TY3H_CAEEL
ID TY3H_CAEEL Reviewed; 519 AA.
AC P90986; E7EM31; F2WZ21; Q5R3Y3; Q5R3Y4;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 4.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Tyrosine 3-monooxygenase;
DE EC=1.14.16.2 {ECO:0000269|PubMed:21087208};
DE AltName: Full=Abnormal catecholamine distribution protein 2;
DE AltName: Full=Tyrosine 3-hydroxylase;
DE Short=TH;
GN Name=cat-2 {ECO:0000312|WormBase:B0432.5c};
GN ORFNames=B0432.5 {ECO:0000312|WormBase:B0432.5c};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND PHOSPHORYLATION AT SER-35.
RC STRAIN=Bristol N2;
RX PubMed=21087208; DOI=10.1042/bj20101561;
RA Calvo A.C., Pey A.L., Miranda-Vizuete A., Doskeland A.P., Martinez A.;
RT "Divergence in enzyme regulation between Caenorhabditis elegans and human
RT tyrosine hydroxylase, the key enzyme in the synthesis of dopamine.";
RL Biochem. J. 434:133-141(2011).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=10572056; DOI=10.1242/dev.126.24.5819;
RA Lints R., Emmons S.W.;
RT "Patterning of dopaminergic neurotransmitter identity among Caenorhabditis
RT elegans ray sensory neurons by a TGFbeta family signaling pathway and a Hox
RT gene.";
RL Development 126:5819-5831(1999).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14739932; DOI=10.1038/sj.emboj.7600057;
RA Sanyal S., Wintle R.F., Kindt K.S., Nuttley W.M., Arvan R., Fitzmaurice P.,
RA Bigras E., Merz D.C., Hebert T.E., van der Kooy D., Schafer W.R.,
RA Culotti J.G., Van Tol H.H.;
RT "Dopamine modulates the plasticity of mechanosensory responses in
RT Caenorhabditis elegans.";
RL EMBO J. 23:473-482(2004).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=14762140; DOI=10.1523/jneurosci.1569-03.2004;
RA Hills T., Brockie P.J., Maricq A.V.;
RT "Dopamine and glutamate control area-restricted search behavior in
RT Caenorhabditis elegans.";
RL J. Neurosci. 24:1217-1225(2004).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=17559503; DOI=10.1111/j.1474-9726.2007.00303.x;
RA Murakami H., Murakami S.;
RT "Serotonin receptors antagonistically modulate Caenorhabditis elegans
RT longevity.";
RL Aging Cell 6:483-488(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17268620; DOI=10.1039/b613414a;
RA Qin J., Wheeler A.R.;
RT "Maze exploration and learning in C. elegans.";
RL Lab. Chip 7:186-192(2007).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17196529; DOI=10.1016/j.neuron.2006.11.015;
RA Ferkey D.M., Hyde R., Haspel G., Dionne H.M., Hess H.A., Suzuki H.,
RA Schafer W.R., Koelle M.R., Hart A.C.;
RT "C. elegans G protein regulator RGS-3 controls sensitivity to sensory
RT stimuli.";
RL Neuron 53:39-52(2007).
RN [9]
RP DISRUPTION PHENOTYPE.
RX PubMed=19545409; DOI=10.1186/1471-2202-10-62;
RA Brown M.K., Luo Y.;
RT "Bilobalide modulates serotonin-controlled behaviors in the nematode
RT Caenorhabditis elegans.";
RL BMC Neurosci. 10:62-62(2009).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF 276-GLN--MET-519.
RX PubMed=19609300; DOI=10.1038/emboj.2009.194;
RA Suo S., Culotti J.G., Van Tol H.H.;
RT "Dopamine counteracts octopamine signalling in a neural circuit mediating
RT food response in C. elegans.";
RL EMBO J. 28:2437-2448(2009).
RN [11]
RP ROLE IN SWIMMING-INDUCED PARALYSIS, AND MUTAGENESIS OF 276-GLN--MET-519.
RX PubMed=20410438; DOI=10.1124/mol.109.062703;
RA Carvelli L., Matthies D.S., Galli A.;
RT "Molecular mechanisms of amphetamine actions in Caenorhabditis elegans.";
RL Mol. Pharmacol. 78:151-156(2010).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF 276-GLN--MET-519.
RX PubMed=23166505; DOI=10.1371/journal.pgen.1003015;
RA Correa P., LeBoeuf B., Garcia L.R.;
RT "C. elegans dopaminergic D2-like receptors delimit recurrent cholinergic-
RT mediated motor programs during a goal-oriented behavior.";
RL PLoS Genet. 8:E1003015-E1003015(2012).
CC -!- FUNCTION: Involved in the synthesis of catecholamines, such as
CC dopamine. Has a role in serotonin signaling. Required for normal
CC explorative and foraging behavior. In response to food, involved in
CC promoting the dopamine-mediated suppression of crh-1/CREB1
CC transcription factor activation in cholinergic SIA neurons
CC (PubMed:19609300). Modulates male mating behavior by controlling the
CC protrusion of copulatory spicules from the tail of males during
CC hermaphrodite vulval location (PubMed:23166505).
CC {ECO:0000269|PubMed:14739932, ECO:0000269|PubMed:14762140,
CC ECO:0000269|PubMed:17196529, ECO:0000269|PubMed:17268620,
CC ECO:0000269|PubMed:19609300, ECO:0000269|PubMed:23166505}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tyrosine + O2 =
CC (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + L-dopa;
CC Xref=Rhea:RHEA:18201, ChEBI:CHEBI:15379, ChEBI:CHEBI:15642,
CC ChEBI:CHEBI:57504, ChEBI:CHEBI:58315, ChEBI:CHEBI:59560;
CC EC=1.14.16.2; Evidence={ECO:0000269|PubMed:21087208};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC -!- ACTIVITY REGULATION: Inhibited by dopamine with an IC(50) of 32.6 uM
CC for the unphosphorylated form and 43.4 uM for the phosphorylated form
CC (PubMed:21087208). Phosphorylation leads to an increase in the
CC catalytic activity (By similarity). {ECO:0000250|UniProtKB:P07101,
CC ECO:0000269|PubMed:21087208}.
CC -!- PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine
CC from L-tyrosine: step 1/2.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P24529}. Cell projection, axon
CC {ECO:0000250|UniProtKB:P24529}. Note=Expressed in dopaminergic axons
CC and axon terminals. {ECO:0000250|UniProtKB:P24529}.
CC -!- TISSUE SPECIFICITY: Expressed in dopaminergic cells. Expressed in
CC neurons in the head and middle body of the hermaphrodite, and six
CC neurons in the tail of the male. {ECO:0000269|PubMed:10572056}.
CC -!- DISRUPTION PHENOTYPE: Reduced (30-40% of wild type) level of dopamine
CC thought to be due to defects in dopamine synthesis. Defects in
CC serotonin signaling. Affects mechanosensory behavior including foraging
CC and exploration activity. Hypersensitivity to odorants. Blocks the
CC enhanced slowing response phenotype caused by bilobalide, a
CC neuroprotective plant chemical. No significant effect on lifespan.
CC {ECO:0000269|PubMed:14739932, ECO:0000269|PubMed:14762140,
CC ECO:0000269|PubMed:17196529, ECO:0000269|PubMed:17268620,
CC ECO:0000269|PubMed:17559503, ECO:0000269|PubMed:19545409}.
CC -!- MISCELLANEOUS: Plays a role in promoting amphetamine-induced loss of
CC motility in water, termed swimming-induced paralysis.
CC {ECO:0000269|PubMed:20410438}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; HQ268827; ADZ54165.1; -; Genomic_DNA.
DR EMBL; BX284602; CCD61947.1; -; Genomic_DNA.
DR PIR; T25453; T25453.
DR RefSeq; NP_001254009.1; NM_001267080.1.
DR AlphaFoldDB; P90986; -.
DR SMR; P90986; -.
DR STRING; 6239.B0432.5a; -.
DR iPTMnet; P90986; -.
DR PaxDb; P90986; -.
DR PeptideAtlas; P90986; -.
DR PRIDE; P90986; -.
DR EnsemblMetazoa; B0432.5c.1; B0432.5c.1; WBGene00000296.
DR GeneID; 173411; -.
DR UCSC; B0432.5a; c. elegans.
DR CTD; 173411; -.
DR WormBase; B0432.5c; CE45548; WBGene00000296; cat-2.
DR eggNOG; KOG3820; Eukaryota.
DR InParanoid; P90986; -.
DR PhylomeDB; P90986; -.
DR Reactome; R-CEL-209905; Catecholamine biosynthesis.
DR UniPathway; UPA00747; UER00733.
DR PRO; PR:P90986; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00000296; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; P90986; baseline and differential.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043204; C:perikaryon; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004511; F:tyrosine 3-monooxygenase activity; IDA:WormBase.
DR GO; GO:0071419; P:cellular response to amphetamine; IMP:UniProtKB.
DR GO; GO:0042416; P:dopamine biosynthetic process; IDA:WormBase.
DR GO; GO:0006585; P:dopamine biosynthetic process from tyrosine; IMP:WormBase.
DR GO; GO:0046959; P:habituation; IMP:WormBase.
DR GO; GO:0007638; P:mechanosensory behavior; IMP:WormBase.
DR GO; GO:0090327; P:negative regulation of locomotion involved in locomotory behavior; IMP:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:1902437; P:positive regulation of male mating behavior; IMP:UniProtKB.
DR GO; GO:0040012; P:regulation of locomotion; IMP:WormBase.
DR GO; GO:0032094; P:response to food; IMP:WormBase.
DR GO; GO:0034609; P:spicule insertion; IMP:UniProtKB.
DR GO; GO:0034607; P:turning behavior involved in mating; IMP:WormBase.
DR CDD; cd03345; eu_TyrOH; 1.
DR Gene3D; 1.10.800.10; -; 1.
DR InterPro; IPR001273; ArAA_hydroxylase.
DR InterPro; IPR018301; ArAA_hydroxylase_Fe/CU_BS.
DR InterPro; IPR036951; ArAA_hydroxylase_sf.
DR InterPro; IPR036329; Aro-AA_hydroxylase_C_sf.
DR InterPro; IPR019774; Aromatic-AA_hydroxylase_C.
DR InterPro; IPR041903; Eu_TyrOH_cat.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF56534; SSF56534; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 1: Evidence at protein level;
KW Behavior; Catecholamine biosynthesis; Cell projection; Cytoplasm; Iron;
KW Metal-binding; Monooxygenase; Neurotransmitter biosynthesis;
KW Oxidoreductase; Phosphoprotein; Reference proteome.
FT CHAIN 1..519
FT /note="Tyrosine 3-monooxygenase"
FT /id="PRO_0000205565"
FT BINDING 347
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 352
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 392
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT MOD_RES 35
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:21087208"
FT MUTAGEN 276..519
FT /note="Missing: In e1112; spontaneously induces activation
FT of the crh-1/CREB1 transcription factor in cholinergic SIA
FT neurons in the absence and presence of food. Reduces
FT swimming-induced paralysis in response to amphetamine.
FT Defective male mating behavior."
FT /evidence="ECO:0000269|PubMed:19609300,
FT ECO:0000269|PubMed:20410438, ECO:0000269|PubMed:23166505"
FT CONFLICT 230
FT /note="F -> L (in Ref. 1; CCD61947)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 58828 MW; AF83716B43B932B8 CRC64;
MSSLTNNTFM EEEPRGVTVI ATKVAENSKN PRRYSLVHQA SCETQHHKGI RRQNTIQHRK
QLTDQMRCQK ILQQLNDEGI EVIFTANDVT PIEFSIILTS TDPTLSNFVS DILQNMSSAK
VQICHVETRG NEASHDVLLA CKATKNQLIH SAELLTQNHV ALTKFSIFAK KLSDEKNQSQ
IWFPRHISEL DQCSKCITKY EPTTDPRHPG HGDVAYIARR KFLNDQALEF KFGDEIGYVD
YTEEEHATWK AVYEKLGDLH LSHTCAVYRQ NLKILQEEKV LTADRIPQIR DVNKFLQKKT
GFELRPCSGL LSARDFLASL AFRVFQTTTY LRHHKSPHHS PEPDLIHELL GHVPMFSDPL
LAQMSQDIGL MSLGASDEHI EKLSTVYWFI VEFGLCKEDG KLKAIGAGLL SAYGELMHAC
SDAPEHKDFD PAVTAVQKYE DDDYQPLYFV ADSIHDALAK LRKYASSMDR PFSVVYDPFT
KSIEAIESSA DLEKAFSRLS NDLSAITHAA DRMKISITM
