EXOC6B (Sec15B) is a component of the exocyst, a conserved multisubunit complex that brings transport vesicles into contact with the plasma membrane before docking and fusion. Through this complex, EXOC6B contributes to intracellular protein delivery, Golgi-to-plasma-membrane transport and exocytosis. Biallelic loss-of-function variants cause spondylo-epi-metaphyseal dysplasia with joint laxity type 3, and shortened primary cilia occur in EXOC6B-deficient patient fibroblasts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000145 exocyst | IBA GO_REF:0000033 | ACCEPT | Summary: EXOC6B is a conserved Sec15-family subunit of the exocyst. Reason: Human EXOC6B belongs to the conserved exocyst complex. The PANTHER v19 target PTN002489451 descends from the asserted PTN000294823; the aligned sequence matches the 811-residue product and no target-path NOT is present. Yeast Sec15 coassembly (PMID:7615633), Dictyostelium complex recovery (PMID:22323285) and mammalian Sec15B/KIAA0919 peptide identification (PMID:11406615) support this ancestral placement. UniProt CC:FUNCTION/SUBUNIT independently records complex membership. The source guide retains the species, sequence and access details; this assignment does not specify identical functions of alternative products or a particular Rab-binding interaction. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000294823 SUPPORTS TRANSFER Actual target ancestry, current exocyst IBD and MSA checked; no target-path NOT. SGD:S000003202 SUPPORTS TRANSFER Yeast Sec15 is recovered with tagged Sec8 and other exocyst subunits in the actually read original PMID:7615633. dictyBase:DDB_G0293936 SUPPORTS TRANSFER Actual PMID:22323285 reports Dictyostelium Sec15 assembly/localization with exocyst components. Supporting Evidence: GO_REF:0000033 file:human/EXOC6B/EXOC6B-uniprot.txt |
| GO:0000145 exocyst | NAS PMID:22420621 Exorcising the exocyst complex. | ACCEPT | Summary: The review supports conserved exocyst membership, corroborated by primary Sec15B identification. Reason: PMID:22420621 describes the conserved eight-subunit exocyst and its Sec15 component. It is a multispecies review, not an EXOC6B-specific human experiment. The independently read mammalian original PMID:11406615 identifies a 92-kDa sheep brain exocyst band by peptide mass mapping to human KIAA0919/BAA76763 and explicitly distinguishes Sec15B from Sec15A (Table I and KIAA0919 Results). The valid target-specific PAINT placement and conserved assembly experiments reinforce complex membership. Neither the RalA pull-down of the assembled complex nor the generic name Sec15 establishes purified direct binding of human EXOC6B to RalA or Rab11. Supporting Evidence: GO_REF:0000033 file:human/EXOC6B/EXOC6B-uniprot.txt |
| GO:0000281 mitotic cytokinesis | NAS PMID:22420621 Exorcising the exocyst complex. | UNDECIDED | Summary: Human Sec15 participation in cytokinesis is positive, but its EXOC6B attribution remains unresolved. Reason: The cited review discusses mammalian exocyst recruitment to the midbody and cites PMID:16213214. That original is now accessible as a reproduced Cell article in a thesis: a human-testis two-hybrid screen recovered a sec15 clone, Sec15 immunofluorescence marks the HeLa midbody (Figure 3A5), and Results p. 81 reports cytokinesis defects after Sec15 depletion as data not shown. The inspected main Methods/Results do not provide the recovered clone accession or a Sec15A-versus-Sec15B distinction; the antibody is referred to Yeaman 2003 and the listed siRNA coordinates cover Sec5, Sec8 and snapin rather than Sec15. Thus there is meaningful human Sec15/exocyst process evidence, but the specific link to EXOC6B is not established by this read. This is an attribution uncertainty, not an assertion that cytokinesis is false, that full text is absent, or that every exocyst subunit must itself sever the membrane. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | KEEP AS NON CORE | Summary: EXOC6B associates with EXOC5 in human-cell tandem-affinity purifications. Reason: The actual PMID:27173435 Methods describe human constructs expressed in HEK293T and SF-TAP purification of associated complexes. Supplementary Data 2 rows 18414–18415 recover EXOC6B with EXOC5 bait; rows 18915–18918 recover EXOC5 with EXOC6B bait. Data 3 row 11 retains the significant scored pair. Data 1 row 85 encodes an EXOC6B insert exactly matching the current 811-residue sequence, while row 84 encodes that sequence without its initial methionine in the N-terminally tagged construct. These are positive associations in cellular assemblies, not purified binary affinity measurements. Retain the supported generic interaction as non-core; exocyst membership and contribution to complex tethering activity are distinct claims, and the experiment does not define a more specific molecular activity for this pair or establish the 672-residue product. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Human ORFeome EXOC6B and the specified SHTN1 product interact in the HuRI yeast two-hybrid screen. Reason: The archived HuRI PSI table contains three method records for EXOC6B Q9Y2D4-1, ORF 100063937, and SHTN1 A0MZ66-4, ORF 15060; current IntAct independently preserves that exact partner identity. The original Results describe pairwise retesting and sequence confirmation across the screen. The records specify human proteins assayed as GAL4 fusions in yeast, not endogenous human neuronal association. Aggregate MAPPIT/GPCA validation is not claimed for this individual pair. The historical accession/Ensembl labels do not independently verify the entire current clone sequence or the 672-residue EXOC6B product. This positive pair supports retention as non-core generic binding, without assigning SHTN1 neuronal signaling or actin-coupling activities to EXOC6B. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI independently supports an EXOC6B–EXOC5 interaction using human ORFeome constructs. Reason: The archived HuRI PSI table contains six EXOC6B Q9Y2D4-1/EXOC5 O00471 records, with both bait orientations represented and array, prey-pooling and validated-two-hybrid methods. Current IntAct maps the same pair to PMID:32296183. The original Results explain retesting and sequence confirmation, while the archived records identify human ORFs 100063937 and 11248 in the yeast assay. This is positive binary-screen evidence, distinct from the cellular complex purifications in PMID:27173435. No pair-specific orthogonal validation, endogenous assembly geometry, autonomous tethering or natural-product equivalence is inferred. Retain the generic binding claim as non-core because these data do not establish a more specific molecular activity of the pair. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex 3.0 reports an EXOC6B–EXOC5 association in the HEK293T network. Reason: The original BioPlex Methods use human ORFeome constructs with C-terminal FLAG-HA tags and anti-HA purification followed by mass spectrometry. The actual 293T network row 103345 contains EXOC6B Q9Y2D4 and EXOC5 O00471 with pInt 0.999998779762378; current IntAct independently records this pair under PMID:33961781. No corresponding pair was found in the inspected HCT116 network, which does not establish biological absence in that cell line. This experiment supports cellular complex association, not purified binary binding, a specific recruitment direction or measured membrane tethering by EXOC6B alone. The historical protein-group identifiers do not establish the 672-residue product. Retain the supported generic association as non-core; no more specific pair activity is demonstrated. Supporting Evidence: |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: The conserved exocyst role supports intracellular protein transport. Reason: InterPro IPR007225 explicitly maps intracellular protein transport and matches human Q9Y2D4 residues 5–804. The conserved Sec15/exocyst role is supported by the reviewed assembly experiments and UniProt CC:FUNCTION/SUBUNIT. Retain the protein-cargo facet alongside the separately supported Golgi-to-plasma-membrane route: the current is_a/part_of graph does not place that route term below this cargo term, so substituting one would lose a distinct aspect. The inference does not establish identical cargo repertoires or activity of both natural products. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR007225 SUPPORTS TRANSFER Actual target match spans residues 5–804 and the current family record explicitly maps both protein transport and Golgi-to-PM transport. Supporting Evidence: GO_REF:0000002 file:human/EXOC6B/EXOC6B-uniprot.txt |
| GO:0006887 exocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: The valid PAINT inference supports participation in exocytosis through the exocyst tethering step. Reason: Human Q9Y2D4 inherits the exocytosis assertion from PAINT node PTN000294823, with no intervening NOT. The current IBD retains yeast and Dictyostelium evidence; the frozen worm donor absent from that IBD remains an explicit version difference. PMID:22323285 documents Sec15 at contractile-vacuole/plasma-membrane contacts and discharge pores, and mammalian Sec15B identification plus UniProt CC:FUNCTION/SUBUNIT support the conserved exocyst role. PMID:36150098 adds human EXOC6B-deficiency context: its authors interpret patient fibroblast findings as impaired exocytosis, but the operative assays measure protein loss and shortened cilia, rather than secretion flux or vesicle-fusion events. It is corroborating disease context, not an independent direct exocytosis assay. The accepted complex role includes tethering under the current exocytosis definition; the detailed Dictyostelium pathway is not transferred wholesale to human cells. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000294823 SUPPORTS TRANSFER Actual current exocytosis IBD is on the target path; placement remains valid despite the donor-list version difference. SGD:S000003202 SUPPORTS TRANSFER Current donor record retains experimental exocytosis PMID:6996832; its original body was not recovered. Independently read yeast assembly and Dictyostelium discharge evidence are distinguished. dictyBase:DDB_G0293936 SUPPORTS TRANSFER Actual full original PMID:22323285 supports Sec15-containing exocyst participation in kiss-and-run discharge. WB:WBGene00016188 SOURCE STALE OR MISSING Present in the frozen GOA WITH, absent from the current exocytosis IBD and current queried worm experimental set; preserved as a source-version boundary, not evidence of target loss. Supporting Evidence: GO_REF:0000033 file:human/EXOC6B/EXOC6B-uniprot.txt |
| GO:0006893 Golgi to plasma membrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: The Sec15-family inference supports Golgi-to-plasma-membrane transport. Reason: IPR007225 maps Golgi-to-plasma-membrane transport and covers human Q9Y2D4 residues 5–804. Conserved Sec15 assembly, mammalian Sec15B complex identification and UniProt CC:FUNCTION/SUBUNIT support secretory-vesicle targeting at the plasma membrane. The yeast PMID:7026045 donor assertion is traced but its original body was not independently recovered. Retain the supported route facet, which the ontology distinguishes from protein-cargo transport and subsequent exocytosis. Neither a human paralog-specific Rab interaction nor autonomous fusion catalysis follows. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR007225 SUPPORTS TRANSFER Target match and current GO mapping verified; conserved secretory tethering role supports the route inference. Supporting Evidence: GO_REF:0000002 file:human/EXOC6B/EXOC6B-uniprot.txt |
| GO:0090148 membrane fission | NAS PMID:22420621 Exorcising the exocyst complex. | UNDECIDED | Summary: The review supports an exocyst-linked abscission model, but the EXOC6B-specific membrane-fission role is unresolved. Reason: GO:0090148 requires participation in the separation of a continuous membrane. PMID:16213214 places exocyst-mediated vesicle delivery/fusion before subsequent cell cleavage; that sequence supports vesicle targeting during cytokinesis but does not identify the exocyst as performing the membrane-scission step. Midbody localization and a Sec15-depletion cytokinesis phenotype therefore leave a mechanistic gap even if the paralog were resolved. Separately, the inspected main article does not identify whether its human Sec15 reagents are EXOC6B or EXOC6, and the Sec15 depletion result is reported as data not shown. Retain UNDECIDED for this source-specific assertion on both grounds, rather than infer membrane-fission participation merely from a requirement for successful cytokinesis. This does not require every participant to catalyze membrane cutting; a demonstrated structural or cofactor contribution to the fission step would also be relevant. |
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Download this section (compressed HTML)Q: Which molecular contact does human EXOC6B contribute to exocyst-mediated membrane tethering, and how does it differ from the corresponding EXOC6/Sec15A contribution?
Q: Is the 672-residue EXOC6B product endogenously expressed and incorporated into functional exocyst complexes, and how does its altered C-terminal region affect recruitment or assembly?
Q: Does the ciliary phenotype of EXOC6B-deficient human cells arise from altered delivery of specific cargo, a secondary turnover response, or another separable activity?
Experiment: Compare acute, paralog-specific EXOC6B and EXOC6 depletion with matched-expression rescue in human cells. Verify exocyst composition and abundance, and measure vesicle arrival, membrane contact and fusion separately. Test compositionally defined complexes with or without EXOC6B, and with interaction-guided variants, in a membrane-tethering assay that distinguishes membrane clustering from fusion. Identify any candidate Rab or membrane interaction directly rather than inferring it from a shared Sec15 name.
Hypothesis: EXOC6B supports tethering through a specific interface that can be separated experimentally from its incorporation into the exocyst.
Type: Paralog-specific rescue and biochemical membrane-tethering analysis
Experiment: Establish endogenous product-specific transcripts and discriminating peptides before comparing Q9Y2D4-1 and Q9Y2D4-2 at matched abundance. Quantify stability, localization, EXOC5 association, complete-complex incorporation and rescue of directly measured transport. Keep the natural products distinct from disease-associated truncations and from engineered affinity-tag constructs; overexpression alone does not establish physiological equivalence.
Hypothesis: The natural C-terminal replacement and deletion in the 672-residue product alter its exocyst incorporation or vesicle-recruitment properties.
Type: Product-resolved expression and controlled functional comparison
Experiment: Use isogenic loss and rescue alongside patient-derived human fibroblasts, measuring ciliary cargo delivery, cilium length and frequency, and autophagic flux over time. Normalize for cell-cycle state and exocyst abundance. Test whether restoring the affected trafficking step rescues the ciliary phenotype independently of bulk turnover changes. This separates a causal transport step from secondary changes accompanying EXOC6B loss.
Hypothesis: A specific defect in cargo delivery precedes ciliary shortening after EXOC6B loss and can be distinguished from downstream changes in protein turnover.
Type: Time-resolved human-cell rescue with cargo transport and turnover measurements
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