OTUD3 PN Consistency Notes
- Generated: 2026-06-18
- Project: PROTEOSTASIS
- Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
- UniProt: Q5T2D3
- AIGR review status: COMPLETE
- Review batch: proteostasis-batch-2026-06-07c
- Batch change status: added
Source Files Checked
Deep Research Files
- No
*-deep-research*.md file found in this gene directory.
AIGR Review Snapshot
- Description: OTUD3 (OTU domain-containing protein 3) is a cysteine-protease deubiquitinase (DUB, EC 3.4.19.12) of the ovarian tumor (OTU) family. Its catalytic OTU domain (active-site nucleophile Cys76, with His182) hydrolyzes isopeptide bonds of ubiquitin chains with a preference for atypical Lys-6 (K6)- and Lys-11 (K11)-linked polyubiquitin, and it also processes heterotypic (mixed/branched) and other homotypic chains; a C-terminal UBA-like domain does not affect catalysis. OTUD3 acts on specific substrates: it deubiquitinates and stabilizes the tumor suppressor PTEN (suppressing PI3K-AKT signaling and tumorigenesis), stabilizes the nuclear receptor PPARD to regulate glucose and lipid metabolism and oxidative phosphorylation in response to nutritional stress (with glucose/fatty-acid-triggered, CBP/CREBBP-dependent acetylation driving its nuclear translocation), and deubiquitinates KPTN to suppress mTORC1 signaling. In ribosome-associated quality control, OTUD3 acts as a negative regulator by deubiquitinating 40S ribosomal proteins RPS10/eS10 and RPS20/uS10, antagonizing ZNF598-mediated 40S ubiquitination. OTUD3 shuttles between the cytoplasm and the nucleus.
- Existing/core annotation action counts: ACCEPT: 32; KEEP_AS_NON_CORE: 5
PN Consistency Summary
- Consistency: Strong. Deep research, review, and PN all agree OTUD3 is an OTU-family Cys-protease DUB (Cys76) with K6/K11 preference; the RQC role (deubiquitinating 40S eS10/uS10, antagonizing ZNF598; PMID:32011234) is captured in description + IDA annotations. No contradictions. Nuance: review/description frame the RQC role as negative regulation (a brake on RQC); PN files OTUD3 as an RQC "Deubiquitination" member, which is correct directionally but the PN-group→GO:0006515 "protein quality control" projection slightly overstates OTUD3's role (it antagonizes, not drives, QC).
- PN story / NEW pressure: GO:0101005 deubiquitinase activity (verified real) is entailed by the existing GO:0004843 cysteine-type DUB activity already annotated (IDA/IBA/TAS) — already captured, no NEW pressure on MF. GO:0006515 (verified real) is new_to_goa and absent from review; given OTUD3 antagonizes RQC, a positive "involved_in protein QC" assertion over-reaches. Conclude: MF already captured; process term over-reaches as a propagation.
- Evidence alignment: PN cites only PMID:23827681 (OTU linkage-specificity); review has it (HIGH/VERIFIED) plus the full substrate literature (26280536 PTEN, 32011234 RQC, 35675826 PPARD, 38288086 KPTN). Review strictly superset; no divergence.
- Verdict: Consistent; PN MF already captured, PN RQC-process projection (GO:0006515) over-reaches because OTUD3 is a negative regulator of RQC. No YAML change needed.
Full Consistency Review
- UniProt: Q5T2D3 · batch: proteostasis-batch-2026-06-07c · review status: COMPLETE (rich, 40 annotations, all ACCEPT/KEEP_AS_NON_CORE)
- PN placement: 3 rows —
Translation|Cytosolic translation|Ribosome-associated QC|Deubiquitination; UPS|DUBs and UBL demodifiers|OTU|other; UPS|Ubiquitin and UBL binding|DUB|OTU|UBA-like (other). PN-node mapping: RQC-type→mapped GO:0101005 deubiquitinase activity; RQC-group→mapped GO:0006515 protein QC (new_to_goa); UPS OTU/UBL nodes mostly no_mapping/context_only. Projected: GO:0006515 (new), GO:0101005 (entailed).
- Consistency: Strong. Deep research, review, and PN all agree OTUD3 is an OTU-family Cys-protease DUB (Cys76) with K6/K11 preference; the RQC role (deubiquitinating 40S eS10/uS10, antagonizing ZNF598; PMID:32011234) is captured in description + IDA annotations. No contradictions. Nuance: review/description frame the RQC role as negative regulation (a brake on RQC); PN files OTUD3 as an RQC "Deubiquitination" member, which is correct directionally but the PN-group→GO:0006515 "protein quality control" projection slightly overstates OTUD3's role (it antagonizes, not drives, QC).
- PN story / NEW pressure: GO:0101005 deubiquitinase activity (verified real) is entailed by the existing GO:0004843 cysteine-type DUB activity already annotated (IDA/IBA/TAS) — already captured, no NEW pressure on MF. GO:0006515 (verified real) is new_to_goa and absent from review; given OTUD3 antagonizes RQC, a positive "involved_in protein QC" assertion over-reaches. Conclude: MF already captured; process term over-reaches as a propagation.
- Mapping strategy: Does not change the node. RQC-type→GO:0101005 redundant with the review's GO:0004843. The group→GO:0006515 propagation is the only divergence and should NOT be projected to OTUD3 (antagonist).
- Evidence alignment: PN cites only PMID:23827681 (OTU linkage-specificity); review has it (HIGH/VERIFIED) plus the full substrate literature (26280536 PTEN, 32011234 RQC, 35675826 PPARD, 38288086 KPTN). Review strictly superset; no divergence.
- Verdict: Consistent; PN MF already captured, PN RQC-process projection (GO:0006515) over-reaches because OTUD3 is a negative regulator of RQC. No YAML change needed.
- Recommended edits: [MAP] Do not propagate GO:0006515 (protein QC) to OTUD3 from the RQC-group node — OTUD3 antagonizes ZNF598-driven 40S ubiquitination (negative RQC regulator), so an
involved_in protein quality control assertion mis-states direction; flag as do-not-project.
PN Dossier Context
- review_batch: proteostasis-batch-2026-06-07c
- review_yaml: genes/human/OTUD3/OTUD3-ai-review.yaml
- PN workbook rows: 3
PN row 1: Translation | Cytosolic translation | Ribosome-associated QC | Deubiquitination
- UniProt: Q5T2D3
- In branches: TR, UPS
- PN-node mapping records (path + ancestors):
- [type] Translation|Cytosolic translation|Ribosome-associated QC|Deubiquitination
status=mapped scope=ok_for_propagation_to_go GO=[GO:0101005 deubiquitinase activity]
rationale: This PN RQC type denotes deubiquitinases acting in ribosome-associated quality control. Deubiquitinase activity is the shared molecular-function target.
- [group] Translation|Cytosolic translation|Ribosome-associated QC
status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
- [class] Translation|Cytosolic translation
status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
- [branch] Translation
status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.
PN row 2: Ubiquitin Proteasome System | DUBs and UBL demodifiers | OTU | other
- UniProt: Q5T2D3
- In branches: TR, UPS
- Signature domains: IPR003323
- Auxiliary domains: (none)
- PN references (titles):
- PN-node mapping records (path + ancestors):
- [type] Ubiquitin Proteasome System|DUBs and UBL demodifiers|OTU|other
status=no_mapping scope= GO=[]
rationale: Reviewed as an OTU-family subtype. Because the family branch includes inactive or ambiguous OTU-like cases, no automatic DUB propagation is made from this subtype.
- [group] Ubiquitin Proteasome System|DUBs and UBL demodifiers|OTU
status=context_only scope=too_broad_to_propagate GO=[GO:0101005 deubiquitinase activity]
rationale: This OTU-family group is DUB-related context, but the subtree includes inactive or ambiguous OTU-like cases. Direct DUB propagation should come from narrower gene-level review rather than this whole family bucket.
- [class] Ubiquitin Proteasome System|DUBs and UBL demodifiers
status=no_mapping scope= GO=[]
rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
PN row 3: Ubiquitin Proteasome System | Ubiquitin and UBL binding | DUB | OTU | UBA-like (other)
- UniProt: Q5T2D3
- In branches: TR, UPS
- Signature domains: PMID: 23827681 (likely @ 228-276)
- Auxiliary domains: IPR003323
- PN references (titles):
- PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|DUB|OTU|UBA-like (other)
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower UBL-binding DUB-domain subdivision. Because this subtree includes noncatalytic or pseudo-DUB cases, active DUB propagation is handled by the DUB-family branch rather than this binding-domain node.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|DUB|OTU
status=no_mapping scope= GO=[]
rationale: Reviewed as a narrower UBL-binding DUB-domain subdivision. Because this subtree includes noncatalytic or pseudo-DUB cases, active DUB propagation is handled by the DUB-family branch rather than this binding-domain node.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|DUB
status=context_only scope=too_broad_to_propagate GO=[GO:0101005 deubiquitinase activity]
rationale: This UBL-binding group is DUB-related context, but it includes noncatalytic or pseudo-DUB domain cases such as NPLOC4/USP39-like entries. Active DUB propagation is handled from the DUB-family branch.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [branch] Ubiquitin Proteasome System
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.
Projected GO annotations (2)
- GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC
- GO:0101005 deubiquitinase activity | scope=ok_for_propagation_to_go | goa_status=entailed_by_goa_closure | from=Translation|Cytosolic translation|Ribosome-associated QC|Deubiquitination
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.