TPH1_CHICK
ID TPH1_CHICK Reviewed; 445 AA.
AC P70080;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Tryptophan 5-hydroxylase 1;
DE EC=1.14.16.4 {ECO:0000250|UniProtKB:P17532};
DE AltName: Full=Tryptophan 5-monooxygenase 1;
GN Name=TPH1; Synonyms=TPH;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=White leghorn; TISSUE=Pineal gland;
RX PubMed=8915576; DOI=10.1016/s0169-328x(96)00104-0;
RA Florez J.C., Seidenman K.J., Barrett R.K., Sangoram A.M., Takahashi J.S.;
RT "Molecular cloning of chick pineal tryptophan hydroxylase and circadian
RT oscillation of its mRNA levels.";
RL Brain Res. Mol. Brain Res. 42:25-30(1996).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 101-414 IN COMPLEX WITH TRYPTOPHAN
RP AND IMIDAZOLE, SUBUNIT, AND IRON-BINDING SITES.
RX PubMed=18937498; DOI=10.1021/bi8015263;
RA Windahl M.S., Petersen C.R., Christensen H.E., Harris P.;
RT "Crystal structure of tryptophan hydroxylase with bound amino acid
RT substrate.";
RL Biochemistry 47:12087-12094(2008).
CC -!- FUNCTION: Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-
CC determining step of serotonin biosynthesis.
CC {ECO:0000250|UniProtKB:P17532}.
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:0000250|UniProtKB:P17532};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:18937498};
CC -!- PATHWAY: Aromatic compound metabolism; serotonin biosynthesis;
CC serotonin from L-tryptophan: step 1/2. {ECO:0000250|UniProtKB:P17532}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:18937498}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; U26428; AAC60036.1; -; mRNA.
DR RefSeq; NP_990287.1; NM_204956.1.
DR PDB; 3E2T; X-ray; 1.90 A; A=101-414.
DR PDBsum; 3E2T; -.
DR AlphaFoldDB; P70080; -.
DR SMR; P70080; -.
DR STRING; 9031.ENSGALP00000010070; -.
DR PaxDb; P70080; -.
DR GeneID; 395799; -.
DR KEGG; gga:395799; -.
DR CTD; 7166; -.
DR VEuPathDB; HostDB:geneid_395799; -.
DR eggNOG; KOG3820; Eukaryota.
DR HOGENOM; CLU_023198_0_1_1; -.
DR InParanoid; P70080; -.
DR PhylomeDB; P70080; -.
DR TreeFam; TF313327; -.
DR BRENDA; 1.14.16.4; 1306.
DR UniPathway; UPA00846; UER00799.
DR EvolutionaryTrace; P70080; -.
DR PRO; PR:P70080; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IBA:GO_Central.
DR GO; GO:0009072; P:aromatic amino acid family metabolic process; IEA:InterPro.
DR GO; GO:0002576; P:platelet degranulation; ISS:UniProtKB.
DR GO; GO:1900046; P:regulation of hemostasis; ISS:UniProtKB.
DR GO; GO:0042427; P:serotonin biosynthetic process; ISS:UniProtKB.
DR CDD; cd03346; eu_TrpOH; 1.
DR Gene3D; 1.10.800.10; -; 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 PANTHER; PTHR11473; PTHR11473; 1.
DR Pfam; PF00351; Biopterin_H; 1.
DR PIRSF; PIRSF000336; TH; 1.
DR PRINTS; PR00372; FYWHYDRXLASE.
DR SUPFAM; SSF55021; SSF55021; 1.
DR SUPFAM; SSF56534; SSF56534; 1.
DR TIGRFAMs; TIGR01270; Trp_5_monoox; 1.
DR PROSITE; PS51671; ACT; 1.
DR PROSITE; PS00367; BH4_AAA_HYDROXYL_1; 1.
DR PROSITE; PS51410; BH4_AAA_HYDROXYL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Serotonin biosynthesis.
FT CHAIN 1..445
FT /note="Tryptophan 5-hydroxylase 1"
FT /id="PRO_0000205572"
FT DOMAIN 19..94
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT BINDING 236
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 258
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 266
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 273
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 278
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 318
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 337
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:18937498"
FT BINDING 367
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:18937498"
FT MOD_RES 58
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT HELIX 113..117
FT /evidence="ECO:0007829|PDB:3E2T"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 140..155
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 169..189
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 192..196
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 215..226
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 239..247
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 250..253
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 285..298
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 303..314
FT /evidence="ECO:0007829|PDB:3E2T"
FT TURN 315..319
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 333..336
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 339..345
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 367..369
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 374..379
FT /evidence="ECO:0007829|PDB:3E2T"
FT HELIX 380..391
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:3E2T"
FT TURN 404..407
FT /evidence="ECO:0007829|PDB:3E2T"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:3E2T"
SQ SEQUENCE 445 AA; 51139 MW; FF0041D7C4B159F6 CRC64;
MIEDNKENKD HAPERGRTAI IFSLKNEVGG LVKALKLFQE KHVNLVHIES RKSKRRNSEF
EIFVDCDSNR EQLNEIFQLL KSHVSIVSMN PTEHFNVQED GDMENIPWYP KKISDLDKCA
NRVLMYGSDL DADHPGFKDN VYRKRRKYFA DLAMNYKHGD PIPEIEFTEE EIKTWGTVYR
ELNKLYPTHA CREYLKNLPL LTKYCGYRED NIPQLEDVSR FLKERTGFTI RPVAGYLSPR
DFLAGLAFRV FHCTQYVRHS SDPLYTPEPD TCHELLGHVP LLAEPSFAQF SQEIGLASLG
ASDEAVQKLA TCYFFTVEFG LCKQEGQLRV YGAGLLSSIS ELKHSLSGSA KVKPFDPKVT
CKQECLITTF QEVYFVSESF EEAKEKMREF AKTIKRPFGV KYNPYTQSVQ ILKDTKSIAS
VVNELRHELD IVSDALSKMG KQLEV
