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Reviewed, UniProtKB/Swiss-Prot P17752 (TPH1_HUMAN)

Last modified June 16, 2009. Version 97. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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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)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length444 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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

Multimer of identical subunits.

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.

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Ontologies

Keywords
   Biological processSerotonin biosynthesis
   Coding sequence diversityAlternative splicing
   LigandIron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   PTMPhosphoprotein
   Technical term3D-structure
Gene Ontology (GO)
   Biological processoxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

serotonin biosynthetic process from tryptophan

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionamino acid binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

tryptophan 5-monooxygenase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

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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

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 444444Tryptophan 5-hydroxylase 1
PRO_0000205568

Regions

Domain18 – 9275ACT

Sites

Metal binding2721Iron
Metal binding2771Iron
Metal binding3171Iron

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

1 ................................................. 444
Helix Strand Turn

Details...

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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.

Checksum: CAFE34D6173BA604
Show »

FASTA46653,394

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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: 2377472] [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: 7986090] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]"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: 9751214] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 388-444 (ISOFORMS 1 AND 2).
[5]"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: 12379098] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 102-402.
+Additional computationally mapped references.

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Cross-references

Sequence databases

X52836 mRNA. Translation: CAA37018.1.
L29306 mRNA. Translation: AAA67050.1.
BC106739 mRNA. Translation: AAI06740.1.
AF057280 Genomic DNA. Translation: AAC69458.1.
AF057280 Genomic DNA. Translation: AAC69459.1.
IPIIPI00016810.
IPI00216828.
PIRS10489.
RefSeqNP_004170.1.
UniGeneHs.591999

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1IN9model-A2-444[»]
1MLWX-ray1.71A102-402[»]
ModBaseSearch...

PTM databases

PhosphoSiteP17752.

Proteomic databases

PRIDEP17752.

Genome annotation databases

EnsemblENSG00000129167. Homo sapiens. [Contig view]
GeneID7166.
KEGGhsa:7166.

Organism-specific databases

GeneCardsGC11M017997.
HGNCHGNC:12008. TPH1.
HPACAB010767.
MIM191060. gene.
PharmGKBPA355.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP17752.
OMAP17752. TWGTVFQ.

Enzyme and pathway databases

BioCycMetaCyc:MON-13402.
BRENDA1.14.16.4. 247.

Gene expression databases

ArrayExpressP17752.
BgeeP17752.
CleanExHS_TPH1.
GermOnlineENSG00000129167. Homo sapiens.

Family and domain databases

InterProIPR002912. ACT_bd.
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]
Gene3DG3DSA:1.10.800.10. Aaa_hydroxylase. 1 hit.
PANTHERPTHR11473. Aaa_hydroxylase. 1 hit.
PfamPF01842. ACT. 1 hit.
PF00351. Biopterin_H. 1 hit.
[Graphical view]
PIRSFPIRSF000336. TH. 1 hit.
PRINTSPR00372. FYWHYDRXLASE.
ProDomPD002559. Aaa_hydroxylase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsTIGR01270. Trp_5_monoox. 1 hit.
PROSITEPS00367. BIOPTERIN_HYDROXYL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00150. L-Tryptophan.
DB00360. Tetrahydrobiopterin.
NextBio28062.
SOURCESearch...

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Entry information

Entry nameTPH1_HUMAN
AccessionPrimary (citable) accession number: P17752
Secondary accession number(s): O95188 expand/collapse secondary AC list , O95189, Q16736, Q3KPG8
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 17, 2006
Last modified: June 16, 2009
This is version 97 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

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

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents