Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P17752

- TPH1_HUMAN

UniProt

P17752 - TPH1_HUMAN

Protein

Tryptophan 5-hydroxylase 1

Gene

TPH1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 4 (17 Oct 2006)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Catalytic activityi

    L-tryptophan + tetrahydrobiopterin + O2 = 5-hydroxy-L-tryptophan + 4a-hydroxytetrahydrobiopterin.

    Cofactori

    Fe2+ ion.

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei235 – 2351TryptophanBy similarity
    Binding sitei257 – 2571TryptophanBy similarity
    Binding sitei265 – 2651TryptophanBy similarity
    Metal bindingi272 – 2721Iron
    Metal bindingi277 – 2771Iron
    Metal bindingi317 – 3171Iron
    Binding sitei336 – 3361TryptophanBy similarity
    Binding sitei366 – 3661Tryptophan; via carbonyl oxygenBy similarity

    GO - Molecular functioni

    1. amino acid binding Source: InterPro
    2. iron ion binding Source: InterPro
    3. tryptophan 5-monooxygenase activity Source: UniProtKB-EC

    GO - Biological processi

    1. aromatic amino acid family metabolic process Source: InterPro
    2. bone remodeling Source: Ensembl
    3. cellular nitrogen compound metabolic process Source: Reactome
    4. circadian rhythm Source: Ensembl
    5. indolalkylamine biosynthetic process Source: Reactome
    6. mammary gland alveolus development Source: Ensembl
    7. negative regulation of ossification Source: Ensembl
    8. response to immobilization stress Source: Ensembl
    9. serotonin biosynthetic process Source: UniProtKB-UniPathway
    10. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Biological processi

    Serotonin biosynthesis

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS05250-MONOMER.
    ReactomeiREACT_15439. Serotonin and melatonin biosynthesis.
    SABIO-RKP17752.
    UniPathwayiUPA00846; UER00799.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tryptophan 5-hydroxylase 1 (EC:1.14.16.4)
    Alternative name(s):
    Tryptophan 5-monooxygenase 1
    Gene namesi
    Name:TPH1
    Synonyms:TPH, TPRH, TRPH
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:12008. TPH1.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. neuron projection Source: Ensembl

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA355.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 444444Tryptophan 5-hydroxylase 1PRO_0000205568Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei58 – 581Phosphoserine; by PKASequence Analysis

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP17752.
    PRIDEiP17752.

    PTM databases

    PhosphoSiteiP17752.

    Expressioni

    Tissue specificityi

    Isoform 2 seems to be less widely expressed than isoform 1.

    Gene expression databases

    ArrayExpressiP17752.
    BgeeiP17752.
    CleanExiHS_TPH1.
    GenevestigatoriP17752.

    Organism-specific databases

    HPAiCAB010767.
    HPA022483.

    Interactioni

    Subunit structurei

    Homotetramer.By similarity

    Protein-protein interaction databases

    BioGridi113019. 2 interactions.
    IntActiP17752. 1 interaction.
    STRINGi9606.ENSP00000250018.

    Structurei

    Secondary structure

    1
    444
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi112 – 1176
    Turni118 – 1203
    Turni134 – 1374
    Helixi139 – 15416
    Helixi168 – 18821
    Helixi191 – 20414
    Helixi214 – 22411
    Beta strandi228 – 2314
    Beta strandi233 – 2353
    Helixi238 – 2458
    Turni246 – 2483
    Beta strandi249 – 2524
    Helixi270 – 2767
    Helixi278 – 2814
    Helixi284 – 29714
    Helixi302 – 31312
    Turni314 – 3185
    Beta strandi320 – 3234
    Beta strandi326 – 3294
    Helixi332 – 3354
    Helixi338 – 3447
    Turni345 – 3473
    Beta strandi349 – 3535
    Helixi356 – 3594
    Beta strandi366 – 3683
    Beta strandi371 – 3755
    Helixi379 – 39012

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IN9model-A2-444[»]
    1MLWX-ray1.71A102-402[»]
    3HF6X-ray1.80A105-393[»]
    3HF8X-ray1.85A105-393[»]
    3HFBX-ray1.92A104-393[»]
    ProteinModelPortaliP17752.
    SMRiP17752. Positions 9-438.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP17752.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini19 – 9476ACTPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 ACT domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG3186.
    HOGENOMiHOG000233373.
    HOVERGENiHBG006841.
    KOiK00502.
    OMAiTWGTVFQ.
    OrthoDBiEOG7KM5T1.
    PhylomeDBiP17752.
    TreeFamiTF313327.

    Family and domain databases

    Gene3Di1.10.800.10. 1 hit.
    InterProiIPR002912. ACT_dom.
    IPR001273. ArAA_hydroxylase.
    IPR018301. ArAA_hydroxylase_Fe/CU_BS.
    IPR019774. Aromatic-AA_hydroxylase_C.
    IPR005963. Trp_5_mOase.
    IPR019773. Tyrosine_3-monooxygenase-like.
    [Graphical view]
    PANTHERiPTHR11473. PTHR11473. 1 hit.
    PfamiPF01842. ACT. 1 hit.
    PF00351. Biopterin_H. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000336. TH. 1 hit.
    PRINTSiPR00372. FYWHYDRXLASE.
    SUPFAMiSSF56534. SSF56534. 1 hit.
    TIGRFAMsiTIGR01270. Trp_5_monoox. 1 hit.
    PROSITEiPS51671. ACT. 1 hit.
    PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
    PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P17752-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MIEDNKENKD HSLERGRASL IFSLKNEVGG LIKALKIFQE KHVNLLHIES    50
    RKSKRRNSEF EIFVDCDINR EQLNDIFHLL KSHTNVLSVN LPDNFTLKED 100
    GMETVPWFPK KISDLDHCAN RVLMYGSELD ADHPGFKDNV YRKRRKYFAD 150
    LAMNYKHGDP IPKVEFTEEE IKTWGTVFQE LNKLYPTHAC REYLKNLPLL 200
    SKYCGYREDN IPQLEDVSNF LKERTGFSIR PVAGYLSPRD FLSGLAFRVF 250
    HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA 300
    SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHALSGHAK 350
    VKPFDPKITC KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK 400
    YNPYTRSIQI LKDTKSITSA MNELQHDLDV VSDALAKVSR KPSI 444
    Length:444
    Mass (Da):50,985
    Last modified:October 17, 2006 - v4
    Checksum:iDFAD501446953A91
    GO
    Isoform 2 (identifier: P17752-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         438-444: VSRKPSI → SLNEDVLQVSVFALLLFLPSLHGECHPDT

    Show »
    Length:466
    Mass (Da):53,394
    Checksum:iCAFE34D6173BA604
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti19 – 191S → T in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti68 – 681I → T in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti90 – 912NL → TP in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti97 – 971L → M in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti100 – 1001D → E in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti104 – 1041T → S in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti151 – 1511L → S in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti154 – 1541N → S in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti157 – 1571H → Y in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti179 – 1791Q → R in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti207 – 2071R → Q in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti217 – 2171V → I in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti344 – 3441A → V in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti414 – 4141T → A in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti419 – 4191S → N in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti425 – 4251Q → R in AAA67050. (PubMed:7986090)Curated
    Sequence conflicti436 – 4361A → G in AAA67050. (PubMed:7986090)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei438 – 4447VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2. CuratedVSP_000546

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52836 mRNA. Translation: CAA37018.1.
    L29306 mRNA. Translation: AAA67050.1.
    CH471064 Genomic DNA. Translation: EAW68421.1.
    CH471064 Genomic DNA. Translation: EAW68422.1.
    BC106739 mRNA. Translation: AAI06740.1.
    AF057280 Genomic DNA. Translation: AAC69458.1.
    AF057280 Genomic DNA. Translation: AAC69459.1.
    CCDSiCCDS7829.1. [P17752-1]
    PIRiS10489.
    RefSeqiNP_004170.1. NM_004179.2. [P17752-1]
    UniGeneiHs.591999.

    Genome annotation databases

    EnsembliENST00000250018; ENSP00000250018; ENSG00000129167. [P17752-1]
    GeneIDi7166.
    KEGGihsa:7166.
    UCSCiuc001mnp.2. human. [P17752-1]

    Polymorphism databases

    DMDMi116242823.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X52836 mRNA. Translation: CAA37018.1 .
    L29306 mRNA. Translation: AAA67050.1 .
    CH471064 Genomic DNA. Translation: EAW68421.1 .
    CH471064 Genomic DNA. Translation: EAW68422.1 .
    BC106739 mRNA. Translation: AAI06740.1 .
    AF057280 Genomic DNA. Translation: AAC69458.1 .
    AF057280 Genomic DNA. Translation: AAC69459.1 .
    CCDSi CCDS7829.1. [P17752-1 ]
    PIRi S10489.
    RefSeqi NP_004170.1. NM_004179.2. [P17752-1 ]
    UniGenei Hs.591999.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IN9 model - A 2-444 [» ]
    1MLW X-ray 1.71 A 102-402 [» ]
    3HF6 X-ray 1.80 A 105-393 [» ]
    3HF8 X-ray 1.85 A 105-393 [» ]
    3HFB X-ray 1.92 A 104-393 [» ]
    ProteinModelPortali P17752.
    SMRi P17752. Positions 9-438.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113019. 2 interactions.
    IntActi P17752. 1 interaction.
    STRINGi 9606.ENSP00000250018.

    Chemistry

    BindingDBi P17752.
    ChEMBLi CHEMBL5689.
    DrugBanki DB00150. L-Tryptophan.
    DB00360. Tetrahydrobiopterin.
    GuidetoPHARMACOLOGYi 1241.

    PTM databases

    PhosphoSitei P17752.

    Polymorphism databases

    DMDMi 116242823.

    Proteomic databases

    PaxDbi P17752.
    PRIDEi P17752.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000250018 ; ENSP00000250018 ; ENSG00000129167 . [P17752-1 ]
    GeneIDi 7166.
    KEGGi hsa:7166.
    UCSCi uc001mnp.2. human. [P17752-1 ]

    Organism-specific databases

    CTDi 7166.
    GeneCardsi GC11M018040.
    HGNCi HGNC:12008. TPH1.
    HPAi CAB010767.
    HPA022483.
    MIMi 191060. gene.
    neXtProti NX_P17752.
    PharmGKBi PA355.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG3186.
    HOGENOMi HOG000233373.
    HOVERGENi HBG006841.
    KOi K00502.
    OMAi TWGTVFQ.
    OrthoDBi EOG7KM5T1.
    PhylomeDBi P17752.
    TreeFami TF313327.

    Enzyme and pathway databases

    UniPathwayi UPA00846 ; UER00799 .
    BioCyci MetaCyc:HS05250-MONOMER.
    Reactomei REACT_15439. Serotonin and melatonin biosynthesis.
    SABIO-RK P17752.

    Miscellaneous databases

    EvolutionaryTracei P17752.
    GeneWikii TPH1.
    GenomeRNAii 7166.
    NextBioi 28062.
    PROi P17752.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P17752.
    Bgeei P17752.
    CleanExi HS_TPH1.
    Genevestigatori P17752.

    Family and domain databases

    Gene3Di 1.10.800.10. 1 hit.
    InterProi IPR002912. ACT_dom.
    IPR001273. ArAA_hydroxylase.
    IPR018301. ArAA_hydroxylase_Fe/CU_BS.
    IPR019774. Aromatic-AA_hydroxylase_C.
    IPR005963. Trp_5_mOase.
    IPR019773. Tyrosine_3-monooxygenase-like.
    [Graphical view ]
    PANTHERi PTHR11473. PTHR11473. 1 hit.
    Pfami PF01842. ACT. 1 hit.
    PF00351. Biopterin_H. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000336. TH. 1 hit.
    PRINTSi PR00372. FYWHYDRXLASE.
    SUPFAMi SSF56534. SSF56534. 1 hit.
    TIGRFAMsi TIGR01270. Trp_5_monoox. 1 hit.
    PROSITEi PS51671. ACT. 1 hit.
    PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
    PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Complete coding sequence of human tryptophan hydroxylase."
      Boulalard S., Darmon M.C., Ganem Y., Launay J.-M., Mallet J.
      Nucleic Acids Res. 18:4257-4257(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Carcinoma.
    2. "Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli."
      Tipper J.P., Citron B.A., Ribeiro P., Kaufman S.
      Arch. Biochem. Biophys. 315:445-453(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Brain.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    5. "Alternative splicing at the 3'-cDNA of human tryptophan hydroxylase."
      Wang G.A., Coon S.L., Kaufman S.
      J. Neurochem. 71:1769-1772(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-444 (ISOFORMS 1 AND 2).
    6. "Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin."
      Wang L., Erlandsen H., Haavik J., Knappskog P.M., Stevens R.C.
      Biochemistry 41:12569-12574(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 102-402.

    Entry informationi

    Entry nameiTPH1_HUMAN
    AccessioniPrimary (citable) accession number: P17752
    Secondary accession number(s): D3DQX6
    , O95188, O95189, Q16736, Q3KPG8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: October 17, 2006
    Last modified: October 1, 2014
    This is version 152 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    4. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3