id: O14986 gene_symbol: PIP5K1B product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- 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. alternative_products: - name: '1' id: O14986-1 - name: 2 (Isoform 1) id: O14986-2 sequence_note: VSP_016010, VSP_016011 - name: '3' id: O14986-3 sequence_note: VSP_054771 existing_annotations: - term: id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: PIP5K1B contributes directly to phosphatidylinositol phosphate biosynthesis by producing PI(4,5)P2 from PI4P. action: ACCEPT reason: The process-level term is broad but appropriate for the core PI phosphate biosynthetic function. supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: 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. action: ACCEPT reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - reference_id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md supporting_text: >- PIP5K1B localizes primarily to the cytoplasmic face of the plasma membrane, where it carries out its principal function of generating PI(4,5)P2 - term: id: GO:0012505 label: endomembrane system evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: PIP5K1B is a cytosolic enzyme that associates with cellular membranes, including plasma membrane and endomembrane contexts where phosphoinositide substrates reside. action: ACCEPT reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: 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.' action: ACCEPT reason: Retain as the specific catalytic function for this type I PIP5 kinase. supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md supporting_text: PIP5K1B catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PI4P, PtdIns4P) to generate phosphatidylinositol 4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md supporting_text: PIP5K1B exhibits primary specificity for PI4P as its physiological substrate - term: id: GO:0046488 label: phosphatidylinositol metabolic process evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: The annotation captures phosphatidylinositol metabolism, but it is broader than the specific PI phosphate biosynthetic role of PIP5K1B. action: MODIFY reason: Replace the broad phosphatidylinositol metabolic/biosynthetic process with phosphatidylinositol phosphate biosynthetic process. proposed_replacement_terms: - id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0051896 label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: 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. action: KEEP_AS_NON_CORE 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_replacement_terms: - id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md supporting_text: >- 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 - term: id: GO:0052742 label: phosphatidylinositol kinase activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Phosphatidylinositol kinase activity is true but too general for PIP5K1B, whose defining activity is PI4P 5-kinase activity. action: MODIFY reason: Use the specific 1-phosphatidylinositol-4-phosphate 5-kinase activity term. proposed_replacement_terms: - id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0006661 label: phosphatidylinositol biosynthetic process evidence_type: TAS original_reference_id: Reactome:R-HSA-1660499 qualifier: involved_in review: summary: The annotation captures phosphatidylinositol metabolism, but it is broader than the specific PI phosphate biosynthetic role of PIP5K1B. action: MODIFY reason: Replace the broad phosphatidylinositol metabolic/biosynthetic process with phosphatidylinositol phosphate biosynthetic process. proposed_replacement_terms: - id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0051896 label: regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction evidence_type: TAS original_reference_id: Reactome:R-HSA-6811558 qualifier: involved_in review: summary: PI3K/AKT pathway effects are downstream of phosphoinositide metabolism and are secondary to the direct PIP5K1B lipid kinase function. action: KEEP_AS_NON_CORE 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_replacement_terms: - id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process - term: id: GO:0000285 label: 1-phosphatidylinositol-3-phosphate 5-kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-1676134 qualifier: enables review: 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. action: KEEP_AS_NON_CORE reason: Keep as non-core biochemical/pathway context and prioritize the PI4P to PI(4,5)P2 reaction as core. supported_by: - reference_id: Reactome:R-HSA-1676134 supporting_text: PIP5K1B - reference_id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md supporting_text: 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 - term: id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-1676082 qualifier: enables review: summary: 'This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2.' action: ACCEPT reason: Retain as the specific catalytic function for this type I PIP5 kinase. supported_by: - reference_id: Reactome:R-HSA-1676082 supporting_text: phosphorylate phosphatidylinositol 4-phosphate (PI4P) to produce phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 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) - term: id: GO:0052810 label: 1-phosphatidylinositol-5-kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-1675810 qualifier: enables review: summary: Reactome assigns this side-reaction/substrate context to PIP5K1B, but it is not the defining physiological activity. action: KEEP_AS_NON_CORE reason: Keep as non-core biochemical/pathway context and prioritize the PI4P to PI(4,5)P2 reaction as core. supported_by: - reference_id: Reactome:R-HSA-1675810 supporting_text: PIP5K1B - term: id: GO:0052742 label: phosphatidylinositol kinase activity evidence_type: TAS original_reference_id: Reactome:R-HSA-1675773 qualifier: enables review: summary: Phosphatidylinositol kinase activity is true but too general for PIP5K1B, whose defining activity is PI4P 5-kinase activity. action: MODIFY reason: Use the specific 1-phosphatidylinositol-4-phosphate 5-kinase activity term. proposed_replacement_terms: - id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: 'This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2.' action: ACCEPT reason: Retain as the specific catalytic function for this type I PIP5 kinase. supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0005886 label: plasma membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: PIP5K1B is a cytosolic enzyme that associates with cellular membranes, including plasma membrane and endomembrane contexts where phosphoinositide substrates reside. action: ACCEPT reason: Retain as a supported membrane location for PIP5K1B catalytic activity and PN-relevant membrane remodeling contexts. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1675773 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1675810 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1676082 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1676134 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1676145 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3772434 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3772436 qualifier: located_in review: summary: Cytosol is a correct broad localization for PIP5K1B, but it does not capture the membrane-associated catalytic biology. action: KEEP_AS_NON_CORE reason: Keep as a broad non-core location while emphasizing membrane-associated PI4P 5-kinase activity. supported_by: - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm, cytosol' - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Cell membrane - term: id: GO:0001931 label: uropod evidence_type: IDA original_reference_id: PMID:20442317 qualifier: located_in review: summary: PIP5KIbeta localizes to the uropod in polarized leukocyte models through an isoform-specific C-terminal motif. action: KEEP_AS_NON_CORE reason: Keep as a supported cell-type-specific localization, not as the core function. supported_by: - reference_id: PMID:20442317 supporting_text: Its final 83 amino acids localize PIP5KIbeta to the uropod of chemotaxing neutrophils and T cells - reference_id: PMID:20442317 supporting_text: interact with ezrin-radixin-moesin (ERM) proteins and EBP50 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20442317 qualifier: enables review: summary: The interaction evidence is real for uropod targeting, but generic protein binding is not informative for PIP5K1B function. action: MARK_AS_OVER_ANNOTATED reason: Replace generic binding with the mechanistic localization/adaptor context in narrative rather than retaining GO:0005515 as a reviewed function. proposed_replacement_terms: - id: GO:0001931 label: uropod supported_by: - reference_id: PMID:20442317 supporting_text: Its final 83 amino acids localize PIP5KIbeta to the uropod of chemotaxing neutrophils and T cells - reference_id: PMID:20442317 supporting_text: interact with ezrin-radixin-moesin (ERM) proteins and EBP50 - term: id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity evidence_type: NAS original_reference_id: PMID:8955136 qualifier: enables review: summary: 'This is the core PIP5K1B molecular function: phosphorylation of PI4P at the 5 position to generate PI(4,5)P2/PIP2.' action: ACCEPT reason: Retain as the specific catalytic function for this type I PIP5 kinase. supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate - term: id: GO:0007040 label: lysosome organization evidence_type: IMP original_reference_id: PMID:22885770 qualifier: involved_in review: 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. action: NEW 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. supported_by: - reference_id: PMID:22885770 supporting_text: clathrin and phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P(2)) regulate ALR - reference_id: PMID:22885770 supporting_text: initiation of autolysosome tubulation, and proto-lysosome budding during ALR - reference_id: url:https://www.nature.com/articles/ncb2557 supporting_text: PIP5K1B is required for the initiation of ALR - reference_id: file:human/PIP5K1B/PIP5K1B-notes.md supporting_text: Figure 3 as "PIP5K1B is required for the initiation of ALR" references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:20442317 title: An isoform-specific PDZ-binding motif targets type I PIP5 kinase beta to the uropod and controls polarization of neutrophil-like HL60 cells. findings: [] - id: PMID:8955136 title: Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. findings: [] - id: Reactome:R-HSA-1660499 title: Synthesis of PIPs at the plasma membrane findings: [] - id: Reactome:R-HSA-1675773 title: PI(3,4)P2 is phosphorylated to PI(3,4,5)P3 by PIP5K1A-C at the plasma membrane findings: [] - id: Reactome:R-HSA-1675810 title: PI is phosphorylated to PI5P by PIP5K1A/B at the plasma membrane findings: [] - id: Reactome:R-HSA-1676082 title: PI4P is phosphorylated to PI(4,5)P2 by PIP5K1A-C at the plasma membrane findings: [] - id: Reactome:R-HSA-1676134 title: PI3P is phosphorylated to PI(3,5)P2 by PIP5K1A/B at the plasma membrane findings: [] - id: Reactome:R-HSA-1676145 title: PI3P is phosphorylated to PI(3,4)P2 by PIP4K2/5K1 at the plasma membrane findings: [] - id: Reactome:R-HSA-3772434 title: Phosphorylated DVL recruits PIP5K1B to the plasma membrane findings: [] - id: Reactome:R-HSA-3772436 title: DVL-associated PIP5K1B phosphorylates PI4P to PI(4,5)P2 findings: [] - id: Reactome:R-HSA-6811558 title: PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling findings: [] - id: PMID:22885770 title: Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. findings: [] - id: url:https://www.nature.com/articles/ncb2557 title: 'Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation | Nature Cell Biology' findings: [] - id: file:human/PIP5K1B/PIP5K1B-deep-research-falcon.md title: Falcon deep research report for PIP5K1B findings: [] reference_review: relevance: MEDIUM correctness: UNVERIFIED review_notes: >- LLM-synthesized (Edison/falcon) report. Cross-checkable, gene-specific claims used to strengthen this review: PIP5K1B catalyzes PI4P + ATP -> PI(4,5)P2 with PI4P as the predominant physiological substrate (PI3P phosphorylation in vitro only); plasma-membrane (cytoplasmic face) as the principal site of PI(4,5)P2 generation; and PI(4,5)P2 as the immediate class I PI3K substrate that makes PI(3,4,5)P3 (basis for the indirect, non-core PI3K/AKT annotation). These are consistent with the cached primary literature (PMID:8955136) and UniProt. The report also asserts a PIP5Kbeta-specific role at the immunological synapse (CD28/Vav1/filamin A; cites Kallikourdis et al. 2016, J Immunol) which is genuinely PIP5K1B-specific but is not currently in GOA and its source paper is not cached, so it was not used to add an annotation. Many broader functional statements (actin remodeling, adhesion, endocytosis, cell migration, cancer) are paralog-generalized from PIP5K1A/PIP5K1C or family-level reviews rather than directly evidenced for PIP5K1B, and the structural/activation-loop and dimerization mechanisms are described at the family/PIP5K1A level; these were treated as speculative and not propagated. The report cites only DOIs (no PMIDs verified against cached publications), hence UNVERIFIED. - id: file:human/PIP5K1B/PIP5K1B-uniprot.txt title: UniProt record for human PIP5K1B findings: [] - id: file:human/PIP5K1B/PIP5K1B-notes.md title: PIP5K1B curation notes findings: [] - id: file:projects/PROTEOSTASIS/mappings/autophagy_lysosome_pathway.yaml title: Proteostasis Network autophagy-lysosome pathway mappings findings: [] core_functions: - description: ATP-dependent phosphorylation of phosphatidylinositol 4-phosphate (PI4P) to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2/PIP2), supporting phosphoinositide signaling and membrane remodeling. molecular_function: id: GO:0016308 label: 1-phosphatidylinositol-4-phosphate 5-kinase activity directly_involved_in: - id: GO:0046854 label: phosphatidylinositol phosphate biosynthetic process locations: - id: GO:0005886 label: plasma membrane - id: GO:0012505 label: endomembrane system supported_by: - reference_id: PMID:8955136 supporting_text: Phosphatidylinositol-4-phosphate 5-kinases (PIP5K) synthesize phosphatidylinositol-4,5-bisphosphate - reference_id: file:human/PIP5K1B/PIP5K1B-uniprot.txt supporting_text: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate proposed_new_terms: - proposed_name: autophagic lysosome reformation proposed_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. proposed_parent: id: GO:0007040 label: lysosome organization supported_by: - reference_id: PMID:22885770 supporting_text: nascent lysosomes are formed from autolysosomal membranes through an evolutionarily conserved cellular process, autophagic lysosome reformation (ALR) - reference_id: PMID:22885770 supporting_text: initiation of autolysosome tubulation, and proto-lysosome budding during ALR suggested_questions: - question: 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? experts: - Li Yu - Yongliang Rong - question: Which PIP5K1B phosphoinositide substrate activities are physiologically important in vivo versus pathway-level or in vitro side reactions? experts: - Richard A. Anderson - Reactome phosphoinositide curator suggested_experiments: - description: 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. experiment_type: genetic rescue/live-cell imaging hypothesis: PIP5K1B kinase activity and membrane recruitment are required for PI(4,5)P2-dependent autophagic lysosome reformation. - description: Measure local PI(4,5)P2 dynamics on autolysosome-derived tubules using phosphoinositide reporters in cells depleted of PIP5K1B, PIP5K1A, or PIP5K1C. experiment_type: lipid reporter imaging/RNAi hypothesis: PIP5K1B supplies a local PI(4,5)P2 pool on ALR membranes that is not fully redundant with other type I PIP5K isoforms.