ID H0X4B5_OTOGA Unreviewed; 445 AA.
AC H0X4B5;
DT 22-FEB-2012, integrated into UniProtKB/TrEMBL.
DT 22-FEB-2012, sequence version 1.
DT 27-MAR-2024, entry version 62.
DE RecName: Full=tryptophan 5-monooxygenase {ECO:0000256|ARBA:ARBA00012002};
DE EC=1.14.16.4 {ECO:0000256|ARBA:ARBA00012002};
GN Name=TPH1 {ECO:0000313|Ensembl:ENSOGAP00000010028.2};
OS Otolemur garnettii (Small-eared galago) (Garnett's greater bushbaby).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lorisiformes;
OC Galagidae; Otolemur.
OX NCBI_TaxID=30611 {ECO:0000313|Ensembl:ENSOGAP00000010028.2, ECO:0000313|Proteomes:UP000005225};
RN [1] {ECO:0000313|Proteomes:UP000005225}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG The Broad Institute Genome Sequencing Platform;
RA Di Palma F., Johnson J., Lander E.S., Lindblad-Toh K., Jaffe D.B.,
RA Gnerre S., MacCallum I., Przybylski D., Ribeiro F.J., Burton J.N.,
RA Walker B.J., Sharpe T., Hall G.;
RT "Version 3 of the genome sequence of Otolemur garnettii (Bushbaby).";
RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSOGAP00000010028.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-
CC determining step of serotonin biosynthesis.
CC {ECO:0000256|ARBA:ARBA00037406}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2
CC = (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin + 5-
CC hydroxy-L-tryptophan; Xref=Rhea:RHEA:16709, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15642, ChEBI:CHEBI:57912, ChEBI:CHEBI:58266,
CC ChEBI:CHEBI:59560; EC=1.14.16.4;
CC Evidence={ECO:0000256|ARBA:ARBA00001456};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000256|ARBA:ARBA00001954,
CC ECO:0000256|PIRSR:PIRSR601273-2};
CC -!- PATHWAY: Aromatic compound metabolism; serotonin biosynthesis;
CC serotonin from L-tryptophan: step 1/2. {ECO:0000256|ARBA:ARBA00004783}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000256|ARBA:ARBA00011881}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000256|ARBA:ARBA00009712}.
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DR EMBL; AAQR03002055; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; H0X4B5; -.
DR STRING; 30611.ENSOGAP00000010028; -.
DR Ensembl; ENSOGAT00000011203.2; ENSOGAP00000010028.2; ENSOGAG00000011200.2.
DR eggNOG; KOG3820; Eukaryota.
DR GeneTree; ENSGT00950000182885; -.
DR HOGENOM; CLU_023198_0_0_1; -.
DR InParanoid; H0X4B5; -.
DR OMA; SEVDMPW; -.
DR TreeFam; TF313327; -.
DR UniPathway; UPA00846; UER00799.
DR Proteomes; UP000005225; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IEA:UniProtKB-EC.
DR GO; GO:0009072; P:aromatic amino acid metabolic process; IEA:InterPro.
DR GO; GO:0046849; P:bone remodeling; IEA:Ensembl.
DR GO; GO:0060749; P:mammary gland alveolus development; IEA:Ensembl.
DR GO; GO:0002576; P:platelet degranulation; IEA:Ensembl.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:1900046; P:regulation of hemostasis; IEA:Ensembl.
DR GO; GO:0042427; P:serotonin biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd04929; ACT_TPH; 1.
DR CDD; cd03346; eu_TrpOH; 1.
DR Gene3D; 1.10.800.10; Aromatic amino acid hydroxylase; 1.
DR InterPro; IPR045865; ACT-like_dom_sf.
DR InterPro; IPR002912; ACT_dom.
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; IPR005963; Trp_5_mOase.
DR InterPro; IPR041904; TrpOH_cat.
DR InterPro; IPR019773; Tyrosine_3-monooxygenase-like.
DR NCBIfam; TIGR01270; Trp_5_monoox; 1.
DR PANTHER; PTHR11473; AROMATIC AMINO ACID HYDROXYLASE; 1.
DR PANTHER; PTHR11473:SF23; TRYPTOPHAN 5-HYDROXYLASE 1; 1.
DR Pfam; PF01842; ACT; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF55021; ACT-like; 1.
DR SUPFAM; SSF56534; Aromatic aminoacid monoxygenases, catalytic and oligomerization domains; 1.
DR PROSITE; PS51671; ACT; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 3: Inferred from homology;
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 Oxidoreductase {ECO:0000256|ARBA:ARBA00023002};
KW Reference proteome {ECO:0000313|Proteomes:UP000005225};
KW Serotonin biosynthesis {ECO:0000256|ARBA:ARBA00023094}.
FT DOMAIN 19..94
FT /note="ACT"
FT /evidence="ECO:0000259|PROSITE:PS51671"
FT DOMAIN 94..440
FT /note="Biopterin-dependent aromatic amino acid hydroxylase
FT family profile"
FT /evidence="ECO:0000259|PROSITE:PS51410"
FT BINDING 236
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 258
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 266
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 273
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 278
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 318
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 337
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 367
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
SQ SEQUENCE 445 AA; 51224 MW; 10CC8E607ED17C64 CRC64;
MIEDNKENKD HSLERGRATL IFSLRNEVGG LIRALKIFQE KHVNLLHIES RKSKRRNSEF
EIFVDCDINR EQLNDIFHLL KSHTNVLSVN PPDNFTVKED GNMETVPWFP KKISDLDHCA
NRVLMYGSEL DADHPGFKDN VYRKRRKYFA DLAMNYKHGD PIPKIEFTEE EIKTWGTVFR
ELNKLYPTHA CREYLKNLPL LSKYCGYRED NIPQLEDVSN FLRERTGFSI RPVAGYLSPR
DFLSGLAFRV FHCTQYVRHS SDPLYTPEPD TCHELLGHVP LLAEPSFAQF SQEIGLASLG
ASEEAVQKLA TCYFFTVEFG LCKQDGQLRV FGAGLLSSIS ELKHALSGHA KVKPFDPKIT
CKQECLITTF QDVYFVSESF EDAKEKMREF TKTMKRPFGV KYNPYTRSIQ ILKDTKSITS
AMDELRHDLD VISDALAKAS RQLSI
//