TPH2_MOUSE
ID TPH2_MOUSE Reviewed; 488 AA.
AC Q8CGV2; Q0VBT4;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Tryptophan 5-hydroxylase 2;
DE EC=1.14.16.4 {ECO:0000305|PubMed:12511643};
DE AltName: Full=Neuronal tryptophan hydroxylase;
DE AltName: Full=Tryptophan 5-monooxygenase 2;
GN Name=Tph2; Synonyms=Ntph;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PATHWAY, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RX PubMed=12511643; DOI=10.1126/science.1078197;
RA Walther D.J., Peter J.-U., Bashammakh S., Hortnagl H., Voits M., Fink H.,
RA Bader M.;
RT "Synthesis of serotonin by a second tryptophan hydroxylase isoform.";
RL Science 299:76-76(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000305|PubMed:12511643};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC -!- PATHWAY: Aromatic compound metabolism; serotonin biosynthesis;
CC serotonin from L-tryptophan: step 1/2. {ECO:0000305|PubMed:12511643}.
CC -!- TISSUE SPECIFICITY: Expressed in brain. {ECO:0000269|PubMed:12511643}.
CC -!- SIMILARITY: Belongs to the biopterin-dependent aromatic amino acid
CC hydroxylase family. {ECO:0000305}.
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DR EMBL; AY090565; AAM08923.1; -; mRNA.
DR EMBL; BC120514; AAI20515.1; -; mRNA.
DR EMBL; BC125430; AAI25431.1; -; mRNA.
DR CCDS; CCDS36061.1; -.
DR RefSeq; NP_775567.2; NM_173391.3.
DR AlphaFoldDB; Q8CGV2; -.
DR SMR; Q8CGV2; -.
DR BioGRID; 229732; 2.
DR IntAct; Q8CGV2; 1.
DR MINT; Q8CGV2; -.
DR STRING; 10090.ENSMUSP00000006949; -.
DR iPTMnet; Q8CGV2; -.
DR PhosphoSitePlus; Q8CGV2; -.
DR MaxQB; Q8CGV2; -.
DR PaxDb; Q8CGV2; -.
DR PRIDE; Q8CGV2; -.
DR ProteomicsDB; 258829; -.
DR Antibodypedia; 17122; 570 antibodies from 37 providers.
DR DNASU; 216343; -.
DR Ensembl; ENSMUST00000006949; ENSMUSP00000006949; ENSMUSG00000006764.
DR GeneID; 216343; -.
DR KEGG; mmu:216343; -.
DR UCSC; uc007haw.2; mouse.
DR CTD; 121278; -.
DR MGI; MGI:2651811; Tph2.
DR VEuPathDB; HostDB:ENSMUSG00000006764; -.
DR eggNOG; KOG3820; Eukaryota.
DR GeneTree; ENSGT00950000182885; -.
DR HOGENOM; CLU_023198_0_0_1; -.
DR InParanoid; Q8CGV2; -.
DR OMA; MASGHVM; -.
DR OrthoDB; 614557at2759; -.
DR PhylomeDB; Q8CGV2; -.
DR TreeFam; TF313327; -.
DR BRENDA; 1.14.16.4; 3474.
DR Reactome; R-MMU-209931; Serotonin and melatonin biosynthesis.
DR UniPathway; UPA00846; UER00799.
DR BioGRID-ORCS; 216343; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Tph2; mouse.
DR PRO; PR:Q8CGV2; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q8CGV2; protein.
DR Bgee; ENSMUSG00000006764; Expressed in dorsal tegmental nucleus and 47 other tissues.
DR Genevisible; Q8CGV2; MM.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004510; F:tryptophan 5-monooxygenase activity; IDA:MGI.
DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0006587; P:serotonin biosynthetic process from tryptophan; IC:MGI.
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 Iron; Metal-binding; Monooxygenase; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Serotonin biosynthesis.
FT CHAIN 1..488
FT /note="Tryptophan 5-hydroxylase 2"
FT /id="PRO_0000205575"
FT DOMAIN 63..138
FT /note="ACT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01007"
FT REGION 34..60
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 316
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 321
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 361
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CGU9"
FT CONFLICT 447
FT /note="P -> R (in Ref. 1; AAM08923)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 488 AA; 55859 MW; 876B59C784E80E4A CRC64;
MQPAMMMFSS KYWARRGLSL DSAVPEDHQL LGSLTQNKAI KSEDKKSGKE PGKGDTTESS
KTAVVFSLKN EVGGLVKALR LFQEKHVNML HIESRRSRRR SSEVEIFVDC ECGKTEFNEL
IQLLKFQTTI VTLNPPESIW TEEEDLEDVP WFPRKISELD RCSHRVLMYG TELDADHPGF
KDNVYRQRRK YFVDVAMGYK YGQPIPRVEY TEEETKTWGV VFRELSKLYP THACREYLKN
LPLLTKYCGY REDNVPQLED VSMFLKERSG FTVRPVAGYL SPRDFLAGLA YRVFHCTQYV
RHGSDPLYTP EPDTCHELLG HVPLLADPKF AQFSQEIGLA SLGASDEDVQ KLATCYFFTI
EFGLCKQEGQ LRAYGAGLLS SIGELKHALS DKACVKSFDP KTTCLQECLI TTFQDAYFVS
DSFEEAKEKM RDFAKSITRP FSVYFNPYTQ SIEILKDTRS IENVVQDLRS DLNTVCDALN
KMNQYLGI
