DTNBP1 encodes dysbindin, a coiled-coil subunit of the BLOC-1 complex. BLOC-1 associates with endosomal membranes and shapes tubular carriers that sort cargo toward lysosome-related organelles and other destinations. Dysbindin contributes to melanosome and platelet dense-granule biogenesis and to neuronal vesicle trafficking. It also regulates synaptic vesicle release and dopamine D2 receptor trafficking. Biallelic loss of DTNBP1 causes Hermansky-Pudlak syndrome type 7, with defects in pigmentation and platelet dense granules. Alternative protein products differ in sequence and have incompletely resolved functional specialization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001956 positive regulation of neurotransmitter secretion | ISS GO_REF:0000024 | ACCEPT | Summary: Conserved positive regulation of transmitter release. Reason: The literal mouse donor has IMP support from PMID:18504299. Sandy chromaffin cells and hippocampal neurons have altered release; acute delivery of purified mouse dysbindin rescues fusion-event kinetics and quantal size, although not release probability or total release in that interval. This supports an active regulatory contribution, not an autonomous fusion enzyme or identical effects on every release parameter. The human transfer is consistent with conserved vesicle trafficking; the experiments themselves are mouse. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0002092 positive regulation of receptor internalization | IEA GO_REF:0000107 | ACCEPT | Summary: Positive control of D2-receptor internalization in the tested cells. Reason: The rat donor record joins PMID:17989303. Dysbindin depletion in human SH-SY5Y cells and rat cortical neurons increases surface D2 receptor and impairs agonist-induced internalization, with D1 receptor controls. Mouse cortical neurons in PMID:19887632 instead show enhanced D2 recycling with little change in internalization. These context-dependent routes both support receptor-trafficking control; the latter does not negate the earlier positive internalization result or establish a universal mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER |
| GO:0005515 protein binding | IPI PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: The original human-construct Y2H study and endogenous HeLa co-IP support this pair. The co-IP records are spoke expansions of a multicomponent complex; the separate two-hybrid records are binary assay evidence, not a native affinity measurement. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | KEEP AS NON CORE | Summary: Supported association with Q8TDH9 (BLOC1S5). Reason: The original human-construct Y2H study and endogenous HeLa co-IP support this pair. The co-IP records are spoke expansions of a multicomponent complex; the separate two-hybrid records are binary assay evidence, not a native affinity measurement. MUTED/BLOC1S5 is a BLOC-1 subunit. This positive association does not by itself mean binding an intact AP-3 complex or a signaling scaffold. Retain it as non-core rather than assign another subunit's molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | KEEP AS NON CORE | Summary: Supported association with Q9UL45 (BLOC1S6). Reason: The original human-construct Y2H study and endogenous HeLa co-IP support this pair. The co-IP records are spoke expansions of a multicomponent complex; the separate two-hybrid records are binary assay evidence, not a native affinity measurement. Pallidin/BLOC1S6 is a BLOC-1 subunit that can itself bind syntaxins and actin. Those are pallidin activities, not the identity of the measured ligand. Retain the positive dysbindin–pallidin association as non-core; assess BLOC-1 membership separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17043677 Disrupted in Schizophrenia 1 Interactome: evidence for the c... | KEEP AS NON CORE | Summary: Supported association with Q9NX95 (SYBU). Reason: The genuine publisher supplementary Screen Results workbook identifies DTNBP1 bait and human FLJ20366/SYBU prey (AY705385), fetal-brain library, PBS B, five clones. In the literal IntAct record EBI-1105796 / IM-16650-62, SYBU is interactor A (prey) with no recorded feature, whereas DTNBP1 is interactor B (bait) with binding-associated region 1–189. The supplementary workbook identifies the pair and library but gives no residue boundaries, so it does not independently resolve the construct extent. The region is therefore attributed only to the DTNBP1 side of that curated record, not to SYBU. This is a positive human fragment-library Y2H observation, not a DTNBP1–DISC1 pair. SYBU/syntabulin is a kinesin-associated trafficking adaptor, not the kinesin motor itself. This positive association does not support kinesin binding by substitution of a different ligand. No more informative binding class is established for the measured adaptor, so retain it as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19349376 TRIM32 is an E3 ubiquitin ligase for dysbindin. | MODIFY | Summary: Supported association with Q13049 (TRIM32). Reason: The original selected Methods/Results include mouse-muscle-library Y2H and co-IP/ubiquitination in HEK293T cells. The human host is not treated as proof that every introduced ORF is human; the human curator assertion is preserved with that construct-species limit. TRIM32 is an E3 ubiquitin ligase, and the original study measures dysbindin association and substrate ubiquitination. Dysbindin is the substrate and binding partner, not the ligase. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20921223 Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-... | KEEP AS NON CORE | Summary: Supported association with O14980 (XPO1). Reason: The original uses human 351-aa dysbindin constructs, recombinant GST-dysbindin capture from HEK293 lysate and FLAG co-IP; endogenous N2a experiments are separate. These support association but are not a purified two-protein affinity assay. XPO1/CRM1 is the nuclear export receptor for the dysbindin NES. It is not a ligand-regulated DNA-binding nuclear receptor, so nuclear receptor binding would be misleading. Retain the experimentally supported export-receptor association as non-core; being exported does not make dysbindin an export catalyst. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: The original reports reconstitution using human proteins. The literal records include dysbindin 1–217 and multicomponent pull-down/spoke expansion; the intact-complex assay must not be represented as every isolated pair having independently measured affinity. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | KEEP AS NON CORE | Summary: Supported association with Q8TDH9 (BLOC1S5). Reason: The original reports reconstitution using human proteins. The literal records include dysbindin 1–217 and multicomponent pull-down/spoke expansion; the intact-complex assay must not be represented as every isolated pair having independently measured affinity. MUTED/BLOC1S5 is a BLOC-1 subunit. This positive association does not by itself mean binding an intact AP-3 complex or a signaling scaffold. Retain it as non-core rather than assign another subunit's molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | KEEP AS NON CORE | Summary: Supported association with Q9UL45 (BLOC1S6). Reason: The original reports reconstitution using human proteins. The literal records include dysbindin 1–217 and multicomponent pull-down/spoke expansion; the intact-complex assay must not be represented as every isolated pair having independently measured affinity. Pallidin/BLOC1S6 is a BLOC-1 subunit that can itself bind syntaxins and actin. Those are pallidin activities, not the identity of the measured ligand. Retain the positive dysbindin–pallidin association as non-core; assess BLOC-1 membership separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23414517 A human skeletal muscle interactome centered on proteins inv... | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: The genuine source describes sequenced human skeletal-muscle cDNA fragments screened in yeast. The literal pair records dysbindin 90–351 and SNAPIN 34–136. The paper's separate co-IP validation methods are not claimed as validation of this particular pair. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with A1L3X0 (ELOVL7). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. ELOVL7 is a fatty-acid elongation enzyme. The verified pair therefore supports enzyme binding; it does not assign elongase activity or fatty-acid synthesis to dysbindin. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with A1L4H1 (SSC5D). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. SSC5D is an extracellular pattern-recognition protein; screening records include a restricted 1483–1573 segment. The positive binding assertion is retained, but an extracellular-matrix ligand or signaling-receptor-specific binding mechanism is not established for this segment. Keep generic binding non-core rather than infer such a mechanism from SSC5D's other activities. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with O00560 (SDCBP). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. SDCBP/syntenin is a multifunctional scaffold/adaptor that assembles signaling and trafficking partners, including receptor-associated complexes. The verified pair supports scaffold-protein binding without assigning dysbindin a particular downstream SDCBP pathway. Proposed replacements: scaffold protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with O60941 (DTNB). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. DTNB/beta-dystrobrevin is a structural scaffold of the dystrophin-associated cytoskeletal membrane complex. Binding its verified human reference sequence supports the cytoskeletal-protein class; it does not establish a role for dysbindin in every dystrophin complex. Proposed replacements: cytoskeletal protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with P14373 (TRIM27). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. TRIM27 is a characterized E3 ubiquitin ligase. The pair supports binding that enzyme class, without showing that dysbindin is a substrate or regulator of TRIM27. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q494R4 (DRC12). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. DRC12 is a component of the axonemal nexin-dynein regulatory complex and therefore a cytoskeletal protein. The positive pair supports that partner class without assigning dysbindin ciliary motility or N-DRC membership. Proposed replacements: cytoskeletal protein binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q7Z3B3 (KANSL1). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. KANSL1 has a documented microtubule-end-associated role in spindle assembly and stability, alongside its separate noncatalytic NSL-complex function. Its cytoskeletal regulatory role supports this binding-class refinement; no histone acetyltransferase activity is attributed to either binding event. Proposed replacements: cytoskeletal regulatory protein binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q7Z4N8 (P4HA3). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. P4HA3 is the catalytic alpha subunit of procollagen prolyl 4-hydroxylase. The positive pair supports enzyme binding, not collagen hydroxylation by dysbindin. Proposed replacements: enzyme binding |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with Q8IY31 (IFT20). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. IFT20 is an intraflagellar transport-particle subunit. Membership in a transport particle is not sufficient to classify the measured partner as a motor or an integral cytoskeletal structural element. Retain the positive pair as non-core without inferring ciliary transport by dysbindin. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with Q8IYE0-2 (CCDC146). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. The literal partner is CCDC146 isoform 2, with a 372–669 interacting segment recorded in the screening entries. Its role in sperm flagellum biogenesis does not establish a more specific molecular binding class for this measured segment. Retain the positive pair and exact isoform scope as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with Q8N3L3 (TXLNB). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. TXLNB/beta-taxilin is a syntaxin-binding protein, not itself a syntaxin. The verified association is positive, but does not justify replacing the ligand with a syntaxin or inferring a SNARE-complex interaction. Keep it as non-core. This pair additionally has a positive anti-tag co-IP record (EBI-10490731), kept distinct from the two-hybrid entries. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with Q8TD31-3 (CCHCR1). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. The literal partner is CCHCR1 isoform 3, with a 90–835 interacting segment recorded in the screen. Its proposed keratinocyte proliferation/differentiation role does not make it a keratin or establish a particular molecular ligand class. Retain the positive pair as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q8WUW1 (BRK1). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. BRK1 is a WAVE regulatory-complex component involved in actin and microtubule organization. The verified pair supports binding a cytoskeletal regulatory protein, without a claim that dysbindin directly binds actin or activates Arp2/3 in this screen. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q96CS2 (HAUS1). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. HAUS1 contributes to mitotic spindle assembly and maintenance as an augmin/HAUS component. The positive pair supports binding a cytoskeletal regulatory protein, not microtubule nucleation by dysbindin. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q9BVG8 (KIFC3). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. KIFC3 is a minus-end-directed kinesin motor. The verified pair supports kinesin binding, not autonomous motor activity or a demonstrated cargo-transport direction for dysbindin. Proposed replacements: kinesin binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Supported association with Q9NUL5 (SHFL). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. SHFL is an RNA-binding regulator of programmed ribosomal frameshifting. Binding SHFL is not RNA binding or ribosome binding by dysbindin. No verified more informative binding class is established for this pair, so retain the positive assertion as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Supported association with Q9Y3C0 (WASHC3). Reason: The literal human pair has pooled-screen, array and validated-two-hybrid entries. The original requires fresh-colony pairwise retesting positive in at least three of four attempts with identity confirmation. ROGID matches the current reference sequences, not an independently reconstructed experimental insert. WASHC3 is a component of the WASH complex that regulates Arp2/3-dependent actin polymerization at endosomes. The verified pair supports cytoskeletal regulatory protein binding without transferring WASH-complex catalytic or process roles. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Supported association with O43482 (OIP5). Reason: The literal human pair is supported by pooled/array and validated-two-hybrid records. HuRI reports quadruplicate retesting and sequence confirmation; dataset-wide orthogonal validation is not asserted for every specific pair. ROGID authenticates the reference sequence, not every experimental insert. OIP5/MIS18B is a centromeric chromatin-assembly factor, not a histone or a catalytic enzyme. The positive pair is retained as non-core without converting the partner's cellular role into an unsupported molecular binding specificity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: The literal human pair is supported by pooled/array and validated-two-hybrid records. HuRI reports quadruplicate retesting and sequence confirmation; dataset-wide orthogonal validation is not asserted for every specific pair. ROGID authenticates the reference sequence, not every experimental insert. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Supported association with O95678 (KRT75). Reason: The literal human pair is supported by pooled/array and validated-two-hybrid records. HuRI reports quadruplicate retesting and sequence confirmation; dataset-wide orthogonal validation is not asserted for every specific pair. ROGID authenticates the reference sequence, not every experimental insert. KRT75 is a keratin intermediate-filament protein. The positive two-hybrid pair supports cytoskeletal protein binding; it does not establish binding to an assembled intermediate filament or a role for dysbindin in hair formation. Proposed replacements: cytoskeletal protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Supported association with Q7Z6G3-2 (NECAB2). Reason: The literal human pair is supported by pooled/array and validated-two-hybrid records. HuRI reports quadruplicate retesting and sequence confirmation; dataset-wide orthogonal validation is not asserted for every specific pair. ROGID authenticates the reference sequence, not every experimental insert. The literal partner is NECAB2 isoform 2; the records also identify a 65–303 dysbindin segment. NECAB2's signaling-scaffold role is presently phrased as putative, and its calcium binding does not show that this pair is calcium-dependent. Retain the positive pair as non-core without asserting either mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Supported association with Q9UL45 (BLOC1S6). Reason: The literal human pair is supported by pooled/array and validated-two-hybrid records. HuRI reports quadruplicate retesting and sequence confirmation; dataset-wide orthogonal validation is not asserted for every specific pair. ROGID authenticates the reference sequence, not every experimental insert. Pallidin/BLOC1S6 is a BLOC-1 subunit that can itself bind syntaxins and actin. Those are pallidin activities, not the identity of the measured ligand. Retain the positive dysbindin–pallidin association as non-core; assess BLOC-1 membership separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Supported association with Q86WT6 (TRIM69). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. TRIM69 is an E3 ubiquitin ligase. The curated positive AP-MS association supports this partner-class refinement, with indirect association still possible; it does not establish dysbindin ubiquitination or regulation by TRIM69. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association with Q8N3L3 (TXLNB). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. TXLNB/beta-taxilin is a syntaxin-binding protein, not itself a syntaxin. The verified association is positive, but does not justify replacing the ligand with a syntaxin or inferring a SNARE-complex interaction. Keep it as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association with Q8TDH9 (BLOC1S5). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. MUTED/BLOC1S5 is a BLOC-1 subunit. This positive association does not by itself mean binding an intact AP-3 complex or a signaling scaffold. Retain it as non-core rather than assign another subunit's molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Supported association with Q8WUW1 (BRK1). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. BRK1 is a cytoskeletal regulatory WAVE-complex component. The curated positive AP-MS association supports the binding class without converting co-purification into a purified binary-contact or actin-polymerization assay. Proposed replacements: cytoskeletal regulatory protein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association with Q9NX95 (SYBU). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. SYBU/syntabulin is a kinesin-associated trafficking adaptor, not the kinesin motor itself. This positive association does not support kinesin binding by substitution of a different ligand. No more informative binding class is established for the measured adaptor, so retain it as non-core. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Supported association with Q9UL45 (BLOC1S6). Reason: BioPlex reports positive human AP-MS associations in 293T/HCT116 context; the exact records are anti-tag co-IP spoke expansions. Co-purification may be indirect and is not an affinity or contact-interface measurement. Pallidin/BLOC1S6 is a BLOC-1 subunit that can itself bind syntaxins and actin. Those are pallidin activities, not the identity of the measured ligand. Retain the positive dysbindin–pallidin association as non-core; assess BLOC-1 membership separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Supported association with O95295 (SNAPIN). Reason: The paper-linked AP-MS graph contains the exact target–partner edge in human U2OS cells. The Methods use C-terminal HA–Flag baits and anti-HA purification. This is measured co-purification, not merely a shared imaging embedding and not a purified binary interface. SNAPIN is an adaptor and BLOC-1 subunit, not itself a SNARE. Binding SNAPIN cannot be relabeled SNARE binding, and no established specific binding term for this subunit is demonstrated. The positive association is retained as non-core under the project instruction; BLOC-1 membership is assessed separately. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Supported association with Q86WT6 (TRIM69). Reason: The paper-linked AP-MS graph contains the exact target–partner edge in human U2OS cells. The Methods use C-terminal HA–Flag baits and anti-HA purification. This is measured co-purification, not merely a shared imaging embedding and not a purified binary interface. TRIM69 is an E3 ubiquitin ligase. The genuine U2OS AP-MS graph contains the target pair; this supports the informative ligase-binding class while preserving possible indirect association and avoiding a substrate claim. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Supported association with Q8TDH9 (BLOC1S5). Reason: The paper-linked AP-MS graph contains the exact target–partner edge in human U2OS cells. The Methods use C-terminal HA–Flag baits and anti-HA purification. This is measured co-purification, not merely a shared imaging embedding and not a purified binary interface. MUTED/BLOC1S5 is a BLOC-1 subunit. This positive association does not by itself mean binding an intact AP-3 complex or a signaling scaffold. Retain it as non-core rather than assign another subunit's molecular activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Supported association with Q9UL45 (BLOC1S6). Reason: The paper-linked AP-MS graph contains the exact target–partner edge in human U2OS cells. The Methods use C-terminal HA–Flag baits and anti-HA purification. This is measured co-purification, not merely a shared imaging embedding and not a purified binary interface. Pallidin/BLOC1S6 is a BLOC-1 subunit that can itself bind syntaxins and actin. Those are pallidin activities, not the identity of the measured ligand. Retain the positive dysbindin–pallidin association as non-core; assess BLOC-1 membership separately. Supporting Evidence: |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A supported nuclear pool is context- and product-dependent. Reason: The UniProt location source is positive. Independent endogenous human SH-SY5Y imaging and nuclear/cytoplasmic fractionation in PMID:19142223, and human-construct shuttling experiments in PMID:20921223, support a nuclear pool. Historical A/B constructs enter nuclei more readily than the N-terminally truncated C construct; that naming is not used to remap modern accessions without sequence evidence. Nuclear localization is retained as contextual, not inferred to be the location of every BLOC-1 activity. PMID:21390302 has the figure-specific limitations described in PMID:38507352 and is not the sole support. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0191 SUPPORTS TRANSFER |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The ortholog-derived nuclear localization has independent human support. Reason: The current mouse donor records cite PMID:11316798 for nuclear localization; the original is available here only at abstract level, so its exact imaging construct is not reconstructed. Endogenous human nuclear fractionation in PMID:19142223 and shuttling experiments in PMID:20921223 independently support the biological location. Retain the contextual nuclear pool without claiming that the donor paper measured the same human product or that all isoforms share its distribution. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Broad cytoplasmic localization encompasses multiple demonstrated pools. Reason: The combined InterPro/UniProt mapping is consistent with diffuse cytoplasmic staining, a soluble cytosolic BLOC-1 pool and membrane-associated pools. Human SH-SY5Y fractionation and human HeLa membrane/cytosol experiments support this breadth. A cytosol-only replacement would discard the membrane-associated component; an exhaustive list is not established for every tissue or natural product. Retain the broad contextual annotation, while the more precise source-supported locations are reviewed separately. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR007531 SUPPORTS TRANSFER UniProtKB-SubCell:SL-0086 SUPPORTS TRANSFER |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The mouse-derived cytoplasmic pool is biologically supported. Reason: The literal mouse donor cites PMID:11316798, whose accessible abstract describes sarcolemmal co-localization and brain axon bundles and terminals; it does not establish widespread cytoplasmic distribution. Its complete imaging methods remain unavailable here. Independent human SH-SY5Y immunostaining and fractionation in PMID:19142223 and endogenous HeLa complex recovery in PMID:16837549 support cytoplasmic pools. Retain the broad contextual location without treating the historical mouse source as a map of every human compartment. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: PMID:19142223 endogenous dysbindin-1 was unambiguously localized to both the nuclear and cytosolic fractions |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000044 | MODIFY | Summary: The supported ER association is localized to the ER membrane. Reason: The UniProt source explicitly transfers ER localization by similarity. The recovered PMID:16980328 original localizes neuronal-cell-body immunoreactivity mainly to ER and Golgi membranes by mouse and macaque immunoelectron microscopy; it does not show equivalent human ultrastructure. ER membrane is therefore the supported refinement of this conserved membrane-associated pool. The 2023 correction supplies corrected figures and states that the study conclusions remain supported; no new correction-figure pixels were inspected. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0095 SUPPORTS TRANSFER Proposed replacements: endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog evidence supports an ER-membrane pool. Reason: The current mouse IDA donor is PMID:16980328. Its actual Methods and Results distinguish mouse/macaque ultrastructure from human autopsy fractionation and describe ER-membrane labeling in neuronal cell bodies. Retain this conserved contextual location; no human ER-specific microscopy or obligatory role at the ER is asserted. PMID:37070456 corrects figure presentation with an editor-supported overall conclusion, rather than retracting the localization study. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0005829 cytosol | TAS Reactome:R-HSA-429815 | ACCEPT | Summary: Cytosolic dysbindin participates in the BLOC-1 trafficking machinery. Reason: The Reactome event resolves to physical entity R-HSA-429819, reference Q96EV8 residues 1–351 in cytosol. Endogenous human HeLa experiments independently recover dysbindin-containing BLOC-1 in cytosol and on membranes. This supports a soluble recruitment pool; it does not imply that all BLOC-1 is cytosolic or transfer every label from the historical Reactome complex to the contemporary subunit composition. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A conserved plasma-membrane-associated pool is contextual. Reason: The literal plasma-membrane IBD at PTN002702071 lies on the verified human target path and is grounded in mouse Dtnbp1 evidence, including the muscle sarcolemmal context of PMID:11316798. That positive pool is not invalidated by the little presynaptic plasma-membrane labeling in the separate neuronal study PMID:16980328. Retain the broad inherited location as contextual; no universal plasma-membrane residence or automatic equivalence between neuronal and muscle compartments is inferred. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0008089 anterograde axonal transport | ISS GO_REF:0000024 | ACCEPT | Summary: Dysbindin contributes to selective anterograde axonal cargo trafficking. Reason: The literal mouse donor is PMID:21998198. Its BLOC-1/AP-3/PI4KII experiments show selective loss of PI4KII from neuronal processes and retention in cell bodies, with cargo controls and distinct mouse neuronal versus rat PC12 assays. Dysbindin supplies a component of cargo-sorting/trafficking machinery; it is not a motor. The participation claim is supported by complex association and selective cargo redistribution, not only by a general neuronal phenotype. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0009966 regulation of signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved signaling regulation is broader than a single measured receptor pathway. Reason: The literal IBD is at PTN001046036 on the verified target path; its source is rat RGD:1590759, whose current records include experimental D2-signaling regulation. The ancestral placement is not rejected because it is deep or has one named donor. Human and rat D2 trafficking/signaling assays support regulation, while other nuclear and cytoskeletal contexts prevent treating a D2-only replacement as an exhaustive account of this broad inherited claim. Retain the broad term as non-core, with the specific D2 rows assessed separately. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001046036 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0010008 endosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Dysbindin-containing BLOC-1 associates with endosomal membranes. Reason: The UniProt location mapping is corroborated by endogenous human MNT-1 anti-dysbindin immunogold localization to transferrin-loaded endosomal tubules in PMID:16837549. The same study distinguishes the tubules from AP-3-rich buds and supports soluble and membrane-associated pools. This is membrane association, not a claim that dysbindin spans the bilayer. The independent BLOC-1 trafficking experiments in PMID:17182842 require its PMID:28137951 correction to the transferrin control. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0100 SUPPORTS TRANSFER |
| GO:0010628 positive regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Nuclear dysbindin can positively affect gene expression in tested models. Reason: The mouse donor joins PMID:20921223. That original tests a human SYN1 promoter reporter in mouse N2a cells, endogenous SynI expression, dysbindin depletion and engineered nuclear-export/localization constructs, alongside rat neuronal experiments. The positive expression effect is retained as contextual. Promoter association is reported through a supplement not recovered here, and these results do not establish dysbindin as an autonomous DNA-binding transcription factor or justify a distinct transcriptional molecular-function core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0014059 regulation of dopamine secretion | ISS GO_REF:0000024 | UNDECIDED | Summary: The secretion-specific donor claim remains unresolved. Reason: The literal mouse donor for this term cites PMID:19887632. Its recovered main Methods/Results directly establish D2-receptor surface trafficking and neuronal excitability; a dopamine-release measurement was not recovered in the selected original or available supplement material. This is an access/claim-resolution gap, not evidence that the curator cited the wrong study. Preserve the original assertion and leave the narrower dopamine-secretion claim undecided rather than substitute receptor trafficking or infer secretion from excitability. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q91WZ8 UNRESOLVED Supporting Evidence: |
| GO:0014069 postsynaptic density | IDA PMID:16980328 Dysbindin-1 is a synaptic and microtubular protein that bind... | ACCEPT | Summary: Human fractionation and ortholog ultrastructure support postsynaptic-density localization. Reason: PMID:16980328 directly reports dysbindin in human hippocampal PSD fractions at variable low-to-moderate levels and separately uses mouse/macaque immunoelectron microscopy to localize postsynaptic labeling to PSDs and microtubules. Human autopsy tissue was not used for the ultrastructural claim. PMID:37070456 corrects reused/edited figure presentation and provides corrected panels; the editors state that the study results remain supported. This positive annotation is retained with that correction disclosed. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000044 | ACCEPT | Summary: The curated postsynaptic-density pool has independent support. Reason: The UniProt location assertion is supported by human hippocampal fractionation in PMID:16980328 and its correction PMID:37070456. PMID:21390302 additionally reports product-dependent human fractionation, but PMID:38507352 leaves unresolved similarities in its Figure 5A PSD95 and synaptophysin marker blots. Retain the independently corroborated PSD location without treating those disputed fraction-purity panels as conclusive evidence of exact natural-product partitioning. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0297 SUPPORTS TRANSFER |
| GO:0015630 microtubule cytoskeleton | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA supports a microtubule-associated cellular pool. Reason: The exact HPA target ENSG00000047579/Q96EV8 has an Enhanced microtubule-cytoskeleton observation, with HPA028053/HPA029615 records in A-431, U-2 OS and U-251 MG as recorded. The separate midbody observation is Approved, not Enhanced; aggregate reliability is not copied to every location. These metadata and captions were inspected without image-pixel interpretation. Keep the microtubule pool as contextual; localization does not establish microtubule binding, polymerization catalysis or a new motor function. Supporting Evidence: https://www.proteinatlas.org/ENSG00000047579-DTNBP1/subcellular |
| GO:0030036 actin cytoskeleton organization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Dysbindin can influence actin-dependent neuronal morphology. Reason: The current mouse donor cites PMID:16980328, whose recovered source primarily establishes localization and discusses possible cytoskeletal effects; it should not be described as a direct actin-polymerization experiment. Independent PMID:20531346 shows dysbindin/Abi1-dependent enhancement of actin polymerization with a cell-immunopurified WAVE2 complex and altered neuronal morphology. The minimal purified WAVE2 fragment did not reproduce the enhancement. Keep the supported contextual process, not an autonomous actin-nucleator claim. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0030424 axon | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat neuronal experiments support an axonal pool. Reason: The rat source joins PMID:20531346, which localizes dysbindin in cultured neurons and distinguishes neurites, cell bodies and spine morphology. This supports conserved axonal localization but is not a direct assay of every human product. Retain the anatomical pool as contextual to trafficking; do not infer motor activity from presence in axons. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0030424 axon | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse localization supports a conserved axonal pool. Reason: The mouse donor includes PMID:11316798 and PMID:16980328. The latter recovered original separately identifies axonal terminals and microtubule-associated axonal profiles in mouse/macaque tissue; its human material provides neuropil and subcellular-fraction evidence, not the same ultrastructural experiment. Retain axonal localization with the correction PMID:37070456 and these organism boundaries. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0030426 growth cone | ISS GO_REF:0000024 | UNDECIDED | Summary: The exact growth-cone donor experiment is not reconstructed. Reason: The matching mouse growth-cone IDA record cites PMID:16980328. The recovered operative source windows establish axonal, synaptic and dendritic localization but do not resolve that specific growth-cone assay. PMID:19428785 independently reports growth-cone localization in cultured neurons at abstract level; its full Methods and exact culture/construct species were not recovered. These are positive curator/source signals, not grounds for removal, but the specific transfer remains undecided rather than conflating a growth cone with any axonal terminal. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q91WZ8 UNRESOLVED |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | MODIFY | Summary: Specific membrane-associated vesicle pools refine the broad mapping. Reason: The UniProt cytoplasmic-vesicle-membrane assertion can be represented by independently supported endosome, synaptic-vesicle and melanosome membrane pools. PMID:16837549 directly localizes endogenous human dysbindin on endosomal membranes and occasionally on the melanosomal limiting membrane; PMID:16980328 combines human synaptic fractionation with ortholog membrane ultrastructure. The current typed ontology places all three beneath cytoplasmic vesicle membrane. These are complementary observed locations, not an assertion that all products occur on every vesicle or that the protein is transmembrane. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: UniProtKB-SubCell:SL-0089 SUPPORTS TRANSFER |
| GO:0030672 synaptic vesicle membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited synaptic-vesicle membrane association is supported. Reason: PTN002702071 and its exact synaptic-vesicle-membrane IBD are on the authenticated target path. Human target evidence is legitimately included among the descendant sources, not circular support. PMID:16980328 provides human vesicle-fraction enrichment and mouse/macaque membrane-localized immunolabeling, while rat PMID:19428785 provides an independent curated donor. Retain this association with the 2023 correction and without universalizing the later product-specific fractionation study affected by PMID:38507352. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0030672 synaptic vesicle membrane | IDA PMID:16980328 Dysbindin-1 is a synaptic and microtubular protein that bind... | ACCEPT | Summary: The original supports a synaptic-vesicle-associated membrane pool. Reason: PMID:16980328 reports strong human hippocampal synaptic-vesicle-fraction enrichment. Its mouse/macaque ultrastructure places immunolabel on or near vesicle membranes, with little labeling at the presynaptic plasma membrane. These complementary assays support the term; the ultrastructural evidence is not mislabeled human. The corrected figure presentation in PMID:37070456 is disclosed, with the editor-supported overall result retained. |
| GO:0030672 synaptic vesicle membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic transfer is consistent with the demonstrated vesicle-membrane pool. Reason: The combined source contains rat Dtnbp1 and UniProt SL-0260. The rat direct record cites PMID:19428785, whose abstract reports presynaptic localization and AP-3-associated vesicular biology but whose complete Methods are unavailable here. Independent human fractionation plus ortholog ultrastructure in PMID:16980328 supports the location at gene level. Retain the electronic inference without inventing the rat paper’s exact topology or assigning it to all natural products. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER UniProtKB-SubCell:SL-0260 SUPPORTS TRANSFER |
| GO:0030672 synaptic vesicle membrane | ISS GO_REF:0000024 | ACCEPT | Summary: The rat-derived vesicle-membrane annotation has independent human support. Reason: The literal rat donor is an IDA assertion to PMID:19428785. Its full experimental detail is not recovered, so that curator assertion is preserved rather than contradicted from the abstract. Human synaptic-vesicle fractionation and separate mouse/macaque membrane immunolabeling in PMID:16980328 independently support the conserved location. No specific human isoform or transmembrane topology is inferred. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER |
| GO:0031083 BLOC-1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: BLOC-1 membership is experimentally grounded and phylogenetically coherent. Reason: The exact BLOC-1 IBD at PTN002702071 lies on the human path, with both mouse and human descendant evidence. Human biochemical complex recovery and recombinant complex assembly establish membership; the target in WITH/FROM is expected grounding, not circularity. The source studies use different full-length and truncated constructs and do not establish equivalent complex incorporation by all three current products. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0031083 BLOC-1 complex | IDA PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | ACCEPT | Summary: The original establishes dysbindin as a BLOC-1 subunit. Reason: The recovered primary Methods and Results use human full-length dysbindin constructs, endogenous HeLa complex immunoprecipitation and distinct bovine tissue preparations. These support membership and multiple subunit associations. The DTNBP1 DNA-binding-domain fusion autoactivated the reporter, so the usable two-hybrid orientation is distinguished from that negative control; neither host nor antibody species is substituted for the construct species. Supporting Evidence: |
| GO:0031083 BLOC-1 complex | IDA PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: Reconstitution and structural analysis support BLOC-1 membership. Reason: PMID:22203680 uses recombinant human BLOC-1 components expressed in bacteria, including dysbindin residues 1–217 in the intact reconstituted assembly. Structural/subcomplex data place dysbindin with SNAPIN and BLOS2. The isolated core is described as residues 48–140 in Methods and 47–140 in Results; that source discrepancy is retained. This demonstrates subunit organization, not complete native-product equivalence or an independent enzymatic activity. Supporting Evidence: |
| GO:0031083 BLOC-1 complex | IPI PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: The interaction-based BLOC-1 membership assertion is supported. Reason: The human recombinant assembly and subcomplex association in PMID:22203680 directly support dysbindin incorporation into BLOC-1. The intact-complex AP-3 pull-down is not relabeled an isolated dysbindin–AP-3 binding assay. Membership and the source construct limitations remain explicit, including the truncated dysbindin used for the reconstituted complex. Supporting Evidence: |
| GO:0031175 neuron projection development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved effects on neuronal projections are contextual. Reason: The exact projection-development IBD at PTN002702071 is positively reconstructed; human target inclusion is legitimate descendant evidence. Mouse BLOC-1 deficiency and the dysbindin/Abi1/WAVE2 perturbation/rescue study support neuronal morphology, while not every BLOC-1 experiment perturbs DTNBP1 specifically. Retain this developmental consequence as non-core, with actual complex-level versus target-level experiments distinguished and no inferred autonomous growth program. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0031175 neuron projection development | IDA PMID:16980328 Dysbindin-1 is a synaptic and microtubular protein that bind... | KEEP AS NON CORE | Summary: Projection development is supported contextually, with source limits. Reason: The imported IDA assertion is preserved. PMID:16980328 principally demonstrates synaptic/microtubular localization and discusses possible developmental mechanisms; it should not be redescribed as a neurite perturbation/rescue study. Independent PMID:20531346 provides target perturbation and rescue in neuronal morphology, and PMID:19546860 provides BLOC-1-level neurite evidence. These support retaining the biological process as contextual without overstating the assay performed by the original source. |
| GO:0032438 melanosome organization | NAS PMID:15102850 Identification of snapin and three novel proteins (BLOS1, BL... | ACCEPT | Summary: Dysbindin contributes structurally to melanosome trafficking machinery. Reason: The NAS source establishes BLOC-1 membership and biochemical organization rather than directly assaying each melanosome-biogenesis step. Independent endogenous human endosomal/melanosomal localization, BLOC-1 cargo-sorting experiments and human HPS7 genetics support participation through the complex’s trafficking role. This is structural machinery, not a melanosome cargo merely consumed by the process. The main BLOC-1 rescue experiments are mostly other-subunit mouse deficiencies; the transferrin-control correction is preserved. |
| GO:0032438 melanosome organization | NAS PMID:22203680 Assembly and architecture of biogenesis of lysosome-related ... | ACCEPT | Summary: BLOC-1 structural participation supports melanosome organization. Reason: PMID:22203680 establishes organization of the recombinant human complex, not a new cell-based melanosome assay. Together with the independent trafficking and HPS7 evidence, it supports the existing NAS process assertion through dysbindin’s structural role in BLOC-1. Intact-complex membrane/cargo interactions are not assigned wholesale to an isolated dysbindin fragment, and the corrected transferrin result from PMID:28137951 is not described as unchanged recycling. |
| GO:0033162 melanosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: A small endogenous human melanosomal limiting-membrane pool is observed. Reason: PMID:16837549 reports anti-dysbindin immunogold in human MNT-1 cells: most signal is on nearby tubulovesicular elements, but 23 of 211 counted particles are on the melanosomal limiting membrane. That directly supports the curated membrane location without claiming it is the predominant pool or that every natural product was separately resolved. It is distinct from simply being adjacent to melanosomes. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0160 SUPPORTS TRANSFER |
| GO:0042383 sarcolemma | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sarcolemmal association is a supported muscle context. Reason: The literal mouse IDA donor cites PMID:11316798, whose abstract describes sarcolemmal localization and dystrobrevin association. Its full target-specific Methods remain unavailable here, so no direct human tissue or precise natural-product claim is manufactured. Retain the conserved muscle localization as contextual; the central BLOC-1 trafficking mechanism does not invalidate a muscle-associated pool. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0043005 neuron projection | IBA GO_REF:0000033 | MODIFY | Summary: Axonal and dendritic pools refine the inherited neuron-projection location. Reason: The exact PTN002702071 IBD is on the verified human lineage, with mouse, rat and human descendant grounding. The original human neuropil/fractionation and separate mouse/macaque ultrastructure in PMID:16980328, together with rat neuronal experiments in PMID:20531346, support both axon and dendrite. The current typed graph places both beneath neuron projection. Both are retained, rather than selecting one or adding nested dendritic-spine coverage as a redundant replacement. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The original broad term is refined to the supported location set without alleging a source identity error. |
| GO:0043005 neuron projection | IDA PMID:16980328 Dysbindin-1 is a synaptic and microtubular protein that bind... | MODIFY | Summary: The demonstrated projection pools include axons and dendrites. Reason: PMID:16980328 distinguishes human neuropil and synaptic-fraction evidence from mouse/macaque ultrastructural localization to axonal terminals and dendritic shafts/spines. Axon and dendrite therefore refine the broad location without pretending that every imaging panel is human or every product is resolved. The linked correction PMID:37070456 is retained; it changes figure presentation, not the editors’ assessment of the overall localization result. |
| GO:0043025 neuronal cell body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A neuronal-cell-body pool is observed in the donor context. Reason: The rat donor joins PMID:20531346, with neuronal immunostaining and cytoskeletal/morphology assays. The body pool is also compatible with the separate neuronal localization in PMID:16980328 and selective cargo retention assays in PMID:21998198. Retain this anatomical context without equating cargo accumulation in a dysbindin-deficient cell body with dysbindin’s own localization or treating it as an exclusive site of action. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER |
| GO:0043197 dendritic spine | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Rat neurons support a contextual dendritic-spine pool. Reason: The literal rat source is PMID:20531346. Its localization and dysbindin perturbation/rescue experiments support spine-associated dysbindin and morphology regulation, while the human rescue construct does not convert the rat localization experiment into a human tissue observation. Retain the precise anatomical location as non-core without extrapolating the distribution to every current natural product. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0043197 dendritic spine | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog ultrastructure supports dendritic-spine localization. Reason: The mouse donor cites PMID:16980328. The recovered original locates postsynaptic label on PSDs and microtubules of dendritic shafts and spines in mouse/macaque tissue; human evidence in that paper is fractionation and light-level neuropil. Retain the conserved spine pool and linked correction without claiming direct human spine ultrastructure or that this is the sole subcellular location. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0045211 postsynaptic membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The curated postsynaptic-membrane pool is retained with product limits. Reason: UniProt distinguishes historical product-dependent postsynaptic membrane/density localization. The label is not silently replaced by PSD because those are distinct component assertions. PMID:16980328 gives independent ortholog dendritic membrane/PSD observations, while PMID:21390302 has unresolved Figure 5A fraction-marker concerns documented in PMID:38507352. Retain the positive contextual membrane assertion without treating uncertain marker purity as definitive topology or assigning all modern products the same pool. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0219 SUPPORTS TRANSFER Supporting Evidence: file:human/DTNBP1/DTNBP1-uniprot.txt |
| GO:0048490 anterograde synaptic vesicle transport | IBA GO_REF:0000033 | ACCEPT | Summary: The inherited anterograde vesicle-trafficking role is supported. Reason: PTN002702071 and the exact anterograde-synaptic-vesicle-transport IBD are on the authenticated target path. The current mouse experimental donor joins PMID:21998198, which shows selective neuronal cargo targeting by BLOC-1/AP-3 machinery. This is participation in vesicle cargo trafficking; no motor ATPase or movement of every synaptic vesicle is claimed. The conserved structural role is supported independently of the number of donor genes. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. Supporting Evidence: |
| GO:0048490 anterograde synaptic vesicle transport | ISS GO_REF:0000024 | ACCEPT | Summary: Mouse BLOC-1 experiments support selective anterograde synaptic cargo trafficking. Reason: The mouse donor cites PMID:21998198. Dysbindin-containing trafficking complexes associate with AP-3/PI4KII, and BLOC-1 deficiencies selectively redistribute PI4KII away from neurites with cargo controls. Rat PC12 FRAP and mouse neuron experiments are kept distinct. Preserve the existing process through the organizing machinery, not through a claim that dysbindin itself walks on microtubules or that all source phenotypes are target-specific knockouts. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0048812 neuron projection morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Projection-shape regulation is a supported neuronal context. Reason: The imported mouse source cites PMID:16980328, whose localization and discussion do not by themselves measure a morphology-control mechanism. Independent PMID:20531346 tests dysbindin depletion and rescue and finds altered neurite/spine morphology, with Abi1/WAVE2-dependent actin effects. Retain the biological context while separating the source’s localization hypothesis from the later functional experiments; no autonomous cytoskeletal polymerase is implied. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q91WZ8 SUPPORTS TRANSFER |
| GO:0060041 retina development in camera-type eye | IEA GO_REF:0000107 | UNDECIDED | Summary: Developmental expression does not resolve the retina-process claim. Reason: The rat source joins an IEP record citing PMID:23954924. The available authentic abstract describes developmental dysbindin expression in Müller cells and retinal tissue, but the full functional experiments could not be accessed. This does not establish that the annotation is wrong, nor does expression timing alone identify a performed developmental step. Preserve the source assertion as undecided pending the full target-specific evidence. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q5M834 UNRESOLVED ensembl:ENSRNOP00000091788 UNRESOLVED Supporting Evidence: |
| GO:0060155 platelet dense granule organization | IBA GO_REF:0000033 | ACCEPT | Summary: Dysbindin contributes to platelet dense-granule biogenesis through BLOC-1. Reason: The exact dense-granule-organization IBD at PTN002702071 is positively reconstructed. Its mouse grounding includes sandy platelet granule/serotonin defects in PMID:1936982, with DTNBP1 identity and human HPS7 dense-granule deficiency established in PMID:12923531. BLOC-1’s structural trafficking role supplies a participation mechanism rather than treating deficiency alone as proof of catalysis. The human clinical genetics and mouse molecular/complex experiments are not conflated. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. |
| GO:0060159 regulation of dopamine receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: D2-receptor trafficking controls downstream dopamine signaling. Reason: The rat donor has direct PMID:17989303 support. Dysbindin depletion changes D2 surface abundance/internalization and agonist-induced CREB phosphorylation, with haloperidol sensitivity and D1 controls; human SH-SY5Y and rat cortical-neuron assays are separately identified. This supports signaling regulation through receptor trafficking, not dysbindin as a dopamine receptor, kinase or dopamine-synthesis enzyme. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0060159 regulation of dopamine receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: The ortholog-based D2-signaling regulation is supported. Reason: The literal rat donor is the PMID:17989303 receptor-trafficking/signaling study. Its functional readouts support a performed regulatory role through D2 handling. Mouse PMID:19887632 finds enhanced receptor recycling rather than the same internalization defect, illustrating context-dependent trafficking routes while preserving the broader signaling-control interpretation. No unmeasured direct receptor-binding mechanism is added. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER |
| GO:0061002 negative regulation of dendritic spine morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Dysbindin restrains abnormal spine elongation in the tested neuronal context. Reason: PMID:20531346 supports the rat transfer with depletion/rescue and Abi1/WAVE2 experiments. Loss produces longer, thinner, less mature protrusions; the density trend is not treated as a significant change. The negative-regulation term is retained for restraint of excessive shape change, not recast as inhibition of all spine formation or maturation. The minimal purified WAVE2-fragment assay was negative, whereas the cell-derived full complex showed the reported actin-polymerization enhancement. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER Supporting Evidence: |
| GO:0061646 positive regulation of glutamate neurotransmitter secretion in response to membrane depolarization | IEA GO_REF:0000107 | ACCEPT | Summary: Dysbindin positively regulates depolarization-evoked glutamatergic release. Reason: The literal rat donor cites PMID:15345706, whose authentic abstract reports dysbindin-dependent glutamate release and synaptic protein effects. Full target-specific Methods are not available here, so the species/construct details beyond the curated donor record are not invented. Independent mouse release experiments in PMID:18504299 support the same biological direction. Retain the curator-grounded function without equating altered transcript abundance with the release measurement or assigning a catalytic release activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q5M834 SUPPORTS TRANSFER ensembl:ENSRNOP00000091788 SUPPORTS TRANSFER |
| GO:1904115 axon cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: The logical axonal-cytoplasm inference is consistent with trafficking evidence. Reason: The supplied electronic sources are the accepted axonal-transport and synaptic-vesicle-transport process terms. The source relationship is retained as a deterministic inference, corroborated by actual axonal dysbindin localization and cargo-trafficking experiments. It does not distinguish soluble from membrane-associated protein within axons, and no such topology or motor activity is inferred from this broad compartment. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0008089 SUPPORTS TRANSFER GO:0048490 SUPPORTS TRANSFER |
| GO:2000300 regulation of synaptic vesicle exocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Dysbindin actively regulates synaptic-vesicle exocytosis. Reason: The precise IBD at PTN002702071 follows the verified human lineage and has current mouse experimental grounding in PMID:18504299. Single-event measurements and acute purified-protein delivery distinguish dysbindin-dependent fusion kinetics/quantal size from slower or unrescued changes in release probability and vesicle populations. Retain the conserved regulatory process without claiming dysbindin is a SNARE or that the experiment proves an autonomous membrane-fusion activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002702071 SUPPORTS TRANSFER The exact ancestral IBD and human descent path are saved; current descendant records are distinguished from direct experimental evidence. The positive claim is retained with the organism, construct and contextual limits stated in the reason. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which regions of dysbindin contact membranes or support bending within assembled BLOC-1, and are the three sequence-authenticated natural products equivalent in that role?
Q: Which molecular partners account for acute release-kinetics rescue versus slower effects on vesicle populations and dopamine receptor trafficking?
Q: Can independent endogenous product-specific measurements resolve nuclear and synaptic distributions without relying on the disputed fraction-marker blots?
Q: What original experiments support the exact dopamine-secretion, growth-cone and retina-development donor assertions that remain unresolved?
Experiment: Reconstitute BLOC-1 with each sequence-authenticated natural dysbindin product and matched truncation controls; measure incorporation, membrane binding and tubulation separately.
Experiment: Compare acute dysbindin restoration with longer rescue in the same neuronal system, measuring release kinetics, vesicle number and receptor recycling with independent controls.
Experiment: Use validated endogenous product-specific tagging or targeted proteomics with independent compartment markers and release uncropped source images.
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