Summary: IBA (PTN000081660, PIAS/Siz node) placing GEI-17 activity on chromatin. Consistent with direct worm data: GEI-17 associates with damaged chromatin and drives SUMO conjugation on mitotic chromatin.

Reason: Node placement across the PIAS/Siz family is sound and GEI-17 has its own experimental chromatin association (PMID:19111656, PMID:25475837).

Summary: Chromatin fractionation of early embryos showed GEI-17 on chromatin, enriched after DNA damage, where it is proposed to SUMOylate POLH-1.

Reason: Direct biochemical localization evidence; matches the site of its core TLS-supporting activity.

Summary: IBA for nucleoplasm from the PIAS/Siz node. GEI-17 is a nuclear enzyme whose known substrates (MUS-101, POLH-1, AIR-2, transcription factors) are nuclear; GFP-GEI-17 is nuclear in germline nuclei.

Reason: Phylogenetically sound and consistent with worm localization data (nuclear envelope-proximal nucleoplasm in pachytene nuclei, chromatin in embryos).

Summary: IBA from a PIAS node for regulation of RNA polymerase II transcription. In worms, GEI-17 is required with UBC-9/SMO-1 for TBX-2-dependent autorepression of the tbx-2 promoter, and SUMOylation of LIN-1 is GEI-17/SUMO dependent.

Reason: Supported by worm RNAi data (PMID:25873636) and family biology, but the effect is via SUMOylation of specific transcription factors and is one of several outputs of the E3 activity rather than its core role.

Summary: gei-17 RNAi embryos are highly sensitive to MMS and show MMS-induced nuclear morphology defects shared with mus-101; GEI-17 SUMOylates MUS-101 in vitro.

Reason: GEI-17 participates in the embryonic DNA damage response through its SUMO ligase activity on MUS-101 and POLH-1 (PMID:15654100, PMID:19111656). The term is broad but correct; the more specific TLS-regulation term is also annotated.

Summary: InterPro Znf_MIZ (SP-RING) mapping. The SP-RING zinc finger (aa 400-485) has four predicted Zn(2+) ligands and its integrity is required for E3 activity (L417A).

Reason: Structural zinc coordination by the SP-RING is a genuine, domain-supported property, though not the functional activity itself.

Summary: IGI from the mus-101 modifier screen: co-depletion of gei-17 with the WITH gene increased embryonic lethality.

Reason: Embryonic lethality is a pleiotropic consequence of losing a SUMO E3 that supports replication of damaged DNA and chromosome segregation; it reflects necessity rather than a specific developmental role.

Summary: gei-17 null alleles are embryonic lethal.

Reason: Correct phenotype-based annotation, but embryonic arrest is a pleiotropic outcome of loss of SUMO conjugation (chromosome segregation, DNA damage tolerance), not a core developmental function.

Summary: gei-17(RNAi) derepresses a Ptbx-2::gfp reporter in seam cells and gut, phenocopying weak tbx-2 mutants.

Reason: Valid but broad; reflects GEI-17-dependent SUMOylation supporting TBX-2 autorepression. Non-core relative to the E3 activity.

Summary: IBA for protein sumoylation from the PIAS/Siz node; GEI-17 itself has multiple experimental SUMOylation annotations.

Reason: Core process directly executed by the E3 ligase; node placement is sound and corroborated by GEI-17 IDA data.

Summary: Reconstituted SUMOylation of MUS-101 required recombinant GEI-17.

Reason: Direct in vitro evidence of GEI-17-catalysed SUMO conjugation to a substrate.

Summary: GEI-17 SUMOylates POLH-1 in vitro and POLH-1 SUMOylation in embryos depends on GEI-17 and DNA damage.

Reason: Direct biochemical evidence for GEI-17-dependent protein sumoylation.

Summary: GEI-17 stimulates SUMO modification of AIR-2 and SUMO chain formation in vitro; metaphase SUMO conjugation in embryos requires GEI-17.

Reason: Direct evidence (in vitro reconstitution and in vivo dependency).

Summary: KLP-19 is SUMOylated in a GEI-17-dependent manner in vitro; GEI-17 auto-SUMOylates.

Reason: Direct biochemical evidence.

Summary: UniPathway mapping (protein sumoylation pathway).

Reason: Correct and consistent with extensive experimental evidence.

Summary: In gei-17/cdt-2 co-depleted embryos the SUMO-modified form of POLH-1 is lost after MMS, showing in vivo dependence of POLH-1 SUMOylation on GEI-17.

Reason: Loss-of-function evidence directly measuring the sumoylation of a substrate.

Summary: IGI: POLH-1 loss after MMS in gei-17 RNAi embryos is suppressed by co-depletion of PCNA or CRL4-Cdt2 components (the WITH gene), showing GEI-17 antagonizes CRL4-Cdt2-mediated POLH-1 proteolysis.

Reason: GEI-17 acts directly on the substrate (SUMOylation of POLH-1) to block its degradation; this is the mechanistic basis of its role in damage tolerance and well supported by epistasis.

Summary: IGI: POLH-1 loss after MMS in gei-17 RNAi embryos is suppressed by co-depletion of PCNA or CRL4-Cdt2 components (the WITH gene), showing GEI-17 antagonizes CRL4-Cdt2-mediated POLH-1 proteolysis.

Reason: GEI-17 acts directly on the substrate (SUMOylation of POLH-1) to block its degradation; this is the mechanistic basis of its role in damage tolerance and well supported by epistasis.

Summary: IGI: POLH-1 loss after MMS in gei-17 RNAi embryos is suppressed by co-depletion of PCNA or CRL4-Cdt2 components (the WITH gene), showing GEI-17 antagonizes CRL4-Cdt2-mediated POLH-1 proteolysis.

Reason: GEI-17 acts directly on the substrate (SUMOylation of POLH-1) to block its degradation; this is the mechanistic basis of its role in damage tolerance and well supported by epistasis.

Summary: IGI: POLH-1 loss after MMS in gei-17 RNAi embryos is suppressed by co-depletion of PCNA or CRL4-Cdt2 components (the WITH gene), showing GEI-17 antagonizes CRL4-Cdt2-mediated POLH-1 proteolysis.

Reason: GEI-17 acts directly on the substrate (SUMOylation of POLH-1) to block its degradation; this is the mechanistic basis of its role in damage tolerance and well supported by epistasis.

Summary: gei-17 RNAi causes rapid CRL4-Cdt2-dependent loss of POLH-1 after DNA damage; GEI-17 controls the timing of POLH-1 destruction.

Reason: Direct role: GEI-17-mediated SUMOylation of POLH-1 protects it from proteolysis (PMID:19111656).

Summary: GEI-17 depletion in oocytes compromises metaphase I chromosome alignment/congression; GEI-17 SUMOylates KLP-19 and builds a SUMO-SIM network assembling the midbivalent ring complex.

Reason: GEI-17 is a component of the ring complex and directly SUMOylates its components, so it does part of the work of congression rather than being merely required.

Summary: IBA from a PIAS1/Su(var)2-10 subnode (PTN000845825) for negative regulation of JAK-STAT receptor signalling. C. elegans has no JAK kinase, so the receptor-JAK-STAT pathway this term regulates does not exist in the organism.

Reason: The function is grounded in human PIAS1 (inhibition of STAT1) and fly Su(var)2-10, and the node placement is sound for those lineages. But the term presupposes a receptor-JAK-STAT pathway, and C. elegans lacks a conserved JAK homolog; its STAT STA-1 acts in a JAK-independent pathway (PMID:28874466). None of the GEI-17 literature (DNA damage tolerance, chromosome segregation, transcription factor SUMOylation, germline silencing) involves STAT. This is the same lineage-inappropriate transfer as the JAK-STAT IBA on worm sta-2; the nematode branch needs an IRD (or GEI-17 a NOT annotation). The PTHR10782 FamilyReview agrees; it rates this node NEEDS_PRUNING and, because SF94 also holds the valid fly seed, records GEI-17 as a member exception to the SF94 scope for this term, anchored to PTN000845825. Liongue & Ward (2013) date assembly of the canonical JAK-STAT pathway to the bilaterian ancestor, before protostomes diverged, which is why the eumetazoan PIAS node is a sound place for the IBD and the nematode JAK absence is a lineage-specific loss calling for an IRD, not a node move. The PIAS name itself is no evidence for the term; Palvimo (2007) notes PIAS functions are not restricted to STATs.

Summary: Yeast two-hybrid interaction between GEI-17 and the T-box transcription factor TBX-2 (cached paper is abstract-only; interaction restated in PMID:25873636).

Reason: The binding partner is an RNA Pol II-specific DNA-binding transcription factor, so the term is informative (unlike protein binding), and TBX-2 is a plausible SUMO substrate. Evidence is Y2H only and the interaction is a facet of substrate recruitment by the E3, so non-core.

Summary: IBA for SUMO ligase activity from the PIAS/Siz node; GEI-17 is itself among the experimental donors.

Reason: Core molecular function; sound node placement corroborated by GEI-17 biochemistry.

Summary: Recombinant GEI-17 stimulates SUMO conjugation to MUS-101 in a reconstituted E1/E2/SUMO system.

Reason: Direct in vitro evidence of E3 activity.

Summary: Recombinant GEI-17 is required for SUMOylation of POLH-1 in vitro.

Reason: Direct in vitro E3 activity.

Summary: GEI-17 SP-RING fragment forms SUMO chains and stimulates AIR-2 SUMOylation; the L417A SP-RING mutation drastically diminishes E3 activity.

Reason: Direct biochemical evidence including a catalytic-domain mutant.

Summary: GEI-17 promotes SUMO conjugation to KLP-19 in vitro and auto-SUMOylates.

Reason: Direct in vitro E3 activity.

Summary: Immunostaining shows GEI-17 at the metaphase plate of mitotic embryos, signal lost on gei-17 RNAi.

Reason: Direct localization evidence with specificity control; this is where GEI-17 drives SUMO conjugation of chromatin proteins such as AIR-2.

Summary: IBA for transcription regulator inhibitor activity from the PIAS1-seeded node PTN000845825 (human PIAS1 blocks STAT1/p65 DNA binding).

Reason: GO:0140416 covers inhibiting a transcription regulator by direct binding or by post-translational modification, so a SUMO E3 that inhibits transcription factors by SUMOylating them would fit it. An earlier version of this review marked the term over-annotated on the grounds that GEI-17's transcriptional effects need its ligase activity; that reading was wrong, because ligase-dependent inhibition is within the term. What the evidence does exclude is a binding route through the SAP domain. An OpenScientist analysis found GEI-17 has no SAP domain detectable by Pfam, PROSITE or InterPro (UniProt lists only PINIT and the SP-RING zinc finger, whereas PIAS1 carries IPR003034), and in human PIAS1 the ligase-independent inhibition does not need the SAP domain anyway; it maps to a C-terminal region that sequesters the transcription factor (PMID:24036127), as for PIASy and Oct4 (PMID:17991485). The modification route is plausible but not shown. GEI-17 inhibits formation of piRNA transcription condensates built by the USTC transcription complex in a SUMOylation-dependent way (PMID:40316696), but the cached abstract does not say whether GEI-17 SUMOylates USTC components directly, and the full text is not available. Other worm SUMOylation targets (TBX-2, LIN-1) are SUMOylated to support, not inhibit, their repressor function. Nor is the ligase-independent binding route excluded, because a positional check finds that GEI-17 keeps a motif-predicted SIM-like core followed by an acidic run (IITLSDDDDEEL, aa 545-556) at essentially the same distance past the SP-RING (+63 vs +62) as PIAS1's SIM-adjacent acidic cluster, the likeliest candidate for the region PMID:24036127 maps the activity to, although whether GEI-17 binds a transcription regulator through it is untested. The IBA is therefore neither confirmed nor refuted.

Summary: IGI: the MMS-induced S-phase delay in gei-17 RNAi embryos is reversed by co-depletion of the checkpoint kinase gene (WITH), showing that gei-17 normally keeps the embryonic DNA damage checkpoint silent.

Reason: The authors attribute silencing to suppression of replication fork stalling via TLS, i.e. GEI-17 removes the checkpoint-activating signal rather than acting on ATL-1/CHK-1 machinery. The regulation is real but indirect, a downstream consequence of its POLH-1-supporting role.

Summary: gei-17 RNAi embryos activate a DNA damage checkpoint after MMS that is silent in wild-type embryos.

Reason: Correct phenotype-based annotation, but indirect: silencing results from GEI-17/POLH-1-dependent prevention of fork stalling.

Summary: IGI: gei-17 knockdown does not further sensitize TLS polymerase mutants to MMS/UV, placing it in the TLS pathway.

Reason: GEI-17 positively regulates TLS by SUMOylating and stabilizing POLH-1 (PMID:19111656); the epistasis here extends this to POLK-1-dependent bypass. Core biological role, executed through its E3 activity on the polymerase.

Summary: gei-17 knockdown sensitizes embryos to MMS and UV with abundant RAD-51 foci, consistent with defective lesion bypass.

Reason: Core role: GEI-17 SUMOylates POLH-1 and protects it from CRL4-Cdt2 proteolysis so that TLS can occur (PMID:19111656).