine + tetrahydrobiopterin + O2 = L-dopa + 4a-hydroxytetrahydrobiopterin.

Cofactori

Enzyme regulationi

Phosphorylation leads to an increase in the catalytic activity.

Pathwayi: dopamine biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes dopamine from L-tyrosine.
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Tyrosine 3-monooxygenase (TH)
  2. Aromatic-L-amino-acid decarboxylase (DDC)
This subpathway is part of the pathway dopamine biosynthesis, which is itself part of Catecholamine biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes dopamine from L-tyrosine, the pathway dopamine biosynthesis and in Catecholamine biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi361IronBy similarity1
Metal bindingi366IronBy similarity1
Metal bindingi406IronBy similarity1

GO - Molecular functioni

  • amino acid binding Source: Ensembl
  • dopamine binding Source: Ensembl
  • enzyme binding Source: ParkinsonsUK-UCL
  • ferric iron binding Source: Ensembl
  • ferrous iron binding Source: Ensembl
  • oxygen binding Source: Ensembl
  • tetrahydrobiopterin binding Source: Ensembl
  • tyrosine 3-monooxygenase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Catecholamine biosynthesis, Neurotransmitter biosynthesis

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BRENDAi1.14.16.2. 2681.
ReactomeiR-HSA-209905. Catecholamine biosynthesis.
SIGNORiP07101.
UniPathwayiUPA00747; UER00733.

Names & Taxonomyi

Protein namesi
Recommended name:
Tyrosine 3-monooxygenase (EC:1.14.16.2)
Alternative name(s):
Tyrosine 3-hydroxylase
Short name:
TH
Gene namesi
Name:TH
Synonyms:TYH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:11782. TH.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic side of plasma membrane Source: BHF-UCL
  • cytoplasmic vesicle Source: BHF-UCL
  • cytosol Source: Reactome
  • dendrite Source: Ensembl
  • melanosome membrane Source: BHF-UCL
  • mitochondrion Source: Ensembl
  • neuron projection Source: BHF-UCL
  • nucleus Source: BHF-UCL
  • perikaryon Source: BHF-UCL
  • smooth endoplasmic reticulum Source: BHF-UCL
  • synaptic vesicle Source: Ensembl
  • terminal bouton Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Segawa syndrome autosomal recessive (ARSEGS)21 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:605407
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07286219S → C Found in a patient with ARSEGS; unknown pathological significance. 1 PublicationCorresponds to variant rs766704202dbSNPEnsembl.1
Natural variantiVAR_072863207C → Y in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072864227D → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014026233R → H in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 4 PublicationsCorresponds to variant rs80338892dbSNPEnsembl.1
Natural variantiVAR_014027236L → P in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and catalytic activity; rare mutation. 3 PublicationsCorresponds to variant rs121917763dbSNPEnsembl.1
Natural variantiVAR_072865241A → T in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072866246H → Y in ARSEGS; loss of about 40% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072867247G → S in ARSEGS; loss of about 50% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant rs762304556dbSNPEnsembl.1
Natural variantiVAR_071715251P → L in ARSEGS. 1 Publication1
Natural variantiVAR_072868259E → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014028276T → P in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs28934581dbSNPEnsembl.1
Natural variantiVAR_071716279C → F in ARSEGS. 1 Publication1
Natural variantiVAR_072869294G → R in ARSEGS. 1 PublicationCorresponds to variant rs755536257dbSNPEnsembl.1
Natural variantiVAR_071717296R → Q in ARSEGS. 1 PublicationCorresponds to variant rs199961079dbSNPEnsembl.1
Natural variantiVAR_072870301P → A in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072871309F → S in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014029314T → M in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs121917764dbSNPEnsembl.1
Natural variantiVAR_071718315G → S in ARSEGS. 2 Publications1
Natural variantiVAR_072872319R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072873328R → W in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014030337R → H in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs28934580dbSNPEnsembl.1
Natural variantiVAR_072874359C → F in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs121917765dbSNPEnsembl.1
Natural variantiVAR_072875375F → L in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 Publications1
Natural variantiVAR_072876376A → V in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_071719382I → T in ARSEGS. 1 Publication1
Natural variantiVAR_072877385A → V in ARSEGS. 1 PublicationCorresponds to variant rs763039181dbSNPEnsembl.1
Natural variantiVAR_072878387L → M in ARSEGS; no effect on tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072879394I → T in ARSEGS; complete loss of tyrosine hydroxylase activity. 3 Publications1
Natural variantiVAR_072880399T → M in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072881408G → R in ARSEGS. 1 PublicationCorresponds to variant rs745551241dbSNPEnsembl.1
Natural variantiVAR_014031412Q → K in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; reduced affinity for L-tyrosine. 3 PublicationsCorresponds to variant rs121917762dbSNPEnsembl.1
Natural variantiVAR_072882414G → R in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 3 PublicationsCorresponds to variant rs370962049dbSNPEnsembl.1
Natural variantiVAR_071720428G → R in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D). 2 Publications1
Natural variantiVAR_072883441R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs367874223dbSNPEnsembl.1
Natural variantiVAR_072884467S → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072885492P → L in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs767635052dbSNPEnsembl.1
Natural variantiVAR_014032494T → M in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs45471299dbSNPEnsembl.1
Natural variantiVAR_072886498D → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 4 PublicationsCorresponds to variant rs771351747dbSNPEnsembl.1
Natural variantiVAR_072887510L → Q in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1

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.

Keywords - Diseasei

Disease mutation, Dystonia, Parkinson disease, Parkinsonism

Organism-specific databases

DisGeNETi7054.
MalaCardsiTH.
MIMi605407. phenotype.
OpenTargetsiENSG00000180176.
Orphaneti101150. Autosomal recessive dopa-responsive dystonia.
PharmGKBiPA351.

Chemistry databases

ChEMBLiCHEMBL1969.
DrugBankiDB00120. L-Phenylalanine.
DB00135. L-Tyrosine.
DB00765. Metyrosine.
DB00360. Tetrahydrobiopterin.

Polymorphism and mutation databases

BioMutaiTH.
DMDMi239938945.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002055612 – 528Tyrosine 3-monooxygenaseAdd BLAST527

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine; by CaMK21 Publication1
Modified residuei62PhosphoserineBy similarity1
Modified residuei71Phosphoserine; by CaMK2 and PKA1 Publication1
Modified residuei502PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP07101.
PeptideAtlasiP07101.
PRIDEiP07101.

PTM databases

iPTMnetiP07101.
PhosphoSitePlusiP07101.

Expressioni

Tissue specificityi

Mainly expressed in the brain and adrenal glands.

Gene expression databases

BgeeiENSG00000180176.
CleanExiHS_TH.
ExpressionAtlasiP07101. baseline and differential.
GenevisibleiP07101. HS.

Organism-specific databases

HPAiCAB002522.
CAB072340.
HPA061003.

Interactioni

GO - Molecular functioni

  • enzyme binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi112912. 13 interactors.
IntActiP07101. 10 interactors.
MINTiMINT-198913.
STRINGi9606.ENSP00000370571.

Chemistry databases

BindingDBiP07101.

Structurei

Secondary structure

1528
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi201 – 206Combined sources6
Turni216 – 218Combined sources3
Turni223 – 226Combined sources4
Helixi228 – 243Combined sources16
Helixi257 – 277Combined sources21
Helixi280 – 292Combined sources13
Helixi303 – 314Combined sources12
Beta strandi317 – 320Combined sources4
Helixi327 – 334Combined sources8
Turni335 – 337Combined sources3
Beta strandi338 – 341Combined sources4
Helixi359 – 365Combined sources7
Helixi367 – 370Combined sources4
Helixi373 – 386Combined sources14
Helixi391 – 403Combined sources13
Turni404 – 407Combined sources4
Beta strandi409 – 412Combined sources4
Beta strandi415 – 418Combined sources4
Helixi421 – 424Combined sources4
Helixi427 – 433Combined sources7
Beta strandi435 – 442Combined sources8
Helixi445 – 449Combined sources5
Beta strandi455 – 457Combined sources3
Beta strandi460 – 466Combined sources7
Helixi468 – 480Combined sources13
Beta strandi485 – 491Combined sources7
Turni492 – 495Combined sources4
Beta strandi496 – 500Combined sources5
Helixi503 – 526Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XSNX-ray2.68A/B/C/D193-528[»]
4J6SX-ray3.08E/F/G/H1-74[»]
ProteinModelPortaliP07101.
SMRiP07101.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi85 – 90Poly-Ala6

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP07101.
KOiK00501.
OMAiPHLEYFV.
OrthoDBiEOG091G05MZ.
PhylomeDBiP07101.
TreeFamiTF313327.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR001273. 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.
[Graphical view]
PANTHERiPTHR11473. PTHR11473. 2 hits.
PfamiPF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 3 hits.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01269. Tyr_3_monoox. 1 hit.
PROSITEiPS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Note: TH transcripts lacking exons 8 and 9 present concomitant splicing in exons 1b and 2.
Isoform 3 (identifier: P07101-1) [UniParc]FASTAAdd to basket
Also known as: TH type 4

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPTPDATTPQ AKGFRRAVSE LDAKQAEAIM VRGQGAPGPS LTGSPWPGTA
60 70 80 90 100
APAASYTPTP RSPRFIGRRQ SLIEDARKER EAAVAAAAAA VPSEPGDPLE
110 120 130 140 150
AVAFEEKEGK AVLNLLFSPR ATKPSALSRA VKVFETFEAK IHHLETRPAQ
160 170 180 190 200
RPRAGGPHLE YFVRLEVRRG DLAALLSGVR QVSEDVRSPA GPKVPWFPRK
210 220 230 240 250
VSELDKCHHL VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI AFQYRHGDPI
260 270 280 290 300
PRVEYTAEEI ATWKEVYTTL KGLYATHACG EHLEAFALLE RFSGYREDNI
310 320 330 340 350
PQLEDVSRFL KERTGFQLRP VAGLLSARDF LASLAFRVFQ CTQYIRHASS
360 370 380 390 400
PMHSPEPDCC HELLGHVPML ADRTFAQFSQ DIGLASLGAS DEEIEKLSTL
410 420 430 440 450
YWFTVEFGLC KQNGEVKAYG AGLLSSYGEL LHCLSEEPEI RAFDPEAAAV
460 470 480 490 500
QPYQDQTYQS VYFVSESFSD AKDKLRSYAS RIQRPFSVKF DPYTLAIDVL
510 520
DSPQAVRRSL EGVQDELDTL AHALSAIG
Length:528
Mass (Da):58,600
Last modified:June 16, 2009 - v5
Checksum:i31D2D49955ACF070
GO
Isoform 1 (identifier: P07101-2) [UniParc]FASTAAdd to basket
Also known as: TH type 3

The sequence of this isoform differs from the canonical sequence as follows:
     31-34: Missing.

Show »
Length:524
Mass (Da):58,160
Checksum:i708422BBD3304A6C
GO
Isoform 2 (identifier: P07101-3) [UniParc]FASTAAdd to basket
Also known as: HTH-1, hTH-Delta1b,2, TH type 1

The sequence of this isoform differs from the canonical sequence as follows:
     31-61: Missing.

Show »
Length:497
Mass (Da):55,612
Checksum:i6CB8EDC9C4874288
GO
Isoform 4 (identifier: P07101-4) [UniParc]FASTAAdd to basket
Also known as: hTH-Delta2, TH type 2

The sequence of this isoform differs from the canonical sequence as follows:
     35-61: Missing.

Show »
Length:501
Mass (Da):56,052
Checksum:iB614295B9CB2921F
GO
Isoform 5 (identifier: P07101-5) [UniParc]FASTAAdd to basket
Also known as: hTH-Delta2,8,9

The sequence of this isoform differs from the canonical sequence as follows:
     35-61: Missing.
     264-357: Missing.

Note: Lacks catalytic activity.
Show »
Length:407
Mass (Da):45,338
Checksum:i71FB6BA8A6061F44
GO
Isoform 6 (identifier: P07101-6) [UniParc]FASTAAdd to basket
Also known as: hTH-Delta1b,2,8,9

The sequence of this isoform differs from the canonical sequence as follows:
     31-61: Missing.
     264-357: Missing.

Note: Lacks catalytic activity.
Show »
Length:403
Mass (Da):44,898
Checksum:iDAD3F18191575F99
GO

Sequence cautioni

The sequence AAA61173 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti373R → H in AAI43615 (PubMed:15489334).Curated1
Sequence conflicti401Y → S in AAA61179 (PubMed:2887169).Curated1
Sequence conflicti401Y → S in CAA28908 (PubMed:2882428).Curated1
Sequence conflicti401Y → S in CAA68472 (PubMed:2888085).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07286219S → C Found in a patient with ARSEGS; unknown pathological significance. 1 PublicationCorresponds to variant rs766704202dbSNPEnsembl.1
Natural variantiVAR_014025112V → M Common polymorphism. 5 PublicationsCorresponds to variant rs6356dbSNPEnsembl.1
Natural variantiVAR_072863207C → Y in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072864227D → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014026233R → H in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 4 PublicationsCorresponds to variant rs80338892dbSNPEnsembl.1
Natural variantiVAR_014027236L → P in ARSEGS; severe parkinsonian symptoms in early infancy; strongly reduced stability and catalytic activity; rare mutation. 3 PublicationsCorresponds to variant rs121917763dbSNPEnsembl.1
Natural variantiVAR_072865241A → T in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072866246H → Y in ARSEGS; loss of about 40% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072867247G → S in ARSEGS; loss of about 50% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 PublicationsCorresponds to variant rs762304556dbSNPEnsembl.1
Natural variantiVAR_071715251P → L in ARSEGS. 1 Publication1
Natural variantiVAR_072868259E → G in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014028276T → P in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs28934581dbSNPEnsembl.1
Natural variantiVAR_071716279C → F in ARSEGS. 1 Publication1
Natural variantiVAR_072869294G → R in ARSEGS. 1 PublicationCorresponds to variant rs755536257dbSNPEnsembl.1
Natural variantiVAR_071717296R → Q in ARSEGS. 1 PublicationCorresponds to variant rs199961079dbSNPEnsembl.1
Natural variantiVAR_072870301P → A in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072871309F → S in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014029314T → M in ARSEGS; parkinsonian symptoms in infancy; loss of about 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs121917764dbSNPEnsembl.1
Natural variantiVAR_071718315G → S in ARSEGS. 2 Publications1
Natural variantiVAR_072872319R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072873328R → W in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_014030337R → H in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs28934580dbSNPEnsembl.1
Natural variantiVAR_072874359C → F in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs121917765dbSNPEnsembl.1
Natural variantiVAR_072875375F → L in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; shifted substrate specificity from tyrosine to phenylalanine and Dopa. 2 Publications1
Natural variantiVAR_072876376A → V in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_071719382I → T in ARSEGS. 1 Publication1
Natural variantiVAR_072877385A → V in ARSEGS. 1 PublicationCorresponds to variant rs763039181dbSNPEnsembl.1
Natural variantiVAR_072878387L → M in ARSEGS; no effect on tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072879394I → T in ARSEGS; complete loss of tyrosine hydroxylase activity. 3 Publications1
Natural variantiVAR_072880399T → M in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072881408G → R in ARSEGS. 1 PublicationCorresponds to variant rs745551241dbSNPEnsembl.1
Natural variantiVAR_014031412Q → K in ARSEGS; loss of over 80% of tyrosine hydroxylase activity; reduced affinity for L-tyrosine. 3 PublicationsCorresponds to variant rs121917762dbSNPEnsembl.1
Natural variantiVAR_072882414G → R in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 3 PublicationsCorresponds to variant rs370962049dbSNPEnsembl.1
Natural variantiVAR_071720428G → R in ARSEGS; phenotype with prominent levodopa-responsive myoconus-dystonia (M-D). 2 Publications1
Natural variantiVAR_072883441R → P in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs367874223dbSNPEnsembl.1
Natural variantiVAR_072884467S → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 2 Publications1
Natural variantiVAR_072885492P → L in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs767635052dbSNPEnsembl.1
Natural variantiVAR_014032494T → M in ARSEGS; parkinsonian symptoms in infancy; no effect on tyrosine hydroxylase activity. 2 PublicationsCorresponds to variant rs45471299dbSNPEnsembl.1
Natural variantiVAR_072886498D → G in ARSEGS; loss of over 80% of tyrosine hydroxylase activity. 4 PublicationsCorresponds to variant rs771351747dbSNPEnsembl.1
Natural variantiVAR_014033499V → M.1 PublicationCorresponds to variant rs1800033dbSNPEnsembl.1
Natural variantiVAR_072887510L → Q in ARSEGS; complete loss of tyrosine hydroxylase activity. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00054431 – 61Missing in isoform 2 and isoform 6. 3 PublicationsAdd BLAST31
Alternative sequenceiVSP_00054331 – 34Missing in isoform 1. 1 Publication4
Alternative sequenceiVSP_00054135 – 61Missing in isoform 4 and isoform 5. 2 PublicationsAdd BLAST27
Alternative sequenceiVSP_054338264 – 357Missing in isoform 5 and isoform 6. 1 PublicationAdd BLAST94

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17589 mRNA. Translation: AAA61179.1.
X05290 mRNA. Translation: CAA28908.1.
Y00414 mRNA. Translation: CAA68472.1.
DQ677336 mRNA. Translation: ABG73364.1.
DQ677337 mRNA. Translation: ABG73365.1.
AC132217 Genomic DNA. No translation available.
M24791, M24787, M24789 Genomic DNA. Translation: AAA61173.1. Sequence problems.
CH471158 Genomic DNA. Translation: EAX02493.1.
BC104967 mRNA. Translation: AAI04968.1.
BC143611 mRNA. Translation: AAI43612.1.
BC143614 mRNA. Translation: AAI43615.1.
M24791, M24787 Genomic DNA. Translation: AAA61170.1.
M20911 mRNA. Translation: AAA61167.1.
CCDSiCCDS31338.1. [P07101-2]
CCDS7730.1. [P07101-3]
CCDS7731.1. [P07101-1]
PIRiA30002. WHHUY4.
RefSeqiNP_000351.2. NM_000360.3. [P07101-3]
NP_954986.2. NM_199292.2. [P07101-1]
NP_954987.2. NM_199293.2. [P07101-2]
XP_011518637.1. XM_011520335.2. [P07101-4]
UniGeneiHs.435609.

Genome annotation databases

EnsembliENST00000333684; ENSP00000328814; ENSG00000180176. [P07101-6]
ENST00000352909; ENSP00000325951; ENSG00000180176. [P07101-3]
ENST00000381175; ENSP00000370567; ENSG00000180176. [P07101-2]
ENST00000381178; ENSP00000370571; ENSG00000180176. [P07101-1]
GeneIDi7054.
KEGGihsa:7054.
UCSCiuc001lvp.3. human. [P07101-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Tyrosine hydroxylase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M17589 mRNA. Translation: AAA61179.1.
X05290 mRNA. Translation: CAA28908.1.
Y00414 mRNA. Translation: CAA68472.1.
DQ677336 mRNA. Translation: ABG73364.1.
DQ677337 mRNA. Translation: ABG73365.1.
AC132217 Genomic DNA. No translation available.
M24791, M24787, M24789 Genomic DNA. Translation: AAA61173.1. Sequence problems.
CH471158 Genomic DNA. Translation: EAX02493.1.
BC104967 mRNA. Translation: AAI04968.1.
BC143611 mRNA. Translation: AAI43612.1.
BC143614 mRNA. Translation: AAI43615.1.
M24791, M24787 Genomic DNA. Translation: AAA61170.1.
M20911 mRNA. Translation: AAA61167.1.
CCDSiCCDS31338.1. [P07101-2]
CCDS7730.1. [P07101-3]
CCDS7731.1. [P07101-1]
PIRiA30002. WHHUY4.
RefSeqiNP_000351.2. NM_000360.3. [P07101-3]
NP_954986.2. NM_199292.2. [P07101-1]
NP_954987.2. NM_199293.2. [P07101-2]
XP_011518637.1. XM_011520335.2. [P07101-4]
UniGeneiHs.435609.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2XSNX-ray2.68A/B/C/D193-528[»]
4J6SX-ray3.08E/F/G/H1-74[»]
ProteinModelPortaliP07101.
SMRiP07101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112912. 13 interactors.
IntActiP07101. 10 interactors.
MINTiMINT-198913.
STRINGi9606.ENSP00000370571.

Chemistry databases

BindingDBiP07101.
ChEMBLiCHEMBL1969.
DrugBankiDB00120. L-Phenylalanine.
DB00135. L-Tyrosine.
DB00765. Metyrosine.
DB00360. Tetrahydrobiopterin.

PTM databases

iPTMnetiP07101.
PhosphoSitePlusiP07101.

Polymorphism and mutation databases

BioMutaiTH.
DMDMi239938945.

Proteomic databases

PaxDbiP07101.
PeptideAtlasiP07101.
PRIDEiP07101.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000333684; ENSP00000328814; ENSG00000180176. [P07101-6]
ENST00000352909; ENSP00000325951; ENSG00000180176. [P07101-3]
ENST00000381175; ENSP00000370567; ENSG00000180176. [P07101-2]
ENST00000381178; ENSP00000370571; ENSG00000180176. [P07101-1]
GeneIDi7054.
KEGGihsa:7054.
UCSCiuc001lvp.3. human. [P07101-1]

Organism-specific databases

CTDi7054.
DisGeNETi7054.
GeneCardsiTH.
GeneReviewsiTH.
H-InvDBHIX0035928.
HGNCiHGNC:11782. TH.
HPAiCAB002522.
CAB072340.
HPA061003.
MalaCardsiTH.
MIMi191290. gene.
605407. phenotype.
neXtProtiNX_P07101.
OpenTargetsiENSG00000180176.
Orphaneti101150. Autosomal recessive dopa-responsive dystonia.
PharmGKBiPA351.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3820. Eukaryota.
COG3186. LUCA.
GeneTreeiENSGT00390000010268.
HOGENOMiHOG000233373.
HOVERGENiHBG006841.
InParanoidiP07101.
KOiK00501.
OMAiPHLEYFV.
OrthoDBiEOG091G05MZ.
PhylomeDBiP07101.
TreeFamiTF313327.

Enzyme and pathway databases

UniPathwayiUPA00747; UER00733.
BRENDAi1.14.16.2. 2681.
ReactomeiR-HSA-209905. Catecholamine biosynthesis.
SIGNORiP07101.

Miscellaneous databases

GeneWikiiTyrosine_hydroxylase.
GenomeRNAii7054.
PROiP07101.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180176.
CleanExiHS_TH.
ExpressionAtlasiP07101. baseline and differential.
GenevisibleiP07101. HS.

Family and domain databases

Gene3Di1.10.800.10. 1 hit.
InterProiIPR001273. 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.
[Graphical view]
PANTHERiPTHR11473. PTHR11473. 2 hits.
PfamiPF00351. Biopterin_H. 1 hit.
PF12549. TOH_N. 3 hits.
[Graphical view]
PIRSFiPIRSF000336. TH. 1 hit.
PRINTSiPR00372. FYWHYDRXLASE.
SUPFAMiSSF56534. SSF56534. 1 hit.
TIGRFAMsiTIGR01269. Tyr_3_monoox. 1 hit.
PROSITEiPS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTY3H_HUMAN
AccessioniPrimary (citable) accession number: P07101
Secondary accession number(s): B7ZL70
, B7ZL73, Q0PWM2, Q0PWM3, Q15585, Q15588, Q15589, Q2M3B4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: June 16, 2009
Last modified: November 30, 2016
This is version 193 of the entry and version 5 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.