ID ITPA_HUMAN Reviewed; 194 AA. AC Q9BY32; A2A2N2; A4UIM5; B2BCH7; O14878; Q5JWH4; Q9BYN1; Q9BYX0; Q9H3H8; DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 23-APR-2003, sequence version 2. DT 24-JAN-2024, entry version 196. DE RecName: Full=Inosine triphosphate pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148, ECO:0000303|PubMed:11278832}; DE Short=ITPase {ECO:0000255|HAMAP-Rule:MF_03148}; DE Short=Inosine triphosphatase {ECO:0000255|HAMAP-Rule:MF_03148}; DE EC=3.6.1.9 {ECO:0000255|HAMAP-Rule:MF_03148, ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17090528}; DE AltName: Full=Non-canonical purine NTP pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148}; DE AltName: Full=Non-standard purine NTP pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148}; DE AltName: Full=Nucleoside-triphosphate diphosphatase {ECO:0000255|HAMAP-Rule:MF_03148}; DE AltName: Full=Nucleoside-triphosphate pyrophosphatase {ECO:0000255|HAMAP-Rule:MF_03148}; DE Short=NTPase {ECO:0000255|HAMAP-Rule:MF_03148}; DE AltName: Full=Putative oncogene protein hlc14-06-p; GN Name=ITPA {ECO:0000255|HAMAP-Rule:MF_03148}; Synonyms=C20orf37; GN ORFNames=My049, OK/SW-cl.9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBSTRATE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=11278832; DOI=10.1074/jbc.m011084200; RA Lin S., McLennan A.G., Ying K., Wang Z., Gu S., Jin H., Wu C., Lu W., RA Yuan Y., Tang R., Xie Y., Mao Y.; RT "Cloning, expression, and characterization of a human inosine triphosphate RT pyrophosphatase encoded by the ITPA gene."; RL J. Biol. Chem. 276:18695-18701(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ITPAD RP THR-32. RC TISSUE=Fetal brain; RA Mao Y.M., Xie Y., Zheng Z.H.; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lung carcinoma; RA Fan M.-Z., Chen Z., Cao Z.-M.; RT "Molecular cloning of cDNA associated with human lung cancer antigen and RT study on its functions."; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RA Danaei Y., Behmanesh M., Sadeghi Zadeh M.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon adenocarcinoma; RA Shichijo S., Itoh K.; RT "Identification of immuno-peptidmics that are recognized by tumor-reactive RT CTL generated from TIL of colon cancer patients."; RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Lung carcinoma, and Neuroblastoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-9; 40-56; 95-110 AND 181-194, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [10] RP PROTEIN SEQUENCE OF 10-56 AND 95-130, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Afjehi-Sadat L., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [11] RP SUBSTRATE SPECIFICITY, FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=17090528; DOI=10.1074/jbc.m608708200; RA Burgis N.E., Cunningham R.P.; RT "Substrate specificity of RdgB protein, a deoxyribonucleoside triphosphate RT pyrophosphohydrolase."; RL J. Biol. Chem. 282:3531-3538(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP INVOLVEMENT IN DEE35, AND VARIANT DEE35 CYS-178. RX PubMed=26224535; DOI=10.1002/ana.24496; RA Kevelam S.H., Bierau J., Salvarinova R., Agrawal S., Honzik T., Visser D., RA Weiss M.M., Salomons G.S., Abbink T.E., Waisfisz Q., van der Knaap M.S.; RT "Recessive ITPA mutations cause an early infantile encephalopathy."; RL Ann. Neurol. 78:649-658(2015). RN [14] {ECO:0007744|PDB:2I5D} RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS). RX PubMed=17077483; DOI=10.1107/s1744309106041790; RA Porta J., Kolar C., Kozmin S.G., Pavlov Y.I., Borgstahl G.E.; RT "Structure of the orthorhombic form of human inosine triphosphate RT pyrophosphatase."; RL Acta Crystallogr. F 62:1076-1081(2006). RN [15] {ECO:0007744|PDB:2CAR, ECO:0007744|PDB:2J4E} RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) ALONE AND IN COMPLEX WITH ITP AND RP MAGNESIUM, AND COFACTOR. RX PubMed=17138556; DOI=10.1074/jbc.m609838200; RA Stenmark P., Kursula P., Flodin S., Graslund S., Landry R., Nordlund P., RA Schueler H.; RT "Crystal structure of human inosine triphosphatase. Substrate binding and RT implication of the inosine triphosphatase deficiency mutation P32T."; RL J. Biol. Chem. 282:3182-3187(2007). RN [16] RP VARIANT ITPAD THR-32. RX PubMed=12384777; DOI=10.1007/s00439-002-0798-z; RA Sumi S., Marinaki A.M., Arenas M., Fairbanks L., Shobowale-Bakre M., RA Rees D.C., Thein S.L., Ansari A., Sanderson J., De Abreu R.A., RA Simmonds H.A., Duley J.A.; RT "Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency."; RL Hum. Genet. 111:360-367(2002). RN [17] RP VARIANT ITPAD THR-32. RX PubMed=12436200; DOI=10.1007/s100380200095; RA Cao H., Hegele R.A.; RT "DNA polymorphisms in ITPA including basis of inosine triphosphatase RT deficiency."; RL J. Hum. Genet. 47:620-622(2002). CC -!- FUNCTION: Pyrophosphatase that hydrolyzes the non-canonical purine CC nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate CC (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate CC (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective CC monophosphate derivatives. The enzyme does not distinguish between the CC deoxy- and ribose forms. Probably excludes non-canonical purines from CC RNA and DNA precursor pools, thus preventing their incorporation into CC RNA and DNA and avoiding chromosomal lesions. {ECO:0000255|HAMAP- CC Rule:MF_03148, ECO:0000269|PubMed:11278832, CC ECO:0000269|PubMed:17090528}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'- CC phosphate + diphosphate + H(+); Xref=Rhea:RHEA:23996, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:58043, ChEBI:CHEBI:61557; EC=3.6.1.9; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148, CC ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17090528}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23997; CC Evidence={ECO:0000305|PubMed:11278832, ECO:0000305|PubMed:17090528}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + H2O = a 2'- CC deoxyribonucleoside 5'-phosphate + diphosphate + H(+); CC Xref=Rhea:RHEA:44644, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:65317; EC=3.6.1.9; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03148, CC ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17090528}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44645; CC Evidence={ECO:0000305|PubMed:11278832, ECO:0000305|PubMed:17090528}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + ITP = diphosphate + H(+) + IMP; Xref=Rhea:RHEA:29399, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:58053, ChEBI:CHEBI:61402; EC=3.6.1.9; CC Evidence={ECO:0000269|PubMed:11278832}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29400; CC Evidence={ECO:0000305|PubMed:11278832}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dITP + H2O = dIMP + diphosphate + H(+); Xref=Rhea:RHEA:28342, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:61194, ChEBI:CHEBI:61382; EC=3.6.1.9; CC Evidence={ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17090528}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28343; CC Evidence={ECO:0000305|PubMed:11278832, ECO:0000305|PubMed:17090528}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H2O + XTP = diphosphate + H(+) + XMP; Xref=Rhea:RHEA:28610, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57464, ChEBI:CHEBI:61314; EC=3.6.1.9; CC Evidence={ECO:0000269|PubMed:11278832}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:28611; CC Evidence={ECO:0000305|PubMed:11278832}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17138556}; CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:17138556}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.51 mM for ITP {ECO:0000269|PubMed:11278832}; CC KM=0.31 mM for dITP {ECO:0000269|PubMed:11278832}; CC KM=0.57 mM for XTP {ECO:0000269|PubMed:11278832}; CC KM=32.5 uM for dITP {ECO:0000269|PubMed:17090528}; CC KM=40.7 uM for dHAPTP {ECO:0000269|PubMed:17090528}; CC KM=993 uM for dGTP {ECO:0000269|PubMed:17090528}; CC Vmax=1520 umol/min/mg enzyme with ITP as substrate CC {ECO:0000269|PubMed:11278832}; CC Vmax=940 umol/min/mg enzyme with dITP as substrate CC {ECO:0000269|PubMed:11278832}; CC Vmax=1680 umol/min/mg enzyme with XTP as substrate CC {ECO:0000269|PubMed:11278832}; CC Note=kcat is 580 sec(-1) with ITP as substrate (PubMed:11278832). CC kcat is 360 sec(-1) with dITP as substrate (PubMed:11278832). kcat is CC 640 sec(-1) with XTP as substrate (PubMed:11278832). kcat is 79.6 CC sec(-1) with dITP as substrate (PubMed:17090528). kcat is 85.3 CC sec(-1) with dHAPTP as substrate (PubMed:17090528). kcat is 12.1 CC sec(-1) with dGTP as substrate (PubMed:17090528). CC {ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17090528}; CC pH dependence: CC Optimum pH is 10. {ECO:0000269|PubMed:11278832}; CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_03148, CC ECO:0000269|PubMed:11278832, ECO:0000269|PubMed:17138556}. CC -!- INTERACTION: CC Q9BY32; Q9BY32: ITPA; NbExp=4; IntAct=EBI-2831363, EBI-2831363; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03148, CC ECO:0000269|PubMed:11278832}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9BY32-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BY32-2; Sequence=VSP_042548; CC Name=3; CC IsoId=Q9BY32-3; Sequence=VSP_045545; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, liver, sex CC glands, thyroid and adrenal gland. CC -!- DISEASE: Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) CC [MIM:613850]: A common inherited condition characterized by the CC abnormal accumulation of inosine triphosphate in erythrocytes. It might CC have pharmacogenomic implications and be related to increased drug CC toxicity of purine analog drugs. {ECO:0000269|PubMed:12384777, CC ECO:0000269|PubMed:12436200, ECO:0000269|Ref.2}. Note=The disease is CC caused by variants affecting the gene represented in this entry. Three CC different human populations have been reported with respect to their CC ITPase activity: high, mean (25% of high) and low activity. The variant CC Thr-32 is associated with complete loss of enzyme activity, may be by CC altering the local secondary structure of the protein. Heterozygotes CC for this polymorphism have 22.5% of the control activity: this is CC consistent with a dimeric structure of the enzyme. CC -!- DISEASE: Developmental and epileptic encephalopathy 35 (DEE35) CC [MIM:616647]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE35 is characterized by onset of seizures in the CC first months of life associated with essentially no normal development. CC Many patients die in early childhood. {ECO:0000269|PubMed:26224535}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the HAM1 NTPase family. {ECO:0000255|HAMAP- CC Rule:MF_03148}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF219116; AAK21848.1; -; mRNA. DR EMBL; AF063607; AAG43165.1; -; mRNA. DR EMBL; AF026816; AAB82608.2; -; mRNA. DR EMBL; EF199841; ABP01354.1; -; mRNA. DR EMBL; EF213026; ABO70316.1; -; mRNA. DR EMBL; AB062127; BAB93459.1; -; mRNA. DR EMBL; AL109976; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL121891; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10541.1; -; Genomic_DNA. DR EMBL; BC010138; AAH10138.1; -; mRNA. DR EMBL; BI115811; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS13051.1; -. [Q9BY32-1] DR CCDS; CCDS46576.1; -. [Q9BY32-2] DR CCDS; CCDS58762.1; -. [Q9BY32-3] DR RefSeq; NP_001254552.1; NM_001267623.1. [Q9BY32-3] DR RefSeq; NP_258412.1; NM_033453.3. [Q9BY32-1] DR RefSeq; NP_852470.1; NM_181493.3. [Q9BY32-2] DR PDB; 2CAR; X-ray; 1.09 A; A/B=1-194. DR PDB; 2I5D; X-ray; 1.63 A; A=1-194. DR PDB; 2J4E; X-ray; 2.80 A; A/B/C/D/E/F/G/H=1-194. DR PDB; 4F95; X-ray; 2.07 A; A=1-194. DR PDBsum; 2CAR; -. DR PDBsum; 2I5D; -. DR PDBsum; 2J4E; -. DR PDBsum; 4F95; -. DR AlphaFoldDB; Q9BY32; -. DR SMR; Q9BY32; -. DR BioGRID; 109909; 97. DR IntAct; Q9BY32; 16. DR STRING; 9606.ENSP00000369456; -. DR BindingDB; Q9BY32; -. DR ChEMBL; CHEMBL4105788; -. DR DrugBank; DB00993; Azathioprine. DR DrugBank; DB04272; Citric acid. DR GlyGen; Q9BY32; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9BY32; -. DR MetOSite; Q9BY32; -. DR PhosphoSitePlus; Q9BY32; -. DR BioMuta; ITPA; -. DR DMDM; 30173120; -. DR EPD; Q9BY32; -. DR jPOST; Q9BY32; -. DR MassIVE; Q9BY32; -. DR MaxQB; Q9BY32; -. DR PaxDb; 9606-ENSP00000369456; -. DR PeptideAtlas; Q9BY32; -. DR ProteomicsDB; 216; -. DR ProteomicsDB; 79572; -. [Q9BY32-1] DR ProteomicsDB; 79573; -. [Q9BY32-2] DR Pumba; Q9BY32; -. DR TopDownProteomics; Q9BY32-1; -. [Q9BY32-1] DR Antibodypedia; 7322; 316 antibodies from 31 providers. DR DNASU; 3704; -. DR Ensembl; ENST00000380113.8; ENSP00000369456.3; ENSG00000125877.13. [Q9BY32-1] DR Ensembl; ENST00000399838.3; ENSP00000382732.3; ENSG00000125877.13. [Q9BY32-3] DR Ensembl; ENST00000455664.6; ENSP00000413282.1; ENSG00000125877.13. [Q9BY32-2] DR GeneID; 3704; -. DR KEGG; hsa:3704; -. DR MANE-Select; ENST00000380113.8; ENSP00000369456.3; NM_033453.4; NP_258412.1. DR UCSC; uc002wid.4; human. [Q9BY32-1] DR AGR; HGNC:6176; -. DR CTD; 3704; -. DR DisGeNET; 3704; -. DR GeneCards; ITPA; -. DR HGNC; HGNC:6176; ITPA. DR HPA; ENSG00000125877; Low tissue specificity. DR MalaCards; ITPA; -. DR MIM; 147520; gene. DR MIM; 613850; phenotype. DR MIM; 616647; phenotype. DR neXtProt; NX_Q9BY32; -. DR OpenTargets; ENSG00000125877; -. DR Orphanet; 457375; ITPA-related lethal infantile neurological disorder with cataract and cardiac involvement. DR PharmGKB; PA29973; -. DR VEuPathDB; HostDB:ENSG00000125877; -. DR eggNOG; KOG3222; Eukaryota. DR GeneTree; ENSGT00390000015399; -. DR HOGENOM; CLU_082080_1_1_1; -. DR InParanoid; Q9BY32; -. DR OMA; YDPIFQP; -. DR OrthoDB; 479at2759; -. DR PhylomeDB; Q9BY32; -. DR TreeFam; TF105614; -. DR BRENDA; 3.6.1.66; 2681. DR BRENDA; 3.6.1.9; 2681. DR PathwayCommons; Q9BY32; -. DR Reactome; R-HSA-74259; Purine catabolism. DR Reactome; R-HSA-9755088; Ribavirin ADME. DR SABIO-RK; Q9BY32; -. DR SignaLink; Q9BY32; -. DR BioGRID-ORCS; 3704; 18 hits in 1161 CRISPR screens. DR ChiTaRS; ITPA; human. DR EvolutionaryTrace; Q9BY32; -. DR GeneWiki; ITPA; -. DR GenomeRNAi; 3704; -. DR Pharos; Q9BY32; Tbio. DR PRO; PR:Q9BY32; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q9BY32; Protein. DR Bgee; ENSG00000125877; Expressed in right lobe of thyroid gland and 197 other cell types or tissues. DR ExpressionAtlas; Q9BY32; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0035870; F:dITP diphosphatase activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0036220; F:ITP diphosphatase activity; IEA:RHEA. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0047429; F:nucleoside triphosphate diphosphatase activity; IBA:GO_Central. DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW. DR GO; GO:0036222; F:XTP diphosphatase activity; IEA:RHEA. DR GO; GO:0051276; P:chromosome organization; IEA:Ensembl. DR GO; GO:0009204; P:deoxyribonucleoside triphosphate catabolic process; IEA:UniProtKB-UniRule. DR GO; GO:0006193; P:ITP catabolic process; IEA:Ensembl. DR GO; GO:0009143; P:nucleoside triphosphate catabolic process; IBA:GO_Central. DR CDD; cd00515; HAM1; 1. DR Gene3D; 3.90.950.10; -; 1. DR HAMAP; MF_03148; HAM1_NTPase; 1. DR InterPro; IPR027502; ITPase. DR InterPro; IPR029001; ITPase-like_fam. DR InterPro; IPR002637; RdgB/HAM1. DR NCBIfam; TIGR00042; RdgB/HAM1 family non-canonical purine NTP pyrophosphatase; 1. DR PANTHER; PTHR11067:SF9; INOSINE TRIPHOSPHATE PYROPHOSPHATASE; 1. DR PANTHER; PTHR11067; INOSINE TRIPHOSPHATE PYROPHOSPHATASE/HAM1 PROTEIN; 1. DR Pfam; PF01725; Ham1p_like; 1. DR SUPFAM; SSF52972; ITPase-like; 1. DR Genevisible; Q9BY32; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Disease variant; Epilepsy; Hydrolase; Magnesium; KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148, FT ECO:0000269|Ref.9" FT CHAIN 2..194 FT /note="Inosine triphosphate pyrophosphatase" FT /id="PRO_0000178280" FT BINDING 14..19 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 44 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 56 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 72..73 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 89 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 149..152 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 172 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT BINDING 177..178 FT /ligand="ITP" FT /ligand_id="ChEBI:CHEBI:61402" FT /evidence="ECO:0000269|PubMed:17138556, FT ECO:0007744|PDB:2J4E" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03148, FT ECO:0000269|Ref.9" FT VAR_SEQ 7..23 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_042548" FT VAR_SEQ 23..63 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_045545" FT VARIANT 32 FT /note="P -> T (in ITPAD; complete loss of enzymatic FT activity at homozygosity; partial loss of activity without FT ITP accumulation in heterozygous individuals; FT dbSNP:rs1127354)" FT /evidence="ECO:0000269|PubMed:12384777, FT ECO:0000269|PubMed:12436200, ECO:0000269|Ref.2" FT /id="VAR_015576" FT VARIANT 178 FT /note="R -> C (in DEE35; uncertain significance; FT dbSNP:rs746930990)" FT /evidence="ECO:0000269|PubMed:26224535" FT /id="VAR_075084" FT CONFLICT 33 FT /note="C -> R (in Ref. 1; AAK21848)" FT /evidence="ECO:0000305" FT CONFLICT 41 FT /note="D -> G (in Ref. 2; AAG43165)" FT /evidence="ECO:0000305" FT HELIX 2..5 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 9..13 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 17..27 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 33..38 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:2J4E" FT HELIX 49..64 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 68..77 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 78..80 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 88..102 FT /evidence="ECO:0007829|PDB:2CAR" FT TURN 103..106 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 111..121 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:2J4E" FT STRAND 130..140 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:2CAR" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:2CAR" FT TURN 164..166 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 169..175 FT /evidence="ECO:0007829|PDB:2CAR" FT HELIX 177..189 FT /evidence="ECO:0007829|PDB:2CAR" SQ SEQUENCE 194 AA; 21446 MW; F0EC6A523722DF05 CRC64; MAASLVGKKI VFVTGNAKKL EEVVQILGDK FPCTLVAQKI DLPEYQGEPD EISIQKCQEA VRQVQGPVLV EDTCLCFNAL GGLPGPYIKW FLEKLKPEGL HQLLAGFEDK SAYALCTFAL STGDPSQPVR LFRGRTSGRI VAPRGCQDFG WDPCFQPDGY EQTYAEMPKA EKNAVSHRFR ALLELQEYFG SLAA //