PIP5K1B encodes phosphatidylinositol 4-phosphate 5-kinase type 1 beta, a membrane-associated lipid kinase whose core function is ATP-dependent phosphorylation of PI4P to generate PI(4,5)P2/PIP2. PI(4,5)P2 supports membrane signaling, actin remodeling, adhesion, vesicle trafficking, and autophagic lysosome reformation. Broader WNT/PI3K pathway signaling and uropod localization are secondary contexts relative to the PI4P 5-kinase/PIP2 biosynthetic role.
Definition: The process in which nascent lysosomes are regenerated from autolysosomal membranes following autophagy, including autolysosome tubule initiation, membrane remodeling, and proto-lysosome budding.
Justification: The ALR literature and PN curation need a term more specific than broad lysosome organization for proteins such as PIP5K1B that regulate autolysosomal membrane composition and tubulation.
Parent term: lysosome organization
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PIP5K1B contributes directly to phosphatidylinositol phosphate biosynthesis by producing PI(4,5)P2 from PI4P. Reason: The process-level term is broad but appropriate for the core PI phosphate biosynthetic function. Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0005829 cytosol | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: PIP5K1B is a cytosolic enzyme that associates with cellular membranes, including plasma membrane and endomembrane contexts where phosphoinositide substrates reside. The falcon deep research reinforces the plasma membrane as the principal site where PIP5K1B generates PI(4,5)P2. Reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md PIP5K1B localizes primarily to the cytoplasmic face of the plasma membrane, where it carries out its principal function of generating PI(4,5)P2 |
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | ACCEPT | Summary: PIP5K1B is a cytosolic enzyme that associates with cellular membranes, including plasma membrane and endomembrane contexts where phosphoinositide substrates reside. Reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0016308 1-phosphatidylinositol-4-phosphate 5-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2. The falcon deep research independently describes PI4P as the predominant physiological substrate, with PI3P phosphorylation reported only as an in vitro side activity, consistent with treating the PI3P-using Reactome side reactions as non-core. Reason: Retain as the specific catalytic function for this type I PIP5 kinase. Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md PIP5K1B catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PI4P, PtdIns4P) to generate phosphatidylinositol 4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md PIP5K1B exhibits primary specificity for PI4P as its physiological substrate |
| GO:0046488 phosphatidylinositol metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: The annotation captures phosphatidylinositol metabolism, but it is broader than the specific PI phosphate biosynthetic role of PIP5K1B. Reason: Replace the broad phosphatidylinositol metabolic/biosynthetic process with phosphatidylinositol phosphate biosynthetic process. Proposed replacements: phosphatidylinositol phosphate biosynthetic process Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: PI3K/AKT pathway effects are downstream of phosphoinositide metabolism and are secondary to the direct PIP5K1B lipid kinase function. The falcon deep research explains the mechanistic basis: PI(4,5)P2 generated by PIP5K1B is the immediate substrate for class I PI3Ks that produce PI(3,4,5)P3, so any influence on PI3K/AKT signaling is indirect via product supply rather than a direct regulatory role. Reason: Keep as non-core pathway context rather than a defining PIP5K1B process; the direct gene-level role is PI4P 5-kinase activity and PI phosphate biosynthesis. Proposed replacements: phosphatidylinositol phosphate biosynthetic process Supporting Evidence: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md PI(4,5)P2 produced by PIP5K1B serves as the immediate substrate for class I phosphatidylinositol 3-kinases (PI3Ks), which phosphorylate PI(4,5)P2 at the 3-position to generate phosphatidylinositol 3,4,5-trisphosphate |
| GO:0052742 phosphatidylinositol kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Phosphatidylinositol kinase activity is true but too general for PIP5K1B, whose defining activity is PI4P 5-kinase activity. Reason: Use the specific 1-phosphatidylinositol-4-phosphate 5-kinase activity term. Proposed replacements: 1-phosphatidylinositol-4-phosphate 5-kinase activity Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0006661 phosphatidylinositol biosynthetic process | TAS Reactome:R-HSA-1660499 | MODIFY | Summary: The annotation captures phosphatidylinositol metabolism, but it is broader than the specific PI phosphate biosynthetic role of PIP5K1B. Reason: Replace the broad phosphatidylinositol metabolic/biosynthetic process with phosphatidylinositol phosphate biosynthetic process. Proposed replacements: phosphatidylinositol phosphate biosynthetic process Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0051896 regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | TAS Reactome:R-HSA-6811558 | KEEP AS NON CORE | Summary: PI3K/AKT pathway effects are downstream of phosphoinositide metabolism and are secondary to the direct PIP5K1B lipid kinase function. Reason: Keep as non-core pathway context rather than a defining PIP5K1B process; the direct gene-level role is PI4P 5-kinase activity and PI phosphate biosynthesis. Proposed replacements: phosphatidylinositol phosphate biosynthetic process |
| GO:0000285 1-phosphatidylinositol-3-phosphate 5-kinase activity | TAS Reactome:R-HSA-1676134 | KEEP AS NON CORE | Summary: Reactome assigns this side-reaction/substrate context to PIP5K1B, but it is not the defining physiological activity. The falcon deep research notes that PI3P phosphorylation by type I PIP5Ks is observed in vitro, while PI4P remains the predominant cellular substrate. Reason: Keep as non-core biochemical/pathway context and prioritize the PI4P to PI(4,5)P2 reaction as core. Supporting Evidence: Reactome:R-HSA-1676134 PIP5K1B file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md While in vitro studies show that Type I PIP5Ks can also phosphorylate phosphatidylinositol 3-phosphate (PI3P) to generate PI(3,4)P2 and PI(3,5)P2, PI4P remains the predominant cellular substrate for PI(4,5)P2 synthesis |
| GO:0016308 1-phosphatidylinositol-4-phosphate 5-kinase activity | TAS Reactome:R-HSA-1676082 | ACCEPT | Summary: This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2. Reason: Retain as the specific catalytic function for this type I PIP5 kinase. Supporting Evidence: Reactome:R-HSA-1676082 phosphorylate phosphatidylinositol 4-phosphate (PI4P) to produce phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) file:human/PIP5K1B/PIP5K1B-uniprot.txt Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) |
| GO:0052810 1-phosphatidylinositol-5-kinase activity | TAS Reactome:R-HSA-1675810 | KEEP AS NON CORE | Summary: Reactome assigns this side-reaction/substrate context to PIP5K1B, but it is not the defining physiological activity. Reason: Keep as non-core biochemical/pathway context and prioritize the PI4P to PI(4,5)P2 reaction as core. Supporting Evidence: Reactome:R-HSA-1675810 PIP5K1B |
| GO:0052742 phosphatidylinositol kinase activity | TAS Reactome:R-HSA-1675773 | MODIFY | Summary: Phosphatidylinositol kinase activity is true but too general for PIP5K1B, whose defining activity is PI4P 5-kinase activity. Reason: Use the specific 1-phosphatidylinositol-4-phosphate 5-kinase activity term. Proposed replacements: 1-phosphatidylinositol-4-phosphate 5-kinase activity Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0016308 1-phosphatidylinositol-4-phosphate 5-kinase activity | ISS GO_REF:0000024 | ACCEPT | Summary: This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2. Reason: Retain as the specific catalytic function for this type I PIP5 kinase. Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: PIP5K1B is a cytosolic enzyme that associates with cellular membranes, including plasma membrane and endomembrane contexts where phosphoinositide substrates reside. Reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1675773 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1675810 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676082 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676134 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1676145 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3772434 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3772436 | KEEP AS NON CORE | Summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. Reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. Supporting Evidence: file:human/PIP5K1B/PIP5K1B-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol file:human/PIP5K1B/PIP5K1B-uniprot.txt Cell membrane |
| GO:0001931 uropod | IDA PMID:20442317 An isoform-specific PDZ-binding motif targets type I PIP5 ki... | KEEP AS NON CORE | Summary: PIP5KIbeta localizes to the uropod in polarized leukocyte models through an isoform-specific C-terminal motif. Reason: Keep as a supported cell-type-specific localization, not as the core function. Supporting Evidence: PMID:20442317 Its final 83 amino acids localize PIP5KIbeta to the uropod of chemotaxing neutrophils and T cells PMID:20442317 interact with ezrin-radixin-moesin (ERM) proteins and EBP50 |
| GO:0005515 protein binding | IPI PMID:20442317 An isoform-specific PDZ-binding motif targets type I PIP5 ki... | MARK AS OVER ANNOTATED | Summary: The interaction evidence is real for uropod targeting, but generic protein binding is not informative for PIP5K1B function. Reason: Replace generic binding with the mechanistic localization/adaptor context in narrative rather than retaining GO:0005515 as a reviewed function. Proposed replacements: uropod Supporting Evidence: PMID:20442317 Its final 83 amino acids localize PIP5KIbeta to the uropod of chemotaxing neutrophils and T cells PMID:20442317 interact with ezrin-radixin-moesin (ERM) proteins and EBP50 |
| GO:0016308 1-phosphatidylinositol-4-phosphate 5-kinase activity | NAS PMID:8955136 Type I phosphatidylinositol-4-phosphate 5-kinases are distin... | ACCEPT | Summary: This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2. Reason: Retain as the specific catalytic function for this type I PIP5 kinase. Supporting Evidence: PMID:8955136 Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate file:human/PIP5K1B/PIP5K1B-uniprot.txt Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate |
| GO:0007040 lysosome organization | IMP PMID:22885770 Clathrin and phosphatidylinositol-4,5-bisphosphate regulate ... | NEW | Summary: PIP5K1B has direct ALR-context evidence through the PI(4,5)P2 pathway required for autolysosome tubulation and proto-lysosome budding. GO lacks a specific ALR term in the local cache, so lysosome organization is the best current broad term. Reason: Add a broad lysosome organization annotation for the experimentally supported autophagic lysosome reformation context, with a proposed new ALR-specific child term to avoid over-broad curation long term. Supporting Evidence: PMID:22885770 clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) regulate ALR PMID:22885770 initiation of autolysosome tubulation, and proto-lysosome budding during ALR url:https://www.nature.com/articles/ncb2557 PIP5K1B is required for the initiation of ALR file:human/PIP5K1B/PIP5K1B-notes.md Figure 3 as "PIP5K1B is required for the initiation of ALR" |
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Download this section (compressed HTML)Q: Should GO add a specific autophagic lysosome reformation term under lysosome organization, and should PIP5K1B be annotated to that term instead of broad GO:0007040?
Suggested experts: Li Yu, Yongliang Rong
Q: Which PIP5K1B phosphoinositide substrate activities are physiologically important in vivo versus pathway-level or in vitro side reactions?
Suggested experts: Richard A. Anderson, Reactome phosphoinositide curator
Experiment: Rescue PIP5K1B-depleted cells during starvation-refeeding with wild-type, kinase-dead, and membrane-targeting mutants while quantifying ALR tubule initiation and proto-lysosome budding.
Hypothesis: PIP5K1B kinase activity and membrane recruitment are required for PI(4,5)P2-dependent autophagic lysosome reformation.
Type: genetic rescue/live-cell imaging
Experiment: Measure local PI(4,5)P2 dynamics on autolysosome-derived tubules using phosphoinositide reporters in cells depleted of PIP5K1B, PIP5K1A, or PIP5K1C.
Hypothesis: PIP5K1B supplies a local PI(4,5)P2 pool on ALR membranes that is not fully redundant with other type I PIP5K isoforms.
Type: lipid reporter imaging/RNAi
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