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P17752

- TPH1_HUMAN

UniProt

P17752 - TPH1_HUMAN

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Protein
Tryptophan 5-hydroxylase 1
Gene
TPH1, TPH, TPRH, TRPH
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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 – 2351Tryptophan By similarity
Binding sitei257 – 2571Tryptophan By similarity
Binding sitei265 – 2651Tryptophan By similarity
Metal bindingi272 – 2721Iron
Metal bindingi277 – 2771Iron
Metal bindingi317 – 3171Iron
Binding sitei336 – 3361Tryptophan By similarity
Binding sitei366 – 3661Tryptophan; via carbonyl oxygen By 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
Complete GO annotation...

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
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA355.

PTM / Processingi

Molecule processing

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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei58 – 581Phosphoserine; by PKA Reviewed prediction

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

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.

Miscellaneous databases

EvolutionaryTraceiP17752.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 9476ACT
Add
BLAST

Sequence similaritiesi

Contains 1 ACT domain.

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei438 – 4447VSRKPSI → SLNEDVLQVSVFALLLFLPS LHGECHPDT in isoform 2.
VSP_000546

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191S → T in AAA67050. 1 Publication
Sequence conflicti68 – 681I → T in AAA67050. 1 Publication
Sequence conflicti90 – 912NL → TP in AAA67050. 1 Publication
Sequence conflicti97 – 971L → M in AAA67050. 1 Publication
Sequence conflicti100 – 1001D → E in AAA67050. 1 Publication
Sequence conflicti104 – 1041T → S in AAA67050. 1 Publication
Sequence conflicti151 – 1511L → S in AAA67050. 1 Publication
Sequence conflicti154 – 1541N → S in AAA67050. 1 Publication
Sequence conflicti157 – 1571H → Y in AAA67050. 1 Publication
Sequence conflicti179 – 1791Q → R in AAA67050. 1 Publication
Sequence conflicti207 – 2071R → Q in AAA67050. 1 Publication
Sequence conflicti217 – 2171V → I in AAA67050. 1 Publication
Sequence conflicti344 – 3441A → V in AAA67050. 1 Publication
Sequence conflicti414 – 4141T → A in AAA67050. 1 Publication
Sequence conflicti419 – 4191S → N in AAA67050. 1 Publication
Sequence conflicti425 – 4251Q → R in AAA67050. 1 Publication
Sequence conflicti436 – 4361A → G in AAA67050. 1 Publication

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]
ENST00000341556; ENSP00000343550; ENSG00000129167. [P17752-2]
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 ]
ENST00000341556 ; ENSP00000343550 ; ENSG00000129167 . [P17752-2 ]
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 151 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

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