INP51 (SJL1) encodes one of the three yeast synaptojanin-like inositol polyphosphate 5-phosphatases. It has an N-terminal Sac1-like domain, a central inositol 5-phosphatase catalytic domain and a C-terminal proline-rich region with an NPF motif. Inp51 is a membrane-associated PI(4,5)P2 5-phosphatase that converts PI(4,5)P2 to PI4P; unlike Inp52/Inp53 it is not known to hydrolyse PI3P, PI4P or PI(3,5)P2. Loss of INP51 raises PI(4,5)P2 2-4-fold and confers cold tolerance, while combined loss with INP52 or INP53 causes plasma membrane invaginations, cell wall thickening, actin and vacuole defects; inp51 inp52 inp53 is inviable. The EH-domain proteins Tax4 and Irs4 bind Inp51 and activate it, downregulating PI(4,5)P2 and cell-integrity (Pkc1) signalling; Inp51 also contributes to PI(4,5)P2 turnover during endocytosis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the inositol 5-phosphatase family (PTHR11200) with many experimentally characterised members (mammalian INPP5/OCRL/synaptojanin, plant and yeast). Inp51 carries an active 5-phosphatase domain with experimental PI(4,5)P2 5-phosphatase activity; correct inherited core activity. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IDA PMID:10224048 SAC1-like domains of yeast SAC1, INP52, and INP53 and of hum... | ACCEPT | Summary: Guo et al. (York lab) assayed the yeast 5-phosphatases; abstract-only in cache and it foregrounds Sac1/Inp52/Inp53, but Inp51 PI(4,5)P2 5-phosphatase activity is independently established (Stolz 1998). Defer to the curator. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IDA PMID:9565610 INP51, a yeast inositol polyphosphate 5-phosphatase required... | ACCEPT | Summary: Stolz et al.: recombinant Inp51p hydrolyses PI(4,5)P2 at the 5-position. Core activity. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA via EC 3.1.3.36/RHEA:22764 (ARBA). Correct; consistent with experimental data for this protein. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IMP PMID:9438131 Disruption of three phosphatidylinositol-polyphosphate 5-pho... | ACCEPT | Summary: Srinivasan et al.: total PI(4,5)P2 5-phosphatase activity is reduced in inp51/inp52/inp53 disruptants. Supporting Evidence: PMID:9438131 Total phosphatidylinositol-(4,5)-bisphosphate 5-phosphatase activity was reduced to varying degrees in each of the strains. |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | IMP PMID:9565610 INP51, a yeast inositol polyphosphate 5-phosphatase required... | ACCEPT | Summary: Stolz et al.: loss of 5-phosphatase catalytic activity accounts for inp51 phenotypes and inp51 cells accumulate PI(4,5)P2. Supporting Evidence: PMID:9565610 Complementation analysis of an inp51 mutant strain demonstrates that the cold tolerance is strictly due to loss of 5-phosphatase catalytic activity. PMID:9565610 Cells lacking INP51 have a 2-4-fold increase in levels of phosphatidylinositol 4,5-bisphosphate |
| GO:0004439 phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity | RCA GO_REF:0000123 | ACCEPT | Summary: YeastPathways PWY3O-242 assigns this protein to PI(4,5)P2 -> PI4P (EC 3.1.3.36); correct and experimentally supported. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0005515 protein binding | IPI PMID:15265867 Negative regulation of phosphatidylinositol 4,5-bisphosphate... | REMOVE | Summary: Morales-Johansson et al.: Irs4 (P36115) binds Inp51 via its NPF motif and activates it. Real regulatory interaction, but bare protein binding is uninformative. Removal does not dispute the interaction itself. Supporting Evidence: PMID:15265867 The EPS15 homology domain-containing proteins TAX4 and IRS4 bind and activate the PI(4,5)P 5-phosphatase INP51 via an Asn-Pro-Phe motif in INP51. |
| GO:0005515 protein binding | IPI PMID:15265867 Negative regulation of phosphatidylinositol 4,5-bisphosphate... | REMOVE | Summary: Morales-Johansson et al.: Tax4 (P47030) binds and activates Inp51. Real regulatory interaction; bare protein binding uninformative. Removal does not dispute the interaction itself. Supporting Evidence: PMID:15265867 The EPS15 homology domain-containing proteins TAX4 and IRS4 bind and activate the PI(4,5)P 5-phosphatase INP51 via an Asn-Pro-Phe motif in INP51. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Proteome-wide AE-MS interactome recovering Inp51-Irs4; uninformative large-scale binding, redundant with focused evidence. Supporting Evidence: PMID:37968396 The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000127779) for cytoplasm is_active_in; consistent with the diffuse cytoplasmic/cortical distribution of the yeast synaptojanins. Supporting Evidence: PMID:17452534 Although Sjl1-GFP mostly localized to the cytoplasm |
| GO:0005737 cytoplasm | IDA PMID:17452534 PtdIns(4,5)P2 turnover is required for multiple stages durin... | ACCEPT | Summary: Sun et al.: functional Sjl1(Inp51)-GFP expressed at endogenous level is mostly cytoplasmic. Supporting Evidence: PMID:17452534 Although Sjl1-GFP mostly localized to the cytoplasm |
| GO:0005829 cytosol | RCA GO_REF:0000123 | KEEP AS NON CORE | Summary: YeastPathways default cytosol. Sjl1-GFP is largely diffuse/cytoplasmic, so a soluble pool exists, but the enzyme acts on membrane PI(4,5)P2 (plasma membrane, endocytic sites, TGN); cytosol is not where the activity occurs. Supporting Evidence: PMID:17452534 Although Sjl1-GFP mostly localized to the cytoplasm |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (PTN000127779) for membrane; the yeast synaptojanins are membrane-associated and act on membrane phosphoinositides. Supporting Evidence: PMID:9560389 Inp51p (108 kD), Inp52p (136 kD) and Inp53p (124 kD) are membrane-associated. |
| GO:0016020 membrane | IDA PMID:9560389 Identification and characterization of an essential family o... | ACCEPT | Summary: Stolz et al. 1998: Inp51p is membrane-associated by fractionation. Supporting Evidence: PMID:9560389 Inp51p (108 kD), Inp52p (136 kD) and Inp53p (124 kD) are membrane-associated. |
| GO:0016791 phosphatase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro IPR000300 (IPPc 5-phosphatase domain)/IPR002013 (SAC domain) mapping to phosphatase activity; correct general parent. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0030479 actin cortical patch | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt subcellular location (actin patch, from the GFP localisation survey PMID:14562095) mapped to GO. Plausible given Inp51 roles in endocytosis, though endogenous Sjl1-GFP is mostly cytoplasmic; non-core. Supporting Evidence: PMID:17452534 Although Sjl1-GFP mostly localized to the cytoplasm |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IEA GO_REF:0000108 | REMOVE | Summary: Inter-ontology inference from GO:0043813 (PI(3,5)P2 5-phosphatase). Inp51 does not hydrolyse PI(3,5)P2 (its SAC domain is not reported active and UniProt records no use of PI(3,5)P2, PI3P or PI4P), so the source MF and this derived process are both unsupported for Inp51. Supporting Evidence: file:yeast/INP51/INP51-uniprot.txt (PtdIns(3)P) and phosphatidylinositol 4-phosphate (PtdIns(4)P). Plays an |
| GO:0043813 phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity | IBA GO_REF:0000033 | REMOVE | Summary: IBA from PTN000878771, seeded by S. pombe Syj1 and Inp52/Inp53 (SGD:S000005050, S000005635), whose PI(3,5)P2 hydrolysis is experimentally shown. Inp51 is the outlier: it is a PI(4,5)P2-selective 5-phosphatase, its Sac domain was not shown catalytic (Guo et al. report activity for Sac1, Inp52 and Inp53 only), and UniProt states it does not use PI(3,5)P2. Target-specific evidence of divergence from the node. Supporting Evidence: PMID:10224048 The 5-phosphatase domains of synaptojanin, Inp52p, and Inp53p are also catalytic file:yeast/INP51/INP51-uniprot.txt (PtdIns(3)P) and phosphatidylinositol 4-phosphate (PtdIns(4)P). Plays an |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | RCA GO_REF:0000123 | MODIFY | Summary: YeastPathways places all PWY3O-242 enzymes under PIP biosynthesis. Inp51 removes the 5-phosphate from PI(4,5)P2; the appropriate process is phosphatidylinositol dephosphorylation. Proposed replacements: phosphatidylinositol dephosphorylation Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0046856 phosphatidylinositol dephosphorylation | IDA PMID:10224048 SAC1-like domains of yeast SAC1, INP52, and INP53 and of hum... | ACCEPT | Summary: Guo et al. (York lab) lipid phosphatase assays; defer to curator, consistent with Inp51 PI(4,5)P2 5-phosphatase activity. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0046856 phosphatidylinositol dephosphorylation | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro (IPR000300, IPR046985) mapping to phosphatidylinositol dephosphorylation; correct. Supporting Evidence: PMID:9565610 recombinant Inp51p exhibits intrinsic phosphatidylinositol 4,5-bisphosphate 5-phosphatase activity |
| GO:0046856 phosphatidylinositol dephosphorylation | IMP PMID:9438131 Disruption of three phosphatidylinositol-polyphosphate 5-pho... | ACCEPT | Summary: Srinivasan et al.: inp51 disruption reduces PI(4,5)P2 5-phosphatase activity. Supporting Evidence: PMID:9438131 Total phosphatidylinositol-(4,5)-bisphosphate 5-phosphatase activity was reduced to varying degrees in each of the strains. |
| GO:0046856 phosphatidylinositol dephosphorylation | IMP PMID:9560389 Identification and characterization of an essential family o... | ACCEPT | Summary: Stolz et al. 1998: inp51 cells accumulate PI(4,5)P2. Supporting Evidence: PMID:9560389 Analysis of inositol metabolites in vivo showed measurable accumulation of phosphatidylinositol 4,5-bisphosphate in the inp51 mutant. |
| GO:0052658 inositol-1,4,5-trisphosphate 5-phosphatase activity | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA from PTN002597976 seeded by mammalian/pombe enzymes hydrolysing soluble Ins(1,4,5)P3. For yeast Inp51 only lipid substrates have been tested; the rise in Ins(1,4,5)P3 in inp51 cells is attributed to increased PI(4,5)P2 available to Plc1, not to loss of IP3 hydrolysis. Soluble IP3 5-phosphatase activity is unproven for Inp51. Supporting Evidence: PMID:9565610 Cells lacking INP51 have a 2-4-fold increase in levels of phosphatidylinositol 4,5-bisphosphate |
Loading supporting content…
Download this section (compressed HTML)Q: Is the Inp51 Sac1-like domain catalytically inactive, and if so which residues of the CX5R motif have diverged relative to Inp52/Inp53?
Experiment: Express and assay the isolated Inp51, Inp52 and Inp53 SAC domains in parallel against PI3P, PI4P and PI(3,5)P2.
Hypothesis: The Inp51 SAC domain lacks polyphosphoinositide phosphatase activity
Type: biochemistry
Phosphatidylinositol 4,5-bisphosphate 5-phosphatase; synaptojanin-like protein with an N-terminal Sac1 domain, plays a role in phosphatidylinositol 4,5-bisphosphate homeostasis and in endocytosis; null mutation confers cold-tolerant growth
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)