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Protein

Inosine triphosphate pyrophosphatase

Gene

ITPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation1 Publication

Catalytic activityi

A nucleoside triphosphate + H2O = a nucleotide + diphosphate.UniRule annotation1 Publication

Cofactori

Mg2+1 PublicationNote: Binds 1 Mg2+ ion per subunit.1 Publication

Kineticsi

Vmax values are similar for dITP, dHAPTP and dGTP.

  1. KM=0.51 mM for ITP2 Publications
  2. KM=0.31 mM for dITP2 Publications
  3. KM=0.57 mM for XTP2 Publications
  4. KM=40.7 µM for dHAPTP2 Publications
  5. KM=933 µM for dGTP2 Publications
  1. Vmax=1520 µmol/min/mg enzyme for ITP2 Publications
  2. Vmax=940 µmol/min/mg enzyme for dITP2 Publications
  3. Vmax=1680 µmol/min/mg enzyme for XTP2 Publications

pH dependencei

Optimum pH is 10.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi44Magnesium1
Binding sitei56Substrate1
Metal bindingi72MagnesiumBy similarity1
Binding sitei172Substrate1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Nucleotide metabolism

Keywords - Ligandi

Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS13184-MONOMER.
BRENDAi3.6.1.19. 2681.
ReactomeiR-HSA-15869. Metabolism of nucleotides.
SABIO-RKQ9BY32.

Names & Taxonomyi

Protein namesi
Recommended name:
Inosine triphosphate pyrophosphataseUniRule annotation (EC:3.6.1.9UniRule annotation1 Publication)
Short name:
ITPaseUniRule annotation
Short name:
Inosine triphosphataseUniRule annotation
Alternative name(s):
Non-canonical purine NTP pyrophosphataseUniRule annotation
Non-standard purine NTP pyrophosphataseUniRule annotation
Nucleoside-triphosphate diphosphataseUniRule annotation
Nucleoside-triphosphate pyrophosphataseUniRule annotation
Short name:
NTPaseUniRule annotation
Putative oncogene protein hlc14-06-p
Gene namesi
Name:ITPAUniRule annotation
Synonyms:C20orf37
ORF Names:My049, OK/SW-cl.9
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:6176. ITPA.

Subcellular locationi

  • Cytoplasm UniRule annotation1 Publication

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD)3 Publications
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.
Disease descriptionA 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.
See also OMIM:613850
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01557632P → T in ITPAD; complete loss of enzymatic activity at homozygosity; partial loss of activity without ITP accumulation in heterozygous individuals. 3 PublicationsCorresponds to variant rs1127354dbSNPEnsembl.1
Epileptic encephalopathy, early infantile, 35 (EIEE35)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. EIEE35 is characterized by onset of seizures in the first months of life associated with essentially no normal development. Many patients die in early childhood.
See also OMIM:616647
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075084178R → C in EIEE35; unknown pathological significance. 1 PublicationCorresponds to variant rs746930990dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi3704.
MalaCardsiITPA.
MIMi613850. phenotype.
616647. phenotype.
OpenTargetsiENSG00000125877.
Orphaneti319684. Inosine triphosphatase deficiency.
284113. Susceptibility to adverse reaction due to mercaptopurine.
PharmGKBiPA29973.

Polymorphism and mutation databases

BioMutaiITPA.
DMDMi30173120.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedUniRule annotation1 Publication
ChainiPRO_00001782802 – 194Inosine triphosphate pyrophosphataseAdd BLAST193

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineUniRule annotation1 Publication1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9BY32.
MaxQBiQ9BY32.
PaxDbiQ9BY32.
PeptideAtlasiQ9BY32.
PRIDEiQ9BY32.
TopDownProteomicsiQ9BY32-1. [Q9BY32-1]

PTM databases

iPTMnetiQ9BY32.
PhosphoSitePlusiQ9BY32.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000125877.
CleanExiHS_ITPA.
ExpressionAtlasiQ9BY32. baseline and differential.
GenevisibleiQ9BY32. HS.

Organism-specific databases

HPAiHPA022824.

Interactioni

Subunit structurei

Homodimer.UniRule annotation2 Publications

Protein-protein interaction databases

BioGridi109909. 53 interactors.
IntActiQ9BY32. 1 interactor.
MINTiMINT-5006578.
STRINGi9606.ENSP00000369456.

Structurei

Secondary structure

1194
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 5Combined sources4
Beta strandi9 – 13Combined sources5
Helixi17 – 27Combined sources11
Beta strandi33 – 38Combined sources6
Beta strandi45 – 47Combined sources3
Helixi49 – 64Combined sources16
Beta strandi68 – 77Combined sources10
Helixi78 – 80Combined sources3
Helixi88 – 102Combined sources15
Turni103 – 106Combined sources4
Beta strandi111 – 121Combined sources11
Beta strandi125 – 127Combined sources3
Beta strandi130 – 140Combined sources11
Helixi152 – 154Combined sources3
Beta strandi155 – 157Combined sources3
Turni164 – 166Combined sources3
Helixi169 – 175Combined sources7
Helixi177 – 189Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9BY32.
SMRiQ9BY32.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9BY32.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 19Substrate binding6
Regioni72 – 73Substrate binding2
Regioni149 – 152Substrate binding4
Regioni177 – 178Substrate binding2

Sequence similaritiesi

Belongs to the HAM1 NTPase family.UniRule annotation

Phylogenomic databases

eggNOGiKOG3222. Eukaryota.
COG0127. LUCA.
GeneTreeiENSGT00390000015399.
HOGENOMiHOG000293320.
HOVERGENiHBG039521.
InParanoidiQ9BY32.
KOiK01519.
OMAiMKIYFAT.
OrthoDBiEOG091G0MUD.
PhylomeDBiQ9BY32.
TreeFamiTF105614.

Family and domain databases

CDDicd00515. HAM1. 1 hit.
Gene3Di3.90.950.10. 1 hit.
HAMAPiMF_03148. HAM1_NTPase. 1 hit.
InterProiIPR002637. Ham1p-like.
IPR027502. ITPase.
IPR029001. ITPase-like_fam.
[Graphical view]
PANTHERiPTHR11067. PTHR11067. 1 hit.
PfamiPF01725. Ham1p_like. 1 hit.
[Graphical view]
SUPFAMiSSF52972. SSF52972. 1 hit.
TIGRFAMsiTIGR00042. TIGR00042. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9BY32-1) [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

        10         20         30         40         50
MAASLVGKKI VFVTGNAKKL EEVVQILGDK FPCTLVAQKI DLPEYQGEPD
60 70 80 90 100
EISIQKCQEA VRQVQGPVLV EDTCLCFNAL GGLPGPYIKW FLEKLKPEGL
110 120 130 140 150
HQLLAGFEDK SAYALCTFAL STGDPSQPVR LFRGRTSGRI VAPRGCQDFG
160 170 180 190
WDPCFQPDGY EQTYAEMPKA EKNAVSHRFR ALLELQEYFG SLAA
Length:194
Mass (Da):21,446
Last modified:April 23, 2003 - v2
Checksum:iF0EC6A523722DF05
GO
Isoform 2 (identifier: Q9BY32-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     7-23: Missing.

Note: No experimental confirmation available.
Show »
Length:177
Mass (Da):19,603
Checksum:iAAE9E3F8713D476D
GO
Isoform 3 (identifier: Q9BY32-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     23-63: Missing.

Note: No experimental confirmation available.
Show »
Length:153
Mass (Da):16,833
Checksum:iDDC0D289C0158A76
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti33C → R in AAK21848 (PubMed:11278832).Curated1
Sequence conflicti41D → G in AAG43165 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01557632P → T in ITPAD; complete loss of enzymatic activity at homozygosity; partial loss of activity without ITP accumulation in heterozygous individuals. 3 PublicationsCorresponds to variant rs1127354dbSNPEnsembl.1
Natural variantiVAR_075084178R → C in EIEE35; unknown pathological significance. 1 PublicationCorresponds to variant rs746930990dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0425487 – 23Missing in isoform 2. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_04554523 – 63Missing in isoform 3. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13051.1. [Q9BY32-1]
CCDS46576.1. [Q9BY32-2]
CCDS58762.1. [Q9BY32-3]
RefSeqiNP_001254552.1. NM_001267623.1. [Q9BY32-3]
NP_258412.1. NM_033453.3. [Q9BY32-1]
NP_852470.1. NM_181493.3. [Q9BY32-2]
UniGeneiHs.415299.

Genome annotation databases

EnsembliENST00000380113; ENSP00000369456; ENSG00000125877. [Q9BY32-1]
ENST00000399838; ENSP00000382732; ENSG00000125877. [Q9BY32-3]
ENST00000455664; ENSP00000413282; ENSG00000125877. [Q9BY32-2]
GeneIDi3704.
KEGGihsa:3704.
UCSCiuc002wid.4. human. [Q9BY32-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13051.1. [Q9BY32-1]
CCDS46576.1. [Q9BY32-2]
CCDS58762.1. [Q9BY32-3]
RefSeqiNP_001254552.1. NM_001267623.1. [Q9BY32-3]
NP_258412.1. NM_033453.3. [Q9BY32-1]
NP_852470.1. NM_181493.3. [Q9BY32-2]
UniGeneiHs.415299.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliQ9BY32.
SMRiQ9BY32.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109909. 53 interactors.
IntActiQ9BY32. 1 interactor.
MINTiMINT-5006578.
STRINGi9606.ENSP00000369456.

PTM databases

iPTMnetiQ9BY32.
PhosphoSitePlusiQ9BY32.

Polymorphism and mutation databases

BioMutaiITPA.
DMDMi30173120.

Proteomic databases

EPDiQ9BY32.
MaxQBiQ9BY32.
PaxDbiQ9BY32.
PeptideAtlasiQ9BY32.
PRIDEiQ9BY32.
TopDownProteomicsiQ9BY32-1. [Q9BY32-1]

Protocols and materials databases

DNASUi3704.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000380113; ENSP00000369456; ENSG00000125877. [Q9BY32-1]
ENST00000399838; ENSP00000382732; ENSG00000125877. [Q9BY32-3]
ENST00000455664; ENSP00000413282; ENSG00000125877. [Q9BY32-2]
GeneIDi3704.
KEGGihsa:3704.
UCSCiuc002wid.4. human. [Q9BY32-1]

Organism-specific databases

CTDi3704.
DisGeNETi3704.
GeneCardsiITPA.
HGNCiHGNC:6176. ITPA.
HPAiHPA022824.
MalaCardsiITPA.
MIMi147520. gene.
613850. phenotype.
616647. phenotype.
neXtProtiNX_Q9BY32.
OpenTargetsiENSG00000125877.
Orphaneti319684. Inosine triphosphatase deficiency.
284113. Susceptibility to adverse reaction due to mercaptopurine.
PharmGKBiPA29973.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3222. Eukaryota.
COG0127. LUCA.
GeneTreeiENSGT00390000015399.
HOGENOMiHOG000293320.
HOVERGENiHBG039521.
InParanoidiQ9BY32.
KOiK01519.
OMAiMKIYFAT.
OrthoDBiEOG091G0MUD.
PhylomeDBiQ9BY32.
TreeFamiTF105614.

Enzyme and pathway databases

BioCyciZFISH:HS13184-MONOMER.
BRENDAi3.6.1.19. 2681.
ReactomeiR-HSA-15869. Metabolism of nucleotides.
SABIO-RKQ9BY32.

Miscellaneous databases

ChiTaRSiITPA. human.
EvolutionaryTraceiQ9BY32.
GeneWikiiITPA.
GenomeRNAii3704.
PROiQ9BY32.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125877.
CleanExiHS_ITPA.
ExpressionAtlasiQ9BY32. baseline and differential.
GenevisibleiQ9BY32. HS.

Family and domain databases

CDDicd00515. HAM1. 1 hit.
Gene3Di3.90.950.10. 1 hit.
HAMAPiMF_03148. HAM1_NTPase. 1 hit.
InterProiIPR002637. Ham1p-like.
IPR027502. ITPase.
IPR029001. ITPase-like_fam.
[Graphical view]
PANTHERiPTHR11067. PTHR11067. 1 hit.
PfamiPF01725. Ham1p_like. 1 hit.
[Graphical view]
SUPFAMiSSF52972. SSF52972. 1 hit.
TIGRFAMsiTIGR00042. TIGR00042. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiITPA_HUMAN
AccessioniPrimary (citable) accession number: Q9BY32
Secondary accession number(s): A2A2N2
, A4UIM5, B2BCH7, O14878, Q5JWH4, Q9BYN1, Q9BYX0, Q9H3H8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: April 23, 2003
Last modified: November 30, 2016
This is version 154 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.