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Protein

Inosine triphosphate pyrophosphatase

Gene

ITPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionHydrolase
Biological processNucleotide metabolism
LigandMagnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.1.19 2681
ReactomeiR-HSA-74259 Purine catabolism
SABIO-RKiQ9BY32

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

EuPathDBiHostDB:ENSG00000125877.12
HGNCiHGNC:6176 ITPA
MIMi147520 gene
neXtProtiNX_Q9BY32

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs1127354EnsemblClinVar.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 dbSNP:rs746930990Ensembl.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

Chemistry databases

DrugBankiDB04272 Citric Acid

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
ProteomicsDBi79572
79573 [Q9BY32-2]
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 Expressed in 212 organ(s), highest expression level in adult mammalian kidney
CleanExiHS_ITPA
ExpressionAtlasiQ9BY32 baseline and differential
GenevisibleiQ9BY32 HS

Organism-specific databases

HPAiHPA022824

Interactioni

Subunit structurei

Homodimer.UniRule annotation2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-2831363,EBI-2831363

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109909, 57 interactors
IntActiQ9BY32, 1 interactor
STRINGi9606.ENSP00000369456

Structurei

Secondary structure

1194
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiYDPIFQP
OrthoDBiEOG091G0MUD
PhylomeDBiQ9BY32
TreeFamiTF105614

Family and domain databases

CDDicd00515 HAM1, 1 hit
Gene3Di3.90.950.10, 1 hit
HAMAPiMF_03148 HAM1_NTPase, 1 hit
InterProiView protein in InterPro
IPR002637 Ham1p-like
IPR027502 ITPase
IPR029001 ITPase-like_fam
PANTHERiPTHR11067 PTHR11067, 1 hit
PfamiView protein in Pfam
PF01725 Ham1p_like, 1 hit
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 dbSNP:rs1127354EnsemblClinVar.1
Natural variantiVAR_075084178R → C in EIEE35; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs746930990Ensembl.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 No translation available.
AL121891 Genomic DNA No translation available.
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

Similar proteinsi

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 No translation available.
AL121891 Genomic DNA No translation available.
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, 57 interactors
IntActiQ9BY32, 1 interactor
STRINGi9606.ENSP00000369456

Chemistry databases

DrugBankiDB04272 Citric Acid

PTM databases

iPTMnetiQ9BY32
PhosphoSitePlusiQ9BY32

Polymorphism and mutation databases

BioMutaiITPA
DMDMi30173120

Proteomic databases

EPDiQ9BY32
MaxQBiQ9BY32
PaxDbiQ9BY32
PeptideAtlasiQ9BY32
PRIDEiQ9BY32
ProteomicsDBi79572
79573 [Q9BY32-2]
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
EuPathDBiHostDB:ENSG00000125877.12
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
OMAiYDPIFQP
OrthoDBiEOG091G0MUD
PhylomeDBiQ9BY32
TreeFamiTF105614

Enzyme and pathway databases

BRENDAi3.6.1.19 2681
ReactomeiR-HSA-74259 Purine catabolism
SABIO-RKiQ9BY32

Miscellaneous databases

ChiTaRSiITPA human
EvolutionaryTraceiQ9BY32
GeneWikiiITPA
GenomeRNAii3704
PROiPR:Q9BY32
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125877 Expressed in 212 organ(s), highest expression level in adult mammalian kidney
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
InterProiView protein in InterPro
IPR002637 Ham1p-like
IPR027502 ITPase
IPR029001 ITPase-like_fam
PANTHERiPTHR11067 PTHR11067, 1 hit
PfamiView protein in Pfam
PF01725 Ham1p_like, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: April 23, 2003
Last sequence update: April 23, 2003
Last modified: October 10, 2018
This is version 165 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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