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Q9BY32 (ITPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 130. 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:
Inosine triphosphate pyrophosphatase

Short name=ITPase
Short name=Inosine triphosphatase
EC=3.6.1.19
Alternative name(s):
Non-canonical purine NTP pyrophosphatase
Non-standard purine NTP pyrophosphatase
Nucleoside-triphosphate diphosphatase
Nucleoside-triphosphate pyrophosphatase
Short name=NTPase
Putative oncogene protein hlc14-06-p
Gene names
Name:ITPA
Synonyms:C20orf37
ORF Names:My049, OK/SW-cl.9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length194 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions. Ref.11

Catalytic activity

A nucleoside triphosphate + H2O = a nucleotide + diphosphate. HAMAP-Rule MF_03148

Cofactor

Binds 1 magnesium ion per subunit. Ref.14

Subunit structure

Homodimer. Ref.1

Subcellular location

Cytoplasm Ref.1.

Tissue specificity

Ubiquitous. Highly expressed in heart, liver, sex glands, thyroid and adrenal gland.

Involvement in disease

Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850]: A common inherited condition characterized by the abnormal accumulation of inosine triphosphate in erythrocytes. It might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs.
Note: The disease is caused by mutations affecting the gene represented in this entry. Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme. Ref.2 Ref.15 Ref.16

Sequence similarities

Belongs to the HAM1 NTPase family.

Biophysicochemical properties

Kinetic parameters:

Vmax values are similar for dITP, dHAPTP and dGTP.

KM=0.51 mM for ITP Ref.1 Ref.11

KM=0.31 mM for dITP

KM=0.57 mM for XTP

KM=40.7 µM for dHAPTP

KM=933 µM for dGTP

Vmax=1520 µmol/min/mg enzyme for ITP

Vmax=940 µmol/min/mg enzyme for dITP

Vmax=1680 µmol/min/mg enzyme for XTP

pH dependence:

Optimum pH is 10.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BY32-1)

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: Q9BY32-2)

The sequence of this isoform differs from the canonical sequence as follows:
     7-23: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q9BY32-3)

The sequence of this isoform differs from the canonical sequence as follows:
     23-63: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.9
Chain2 – 194193Inosine triphosphate pyrophosphatase HAMAP-Rule MF_03148
PRO_0000178280

Regions

Region14 – 196Substrate binding HAMAP-Rule MF_03148
Region72 – 732Substrate binding HAMAP-Rule MF_03148
Region149 – 1524Substrate binding HAMAP-Rule MF_03148
Region177 – 1782Substrate binding HAMAP-Rule MF_03148

Sites

Metal binding441Magnesium
Metal binding721Magnesium By similarity
Binding site561Substrate
Binding site1721Substrate

Amino acid modifications

Modified residue21N-acetylalanine Ref.9

Natural variations

Alternative sequence7 – 2317Missing in isoform 2.
VSP_042548
Alternative sequence23 – 6341Missing in isoform 3.
VSP_045545
Natural variant321P → T in ITPAD; complete loss of enzymatic activity at homozygosity; partial loss of activity without ITP accumulation in heterozygous individuals. Ref.2 Ref.15 Ref.16
Corresponds to variant rs1127354 [ dbSNP | Ensembl ].
VAR_015576

Experimental info

Sequence conflict331C → R in AAK21848. Ref.1
Sequence conflict411D → G in AAG43165. Ref.2

Secondary structure

................................ 194
Helix Strand Turn

Details...

Sequences

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

Last modified April 23, 2003. Version 2.
Checksum: F0EC6A523722DF05

FASTA19421,446
        10         20         30         40         50         60 
MAASLVGKKI VFVTGNAKKL EEVVQILGDK FPCTLVAQKI DLPEYQGEPD EISIQKCQEA 

        70         80         90        100        110        120 
VRQVQGPVLV EDTCLCFNAL GGLPGPYIKW FLEKLKPEGL HQLLAGFEDK SAYALCTFAL 

       130        140        150        160        170        180 
STGDPSQPVR LFRGRTSGRI VAPRGCQDFG WDPCFQPDGY EQTYAEMPKA EKNAVSHRFR 

       190 
ALLELQEYFG SLAA 

« Hide

Isoform 2 [UniParc].

Checksum: AAE9E3F8713D476D
Show »

FASTA17719,603
Isoform 3 [UniParc].

Checksum: DDC0D289C0158A76
Show »

FASTA15316,833

References

« Hide 'large scale' references
[1]"Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the ITPA gene."
Lin S., McLennan A.G., Ying K., Wang Z., Gu S., Jin H., Wu C., Lu W., Yuan Y., Tang R., Xie Y., Mao Y.
J. Biol. Chem. 276:18695-18701(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBUNIT, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Fetal brain.
[2]Mao Y.M., Xie Y., Zheng Z.H.
Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ITPAD THR-32.
Tissue: Fetal brain.
[3]"Molecular cloning of cDNA associated with human lung cancer antigen and study on its functions."
Fan M.-Z., Chen Z., Cao Z.-M.
Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Lung carcinoma.
[4]Danaei Y., Behmanesh M., Sadeghi Zadeh M.
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[5]"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients."
Shichijo S., Itoh K.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Colon adenocarcinoma.
[6]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton 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].
[8]"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] (ISOFORMS 1 AND 3).
Tissue: Lung carcinoma and Neuroblastoma.
[9]Bienvenut W.V., Waridel P., Quadroni M.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-9; 40-56; 95-110 AND 181-194, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[10]Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 10-56 AND 95-130, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[11]"Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate pyrophosphohydrolase."
Burgis N.E., Cunningham R.P.
J. Biol. Chem. 282:3531-3538(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBSTRATE SPECIFICITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[12]"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].
[13]"Structure of the orthorhombic form of human inosine triphosphate pyrophosphatase."
Porta J., Kolar C., Kozmin S.G., Pavlov Y.I., Borgstahl G.E.
Acta Crystallogr. F 62:1076-1081(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS).
[14]"Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T."
Stenmark P., Kursula P., Flodin S., Graslund S., Landry R., Nordlund P., Schueler H.
J. Biol. Chem. 282:3182-3187(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) ALONE AND IN COMPLEX WITH ITP, COFACTOR, MAGNESIUM-BINDING SITES, SUBSTRATE-BINDING SITES.
[15]"Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency."
Sumi S., Marinaki A.M., Arenas M., Fairbanks L., Shobowale-Bakre M., Rees D.C., Thein S.L., Ansari A., Sanderson J., De Abreu R.A., Simmonds H.A., Duley J.A.
Hum. Genet. 111:360-367(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ITPAD THR-32.
[16]"DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency."
Cao H., Hegele R.A.
J. Hum. Genet. 47:620-622(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ITPAD THR-32.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF219116 mRNA. Translation: AAK21848.1.
AF063607 mRNA. Translation: AAG43165.1.
AF026816 mRNA. Translation: AAB82608.2.
EF199841 mRNA. Translation: ABP01354.1.
EF213026 mRNA. Translation: ABO70316.1.
AB062127 mRNA. Translation: BAB93459.1.
AL109976 Genomic DNA. Translation: CAC16798.3.
AL121891, AL109976 Genomic DNA. Translation: CAI19399.1.
AL121891, AL109976 Genomic DNA. Translation: CAM27676.1.
AL109976, AL121891 Genomic DNA. Translation: CAM28311.1.
CH471133 Genomic DNA. Translation: EAX10541.1.
BC010138 mRNA. Translation: AAH10138.1.
BI115811 mRNA. No translation available.
CCDSCCDS13051.1. [Q9BY32-1]
CCDS46576.1. [Q9BY32-2]
CCDS58762.1. [Q9BY32-3]
RefSeqNP_001254552.1. NM_001267623.1. [Q9BY32-3]
NP_258412.1. NM_033453.3. [Q9BY32-1]
NP_852470.1. NM_181493.2. [Q9BY32-2]
UniGeneHs.415299.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CARX-ray1.09A/B1-194[»]
2I5DX-ray1.63A1-194[»]
2J4EX-ray2.80A/B/C/D/E/F/G/H1-194[»]
4F95X-ray2.07A1-194[»]
ProteinModelPortalQ9BY32.
SMRQ9BY32. Positions 1-194.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109909. 3 interactions.
IntActQ9BY32. 1 interaction.
MINTMINT-5006578.
STRING9606.ENSP00000369456.

PTM databases

PhosphoSiteQ9BY32.

Polymorphism databases

DMDM30173120.

Proteomic databases

MaxQBQ9BY32.
PaxDbQ9BY32.
PeptideAtlasQ9BY32.
PRIDEQ9BY32.

Protocols and materials databases

DNASU3704.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000380113; ENSP00000369456; ENSG00000125877. [Q9BY32-1]
ENST00000399838; ENSP00000382732; ENSG00000125877. [Q9BY32-3]
ENST00000455664; ENSP00000413282; ENSG00000125877. [Q9BY32-2]
GeneID3704.
KEGGhsa:3704.
UCSCuc002wid.4. human. [Q9BY32-1]
uc002wie.4. human. [Q9BY32-2]
uc031rsg.1. human.

Organism-specific databases

CTD3704.
GeneCardsGC20P003189.
HGNCHGNC:6176. ITPA.
HPAHPA022824.
MIM147520. gene.
613850. phenotype.
neXtProtNX_Q9BY32.
Orphanet319684. Inosine triphosphatase deficiency.
284113. Susceptibility to adverse reaction due to mercaptopurine.
PharmGKBPA29973.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0127.
HOGENOMHOG000293320.
HOVERGENHBG039521.
InParanoidQ9BY32.
KOK01519.
OMAPGAYIKW.
OrthoDBEOG7X0VJG.
PhylomeDBQ9BY32.
TreeFamTF105614.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKQ9BY32.

Gene expression databases

ArrayExpressQ9BY32.
BgeeQ9BY32.
CleanExHS_ITPA.
GenevestigatorQ9BY32.

Family and domain databases

Gene3D3.90.950.10. 1 hit.
HAMAPMF_03148. HAM1_NTPase.
InterProIPR002637. Ham1p-like.
IPR027502. ITPase.
IPR029001. ITPase-like_fam.
[Graphical view]
PANTHERPTHR11067. PTHR11067. 1 hit.
PfamPF01725. Ham1p_like. 1 hit.
[Graphical view]
SUPFAMSSF52972. SSF52972. 1 hit.
TIGRFAMsTIGR00042. TIGR00042. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9BY32.
GeneWikiITPA.
GenomeRNAi3704.
NextBio14515.
PROQ9BY32.
SOURCESearch...

Entry information

Entry nameITPA_HUMAN
AccessionPrimary (citable) accession number: Q9BY32
Secondary accession number(s): A2A2N2 expand/collapse secondary AC list , A4UIM5, B2BCH7, O14878, Q5JWH4, Q9BYN1, Q9BYX0, Q9H3H8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: April 23, 2003
Last modified: July 9, 2014
This is version 130 of the entry and version 2 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 20

Human chromosome 20: entries, gene names and cross-references to MIM