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Details on Person UniProt:Q9Z1T6 Pikfyve
| Class:Id | ReferenceGeneProduct:90759 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-2097 added on Sat February 7 2015;initiator methionine:1 for 90759 removed on Fri Nov 03 2023;initiator methionine: for 90759 added on Fri Nov 03 2023;initiator methionine: for 90759 removed on Fri Aug 15 2025;initiator methionine:1 for 90759 added on Fri Aug 15 2025 |
| _displayName | UniProt:Q9Z1T6 Pikfyve |
| _timestamp | 2025-08-15 21:52:55 |
| chain | initiator methionine:1 chain:2-2097 |
| checksum | 8C529E86FBEED8E6 |
| comment | FUNCTION Dual specificity kinase implicated in myriad essential cellular processes such as maintenance of endomembrane homeostasis, and endocytic-vacuolar pathway, lysosomal trafficking, nuclear transport, stress- or hormone-induced signaling and cell cycle progression (PubMed:17909029, PubMed:19037259, PubMed:22621786). The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Sole enzyme to catalyze the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo-inositol ring, to form (PtdIns(3,5)P2) (PubMed:10419465, PubMed:10567352). Also catalyzes the phosphorylation of phosphatidylinositol on the fifth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:10419465, PubMed:22621786). Has serine-protein kinase activity and is able to autophosphorylate and transphosphorylate. Autophosphorylation inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (By similarity) (PubMed:11123925). Involved in key endosome operations such as fission and fusion in the course of endosomal cargo transport (PubMed:22621786). Required for the maturation of early into late endosomes, phagosomes and lysosomes (By similarity). Regulates vacuole maturation and nutrient recovery following engulfment of macromolecules, initiates the redistribution of accumulated lysosomal contents back into the endosome network (PubMed:27623384). Critical regulator of the morphology, degradative activity, and protein turnover of the endolysosomal system in macrophages and platelets (PubMed:25178411, PubMed:31427458). In neutrophils, critical to perform chemotaxis, generate ROS, and undertake phagosome fusion with lysosomes (PubMed:28779020). Plays a key role in the processing and presentation of antigens by major histocompatibility complex class II (MHC class II) mediated by CTSS (By similarity). Regulates melanosome biogenesis by controlling the delivery of proteins from the endosomal compartment to the melanosome (PubMed:29584722). Essential for systemic glucose homeostasis, mediates insulin-induced signals for endosome/actin remodeling in the course of GLUT4 translocation/glucose uptake activation (PubMed:22621786, PubMed:23673157). Supports microtubule-based endosome-to-trans-Golgi network cargo transport, trhough association with SPAG9 and RABEPK (PubMed:14530284, PubMed:19056739). Mediates EGFR trafficking to the nucleus (PubMed:17909029).CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + ADP + H(+)CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ADP + H(+)CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)COFACTOR Inhibited by apilimod and YM201636.SUBUNIT Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities (PubMed:19037259). Interacts (via chaperonin-like domain) with RABEPK; the interaction recruits RABEPK to the endosomal membrane (PubMed:14530284). Interacts with SPAG9 (PubMed:19056739). Interacts with EGFR (PubMed:17909029).SUBCELLULAR LOCATION Mainly associated with membranes of the late endocytic pathway.ALTERNATIVE PRODUCTS Ubiquitous.DOMAIN Interaction of FYVE-type domain with phosphatidylinositol 3-phosphate (PtdIns(3)P) is necessary for targeting to the membranes of the late endocytic pathway.PTM Phosphorylated in response to insulin at Ser-318 in a protein kinase B (PKB)-dependent manner (PubMed:20513353). Autophosphorylates which down-regulates lipid product formation (PubMed:11123925).PTM Autophosphorylates which inhibits its own phosphatidylinositol 3-phosphate 5-kinase activity, stimulates FIG4 lipid phosphatase activity and down-regulates lipid product formation (PubMed:11123925). Dephosphorylated by FIG4 in the PI(3,5)P2 regulatory complex, at Ser-48, Ser-1668 and Ser-2052 (By similarity). Phosphorylated in response to insulin at Ser-318 in a protein kinase B (PKB)-dependent manner (PubMed:20513353).DISRUPTION PHENOTYPE Knockout embryos die before the 32-64-cell stage (PubMed:21349843). Melanocyte-specific knockout mice exhibit greying of the mouse coat and the accumulation of single membrane vesicle structures in melanocytes resembling multivesicular endosomes (PubMed:29584722). Myeloid cell-specific knockout micedevelop diffuse tissue infiltration of foamy macrophages, hepatosplenomegaly and systemic inflammation (PubMed:31427458). Striated muscle-specific knockout mice exhibit systemic glucose intolerance and insulin resistance at an early age but have unaltered muscle mass. From 10 weeks of age, mice progressively accumulate greater body weight and fat mass (PubMed:23673157). Platelet-specific knockout mice exhibit mild growth delay and body hair loss. Over time, they develop coarse facial features, abdominal distention, an increase in the bulk of their soft tissues and body weight gain. They also have decreased bone mineral density. As mutants aged, they remain infertile and their general body functions deteriorate. The majority die before 28 weeks of age. Animals show massive accelerated arterial thrombosis and organomegaly with inappropriate inflammatory responses characterized by macrophage accumulation in multiple tissues (PubMed:25178411).SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: fullName evidence="28"1-phosphatidylinositol 3-phosphate 5-kinase shortName: Phosphatidylinositol 3-phosphate 5-kinase ecNumber evidence="7"2.7.1.150 alternativeName: FYVE finger-containing phosphoinositide kinase alternativeName: PIKfyve alternativeName: Phosphatidylinositol 3-phosphate 5-kinase type III shortName: PIPkin-III shortName: Type III PIP kinase alternativeName: fullName evidence="24"Serine-protein kinase PIKFYVE ecNumber evidence="8"2.7.11.1 alternativeName: fullName evidence="23"p235 |
| geneName | Pikfyve Fab1 Kiaa0981 Pip5k3 |
| identifier | Q9Z1T6 |
| isSequenceChanged | FALSE |
| keyword | Acetylation Alternative splicing ATP-binding Cytoplasmic vesicle Endosome Kinase Lipid metabolism Membrane Metal-binding Nucleotide-binding Phosphoprotein Reference proteome Transferase Zinc Zinc-finger |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9706439] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9767224] Weiser, Joel [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | Pikfyve |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | FYV1_MOUSE E9QL40 Q3TNE4 Q3UTT6 Q69ZU1 Q9CU94 |
| sequenceLength | 2097 |
| species | [Species:48892] Mus musculus |
| (isoformParent) | [ReferenceIsoform:147610] UniProt:Q9Z1T6-2 Pikfyve [Mus musculus] [ReferenceIsoform:385113] UniProt:Q9Z1T6-3 Pikfyve [Mus musculus] [ReferenceIsoform:416218] UniProt:Q9Z1T6-1 Pikfyve [Mus musculus] |
| (referenceEntity) | [EntityWithAccessionedSequence:1460260] Pikfyve [endosome membrane] [Mus musculus] [EntityWithAccessionedSequence:1460298] p-S318-Pikfyve [endosome membrane] [Mus musculus] [EntityWithAccessionedSequence:1806206] Pikfyve [Golgi membrane] [Mus musculus] [EntityWithAccessionedSequence:1806275] Pikfyve [early endosome membrane] [Mus musculus] [EntityWithAccessionedSequence:1806288] Pikfyve [late endosome membrane] [Mus musculus] |
| (referenceSequence) | [ModifiedResidue:1460312] O-phospho-L-serine at 318 |
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No pathways have been reviewed or authored by UniProt:Q9Z1T6 Pikfyve (90759)
