USO1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045056 transcytosis	IBA GO_REF:0000033	REMOVE	Summary: IBA annotation based on phylogenetic inference. USO1/p115 functions primarily in ER-to-Golgi anterograde transport and intra-Golgi retrograde transport. While transcytosis involves vesicular transport across cells, there is no direct experimental evidence that USO1 functions specifically in transcytosis. The core function is ER-Golgi trafficking, not transcellular transport. This annotation may represent over-inference from general vesicular transport function. Recommend removal - no direct evidence for transcytosis.
GO:0061025 membrane fusion	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. USO1 is directly involved in membrane fusion through regulation of SNARE complex assembly, which is the core mechanism of membrane fusion. Recent studies (eLife 2024) demonstrate USO1's essential function is facilitating trans-SNARE complex formation between vesicle and target membranes. While USO1 doesn't directly catalyze fusion, it is an integral component of the fusion machinery. Accept as core function. Supporting Evidence: file:human/USO1/USO1-deep-research-openai.md See deep research file for comprehensive analysis file:human/USO1/USO1-deep-research-falcon.md p115/USO1 is described as a Golgi vesicle tethering protein that promotes vesicle docking and fusion, in part through binding to SNARE machinery and Rab GTPase–dependent recruitment.
GO:0005783 endoplasmic reticulum	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation. USO1 localizes to ER-derived COPII vesicles but not to bulk ER. The protein is recruited to nascent COPII vesicles budding from ER exit sites by Rab1-GTP. While technically associated with ER-derived membranes, the primary localizations are transport vesicles and Golgi. This annotation is technically correct but not a primary localization.
GO:0005795 Golgi stack	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. USO1/p115 localizes specifically to early Golgi cisternae (cis-Golgi) and is essential for maintaining Golgi stack structure. High colocalization with early Golgi markers. Critical for cisternal stacking and Golgi ribbon organization. Accept as core localization.
GO:0006886 intracellular protein transport	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA annotation. USO1 functions in intracellular protein transport through the secretory pathway, specifically ER-to-Golgi trafficking. However, this term is very broad and doesn't capture the specific function. The more specific term GO:0006888 (ER to Golgi vesicle-mediated transport) better represents the core function. Keep but mark as non-core due to lack of specificity.
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. This represents the primary and essential biological process for USO1. The protein is absolutely required for ER-to-Golgi transport through regulation of SNARE complex assembly and vesicle docking. Rab1 recruits USO1 to COPII vesicles for fusion with ERGIC/cis-Golgi. Well-supported by extensive experimental evidence. Accept as core function. Supporting Evidence: file:human/USO1/USO1-deep-research-falcon.md Human USO1/p115 is a conserved ERGIC/cis-Golgi vesicle tether/fusion factor in early secretory trafficking, connecting Rab1-regulated vesicle capture/docking with SNARE-dependent membrane fusion. file:human/USO1/USO1-deep-research-falcon.md p115/USO1 is a Golgi vesicle tether required for ER-to-Golgi/early secretory trafficking, vesicle docking, and secretion efficiency; recent human-cell work also supports direct binding of p115 to Sec16A, an ER exit site organizer, linking p115 to early secretory pathway organization.
GO:0012507 ER to Golgi transport vesicle membrane	IBA GO_REF:0000033	ACCEPT	Summary: IBA annotation. USO1 is specifically recruited to ER to Golgi transport vesicle membranes (COPII vesicles) by Rab1-GTP. This is a primary and well-characterized localization. The protein associates with both the vesicle membrane and the target Golgi membrane during tethering and fusion. Accept as core localization.
GO:0048211 Golgi vesicle docking	IBA GO_REF:0000033	MODIFY	Summary: IBA annotation. USO1 mediates Golgi vesicle docking through its tethering function and interactions with GM130 and giantin. While recent studies show the essential function is SNARE assembly rather than tethering per se, docking is still a well-characterized activity. In vitro reconstitution shows Uso1p-mediated vesicle docking. Falcon deep research corroborates a role in vesicle docking/fusion and Rab1-dependent recruitment, while noting that homolog evidence suggests the essential function may lie in direct SNARE regulation rather than long-range tethering. GO:0048211 was obsoleted (GO release 2026-07-26) because it represents a molecular function; GO directs annotations to GO:0160321 vesicle docking activity or GO:7770062 vesicle membrane tethering activity. p115/USO1 is the canonical long-range Golgi vesicle tether, so the tethering MF is the appropriate transfer. Reason: GO:0048211 Golgi vesicle docking was obsoleted (GO release 2026-07-26) because it represents a molecular function; the consider targets are GO:0160321 vesicle docking activity and GO:7770062 vesicle membrane tethering activity. p115/USO1 is recruited by Rab1 to COPII vesicles and bridges them to cis-Golgi membranes through GM130/giantin, which is the long-range tethering activity described by GO:7770062, so that is the appropriate transfer. The tethering activity is real but is kept out of core_functions: fungal Uso1 genetics indicate that the essential activity is direct SNARE binding by the globular head, with coiled-coil tethering dispensable when the head is overexpressed, so the core molecular functions remain GO:0000149 SNARE binding and GO:0031267 small GTPase binding. Proposed replacements: vesicle membrane tethering activity Supporting Evidence: file:human/USO1/USO1-deep-research-falcon.md p115/USO1 is described as a Golgi vesicle tethering protein that promotes vesicle docking and fusion, in part through binding to SNARE machinery and Rab GTPase–dependent recruitment.
GO:0000139 Golgi membrane	IEA GO_REF:0000120	ACCEPT	Summary: IEA computational annotation. USO1 is a peripheral Golgi membrane protein that associates with Golgi membranes in its dephosphorylated state. Well-supported by experimental evidence including the key study PMID:9478999 showing phosphorylation-dependent Golgi membrane association. Accept as core localization.
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: IEA computational annotation. USO1 is indeed found in cytoplasm, but this is too broad. The more specific term GO:0005829 (cytosol) better captures the soluble cytoplasmic pool. Cytoplasm includes all organelles, while the relevant pool is the cytosolic fraction. Keep as non-core.
GO:0005829 cytosol	IEA GO_REF:0000120	ACCEPT	Summary: IEA computational annotation. USO1 cycles between cytosol and Golgi membrane. The phosphorylated form is found exclusively in cytosol (PMID:9478999). This is a well-characterized localization representing the soluble pool during the protein's dynamic membrane cycling. Accept as core localization.
GO:0006886 intracellular protein transport	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Duplicate annotation with different evidence code (also annotated as IBA above). Same rationale applies - too broad, covered by more specific terms. Keep as non-core.
GO:0015031 protein transport	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: IEA annotation based on keyword mapping. Extremely broad term that encompasses all protein transport. USO1 does function in protein transport but the more specific ER-to-Golgi transport term is more informative. Keep as non-core due to lack of specificity.
GO:0016192 vesicle-mediated transport	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: IEA computational annotation. USO1 functions in vesicle-mediated transport specifically at the ER-Golgi interface. This is accurate but broad - the more specific GO:0006888 (ER to Golgi vesicle-mediated transport) is preferred. Keep as non-core.
GO:0048193 Golgi vesicle transport	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation based on InterPro. USO1 functions in both anterograde ER-to-Golgi and retrograde intra-Golgi COPI vesicle transport. Accurate and reasonably specific term for the retrograde function. Accept as core function covering both COPII and COPI vesicle trafficking.
GO:0048280 vesicle fusion with Golgi apparatus	IEA GO_REF:0000002	ACCEPT	Summary: IEA annotation based on InterPro domain. This is highly accurate - USO1 mediates vesicle fusion with Golgi apparatus through SNARE complex assembly and vesicle tethering. This is a core biological process for the protein. Accept as core function.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	REMOVE	Summary: IPI evidence from human interactome network study. While USO1 does bind proteins (SNAREs, Rab1, GM130, giantin), "protein binding" is uninformative as it doesn't specify the functionally relevant interactions. Nearly all proteins bind other proteins. More specific MF terms should be used (SNARE binding, small GTPase binding, etc.). Remove in favor of specific molecular function terms. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Duplicate protein binding annotation from cell-specific interactome study. Same rationale as above - uninformative without specificity. Remove. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:36217029 A proteome-scale map of the SARS-CoV-2-human contactome.	REMOVE	Summary: IPI from SARS-CoV-2 contactome study showing interaction with viral N protein. While this interaction may occur, it is not a core function of USO1 but rather an opportunistic viral interaction. The generic "protein binding" term is uninformative. Remove as not representing core function. Supporting Evidence: PMID:36217029 2022 Oct 10. A proteome-scale map of the SARS-CoV-2-human contactome.
GO:0007030 Golgi organization	IEA GO_REF:0000107	ACCEPT	Summary: IEA from Ensembl ortholog transfer. USO1 is essential for Golgi organization including cisternal stacking, Golgi ribbon formation, and post-mitotic Golgi reassembly. Functions with GM130 and giantin to maintain Golgi structure. Well-supported by experimental evidence; falcon deep research notes that a tumor-associated USO1 isoform causes Golgi unstacking, consistent with a role in maintaining Golgi structure. Accept as core function. Supporting Evidence: file:human/USO1/USO1-deep-research-falcon.md in human HCC, a tumor-associated isoform USO1-T correlates with poorer prognosis, promotes aggressive behavior, causes Golgi unstacking, and accelerates trafficking from ER to Golgi/plasma membrane; modeling suggests weakened dimerization/GM130 tethering and involvement of ERK and GRASP65.
GO:0007264 small GTPase-mediated signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: IEA from Ensembl. USO1 is an effector of Rab1 GTPase and participates in Rab1-mediated signaling. However, this term is overly broad and typically used for signaling cascades rather than direct effector functions in membrane trafficking. The relationship with Rab1 is better captured as a molecular function (small GTPase binding). Mark as non-core or over-annotation.
GO:0032252 secretory granule localization	IEA GO_REF:0000107	REMOVE	Summary: IEA from Ensembl ortholog transfer. This annotation likely comes from studies in specialized secretory cells. While USO1 may play a role in general secretory pathway function, there is no direct evidence it specifically localizes secretory granules. This appears to be over-annotation from general secretory pathway function. Remove.
GO:0048471 perinuclear region of cytoplasm	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: IEA from Ensembl. The Golgi apparatus is typically located in the perinuclear region, so USO1 as a Golgi protein would be found there. However, this is a consequence of Golgi localization, not a primary or functionally significant localization per se. The Golgi-specific terms are more informative. Keep as non-core.
GO:1900076 regulation of cellular response to insulin stimulus	IEA GO_REF:0000107	REMOVE	Summary: IEA from Ensembl ortholog transfer. No direct evidence that USO1 regulates cellular response to insulin. This may be inferred from general requirements for secretory pathway function in insulin signaling, but represents over-annotation. USO1's core function is ER-Golgi transport, not insulin response regulation. Remove.
GO:0005794 Golgi apparatus	IDA GO_REF:0000052	ACCEPT	Summary: IDA evidence from immunofluorescence localization (HPA - Human Protein Atlas). USO1/p115 localizes to the Golgi apparatus as a peripheral membrane protein. Well-established by microscopy and cell fractionation. This is a core cellular component annotation. Accept.
GO:0005815 microtubule organizing center	TAS Reactome:R-NUL-9646387	KEEP AS NON CORE	Summary: TAS from Reactome pathway database. Recent studies show USO1 localizes to spindle poles (centrosomes/ microtubule organizing centers) during mitosis through interaction with gamma-tubulin. This is a well-characterized non-canonical localization important for mitotic spindle function. However, this is a mitosis-specific function, not core to the primary ER-Golgi transport role. Keep as non-core.
GO:0045296 cadherin binding	HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by...	REMOVE	Summary: HDA evidence from E-cadherin interactome study (high-throughput). This is likely an indirect or weak interaction detected in pull-down experiments. No functional evidence that cadherin binding is relevant to USO1 function. The core interactions are with SNAREs, Rab1, and golgins. Remove as likely artifact or non-functional interaction. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics.
GO:0030133 transport vesicle	TAS Reactome:R-HSA-6807877	ACCEPT	Summary: TAS from Reactome COPI pathway. USO1 associates with transport vesicles (both COPII and COPI) as part of its core function in vesicle tethering and fusion. Accept as core localization.
GO:0030133 transport vesicle	TAS Reactome:R-HSA-6809003	ACCEPT	Summary: Duplicate transport vesicle annotation from different Reactome pathway (ERGIC-to-Golgi vesicles bind dynein). Same core localization, redundant with above. Accept.
GO:0030133 transport vesicle	TAS Reactome:R-HSA-6809006	ACCEPT	Summary: Duplicate transport vesicle annotation from Reactome vesicle tethering pathway. Redundant. Accept.
GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport	ISS GO_REF:0000024	ACCEPT	Summary: ISS annotation (manual transfer from orthologs). Duplicate of IBA annotation already reviewed. Core function of USO1. The protein is essential for ER-to-Golgi transport. Accept.
GO:0005829 cytosol	TAS Reactome:R-HSA-5694418	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-5694446	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807864	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807866	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807868	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807872	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807875	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6807877	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-6809010	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0005829 cytosol	TAS Reactome:R-NUL-9646387	ACCEPT	Summary: TAS from Reactome pathways. Duplicate cytosol annotation already reviewed with IEA/IBA evidence. USO1 cycles between cytosol and Golgi. Accept as core localization.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: HDA from membrane proteome study (PMID:19946888). USO1 is indeed a peripheral membrane protein associating with Golgi and vesicle membranes. However, this term is very broad - more specific terms (Golgi membrane, transport vesicle membrane) are preferred. Keep as non-core. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells.
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	REMOVE	Summary: HDA from mRNA-binding proteins atlas (PMID:22658674). This high-throughput study identified many proteins with potential RNA binding. However, there is no functional evidence that RNA binding is relevant to USO1 function. The protein functions in vesicle trafficking, not RNA metabolism. Remove as likely non-specific interaction. Supporting Evidence: PMID:22658674 May 31. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-6809006	ACCEPT	Summary: TAS from Reactome. Duplicate Golgi membrane annotation already reviewed. Accept as core localization.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-6809010	ACCEPT	Summary: TAS from Reactome. Duplicate Golgi membrane annotation already reviewed. Accept as core localization.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-6809011	ACCEPT	Summary: TAS from Reactome. Duplicate Golgi membrane annotation already reviewed. Accept as core localization.
GO:0012507 ER to Golgi transport vesicle membrane	TAS Reactome:R-HSA-5694418	ACCEPT	Summary: TAS from Reactome. Duplicate ER to Golgi transport vesicle membrane annotation already reviewed. Accept as core localization.
GO:0012507 ER to Golgi transport vesicle membrane	TAS Reactome:R-HSA-5694441	ACCEPT	Summary: TAS from Reactome. Duplicate ER to Golgi transport vesicle membrane annotation already reviewed. Accept as core localization.
GO:0012507 ER to Golgi transport vesicle membrane	TAS Reactome:R-HSA-5694446	ACCEPT	Summary: TAS from Reactome. Duplicate ER to Golgi transport vesicle membrane annotation already reviewed. Accept as core localization.
GO:0000139 Golgi membrane	TAS PMID:9478999 Phosphorylation of the vesicle docking protein p115 regulate...	ACCEPT	Summary: TAS from key phosphorylation study (PMID:9478999) showing USO1 associates with Golgi membrane in dephosphorylated form and dissociates upon phosphorylation at Ser942. Direct experimental evidence for Golgi membrane localization. Accept as core. Supporting Evidence: PMID:9478999 Phosphorylation of the vesicle docking protein p115 regulates its association with the Golgi membrane.
GO:0000149 SNARE binding	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: file:human/USO1/USO1-uniprot.txt Based on functional studies and literature review documented in deep research files and USO1-notes.md file:human/USO1/USO1-deep-research-falcon.md A 2023 eLife study (fungal Uso1; homolog of human p115) reports that the globular head domain directly binds SNAREs (including Bet1 and Bos1/membrin family members) and that a monomeric head domain can complement loss of full-length Uso1 in vivo when overexpressed—arguing that long-range coiled-coil tethering can be dispensable and that the essential role can involve direct regulation of SNARE machinery.
GO:0031267 small GTPase binding	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. Supporting Evidence: file:human/USO1/USO1-uniprot.txt Based on functional studies and literature review documented in deep research files and USO1-notes.md file:human/USO1/USO1-deep-research-falcon.md A 2023 thesis synthesis explicitly states that p115 has been shown to interact with Rab1A via its N-terminus and that p115 interacts with cis-Golgi SNAREs (e.g., Sec22b, Bet1, GOSR2, syntaxin-5) in proposed fusion models.

Gene Description

Proposed New Ontology Terms

Golgi ribbon formation

regulation of cognate SNARE pairing

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

OpenAI

Perplexity

Perplexity

📚 Additional Documentation

Notes

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