Gene/Proteome Database (LMPD)
LMPD ID
LMP001244
Gene ID
Species
Homo sapiens (Human)
Gene Name
phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Gene Symbol
Synonyms
LCCS3; PIP5K-GAMMA; PIP5K1-gamma; PIP5Kgamma
Chromosome
19
Map Location
19p13.3
EC Number
2.7.1.68
Summary
This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Sep 2010]
Orthologs
Proteins
| phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 1 | |
|---|---|
| Refseq ID | NP_001182662 |
| Protein GI | 307691174 |
| UniProt ID | O60331 |
| mRNA ID | NM_001195733 |
| Length | 640 |
| RefSeq Status | REVIEWED |
| MELEVPDEAESAEAGAVPSEAAWAAESGAAAGLAQKKAAPTEVLSMTAQPGPGHGKKLGHRGVDASGETTYKKTTSSTLKGAIQLGIGYTVGHLSSKPERDVLMQDFYVVESIFFPSEGSNLTPAHHFQDFRFKTYAPVAFRYFRELFGIRPDDYLYSLCNEPLIELSNPGASGSLFYVTSDDEFIIKTVMHKEAEFLQKLLPGYYMNLNQNPRTLLPKFYGLYCVQSGGKNIRVVVMNNILPRVVKMHLKFDLKGSTYKRRASKKEKEKSFPTYKDLDFMQDMPEGLLLDADTFSALVKTLQRDCLVLESFKIMDYSLLLGVHNIDQHERERQAQGAQSTSDEKRPVGQKALYSTAMESIQGGAARGEAIESDDTMGGIPAVNGRGERLLLHIGIIDILQSYRFIKKLEHTWKALVHDGDTVSVHRPSFYAERFFKFMSNTVFRKNSSLKSSPSKKGRGGALLAVKPLGPTAAFSASQIPSEREEAQYDLRGARSYPTLEDEGRPDLLPCTPPSFEEATTASIATTLSSTSLSIPERSPSETSEQPRYRRRTQSSGQDGRPQEEPPAEEDLQQITVQVEPACSVEIVVPKEEDAGVEASPAGASAAVEVETASQASDEEGAPASQASDEEDAPATDIYF | |
| phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 2 | |
|---|---|
| Refseq ID | NP_036530 |
| Protein GI | 31317309 |
| UniProt ID | O60331 |
| mRNA ID | NM_012398 |
| Length | 668 |
| RefSeq Status | REVIEWED |
| MELEVPDEAESAEAGAVPSEAAWAAESGAAAGLAQKKAAPTEVLSMTAQPGPGHGKKLGHRGVDASGETTYKKTTSSTLKGAIQLGIGYTVGHLSSKPERDVLMQDFYVVESIFFPSEGSNLTPAHHFQDFRFKTYAPVAFRYFRELFGIRPDDYLYSLCNEPLIELSNPGASGSLFYVTSDDEFIIKTVMHKEAEFLQKLLPGYYMNLNQNPRTLLPKFYGLYCVQSGGKNIRVVVMNNILPRVVKMHLKFDLKGSTYKRRASKKEKEKSFPTYKDLDFMQDMPEGLLLDADTFSALVKTLQRDCLVLESFKIMDYSLLLGVHNIDQHERERQAQGAQSTSDEKRPVGQKALYSTAMESIQGGAARGEAIESDDTMGGIPAVNGRGERLLLHIGIIDILQSYRFIKKLEHTWKALVHDGDTVSVHRPSFYAERFFKFMSNTVFRKNSSLKSSPSKKGRGGALLAVKPLGPTAAFSASQIPSEREEAQYDLRGARSYPTLEDEGRPDLLPCTPPSFEEATTASIATTLSSTSLSIPERSPSETSEQPRYRRRTQSSGQDGRPQEEPPAEEDLQQITVQVEPACSVEIVVPKEEDAGVEASPAGASAAVEVETASQASDEEGAPASQASDEEDAPATDIYFPTDERSWVYSPLHYSAQAPPASDGESDT | |
| phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 3 | |
|---|---|
| Refseq ID | NP_001287778 |
| Protein GI | 664806078 |
| UniProt ID | O60331 |
| mRNA ID | NM_001300849 |
| Length | 707 |
| RefSeq Status | REVIEWED |
| MELEVPDEAESAEAGAVPSEAAWAAESGAAAGLAQKKAAPTEVLSMTAQPGPGHGKKLGHRGVDASGETTYKKTTSSTLKGAIQLGIGYTVGHLSSKPERDVLMQDFYVVESIFFPSEGSNLTPAHHFQDFRFKTYAPVAFRYFRELFGIRPDDYLYSLCNEPLIELSNPGASGSLFYVTSDDEFIIKTVMHKEAEFLQKLLPGYYMNLNQNPRTLLPKFYGLYCVQSGGKNIRVVVMNNILPRVVKMHLKFDLKGSTYKRRASKKEKEKSFPTYKDLDFMQDMPEGLLLDADTFSALVKTLQRDCLVLESFKIMDYSLLLGVHNIDQHERERQAQGAQSTSDEKRPVGQKALYSTAMESIQGGAARGEAIESDDTMGGIPAVNGRGERLLLHIGIIDILQSYRFIKKLEHTWKALVHDGDTVSVHRPSFYAERFFKFMSNTVFRKNSSLKSSPSKKGRGGALLAVKPLGPTAAFSASQIPSEREEAQYDLRGARSYPTLEDEGRPDLLPCTPPSFEEATTASIATTLSSTSLSIPERSPSETSEQPRYRRRTQSSGQDGRPQEEPPAEEDLQQITVQVEPACSVEIVVPKEEDAGVEASPAGASAAVEVETASQASDEEGAPASQASDEEDAPATDIYFFTDGRYWIYSPRHRRLRAVTLSASGTVSDRSRPPWGEGAVPLGQQGAAGPRPEAQCLTSVVFQKGFG | |
Gene Information
Entrez Gene ID
Gene Name
phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005829 | TAS:Reactome | C | cytosol |
| GO:0005925 | TAS:UniProtKB | C | focal adhesion |
| GO:0005634 | IEA:UniProtKB-KW | C | nucleus |
| GO:0005886 | IEA:UniProtKB-KW | C | plasma membrane |
| GO:0001931 | TAS:UniProtKB | C | uropod |
| GO:0016308 | IEA:UniProtKB-EC | F | 1-phosphatidylinositol-4-phosphate 5-kinase activity |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0030036 | TAS:UniProtKB | P | actin cytoskeleton organization |
| GO:0034333 | TAS:UniProtKB | P | adherens junction assembly |
| GO:0007411 | TAS:Reactome | P | axon guidance |
| GO:0072583 | TAS:UniProtKB | P | clathrin-mediated endocytosis |
| GO:0007016 | IEA:Ensembl | P | cytoskeletal anchoring at plasma membrane |
| GO:0030593 | TAS:UniProtKB | P | neutrophil chemotaxis |
| GO:0006909 | TAS:UniProtKB | P | phagocytosis |
| GO:0006661 | TAS:Reactome | P | phosphatidylinositol biosynthetic process |
| GO:0006644 | TAS:Reactome | P | phospholipid metabolic process |
| GO:0070527 | IEA:Ensembl | P | platelet aggregation |
| GO:0016337 | TAS:UniProtKB | P | single organismal cell-cell adhesion |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0048488 | TAS:UniProtKB | P | synaptic vesicle endocytosis |
| GO:0016079 | TAS:UniProtKB | P | synaptic vesicle exocytosis |
KEGG Pathway Links
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR023610 | Phosphatidylinositol-4-phosphate 5-kinase |
| IPR027483 | Phosphatidylinositol-4-phosphate 5-kinase, C-terminal |
| IPR027484 | Phosphatidylinositol-4-phosphate 5-kinase, N-terminal domain |
| IPR002498 | Phosphatidylinositol-4-phosphate 5-kinase, core |
| IPR016034 | Phosphatidylinositol-4-phosphate 5-kinase, core, subgroup |
UniProt Annotations
Entry Information
Gene Name
phosphatidylinositol-4-phosphate 5-kinase, type I, gamma
Protein Entry
O60331_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=PIPKIgamma-90, PIPKIgamma-668, PIPkinIgamma-a, PIPKIgamma_i2; IsoId=O60331-1; Sequence=Displayed; Name=2; Synonyms=variant 700, PIPKIgamma-700, PIPKIgamma_i4; IsoId=O60331-2; Sequence=VSP_042078; Name=3; Synonyms=variant 707, PIPKIgamma-707, PIPKIgamma_i5; IsoId=O60331-3; Sequence=VSP_042080; Name=4; Synonyms=PIPKIgamma-87, PIPKIgamma-640, PIPkinIgamma-b, PIPKIgamma_i1; IsoId=O60331-4; Sequence=VSP_042079; |
| Catalytic Activity | ATP + 1-phosphatidyl-1D-myo-inositol 4- phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate. |
| Disease | Lethal congenital contracture syndrome 3 (LCCS3) [MIM |
| Enzyme Regulation | Activated by interaction with TLN2. |
| Function | 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. {ECO |
| Interaction | P46940:IQGAP1; NbExp=6; IntAct=EBI-8838062, EBI-297509; |
| Ptm | 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. |
| Ptm | Phosphorylation on Ser-650 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is necessary for targeting to focal adhesions. Phosphorylation on Ser-650 and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK (By similarity). Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and TLN2). According to PubMed:15738269 phosphorylation at Tyr-649 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-650. |
| Sequence Caution | Sequence=BAA25515.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence= ; |
| Similarity | Contains 1 PIPK domain. {ECO |
| Subcellular Location | 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. Note=Detected in plasma membrane invaginations. Isoform 3 is detected in intracellular vesicle-like structures. |
| Subcellular Location | Isoform 2: Cytoplasm. Nucleus. |
| Subunit | Interacts with TLN1 (By similarity). Interacts with TLN2; interaction stimulates lipid kinase activity. May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6. Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C (By similarity). Interacts with CDH1. Interacts with CSK (By similarity). Interacts with PLCG1; interaction is abolished upon EGF stimulation (By similarity). |
| Tissue Specificity | Isoform 1 is strongly expressed in brain and also detected in heart and lung. Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney. Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney. |
Identical and Related Proteins
Unique RefSeq proteins for LMP001244 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 307691174 | RefSeq | NP_001182662 | 640 | phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 1 |
| 31317309 | RefSeq | NP_036530 | 668 | phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 2 |
| 664806078 | RefSeq | NP_001287778 | 707 | phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 3 |
Identical Sequences to LMP001244 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:31317309 | DBBJ | BAG11210.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, partial [synthetic construct] |
| GI:31317309 | GenBank | EAW69295.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, isoform CRA_a [Homo sapiens] |
| GI:31317309 | GenBank | AAI67798.1 | 668 | Phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [synthetic construct] |
| GI:664806078 | GenBank | ACS73484.1 | 707 | phosphatidylinositol 4-phosphate 5-kinase type I gamma splice variant 707 [Homo sapiens] |
| GI:664806078 | GenBank | AGD79098.1 | 707 | Sequence 4 from patent US 8357790 |
| GI:31317309 | SwissProt | O60331.2 | 668 | RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma; Short=PIP5K1-gamma; Short=PtdIns(4)P-5-kinase 1 gamma; AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I gamma; Short=PIP5KIgamma [Homo sapiens] |
Related Sequences to LMP001244 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:307691174 | DBBJ | BAA25515.1 | 687 | KIAA0589 protein, partial [Homo sapiens] |
| GI:31317309 | DBBJ | BAA25515.1 | 687 | KIAA0589 protein, partial [Homo sapiens] |
| GI:307691174 | DBBJ | BAG11210.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, partial [synthetic construct] |
| GI:307691174 | GenBank | EAW69295.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, isoform CRA_a [Homo sapiens] |
| GI:31317309 | GenBank | EAW69296.1 | 735 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma, isoform CRA_b [Homo sapiens] |
| GI:307691174 | GenBank | AAI67798.1 | 668 | Phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [synthetic construct] |
| GI:31317309 | GenBank | JAA09663.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [Pan troglodytes] |
| GI:31317309 | GenBank | JAA16562.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [Pan troglodytes] |
| GI:31317309 | GenBank | JAA32171.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [Pan troglodytes] |
| GI:31317309 | GenBank | JAA39466.1 | 668 | phosphatidylinositol-4-phosphate 5-kinase, type I, gamma [Pan troglodytes] |
| GI:664806078 | GenBank | AGD79104.1 | 707 | Sequence 12 from patent US 8357790 |
| GI:307691174 | RefSeq | NP_036530.1 | 668 | phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform 2 [Homo sapiens] |
| GI:664806078 | RefSeq | XP_002801072.1 | 981 | PREDICTED: phosphatidylinositol-4-phosphate 5-kinase type-1 gamma-like [Macaca mulatta] |
| GI:664806078 | RefSeq | XP_005587577.1 | 800 | PREDICTED: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [Macaca fascicularis] |
| GI:664806078 | RefSeq | XP_005587579.1 | 666 | PREDICTED: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X3 [Macaca fascicularis] |
| GI:664806078 | RefSeq | XP_006722775.1 | 696 | PREDICTED: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X2 [Homo sapiens] |
| GI:664806078 | RefSeq | XP_010365580.1 | 838 | PREDICTED: phosphatidylinositol 4-phosphate 5-kinase type-1 gamma isoform X1 [Rhinopithecus roxellana] |
| GI:307691174 | SwissProt | O60331.2 | 668 | RecName: Full=Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma; Short=PIP5K1-gamma; Short=PtdIns(4)P-5-kinase 1 gamma; AltName: Full=Phosphatidylinositol 4-phosphate 5-kinase type I gamma; Short=PIP5KIgamma [Homo sapiens] |