UniProt functional annotation for Q13572



	UniProt functional annotation for Q13572

UniProt code: Q13572.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha- induced apoptosis by interfering with the activation of TNFRSF1A- associated death domain (PubMed:11909533, PubMed:12925536, PubMed:17616525). Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:17616525). {ECO:0000269|PubMed:11909533, ECO:0000269|PubMed:12925536, ECO:0000269|PubMed:17616525}.

Catalytic activity: Reaction=1D-myo-inositol 3,4,5,6-tetrakisphosphate + ATP = 1D-myo- inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+); Xref=Rhea:RHEA:12452, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:456216; EC=2.7.1.134;

Catalytic activity: Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:13253, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57895, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;

Catalytic activity: Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:20940, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:8662638}; Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:8662638};

Biophysicochemical properties: Kinetic parameters: KM=0.3 uM for Ins(1,3,4)P3 {ECO:0000269|PubMed:11042108}; KM=0.1 uM for Ins(3,4,5,6)P4 {ECO:0000269|PubMed:11042108}; Vmax=320 pmol/min/ug enzyme with Ins(1,3,4)P3 as substrate {ECO:0000269|PubMed:11042108}; Vmax=780 pmol/min/ug enzyme with Ins(3,4,5,6)P4 as substrate {ECO:0000269|PubMed:11042108};

Subunit: Monomer. Interacts with GPS1/COPS1. {ECO:0000269|PubMed:12324474, ECO:0000269|PubMed:17616525}.

Tissue specificity: Expressed in brain > heart > skeletal muscle = kidney = pancreas = liver = placenta > lung. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal cord, occipital lobe, frontal lobe, temporal lobe and putamen. {ECO:0000269|PubMed:8662638}.

Ptm: Acetylation by EP300 and CREBBP destabilizes ITPK1, and down- regulates enzymatic activity. Deacetylated by SIRT1. {ECO:0000269|PubMed:22308441}.

Similarity: Belongs to the ITPK1 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylate Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha- induced apoptosis by interfering with the activation of TNFRSF1A- associated death domain (PubMed:11909533, PubMed:12925536, PubMed:17616525). Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:17616525). {ECO:0000269\|PubMed:11909533, ECO:0000269\|PubMed:12925536, ECO:0000269\|PubMed:17616525}.


Catalytic activity:		Reaction=1D-myo-inositol 3,4,5,6-tetrakisphosphate + ATP = 1D-myo- inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+); Xref=Rhea:RHEA:12452, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57539, ChEBI:CHEBI:57733, ChEBI:CHEBI:456216; EC=2.7.1.134;
Catalytic activity:		Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:13253, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57895, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
Catalytic activity:		Reaction=1D-myo-inositol 1,3,4-trisphosphate + ATP = 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ADP + H(+); Xref=Rhea:RHEA:20940, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57660, ChEBI:CHEBI:58414, ChEBI:CHEBI:456216; EC=2.7.1.159;
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:8662638}; Note=Binds 2 magnesium ions per subunit. {ECO:0000269\|PubMed:8662638};
Biophysicochemical properties:		Kinetic parameters: KM=0.3 uM for Ins(1,3,4)P3 {ECO:0000269\|PubMed:11042108}; KM=0.1 uM for Ins(3,4,5,6)P4 {ECO:0000269\|PubMed:11042108}; Vmax=320 pmol/min/ug enzyme with Ins(1,3,4)P3 as substrate {ECO:0000269\|PubMed:11042108}; Vmax=780 pmol/min/ug enzyme with Ins(3,4,5,6)P4 as substrate {ECO:0000269\|PubMed:11042108};
Subunit:		Monomer. Interacts with GPS1/COPS1. {ECO:0000269\|PubMed:12324474, ECO:0000269\|PubMed:17616525}.
Tissue specificity:		Expressed in brain > heart > skeletal muscle = kidney = pancreas = liver = placenta > lung. In brain, it is expressed in cerebellum, cerebral cortex, medulla, spinal cord, occipital lobe, frontal lobe, temporal lobe and putamen. {ECO:0000269\|PubMed:8662638}.
Ptm:		Acetylation by EP300 and CREBBP destabilizes ITPK1, and down- regulates enzymatic activity. Deacetylated by SIRT1. {ECO:0000269\|PubMed:22308441}.
Similarity:		Belongs to the ITPK1 family. {ECO:0000305}.