[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). DOI=10.1016/0006-291X(87)90742-X; PubMed=2887169 [NCBI, ExPASy, EBI, Israel, Japan] Kaneda N., Kobayashi K., Ichinose H., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., Nagatsu T.; "Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene."; Biochem. Biophys. Res. Commun. 146:971-975(1987).
[2]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING. DOI=10.1038/326707a0; PubMed=2882428 [NCBI, ExPASy, EBI, Israel, Japan] Grima B., Lamouroux A., Boni C., Julien J.-F., Javoy-Agid F., Mallet J.; "A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics."; Nature 326:707-711(1987).
[3]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). DOI=10.1093/nar/15.16.6733; PubMed=2888085 [NCBI, ExPASy, EBI, Israel, Japan] Kobayashi K., Kaneda N., Ichinose H., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., Nagatsu T.; "Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3."; Nucleic Acids Res. 15:6733-6733(1987).
[4]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING. PubMed=2902075 [NCBI, ExPASy, EBI, Israel, Japan] Kobayashi K., Kaneda N., Ichinose H., Kishi F., Nakazawa A., Kurosawa Y., Fujita K., Nagatsu T.; "Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types."; J. Biochem. 103:907-912(1988).
[5]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. DOI=10.1038/nature04632; PubMed=16554811 [NCBI, ExPASy, EBI, Israel, Japan] Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.; "Human chromosome 11 DNA sequence and analysis including novel gene identification."; Nature 440:497-500(2006).
[6]	PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1111/j.1471-4159.1988.tb03009.x; PubMed=2892893 [NCBI, ExPASy, EBI, Israel, Japan] le Bourdelles B., Boularand S., Boni C., Horellou P., Dumas S., Grima B., Mallet J.; "Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms."; J. Neurochem. 50:988-991(1988).
[7]	NUCLEOTIDE SEQUENCE [MRNA] OF 1-30. PubMed=2896667 [NCBI, ExPASy, EBI, Israel, Japan] Ginns E.I., Rehavi M., Martin B.M., Weller M., O'Malley K.L., Lamarca M.E., McAllister C.G., Paul S.M.; "Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector."; J. Biol. Chem. 263:7406-7410(1988).
[8]	VARIANT ARDRD LYS-412. DOI=10.1007/BF00225091; PubMed=7814018 [NCBI, ExPASy, EBI, Israel, Japan] Luedecke B., Dworniczak B., Bartholome K.; "A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome."; Hum. Genet. 95:123-125(1995).
[9]	VARIANT MET-112. DOI=10.1007/BF00209496; PubMed=7789962 [NCBI, ExPASy, EBI, Israel, Japan] Luedecke B., Bartholome K.; "Frequent sequence variant in the human tyrosine hydroxylase gene."; Hum. Genet. 95:716-716(1995).
[10]	CHARACTERIZATION OF VARIANT ARDRD LYS-412. DOI=10.1093/hmg/4.7.1209; PubMed=8528210 [NCBI, ExPASy, EBI, Israel, Japan] Knappskog P.M., Flatmark T., Mallet J., Luedecke B., Bartholome K.; "Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene."; Hum. Mol. Genet. 4:1209-1212(1995).
[11]	CHARACTERIZATION OF VARIANT ARDRD PRO-236. DOI=10.1093/hmg/5.7.1023; PubMed=8817341 [NCBI, ExPASy, EBI, Israel, Japan] Luedecke B., Knappskog P.M., Clayton P.T., Surtees R.A.H., Clelland J.D., Heales S.J.R., Brand M.P., Bartholome K., Flatmark T.; "Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene."; Hum. Mol. Genet. 5:1023-1028(1996).
[12]	VARIANT ARDRD PRO-236, AND VARIANT MET-112. DOI=10.1002/(SICI)1096-8628(19980328)81:2<131::AID-AJMG2>3.3.CO;2-X; PubMed=9613851 [NCBI, ExPASy, EBI, Israel, Japan] Kunugi H., Kawada Y., Hattori M., Ueki A., Otsuka M., Nanko S.; "Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease."; Am. J. Med. Genet. 81:131-133(1998).
[13]	VARIANT MET-499. DOI=10.1002/(SICI)1096-8628(19980907)81:5<388::AID-AJMG7>3.3.CO;2-F; PubMed=9754624 [NCBI, ExPASy, EBI, Israel, Japan] Ishiguro H., Arinami T., Saito T., Akazawa S., Enomoto M., Mitushio H., Fujishiro H., Tada K., Akimoto Y., Mifune H., Shiozuka S., Hamaguchi H., Toru M., Shibuya H.; "Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism."; Am. J. Med. Genet. 81:388-396(1998).
[14]	VARIANT ARDRD HIS-233. DOI=10.1007/s004390050756; PubMed=9703425 [NCBI, ExPASy, EBI, Israel, Japan] van den Heuvel L.P.W.J., Luiten B., Smeitink J.A.M., de Rijk-van Andel J.F., Hyland K., Steenbergen-Spanjers G.C.H., Janssen R.J.T., Wevers R.A.; "A common point mutation in the tyrosine hydroxylase gene in autosomal recessive L-DOPA-responsive dystonia in the Dutch population."; Hum. Genet. 102:644-646(1998).
[15]	VARIANT MET-112. DOI=10.1038/10290; PubMed=10391209 [NCBI, ExPASy, EBI, Israel, Japan] Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; "Characterization of single-nucleotide polymorphisms in coding regions of human genes."; Nat. Genet. 22:231-238(1999).
[16]	ERRATUM. Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; Nat. Genet. 23:373-373(1999).
[17]	VARIANTS ARDRD PRO-276; MET-314; HIS-337 AND MET-494. DOI=10.1046/j.1469-1809.2000.6410025.x; PubMed=11246459 [NCBI, ExPASy, EBI, Israel, Japan] Swaans R.J.M., Rondot P., Renier W.O., Van Den Heuvel L.P.W.J., Steenbergen-Spanjers G.C.H., Wevers R.A.; "Four novel mutations in the tyrosine hydroxylase gene in patients with infantile parkinsonism."; Ann. Hum. Genet. 64:25-31(2000).

Comments

FUNCTION: Plays an important role in the physiology of adrenergic neurons.
CATALYTIC ACTIVITY: L-tyrosine + tetrahydrobiopterin + O₂ = 3,4-dihydroxy-L-phenylalanine + 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 .

ALTERNATIVE PRODUCTS: 4 named isoforms [FASTA] produced by alternative splicing.

Name	3
Isoform ID	P07101-1
This is the isoform sequence displayed in this entry.

Name	1
Isoform ID	P07101-2
Features which should be applied to build the isoform sequence: VSP_000543.

Name	2
Isoform ID	P07101-3
Features which should be applied to build the isoform sequence: VSP_000544.

Name	4
Isoform ID	P07101-4
Features which should be applied to build the isoform sequence: VSP_000541, VSP_000542.

TISSUE SPECIFICITY: Mainly expressed in the brain and adrenal glands.
DISEASE: Defects in TH are the cause of dystonia DOPA-responsive autosomal recessive (ARDRD) [MIM:605407]; also known as autosomal recessive Segawa syndrome. ARDRD is 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 of ARDRD 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.
SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=TH";.
WEB RESOURCE: Name=Wikipedia; Note=Tyrosine hydroxylase entry; URL="http://en.wikipedia.org/wiki/Tyrosine_hydroxylase";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M17589; AAA61179.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X05290; CAA28908.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Y00414; CAA68472.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AC132217; -; NOT_ANNOTATED_CDS; Genomic_DNA.	[EMBL / GenBank / DDBJ]
M24791; AAA61173.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M24787; AAA61173.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M24789; AAA61173.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M24791; AAA61170.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M24787; AAA61170.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
M20911; AAA61167.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00010178; -.
IPI00218275; -.
IPI00218276; -.
IPI00398179; -.

A30002; WHHUY4.

NP_000351.2; -.

3D structure databases

HSSP

P04177; 1TOH. [HSSP ENTRY / PDB]

SMR

P07101; 192-526, 193-527.

ModBase

P07101.

PTM databases

PhosphoSite

P07101; -.

Enzyme and pathway databases

BRENDA

1.14.16.2; 247.

Pathway_Interaction_DB

alphasynuclein_pathway; Alpha-synuclein signaling.
p38_mk2pathway; p38 signaling mediated by MAPKAP kinases.

Organism-specific databases

GC11M002141; -.

HIX0035928; -.

HGNC:11782; TH.

TH.

CAB002522; -.

191290; gene. [NCBI / EBI]
605407; phenotype. [NCBI / EBI]

Orphanet

255; Dystonia, dopa-responsive.
101150; Dystonia, dopa-responsive, autosomal recessive.

PharmGKB

PA27004; -.

Gene expression databases

P07101; -.

P07101; -.

HS_TH; -.

ENSG00000180176; Homo sapiens.

Ontologies

GO:0009898;	Cellular component: internal side of plasma membrane (inferred from direct assay from UniProtKB).
GO:0033162;	Cellular component: melanosome membrane (inferred from direct assay from UniProtKB).
GO:0043005;	Cellular component: neuron projection (inferred from direct assay from UniProtKB).
GO:0005634;	Cellular component: nucleus (inferred from sequence or structural similarity from UniProtKB).
GO:0043204;	Cellular component: perikaryon (inferred from sequence or structural similarity from UniProtKB).
GO:0005790;	Cellular component: smooth endoplasmic reticulum (inferred from direct assay from UniProtKB).
GO:0005506;	Molecular function: iron ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0004511;	Molecular function: tyrosine 3-monooxygenase activity (inferred from direct assay from UniProtKB).
GO:0006585;	Biological process: dopamine biosynthetic process from tyrosine (non-traceable author statement from UniProtKB).
GO:0048596;	Biological process: embryonic camera-type eye morphogenesis (inferred from sequence or structural similarity from UniProtKB).
GO:0042418;	Biological process: epinephrine biosynthetic process (inferred from direct assay from UniProtKB).
GO:0042462;	Biological process: eye photoreceptor cell development (inferred from sequence or structural similarity from UniProtKB).
GO:0003007;	Biological process: heart morphogenesis (non-traceable author statement from UniProtKB).
GO:0007612;	Biological process: learning (inferred from sequence or structural similarity from UniProtKB).
GO:0007626;	Biological process: locomotory behavior (inferred from sequence or structural similarity from UniProtKB).
GO:0007613;	Biological process: memory (inferred from sequence or structural similarity from UniProtKB).
GO:0042136;	Biological process: neurotransmitter biosynthetic process (inferred from electronic annotation from UniProtKB-KW).
GO:0042421;	Biological process: norepinephrine biosynthetic process (inferred from direct assay from UniProtKB).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0043473;	Biological process: pigmentation (traceable author statement from UniProtKB).
GO:0008016;	Biological process: regulation of heart contraction (inferred from sequence or structural similarity from UniProtKB).
GO:0045471;	Biological process: response to ethanol (inferred from direct assay from UniProtKB).
GO:0001666;	Biological process: response to hypoxia (inferred from direct assay from UniProtKB).
GO:0001963;	Biological process: synaptic transmission, dopaminergic (inferred from sequence or structural similarity from UniProtKB).
GO:0007601;	Biological process: visual perception (inferred from sequence or structural similarity from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR001273; ArAA_hydroxylase.
IPR018301; ArAA_hydroxylase_Fe/CU_BS.
IPR019774; Aromatic-AA_hydroxylase_C.
IPR005962; Tyr_3_mOase.
IPR019773; Tyrosine_3-monooxygenase-like.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.800.10; Aaa_hydroxylase; 1.

PANTHER

PTHR11473; Aaa_hydroxylase; 1.

Pfam

PF00351; Biopterin_H; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000336; TH; 1.

PRINTS

PR00372; FYWHYDRXLASE.

ProDom

PD002559; Aaa_hydroxylase; 1.
[Domain structure / List of seq. sharing at least 1 domain]

TIGRFAMs

TIGR01269; Tyr_3_monoox; 1.

PROSITE

PS00367; BIOPTERIN_HYDROXYL; 1.

Proteomic databases

PRIDE

P07101; -.

Genome annotation databases

Ensembl

ENSG00000180176; Homo sapiens. [Contig view]

GeneID

7054; -.

KEGG

hsa:7054; -.

Phylogenomic databases

HOGENOM

P07101; -.

HOVERGEN

P07101; -.

Other

DrugBank

DB00120; L-Phenylalanine.
DB00135; L-Tyrosine.
DB00765; Metyrosine.
DB00360; Tetrahydrobiopterin.

27583; -.

TH; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Catecholamine biosynthesis; Disease mutation; Dystonia; Iron; Metal-binding; Monooxygenase; Neurotransmitter biosynthesis; Oxidoreductase; Parkinsonism; Phosphoprotein; Polymorphism.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed (By similarity).`
`CHAIN`	`2 528`	`527`	`Tyrosine 3-monooxygenase.`	`PRO_0000205561`
`COMPBIAS`	`85 90`	`6`	`Poly-Ala.`
`METAL`	`361 361`		`Iron (By similarity).`
`METAL`	`366 366`		`Iron (By similarity).`
`METAL`	`406 406`		`Iron (By similarity).`
`MOD_RES`	`19 19`		`Phosphoserine (By similarity).`
`MOD_RES`	`62 62`		`Phosphoserine (By similarity).`
`MOD_RES`	`71 71`		`Phosphoserine; by PKA (By similarity).`
`VAR_SEQ`	`1 33`		`Missing (in isoform 4).`	`VSP_000541`
`VAR_SEQ`	`31 61`		`Missing (in isoform 2).`	`VSP_000544`
`VAR_SEQ`	`31 34`		`Missing (in isoform 1).`	`VSP_000543`
`VAR_SEQ`	`34 34`		`Q -> M (in isoform 4).`	`VSP_000542`
`VARIANT`	`112 112`	`1`	`V -> M (common polymorphism; dbSNP:rs6356 [NCBI]).`	`VAR_014025`
`VARIANT`	`233 233`	`1`	`R -> H (in ARDRD).`	`VAR_014026 [3D]`
`VARIANT`	`236 236`	`1`	`L -> P (in ARDRD; severe parkinsonian symptoms in early infancy; strongly reduced stability and catalytic activity; rare mutation).`	`VAR_014027 [3D]`
`VARIANT`	`276 276`	`1`	`T -> P (in ARDRD; parkinsonian symptoms in infancy; dbSNP:rs28934581 [NCBI]).`	`VAR_014028 [3D]`
`VARIANT`	`314 314`	`1`	`T -> M (in ARDRD; parkinsonian symptoms in infancy).`	`VAR_014029 [3D]`
`VARIANT`	`337 337`	`1`	`R -> H (in ARDRD; parkinsonian symptoms in infancy; dbSNP:rs28934580 [NCBI]).`	`VAR_014030 [3D]`
`VARIANT`	`412 412`	`1`	`Q -> K (in ARDRD; reduced affinity for L-tyrosine).`	`VAR_014031 [3D]`
`VARIANT`	`494 494`	`1`	`T -> M (in ARDRD; parkinsonian symptoms in infancy; dbSNP:rs45471299 [NCBI]).`	`VAR_014032 [3D]`
`VARIANT`	`499 499`	`1`	`V -> M (in dbSNP:rs1800033 [NCBI]).`	`VAR_014033 [3D]`
`CONFLICT`	`401 401`		`Y -> S (in Ref. 1; AAA61179, 2; CAA28908 and 3; CAA68472).`

Sequence information

Length: 528 AA [This is the length of the unprocessed precursor]

Molecular weight: 58600 Da [This is the MW of the unprocessed precursor]

CRC64: 31D2D49955ACF070 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MPTPDATTPQ AKGFRRAVSE LDAKQAEAIM VRGQGAPGPS LTGSPWPGTA APAASYTPTP 

        70         80         90        100        110        120 
RSPRFIGRRQ SLIEDARKER EAAVAAAAAA VPSEPGDPLE AVAFEEKEGK AVLNLLFSPR 

       130        140        150        160        170        180 
ATKPSALSRA VKVFETFEAK IHHLETRPAQ RPRAGGPHLE YFVRLEVRRG DLAALLSGVR 

       190        200        210        220        230        240 
QVSEDVRSPA GPKVPWFPRK VSELDKCHHL VTKFDPDLDL DHPGFSDQVY RQRRKLIAEI 

       250        260        270        280        290        300 
AFQYRHGDPI PRVEYTAEEI ATWKEVYTTL KGLYATHACG EHLEAFALLE RFSGYREDNI 

       310        320        330        340        350        360 
PQLEDVSRFL KERTGFQLRP VAGLLSARDF LASLAFRVFQ CTQYIRHASS PMHSPEPDCC 

       370        380        390        400        410        420 
HELLGHVPML ADRTFAQFSQ DIGLASLGAS DEEIEKLSTL YWFTVEFGLC KQNGEVKAYG 

       430        440        450        460        470        480 
AGLLSSYGEL LHCLSEEPEI RAFDPEAAAV QPYQDQTYQS VYFVSESFSD AKDKLRSYAS 

       490        500        510        520 
RIQRPFSVKF DPYTLAIDVL DSPQAVRRSL EGVQDELDTL AHALSAIG

P07101 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools