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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}.
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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
 
 
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