Ugt2a1

Summary: glucuronosyltransferase activity is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (IBA, GO_REF:0000033).

Reason: glucuronosyltransferase activity is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.

Summary: UDP-glycosyltransferase activity captures part of Ugt2a1 biology, but more specific replacement term(s) better represent the supported function (IEA, GO_REF:0000002).

Reason: UDP-glycosyltransferase activity is too broad or imprecise for Ugt2a1; replace with the more specific supported term(s): GO:0015020 glucuronosyltransferase activity.

Proposed replacements: glucuronosyltransferase activity

Summary: glucuronosyltransferase activity is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (IEA, GO_REF:0000120).

Reason: glucuronosyltransferase activity is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.

Summary: membrane is too broad; immunogold EM localizes UGT2A1 to the plasma membrane of olfactory cilia (sensory neurons) and to the endoplasmic reticulum of sustentacular cells, supporting the specific ciliary membrane and ER membrane terms (IEA, GO_REF:0000044).

Reason: membrane is overly generic. In rat olfactory epithelium, immunohistochemistry and immunogold electron microscopy localize UGT2A1 to the plasma membrane of the olfactory cilia of the olfactory sensory neurons (primary evidence PMID:33765098), a cell-projection/plasma-membrane location proximal to odorant receptors, so the annotation is upgraded to the more specific CC term GO:0060170 ciliary membrane. The same study also reports UGT2A1 in the endoplasmic reticulum of the sustentacular cells (immunogold EM, its S1 Fig), so GO:0005789 endoplasmic reticulum membrane is added as a second specific descendant of GO:0016020. On topology, the ER pool is the canonical, expected location for a UGT (a type-I ER membrane protein with a lumen-facing catalytic domain), so the ER membrane term carries no caveat; it is only the olfactory-ciliary plasma-membrane pool that is the non-default claim, and that rests on the same single immunolocalization study (cilia plasma membrane in sensory neurons), not on structural/biochemical topology data.

Proposed replacements: ciliary membrane endoplasmic reticulum membrane

Summary: xenobiotic metabolic process is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (ISO, GO_REF:0000121).

Reason: xenobiotic metabolic process is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.

Summary: response to symbiont should not be retained for Ugt2a1 based on the combined gene function and cited/source evidence (ISO, GO_REF:0000121).

Reason: The ISO row transfers a human UGT2A1 (P0DTE4) IDA for response to symbiont whose reference is PMID:19858781, a recombinant-enzyme characterization of human UGT2A1-2A3. The cached full text of that paper describes tissue expression and glucuronidation assays of UGTs expressed in baculovirus-infected insect cells; it reports no host response to a symbiont or pathogen. Nothing in the rat Ugt2a1 record (an olfactory-epithelium odorant/xenobiotic glucuronosyltransferase) supports a symbiont-response process either, so the transfer is not retained. Removal concerns the rat transfer; the human source row is left for its own curators.

Summary: glucuronosyltransferase activity is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (ISS, GO_REF:0000024).

Reason: glucuronosyltransferase activity is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.

Summary: glucuronosyltransferase activity is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (ISO, GO_REF:0000121).

Reason: glucuronosyltransferase activity is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.

Summary: membrane is too broad; immunogold EM localizes UGT2A1 to the plasma membrane of olfactory cilia (sensory neurons) and to the endoplasmic reticulum of sustentacular cells, supporting the specific ciliary membrane and ER membrane terms (ISS, GO_REF:0000024).

Reason: membrane is overly generic. In rat olfactory epithelium, immunohistochemistry and immunogold electron microscopy localize UGT2A1 to the plasma membrane of the olfactory cilia of the olfactory sensory neurons (primary evidence PMID:33765098), a cell-projection/plasma-membrane location proximal to odorant receptors, so the annotation is upgraded to the more specific CC term GO:0060170 ciliary membrane. The same study also reports UGT2A1 in the endoplasmic reticulum of the sustentacular cells (immunogold EM, its S1 Fig), so GO:0005789 endoplasmic reticulum membrane is added as a second specific descendant of GO:0016020. On topology, the ER pool is the canonical, expected location for a UGT (a type-I ER membrane protein with a lumen-facing catalytic domain), so the ER membrane term carries no caveat; it is only the olfactory-ciliary plasma-membrane pool that is the non-default claim, and that rests on the same single immunolocalization study (cilia plasma membrane in sensory neurons), not on structural/biochemical topology data.

Proposed replacements: ciliary membrane endoplasmic reticulum membrane

Summary: sensory perception of chemical stimulus is kept as a non-core process for Ugt2a1. Its enzymatic activity modulates odorant availability in the perireceptor space rather than executing the neurological transduction cascade itself (ISO, GO_REF:0000121).

Reason: GO:0007606 is defined as a neurological process in which an organism receives a chemical stimulus, converts it to a molecular signal, and recognizes/characterizes it. This transduction cascade is executed by olfactory receptor neurons, not by a metabolic enzyme. UGT2A1 glucuronidates odorants and thereby modulates odorant concentration in the perireceptor space (ex vivo electroolfactogram shows topical beta-glucuronidase selectively increases the eugenol response), so it is a modulator of odorant availability rather than a component of the sensory transduction cascade. The annotation is retained as a non-core contextual involvement rather than ACCEPTed as a core function. There is no GO odorant metabolic process term to MODIFY to (the previously suggested GO:0042545 is cell wall modification, a plant term, and GO:0052697 xenobiotic glucuronidation is obsolete); the core metabolic role is captured by the xenobiotic metabolic process and glucuronosyltransferase activity annotations.

Summary: bile acid metabolic process is retained as contextual support for Ugt2a1, but it is not the core function (ISO, GO_REF:0000121).

Reason: bile acid metabolic process records a physiological/substrate context rather than the defining molecular activity of Ugt2a1. This is an ISO annotation transferred from human UGT2A1 (P0DTE4); the supporting Falcon evidence (bile-acid glucuronidation activity) is from human studies, consistent with the ISO basis, and supports retention as a non-core detoxification process distinct from the primary olfactory role.

Summary: response to toxic substance is an over-annotation for Ugt2a1; PMID:1900353 supports odorant glucuronidation and olfactory signal termination rather than a toxicological response process.

Reason: The cited paper establishes glucuronosyltransferase activity toward odorants. That supports the MF annotation and olfactory chemical-stimulus context, but not a broad response to toxic substance biological process. Falcon deep research frames nasal UGTs (including UGT2A1) as a protective metabolic barrier; this is a constitutive detoxification/clearance role rather than an inducible response-to-toxin process, reinforcing that GO:0009636 is an over-annotation.

Summary: glucuronosyltransferase activity is retained for Ugt2a1 because it matches the documented core enzymatic role or its direct pathway consequence (TAS, PMID:1900353).

Reason: glucuronosyltransferase activity is directly supported by the curated function of Ugt2a1 and is not merely a downstream phenotype or expression response.