A0A2I0M3K7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0001522 pseudouridine synthesis	IEA GO_REF:0000002	MODIFY	Summary: Correct biological process. TRUB2 catalyzes pseudouridine formation in mitochondrial tRNAs and mRNAs; pseudouridine synthesis is its core biological process. However, a more specific term exists: GO:0070902 (mitochondrial tRNA pseudouridine synthesis) better captures the primary process for this mitochondrial enzyme. Reason: The general term is accurate but too broad. TRUB2 is specifically a mitochondrial pseudouridine synthase; GO:0070902 (mitochondrial tRNA pseudouridine synthesis) is the appropriate specific process based on mammalian ortholog evidence. Proposed replacements: mitochondrial tRNA pseudouridine synthesis
GO:0003723 RNA binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct but generic. As a pseudouridine synthase that acts directly on RNA substrates (mitochondrial tRNAs and mRNAs), TRUB2 necessarily binds RNA. The TruB family uses a substrate-flipping mechanism that requires direct RNA contact. However, RNA binding is ancillary to the catalytic function and does not provide informative annotation beyond what the pseudouridine synthase activity already implies. Reason: RNA binding is an inherent mechanistic property of this RNA-modifying enzyme, not a distinct core function. It is accurate but uninformative beyond the primary catalytic annotation.
GO:0006396 RNA processing	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Pseudouridylation is a post-transcriptional RNA modification, which falls under the umbrella of RNA processing. However, the more precise term GO:0009451 (RNA modification) is already annotated and better captures the nature of TRUB2's activity. RNA processing is overly broad and could imply splicing, cleavage, or other processing events that TRUB2 does not perform. Reason: Too broad. GO:0009451 (RNA modification), which is already annotated, is the correct parent-level process term. RNA processing implies a wider range of activities than what TRUB2 performs.
GO:0009451 RNA modification	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Correct general biological process. TRUB2 performs RNA modification (specifically pseudouridylation). This is a valid parent term of the more specific pseudouridine synthesis process. Since a more specific term (pseudouridine synthesis / mitochondrial tRNA pseudouridine synthesis) is available and preferred, this annotation is redundant but not incorrect. Reason: Accurate parent-level process term, but redundant given the more specific pseudouridine synthesis annotation. Kept as non-core since it adds no specificity beyond the more informative annotations.
GO:0009982 pseudouridine synthase activity	IEA GO_REF:0000002	MODIFY	Summary: Correct molecular function. TRUB2 is a bona fide pseudouridine synthase that catalyzes uridine-to-pseudouridine isomerization. However, a more specific term exists: GO:0160148 (tRNA pseudouridine(55) synthase activity) precisely describes the established enzymatic specificity of TRUB2 for the Psi55 position in tRNAs. GO:0106029 (tRNA pseudouridine synthase activity) would also be appropriate as an intermediate-specificity annotation. Reason: The general pseudouridine synthase activity term is accurate but too broad. Based on mammalian ortholog evidence, TRUB2 specifically catalyzes tRNA pseudouridine-55 formation; GO:0160148 (tRNA pseudouridine(55) synthase activity) captures this specificity. The ProtNLM2 prediction review also noted that GO:0106029 (tRNA pseudouridine synthase activity) is a more specific correct term. Proposed replacements: tRNA pseudouridine(55) synthase activity

GO Term

Evidence

Action

Reason

GO:0001522 pseudouridine synthesis

IEA
GO_REF:0000002

MODIFY

Summary: Correct biological process. TRUB2 catalyzes pseudouridine formation in mitochondrial tRNAs and mRNAs; pseudouridine synthesis is its core biological process. However, a more specific term exists: GO:0070902 (mitochondrial tRNA pseudouridine synthesis) better captures the primary process for this mitochondrial enzyme.

Reason: The general term is accurate but too broad. TRUB2 is specifically a mitochondrial pseudouridine synthase; GO:0070902 (mitochondrial tRNA pseudouridine synthesis) is the appropriate specific process based on mammalian ortholog evidence.

Proposed replacements: mitochondrial tRNA pseudouridine synthesis

GO:0003723 RNA binding

IEA
GO_REF:0000002

KEEP AS NON CORE

Summary: Correct but generic. As a pseudouridine synthase that acts directly on RNA substrates (mitochondrial tRNAs and mRNAs), TRUB2 necessarily binds RNA. The TruB family uses a substrate-flipping mechanism that requires direct RNA contact. However, RNA binding is ancillary to the catalytic function and does not provide informative annotation beyond what the pseudouridine synthase activity already implies.

Reason: RNA binding is an inherent mechanistic property of this RNA-modifying enzyme, not a distinct core function. It is accurate but uninformative beyond the primary catalytic annotation.

GO:0006396 RNA processing

IEA
GO_REF:0000002

MARK AS OVER ANNOTATED

Summary: Pseudouridylation is a post-transcriptional RNA modification, which falls under the umbrella of RNA processing. However, the more precise term GO:0009451 (RNA modification) is already annotated and better captures the nature of TRUB2's activity. RNA processing is overly broad and could imply splicing, cleavage, or other processing events that TRUB2 does not perform.

Reason: Too broad. GO:0009451 (RNA modification), which is already annotated, is the correct parent-level process term. RNA processing implies a wider range of activities than what TRUB2 performs.

GO:0009451 RNA modification

IEA
GO_REF:0000002

KEEP AS NON CORE

Summary: Correct general biological process. TRUB2 performs RNA modification (specifically pseudouridylation). This is a valid parent term of the more specific pseudouridine synthesis process. Since a more specific term (pseudouridine synthesis / mitochondrial tRNA pseudouridine synthesis) is available and preferred, this annotation is redundant but not incorrect.

Reason: Accurate parent-level process term, but redundant given the more specific pseudouridine synthesis annotation. Kept as non-core since it adds no specificity beyond the more informative annotations.

GO:0009982 pseudouridine synthase activity

IEA
GO_REF:0000002

MODIFY

Summary: Correct molecular function. TRUB2 is a bona fide pseudouridine synthase that catalyzes uridine-to-pseudouridine isomerization. However, a more specific term exists: GO:0160148 (tRNA pseudouridine(55) synthase activity) precisely describes the established enzymatic specificity of TRUB2 for the Psi55 position in tRNAs. GO:0106029 (tRNA pseudouridine synthase activity) would also be appropriate as an intermediate-specificity annotation.

Reason: The general pseudouridine synthase activity term is accurate but too broad. Based on mammalian ortholog evidence, TRUB2 specifically catalyzes tRNA pseudouridine-55 formation; GO:0160148 (tRNA pseudouridine(55) synthase activity) captures this specificity. The ProtNLM2 prediction review also noted that GO:0106029 (tRNA pseudouridine synthase activity) is a more specific correct term.

Proposed replacements: tRNA pseudouridine(55) synthase activity

Core Functions

Mitochondrial tRNA pseudouridine-55 synthase that catalyzes the isomerization of U55 to Psi55 in the TPC loop of select mitochondrial tRNAs, stabilizing tRNA tertiary structure. The enzyme requires a U54-A58 reverse Hoogsteen base pair for efficient catalysis. Also contributes to pseudouridylation of specific mitochondrial mRNAs (MT-CO1, MT-CO3). These modifications are essential for mitochondrial translation and oxidative phosphorylation complex assembly.

Molecular Function:

tRNA pseudouridine(55) synthase activity

Directly Involved In:

mitochondrial tRNA pseudouridine synthesis

Cellular Locations:

mitochondrial matrix

Supporting Evidence:

file:COLLI/A0A2I0M3K7/A0A2I0M3K7-deep-research-falcon.md
TRUB2 functions as a mitochondrial tRNA Psi55 synthase, catalyzing the formation of pseudouridine at position 55 in the TPC loop of select mitochondrial tRNAs

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · A0A2I0M3K7-protnlm-predictions-review.yaml · Review status: COMPLETE

The short TRUB2-family sequence supports a pseudouridine-synthase relationship, but tRNA substrate specificity is unresolved.

Source documents: genes/COLLI/A0A2I0M3K7/A0A2I0M3K7-uniprot.txt · genes/COLLI/A0A2I0M3K7/A0A2I0M3K7-goa.tsv · publications/PMID_27974379.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0106029 tRNA pseudouridine synthase activity GO_MF

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt 2024_06 pilot

Review rationale: The target has TRUB2-specific family assignments and a partial pseudouridine-synthase architecture in only 142 residues. Human TRUB2/RPUSD3 perturbation implicates these proteins in mitochondrial mRNA pseudouridylation (PMID:27974379); this does not establish the tRNA-specific activity predicted here. Generic pseudouridine synthase activity in the cached annotations is not equivalent to tRNA pseudouridine synthase activity. A complete catalytic sequence and evidence for tRNA as a substrate are needed, while the available study does not by itself exclude additional tRNA activity.

Supporting Evidence:

file:COLLI/A0A2I0M3K7/A0A2I0M3K7-uniprot.txt: "ID A0A2I0M3K7_COLLI Unreviewed; 142 AA. ... DR InterPro; IPR039048; Trub2. ... DR PANTHER; PTHR13195:SF0; PSEUDOURIDYLATE SYNTHASE TRUB2, MITOCHONDRIAL; 1. ... FT DOMAIN 1..54 ... FT /note="Pseudouridine synthase II N-terminal""
PMID:27974379: "TRUB2/RPUSD3 were similarly involved in pseudouridylating specific residues in mitochondrial mRNAs"

Gene Description

Existing Annotations Review

Core Functions

References

External Prediction Reviews

ProtNLM2 External predictions

Deep Research

Falcon

📄 View Raw YAML