ARG82 (ArgRIII, IPK2, YDR173C) encodes the Saccharomyces cerevisiae inositol polyphosphate multikinase (IPMK), the sole inositol trisphosphate kinase of yeast. In the nucleus, Arg82 phosphorylates the phospholipase C product Ins(1,4,5)P3 predominantly at the 6-position and then the 3-position (Ins(1,4,5)P3 -> Ins(1,4,5,6)P4 -> Ins(1,3,4,5,6)P5), and can also phosphorylate IP3 at the 3-position and Ins(1,3,4,5)P4 at the 6-position; IP5 is then converted to IP6 by Ipk1. Arg82 also pyrophosphorylates IP5 to PP-IP4 and has a reported nuclear PI(4,5)P2 3-kinase activity. arg82 cells accumulate IP3, lack IP6 and inositol pyrophosphates, and are defective in mRNA export, PHO gene repression, NCR gene activation, vacuole biogenesis and stress responses. Independently of its kinase activity, an acidic polyaspartate domain lets Arg82 bind and stabilize the MADS-box transcription factors Mcm1 and Arg80 (ArgRI), which is required for arginine-dependent regulation of arginine anabolic and catabolic genes by the ArgR-Mcm1 complex.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:12828642 Arg82p is a bifunctional protein whose inositol polyphosphat... | KEEP AS NON CORE | Summary: IMP from El Alami et al. 2003: arg82 (and kcs1) cells derepress PHO genes on high phosphate, and only the kinase activity is required for repression. Arg82's role is to supply precursors for Kcs1-made inositol pyrophosphates, which act on the PHO pathway; the transcriptional effect is real but indirect (via metabolites), hence non-core. Supporting Evidence: PMID:12828642 we observed a derepressed expression of genes regulated by phosphate (PHO) on high phosphate medium and a strong decrease in the expression of genes regulated by the quality of nitrogen source (NCR) PMID:12828642 Only the catalytic activity of both kinases was required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | EXP PMID:10683435 Inositol polyphosphate multikinase (ArgRIII) determines nucl... | ACCEPT | Summary: EXP from Saiardi et al. 2000 (arg82 disruption raises IP3 170-fold and lowers IP6). Arg82 is the IP3 6-kinase that initiates the Plc1-Arg82-Ipk1 route. Supporting Evidence: PMID:10683435 increased cellular [InsP(3)] 170-fold and decreased [InsP(6)] 100-fold, indicating reduced phosphorylation of InsP(3) to InsP(6) file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | EXP PMID:7945194 Inositol trisphosphate metabolism in Saccharomyces cerevisia... | ACCEPT | Summary: EXP from Estevez et al. 1994: purification of the soluble Ins(1,4,5)P3 6-kinase from yeast extracts (~40 kDa), later shown to be Arg82/Ipk2. Core activity. Supporting Evidence: PMID:7945194 The yeast enzyme is thus an Ins(1,4,5)P3 6-kinase. PMID:7945194 The enzyme appeared to be the first step in the conversion of Ins(1,4,5)P3 into an InsP5 |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | IDA PMID:10574768 Synthesis of diphosphoinositol pentakisphosphate by a newly ... | ACCEPT | Summary: IDA from Saiardi et al. 1999: recombinant ArgRIII phosphorylates InsP3 to InsP4 and beyond. Core activity. Supporting Evidence: PMID:10574768 the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6) |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | IDA PMID:10720331 A role for nuclear inositol 1,4,5-trisphosphate kinase in tr... | ACCEPT | Summary: IDA from Odom et al. 2000: Ipk2/Arg82 identified as the IP3 kinase of the PLC pathway producing Ins(1,4,5,6)P4. Core activity. Supporting Evidence: PMID:10720331 The inositol 1,4,5-trisphosphate kinase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was found to be identical to Arg82 PMID:10720331 Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was required for gene regulation through ArgR-Mcm1. |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA (RHEA:17717) from the UniProt catalytic-activity annotation. Correct. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Inositol phosphate kinase with both monophosphoinositol and |
| GO:0000823 inositol-1,4,5-trisphosphate 6-kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402. Correct; this 6-kinase step is the main in vivo entry of IP3 into higher inositol phosphates. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0000824 inositol-1,4,5,6-tetrakisphosphate 3-kinase activity | EXP PMID:10683435 Inositol polyphosphate multikinase (ArgRIII) determines nucl... | ACCEPT | Summary: EXP from Saiardi et al. 2000: loss of Arg82 blocks phosphorylation of IP3 through to IP5/IP6, consistent with the Ins(1,4,5,6)P4 3-kinase step. Supporting Evidence: PMID:10683435 increased cellular [InsP(3)] 170-fold and decreased [InsP(6)] 100-fold, indicating reduced phosphorylation of InsP(3) to InsP(6) |
| GO:0000824 inositol-1,4,5,6-tetrakisphosphate 3-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000963723 seeded by ARG82 itself. Arg82 has direct experimental evidence for this activity; the self-donor reflects its own grounding. Supporting Evidence: PMID:10574768 the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6) file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0000824 inositol-1,4,5,6-tetrakisphosphate 3-kinase activity | IDA PMID:10574768 Synthesis of diphosphoinositol pentakisphosphate by a newly ... | ACCEPT | Summary: IDA from Saiardi et al. 1999: ArgRIII converts InsP4 to InsP5. Supporting Evidence: PMID:10574768 the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6) |
| GO:0000824 inositol-1,4,5,6-tetrakisphosphate 3-kinase activity | IDA PMID:10720331 A role for nuclear inositol 1,4,5-trisphosphate kinase in tr... | ACCEPT | Summary: IDA from Odom et al. 2000: Ipk2/Arg82 converts IP3 via Ins(1,4,5,6)P4 to IP5. Supporting Evidence: PMID:10720331 The inositol 1,4,5-trisphosphate kinase of this pathway in Saccharomyces cerevisiae, designated Ipk2, was found to be identical to Arg82 PMID:10720331 Synthesis of inositol 1,4,5,6-tetrakisphosphate, but not IP6, was required for gene regulation through ArgR-Mcm1. |
| GO:0000824 inositol-1,4,5,6-tetrakisphosphate 3-kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA (RHEA:11856). Correct. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Inositol phosphate kinase with both monophosphoinositol and |
| GO:0000825 inositol-1,3,4,5-tetrakisphosphate 6-kinase activity | IDA PMID:11311242 The transcriptional regulator, Arg82, is a hybrid kinase wit... | ACCEPT | Summary: IDA from Zhang et al. 2001: Arg82 phosphorylates Ins(1,3,4,5)P4 to IP5 (6-kinase on the 3-kinase product). Supporting Evidence: PMID:11311242 We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate |
| GO:0000827 inositol-1,3,4,5,6-pentakisphosphate kinase activity | IDA PMID:11311242 The transcriptional regulator, Arg82, is a hybrid kinase wit... | ACCEPT | Summary: IDA from Zhang et al. 2001: Arg82 converts Ins(1,3,4,5,6)P5 to two isomers of diphosphoinositol tetrakisphosphate (PP-IP4), matching the GO definition. A minor activity compared with the 6-/3-kinase route. Supporting Evidence: PMID:11311242 We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate |
| GO:0005634 nucleus | EXP PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w... | ACCEPT | Summary: EXP from Resnick et al. 2005: IPMK/Arg82 is localized to nuclei. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in nucleus) from PTN000963625 (mammalian IPMK/IP6K, Arabidopsis IPK2, ARG82). Consistent with direct yeast data. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10632874, PMID:3311884 Our results show that the three ARGR proteins are localized in the nucleus |
| GO:0005634 nucleus | IDA PMID:10720331 A role for nuclear inositol 1,4,5-trisphosphate kinase in tr... | ACCEPT | Summary: IDA from Odom et al. 2000: nuclear Ipk2/Arg82 inositol phosphate kinase. Supporting Evidence: PMID:10720331 multiple IP messengers that modulate distinct nuclear processes |
| GO:0005634 nucleus | IDA PMID:3311884 Regulation of arginine metabolism in Saccharomyces cerevisia... | ACCEPT | Summary: IDA from Bercy et al. 1987: ARGR-lacZ fusions show the ARGR proteins, including ArgRIII/Arg82, in the nucleus. Supporting Evidence: PMID:3311884 Our results show that the three ARGR proteins are localized in the nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: IEA from UniProt subcellular location (SL-0191). Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10632874, |
| GO:0005634 nucleus | NAS PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | ACCEPT | Summary: NAS from El Bakkoury et al. 2000 (ArgRIII recruitment of ArgRI/Mcm1). Consistent with experimental nuclear localization. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10632874, |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA (is_active_in cytoplasm) from PTN000963625, donors are mammalian IP6K/ITPK and fly/fission yeast proteins rather than IPMK orthologues. All yeast experimental localizations place Arg82 in the nucleus; a small cytoplasmic pool is not excluded but is not supported by yeast data. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000963625 · IPK family node (IPMK + IP6K + ITPK) SUPPORTS SOURCE BUT NOT TARGET Cytoplasmic donors are IP6K/ITPK subfamily members; the IPMK branch including Arg82 is nuclear. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10632874, PMID:3311884 Our results show that the three ARGR proteins are localized in the nucleus |
| GO:0005829 cytosol | RCA GO_REF:0000123 | MARK AS OVER ANNOTATED | Summary: RCA from YeastPathways PWY3O-402, which places all inositol phosphate biosynthesis reactions in the cytosol by default. For Arg82 the experimental localization is nuclear; the YeastCyc compartment is a pathway default, not evidence for Arg82. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10632874, PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0008440 inositol-1,4,5-trisphosphate 3-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000963723 seeded by ARG82. Arg82 phosphorylates IP3 at both the 3- and 6-positions (3-position giving Ins(1,3,4,5)P4); the 6-kinase route predominates in vivo. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Inositol phosphate kinase with both monophosphoinositol and PMID:11311242 We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate |
| GO:0008440 inositol-1,4,5-trisphosphate 3-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (RHEA:11020, EC 2.7.1.127). Correct per UniProt; a genuine, if secondary, Arg82 activity. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Inositol phosphate kinase with both monophosphoinositol and |
| GO:0008440 inositol-1,4,5-trisphosphate 3-kinase activity | IMP PMID:10683435 Inositol polyphosphate multikinase (ArgRIII) determines nucl... | ACCEPT | Summary: IMP from Saiardi et al. 2000: arg82 cells accumulate IP3 170-fold, so Arg82 is the IP3 kinase in vivo; Arg82 is the sole IP3 kinase of yeast. Supporting Evidence: PMID:10683435 increased cellular [InsP(3)] 170-fold and decreased [InsP(6)] 100-fold, indicating reduced phosphorylation of InsP(3) to InsP(6) PMID:22992733 In yeast, the IPMK homologue, Arg82, is the sole inositol-trisphosphate kinase. |
| GO:0008440 inositol-1,4,5-trisphosphate 3-kinase activity | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402 (EC 2.7.1.127). Correct, though the in vivo flux goes mainly via the 6-kinase product Ins(1,4,5,6)P4. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0016236 macroautophagy | IMP PMID:19793921 A genomic screen for yeast mutants defective in selective mi... | MARK AS OVER ANNOTATED | Summary: IMP from the Kanki et al. 2009 genome-wide mitophagy screen, which identified many deletion mutants with reduced mitophagy beyond the core ATG genes. arg82 deletion has pleiotropic effects on inositol phosphate levels, growth and transcription; the screen phenotype does not show that Arg82 participates in autophagy machinery. Retained as an over-annotation rather than removed, as the full screen data were not examined. Supporting Evidence: PMID:19793921 A genome-wide yeast mutant screen for mitophagy-defective strains identified 32 mutants with a block in mitophagy |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: IEA from InterPro IPR005522 (inositol polyphosphate kinase) to kinase activity. Too general; Arg82's defining activity is inositol-1,4,5-trisphosphate 6-kinase (with Ins(1,4,5,6)P4 3-kinase). Proposed replacements: inositol-1,4,5-trisphosphate 6-kinase activity Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IDA PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w... | KEEP AS NON CORE | Summary: IDA from Resnick et al. 2005 for 1-phosphatidylinositol-3-kinase activity. Resnick et al. 2005 report a wortmannin-insensitive nuclear phosphoinositide 3-kinase activity of IPMK that, in yeast, regulates transcription. Yeast has no class I PI3K and PIP3 is barely detectable, so the physiological scope of this lipid kinase activity remains debated; it is retained as a secondary (non-core) activity, deferring to the curators on full-text details. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. PMID:16123124 In yeast, this inositol lipid kinase activity physiologically regulates transcription. |
| GO:0030674 protein-macromolecule adaptor activity | IMP PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | ACCEPT | Summary: IMP from El Bakkoury et al. 2000: Arg82 (ArgRIII) binds the MADS-box proteins ArgRI (Arg80) and Mcm1 and is required for their stability; it is not itself part of the DNA-bound arginine-box complex. The non-catalytic polyaspartate domain mediates this chaperone-like role. Adaptor activity is a reasonable curator choice for this non-catalytic function, which is the second, kinase-independent core role of Arg82. Supporting Evidence: PMID:10632874 We show that the impairment of arginine regulation in an argRIII deletant strain is a result of a lack of stability of ArgRI and Mcm1. PMID:12828642 Mcm1p and Arg80p chaperoning by Arg82p does not involve the inositol polyphosphate kinase activity of Arg82p, but requires its polyaspartate domain |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | ACCEPT | Summary: IPI with SGD:S000004645 (one of the MADS-box partners, Arg80/ArgRI or Mcm1) from El Bakkoury et al. 2000; two-hybrid and affinity chromatography interaction underlying MADS-box protein stabilization (kinase-independent core role). Supporting Evidence: PMID:10632874 Interactions between the two MADS-box proteins and ArgRIII were confirmed using affinity chromatography. |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | ACCEPT | Summary: IPI with SGD:S000004646 (the other MADS-box partner) from El Bakkoury et al. 2000; interaction via the MADS-box alpha helix required for partner stability (kinase-independent core role). Supporting Evidence: PMID:10632874 Interactions between the two MADS-box proteins and ArgRIII were confirmed using affinity chromatography. |
| GO:0032958 inositol phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN004357288 (donors include ARG82 and KCS1). Core process. Supporting Evidence: PMID:10574768 the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6) |
| GO:0032958 inositol phosphate biosynthetic process | IDA PMID:10574768 Synthesis of diphosphoinositol pentakisphosphate by a newly ... | ACCEPT | Summary: IDA from Saiardi et al. 1999: ArgRIII converts InsP3 to higher inositol phosphates. Supporting Evidence: PMID:10574768 the yeast protein, ArgRIII, is an inositol-polyphosphate kinase that can convert InsP(3) to InsP(4), InsP(5) and InsP(6) |
| GO:0032958 inositol phosphate biosynthetic process | IDA PMID:11311242 The transcriptional regulator, Arg82, is a hybrid kinase wit... | ACCEPT | Summary: IDA from Zhang et al. 2001: Arg82 synthesises IP5 and PP-IP4. Supporting Evidence: PMID:11311242 We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate |
| GO:0032958 inositol phosphate biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: IEA from InterPro IPR005522. Correct. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Inositol phosphate kinase with both monophosphoinositol and |
| GO:0032958 inositol phosphate biosynthetic process | RCA GO_REF:0000123 | ACCEPT | Summary: RCA from YeastPathways PWY3O-402. Correct; Arg82 catalyses the IP3 -> IP4 -> IP5 steps of the pathway. Supporting Evidence: file:yeast/ARG82/ARG82-uniprot.txt Its predominant in vivo catalytic function is to |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: IEA inferred from the IDA GO:0016303 (PI 3-kinase) annotation via inter-ontology links. Follows from the curated lipid-kinase activity; Resnick et al. 2005 report a wortmannin-insensitive nuclear phosphoinositide 3-kinase activity of IPMK that, in yeast, regulates transcription. Yeast has no class I PI3K and PIP3 is barely detectable, so the physiological scope of this lipid kinase activity remains debated; it is retained as a secondary (non-core) activity, deferring to the curators on full-text details. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:12828642 Arg82p is a bifunctional protein whose inositol polyphosphat... | KEEP AS NON CORE | Summary: IMP from El Alami et al. 2003: arg82 cells show strongly decreased expression of NCR genes, and the kinase activity is required for NCR gene activation. Indirect regulatory role via inositol phosphate products; non-core. Supporting Evidence: PMID:12828642 we observed a derepressed expression of genes regulated by phosphate (PHO) on high phosphate medium and a strong decrease in the expression of genes regulated by the quality of nitrogen source (NCR) PMID:12828642 Only the catalytic activity of both kinases was required for PHO gene repression by phosphate and for NCR gene activation in response to nitrogen availability |
| GO:0045944 positive regulation of transcription by RNA polymerase II | NAS PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | KEEP AS NON CORE | Summary: NAS from El Bakkoury et al. 2000: Arg82 is required for Mcm1-dependent gene expression and arginine regulation by stabilizing Mcm1 and ArgRI. A genuine non-catalytic role, non-core relative to the kinase function. Supporting Evidence: PMID:10632874 ArgRIII integrity is crucial for Mcm1 function, as shown by the marked decreased expression of five genes controlled by Mcm1. |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000274018 (ARG82 itself plus human IPMK and ITPKA/B donors). Accepted as a secondary activity consistent with the Arg82 IDA. Resnick et al. 2005 report a wortmannin-insensitive nuclear phosphoinositide 3-kinase activity of IPMK that, in yeast, regulates transcription. Yeast has no class I PI3K and PIP3 is barely detectable, so the physiological scope of this lipid kinase activity remains debated; it is retained as a secondary (non-core) activity, deferring to the curators on full-text details. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IDA PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w... | KEEP AS NON CORE | Summary: IDA from Resnick et al. 2005. Resnick et al. 2005 report a wortmannin-insensitive nuclear phosphoinositide 3-kinase activity of IPMK that, in yeast, regulates transcription. Yeast has no class I PI3K and PIP3 is barely detectable, so the physiological scope of this lipid kinase activity remains debated; it is retained as a secondary (non-core) activity, deferring to the curators on full-text details. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. PMID:16123124 In yeast, this inositol lipid kinase activity physiologically regulates transcription. |
| GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity | EXP PMID:16123124 Inositol polyphosphate multikinase is a nuclear PI3-kinase w... | KEEP AS NON CORE | Summary: EXP from Resnick et al. 2005: IPMK converts PI(4,5)P2 to PI(3,4,5)P3. Resnick et al. 2005 report a wortmannin-insensitive nuclear phosphoinositide 3-kinase activity of IPMK that, in yeast, regulates transcription. Yeast has no class I PI3K and PIP3 is barely detectable, so the physiological scope of this lipid kinase activity remains debated; it is retained as a secondary (non-core) activity, deferring to the curators on full-text details. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0046934 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: IEA (RHEA:21292) from UniProt catalytic activity, based on Resnick et al. 2005. Secondary activity. Supporting Evidence: PMID:16123124 We now report the robust, physiologic, and evolutionarily conserved phosphoinositide 3-kinase activity of inositol polyphosphate multikinase, which is localized to nuclei and unaffected by wortmannin. |
| GO:0050821 protein stabilization | IMP PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | ACCEPT | Summary: IMP from El Bakkoury et al. 2000: in arg82 cells ArgRI and Mcm1 are unstable. Arg82 directly binds and protects these MADS-box proteins; a real, kinase-independent second core function. Supporting Evidence: PMID:10632874 We show that the impairment of arginine regulation in an argRIII deletant strain is a result of a lack of stability of ArgRI and Mcm1. |
| GO:0050821 protein stabilization | IMP PMID:12828642 Arg82p is a bifunctional protein whose inositol polyphosphat... | ACCEPT | Summary: IMP from El Alami et al. 2003: chaperoning of Mcm1 and Arg80 requires the polyaspartate domain but not the kinase activity of Arg82. Supporting Evidence: PMID:12828642 Mcm1p and Arg80p chaperoning by Arg82p does not involve the inositol polyphosphate kinase activity of Arg82p, but requires its polyaspartate domain |
| GO:0090575 RNA polymerase II transcription regulator complex | NAS PMID:10632874 Recruitment of the yeast MADS-box proteins, ArgRI and Mcm1 b... | MARK AS OVER ANNOTATED | Summary: NAS from El Bakkoury et al. 2000 placing Arg82 in the RNA polymerase II transcription regulator complex. The same paper's data indicate ArgRIII is not present in the DNA-bound ArgR-Mcm1 complex on the arginine boxes and that its requirement can be bypassed by overproducing ArgRI or Mcm1; Arg82 acts by stabilizing the complex subunits rather than as a stable component. Not removed, as UniProt and earlier literature describe an ArgR-Mcm1 complex including Arg82. Supporting Evidence: PMID:10632874 which indicates that ArgRIII is not present in the protein complex formed with the 'arginine boxes' PMID:10632874 We show that the impairment of arginine regulation in an argRIII deletant strain is a result of a lack of stability of ArgRI and Mcm1. |
| GO:0120517 inositol pentakisphosphate kinase activity | RCA GO_REF:0000123 | MODIFY | Summary: RCA from YeastPathways PWY3O-402 for the reaction ATP + Ins(1,3,4,5,6)P5 -> diphospho-IP4. The GO term (inositol pentakisphosphate kinase activity) is defined as IP5 -> IP6, which is the Ipk1 reaction; Arg82 does not make IP6 from IP5. Its IP5 pyrophosphorylation activity is GO:0000827. Proposed replacements: inositol-1,3,4,5,6-pentakisphosphate kinase activity Supporting Evidence: PMID:11311242 We now show that Arg82 phosphorylates inositol 1,3,4,5-tetrakisphosphate to inositol pentakisphosphate, which is itself converted to two isomers of diphosphoinositol tetrakisphosphate |
| GO:1900079 regulation of arginine biosynthetic process | IMP PMID:22992733 Arginine transcriptional response does not require inositol ... | KEEP AS NON CORE | Summary: IMP from Bosch & Saiardi 2012: Arg82 protein is needed for the arginine-dependent transcriptional response, but catalytically inactive Arg82 fully restores it, so this regulation of arginine metabolism is a non-catalytic (MADS-box stabilizing) function of Arg82. Supporting Evidence: PMID:22992733 catalytically inactive Arg82 fully restored the arginine-dependent transcriptional response |
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Download this section (compressed HTML)Q: Is the nuclear PI(4,5)P2 3-kinase activity of Arg82 physiologically relevant in yeast, given the near absence of detectable PIP3, and which transcriptional outputs depend on it rather than on soluble inositol phosphates?
Q: Does Arg82 act as a chaperone that prevents degradation of free Mcm1/Arg80, or does it transiently assemble with the ArgR-Mcm1 complex on promoters? A more specific MF term than adaptor activity may be warranted.
Q: YeastPathways maps Arg82 and Kcs1 IP5 pyrophosphorylation to GO:0120517 (IP5 -> IP6); should the YeastPathways-to-GO mapping for this reaction be corrected to GO:0000827?
Experiment: Compare arg82 null, kinase-dead and polyaspartate-deletion alleles by targeted inositol-lipid and inositol-phosphate profiling and RNA-seq to partition transcriptional effects between soluble InsPs, lipid 3-kinase activity and MADS-box stabilization.
Inositol polyphosphate multikinase (IPMK); sequentially phosphorylates Ins(1,4,5)P3 to form Ins(1,3,4,5,6)P5; also has diphosphoinositol polyphosphate synthase activity; regulates genes responsive to arginine, phosphate, and nitrogen; needed by most [PSI+] variants for prion propagation
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