ID A0A8I6AXT4_RAT Unreviewed; 403 AA.
AC A0A8I6AXT4;
DT 25-MAY-2022, integrated into UniProtKB/TrEMBL.
DT 25-MAY-2022, sequence version 1.
DT 05-FEB-2025, entry version 16.
DE RecName: Full=Tyrosine 3-monooxygenase {ECO:0000256|ARBA:ARBA00017181};
DE EC=1.14.16.2 {ECO:0000256|ARBA:ARBA00011993};
DE AltName: Full=Tyrosine 3-hydroxylase {ECO:0000256|ARBA:ARBA00032379};
GN Name=Th {ECO:0000313|Ensembl:ENSRNOP00000093950.1,
GN ECO:0000313|RGD:3853};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000093950.1, ECO:0000313|Proteomes:UP000002494};
RN [1] {ECO:0000313|Ensembl:ENSRNOP00000093950.1, ECO:0000313|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000093950.1,
RC ECO:0000313|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RG Rat Genome Sequencing Project Consortium;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000313|Ensembl:ENSRNOP00000093950.1}
RP IDENTIFICATION.
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000093950.1};
RG Ensembl;
RL Submitted (OCT-2024) to UniProtKB.
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:0000256|ARBA:ARBA00033689};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18202;
CC Evidence={ECO:0000256|ARBA:ARBA00033689};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000256|ARBA:ARBA00001954,
CC ECO:0000256|PIRSR:PIRSR601273-2};
CC -!- PATHWAY: Catecholamine biosynthesis; dopamine biosynthesis; dopamine
CC from L-tyrosine: step 1/2. {ECO:0000256|ARBA:ARBA00004700}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000256|ARBA:ARBA00004556}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000256|ARBA:ARBA00009712}.
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DR Ensembl; ENSRNOT00000105945.1; ENSRNOP00000093950.1; ENSRNOG00000020410.6.
DR RGD; 3853; Th.
DR GeneTree; ENSGT00950000182885; -.
DR UniPathway; UPA00747; UER00733.
DR Proteomes; UP000002494; Chromosome 1.
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; IEA:InterPro.
DR GO; GO:0009072; P:aromatic amino acid metabolic process; IEA:InterPro.
DR GO; GO:0042416; P:dopamine biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd03345; eu_TyrOH; 1.
DR FunFam; 1.10.800.10:FF:000002; Tyrosine 3-monooxygenase; 1.
DR Gene3D; 3.30.70.260; -; 1.
DR Gene3D; 1.10.800.10; Aromatic amino acid hydroxylase; 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; IPR049321; TH_ACT.
DR InterPro; IPR005962; Tyr_3_mOase.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR NCBIfam; TIGR01269; Tyr_3_monoox; 1.
DR PANTHER; PTHR11473; AROMATIC AMINO ACID HYDROXYLASE; 1.
DR PANTHER; PTHR11473:SF18; TYROSINE 3-MONOOXYGENASE; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR Pfam; PF21417; TH_ACT; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF56534; Aromatic aminoacid monoxygenases, catalytic and oligomerization domains; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 3: Inferred from homology;
KW Catecholamine biosynthesis {ECO:0000256|ARBA:ARBA00022584};
KW Cytoplasm {ECO:0000256|ARBA:ARBA00022490};
KW Iron {ECO:0000256|ARBA:ARBA00023004, ECO:0000256|PIRSR:PIRSR000336-1};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR000336-1};
KW Monooxygenase {ECO:0000256|ARBA:ARBA00023033};
KW Neurotransmitter biosynthesis {ECO:0000256|ARBA:ARBA00022979};
KW Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Reference proteome {ECO:0000313|Proteomes:UP000002494}.
FT DOMAIN 57..403
FT /note="Biopterin-dependent aromatic amino acid hydroxylase
FT family profile"
FT /evidence="ECO:0000259|PROSITE:PS51410"
FT BINDING 236
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 241
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 281
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
SQ SEQUENCE 403 AA; 45947 MW; F172D8593C25170F CRC64;
MPTAERLVPE TFEAKIHHLE TRPAQRPLAG SPHLEYFVRF EVPSGDLAAL LSSVRRVSDD
VRSAREDKVP WFPRKVSELD KCHHLVTKFD PDLDLDHPGF SDQVYRQRRK LIAEIAFQYK
HGEPIPHVEY TAEEIATWKE VYVTLKGLYA THACREHLEG FQLLERYCGY REDSIPQLED
VSRFLKERTG FQLRPVAGLL SARDFLASLA FRVFQCTQYI RHASSPMHSP EPDCCHELLG
HVPMLADRTF AQFSQDIGLA SLGASDEEIE KLSTVYWFTV EFGLCKQNGE LKAYGAGLLS
SYGELLHSLS EEPEVRAFDP DTAAVQPYQD QTYQPVYFVS ESFNDAKDKL RNYASRIQRP
FSVKFDPYTL AIDVLDSPHT IQRSLEGVQD ELHTLAHALS AIS
//