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Q9BU02 (THTPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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:
Thiamine-triphosphatase

Short name=ThTPase
EC=3.6.1.28
Gene names
Name:THTPA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length230 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolase highly specific for thiamine triphosphate (ThTP). Ref.1 Ref.10

Catalytic activity

Thiamine triphosphate + H2O = thiamine diphosphate + phosphate. Ref.10

Cofactor

Binds 1 Mg2+ ion per subunit. Ref.10

Subunit structure

Monomer. Ref.10

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Widely expressed but at a low level. Ref.1

Sequence similarities

Belongs to the ThTPase family.

Contains 1 CYTH domain.

Biophysicochemical properties

Kinetic parameters:

KM=8 µM for thiamine triphosphate Ref.10

Vmax=59 µmol/min/mg enzyme

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BU02-1)

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: Q9BU02-2)

The sequence of this isoform differs from the canonical sequence as follows:
     96-105: LRADGLGAGD → CLHRRQHQPS
     106-230: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 230229Thiamine-triphosphatase
PRO_0000221490

Regions

Domain5 – 201197CYTH

Sites

Metal binding71Magnesium By similarity
Metal binding91Magnesium By similarity
Metal binding1451Magnesium By similarity
Metal binding1571Magnesium By similarity
Metal binding1591Magnesium By similarity
Binding site111Substrate
Binding site551Substrate
Binding site571Substrate
Binding site651Substrate
Binding site1251Substrate
Binding site1571Substrate
Binding site1931Substrate Probable

Amino acid modifications

Modified residue21N-acetylalanine Ref.8 Ref.9

Natural variations

Alternative sequence96 – 10510LRADGLGAGD → CLHRRQHQPS in isoform 2.
VSP_047213
Alternative sequence106 – 230125Missing in isoform 2.
VSP_047214
Natural variant1761H → R.
Corresponds to variant rs34015250 [ dbSNP | Ensembl ].
VAR_062152

Experimental info

Mutagenesis111K → A: Mildly decreases enzyme activity. Ref.10
Mutagenesis371D → A: Strongly decreases affinity for thiamine triphosphate and enzyme activity. Ref.10
Mutagenesis391Y → A: Strongly decreases affinity for thiamine triphosphate and enzyme activity. Ref.10
Mutagenesis531W → A: Strongly decreases affinity for thiamine triphosphate and enzyme activity. Ref.10
Mutagenesis651K → A: Strongly decreases enzyme activity. No effect on affinity for thiamine triphosphate. Ref.10
Mutagenesis791Y → A: Decreases enzyme activity. Ref.10
Mutagenesis811E → A: Mildly decreases enzyme activity. Ref.10
Mutagenesis1471D → A: Strongly decreases affinity for thiamine triphosphate and enzyme activity. Ref.10
Mutagenesis1931K → A: Strongly decreases affinity for thiamine triphosphate and enzyme activity. Ref.10

Secondary structure

.................................. 230
Helix Strand Turn

Details...

Sequences

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

Last modified January 23, 2007. Version 3.
Checksum: 49B79C6C1D19D91D

FASTA23025,566
        10         20         30         40         50         60 
MAQGLIEVER KFLPGPGTEE RLQELGGTLE YRVTFRDTYY DTPELSLMQA DHWLRRREDS 

        70         80         90        100        110        120 
GWELKCPGAA GVLGPHTEYK ELTAEPTIVA QLCKVLRADG LGAGDVAAVL GPLGLQEVAS 

       130        140        150        160        170        180 
FVTKRSAWKL VLLGADEEEP QLRVDLDTAD FGYAVGEVEA LVHEEAEVPT ALEKIHRLSS 

       190        200        210        220        230 
MLGVPAQETA PAKLIVYLQR FRPQDYQRLL EVNSSRERPQ ETEDPDHCLG 

« Hide

Isoform 2 [UniParc].

Checksum: D326E9A8991B8A1F
Show »

FASTA10512,038

References

« Hide 'large scale' references
[1]"Molecular characterization of a specific thiamine triphosphatase widely expressed in mammalian tissues."
Lakaye B., Makarchikov A.F., Antunes A.F., Zorzi W., Coumans B., De Pauw E., Wins P., Grisar T., Bettendorff L.
J. Biol. Chem. 277:13771-13777(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Trachea.
[3]"Full-length cDNA libraries and normalization."
Li W.B., Gruber C., Jessee J., Polayes D.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Placenta.
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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].
[6]"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).
Tissue: Lung.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Structural determinants of specificity and catalytic mechanism in mammalian 25-kDa thiamine triphosphatase."
Delvaux D., Kerff F., Murty M.R., Lakaye B., Czerniecki J., Kohn G., Wins P., Herman R., Gabelica V., Heuze F., Tordoir X., Maree R., Matagne A., Charlier P., De Pauw E., Bettendorff L.
Biochim. Biophys. Acta 1830:4513-4523(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH TRIPHOSPHATE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, MUTAGENESIS OF LYS-11; ASP-37; TYR-39; TRP-53; LYS-65; TYR-79; GLU-81; ASP-147 AND LYS-193.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF432862 mRNA. Translation: AAM22403.1.
AK057691 mRNA. Translation: BAB71546.1.
BX161435 mRNA. Translation: CAD61907.1.
BX378775 mRNA. No translation available.
AL135999 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW66140.1.
CH471078 Genomic DNA. Translation: EAW66141.1.
BC002984 mRNA. Translation: AAH02984.1.
RefSeqNP_001119811.1. NM_001126339.3.
NP_001242991.1. NM_001256062.2.
NP_001243250.1. NM_001256321.2.
NP_001243251.1. NM_001256322.2.
NP_001243252.1. NM_001256323.2.
NP_077304.1. NM_024328.5.
UniGeneHs.655179.
Hs.732304.
Hs.736905.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BHDX-ray1.50A/B1-215[»]
3TVLX-ray2.30A/B1-230[»]
ProteinModelPortalQ9BU02.
SMRQ9BU02. Positions 3-208.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122595. 6 interactions.
IntActQ9BU02. 1 interaction.
STRING9606.ENSP00000288014.

Chemistry

DrugBankDB00152. Thiamine.

PTM databases

PhosphoSiteQ9BU02.

Polymorphism databases

DMDM37538018.

Proteomic databases

PaxDbQ9BU02.
PeptideAtlasQ9BU02.
PRIDEQ9BU02.

Protocols and materials databases

DNASU79178.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000288014; ENSP00000288014; ENSG00000259431. [Q9BU02-1]
ENST00000404535; ENSP00000384580; ENSG00000259431. [Q9BU02-1]
ENST00000554789; ENSP00000450459; ENSG00000259431. [Q9BU02-2]
ENST00000556015; ENSP00000451835; ENSG00000259431. [Q9BU02-2]
GeneID79178.
KEGGhsa:79178.
UCSCuc001wkg.5. human. [Q9BU02-1]
uc031qnv.1. human.

Organism-specific databases

CTD79178.
GeneCardsGC14P024025.
HGNCHGNC:18987. THTPA.
HPAHPA028876.
MIM611612. gene.
neXtProtNX_Q9BU02.
PharmGKBPA38774.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42323.
HOGENOMHOG000154571.
HOVERGENHBG057173.
InParanoidQ9BU02.
KOK05307.
OMARDTYYDT.
OrthoDBEOG7288SN.
PhylomeDBQ9BU02.
TreeFamTF333398.

Enzyme and pathway databases

BRENDA3.6.1.28. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.

Gene expression databases

BgeeQ9BU02.
CleanExHS_THTPA.
GenevestigatorQ9BU02.

Family and domain databases

Gene3D2.40.320.10. 1 hit.
InterProIPR023577. CYTH-like_domain.
IPR012177. ThTPase.
[Graphical view]
PANTHERPTHR14586. PTHR14586. 1 hit.
PfamPF01928. CYTH. 1 hit.
[Graphical view]
PIRSFPIRSF036561. ThTPase. 1 hit.
SUPFAMSSF55154. SSF55154. 1 hit.
PROSITEPS51707. CYTH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9BU02.
GenomeRNAi79178.
NextBio68161.
PROQ9BU02.
SOURCESearch...

Entry information

Entry nameTHTPA_HUMAN
AccessionPrimary (citable) accession number: Q9BU02
Secondary accession number(s): D3DS50, G3V4J3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 117 of the entry and version 3 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM