Q5I6B8 (PI51C_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 67. History...
Names and origin
|Protein names||Recommended name:|
Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma
Short name=PtdIns(4)P-5-kinase 1 gamma
Phosphatidylinositol 4-phosphate 5-kinase type I gamma
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||688 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth By similarity. Ref.2
ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
Activated by interaction with ARF6.
Interacts with TLN1 By similarity. Interacts with TLN2; interaction stimulates lipid kinase activity By similarity. May compete with beta-integrins for the same binding site on TLN1 and TLN2 By similarity. Interacts with ARF6. Interacts with AP2B1 By similarity. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C By similarity. Interacts with CDH1 By similarity. Interacts with CSK By similarity. Interacts with PLCG1; interaction is abolished upon EGF stimulation By similarity. Ref.2
Cell membrane; Peripheral membrane protein; Cytoplasmic side. Endomembrane system. Cytoplasm. Cell junction › focal adhesion. Cell junction › adherens junction. Cell projection › ruffle membrane. Cell projection › phagocytic cup. Cell projection › uropodium Ref.2.
Phosphorylation on Ser-672 negatively regulates binding to TLN2 and is strongly stimulated in mitosis By similarity. Phosphorylation on Tyr-671 is necessary for targeting to focal adhesions By similarity. Phosphorylation on Ser-672 and Tyr-671 are mutually exclusive By similarity. Phosphorylated by SYK and CSK By similarity. Tyrosine phosphorylation is enhanced by PTK2 signaling By similarity. Phosphorylated at Tyr-635 upon EGF stimulation By similarity. Some studies suggest that phosphorylation on Tyr-671 enhances binding to tailins (TLN1 and TLN2) By similarity; others that phosphorylation at Tyr-671 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-672 By similarity.
Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells By similarity.
Contains 1 PIPK domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 688||688||Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma||PRO_0000185464|
|Domain||75 – 443||369||PIPK|
Amino acid modifications
|Modified residue||265||1||N6-acetyllysine By similarity|
|Modified residue||268||1||N6-acetyllysine By similarity|
|Modified residue||635||1||Phosphotyrosine; by EGFR By similarity|
|Modified residue||671||1||Phosphotyrosine; by CSK By similarity|
|Modified residue||672||1||Phosphoserine; by CDK5, MAPK1 and CDK1 By similarity|
|Mutagenesis||188||1||K → A: Reduces activity by over 99%. Ref.1|
|Mutagenesis||316||1||D → K: Loss of kinase activity. Ref.1|
|||"A novel neuronal-specific splice variant of Type I phosphatidylinositol 4-phosphate 5-kinase isoform gamma."|
Giudici M.-L., Emson P.C., Irvine R.F.
Biochem. J. 379:489-496(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF LYS-188 AND ASP-316, TISSUE SPECIFICITY.
|||"ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma."|
Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V.
J. Cell Biol. 162:113-124(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ARF6, SUBCELLULAR LOCATION.
|AY850259 mRNA. Translation: AAW34235.1.|
|RefSeq||NP_001009967.2. NM_001009967.2. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:1309938. rat. |
|RGD||1309938. Pip5k1c. |
Gene expression databases
Family and domain databases
|InterPro||IPR023610. PInositol-4-P-5-kinase. |
|PANTHER||PTHR23086. PTHR23086. 1 hit. |
|Pfam||PF01504. PIP5K. 1 hit. |
|SMART||SM00330. PIPKc. 1 hit. |
|PROSITE||PS51455. PIPK. 1 hit. |
|Accession||Primary (citable) accession number: Q5I6B8|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families