UniProt functional annotation for P78356

UniProt code: P78356.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
Function: Participates in the biosynthesis of phosphatidylinositol 4,5- bisphosphate (PubMed:9038203, PubMed:26774281). Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration (PubMed:26774281). Its GTP-sensing activity is critical for metabolic adaptation (PubMed:26774281). PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3 (PubMed:31091439). {ECO:0000269|PubMed:26774281, ECO:0000269|PubMed:31091439, ECO:0000269|PubMed:9038203}.
 
Catalytic activity: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5- phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo- inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:12280, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57795, ChEBI:CHEBI:58456, ChEBI:CHEBI:456216; EC=2.7.1.149; Evidence={ECO:0000305|PubMed:26774281}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12281; Evidence={ECO:0000305|PubMed:26774281};
Catalytic activity: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5- phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo- inositol-4,5-bisphosphate) + ADP + H(+); Xref=Rhea:RHEA:55992, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:83423, ChEBI:CHEBI:84968, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:26774281}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55993; Evidence={ECO:0000305|PubMed:26774281};
Catalytic activity: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5- phosphate) + GTP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo- inositol-4,5-bisphosphate) + GDP + H(+); Xref=Rhea:RHEA:55964, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:83423, ChEBI:CHEBI:84968; Evidence={ECO:0000269|PubMed:26774281}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55965; Evidence={ECO:0000305|PubMed:26774281};
Biophysicochemical properties: Kinetic parameters: KM=30 uM for phosphatidylinositol-5- phosphate {ECO:0000269|PubMed:20583997}; KM=88 uM for ATP {ECO:0000269|PubMed:26774281}; KM=236 uM for GTP {ECO:0000269|PubMed:26774281}; Vmax=0.2 pmol/min/ug enzyme {ECO:0000269|PubMed:20583997}; Vmax=57 umol/min/mg enzyme toward ATP {ECO:0000269|PubMed:26774281}; Vmax=88 umol/min/mg enzyme toward GTP {ECO:0000269|PubMed:26774281};
Subunit: Homodimer. Binds TNFRSF1A (PubMed:9038203). Interacts with PIP4K2A; the interaction suppresses ubiquitination by the SPOP/CUL3 complex (PubMed:20583997). {ECO:0000269|PubMed:20583997, ECO:0000269|PubMed:9038203}.
Subcellular location: Endoplasmic reticulum membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Nucleus {ECO:0000269|PubMed:20583997}. Cytoplasm {ECO:0000269|PubMed:20583997}. Note=Associated with the plasma membrane and the endoplasmic reticulum. {ECO:0000250}.
Tissue specificity: Highly expressed in brain, heart, pancreas, skeletal muscle and kidney. Detected at lower levels in placenta, lung and liver. {ECO:0000269|PubMed:9038203}.
Ptm: Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is stimulated by PtdIns5P levels. {ECO:0000269|PubMed:20583997}.
Ptm: Phosphorylated on serine residues. {ECO:0000269|PubMed:19369195}.

Annotations taken from UniProtKB at the EBI.