Pias1 (protein inhibitor of activated STAT 1) is a nuclear SP-RING-type SUMO E3 ligase of the PIAS family (related to yeast Siz1/Siz2) and a transcriptional coregulator. It has an N-terminal SAP domain that binds A/T-rich DNA and chromatin, a PINIT domain, a zinc-coordinating SP-RING that binds the SUMO E2 Ubc9 (UBE2I), a SUMO-interacting motif and a Ser/Thr-rich C-terminus. By bridging Ubc9 and substrates it catalyses SUMO conjugation to many nuclear proteins, mostly transcription factors, including C/EBPbeta (promoting its degradation and restraining adipogenesis), GATA4, FOXA2, PPARgamma (enabling PPARgamma transrepression of inflammatory genes in macrophages), the Tr2 nuclear receptor, PML and PML-RARA (priming their ubiquitin-mediated degradation), and DNA repair proteins such as MRE11. Independently of substrate sumoylation, Pias1 binds activated transcription factors and blocks their DNA binding: it inhibits recruitment of interferon-activated STAT1 and of NF-kB p65 to target promoters, so Pias1-deficient mice overexpress subsets of interferon- and NF-kB-inducible genes, show elevated proinflammatory cytokines and resist some infections. This repression is switched on during inflammation by IKKalpha-mediated Ser90 phosphorylation. Depending on the partner Pias1 can also coactivate transcription (e.g. GATA4) or act as a cofactor that directs a transcription factor to its targets (tethering Msx1 to the nuclear periphery and the MyoD enhancer), and it binds TBP. Pias1 is found in the nucleoplasm, on chromatin, in nuclear speckles and in PML nuclear bodies, with a minor pool at hippocampal synapses.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000082 G1/S transition of mitotic cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara projection (from rat Pias1) asserting involvement in the G1/S transition. No mouse data show Pias1 executing a cell-cycle step. Reason: PIAS1 is a SUMO E3 ligase and inhibitor/coregulator of transcription factors; it does not execute steps of this process. Effects on it are downstream consequences of substrate sumoylation or transcription factor inhibition (pleiotropic), so the process annotation overstates its role. Consistent with the human PIAS1 review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0000082 G1/S transition of mitotic cell cycle | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Rat-to-mouse ISO transfer for G1/S transition of mitotic cell cycle (RGD Pias1). Any cell-cycle effect of PIAS1 (e.g. via KLF8 sumoylation) is indirect. Reason: PIAS1 is a SUMO E3 ligase and inhibitor/coregulator of transcription factors; it does not execute steps of this process. Effects on it are downstream consequences of substrate sumoylation or transcription factor inhibition (pleiotropic), so the process annotation overstates its role. Consistent with the human PIAS1 review. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:1307843 Β· Pias1 UNRESOLVED Rat Pias1 source annotation not traced to its primary paper here; the same downstream-phenotype concern applies to it. Cell-cycle effects follow from transcription factor (e.g. KLF8) sumoylation. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: PIAS family members negatively regulate RNA polymerase II transcription. Mouse PIAS1 blocks STAT1 and p65 recruitment to target promoters (shown with Pias1-/- cells). Reason: Supported by mouse genetic evidence for STAT1 and NF-kB target gene repression; the PAINT node placement across PIAS orthologs is sound. Supporting Evidence: PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo PMID:15657437 the binding of p65 to the promoters of NF-kappaB-regulated genes is significantly enhanced in Pias1-/- cells |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:16127449 A SUMOylation-dependent pathway mediates transrepression of ... | ACCEPT | Summary: IMP: siRNA knockdown of PIAS1 in mouse macrophages abolished PPARgamma-dependent transrepression of the iNOS promoter; PIAS1 sumoylates PPARgamma, targeting it to NCoR corepressor complexes on inflammatory promoters. Reason: PIAS1 does the work in this repression mechanism (it is the E3 that sumoylates the repressor-converting PPARgamma), and repression of Pol II genes is a core output of PIAS1 more generally. Supporting Evidence: PMID:16127449 siRNA-mediated knockdown of PIAS1 in primary macrophages abolished PPARΞ³ transrepression of the endogenous iNOS gene PMID:16127449 These results suggest that PIAS1/Ubc9-mediated sumoylation is required for PPARΞ³-dependent transrepression. |
| GO:0000724 double-strand break repair via homologous recombination | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1: PIAS1 and PIAS4 promote DSB repair and IR resistance; PIAS1 SUMOylates MRE11 on damaged chromatin to stabilise it for end resection, the first step of homologous recombination. Reason: PIAS1 acts directly at DSBs as the SUMO E3 for repair proteins (MRE11, BRCA1), so it performs a modifying step in HR repair rather than having an indirect effect. Transfer to mouse is reasonable given conservation of the SAP and SP-RING domains. Supporting Evidence: PMID:20016603 we show that PIAS1 and PIAS4 promote DSB repair and confer IR resistance PMID:36050397 PIAS1 is recruited to damaged chromatin, which facilitates MRE11 SUMOylation to enhance MRE11 stability by antagonizing ubiquitylation. |
| GO:0000729 DNA double-strand break processing | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for DNA double-strand break processing (end resection): PIAS1 SUMOylates MRE11 on damaged chromatin, antagonising its ubiquitylation and stabilising it during resection. Reason: Directly supported by the human MRE11 study (PIAS1 is the major SUMO E3 for MRE11 in resection); conserved enzyme, so the ortholog transfer is sound. Supporting Evidence: PMID:36050397 PIAS1 is recruited to damaged chromatin, which facilitates MRE11 SUMOylation to enhance MRE11 stability by antagonizing ubiquitylation. |
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: IBA placing PIAS proteins on chromatin. PIAS1 binds A/T-rich DNA/chromatin via its SAP domain; in mouse jejunal epithelium PIAS1 is recruited to the GATA4-regulated IFABP promoter by ChIP. Reason: Chromatin association via the SAP domain is a conserved PIAS/Siz property, experimentally supported for mouse PIAS1 at promoters. Supporting Evidence: PMID:22539995 In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter file:mouse/Pias1/Pias1-uniprot.txt In vitro, binds A/T-rich DNA (By similarity). |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | KEEP AS NON CORE | Summary: IDA: PIAS1 enables Msx1 to bind selectively to the core enhancer region (CER) of MyoD in myoblasts; UniProt records that PIAS1 is capable of binding the TAAT core enhancer. The cached record is abstract-only. Reason: Experimental annotation the curator made from the full text; PIAS1 occupancy of cis-regulatory regions is real but largely as a cofactor of DNA-binding transcription factors (Msx1, GATA4) via low-specificity SAP-domain DNA binding, so it is accessory to the core E3/inhibitor roles. Consistent with the human review. Supporting Evidence: PMID:16600910 PIAS1 enables Msx1 to bind selectively to a key regulatory element in MyoD, the CER PMID:22539995 In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter |
| GO:0003714 transcription corepressor activity | ISO PMID:9724754 Inhibition of Stat1-mediated gene activation by PIAS1. | MODIFY | Summary: ISO from human PIAS1 (PMID:9724754) for transcription corepressor activity. PIAS1 inhibits STAT1 by binding the activated STAT1 dimer and blocking its DNA binding, not by bridging it to repressive machinery. Reason: GO:0140416 transcription regulator inhibitor activity matches the mechanism (direct binding that blocks DNA binding, independent of STAT1 sumoylation) and is already supported by IBA; same MODIFY as in the human review. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O75925 Β· PIAS1 SOURCE STALE OR MISSING Current human GOA carries transcription corepressor activity only as TAS PMID:10805787 (MODIFIED to GO:0140416 in the human review), not with PMID:9724754. Proposed replacements: transcription regulator inhibitor activity Supporting Evidence: PMID:9724754 PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon PMID:12764129 inhibition of STAT1 by PIAS proteins does not require SUMO modification of STAT1 PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter |
| GO:0005515 protein binding | IPI PMID:14611647 The negative regulator of Gli, Suppressor of fused (Sufu), i... | REMOVE | Summary: IPI from a yeast two-hybrid screen with mouse Sufu as bait that recovered PIAS1 among several nuclear prey; the cached abstract confirms only the Sufu-SAP18 and Sufu-Galectin3 interactions by independent assays. Reason: Generic protein binding is uninformative, and the Sufu-PIAS1 interaction is an unconfirmed screen hit with no functional consequence described, so no more specific MF can be supported. Removal does not imply the interaction is false. Supporting Evidence: PMID:14611647 A yeast two-hybrid screen with mSufu as bait allowed us to identify several nuclear proteins as potential partners of mSufu PMID:14611647 We confirmed the mSufu-SAP18 and mSufu-Galectin3 interactions by independent biochemical assays |
| GO:0005515 protein binding | IPI PMID:16127449 A SUMOylation-dependent pathway mediates transrepression of ... | MODIFY | Summary: IPI: PIAS1 interacts with PPARgamma (Y2H with macrophage library, co-IP of endogenous proteins in RAW264.7 cells and primary macrophages); PIAS1 sumoylates ligand-bound PPARgamma to drive transrepression of inflammatory genes. Reason: The partner is the nuclear receptor PPARgamma, which PIAS1 binds and sumoylates; GO:0042975 peroxisome proliferator activated receptor binding is the evidence-backed informative replacement for generic protein binding. Proposed replacements: peroxisome proliferator activated receptor binding Supporting Evidence: PMID:16127449 co-immunoprecipitation experiments using antibodies directed against either endogenous or epitope-tagged PPARΞ³ and PIAS1, demonstrated a basal interaction in RAW264.7 cells or in primary macrophages PMID:16127449 These results suggest that PIAS1/Ubc9-mediated sumoylation is required for PPARΞ³-dependent transrepression. |
| GO:0005515 protein binding | IPI PMID:16522640 Interaction of protein inhibitor of activated STAT (PIAS) pr... | MODIFY | Summary: IPI: PIAS1 binds the TATA-binding protein core (TBPCORE) through a conserved 39-residue C-terminal region; endogenous proteins co-IP from mouse liver/spleen nuclear extracts and in vitro-translated proteins interact directly. Reason: Direct, mapped interaction with TBP is shown, so GO:0017025 TBP-class protein binding is an evidence-backed informative replacement. Its functional consequence is not yet established, so it is not treated as core. Proposed replacements: TBP-class protein binding Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts PMID:16522640 In vitro-translated PIAS1 and TBP co-immunoprecipitated, which indicated that other nuclear proteins were not required for the interaction |
| GO:0005515 protein binding | IPI PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | MODIFY | Summary: IPI: PIAS1 (via its N-terminus) binds the Msx1 homeoprotein (via its C-terminus); the interaction, not Msx1 sumoylation, is required for Msx1 to repress myogenic genes and to localize to the nuclear periphery. Abstract-only cache. Reason: Msx1 is a sequence-specific DNA-binding transcription factor, and the paper shows a functional PIAS1-Msx1 interaction; GO:0140297 DNA-binding transcription factor binding is the informative replacement (as used for transcription factor partners in the human review). Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:16600910 We demonstrate that the interaction of Msx1 with PIAS1, but not its sumoylation, is required for Msx1 to function as an inhibitor of myoblast differentiation PMID:16600910 We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells |
| GO:0005515 protein binding | IPI PMID:17187077 SUMOylation of Tr2 orphan receptor involves Pml and fine-tun... | MODIFY | Summary: IPI with the Tr2 orphan nuclear receptor (Nr2c1) from a study of Tr2 SUMOylation in stem cells; UniProt records that PIAS1 interacts with NR2C1 and that the interaction promotes its sumoylation. The cached record is abstract-only and does not name PIAS1. Reason: Nr2c1 is a nuclear receptor, and UniProt curation of the full paper states the interaction promotes Tr2 sumoylation (a substrate relationship), so GO:0016922 nuclear receptor binding is a defensible informative replacement that defers to the curator on the interaction itself. Proposed replacements: nuclear receptor binding Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Interacts with NR2C1; the interaction promotes its PMID:17187077 The Tr2 orphan nuclear receptor can be SUMOylated |
| GO:0005515 protein binding | IPI PMID:22406621 The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML ... | REMOVE | Summary: IPI with PML (isoform PML-12): PIAS1 interacts with the PML RBCC/Box2-CC region in PML-NBs and SUMOylates PML, promoting CK2-dependent PML degradation. Reason: Generic protein binding is uninformative. PML is a SUMOylation substrate and this enzyme-substrate relationship is already captured by the SUMO ligase activity / protein sumoylation annotations from the same paper; no distinct informative MF term applies. Removal does not mean the interaction is false. Supporting Evidence: PMID:22406621 These experiments indicate that PIAS1 and PIASxΞ± interact with PML in PML-NBs PMID:22406621 By performing in vitro SUMOylation assays, we discovered that both PIAS1 and PIASxΞ± SUMOylate PML. |
| GO:0005634 nucleus | EXP PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | ACCEPT | Summary: EXP: mouse PIAS1 is nuclear in myoblasts, where it localizes with Msx1 at the nuclear periphery. Reason: Nuclear localization is well established for PIAS1 and matches its function as a nuclear SUMO E3 and transcriptional coregulator. Supporting Evidence: PMID:16600910 We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells |
| GO:0005634 nucleus | IDA PMID:16522640 Interaction of protein inhibitor of activated STAT (PIAS) pr... | ACCEPT | Summary: IDA: endogenous PIAS1 present in mouse liver and spleen nuclear extracts, where it co-IPs with TBP. Reason: Direct evidence for nuclear PIAS1 in mouse tissues. Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for nucleus. Reason: Consistent with experimental data. Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts PMID:16600910 We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells |
| GO:0005634 nucleus | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for nucleus. Reason: Consistent with mouse and human experimental data. Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts |
| GO:0005654 nucleoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: PIAS proteins are active in the nucleoplasm. Reason: Consistent with the nuclear SUMO E3 and coregulator functions of PIAS1. Supporting Evidence: PMID:22539995 In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0005654 nucleoplasm | IDA PMID:22539995 PIAS1 is a GATA4 SUMO ligase that regulates GATA4-dependent ... | ACCEPT | Summary: IDA from the GATA4 study in intestinal cells; PIAS1 SUMOylates and coactivates GATA4 in the nucleus and is recruited to the IFABP promoter. Reason: PIAS1 acts on nuclear transcription factors; nucleoplasm is the appropriate compartment. Supporting Evidence: PMID:22539995 PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366 PMID:22539995 In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-4717491 | ACCEPT | Summary: Reactome TAS (mouse inferred event) placing PIAS1 in the nucleoplasm. Reason: Consistent with experimental localization. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0005654 nucleoplasm | TAS Reactome:R-MMU-4717507 | ACCEPT | Summary: Reactome TAS (mouse inferred event) placing PIAS1 in the nucleoplasm. Reason: Consistent with experimental localization. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: IEA from UniProt subcellular location (Cytoplasm, cytoskeleton, by similarity to human). UniProt notes only a partial redistribution along the cytoskeleton upon CSRP2 interaction. Reason: A partial, overexpression-induced redistribution does not make the cytoskeleton a functional location of a nuclear SUMO E3; same decision as the human review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt CSRP2 may induce a partial redistribution along the cytoskeleton (By |
| GO:0006974 DNA damage response | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection for DNA damage response. Reason: PIAS1 is recruited to damaged chromatin and SUMOylates MRE11 and other DSB repair proteins (human data, conserved enzyme). Supporting Evidence: PMID:36050397 PIAS1 is recruited to damaged chromatin, which facilitates MRE11 SUMOylation to enhance MRE11 stability by antagonizing ubiquitylation. PMID:20016603 we show that PIAS1 and PIAS4 promote DSB repair and confer IR resistance |
| GO:0006974 DNA damage response | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for DNA damage response. Reason: Supported by human DSB-response studies; transfer to the mouse ortholog is reasonable. Supporting Evidence: PMID:36050397 PIAS1 is recruited to damaged chromatin, which facilitates MRE11 SUMOylation to enhance MRE11 stability by antagonizing ubiquitylation. PMID:20016603 we show that PIAS1 and PIAS4 promote DSB repair and confer IR resistance |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | ISO PMID:9724754 Inhibition of Stat1-mediated gene activation by PIAS1. | MODIFY | Summary: ISO from human PIAS1 (PMID:9724754) for cell surface receptor signaling pathway via JAK-STAT. PIAS1 inhibits, rather than mediates, JAK-STAT signalling. Reason: PIAS1 blocks activated STAT1 DNA binding and, in Pias1-/- mice, restrains a subset of IFN-inducible genes, so the correct term is the negative regulation term GO:0046426 (already supported by IBA/IEA). Same MODIFY as human. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:O75925 Β· PIAS1 SOURCE STALE OR MISSING Current human GOA carries this term only as TAS PMID:10805787 (MODIFIED to GO:0046426 in the human review), not with PMID:9724754. Proposed replacements: negative regulation of receptor signaling pathway via JAK-STAT Supporting Evidence: PMID:9724754 PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara projection for spermatogenesis. Pias1 is highly expressed in testis, but no data show PIAS1 executing a step of spermatogenesis. Reason: PIAS1 is a SUMO E3 ligase and inhibitor/coregulator of transcription factors; it does not execute steps of this process. Effects on it are downstream consequences of substrate sumoylation or transcription factor inhibition (pleiotropic), so the process annotation overstates its role. Consistent with the human PIAS1 review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO zinc ion binding from the SP-RING/Znf-MIZ domain, a zinc-coordinating RING-like module. Reason: The SP-RING is a zinc finger (C351 is required for UBE2I binding); zinc binding is structurally accurate. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0008542 visual learning | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara projection for visual learning (from rat Pias1 hippocampal knockdown behaviour studies). Reason: Behavioural learning effects reflect sumoylation of neuronal transcription factors (e.g. CREB) rather than PIAS1 executing a learning process; same decision as the human review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0008542 visual learning | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Rat-to-mouse ISO transfer for visual learning (RGD Pias1). Reason: As for the IEA: a behavioural phenotype downstream of PIAS1 E3 activity on neuronal transcription factors, not a process PIAS1 performs. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION CONTEXT OR TISSUE MISMATCH Sources checked: RGD:1307843 Β· Pias1 UNRESOLVED Rat Pias1 source annotation not traced to its primary paper here; the same downstream-phenotype concern applies to it. Rat hippocampal behaviour reflects sumoylation of neuronal transcription factors. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0016605 PML body | IDA PMID:22406621 The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML ... | ACCEPT | Summary: IDA colocalizes_with PML body: PIAS1 interacts with PML in PML-NBs and colocalizes with SUMO1/SUMO2 there. Reason: PIAS1 is a constituent PML-NB protein (also shown for human PIAS1), and PML is one of its substrates. Supporting Evidence: PMID:22406621 These experiments indicate that PIAS1 and PIASxΞ± interact with PML in PML-NBs PMID:27099310 PIAS1 is a constituent PML-NB protein. |
| GO:0016605 PML body | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt subcellular location) for PML body. Reason: Supported by experimental data in mouse and human. Supporting Evidence: PMID:22406621 These experiments indicate that PIAS1 and PIASxΞ± interact with PML in PML-NBs PMID:27099310 PIAS1 is a constituent PML-NB protein. |
| GO:0016607 nuclear speck | IEA GO_REF:0000044 | ACCEPT | Summary: IEA (UniProt subcellular location) for nuclear speck. Reason: Nuclear speckle localization is recorded for PIAS1 and is consistent with its SAP-domain chromatin association; accepted as for human. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt speckle {ECO:0000250|UniProtKB:O75925}. Nucleus, PML body |
| GO:0016607 nuclear speck | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from human PIAS1 for nuclear speck. Reason: Supported by human data; conserved localization. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt speckle {ECO:0000250|UniProtKB:O75925}. Nucleus, PML body |
| GO:0016925 protein sumoylation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: PIAS family proteins participate in protein sumoylation as E3 ligases. Reason: Core process; the E3 directly catalyses SUMO transfer. Well supported by mouse experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis PMID:22539995 PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366 |
| GO:0016925 protein sumoylation | IDA PMID:22406621 The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML ... | ACCEPT | Summary: IDA: PIAS1 SUMOylates PML and PML-RARA in vitro and in cells. Reason: Direct evidence of PIAS1-catalysed sumoylation. Supporting Evidence: PMID:22406621 By performing in vitro SUMOylation assays, we discovered that both PIAS1 and PIASxΞ± SUMOylate PML. file:mouse/Pias1/Pias1-uniprot.txt resection (By similarity). Sumoylates PML (at 'Lys-65' and 'Lys-160') |
| GO:0016925 protein sumoylation | IDA PMID:22539995 PIAS1 is a GATA4 SUMO ligase that regulates GATA4-dependent ... | ACCEPT | Summary: IDA: PIAS1 promotes SUMO-1 modification of GATA4 on K366. Reason: Direct evidence of PIAS1-catalysed sumoylation. Supporting Evidence: PMID:22539995 PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366 PMID:22539995 our results demonstrate that PIAS1 is a SUMO ligase for GATA4 |
| GO:0016925 protein sumoylation | IDA PMID:24061474 Protein inhibitor of activated STAT 1 (PIAS1) is identified ... | ACCEPT | Summary: IDA: PIAS1 SUMOylates C/EBPbeta via its SAP domain during 3T3-L1 adipogenesis. Reason: Direct evidence of PIAS1-catalysed sumoylation. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis file:mouse/Pias1/Pias1-uniprot.txt Plays a dynamic role in adipogenesis by promoting the SUMOylation and |
| GO:0016925 protein sumoylation | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA for protein sumoylation. Reason: Consistent with experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0016925 protein sumoylation | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for protein sumoylation. Reason: Consistent with mouse and human experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0019789 SUMO transferase activity | EXP PMID:15123625 Transcriptional activity of peroxisome proliferator-activate... | ACCEPT | Summary: EXP: PIAS1 functions as an E3 ligase for PPARgamma SUMO-1 modification. Reason: SUMO transferase activity (parent of SUMO ligase activity) is correct for PIAS1; the abstract directly states PIAS1 acts as an E3 for PPARgamma. Supporting Evidence: PMID:15123625 we show that the PIAS family proteins, PIAS1 and PIASxbeta, function as E3 ligases |
| GO:0019789 SUMO transferase activity | EXP PMID:15229330 Control of peroxisome proliferator-activated receptor gamma2... | ACCEPT | Summary: EXP from a PPARgamma2 K107 SUMOylation study using recombinant SUMOylation pathway proteins. The cached abstract does not name PIAS1; the curator presumably used the full text. Reason: The function is clearly correct for PIAS1 and independently established (PMID:15123625, PMID:24061474); defer to the curator rather than overrule from an abstract. Supporting Evidence: PMID:15229330 In vitro, SUMOylation studies showed that lysine 107 of PPARgamma2 is a major SUMOylation site PMID:15123625 we show that the PIAS family proteins, PIAS1 and PIASxbeta, function as E3 ligases PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0019789 SUMO transferase activity | EXP PMID:15507114 The transactivating function of peroxisome proliferator-acti... | ACCEPT | Summary: EXP from a study of PPARgamma SUMOylation in the AF-1 repression domain. The cached abstract does not name PIAS1; the curator presumably used the full text. Reason: The function is clearly correct for PIAS1 and independently established; defer to the curator. Supporting Evidence: PMID:15507114 We have found PPARgamma2 and its isoform, PPARgamma1, to be modified by small ubiquitin-related modifier (SUMO)-1 in vivo PMID:15123625 we show that the PIAS family proteins, PIAS1 and PIASxbeta, function as E3 ligases PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0019789 SUMO transferase activity | EXP PMID:18832723 Sumoylation of peroxisome proliferator-activated receptor ga... | ACCEPT | Summary: EXP: in RAW264.7 macrophages, PIAS1 is the SUMO E3 required for apoptotic-cell-induced PPARgamma SUMOylation that blocks NF-kB transactivation. Reason: PIAS1 SUMO transferase activity toward PPARgamma; consistent with PMID:16127449. Supporting Evidence: PMID:18832723 knockdown of the small ubiquitin-like modifier (SUMO) E3 ligase PIAS1 (protein inhibitor of activated STAT1), eliminated the ability of AC to suppress NF-kappaB PMID:16127449 These results suggest that PIAS1/Ubc9-mediated sumoylation is required for PPARΞ³-dependent transrepression. |
| GO:0019789 SUMO transferase activity | EXP PMID:23118920 Forkhead box protein A2 (FOXA2) protein stability and activi... | ACCEPT | Summary: EXP: PIAS1, but not a ligase-deficient mutant, increases FOXA2 SUMOylation. Reason: Catalytic-mutant control directly supports SUMO transferase activity. Supporting Evidence: PMID:23118920 FOXA2 sumoylation and FOXA2 protein levels were increased by PIAS1 SUMO ligase but not a SUMO ligase activity deficient PIAS1 mutant |
| GO:0019789 SUMO transferase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA for SUMO transferase activity. Reason: Consistent with extensive experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0019789 SUMO transferase activity | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for SUMO transferase activity. Reason: Consistent with mouse and human experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0019899 enzyme binding | IEA GO_REF:0000107 | TOO GENERAL | Summary: Ensembl Compara projection of enzyme binding. Reason: Enzyme binding is a generic binding term that adds no functional information beyond the specific E3-substrate and E2 interactions of PIAS1; the human source annotation (CBS binding, IPI) was removed in the human review. TOO_GENERAL rather than REMOVE: ubiquitin protein ligase binding, kept in this review, entails this term, so the claim is true but less informative. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0019899 enzyme binding | ISO GO_REF:0000119 | TOO GENERAL | Summary: ISO from human PIAS1 (enzyme binding; source is a human IPI with cystathionine beta-synthase as a sumoylation substrate). Reason: Same reasoning as the human review: the substrate relationship is captured by SUMO ligase activity; generic enzyme binding is uninformative. TOO_GENERAL rather than REMOVE: ubiquitin protein ligase binding, kept in this review, entails this term, so the claim is true but less informative. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB:O75925 Β· PIAS1 SUPPORTS TRANSFER Human source is IPI PMID:17087506 with cystathionine beta-synthase (a sumoylation substrate); the interaction may be real but the generic term was REMOVED in the human review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0019904 protein domain specific binding | IEA GO_REF:0000107 | REMOVE | Summary: Ensembl Compara projection of protein domain specific binding. Reason: Uninformative generic binding term; removed in the human review. PIAS1 domain-mediated interactions are better described by the specific transcription factor/nuclear receptor binding terms. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0019904 protein domain specific binding | ISO GO_REF:0000096 | REMOVE | Summary: Rat-to-mouse ISO transfer of protein domain specific binding. Reason: As for the IEA: uninformative generic binding term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: RGD:1307843 Β· Pias1 UNRESOLVED Generic binding term; uninformative regardless of the rat source evidence. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:16816390 The interaction of Piasy with Trim32, an E3-ubiquitin ligase... | KEEP AS NON CORE | Summary: IPI with Trim32 (an E3 ubiquitin ligase) from a study showing Trim32 ubiquitinates and degrades Piasy (PIAS4). The cached record is abstract-only; the PIAS1 interaction was presumably shown in the full text. Reason: Experimental annotation that cannot be checked against the full text; retained as a non-core, regulatory interaction (PIAS proteins as targets of ubiquitin ligases), consistent with the human KEEP_AS_NON_CORE. Supporting Evidence: PMID:16816390 Here we report that Trim32 interacts with Piasy and promotes Piasy ubiquitination and degradation |
| GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process | IMP PMID:22406621 The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML ... | KEEP AS NON CORE | Summary: IMP: PIAS1 SUMOylation of PML promotes its CK2-dependent ubiquitination and proteasomal degradation; PIAS1 knockdown raises PML levels. PIAS1 SUMOylation of C/EBPbeta likewise promotes its degradation. Reason: PIAS1 does work in this regulation (it installs the SUMO mark that primes degradation of specific substrates), but it is substrate-specific and not a general function; kept as non-core as in the human review. Supporting Evidence: PMID:22406621 PIAS1-mediated SUMOylation of PML promoted CK2 interaction and ubiquitin/proteasome-mediated degradation of PML file:mouse/Pias1/Pias1-uniprot.txt resection (By similarity). Sumoylates PML (at 'Lys-65' and 'Lys-160') |
| GO:0033235 positive regulation of protein sumoylation | IEA GO_REF:0000120 | MODIFY | Summary: Combined IEA for positive regulation of protein sumoylation. Reason: PIAS1 is the E3 that catalyses sumoylation, so it participates directly in protein sumoylation rather than regulating it; same MODIFY as human. Proposed replacements: protein sumoylation Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis PMID:22539995 PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366 |
| GO:0033235 positive regulation of protein sumoylation | ISO GO_REF:0000096 | MODIFY | Summary: Rat-to-mouse ISO transfer of positive regulation of protein sumoylation. Reason: PIAS1 directly catalyses sumoylation; protein sumoylation is the appropriate term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:1307843 Β· Pias1 SUPPORTS TRANSFER Rat evidence for enhanced substrate sumoylation transfers, but PIAS1 is the E3 itself, so protein sumoylation is the right term. Proposed replacements: protein sumoylation Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0033235 positive regulation of protein sumoylation | ISO GO_REF:0000119 | MODIFY | Summary: ISO from human PIAS1 for positive regulation of protein sumoylation. Reason: Same as human review: PIAS1 is the E3 itself. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: UniProtKB:O75925 Β· PIAS1 SUPPORTS TRANSFER Human PIAS1 IDA rows (PMID:17696781, PMID:21965678) were MODIFIED to protein sumoylation in the human review for the same reason. Proposed replacements: protein sumoylation Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0033235 positive regulation of protein sumoylation | ISS GO_REF:0000024 | MODIFY | Summary: ISS from human PIAS1 for positive regulation of protein sumoylation. Reason: PIAS1 directly catalyses sumoylation. Proposed replacements: protein sumoylation Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0034399 nuclear periphery | IDA PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | KEEP AS NON CORE | Summary: IDA: PIAS1 localizes with Msx1 at the nuclear periphery in myoblasts, where Msx1-repressed myogenic genes reside. Abstract-only cache. Reason: Experimental, cell-type-specific localization tied to the Msx1 partnership; real but not the main site of PIAS1 action. Consistent with the human review. Supporting Evidence: PMID:16600910 We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells file:mouse/Pias1/Pias1-uniprot.txt and localization of MSX1 to the nuclear periphery, whereby MSX1 is |
| GO:0042127 regulation of cell population proliferation | IMP PMID:22406621 The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML ... | MARK AS OVER ANNOTATED | Summary: IMP: stable PIAS1 knockdown in NSCLC cells has anti-proliferative effects, attributed to PML stabilisation. Reason: A proliferation phenotype downstream of PML sumoylation/degradation; PIAS1 does not execute proliferation control. Same decision as human. Supporting Evidence: PMID:22406621 we discovered that stable knockdown of PIAS1 leads to significant anti-proliferative effects |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara projection of negative regulation of apoptotic process. Reason: PIAS1 is a SUMO E3 ligase and inhibitor/coregulator of transcription factors; it does not execute steps of this process. Effects on it are downstream consequences of substrate sumoylation or transcription factor inhibition (pleiotropic), so the process annotation overstates its role. Consistent with the human PIAS1 review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0043066 negative regulation of apoptotic process | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Rat-to-mouse ISO transfer of negative regulation of apoptotic process. Reason: PIAS1 is a SUMO E3 ligase and inhibitor/coregulator of transcription factors; it does not execute steps of this process. Effects on it are downstream consequences of substrate sumoylation or transcription factor inhibition (pleiotropic), so the process annotation overstates its role. Consistent with the human PIAS1 review. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:1307843 Β· Pias1 UNRESOLVED Rat Pias1 source annotation not traced to its primary paper here; the same downstream-phenotype concern applies to it. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0045444 fat cell differentiation | IDA PMID:24061474 Protein inhibitor of activated STAT 1 (PIAS1) is identified ... | MODIFY | Summary: IDA: PIAS1 is transiently induced during 3T3-L1 differentiation and SUMOylates C/EBPbeta, promoting its degradation; PIAS1 overexpression inhibits and knockdown promotes adipogenesis, dependent on its E3 activity. Reason: The data show PIAS1 restrains adipogenesis by limiting C/EBPbeta, i.e. negative regulation of fat cell differentiation (GO:0045599), not participation in differentiation itself. Kept as a non-core developmental role. Proposed replacements: negative regulation of fat cell differentiation Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis PMID:24061474 the catalytic activity of SUMO E3 ligase was required for PIAS1 to restrain adipogenesis PMID:24061474 adipogenesis was inhibited by overexpression of wild-type PIAS1 and promoted by knockdown of PIAS1 |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection of positive regulation of DNA-templated transcription. Reason: PIAS1 can coactivate some transcription factors; in mouse intestinal cells it coactivates GATA4 independently of its ligase activity. Context-dependent, non-core. Supporting Evidence: PMID:22539995 neither GATA4 sumoylation nor the SUMO ligase activity of PIAS1 was required for coactivation of IFABP promoter by GATA4 and PIAS1 |
| GO:0045893 positive regulation of DNA-templated transcription | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat-to-mouse ISO transfer of positive regulation of DNA-templated transcription. Reason: Context-dependent coactivation (e.g. GATA4); non-core. Supporting Evidence: PMID:22539995 neither GATA4 sumoylation nor the SUMO ligase activity of PIAS1 was required for coactivation of IFABP promoter by GATA4 and PIAS1 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ISO from human PIAS1 (based on PIAS1 sumoylation of ZNF76 relieving its repression of TBP-dependent transcription) for positive regulation of transcription by RNA polymerase II. Reason: Context-dependent positive effect on Pol II transcription (human ZNF76, mouse GATA4); non-core, consistent with the human review. Supporting Evidence: PMID:22539995 neither GATA4 sumoylation nor the SUMO ligase activity of PIAS1 was required for coactivation of IFABP promoter by GATA4 and PIAS1 |
| GO:0046426 negative regulation of receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: PIAS proteins negatively regulate JAK-STAT signalling. Reason: Core: in Pias1-/- mice PIAS1 restrains STAT1 promoter recruitment and IFN-induced genes. Supporting Evidence: PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter PMID:9724754 PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon |
| GO:0046426 negative regulation of receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection of negative regulation of receptor signaling pathway via JAK-STAT. Reason: Supported by mouse knockout data. Supporting Evidence: PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter |
| GO:0051152 positive regulation of smooth muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection of positive regulation of smooth muscle cell differentiation. Reason: A context-specific developmental effect of PIAS1 coregulator activity; not core. Consistent with the human review. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0051152 positive regulation of smooth muscle cell differentiation | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: Rat-to-mouse ISO transfer of positive regulation of smooth muscle cell differentiation. Reason: As for the IEA; non-core. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt Functions as an E3-type small ubiquitin-like modifier (SUMO) |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection of positive regulation of transcription initiation by RNA polymerase II. Reason: Derived from the human ZNF76/TBP study; PIAS1 also directly binds TBP. Context-dependent, non-core. Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ISO from human PIAS1 for positive regulation of transcription initiation by RNA polymerase II. Reason: As for the IEA. Supporting Evidence: PMID:16522640 Endogenous PIAS1 and TBP co-immunoprecipitated from nuclear extracts |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | REMOVE | Summary: IEA from EC mapping (EC 2.3.2.27, RING-type E3 ubiquitin transferase) to ubiquitin protein ligase activity. Reason: UniProt applies the RING-type E3 EC number to SUMO E3s by convention, but PIAS1 is a SUMO E3 ligase; there is no evidence it ligates ubiquitin. The EC-to-GO mapping is therefore wrong for this protein; SUMO ligase activity captures the real function. Supporting Evidence: file:mouse/Pias1/Pias1-uniprot.txt RecName: Full=E3 SUMO-protein ligase PIAS1; PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0061665 SUMO ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: PIAS/Siz family SUMO ligase activity. Reason: Core activity of PIAS1, supported by multiple mouse experimental studies. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis PMID:22539995 our results demonstrate that PIAS1 is a SUMO ligase for GATA4 |
| GO:0061665 SUMO ligase activity | IDA PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | ACCEPT | Summary: IDA from the Msx1 study (abstract-only cache); the full text presumably shows PIAS1-dependent Msx1 sumoylation (UniProt lists mutagenesis of the SP-RING residues C351 and W372 from this paper). Reason: The activity is clearly correct for PIAS1; defer to the curator. Supporting Evidence: PMID:16600910 We demonstrate that the interaction of Msx1 with PIAS1, but not its sumoylation, is required for Msx1 to function as an inhibitor of myoblast differentiation PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0061665 SUMO ligase activity | IDA PMID:22539995 PIAS1 is a GATA4 SUMO ligase that regulates GATA4-dependent ... | ACCEPT | Summary: IDA: PIAS1 is a SUMO ligase for GATA4. Reason: Direct evidence. Supporting Evidence: PMID:22539995 our results demonstrate that PIAS1 is a SUMO ligase for GATA4 PMID:22539995 PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366 |
| GO:0061665 SUMO ligase activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection of SUMO ligase activity. Reason: Consistent with experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0061665 SUMO ligase activity | ISO GO_REF:0000119 | ACCEPT | Summary: ISO from human PIAS1 for SUMO ligase activity. Reason: Consistent with mouse and human experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0061665 SUMO ligase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from human PIAS1 for SUMO ligase activity. Reason: Consistent with mouse and human experimental data. Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis |
| GO:0065004 protein-DNA complex assembly | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara projection of protein-DNA complex assembly. Reason: PIAS1 mostly opposes transcription factor-DNA complex formation (STAT1, p65) and only conditionally promotes it (Msx1); describing it as executing protein-DNA complex assembly overstates its role. Same as human. Supporting Evidence: PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo PMID:16600910 PIAS1 enables Msx1 to bind selectively to a key regulatory element in MyoD, the CER |
| GO:0065004 protein-DNA complex assembly | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: Rat-to-mouse ISO transfer of protein-DNA complex assembly. Reason: As for the IEA. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: RGD:1307843 Β· Pias1 UNRESOLVED Rat Pias1 source annotation not traced to its primary paper here; the same downstream-phenotype concern applies to it. PIAS1 mostly blocks transcription factor-DNA binding (STAT1, p65). Supporting Evidence: PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo PMID:16600910 PIAS1 enables Msx1 to bind selectively to a key regulatory element in MyoD, the CER |
| GO:0098978 glutamatergic synapse | IDA PMID:34459572 Super-resolution study of PIAS SUMO E3-ligases in hippocampa... | KEEP AS NON CORE | Summary: IDA (SynGO) glutamatergic synapse, from super-resolution imaging of cultured mouse hippocampal and cortical neurons. Reason: Only partial colocalization with synaptic markers in hippocampal neurons (rare in cortical neurons); a minor extranuclear pool, not the principal site of action. Supporting Evidence: PMID:34459572 The results indicate partial co-localization of PIAS1 and PIAS3 with synaptic markers in hippocampal neurons and much rarer occurrence in cortical neurons. |
| GO:0099523 presynaptic cytosol | IDA PMID:34459572 Super-resolution study of PIAS SUMO E3-ligases in hippocampa... | KEEP AS NON CORE | Summary: IDA (SynGO) presynaptic cytosol from the same imaging study. Reason: Partial colocalization; minor pool. Supporting Evidence: PMID:34459572 The results indicate partial co-localization of PIAS1 and PIAS3 with synaptic markers in hippocampal neurons and much rarer occurrence in cortical neurons. |
| GO:0099524 postsynaptic cytosol | IDA PMID:34459572 Super-resolution study of PIAS SUMO E3-ligases in hippocampa... | KEEP AS NON CORE | Summary: IDA (SynGO) postsynaptic cytosol from the same imaging study. Reason: Partial colocalization; minor pool. Supporting Evidence: PMID:34459572 The results indicate partial co-localization of PIAS1 and PIAS3 with synaptic markers in hippocampal neurons and much rarer occurrence in cortical neurons. |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:24061474 Protein inhibitor of activated STAT 1 (PIAS1) is identified ... | ACCEPT | Summary: IPI: PIAS1 interacts with C/EBPbeta through its SAP domain and SUMOylates it. Reason: DNA-binding transcription factor binding accurately describes PIAS1 recognition of its transcription factor substrates and targets (C/EBPbeta, GATA4, Msx1, STAT1, p65). Supporting Evidence: PMID:24061474 PIAS1 functions as a SUMO E3 ligase of C/EBPΞ² to regulate adipogenesis PMID:24061474 PIAS1 was found to interact with C/EBPΞ² through the SAP (scaffold attachment factor A/B/acinus/PIAS) domain and SUMOylate it |
| GO:0140416 transcription regulator inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: transcription regulator inhibitor activity for PIAS proteins. Reason: Core: PIAS1 binds activated STAT1 and p65 and blocks their DNA binding / promoter recruitment (mouse knockout evidence), independently of STAT1 sumoylation. Supporting Evidence: PMID:15311277 PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo PMID:12764129 inhibition of STAT1 by PIAS proteins does not require SUMO modification of STAT1 |
| GO:0140416 transcription regulator inhibitor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara projection of transcription regulator inhibitor activity. Reason: As for the IBA. Supporting Evidence: PMID:9724754 PIAS1, but not other PIAS proteins, blocked the DNA binding activity of Stat1 and inhibited Stat1-mediated gene activation in response to interferon PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo |
| GO:1904377 positive regulation of protein localization to cell periphery | IDA PMID:16600910 PIAS1 confers DNA-binding specificity on the Msx1 homeoprote... | MODIFY | Summary: IDA from the Msx1 study: PIAS1 is required for localization and retention of Msx1 at the nuclear periphery in myoblasts. The GO term used refers to the cell periphery (plasma membrane region), not the nuclear periphery. Reason: The evidence concerns relocation of Msx1 to the nuclear periphery, so the cell-periphery term mis-states the compartment. GO:1990139 protein localization to nuclear periphery captures what PIAS1 does (it tethers Msx1 there); retain as non-core. Proposed replacements: protein localization to nuclear periphery Supporting Evidence: PMID:16600910 We show that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells file:mouse/Pias1/Pias1-uniprot.txt and localization of MSX1 to the nuclear periphery, whereby MSX1 is |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:15657437 Negative regulation of NF-kappaB signaling by PIAS1. | NEW | Summary: After cytokine stimulation nuclear p65 binds PIAS1, which blocks p65 DNA binding; Pias1-/- cells show enhanced p65 occupancy of NF-kB target promoters and increased expression of a subset of TNF/LPS-induced genes, and Pias1-null mice have elevated proinflammatory cytokines. Reason: Participation: PIAS1 itself performs the inhibitory step (binding p65 and occluding its DNA binding), switched on by IKKalpha-mediated Ser90 phosphorylation. Comparator check (QuickGO 2026-10, mouse, exact term): Nfkbie, Nfkbid, Tnfaip3 and Hdac1 carry GO:0043124, so the term is used for gene products in this inhibitory role. No current Pias1 annotation covers NF-kB inhibition. Mirrors the human PIAS1 NEW annotation. Supporting Evidence: PMID:15657437 PIAS1 blocks the DNA binding activity of p65 both in vitro and in vivo PMID:15657437 the binding of p65 to the promoters of NF-kappaB-regulated genes is significantly enhanced in Pias1-/- cells PMID:17540171 IKKalpha, but not IKKbeta, interacts with PIAS1 in vivo and mediates PIAS1 Ser90 phosphorylation, a process that requires the SUMO ligase activity of PIAS1 file:mouse/Pias1/Pias1-deep-research-openscientist.md Its defining, physiologically validated role is as an **inducible negative-feedback brake on interferon and inflammatory (NF-ΞΊB) gene transcription** |
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Download this section (compressed HTML)Q: Which phenotypes of Pias1-/- mice (enhanced interferon responses, elevated proinflammatory cytokines, pathogen resistance) require PIAS1 SP-RING E3 activity versus binding-based blockade of STAT1/p65 DNA binding?
Q: Is PIAS1-mediated tethering of transcription factors to the nuclear periphery (shown for Msx1) a general mechanism for directing homeoproteins and other factors to repressed target genes?
Q: What is the functional consequence of the conserved PIAS C-terminal TBP-binding region; does PIAS1 dock at TBP to sumoylate promoter-bound factors?
Q: Is the high testis expression of Pias1 associated with specific spermatogenic substrates, or is any spermatogenesis phenotype indirect?
Experiment: Generate knock-in mice carrying an SP-RING catalytic mutant (C351S), a STAT1-binding-deficient C-terminal deletion, or S90A, and compare IFN- and TNF/LPS-induced gene expression, STAT1/p65 promoter occupancy and infection outcomes with Pias1-/- mice.
Hypothesis: PIAS1 restrains inflammatory gene expression primarily by binding-based inhibition of STAT1/p65, with E3 activity required mainly for Ser90 activation.
Type: genetic separation-of-function
Experiment: SUMO-site proteomics (K-epsilon-GG/SUMO-remnant enrichment) in wild-type versus Pias1-/- macrophages, adipocyte precursors and testis to define endogenous PIAS1 substrates.
Hypothesis: PIAS1 has a tissue-specific substrate repertoire dominated by transcription factors (C/EBPbeta, GATA4, PPARgamma).
Type: proteomics
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