Protein: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (EC 2.7.1.149) (1-phosphatidylinositol 5-phosphate 4-kinase 2-alpha) (Diphosphoinositide kinase 2-alpha) (PIP5KIII) (Phosphatidylinositol 5-Phosphate 4-Kinase) (PI5P4Kalpha) (Phosphatidylinositol 5-phosphate 4-kinase type II alpha) (PI(5)P 4-kinase type II alpha) (PIP4KII-alpha) (PtdIns(4)P-5-kinase B isoform) (PtdIns(4)P-5-kinase C isoform) (PtdIns(5)P-4-kinase isoform 2-alpha) (P48426)
Organism: Homo sapiens (Human)
Function: Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Has both ATP- and GTP-dependent kinase activities. May exert its function by regulating the levels of PtdIns5P, which functions in the cytosol by increasing AKT activity and in the nucleus signals through ING2. May regulate the pool of cytosolic PtdIns5P in response to the activation of tyrosine phosphorylation (By similarity). Required for lysosome-peroxisome membrane contacts and intracellular cholesterol transport through modulating peroxisomal PtdIns(4,5)P2 level. In collaboration with PIP4K2B, has a role in mediating autophagy in times of nutrient stress (By similarity). Required for autophagosome-lysosome fusion and the regulation of cellular lipid metabolism. May be involved in thrombopoiesis, and the terminal maturation of megakaryocytes and regulation of their size (By similarity). Negatively regulates insulin signaling through a catalytic-independent mechanism. PIP4Ks interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3.
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:O70172}. Nucleus {ECO:0000269|PubMed:20583997}. Lysosome {ECO:0000250|UniProtKB:O70172}. Cytoplasm {ECO:0000269|PubMed:20583997}. Photoreceptor inner segment {ECO:0000250|UniProtKB:O70172}. Cell projection, cilium, photoreceptor outer segment {ECO:0000250|UniProtKB:O70172}. Note=May translocate from the cytosol to the cell membrane upon activation of tyrosine phosphorylation. May translocate from the inner to the outer segments of the rod photoreceptor cells in response to light (By similarity). Localization to the nucleus is modulated by the interaction with PIP4K2B. {ECO:0000250|UniProtKB:O70172, ECO:0000269|PubMed:20583997}.
Interaction partners:
- Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma
- Phosphatidylinositol 5-phosphate 4-kinase type-2 beta
- Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN
- Type 2 phosphatidylinositol 4,5-bisphosphate 4-phosphatase
- 1-phosphatidylinositol 3-phosphate 5-kinase
- Type 1 phosphatidylinositol 4,5-bisphosphate 4-phosphatase
- Synaptojanin-1
- Inositol polyphosphate 5-phosphatase OCRL
- Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha
- Synaptojanin-2
Sequence:
MATPGNLGSSVLASKTKTKKKHFVAQKVKLFRASDPLLSVLMWGVNHSINELSHVQIPVMLMPDDFKAYSKIKVDNHLFNKENMPSHFKFKEYCPMVFRNLRERFGIDDQDFQNSLTRSAPLPNDSQARSGARFHTSYDKRYIIKTITSEDVAEMHNILKKYHQYIVECHGITLLPQFLGMYRLNVDGVEIYVIVTRNVFSHRLSVYRKYDLKGSTVAREASDKEKAKELPTLKDNDFINEGQKIYIDDNNKKVFLEKLKKDVEFLAQLKLMDYSLLVGIHDVERAEQEEVECEENDGEEEGESDGTHPVGTPPDSPGNTLNSSPPLAPGEFDPNIDVYGIKCHENSPRKEVYFMAIIDILTHYDAKKKAAHAAKTVKHGAGAEISTVNPEQYSKRFLDFIGHILT