BLOC1S5, also called MUTED, is a small nonenzymatic subunit of the eight-subunit BLOC-1 complex. It stabilizes the assembly that sorts membrane cargo from early endosomes to melanosomes and other lysosome-related organelles. Human MUTED restores BLOC-1 stability, pigmentation and cargo delivery in muted mouse melanocytes. BLOC-1 also supports selected neuronal cargo-trafficking routes. Biallelic BLOC1S5 defects cause Hermansky-Pudlak syndrome type 11, with hypopigmentation and platelet dense-granule deficiency.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:12191018 Pallidin is a component of a multi-protein complex involved ... | KEEP AS NON CORE | Summary: MUTED physically associates with BLOC1S6/pallidin in the stated interaction context. Reason: The cached abstract explicitly identifies Muted in the pallidin-containing heterooligomer and reports reduced pallidin in muted mouse fibroblasts. This supports the curated interaction with BLOC1S6/pallidin in an assembly context, without identifying an isolated binary interface. Generic protein binding is retained as non-core. |
| GO:0005515 protein binding | IPI PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | KEEP AS NON CORE | Summary: MUTED physically associates with BLOC1S2 in the stated interaction context. Reason: The cached abstract describes endogenous BLOC-1 co-immunoprecipitation/co-fractionation and a yeast-two-hybrid interaction network including all subunits. The curated BLOC1S2 interaction also appears in the human UniProt interaction record. The exact pair matrix was not re-read; there is no basis to reject this experimental annotation. Retain the interaction as non-core rather than using generic binding as the core molecular function. |
| GO:0005515 protein binding | IPI PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | KEEP AS NON CORE | Summary: MUTED physically associates with DTNBP1/dysbindin in the stated interaction context. Reason: The cached abstract describes endogenous BLOC-1 co-immunoprecipitation/co-fractionation and a yeast-two-hybrid interaction network including all subunits. The curated DTNBP1/dysbindin interaction also appears in the human UniProt interaction record. The exact pair matrix was not re-read; there is no basis to reject this experimental annotation. Retain the interaction as non-core rather than using generic binding as the core molecular function. |
| GO:0005515 protein binding | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | KEEP AS NON CORE | Summary: MUTED physically associates with DTNBP1/dysbindin in the stated interaction context. Reason: The inspected full-text reconstitution establishes Muted and dysbindin in the same human BLOC-1 octamer. The isolated dysbindin-core trimer excludes Muted, so that subcomplex assay does not map a direct Muted interface. Retain the curated physical association, independently represented in UniProt, as non-core and do not equate co-complex evidence with a resolved binary binding surface. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: MUTED physically associates with TSNAX in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact TSNAX pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with OIP5 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact OIP5 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with HSBP1 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact HSBP1 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with PBX2 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact PBX2 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with PKNOX1 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact PKNOX1 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with SMARCD1 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact SMARCD1 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with TSNAX in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact TSNAX pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with ABI2 isoform 2 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact ABI2 isoform 2 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: MUTED physically associates with ABI3 in the stated interaction context. Reason: This source reports a systematic human binary interaction map; the exact ABI3 pair is also recorded in the human UniProt interaction section. The cached abstract and selected text establish assay scope, while the pair-level supplementary matrix was not independently inspected. Retain the curated IPI assertion as non-core; it does not by itself establish that MUTED performs the partner's biological role. The source partner identifier is preserved. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: MUTED physically associates with BLOC1S2 in the stated interaction context. Reason: BioPlex is an affinity-purification mass-spectrometry interaction map in human cell lines. The BLOC1S2 association is consistent with BLOC-1 membership and the UniProt interaction record. The pair-level supplementary table was not independently inspected; AP-MS association need not mean direct binary contact. Retain this experimental source as non-core. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: MUTED physically associates with DTNBP1/dysbindin in the stated interaction context. Reason: BioPlex is an affinity-purification mass-spectrometry interaction map in human cell lines. The DTNBP1/dysbindin association is consistent with BLOC-1 membership and the UniProt interaction record. The pair-level supplementary table was not independently inspected; AP-MS association need not mean direct binary contact. Retain this experimental source as non-core. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: MUTED physically associates with BLOC1S2 in the stated interaction context. Reason: This study integrates protein interaction and spatial information in a multimodal human cell map. The curated BLOC1S2 association agrees with established BLOC-1 membership. Only the cached abstract and source-level assay scope were inspected, not the pair-level supporting dataset. Retain the experimental interaction as non-core without promoting generic protein binding into the mechanistic core. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: MUTED physically associates with DTNBP1/dysbindin in the stated interaction context. Reason: This study integrates protein interaction and spatial information in a multimodal human cell map. The curated DTNBP1/dysbindin association agrees with established BLOC-1 membership. Only the cached abstract and source-level assay scope were inspected, not the pair-level supporting dataset. Retain the experimental interaction as non-core without promoting generic protein binding into the mechanistic core. |
| GO:0008089 anterograde axonal transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BLOC-1 supports forward neuronal cargo delivery. Reason: PMID:21998198 directly includes FLAG-muted-containing complexes in human SH-SY5Y cells and reduced dentate-gyrus PI4KIIalpha in muted-null mice. These data support a BLOC-1 contribution to neuronal cargo sorting, rather than MUTED acting as a motor. The detailed compartmental and trafficking experiments also use other BLOC-1/AP-3 mutants; the reviewed human annotation remains an orthology-based inference. Retain this neuronal specialization as non-core. |
| GO:0008089 anterograde axonal transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BLOC-1 supports forward neuronal cargo delivery. Reason: PMID:21998198 directly includes FLAG-muted-containing complexes in human SH-SY5Y cells and reduced dentate-gyrus PI4KIIalpha in muted-null mice. These data support a BLOC-1 contribution to neuronal cargo sorting, rather than MUTED acting as a motor. The detailed compartmental and trafficking experiments also use other BLOC-1/AP-3 mutants; the reviewed human annotation remains an orthology-based inference. Retain this neuronal specialization as non-core. |
| GO:0010467 gene expression | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact mouse gene-expression donor experiment remains unresolved. Reason: The electronic source transfers mouse Q8R015/ENSMUSP00000036614. The official gene-expression definition concerns production of mature RNA or protein from genetic information. Expression of MUTED itself or altered cargo abundance does not distinguish participation in this process from trafficking, degradation or a downstream phenotype. The exact donor experiment has not been recovered; preserve the assertion as undecided without assigning an unverified study or alleging a propagation error. The assembly and cargo-sorting evidence cited here describes the established role; it is not negative evidence against an unexamined donor assay. A fresh direct QuickGO donor query was inaccessible. No specific transcription or translation mechanism is assigned. |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | MODIFY | Summary: Endosomal cargo delivery to melanosomes is the supported specific transport function. Reason: The broad vesicle-mediated transport assertion is consistent with BLOC-1 function, but the human MUTED rescue experiments resolve endosome-to-melanosome cargo transport more specifically. Refine this general annotation to GO:0035646, already present with independent source evidence, without adding a NEW row. This does not challenge the PAINT node placement or the separately retained neuronal transport roles. The structured category records only term granularity: the PAINT phylogeny and IBD node were not inspected here, and no source-annotation or propagation error is alleged. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: endosome to melanosome transport |
| GO:0030133 transport vesicle | IDA PMID:17182842 BLOC-1 is required for cargo-specific sorting from vacuolar ... | KEEP AS NON CORE | Summary: MUTED-containing BLOC-1 associates with endosomal transport carriers. Reason: The selected full text of PMID:17182842 reports reconstituted BLOC-1 in human MuHA-complemented mouse melanocytes on tubulovesicular structures (Supplementary Figure S3b/c). This is target-containing complex localization, stronger than extrapolating localization from an unrelated subunit. The supplementary images/captions were not independently inspected, and the term describes a broad vesicle class; retain the curated carrier association as non-core without claiming a separately resolved MUTED membrane topology. Supporting Evidence: |
| GO:0030133 transport vesicle | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: MUTED-containing BLOC-1 associates with endosomal transport carriers. Reason: The selected full text of PMID:17182842 reports reconstituted BLOC-1 in human MuHA-complemented mouse melanocytes on tubulovesicular structures (Supplementary Figure S3b/c). This is target-containing complex localization, stronger than extrapolating localization from an unrelated subunit. The supplementary images/captions were not independently inspected, and the term describes a broad vesicle class; retain the curated carrier association as non-core without claiming a separately resolved MUTED membrane topology. The InterPro mapping is consistent with this experimentally grounded family context; it is not an independent localization assay. Supporting Evidence: |
| GO:0031083 BLOC-1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. The target accession in the IBA WITH/FROM set is legitimate descendant experimental grounding, not circularity; the full PAINT tree was not reanalyzed. |
| GO:0031083 BLOC-1 complex | IDA PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. |
| GO:0031083 BLOC-1 complex | IDA PMID:17182842 BLOC-1 is required for cargo-specific sorting from vacuolar ... | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. |
| GO:0031083 BLOC-1 complex | IDA PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. |
| GO:0031083 BLOC-1 complex | IEA GO_REF:0000120 | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. |
| GO:0031083 BLOC-1 complex | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: MUTED is a BLOC-1 complex subunit. Reason: Endogenous complex studies and reconstitution of the human eight-subunit assembly directly support BLOC1S5 membership. The complete complex contains Muted even though the two isolated stable trimers do not. |
| GO:0031175 neuron projection development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BLOC-1 contributes to neuronal process development. Reason: The selected primary experiments in PMID:19546860 test neurite extension in pallid mouse hippocampal neurons and implicate the BLOC-1 assembly. They do not isolate a human MUTED-specific morphogenesis mechanism. The source is an explicitly orthology-based annotation and UniProt describes the complex role as proposed; retain this developmental consequence as non-core. |
| GO:0032402 melanosome transport | IDA PMID:17182842 BLOC-1 is required for cargo-specific sorting from vacuolar ... | UNDECIDED | Summary: Cargo delivery to melanosomes is supported; whole-melanosome movement is unresolved. Reason: GO:0032402 denotes directed movement of melanosomes. The inspected PMID:17182842 methods and results show Tyrp1 cargo routing, endosomal exit and pigmentation rescue by human MuHA in muted mouse melanocytes. These measurements do not themselves establish movement of whole melanosomes. The exact curator basis may involve figure or supplementary material not inspected here, so preserve this experimental assertion as undecided rather than remove it on incomplete evidence. If the annotation is intended to describe the cargo-routing assay, MODIFY to the already-present GO:0035646 would express that result. The uninspected curator basis for whole-organelle movement remains unresolved, so this proposal retains UNDECIDED. Supporting Evidence: |
| GO:0032438 melanosome organization | NAS PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | ACCEPT | Summary: BLOC-1 contributes to melanosome organization through cargo delivery. Reason: MUTED is an integral BLOC-1 subunit. Complex composition and assembly studies, together with human MUTED rescue of pigment and cargo sorting in muted melanocytes, support a role in melanosome biogenesis and organization. This is an assembly-mediated function, not evidence that MUTED catalyzes pigment synthesis. Independent PMID:32565547 selected Results show full-length human BLOC1S5 rescue of BLOC-1 stability and TYRP1 localization in muted mouse melanocytes, whereas patient-derived truncated constructs fail to rescue. |
| GO:0032438 melanosome organization | NAS PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: BLOC-1 contributes to melanosome organization through cargo delivery. Reason: MUTED is an integral BLOC-1 subunit. Complex composition and assembly studies, together with human MUTED rescue of pigment and cargo sorting in muted melanocytes, support a role in melanosome biogenesis and organization. This is an assembly-mediated function, not evidence that MUTED catalyzes pigment synthesis. Independent PMID:32565547 selected Results show full-length human BLOC1S5 rescue of BLOC-1 stability and TYRP1 localization in muted mouse melanocytes, whereas patient-derived truncated constructs fail to rescue. |
| GO:0035646 endosome to melanosome transport | IBA GO_REF:0000033 | ACCEPT | Summary: MUTED-containing BLOC-1 supports cargo delivery from endosomes to melanosomes. Reason: The inspected PMID:17182842 results directly compare muted-deficient melanocytes with human MuHA rescue and resolve altered Tyrp1 cargo routing. The 2017 correction invalidates the original transferrin-FITC control; corrected repeat experiments support a mild early recycling defect, and the central cargo-sorting conclusion is retained. The PAINT target self-entry is experimental grounding, not circularity; no unsupported challenge to PTN002838968 placement is made. Independent PMID:32565547 selected Results show full-length human BLOC1S5 rescue of BLOC-1 stability and TYRP1 localization in muted mouse melanocytes, whereas patient-derived truncated constructs fail to rescue. |
| GO:0035646 endosome to melanosome transport | IDA PMID:17182842 BLOC-1 is required for cargo-specific sorting from vacuolar ... | ACCEPT | Summary: MUTED-containing BLOC-1 supports cargo delivery from endosomes to melanosomes. Reason: The inspected PMID:17182842 results directly compare muted-deficient melanocytes with human MuHA rescue and resolve altered Tyrp1 cargo routing. The 2017 correction invalidates the original transferrin-FITC control; corrected repeat experiments support a mild early recycling defect, and the central cargo-sorting conclusion is retained. Preserve the original IDA source and do not broaden this into whole-organelle transport. Independent PMID:32565547 selected Results show full-length human BLOC1S5 rescue of BLOC-1 stability and TYRP1 localization in muted mouse melanocytes, whereas patient-derived truncated constructs fail to rescue. |
| GO:0035651 AP-3 adaptor complex binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The intact BLOC-1 complex associates with AP-3. Reason: Selected full-text Results of PMID:22203680, read from the authenticated normal-fetch full-text variant, show recombinant BLOC-1 pulling down endogenous AP-3 from MNT1 and melan-a cells with GST and GST-AP-2 controls (Figure 1D). Its canonical cache is abstract-only; the cited result comes from the separately inspected full-text variant. PMID:21998198 independently places Muted-containing complexes with AP-3 and neuronal cargo. These are intact-complex associations and do not identify an isolated MUTED–AP-3 interface. Retain the existing mouse-derived binding inference as non-core. |
| GO:0036269 swimming behavior | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The mouse swimming phenotype is consistent with a non-core vestibular consequence. Reason: The official MGI muted homozygous genotype record (MGI:3587678) attributes variable swimming impairment to J:89392, identified by MouseMine as PMID:15109702. The complete cached abstract includes muted among mouse strains studied for otoconial deficits, vestibular responses and swimming, and reports behavioral adaptation in some animals. Retain this existing human orthology inference as a non-core vestibular consequence, without asserting a direct locomotor mechanism, universal inability to swim or a human assay. The full paper and the exact current donor GO edge were not reconstructed. Indexed metadata lists an erratum in Hearing Research 194:143 (2004); its content was not verified, so no claim is made that all original measurements are unaffected. Supporting Evidence: |
| GO:0048490 anterograde synaptic vesicle transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BLOC-1 contributes to delivery of selected neuronal vesicle cargo. Reason: PMID:21998198 directly includes FLAG-muted-containing complexes in human SH-SY5Y cells and reduced dentate-gyrus PI4KIIalpha in muted-null mice. These data support a BLOC-1 contribution to neuronal cargo sorting, rather than MUTED acting as a motor. The detailed compartmental and trafficking experiments also use other BLOC-1/AP-3 mutants; the reviewed human annotation remains an orthology-based inference. The evidence concerns selected cargo supply to neurites and nerve terminals; it does not make MUTED the motor of every mature synaptic vesicle. The ancestral PAINT inference is retained without an unsupported node-placement challenge. |
| GO:0048490 anterograde synaptic vesicle transport | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BLOC-1 contributes to delivery of selected neuronal vesicle cargo. Reason: PMID:21998198 directly includes FLAG-muted-containing complexes in human SH-SY5Y cells and reduced dentate-gyrus PI4KIIalpha in muted-null mice. These data support a BLOC-1 contribution to neuronal cargo sorting, rather than MUTED acting as a motor. The detailed compartmental and trafficking experiments also use other BLOC-1/AP-3 mutants; the reviewed human annotation remains an orthology-based inference. The evidence concerns selected cargo supply to neurites and nerve terminals; it does not make MUTED the motor of every mature synaptic vesicle. Keep this specialized neuronal annotation as non-core. |
| GO:0048490 anterograde synaptic vesicle transport | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BLOC-1 contributes to delivery of selected neuronal vesicle cargo. Reason: PMID:21998198 directly includes FLAG-muted-containing complexes in human SH-SY5Y cells and reduced dentate-gyrus PI4KIIalpha in muted-null mice. These data support a BLOC-1 contribution to neuronal cargo sorting, rather than MUTED acting as a motor. The detailed compartmental and trafficking experiments also use other BLOC-1/AP-3 mutants; the reviewed human annotation remains an orthology-based inference. The evidence concerns selected cargo supply to neurites and nerve terminals; it does not make MUTED the motor of every mature synaptic vesicle. Keep this specialized neuronal annotation as non-core. |
| GO:0048840 otolith development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mouse muted phenotypes support a non-core role in otolith development. Reason: The selected primary publisher description of muted mice reports variable otolith loss with a normal bony labyrinth (https://doi.org/10.1017/S0016672300002007). Official MGI genotype and phenotype records corroborate the attribution to Bloc1s5. A historical MGI comparative GO graph generated in 2023 explicitly links mouse otolith morphogenesis to the muted allele and this paper; it is not a reconstruction of the current exact GO:0048840 transfer. The phenotype is consistent with the developmental term, so retain the existing human orthology inference as non-core without claiming a direct mineralization mechanism or human assay. The whole paper was not inspected. The normal PMID:5367369 cache contains citation metadata only, with no indexed abstract; the phenotypic detail comes from the separately read selected publisher first page, not from a newly available complete paper. Supporting Evidence: |
| GO:0050942 positive regulation of pigment cell differentiation | IDA PMID:17182842 BLOC-1 is required for cargo-specific sorting from vacuolar ... | UNDECIDED | Summary: Pigmentation rescue does not by itself distinguish pigment-cell differentiation. Reason: GO:0050942 regulates acquisition of a differentiated pigment-cell state. The inspected human MuHA rescue experiments in PMID:17182842 restore pigmentation and cargo sorting in established mouse melanocyte lines. This supports melanosome function but does not by itself resolve a differentiation process. The experimental annotation is retained as undecided because the exact curator basis, including uninspected supplementary material, is unresolved. GO:0032438 melanosome organization and GO:0035646 endosome to melanosome transport describe the established rescue phenotypes; neither by itself establishes positive regulation of pigment-cell differentiation. Supporting Evidence: |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000120 | UNDECIDED | Summary: Neuronal cargo-sorting evidence supports the pathway, but MUTED localization to axon cytoplasm remains unresolved. Reason: This combined electronic localization inference uses GO:0008089 axonal transport and GO:0048490 synaptic vesicle transport. PMID:21998198 directly detects Muted-containing complexes in human SH-SY5Y extracts and reduced neuropil cargo in muted-null mice. These results support neuronal cargo sorting, but do not measure the compartment occupied by MUTED itself. Selected Discussion describes the cell body as the most upstream sorting site and cites positive axonal localization of BLOC-1 subunits generally; it does not resolve MUTED-specific axon-cytoplasm localization. Keep this precise compartment assignment undecided without inferring that MUTED is absent from axons or rejecting the existing neuronal process annotations. Supporting Evidence: |
| GO:1990742 microvesicle | IEA GO_REF:0000107 | UNDECIDED | Summary: Extracellular microvesicle localization requires the unresolved donor experiment. Reason: GO:1990742 describes an extracellular vesicle released from the plasma membrane. The inspected PC12 protocol in PMID:21998198 mechanically homogenizes cells before vesicle fractionation; that intracellular preparation does not establish released extracellular microvesicles. Official mouse summaries list the term, but the exact donor evidence and reference remain unresolved. This does not establish that curators relied on the intracellular protocol or confused vesicle names, so preserve the transferred assertion as undecided. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which MUTED contacts support BLOC-1 assembly, and can a MUTED-specific molecular activity be separated experimentally from general octamer destabilization?
Q: Which BLOC-1-dependent cargo-sorting step fails during platelet dense-granule formation in BLOC1S5 deficiency, and does wild-type human BLOC1S5 restore that step in patient-derived megakaryocytes?
Experiment: Reconstitute BLOC-1 with defined MUTED interface variants; measure octamer integrity and membrane-cargo sorting in parallel, retaining variants with comparable protein abundance and using wild-type MUTED rescue as a control.
Hypothesis: MUTED interface variants can distinguish loss of BLOC-1 assembly from a selective cargo-sorting defect.
Type: Complex reconstitution, interaction mapping and cargo-trafficking rescue
Experiment: Compare patient-derived megakaryocytes and isogenic corrected cells for BLOC-1 stability, trafficking of established dense-granule cargos, granule maturation and released platelet granule content. Distinguish cargo delivery from granule number and stimulus-dependent secretion.
Hypothesis: Restoring BLOC1S5 rescues a specific dense-granule cargo-sorting defect in patient-derived megakaryocytes.
Type: Isogenic rescue and platelet dense-granule trafficking analysis
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