UMAD1 is a poorly characterized 137 amino acid human protein containing a predicted C-terminal UMA domain. Its name and domain architecture place it in the UBAP1/MVB12-associated UMA-domain protein family, but current local evidence does not establish a specific ESCRT-I complex, endosomal sorting, autophagy, membrane fission, or viral budding function for UMAD1. UniProt lists no FUNCTION comment or GO cross-references for UMAD1, and GOA currently contains only broad IntAct protein-binding evidence from a large-scale binary interactome map.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005515
protein binding
|
IPI
PMID:32296183 A reference map of the human binary protein interactome. |
MARK AS OVER ANNOTATED |
Summary: This annotation comes from IntAct records based on the HuRI human binary interactome map, with UMAD1 interactions to TH isoform 3 and GABARAPL1 present in the local UniProt record. The interaction-screen evidence supports that UMAD1 can score in binary protein-interaction assays, but the GO term "protein binding" is too generic to represent a meaningful molecular function, and the partners do not establish a coherent UMAD1 core role.
Reason: Generic protein binding is discouraged because it does not describe the actual activity or pathway role of the gene product. Here, the evidence is a large-scale interactome screen rather than a targeted functional study, and no more specific UMAD1 molecular function can be assigned from the local evidence. The Falcon deep research report proposes a specific ESCRT-I-adaptor molecular function for UMAD1 (selective binding to TSG101, VPS28, and VPS37C/VPS37B via a VPF motif), but that proposal derives from a single uncached primary study (Glover et al. 2023) that could not be verified here, and the report itself concedes that several UMAD1-specific roles "remains an important area for future investigation." This does not provide a verifiable basis to replace the generic protein-binding term, so the over-annotation call is retained.
Supporting Evidence:
UniProt:C9J7I0
CC C9J7I0; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-10989060, EBI-746969;
UniProt:C9J7I0
CC C9J7I0; P07101-3: TH; NbExp=3; IntAct=EBI-10989060, EBI-12001016;
PMID:32296183
To map the reference interactome, we performed nine screens of Space III, followed by pairwise verification by quadruplicate retesting and sequence confirmation.
file:human/UMAD1/UMAD1-notes.md
The existing `GO:0005515 protein binding` annotation is supported as a broad interaction-screen observation, but it is uninformative as a molecular function and should be marked as over-annotated.
file:human/UMAD1/UMAD1-deep-research-falcon.md
though direct experimental demonstration of UMAD1-specific roles in endosomal cargo sorting, autophagosome closure, or membrane repair remains an important area for future investigation.
|
Q: Does endogenous UMAD1 assemble with TSG101, VPS28, and any VPS37 paralog into a stable ESCRT-I complex in human cells?
Q: If UMAD1 forms an ESCRT-I variant, what cargoes, membranes, or tissues require the UMAD1-containing complex rather than MVB12A, MVB12B, or UBAP1 variants?
Q: Are the HuRI interactions with GABARAPL1 or TH isoform 3 reproducible at endogenous expression levels and relevant to a cellular process?
Experiment: Perform endogenous tagging or validated-antibody co-immunoprecipitation of UMAD1 followed by targeted immunoblotting or mass spectrometry for TSG101, VPS28, VPS37 paralogs, MVB12A, MVB12B, and UBAP1.
Hypothesis: UMAD1 may assemble into a specific ESCRT-I variant, but this must be shown directly before ESCRT-I complex annotations are justified.
Experiment: Use CRISPR knockout or acute depletion of UMAD1 with assays for ubiquitinated cargo sorting, intralumenal vesicle formation, and endosome morphology.
Hypothesis: If UMAD1 is a functional ESCRT-I fourth subunit, loss of UMAD1 should cause a measurable defect in at least one ESCRT-dependent endosomal sorting workflow.
Experiment: Validate the HuRI GABARAPL1 and TH isoform 3 interactions with reciprocal co-immunoprecipitation or purified-protein binding assays.
Hypothesis: The binary-interactome partners may be reproducible physical interactors, but they do not yet define UMAD1 molecular function.
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: It is unresolved whether endogenous UMAD1 assembles into a stable human ESCRT-I complex, and if so which TSG101/VPS28/VPS37-containing complex it joins and what molecular role its UMA domain performs.
OPEN BIOLOGYCURATION MF_DARK
What is known: UMAD1 has a predicted UMA domain and is listed by Flower et al. 2020 among possible UMA-domain fourth subunits of human ESCRT-I. Local evidence does not verify a UMAD1-containing ESCRT-I complex, and the only GOA evidence is broad HuRI protein binding to GABARAPL1 and TH isoform 3.
Significance: ESCRT-I complex membership would be the key molecular anchor for all more specific UMAD1 process annotations. Without direct assembly evidence, adding ESCRT-I, membrane-fission, ubiquitin-binding, or adaptor-function terms would overstate the local evidence.
What would resolve it: Endogenous UMAD1 tagging or validated-antibody immunoprecipitation with TSG101, VPS28, VPS37 paralogs, MVB12A/B, UBAP1, and ALIX, plus purified UMA-domain binding assays and motif mutants, would establish whether UMAD1 is an ESCRT-I subunit and define its molecular partners.
Provenance (the field's own admissions):
Gap: The biological process in which UMAD1 acts is unresolved. Cytokinetic abscission is proposed by an uncached 2023 primary study summarized in Falcon deep research, while endosomal sorting, autophagosome closure, membrane repair, and viral budding remain family-level ESCRT inferences rather than locally verified UMAD1 functions.
OPEN BIOLOGYCURATION BP_DARK
What is known: The Falcon report identifies a potentially decisive Glover et al. 2023 cytokinesis paper, but that paper is not in the local cache and was not read for this review. The locally cached Flower et al. paper supports UMA-domain ESCRT-I architectural context but does not establish a UMAD1-specific process.
Significance: UMAD1 currently cannot be assigned a defensible biological-process term beyond treating protein-binding evidence as over-annotated. Resolving this gap would determine whether UMAD1 belongs in cytokinesis, endosomal MVB sorting, autophagy, membrane repair, or no currently supported ESCRT-dependent process.
What would resolve it: Cache and review the Glover et al. 2023 article, verify its UMAD1-specific supporting text, then test UMAD1 perturbation in cytokinetic abscission, endosomal cargo sorting, autophagosome closure, and membrane repair assays with rescue by wild-type and ESCRT-binding-defective UMAD1.
Provenance (the field's own admissions):
Gap: The compartment where UMAD1 acts is unresolved. Midbody localization is asserted in the unverified cytokinesis model, while endosomal localization is inferred from ESCRT-I family context; neither compartment is established from locally reviewed endogenous UMAD1 evidence.
OPEN BIOLOGYCURATION CC_DARK
What is known: UMAD1's domain architecture places it among UMA-domain ESCRT-I-associated proteins, and the Falcon report describes context-dependent midbody and expected endosomal localization. The local review does not accept those locations as established cellular-component annotations.
Significance: Distinguishing midbody, endosomal, autophagosome-associated, or other pools is essential for deciding whether UMAD1 should receive ESCRT-I complex, midbody, endosome, or autophagy-related location annotations.
What would resolve it: Use endogenous tagging or validated antibodies for UMAD1 localization through the cell cycle and during ESCRT-dependent endosomal/autophagy perturbations, paired with CEP55, TSG101, VPS37, ALIX, endosome, and autophagosome markers.
Provenance (the field's own admissions):
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The human gene UMAD1 (UniProt: C9J7I0) encodes UBAP1-MVB12-associated domain containing protein 1, a recently characterized component of the endosomal sorting complex required for transport (ESCRT) machinery (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 3-6). UMAD1 is also known by alternative names RPA3-AS1 and RPA3OS in genomic annotations, though the functional literature focuses on its protein-coding capacity as an ESCRT-I subunit (glover2023umad1contributesto pages 1-3). The protein is conserved across vertebrates and shows ubiquitous expression in human tissues (glover2023umad1contributesto pages 3-6).
UMAD1 belongs to the MVB12-like protein family and contains a conserved N-terminal UMA (UBAP1-MVB12-associated) domain (glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 1-2). This domain defines a family of mammalian proteins that occupy equivalent positions to yeast Mvb12 in the ESCRT-I complex (flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 2-3). The critical functional element within the UMA domain is a signature VPF motif at positions V89-P90-F91 (glover2023umad1contributesto pages 3-6). This motif is essential for ESCRT-I incorporation, as mutation of VPF to AAA completely abolishes binding to the ESCRT-I headpiece complex (glover2023umad1contributesto pages 3-6). Structural analysis reveals that the VPF motif makes direct contact with a hydrophobic pocket formed at the interface between TSG101 and VPS37 subunits within the ESCRT-I headpiece (glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 2-3). AlphaFold2 structural predictions support conserved interactions between the UMAD1 VPF motif and the TSG101-VPS37C heterodimer (glover2023umad1contributesto pages 3-6).
UMAD1 functions as a heterotetramer-forming subunit of ESCRT-I, where it selectively associates with the core ESCRT-I components TSG101 and VPS28, along with specific VPS37 isoforms (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 3-6). A defining feature of UMAD1 is its selective pairing preference for VPS37 subunits. UMAD1 shows the strongest association with VPS37C, followed by weaker but reproducible interaction with VPS37B (glover2023umad1contributesto pages 3-6). Under tested conditions, UMAD1 exhibits only marginal association with VPS37D and no detectable incorporation into complexes containing VPS37A (glover2023umad1contributesto pages 3-6). This selectivity distinguishes UMAD1 from other MVB12-like proteins; for example, UBAP1 preferentially pairs with VPS37A to form ubiquitin-binding ESCRT-I modules specialized for endosomal sorting (glover2023umad1contributesto pages 6-8).
The incorporation of MVB12-like subunits into ESCRT-I is mutually exclusive, as demonstrated by quantitative mass spectrometry showing that in UMAD1 knockout cells, the association of UBAP1 and MVB12A with TSG101 significantly increases, consistent with competition for the same binding site on the ESCRT-I headpiece (glover2023umad1contributesto pages 6-8). This mutually exclusive assembly pattern suggests that cells can form functionally distinct ESCRT-I complexes tailored to specific cellular processes based on which MVB12-like subunit and VPS37 isoform are incorporated.
The most thoroughly characterized function of UMAD1 is its essential role in cytokinetic abscission, the terminal membrane scission event that completes cell division by resolving the midbody between daughter cells (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8). UMAD1 is recruited to the midbody during late stages of cytokinesis, where it colocalizes with TSG101 and persists until midbody resolution is complete (glover2023umad1contributesto pages 8-10). This recruitment is hierarchical: UMAD1 localization to the midbody requires both the midbody organizer CEP55 and the core ESCRT-I subunit TSG101 (glover2023umad1contributesto pages 8-10). Depletion of either CEP55 or TSG101 prevents UMAD1 recruitment to the midbody, and mutation of the VPF motif reduces UMAD1 midbody localization to background levels, confirming that ESCRT-I interaction is necessary for proper subcellular targeting (glover2023umad1contributesto pages 8-10).
UMAD1 plays a critical role in stabilizing the interaction between CEP55 and TSG101, thereby promoting formation of abscission-competent ESCRT-I assemblies at the midbody (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 3-6, glover2023umad1contributesto pages 10-13). The precise molecular mechanism by which UMAD1 stabilizes this interaction remains under investigation, but it may involve providing additional contact points between TSG101's proline-rich region and the ESCRT and ALIX-binding region (EABR) of CEP55, or inducing conformational changes in TSG101 that favor CEP55 engagement (glover2023umad1contributesto pages 8-10).
Loss of UMAD1 function produces several cellular phenotypes consistent with impaired cytokinesis. UMAD1 knockout cells show a 4-fold reduction in clonogenic growth compared to wild-type cells (glover2023umad1contributesto pages 6-8). At the cellular level, UMAD1-deficient cells exhibit modest increases in multinucleation at steady state and display delayed midbody resolution during live-cell imaging (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10). These phenotypes are similar to those observed with TSG101 depletion, supporting the model that UMAD1 specifically functions within the ESCRT-I-mediated arm of the abscission pathway (glover2023umad1contributesto pages 6-8).
A particularly important mechanistic insight from recent research is that UMAD1's primary function is not simply recruiting ESCRT-III to the midbody, but rather facilitating the dynamic turnover and exchange of ESCRT-III subunits at this site (glover2023umad1contributesto pages 10-13, glover2023umad1contributesto pages 8-10). Fluorescence recovery after photobleaching (FRAP) experiments using CHMP4B-L-GFP as an ESCRT-III marker revealed that while ESCRT-III recruitment to the midbody is not significantly impaired in UMAD1-deficient cells, the dynamic exchange of ESCRT-III subunits with the cytoplasmic pool is substantially reduced (glover2023umad1contributesto pages 8-10). This dynamic turnover is essential for productive ESCRT-III filament growth and membrane scission activity. The UMAD1-dependent facilitation of ESCRT-III dynamics may involve ensuring proper midbody architecture for ESCRT-III nucleation, stabilizing interactions that promote VPS4-mediated ESCRT-III polymer remodeling, or coordinating with ALIX to scaffold ESCRT-III assembly (glover2023umad1contributesto pages 10-13).
UMAD1 exhibits functional redundancy and synergy with ALIX, another major ESCRT-associated protein that recruits ESCRT-III to the midbody through a parallel pathway (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10). While partial depletion of ALIX alone or UMAD1 loss alone produces modest cytokinesis defects, co-depletion of both factors causes synergistic increases in multinucleation and severe delays in abscission (glover2023umad1contributesto pages 6-8). This synergy occurs despite the fact that ESCRT-III recruitment to the midbody remains largely intact in doubly-depleted cells, reinforcing the conclusion that UMAD1 and ALIX cooperate primarily to support ESCRT-III dynamic exchange rather than initial recruitment (glover2023umad1contributesto pages 8-10). The existence of parallel UMAD1/ESCRT-I and ALIX-dependent pathways likely provides functional plasticity that allows cells to adapt cytokinesis to different tissue environments with varying expression levels of ESCRT components (glover2023umad1contributesto pages 10-13).
UMAD1 exhibits context-dependent subcellular localization. During cell division, UMAD1 localizes to the midbody during late cytokinesis, where it remains until abscission is completed (glover2023umad1contributesto pages 8-10). This midbody recruitment is entirely dependent on CEP55 and TSG101, positioning UMAD1 downstream of these factors in the abscission pathway (glover2023umad1contributesto pages 8-10). Outside of mitosis, as a component of the ESCRT-I machinery, UMAD1 is expected to function at endosomal membranes, consistent with the general role of ESCRT-I in endosomal sorting and multivesicular body (MVB) biogenesis (flower2020ahelicalassembly pages 1-2, gentili2023escrtdependentstingdegradation pages 1-2). While direct endosomal localization of UMAD1 has not been extensively documented in the available literature, the broader ESCRT framework and the identification of UMA-domain proteins in endosomal proteomics studies support this inference (gentili2023escrtdependentstingdegradation pages 3-4).
UMAD1 participates in multiple ESCRT-mediated cellular processes:
Cytokinetic abscission pathway: UMAD1 forms cytokinesis-specific ESCRT-I assemblies containing VPS37B or VPS37C that are recruited by CEP55 to facilitate ESCRT-III-mediated membrane scission at the midbody (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 10-13).
Endosomal sorting and protein degradation: As a component of ESCRT-I, UMAD1 belongs to the cellular machinery responsible for sorting ubiquitinated cargo into multivesicular bodies for lysosomal degradation (flower2020ahelicalassembly pages 1-2). Recent work on ESCRT-mediated STING degradation identified VPS37A and UBAP1 as key ESCRT-I components required for STING trafficking to lysosomes (gentili2023escrtdependentstingdegradation pages 1-2, gentili2023escrtdependentstingdegradation pages 3-4). While this specific study focused on UBAP1 rather than UMAD1, both proteins are UMA-domain-containing ESCRT-I subunits that occupy equivalent structural positions, suggesting that UMAD1 likely participates in analogous endosomal sorting processes with different cargo or VPS37 partner preferences (gentili2023escrtdependentstingdegradation pages 3-4).
ESCRT-mediated membrane remodeling: The ESCRT machinery functions in diverse membrane remodeling events including autophagosome closure, membrane repair, and viral budding (flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 5-6). As an ESCRT-I component, UMAD1 is positioned to contribute to these processes, though specific roles beyond cytokinesis remain to be experimentally demonstrated.
The UMA domain represents a mammalian innovation in ESCRT-I architecture. While yeast ESCRT-I contains a single Mvb12 subunit, mammalian cells have evolved a family of UMA-domain proteins (MVB12A, MVB12B, UBAP1, UBA1L, and UMAD1) that can occupy this position (flower2020ahelicalassembly pages 1-2). Structural studies of the human ESCRT-I headpiece containing MVB12A revealed that the UMA-N segment adopts an S-shaped conformation comprising two short 310 helices followed by an antiparallel Ξ²-sheet formed with TSG101 (flower2020ahelicalassembly pages 2-3). Although the precise conformation differs from yeast Mvb12, which adopts an Ξ±-helical structure, both bind to the same region of the ESCRT-I headpiece (flower2020ahelicalassembly pages 2-3). This structural versatility in UMA domain binding, combined with selective VPS37 pairing, allows mammalian cells to generate a diverse repertoire of ESCRT-I complexes with specialized functions.
UMAD1 was first identified and functionally characterized in a 2023 study by Glover et al., making it one of the most recently described human ESCRT components (glover2023umad1contributesto pages 1-3). The strongest experimental evidence supports UMAD1's role in cytokinetic abscission, with comprehensive biochemical, cell biological, and functional rescue experiments establishing its mechanism of action at the midbody (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10). The identification of UMAD1 in proteomic datasets and its structural classification as a UMA-domain protein provide strong inference for its participation in broader ESCRT-I functions at endosomes (flower2020ahelicalassembly pages 1-2, gentili2023escrtdependentstingdegradation pages 3-4), though direct experimental demonstration of UMAD1-specific roles in endosomal cargo sorting, autophagosome closure, or membrane repair remains an important area for future investigation.
| Feature | UMAD1 summary | Evidence |
|---|---|---|
| Verified identity | Human UMAD1 encodes UBAP1-MVB12-associated domain-containing protein 1; literature also notes it as a genuinely expressed vertebrate protein and a novel MVB12-like ESCRT-I subunit. This matches the UniProt-provided identity for Homo sapiens C9J7I0. | (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 3-6) |
| Alternative names / symbol context | UniProt aliases include RPA3-AS1 and RPA3OS, but the protein-focused literature specifically studies the protein-coding UMAD1 product in human cells as an ESCRT-associated factor; care is needed not to confuse the locus with antisense-RNA nomenclature. | (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 3-6) |
| Protein family / class | MVB12-like, UMA-domain-containing ESCRT-I accessory subunit. UMAD1 is incorporated into a subset of mammalian ESCRT-I heterotetramers together with TSG101, VPS28, and selected VPS37 isoforms. | (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 1-2) |
| Key domains | UMAD1 contains a conserved UMA (UBAP1-MVB12-associated) domain in its N-terminal region; UMA proteins occupy the MVB12-like position in human ESCRT-I headpieces. | (glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 2-3) |
| Critical motif | The VPF motif in UMAD1βs UMA domain (V89-P90-F91) is essential for ESCRT-I binding. Mutation of this motif abolishes ESCRT-I association and eliminates UMAD1 rescue of cytokinesis defects. | (glover2023umad1contributesto pages 3-6, glover2023umad1contributesto pages 6-8) |
| Structural interpretation | By analogy to structural work on human ESCRT-I with MVB12A, UMA-containing proteins bind a conserved site on the TSG101βVPS37βVPS28 headpiece. Glover et al. further report AlphaFold2-supported conserved contacts between UMAD1βs VPF motif and TSG101/VPS37C. | (glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 1-2, flower2020ahelicalassembly pages 2-3) |
| Core binding partners | Directly or selectively associated partners include TSG101, VPS28, VPS37C, VPS37B, and CEP55; UMAD1 does not appreciably enrich ESCRT-II in the reported affinity purifications. | (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 3-6) |
| VPS37 subunit preference | UMAD1 shows strongest pairing with VPS37C, weaker but reproducible pairing with VPS37B, marginal association with VPS37D, and no clear incorporation with VPS37A under the tested conditions. | (glover2023umad1contributesto pages 3-6) |
| Relationship to other MVB12-like subunits | UMAD1 is mutually exclusive with other MVB12-like ESCRT-I subunits; in UMAD1-knockout cells, UBAP1 and MVB12A incorporation into TSG101 complexes increases, consistent with competition for the same ESCRT-I position. | (glover2023umad1contributesto pages 6-8) |
| Primary molecular function | UMAD1 acts as a cytokinesis-specialized ESCRT-I subunit/adaptor, stabilizing the CEP55βTSG101/ESCRT-I interaction and thereby supporting abscission-competent ESCRT assembly at the midbody. | (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10) |
| Primary biological process | The best-supported primary role is in cytokinetic abscission, the terminal step of cell division. UMAD1 depletion causes abscission delay, increased multinucleation, and reduced clonogenic growth. | (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10) |
| Mechanistic role in abscission | UMAD1 is required not mainly for initial ESCRT-III recruitment, but for efficient dynamic turnover/exchange of ESCRT-III subunits at the midbody, a property needed for productive membrane scission. | (glover2023umad1contributesto pages 8-10, glover2023umad1contributesto pages 10-13) |
| Functional relationship with ALIX | UMAD1 function is partially redundant/synergistic with the ALIX arm of abscission. Co-depletion of UMAD1 and partial ALIX loss strongly worsens cytokinesis failure despite preserved CHMP4B recruitment. | (glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 8-10, glover2023umad1contributesto pages 10-13) |
| Subcellular localization | UMAD1 co-localizes with TSG101 at the midbody during late cytokinesis and persists there until midbody resolution. Its recruitment requires CEP55 and TSG101/ESCRT-I interaction. | (glover2023umad1contributesto pages 8-10) |
| Localization dependency | Depletion of TSG101 or CEP55 blocks UMAD1 recruitment to the midbody, and the VPF-mutant UMAD1 shows only background midbody localization, indicating ESCRT-I-dependent targeting downstream of CEP55. | (glover2023umad1contributesto pages 8-10) |
| Endosomal/lysosomal relevance | Broader ESCRT literature places UMA-containing ESCRT-I proteins in endosomal sorting. STING-trafficking datasets identify UBAP1-containing ESCRT-I as a key endosomal STING-degradation module and list UMAD1 among human UMA-domain ESCRT-I options, supporting inference that UMAD1 belongs to the same ESCRT-I architectural class even though direct STING evidence is for UBAP1 rather than UMAD1. | (flower2020ahelicalassembly pages 1-2, gentili2023escrtdependentstingdegradation pages 1-2, gentili2023escrtdependentstingdegradation pages 3-4) |
| What UMAD1 is not | UMAD1 is not an enzyme or transporter in the current literature; no catalytic reaction or transported substrate has been established. Its role is best described as a scaffolding/adaptor component that specifies ESCRT-I composition and function in membrane-remodeling pathways. | (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 3-6, flower2020ahelicalassembly pages 1-2) |
Table: This table summarizes the verified identity, domains, binding partners, localization, and best-supported functions of human UMAD1. It is useful for functional annotation because it separates directly demonstrated UMAD1 roles in cytokinetic ESCRT-I from broader ESCRT inferences about endosomal processes.
UMAD1 functions as a specialized scaffolding and adaptor protein rather than as an enzyme or transporter. Its primary role is to specify the composition and function of ESCRT-I complexes in cytokinetic abscission. Through its UMA domain and signature VPF motif, UMAD1 selectively incorporates into ESCRT-I assemblies containing VPS37C or VPS37B, stabilizes the CEP55-ESCRT-I interaction at the midbody, and facilitates the dynamic exchange of ESCRT-III subunits necessary for productive membrane scission during cell division (glover2023umad1contributesto pages 1-3, glover2023umad1contributesto pages 6-8, glover2023umad1contributesto pages 3-6, glover2023umad1contributesto pages 10-13, glover2023umad1contributesto pages 8-10). As a member of the UMA-domain protein family, UMAD1 likely contributes to additional ESCRT-mediated membrane remodeling processes at endosomal compartments, though these functions are less well characterized experimentally compared to its established role in cytokinesis.
References
(glover2023umad1contributesto pages 1-3): James Glover, Edward J. Scourfield, Leandro N. Ventimiglia, Xiaoping Yang, Steven Lynham, Monica Agromayor, and Juan Martin-Serrano. Umad1 contributes to escrt-iii dynamic subunit turnover during cytokinetic abscission. Journal of Cell Science, Aug 2023. URL: https://doi.org/10.1242/jcs.261097, doi:10.1242/jcs.261097. This article has 4 citations and is from a domain leading peer-reviewed journal.
(glover2023umad1contributesto pages 3-6): James Glover, Edward J. Scourfield, Leandro N. Ventimiglia, Xiaoping Yang, Steven Lynham, Monica Agromayor, and Juan Martin-Serrano. Umad1 contributes to escrt-iii dynamic subunit turnover during cytokinetic abscission. Journal of Cell Science, Aug 2023. URL: https://doi.org/10.1242/jcs.261097, doi:10.1242/jcs.261097. This article has 4 citations and is from a domain leading peer-reviewed journal.
(flower2020ahelicalassembly pages 1-2): Thomas G. Flower, Yoshinori Takahashi, Arpa Hudait, Kevin Rose, Nicholas Tjahjono, Alexander J. Pak, Adam L. Yokom, Xinwen Liang, Hong-Gang Wang, Fadila Bouamr, Gregory A. Voth, and James H. Hurley. A helical assembly of human escrt-i scaffolds reverse-topology membrane scission. Nature Structural & Molecular Biology, 27:570-580, May 2020. URL: https://doi.org/10.1038/s41594-020-0426-4, doi:10.1038/s41594-020-0426-4. This article has 75 citations and is from a highest quality peer-reviewed journal.
(flower2020ahelicalassembly pages 2-3): Thomas G. Flower, Yoshinori Takahashi, Arpa Hudait, Kevin Rose, Nicholas Tjahjono, Alexander J. Pak, Adam L. Yokom, Xinwen Liang, Hong-Gang Wang, Fadila Bouamr, Gregory A. Voth, and James H. Hurley. A helical assembly of human escrt-i scaffolds reverse-topology membrane scission. Nature Structural & Molecular Biology, 27:570-580, May 2020. URL: https://doi.org/10.1038/s41594-020-0426-4, doi:10.1038/s41594-020-0426-4. This article has 75 citations and is from a highest quality peer-reviewed journal.
(glover2023umad1contributesto pages 6-8): James Glover, Edward J. Scourfield, Leandro N. Ventimiglia, Xiaoping Yang, Steven Lynham, Monica Agromayor, and Juan Martin-Serrano. Umad1 contributes to escrt-iii dynamic subunit turnover during cytokinetic abscission. Journal of Cell Science, Aug 2023. URL: https://doi.org/10.1242/jcs.261097, doi:10.1242/jcs.261097. This article has 4 citations and is from a domain leading peer-reviewed journal.
(glover2023umad1contributesto pages 8-10): James Glover, Edward J. Scourfield, Leandro N. Ventimiglia, Xiaoping Yang, Steven Lynham, Monica Agromayor, and Juan Martin-Serrano. Umad1 contributes to escrt-iii dynamic subunit turnover during cytokinetic abscission. Journal of Cell Science, Aug 2023. URL: https://doi.org/10.1242/jcs.261097, doi:10.1242/jcs.261097. This article has 4 citations and is from a domain leading peer-reviewed journal.
(glover2023umad1contributesto pages 10-13): James Glover, Edward J. Scourfield, Leandro N. Ventimiglia, Xiaoping Yang, Steven Lynham, Monica Agromayor, and Juan Martin-Serrano. Umad1 contributes to escrt-iii dynamic subunit turnover during cytokinetic abscission. Journal of Cell Science, Aug 2023. URL: https://doi.org/10.1242/jcs.261097, doi:10.1242/jcs.261097. This article has 4 citations and is from a domain leading peer-reviewed journal.
(gentili2023escrtdependentstingdegradation pages 1-2): Matteo Gentili, Bingxu Liu, Malvina Papanastasiou, Deborah Dele-Oni, Marc A. Schwartz, Rebecca J. Carlson, Aziz M. AlβKhafaji, Karsten Krug, Adam Brown, John G. Doench, Steven A. Carr, and Nir Hacohen. Escrt-dependent sting degradation inhibits steady-state and cgamp-induced signalling. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36132-9, doi:10.1038/s41467-023-36132-9. This article has 138 citations and is from a highest quality peer-reviewed journal.
(gentili2023escrtdependentstingdegradation pages 3-4): Matteo Gentili, Bingxu Liu, Malvina Papanastasiou, Deborah Dele-Oni, Marc A. Schwartz, Rebecca J. Carlson, Aziz M. AlβKhafaji, Karsten Krug, Adam Brown, John G. Doench, Steven A. Carr, and Nir Hacohen. Escrt-dependent sting degradation inhibits steady-state and cgamp-induced signalling. Nature Communications, Feb 2023. URL: https://doi.org/10.1038/s41467-023-36132-9, doi:10.1038/s41467-023-36132-9. This article has 138 citations and is from a highest quality peer-reviewed journal.
(flower2020ahelicalassembly pages 5-6): Thomas G. Flower, Yoshinori Takahashi, Arpa Hudait, Kevin Rose, Nicholas Tjahjono, Alexander J. Pak, Adam L. Yokom, Xinwen Liang, Hong-Gang Wang, Fadila Bouamr, Gregory A. Voth, and James H. Hurley. A helical assembly of human escrt-i scaffolds reverse-topology membrane scission. Nature Structural & Molecular Biology, 27:570-580, May 2020. URL: https://doi.org/10.1038/s41594-020-0426-4, doi:10.1038/s41594-020-0426-4. This article has 75 citations and is from a highest quality peer-reviewed journal.
just fetch-gene human UMAD1 created the review stub, UniProt record, and GOA table. The UniProt entry is UMAD1_HUMAN, accession C9J7I0, a 137 aa protein named "UBAP1-MVB12-associated (UMA)-domain containing protein 1" with synonyms RPA3-AS1 and RPA3OS. UniProt does not provide a FUNCTION comment or GO cross-references for UMAD1, but records a predicted UMA domain at residues 86-134 and classifies the protein in InterPro IPR053292/IPR023340 and PANTHER PTHR36291 [UniProt:C9J7I0, "DR InterPro; IPR053292; UBAP1-MVB12_assoc_domain."; UniProt:C9J7I0, "DR PROSITE; PS51497; UMA; 1."].just deep-research-falcon human UMAD1 was attempted and timed out after 600 seconds, producing no Falcon report. The review therefore relies on the local UniProt, GOA, cached publication, and PN-context evidence below.GO:0005515 protein binding from IntAct/PMID:32296183, with WITH/FROM partners P07101-3 and Q9H0R8. UniProt lists the corresponding interactors as TH isoform 3 and GABARAPL1 [UniProt:C9J7I0, "CC C9J7I0; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-10989060, EBI-746969;"; UniProt:C9J7I0, "CC C9J7I0; P07101-3: TH; NbExp=3; IntAct=EBI-10989060, EBI-12001016;"].UMAD1 should be treated as a poorly characterized UMA-domain protein rather than as an experimentally established ESCRT-I subunit in this review. The name and domain architecture make ESCRT-I membership plausible, and the proteostasis network entry is useful search context, but the local evidence does not show UMAD1 incorporation into an ESCRT-I complex, endosomal cargo sorting, membrane fission, autophagy, or viral budding.
The existing GO:0005515 protein binding annotation is supported as a broad interaction-screen observation, but it is uninformative as a molecular function and should be marked as over-annotated. The interaction partners in the local records, TH isoform 3 and GABARAPL1, do not by themselves establish a coherent UMAD1 core function or a proteostasis pathway role.
No core GO function is assigned in this review. Adding ESCRT-I complex membership, MVB sorting, ubiquitin binding, phospholipid binding, membrane fission, or macroautophagy terms would overstate the available evidence.
The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.
*-deep-research*.md file found in this gene directory.β¦|Sealing of autophagophore membrane|ESCRT-I complex component ; PN-node mapping: leaf mapped/ok_for_propagation GO:0000813 ESCRT I complex; group mapped GO:0000045 autophagosome assembly (both flagged new_to_goa).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.
id: C9J7I0
gene_symbol: UMAD1
product_type: PROTEIN
aliases:
- RPA3-AS1
- RPA3OS
- UBAP1-MVB12-associated (UMA)-domain containing protein 1
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
UMAD1 is a poorly characterized 137 amino acid human protein containing a predicted C-terminal UMA
domain. Its name and domain architecture place it in the UBAP1/MVB12-associated UMA-domain protein
family, but current local evidence does not establish a specific ESCRT-I complex, endosomal sorting,
autophagy, membrane fission, or viral budding function for UMAD1. UniProt lists no FUNCTION comment
or GO cross-references for UMAD1, and GOA currently contains only broad IntAct protein-binding
evidence from a large-scale binary interactome map.
references:
- id: UniProt:C9J7I0
title: UniProt entry for UMAD1 (C9J7I0)
findings:
- statement: >-
UniProt names the protein "UBAP1-MVB12-associated (UMA)-domain containing
protein 1", records a UMA domain, lists interactions with GABARAPL1 and TH
isoform 3, and has no GO cross-references or FUNCTION comment for UMAD1.
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings:
- statement: >-
PMID:32296183 generated the HuRI binary interactome by systematic yeast
two-hybrid screening and follow-up verification; it is not a focused UMAD1
functional study.
- id: PMID:32424346
title: 'A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission.'
findings:
- statement: >-
The paper lists UMAD1 among possible UMA-domain fourth subunits of human
ESCRT-I, but the experimental structure and mechanism use other ESCRT-I
subunits and the discussion notes that some theoretical complexes may not
form.
- id: file:human/UMAD1/UMAD1-notes.md
title: Local curation notes for UMAD1
findings:
- statement: >-
Local synthesis found no direct evidence supporting UMAD1 as an established
ESCRT-I subunit or proteostasis-pathway effector.
- id: file:human/UMAD1/UMAD1-deep-research-falcon.md
title: Falcon deep research report for UMAD1
findings:
- statement: >-
The Falcon report asserts that UMAD1 is a cytokinesis-specialized ESCRT-I
subunit that pairs with VPS37C/VPS37B, stabilizes the CEP55-TSG101
interaction at the midbody, and facilitates ESCRT-III dynamic subunit
turnover during abscission, with partial functional redundancy with ALIX.
Nearly all of these specific claims trace to a single primary source
(Glover et al. 2023, J Cell Sci, doi:10.1242/jcs.261097) that is NOT
present in the local publications cache and could not be verified here.
- statement: >-
The report itself notes that direct experimental demonstration of
UMAD1-specific roles in endosomal cargo sorting, autophagosome closure, or
membrane repair remains an open area, and that the STING-degradation
evidence it cites is for UBAP1 rather than UMAD1. These broader ESCRT roles
are therefore inferences by family analogy, not UMAD1-specific data.
reference_review:
relevance: MEDIUM
correctness: UNVERIFIED
review_notes: >-
Relevance is MEDIUM because the report plausibly identifies the relevant
biological context (UMA-domain ESCRT-I accessory subunit family) and a
primary functional study (Glover et al. 2023) that, if verified, would
substantially inform UMAD1 function. Correctness is UNVERIFIED: the strong
claims ("Primary Function: Role in Cytokinetic Abscission" and "Functional
Redundancy with ALIX") rest almost entirely on the Glover 2023 paper, which
is not in the local cache and was not read; the report's per-claim
"citations" are page-range tags rather than checkable quotes. The
well-supported, cross-checkable elements are the family/architecture
statements that agree with the locally cached Flower 2020 paper
(PMID:32424346) and UniProt (UMA domain, MVB12-like position in human
ESCRT-I; "some theoretical complexes may not form"). The abscission,
CEP55/TSG101-stabilization, ESCRT-III-turnover, and ALIX-redundancy claims
should be treated as DISPUTED/unverified pending direct reading of Glover
2023, and were NOT promoted into accepted GO functions, core_functions, or
the description in this review.
existing_annotations:
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: >-
This annotation comes from IntAct records based on the HuRI human binary
interactome map, with UMAD1 interactions to TH isoform 3 and GABARAPL1
present in the local UniProt record. The interaction-screen evidence supports
that UMAD1 can score in binary protein-interaction assays, but the GO term
"protein binding" is too generic to represent a meaningful molecular
function, and the partners do not establish a coherent UMAD1 core role.
action: MARK_AS_OVER_ANNOTATED
reason: >-
Generic protein binding is discouraged because it does not describe the
actual activity or pathway role of the gene product. Here, the evidence is a
large-scale interactome screen rather than a targeted functional study, and
no more specific UMAD1 molecular function can be assigned from the local
evidence. The Falcon deep research report proposes a specific
ESCRT-I-adaptor molecular function for UMAD1 (selective binding to TSG101,
VPS28, and VPS37C/VPS37B via a VPF motif), but that proposal derives from a
single uncached primary study (Glover et al. 2023) that could not be
verified here, and the report itself concedes that several UMAD1-specific
roles "remains an important area for future investigation." This does not
provide a verifiable basis to replace the generic protein-binding term, so
the over-annotation call is retained.
supported_by:
- reference_id: UniProt:C9J7I0
supporting_text: "CC C9J7I0; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-10989060, EBI-746969;"
- reference_id: UniProt:C9J7I0
supporting_text: "CC C9J7I0; P07101-3: TH; NbExp=3; IntAct=EBI-10989060, EBI-12001016;"
- reference_id: PMID:32296183
supporting_text: "To map the reference interactome, we performed nine screens of Space III, followed by pairwise verification by quadruplicate retesting and sequence confirmation."
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: "The existing `GO:0005515 protein binding` annotation is supported as a broad interaction-screen observation, but it is uninformative as a molecular function and should be marked as over-annotated."
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: "though direct experimental demonstration of UMAD1-specific roles in endosomal cargo sorting, autophagosome closure, or membrane repair remains an important area for future investigation."
core_functions:
- description: >-
Molecular function unknown for this poorly characterized UMA-domain protein;
no direct evidence reviewed here supports a specific ESCRT-I, endosomal
sorting, autophagy, membrane fission, or viral budding function for UMAD1. A
Falcon deep research report proposes that UMAD1 is a cytokinesis-specialized
ESCRT-I accessory subunit (pairing with TSG101/VPS28/VPS37C and acting at the
midbody), but this rests on a single primary study (Glover et al. 2023) that
is not in the local cache and could not be verified, so no core function is
assigned here.
supported_by:
- reference_id: UniProt:C9J7I0
supporting_text: "DR PAN-GO; C9J7I0; 0 GO annotations based on evolutionary models."
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: "No core GO function is assigned in this review."
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: "As an ESCRT-I component, UMAD1 is positioned to contribute to these processes, though specific roles beyond cytokinesis remain to be experimentally demonstrated."
proposed_new_terms: []
suggested_questions:
- question: >-
Does endogenous UMAD1 assemble with TSG101, VPS28, and any VPS37 paralog into
a stable ESCRT-I complex in human cells?
- question: >-
If UMAD1 forms an ESCRT-I variant, what cargoes, membranes, or tissues require
the UMAD1-containing complex rather than MVB12A, MVB12B, or UBAP1 variants?
- question: >-
Are the HuRI interactions with GABARAPL1 or TH isoform 3 reproducible at
endogenous expression levels and relevant to a cellular process?
suggested_experiments:
- description: >-
Perform endogenous tagging or validated-antibody co-immunoprecipitation of
UMAD1 followed by targeted immunoblotting or mass spectrometry for TSG101,
VPS28, VPS37 paralogs, MVB12A, MVB12B, and UBAP1.
hypothesis: >-
UMAD1 may assemble into a specific ESCRT-I variant, but this must be shown
directly before ESCRT-I complex annotations are justified.
- description: >-
Use CRISPR knockout or acute depletion of UMAD1 with assays for ubiquitinated
cargo sorting, intralumenal vesicle formation, and endosome morphology.
hypothesis: >-
If UMAD1 is a functional ESCRT-I fourth subunit, loss of UMAD1 should cause a
measurable defect in at least one ESCRT-dependent endosomal sorting workflow.
- description: >-
Validate the HuRI GABARAPL1 and TH isoform 3 interactions with reciprocal
co-immunoprecipitation or purified-protein binding assays.
hypothesis: >-
The binary-interactome partners may be reproducible physical interactors, but
they do not yet define UMAD1 molecular function.
knowledge_gaps:
- gap_statement: >-
It is unresolved whether endogenous UMAD1 assembles into a stable human ESCRT-I
complex, and if so which TSG101/VPS28/VPS37-containing complex it joins and what
molecular role its UMA domain performs.
boundary: >-
UMAD1 has a predicted UMA domain and is listed by Flower et al. 2020 among possible
UMA-domain fourth subunits of human ESCRT-I. Local evidence does not verify a
UMAD1-containing ESCRT-I complex, and the only GOA evidence is broad HuRI protein
binding to GABARAPL1 and TH isoform 3.
gap_kind:
- BIOLOGY
- CURATION
dark_aspect: MF_DARK
status: OPEN
significance: >-
ESCRT-I complex membership would be the key molecular anchor for all more specific
UMAD1 process annotations. Without direct assembly evidence, adding ESCRT-I,
membrane-fission, ubiquitin-binding, or adaptor-function terms would overstate
the local evidence.
resolution: >-
Endogenous UMAD1 tagging or validated-antibody immunoprecipitation with TSG101,
VPS28, VPS37 paralogs, MVB12A/B, UBAP1, and ALIX, plus purified UMA-domain binding
assays and motif mutants, would establish whether UMAD1 is an ESCRT-I subunit and
define its molecular partners.
provenance:
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: UMAD1 should be treated as a poorly characterized UMA-domain protein rather than as an experimentally established ESCRT-I subunit in this review.
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: The name and domain architecture make ESCRT-I membership plausible, and the proteostasis network entry is useful search context, but the local evidence does not show UMAD1 incorporation into an ESCRT-I complex
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: No core GO function is assigned in this review.
- gap_statement: >-
The biological process in which UMAD1 acts is unresolved. Cytokinetic abscission
is proposed by an uncached 2023 primary study summarized in Falcon deep research,
while endosomal sorting, autophagosome closure, membrane repair, and viral budding
remain family-level ESCRT inferences rather than locally verified UMAD1 functions.
boundary: >-
The Falcon report identifies a potentially decisive Glover et al. 2023 cytokinesis
paper, but that paper is not in the local cache and was not read for this review.
The locally cached Flower et al. paper supports UMA-domain ESCRT-I architectural
context but does not establish a UMAD1-specific process.
gap_kind:
- BIOLOGY
- CURATION
dark_aspect: BP_DARK
status: OPEN
significance: >-
UMAD1 currently cannot be assigned a defensible biological-process term beyond
treating protein-binding evidence as over-annotated. Resolving this gap would
determine whether UMAD1 belongs in cytokinesis, endosomal MVB sorting, autophagy,
membrane repair, or no currently supported ESCRT-dependent process.
resolution: >-
Cache and review the Glover et al. 2023 article, verify its UMAD1-specific
supporting text, then test UMAD1 perturbation in cytokinetic abscission, endosomal
cargo sorting, autophagosome closure, and membrane repair assays with rescue by
wild-type and ESCRT-binding-defective UMAD1.
provenance:
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: though direct experimental demonstration of UMAD1-specific roles in endosomal cargo sorting, autophagosome closure, or membrane repair remains an important area for future investigation.
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: As an ESCRT-I component, UMAD1 is positioned to contribute to these processes, though specific roles beyond cytokinesis remain to be experimentally demonstrated.
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: Adding ESCRT-I complex membership, MVB sorting, ubiquitin binding, phospholipid binding, membrane fission, or macroautophagy terms would overstate the available evidence.
- gap_statement: >-
The compartment where UMAD1 acts is unresolved. Midbody localization is asserted
in the unverified cytokinesis model, while endosomal localization is inferred from
ESCRT-I family context; neither compartment is established from locally reviewed
endogenous UMAD1 evidence.
boundary: >-
UMAD1's domain architecture places it among UMA-domain ESCRT-I-associated proteins,
and the Falcon report describes context-dependent midbody and expected endosomal
localization. The local review does not accept those locations as established
cellular-component annotations.
gap_kind:
- BIOLOGY
- CURATION
dark_aspect: CC_DARK
status: OPEN
significance: >-
Distinguishing midbody, endosomal, autophagosome-associated, or other pools is
essential for deciding whether UMAD1 should receive ESCRT-I complex, midbody,
endosome, or autophagy-related location annotations.
resolution: >-
Use endogenous tagging or validated antibodies for UMAD1 localization through the
cell cycle and during ESCRT-dependent endosomal/autophagy perturbations, paired
with CEP55, TSG101, VPS37, ALIX, endosome, and autophagosome markers.
provenance:
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: While direct endosomal localization of UMAD1 has not been extensively documented in the available literature
- reference_id: file:human/UMAD1/UMAD1-notes.md
supporting_text: the local evidence does not show UMAD1 incorporation into an ESCRT-I complex, endosomal cargo sorting, membrane fission, autophagy, or viral budding.
- reference_id: file:human/UMAD1/UMAD1-deep-research-falcon.md
supporting_text: UMAD1 exhibits context-dependent subcellular localization.