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P17752 (TPH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tryptophan 5-hydroxylase 1

EC=1.14.16.4
Alternative name(s):
Tryptophan 5-monooxygenase 1
Gene names
Name:TPH1
Synonyms:TPH, TPRH, TRPH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

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

Cofactor

Fe2+ ion.

Pathway

Aromatic compound metabolism; serotonin biosynthesis; serotonin from L-tryptophan: step 1/2.

Subunit structure

Homotetramer By similarity.

Tissue specificity

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

Sequence similarities

Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Contains 1 ACT domain.

Ontologies

Keywords
   Biological processSerotonin biosynthesis
   Coding sequence diversityAlternative splicing
   LigandIron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaromatic amino acid family metabolic process

Inferred from electronic annotation. Source: InterPro

bone remodeling

Inferred from electronic annotation. Source: Ensembl

cellular nitrogen compound metabolic process

Traceable author statement. Source: Reactome

circadian rhythm

Inferred from electronic annotation. Source: Ensembl

indolalkylamine biosynthetic process

Traceable author statement. Source: Reactome

mammary gland alveolus development

Inferred from electronic annotation. Source: Ensembl

negative regulation of ossification

Inferred from electronic annotation. Source: Ensembl

response to immobilization stress

Inferred from electronic annotation. Source: Ensembl

serotonin biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-UniPathway

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

neuron projection

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionamino acid binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

tryptophan 5-monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P17752-1)

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.
Isoform 2 (identifier: P17752-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 444444Tryptophan 5-hydroxylase 1
PRO_0000205568

Regions

Domain19 – 9476ACT

Sites

Metal binding2721Iron
Metal binding2771Iron
Metal binding3171Iron
Binding site2351Tryptophan By similarity
Binding site2571Tryptophan By similarity
Binding site2651Tryptophan By similarity
Binding site3361Tryptophan By similarity
Binding site3661Tryptophan; via carbonyl oxygen By similarity

Amino acid modifications

Modified residue581Phosphoserine; by PKA Potential

Natural variations

Alternative sequence438 – 4447VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2.
VSP_000546

Experimental info

Sequence conflict191S → T in AAA67050. Ref.2
Sequence conflict681I → T in AAA67050. Ref.2
Sequence conflict90 – 912NL → TP in AAA67050. Ref.2
Sequence conflict971L → M in AAA67050. Ref.2
Sequence conflict1001D → E in AAA67050. Ref.2
Sequence conflict1041T → S in AAA67050. Ref.2
Sequence conflict1511L → S in AAA67050. Ref.2
Sequence conflict1541N → S in AAA67050. Ref.2
Sequence conflict1571H → Y in AAA67050. Ref.2
Sequence conflict1791Q → R in AAA67050. Ref.2
Sequence conflict2071R → Q in AAA67050. Ref.2
Sequence conflict2171V → I in AAA67050. Ref.2
Sequence conflict3441A → V in AAA67050. Ref.2
Sequence conflict4141T → A in AAA67050. Ref.2
Sequence conflict4191S → N in AAA67050. Ref.2
Sequence conflict4251Q → R in AAA67050. Ref.2
Sequence conflict4361A → G in AAA67050. Ref.2

Secondary structure

.................................................. 444
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 4.
Checksum: DFAD501446953A91

FASTA44450,985
        10         20         30         40         50         60 
MIEDNKENKD HSLERGRASL IFSLKNEVGG LIKALKIFQE KHVNLLHIES RKSKRRNSEF 

        70         80         90        100        110        120 
EIFVDCDINR EQLNDIFHLL KSHTNVLSVN LPDNFTLKED GMETVPWFPK KISDLDHCAN 

       130        140        150        160        170        180 
RVLMYGSELD ADHPGFKDNV YRKRRKYFAD LAMNYKHGDP IPKVEFTEEE IKTWGTVFQE 

       190        200        210        220        230        240 
LNKLYPTHAC REYLKNLPLL SKYCGYREDN IPQLEDVSNF LKERTGFSIR PVAGYLSPRD 

       250        260        270        280        290        300 
FLSGLAFRVF HCTQYVRHSS DPFYTPEPDT CHELLGHVPL LAEPSFAQFS QEIGLASLGA 

       310        320        330        340        350        360 
SEEAVQKLAT CYFFTVEFGL CKQDGQLRVF GAGLLSSISE LKHALSGHAK VKPFDPKITC 

       370        380        390        400        410        420 
KQECLITTFQ DVYFVSESFE DAKEKMREFT KTIKRPFGVK YNPYTRSIQI LKDTKSITSA 

       430        440 
MNELQHDLDV VSDALAKVSR KPSI 

« Hide

Isoform 2 [UniParc].

Checksum: CAFE34D6173BA604
Show »

FASTA46653,394

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS10489.
RefSeqNP_004170.1. NM_004179.2.
UniGeneHs.591999.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
3HF6X-ray1.80A105-393[»]
3HF8X-ray1.85A105-393[»]
3HFBX-ray1.92A105-393[»]
ProteinModelPortalP17752.
SMRP17752. Positions 9-438.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113019. 2 interactions.
IntActP17752. 1 interaction.
STRING9606.ENSP00000250018.

Chemistry

BindingDBP17752.
ChEMBLCHEMBL5689.
DrugBankDB00150. L-Tryptophan.
DB00360. Tetrahydrobiopterin.
GuidetoPHARMACOLOGY1241.

PTM databases

PhosphoSiteP17752.

Polymorphism databases

DMDM116242823.

Proteomic databases

PaxDbP17752.
PRIDEP17752.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250018; ENSP00000250018; ENSG00000129167. [P17752-1]
ENST00000341556; ENSP00000343550; ENSG00000129167. [P17752-2]
GeneID7166.
KEGGhsa:7166.
UCSCuc001mnp.2. human. [P17752-1]

Organism-specific databases

CTD7166.
GeneCardsGC11M018040.
HGNCHGNC:12008. TPH1.
HPACAB010767.
HPA022483.
MIM191060. gene.
neXtProtNX_P17752.
PharmGKBPA355.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3186.
HOGENOMHOG000233373.
HOVERGENHBG006841.
KOK00502.
OMATWGTVFQ.
OrthoDBEOG7KM5T1.
PhylomeDBP17752.
TreeFamTF313327.

Enzyme and pathway databases

BioCycMetaCyc:HS05250-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP17752.
UniPathwayUPA00846; UER00799.

Gene expression databases

ArrayExpressP17752.
BgeeP17752.
CleanExHS_TPH1.
GenevestigatorP17752.

Family and domain databases

Gene3D1.10.800.10. 1 hit.
InterProIPR002912. 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]
PANTHERPTHR11473. PTHR11473. 1 hit.
PfamPF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFPIRSF000336. TH. 1 hit.
PRINTSPR00372. FYWHYDRXLASE.
SUPFAMSSF56534. SSF56534. 1 hit.
TIGRFAMsTIGR01270. Trp_5_monoox. 1 hit.
PROSITEPS51671. ACT. 1 hit.
PS00367. BH4_AAA_HYDROXYL_1. 1 hit.
PS51410. BH4_AAA_HYDROXYL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP17752.
GeneWikiTPH1.
GenomeRNAi7166.
NextBio28062.
PROP17752.
SOURCESearch...

Entry information

Entry nameTPH1_HUMAN
AccessionPrimary (citable) accession number: P17752
Secondary accession number(s): D3DQX6 expand/collapse secondary AC list , O95188, O95189, Q16736, Q3KPG8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 148 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM