ITPA_HUMAN
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 03-AUG-2022, entry version 188.
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 sec(-
CC 1) with dHAPTP as substrate (PubMed:17090528). kcat is 12.1 sec(-1)
CC 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; 79.
DR IntAct; Q9BY32; 15.
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; Q9BY32; -.
DR PeptideAtlas; Q9BY32; -.
DR PRIDE; Q9BY32; -.
DR ProteomicsDB; 216; -.
DR ProteomicsDB; 79572; -. [Q9BY32-1]
DR ProteomicsDB; 79573; -. [Q9BY32-2]
DR TopDownProteomics; Q9BY32-1; -. [Q9BY32-1]
DR Antibodypedia; 7322; 293 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 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 Orphanet; 284113; Prediction of susceptibility to adverse reaction due to mercaptopurine.
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; DCFADDT; -.
DR OrthoDB; 1298391at2759; -.
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 SABIO-RK; Q9BY32; -.
DR SignaLink; Q9BY32; -.
DR BioGRID-ORCS; 3704; 17 hits in 1081 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 195 other tissues.
DR ExpressionAtlas; Q9BY32; baseline and differential.
DR Genevisible; Q9BY32; HS.
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:0036218; F:dTTP diphosphatase activity; IEA:UniProtKB-EC.
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:0035529; F:NADH pyrophosphatase activity; IEA:UniProtKB-EC.
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; IPR002637; Ham1p-like.
DR InterPro; IPR027502; ITPase.
DR InterPro; IPR029001; ITPase-like_fam.
DR PANTHER; PTHR11067; PTHR11067; 1.
DR Pfam; PF01725; Ham1p_like; 1.
DR SUPFAM; SSF52972; SSF52972; 1.
DR TIGRFAMs; TIGR00042; TIGR00042; 1.
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; unknown pathological 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