ID Q1LUE3_DANRE Unreviewed; 473 AA.
AC Q1LUE3; A0A8M1PK25;
DT 30-MAY-2006, integrated into UniProtKB/TrEMBL.
DT 30-MAY-2006, sequence version 1.
DT 27-MAR-2024, entry version 113.
DE RecName: Full=Tryptophan 5-hydroxylase 2 {ECO:0000256|ARBA:ARBA00040889};
DE EC=1.14.16.4 {ECO:0000256|ARBA:ARBA00012002};
DE AltName: Full=Tryptophan 5-monooxygenase 2 {ECO:0000256|ARBA:ARBA00042662};
GN Name=tph2 {ECO:0000313|Ensembl:ENSDARP00000102919,
GN ECO:0000313|RefSeq:NP_999960.2, ECO:0000313|ZFIN:ZDB-GENE-040624-4};
GN Synonyms=tphR {ECO:0000313|RefSeq:NP_999960.2}, wu:fq15a04
GN {ECO:0000313|RefSeq:NP_999960.2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000313|Ensembl:ENSDARP00000102919};
RN [1] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=15281067; DOI=10.1002/neu.20023;
RA Teraoka H., Russell C., Regan J., Chandrasekhar A., Concha M.L.,
RA Yokoyama R., Higashi K., Take-Uchi M., Dong W., Hiraga T., Holder N.,
RA Wilson S.W.;
RT "Hedgehog and Fgf signaling pathways regulate the development of tphR-
RT expressing serotonergic raphe neurons in zebrafish embryos.";
RL J. Neurobiol. 60:275-288(2004).
RN [2] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=15652156; DOI=10.1016/j.bbaexp.2004.11.005;
RA Candy J., Collet C.;
RT "Two tyrosine hydroxylase genes in teleosts.";
RL Biochim. Biophys. Acta 1727:35-44(2005).
RN [3] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=15677724;
RA Norton W.H., Mangoli M., Lele Z., Pogoda H.M., Diamond B., Mercurio S.,
RA Russell C., Teraoka H., Stickney H.L., Rauch G.J., Heisenberg C.P.,
RA Houart C., Schilling T.F., Frohnhoefer H.G., Rastegar S., Neumann C.J.,
RA Gardiner R.M., Strahle U., Geisler R., Rees M., Talbot W.S., Wilson S.W.;
RT "Monorail/Foxa2 regulates floorplate differentiation and specification of
RT oligodendrocytes, serotonergic raphe neurones and cranial motoneurones.";
RL Development 132:645-658(2005).
RN [4] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=16498236; DOI=10.1620/tjem.208.267;
RA Wang Y., Takai R., Yoshioka H., Shirabe K.;
RT "Characterization and expression of serotonin transporter genes in
RT zebrafish.";
RL Tohoku J. Exp. Med. 208:267-274(2006).
RN [5] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=17304529; DOI=10.1002/dvdy.21095;
RA Lillesaar C., Tannhauser B., Stigloher C., Kremmer E., Bally-Cuif L.;
RT "The serotonergic phenotype is acquired by converging genetic mechanisms
RT within the zebrafish central nervous system.";
RL Dev. Dyn. 236:1072-1084(2007).
RN [6] {ECO:0000313|Ensembl:ENSDARP00000102919, ECO:0000313|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000102919};
RX PubMed=23594743; DOI=10.1038/nature12111;
RG Genome Reference Consortium Zebrafish;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [7] {ECO:0000313|Ensembl:ENSDARP00000102919}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000102919};
RG Ensembl;
RL Submitted (AUG-2013) to UniProtKB.
RN [8] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=29775928;
RA Xiao W.Y., Li Y.W., Chen Q.L., Liu Z.H.;
RT "Tributyltin impaired reproductive success in female zebrafish through
RT disrupting oogenesis, reproductive behaviors and serotonin synthesis.";
RL Aquat. Toxicol. 200:206-216(2018).
RN [9] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=29421749;
RA Wang F., Fang M., Hinton D.E., Chernick M., Jia S., Zhang Y., Xie L.,
RA Dong W., Dong W.;
RT "Increased coiling frequency linked to apoptosis in the brain and altered
RT thyroid signaling in zebrafish embryos (Danio rerio) exposed to the PBDE
RT metabolite 6-OH-BDE-47.";
RL Chemosphere 198:342-350(2018).
RN [10] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=29945867; DOI=10.1242/dev.163477;
RA Schredelseker T., Driever W.;
RT "Bsx controls pineal complex development. .";
RL Development 145:dev163477-dev163477(2018).
RN [11] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=29867763;
RA Ulhaq Z.S., Kishida M.;
RT "Brain Aromatase Modulates Serotonergic Neuron by Regulating Serotonin
RT Levels in Zebrafish Embryos and Larvae.";
RL Front. Endocrinol. 9:230-230(2018).
RN [12] {ECO:0000313|RefSeq:NP_999960.2}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RX PubMed=30765816;
RA Sahu M.P., Pazos-Boubeta Y., Pajanoja C., Rozov S., Panula P., Castren E.;
RT "Neurotrophin receptor Ntrk2b function in the maintenance of dopamine and
RT serotonin neurons in zebrafish.";
RL Sci. Rep. 9:2036-2036(2019).
RN [13] {ECO:0000313|RefSeq:NP_999960.2}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:NP_999960.2};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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 -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000256|ARBA:ARBA00009712}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BX950194; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_999960.2; NM_214795.2.
DR Ensembl; ENSDART00000112627; ENSDARP00000102919; ENSDARG00000057239.
DR Ensembl; ENSDART00000112627.5; ENSDARP00000102919.3; ENSDARG00000057239.7.
DR GeneID; 407712; -.
DR AGR; ZFIN:ZDB-GENE-040624-4; -.
DR CTD; 121278; -.
DR ZFIN; ZDB-GENE-040624-4; tph2.
DR HOGENOM; CLU_023198_0_1_1; -.
DR OrthoDB; 275463at2759; -.
DR UniPathway; UPA00846; UER00799.
DR Proteomes; UP000000437; Alternate scaffold 18.
DR Proteomes; UP000000437; Chromosome 18.
DR Bgee; ENSDARG00000057239; Expressed in brain and 10 other cell types or tissues.
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 metabolic process; IEA:InterPro.
DR GO; GO:1902036; P:regulation of hematopoietic stem cell differentiation; IMP:ZFIN.
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:SF16; TRYPTOPHAN 5-HYDROXYLASE 2; 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:UP000000437};
KW Serotonin biosynthesis {ECO:0000256|ARBA:ARBA00023094}.
FT DOMAIN 35..110
FT /note="ACT"
FT /evidence="ECO:0000259|PROSITE:PS51671"
FT DOMAIN 122..468
FT /note="Biopterin-dependent aromatic amino acid hydroxylase
FT family profile"
FT /evidence="ECO:0000259|PROSITE:PS51410"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 264
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 286
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 294
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 301
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 306
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 346
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000256|PIRSR:PIRSR000336-1"
FT BINDING 365
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
FT BINDING 395
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000256|PIRSR:PIRSR601273-1"
SQ SEQUENCE 473 AA; 54432 MW; B66E024E6E2DC7E4 CRC64;
MTNSTLHPPW TSFNRIDERP DKEEQKSTHD LGKLAVIFSL KNEVGFLVKA LRLFQEKHVN
LAHIESRRSK RLTNEIEIYA ECNCTKKEFN ELVQHLKDHV NIVSYNTPQH VWSAETDCLD
CVCVLGGLPD GEGIPWFPQK ISELDQCSHR VLMYGSELDA DHPGFKDKVY RQRRKYFVEV
AMNYKFGQPI PRIEYTAEEV KTWGVVYREL TKLYPTHACR EYLKNLPLLT KHCGYREDNI
PQLEDVSLFL RERSGFTVRP VAGYLSPRDF LAGLAYRVFN CTQYIRHSTD PLYTPEPDTC
HELLGHVPLL ADPKFAQFSQ EIGLASLGAS DEDVQKLATC YFFTIEFGLC KQDGQLRVYG
AGLLSSIGEL RHALSDKATV KVFDPKTTCY QECLITTFQD VYFVSESFEE AKEKMREFAK
SIKRPFSVYY NPYTQSIDLL KDTRSIENVV QDLRSDLTTV CDALGKMNKY LGI
//
