VAPB (vesicle-associated membrane protein-associated protein B) is a ubiquitously expressed, tail-anchored protein of the endoplasmic reticulum membrane. Its N-terminal MSP (major sperm protein) domain faces the cytosol and binds short FFAT (two phenylalanines in an acidic tract) and phosphorylation-dependent phospho-FFAT motifs in partner proteins; a central coiled-coil and C-terminal transmembrane helix mediate homodimerisation and heterodimerisation with its paralog VAPA. By recruiting FFAT-bearing proteins anchored on other organelles, VAPB acts as an ER-side receptor that builds membrane contact sites: with PTPIP51 (RMDN3) at ER-mitochondria contacts, where it supports Ca2+ transfer; with STARD3, STARD3NL and WDR44 at ER-endosome contacts; with OSBP/ORP proteins, CERT and FAPP1-Sac1 at ER-trans-Golgi contacts; and with Kv2 channels and PITPNM1 at ER-plasma membrane junctions. These contacts host non-vesicular lipid transfer (sterol, ceramide, phosphoinositides) carried out by the recruited partners. VAPB also modulates the IRE1/XBP1 branch of the unfolded protein response and is co-opted by hepatitis C virus NS5A/NS5B for viral RNA replication; a short splice isoform, VAP-C, lacks the coiled-coil and transmembrane region and antagonises HCV replication. The MSP domain can be cleaved and secreted and binds Eph receptors in vitro. Dominant missense variants in the MSP domain (P56S, T46I) cause ALS8 and late-onset spinal muscular atrophy, producing insoluble aggregates that trap wild-type VAPB.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | REMOVE | Summary: Interaction with HCV NS5A/polyprotein (yeast two-hybrid and co-IP). The host-virus role is captured by the viral genome replication process rows. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | REMOVE | Summary: Interaction with HCV NS5A/NS5B (co-IP). The host-virus role is captured by the viral genome replication process rows. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | MODIFY | Summary: VAPB forms heterodimers with VAPA (co-immunoprecipitation; via the transmembrane domains). Reason: Bare protein binding is uninformative. The interaction with VAPA is a well-characterised VAPA-VAPB heterodimer, so the informative replacement is GO:0046982 protein heterodimerization activity, which this review already keeps from the same paper. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16227268 Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. PMID:9920726 hVAP-A and hVAP-B associated with each other through their respective TMDs. |
| GO:0005515 protein binding | IPI PMID:18160438 Human butyrate-induced transcript 1 interacts with hepatitis... | REMOVE | Summary: Interaction with HACD3 (BIND1), identified as an HCV NS5A-binding host protein. No informative VAPB activity is defined by this interaction. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:18555774 The amyotrophic lateral sclerosis 8 protein VAPB is cleaved,... | MODIFY | Summary: The VAPB MSP domain is cleaved, secreted and binds the EphA4 ectodomain directly, competing with ephrin-B2. This is an extracellular, non-canonical activity of a cleavage fragment. Reason: Bare protein binding is uninformative. The paper shows binding of the secreted human VAPB MSP domain to the extracellular domain of an Eph receptor, which is captured by GO:0046875 ephrin receptor binding. This is non-core: it concerns a cleaved, secreted fragment and was shown with recombinant proteins and the mouse receptor ectodomain. Proposed replacements: ephrin receptor binding Supporting Evidence: PMID:18555774 Here we show that the MSP domains of VAP proteins are cleaved and secreted ligands for Eph receptors. PMID:18555774 suggesting that hVAP MSP binds to the EphA4 ectodomain directly |
| GO:0005515 protein binding | IPI PMID:19289470 Promotion of neurite extension by protrudin requires its int... | MODIFY | Summary: Interaction with UniProtKB:Q5T4F4 (ZFYVE27) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. Protrudin (ZFYVE27) carries an FFAT motif that mediates its binding to VAP proteins; UniProt records the VAPB interaction as MSP-domain mediated. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:19289470 Both the interaction between protrudin and VAP-A as well as the induction of process formation by protrudin were markedly inhibited by mutation of the FFAT motif. file:human/VAPB/VAPB-uniprot.txt Interacts (via MSP domain) with ZFYVE27 (PubMed:19289470, |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: USP20 interaction from a human deubiquitinase interaction landscape screen (AP-MS). Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:21976701 Protrudin serves as an adaptor molecule that connects KIF5 a... | REMOVE | Summary: KIF5A co-immunoprecipitates with VAPB only via the adaptor protrudin (ZFYVE27), so this is an indirect, complex-level association. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:21976701 Protrudin serves as an adaptor molecule that connects KIF5 a... | MODIFY | Summary: Interaction with UniProtKB:Q5T4F4 (ZFYVE27) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. Direct in vitro pulldown showed protrudin binds VAP-B; protrudin binds VAPs through its FFAT motif. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:21976701 A similar pulldown assay in vitro revealed the direct interaction of protrudin with VAP-B (Figure S10, A and B) PMID:19289470 Both the interaction between protrudin and VAP-A as well as the induction of process formation by protrudin were markedly inhibited by mutation of the FFAT motif. |
| GO:0005515 protein binding | IPI PMID:22131369 VAPB interacts with the mitochondrial protein PTPIP51 to reg... | MODIFY | Summary: Interaction with UniProtKB:Q96TC7 (RMDN3) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. PTPIP51/RMDN3 binds VAPB at ER-mitochondria contacts; later work mapped the binding to PTPIP51 FFAT and phospho-FFAT motifs recognised by the VAPB MSP domain. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:22131369 Here, we report that the integral ER protein VAPB interacts with the outer mitochondrial membrane protein PTPIP51 and that a proportion of VAPB is present in MAM. PMID:33124732 a mitochondria protein involved in ER‐mitochondria contact formation and possessing two FFATs |
| GO:0005515 protein binding | IPI PMID:23736259 The ALS8 protein VAPB interacts with the ER-Golgi recycling ... | REMOVE | Summary: YIF1A binds VAPB through its transmembrane regions (rat neurons/heterologous cells). The interaction is real but not a defined molecular activity for VAPB beyond membrane-protein association. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:25616068 A combined proteomics/genomics approach links hepatitis C vi... | REMOVE | Summary: Interaction with an HCV JFH-1 polyprotein chain from a combined proteomics/genomics HCV-host screen. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Interaction with UniProtKB:P50402 (EMD) reported in a high-throughput interaction study (PMID:25910212). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Interaction with UniProtKB:Q9P0L0 (VAPA) reported in a high-throughput interaction study (PMID:26496610). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:26618866 ∆F508 CFTR interactome remodelling promotes rescue of cystic... | REMOVE | Summary: Interaction with UniProtKB:P13569 (CFTR) reported in a high-throughput interaction study (PMID:26618866). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:28377464 STARD3 mediates endoplasmic reticulum-to-endosome cholestero... | MODIFY | Summary: Interaction with UniProtKB:Q14849 (STARD3) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. STARD3 binds VAPB through its (phospho-)FFAT motif, forming an ER-endosome tether. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:33124732 Like VAP‐A, VAP‐B bound to wild‐type STARD3, but not with its non‐phosphorylatable mutant STARD3 S209A (Fig 4B). PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interaction with UniProtKB:Q96LZ7 (RMDN2) reported in a high-throughput interaction study (PMID:28514442). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interaction with UniProtKB:Q9BXW6 (OSBPL1A) reported in a high-throughput interaction study (PMID:28514442). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Interaction with UniProtKB:Q9Y2K6 (USP20) reported in a high-throughput interaction study (PMID:28514442). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:29858488 Identification of MOSPD2, a novel scaffold for endoplasmic r... | MODIFY | Summary: Interaction with UniProtKB:Q9BXW6 (OSBPL1A) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. The MOSPD2 paper used the ORP1 (OSBPL1A) FFAT peptide and showed it binds the VAP-B MSP domain directly. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:29858488 A dose‐dependent signal increase showed that the MSP domains of either MOSPD2 (Fig 3A), VAP‐A (Fig 3B), or VAP‐B (Fig 3C) interacted with the FFAT peptide. |
| GO:0005515 protein binding | IPI PMID:30659099 The activity of Sac1 across ER-TGN contact sites requires th... | REMOVE | Summary: FAPP1 (PLEKHA3) forms a ternary complex with VAP proteins and Sac1 at ER-TGN contacts. The cached text shows direct FAPP1-VAPA pulldown; the motif mediating FAPP1-VAPB binding is not stated, so no FFAT replacement is asserted. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:30659099 The activity of Sac1 across ER-TGN contact sites requires th... | REMOVE | Summary: Sac1 (SACM1L) forms a ternary complex with FAPP1 and VAP proteins at ER-TGN contacts. Sac1 is itself ER-resident and no FFAT-type recognition is described. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:30741634 Human VPS13A is associated with multiple organelles and infl... | MODIFY | Summary: Interaction with UniProtKB:Q96RL7 (VPS13A) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. VPS13A binds VAP proteins via its FFAT motif; UniProt records the VAPB interaction as FFAT-mediated. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:30741634 VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. file:human/VAPB/VAPB-uniprot.txt Interacts with VPS13A (via FFAT motif) (PubMed:30741634). |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Interaction with UniProtKB:Q9H1P3 (OSBPL2) reported in a high-throughput interaction study (PMID:31515488). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | REMOVE | Summary: Interaction with UniProtKB:Q9Y2K6 (USP20) reported in a high-throughput interaction study (PMID:31515488). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:O00155 (GPR25) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:O00559 (EBAG9) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:O14684 (PTGES) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:O15209 (ZBTB22) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:P11912 (CD79A) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:P49447 (CYB561) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q13520 (AQP6) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q15125 (EBP) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q53TN4 (CYBRD1) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q5VTQ0 (TTC39B) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q6P5S7 (RNASEK) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q7Z5P4 (HSD17B13) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q86VR2 (RETREG3) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q8N5M9 (JAGN1) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q8N6L7 (TMEM252) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q8TBP5 (FAM174A) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q96IK0 (TMEM101) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q96LZ7 (RMDN2) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q96MV8 (ZDHHC15) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9GZR5 (ELOVL4) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9H6H4 (REEP4) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9NQQ7-3 (SLC35H1) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9NVV5-2 (AIG1) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9NY72 (SCN3B) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9Y2K6 (USP20) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Interaction with UniProtKB:Q9Y320 (TMX2) reported in a high-throughput interaction study (PMID:32296183). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32344433 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export... | MODIFY | Summary: Interaction with UniProtKB:Q5JSH3 (WDR44) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. WDR44 binds VAPB through its FFAT motif to align Rab-positive endosomal tubules with the ER. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:32344433 Endogenous WDR44 tubules can be described as a subset of tubular endosomes that are closely aligned with the ER via binding to VAPA and VAPB. file:human/VAPB/VAPB-uniprot.txt domain) with WDR44 (via FFAT motif); the interactions connect the |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interaction with UniProtKB:O00560 (SDCBP) reported in a high-throughput interaction study (PMID:32814053). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interaction with UniProtKB:P63010-2 (AP2B1) reported in a high-throughput interaction study (PMID:32814053). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interaction with UniProtKB:Q0P5N6 (ARL16) reported in a high-throughput interaction study (PMID:32814053). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interaction with UniProtKB:Q9BYQ4 (KRTAP9-2) reported in a high-throughput interaction study (PMID:32814053). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Interaction with UniProtKB:Q9GZS3 (SKIC8) reported in a high-throughput interaction study (PMID:32814053). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | MODIFY | Summary: Interaction with UniProtKB:Q14721 (KCNB1), UniProtKB:Q14849 (STARD3), UniProtKB:Q7L4E1 (MIGA2), UniProtKB:Q8TDY2 (RB1CC1), UniProtKB:Q92953 (KCNB2), UniProtKB:Q96TC7 (RMDN3), UniProtKB:Q9BXW6 (OSBPL1A) is an FFAT-motif-dependent recruitment of the partner by the VAPB MSP domain. This row aggregates seven partners (STARD3, RB1CC1, MIGA2, RMDN3, OSBPL1A, KCNB1, KCNB2) whose binding to VAPB depends on conventional or phospho-FFAT motifs, as shown by peptide pulldown, SPR and K43L mutagenesis of VAPB. Reason: Bare protein binding carries no functional information. For this partner the interaction is mediated by an FFAT (or phospho-FFAT) motif in the partner bound by the VAPB MSP domain, which is VAPB's core molecular activity. The informative replacement is GO:0033149 FFAT motif binding, which VAPB already carries (IDA, IMP, IPI). Proposed replacements: FFAT motif binding Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Like VAP‐A, VAP‐B bound to wild‐type STARD3, but not with its non‐phosphorylatable mutant STARD3 S209A (Fig 4B). PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q5VTQ0 (TTC39B) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q96LZ7 (RMDN2) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q9BXW6 (OSBPL1A) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q9H1P3 (OSBPL2) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q9P0L0 (VAPA) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Interaction with UniProtKB:Q9Y2K6 (USP20) reported in a high-throughput interaction study (PMID:33961781). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | REMOVE | Summary: Interaction with UniProtKB:P13569 (CFTR) reported in a high-throughput interaction study (PMID:35156780). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with UniProtKB:P50402 (EMD) reported in a high-throughput interaction study (PMID:35271311). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with UniProtKB:Q96LZ7 (RMDN2) reported in a high-throughput interaction study (PMID:35271311). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Interaction with UniProtKB:Q9P0L0 (VAPA) reported in a high-throughput interaction study (PMID:35271311). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | REMOVE | Summary: Interaction with UniProtKB:P13569 (CFTR) reported in a high-throughput interaction study (PMID:36012204). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction with UniProtKB:Q5VTQ0 (TTC39B) reported in a high-throughput interaction study (PMID:40205054). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction with UniProtKB:Q96LZ7 (RMDN2) reported in a high-throughput interaction study (PMID:40205054). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction with UniProtKB:Q9H1P3 (OSBPL2) reported in a high-throughput interaction study (PMID:40205054). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Interaction with UniProtKB:Q9P0L0 (VAPA) reported in a high-throughput interaction study (PMID:40205054). Reason: Bare GO:0005515 from a proteome-scale interaction screen (yeast two-hybrid, affinity purification-mass spectrometry, proximity labelling or a variant-perturbation screen). The screen records that the pair can co-purify or interact, but does not establish what VAPB does with the partner, so the annotation carries no functional information. Removal does not mean the interaction is false. VAPB's informative molecular functions (FFAT motif binding, protein-membrane adaptor activity, homo/heterodimerization) are captured elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:9920726 Molecular cloning and characterization of mammalian homologu... | REMOVE | Summary: VAMP1 binding was the founding observation for the VAP family (yeast two-hybrid/in vitro). Its physiological significance in human cells is unclear and no informative MF term is supported. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005515 protein binding | IPI PMID:9920726 Molecular cloning and characterization of mammalian homologu... | REMOVE | Summary: VAMP2 binding was the founding observation for the VAP family (yeast two-hybrid/in vitro). Its physiological significance in human cells is unclear and no informative MF term is supported. Reason: Bare GO:0005515 carries no functional information, and the cited evidence does not establish a more informative molecular function for VAPB with this partner. Removal does not mean the interaction is false; VAPB's informative activities are captured by other rows in this review. |
| GO:0005737 cytoplasm | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | TOO GENERAL | Summary: VAPB detected in the cytoplasm-associated fraction of an E-cadherin interactome proteomic study. Reason: True but uninformative: VAPB is a tail-anchored ER membrane protein whose MSP and coiled-coil domains face the cytosol. GO:0005789 endoplasmic reticulum membrane, accepted elsewhere in this review, is part_of cytoplasm and already entails this term. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005783 endoplasmic reticulum | IDA GO_REF:0000052 | ACCEPT | Summary: VAPB localises to the endoplasmic reticulum. Reason: VAPB is an ER-resident tail-anchored protein; ER localisation is demonstrated by imaging and fractionation in human cells. The more precise GO:0005789 ER membrane is also accepted. Supporting Evidence: PMID:15372378 In comparison with ER-DsRed, wild-type VAPB-EGFP predominantly localized to the ER PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005783 endoplasmic reticulum | IDA PMID:15372378 A mutation in the vesicle-trafficking protein VAPB causes la... | ACCEPT | Summary: VAPB localises to the endoplasmic reticulum. Reason: VAPB is an ER-resident tail-anchored protein; ER localisation is demonstrated by imaging and fractionation in human cells. The more precise GO:0005789 ER membrane is also accepted. Supporting Evidence: PMID:15372378 In comparison with ER-DsRed, wild-type VAPB-EGFP predominantly localized to the ER PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005783 endoplasmic reticulum | IDA PMID:16891305 Characterization of amyotrophic lateral sclerosis-linked P56... | ACCEPT | Summary: VAPB localises to the endoplasmic reticulum. Reason: VAPB is an ER-resident tail-anchored protein; ER localisation is demonstrated by imaging and fractionation in human cells. The more precise GO:0005789 ER membrane is also accepted. Supporting Evidence: PMID:15372378 In comparison with ER-DsRed, wild-type VAPB-EGFP predominantly localized to the ER PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005783 endoplasmic reticulum | IDA PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | ACCEPT | Summary: VAPB localises to the endoplasmic reticulum. Reason: VAPB is an ER-resident tail-anchored protein; ER localisation is demonstrated by imaging and fractionation in human cells. The more precise GO:0005789 ER membrane is also accepted. Supporting Evidence: PMID:15372378 In comparison with ER-DsRed, wild-type VAPB-EGFP predominantly localized to the ER PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000107 | ACCEPT | Summary: VAPB localises to the endoplasmic reticulum. Reason: VAPB is an ER-resident tail-anchored protein; ER localisation is demonstrated by imaging and fractionation in human cells. The more precise GO:0005789 ER membrane is also accepted. Supporting Evidence: PMID:15372378 In comparison with ER-DsRed, wild-type VAPB-EGFP predominantly localized to the ER PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: VAPB is a tail-anchored ER membrane protein with its MSP domain facing the cytosol. Reason: Core location. A C-terminal transmembrane anchor (residues 223-243) inserts VAPB in the ER membrane; experimental studies in human cells confirm ER membrane residence. The IBA (PTN000087323) reflects a deep, family-wide property shared with VAPA and yeast Scs2/Scs22. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:32344433 VAPA and VAPB have a cytoplasmic Major Sperm Protein (MSP) domain, a coiled coil (CC) region, and a transmembrane (TM) tail for anchoring in the ER. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | ACCEPT | Summary: VAPB is a tail-anchored ER membrane protein with its MSP domain facing the cytosol. Reason: Core location. A C-terminal transmembrane anchor (residues 223-243) inserts VAPB in the ER membrane; experimental studies in human cells confirm ER membrane residence. The IBA (PTN000087323) reflects a deep, family-wide property shared with VAPA and yeast Scs2/Scs22. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:32344433 VAPA and VAPB have a cytoplasmic Major Sperm Protein (MSP) domain, a coiled coil (CC) region, and a transmembrane (TM) tail for anchoring in the ER. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:32344433 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export... | ACCEPT | Summary: VAPB is a tail-anchored ER membrane protein with its MSP domain facing the cytosol. Reason: Core location. A C-terminal transmembrane anchor (residues 223-243) inserts VAPB in the ER membrane; experimental studies in human cells confirm ER membrane residence. The IBA (PTN000087323) reflects a deep, family-wide property shared with VAPA and yeast Scs2/Scs22. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:32344433 VAPA and VAPB have a cytoplasmic Major Sperm Protein (MSP) domain, a coiled coil (CC) region, and a transmembrane (TM) tail for anchoring in the ER. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | ACCEPT | Summary: VAPB is a tail-anchored ER membrane protein with its MSP domain facing the cytosol. Reason: Core location. A C-terminal transmembrane anchor (residues 223-243) inserts VAPB in the ER membrane; experimental studies in human cells confirm ER membrane residence. The IBA (PTN000087323) reflects a deep, family-wide property shared with VAPA and yeast Scs2/Scs22. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:32344433 VAPA and VAPB have a cytoplasmic Major Sperm Protein (MSP) domain, a coiled coil (CC) region, and a transmembrane (TM) tail for anchoring in the ER. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: VAPB is a tail-anchored ER membrane protein with its MSP domain facing the cytosol. Reason: Core location. A C-terminal transmembrane anchor (residues 223-243) inserts VAPB in the ER membrane; experimental studies in human cells confirm ER membrane residence. The IBA (PTN000087323) reflects a deep, family-wide property shared with VAPA and yeast Scs2/Scs22. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:32344433 VAPA and VAPB have a cytoplasmic Major Sperm Protein (MSP) domain, a coiled coil (CC) region, and a transmembrane (TM) tail for anchoring in the ER. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-429730 | ACCEPT | Summary: Reactome places VAPA/B in the ER membrane in complex with PPM1L, where multiphospho-CERT is dephosphorylated. Reason: Consistent with the experimental ER-membrane localisation of VAPB. Supporting Evidence: Reactome:R-HSA-429730 associates with the complex of VAPA/B (VAMP-associated proteins A or B) and PPM1L (protein phosphatase 1-like) in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9956909 | ACCEPT | Summary: Reactome places VAPA or VAPB at the cytosolic face of the ER membrane in a complex with CERT1-2 and PPM1L. Reason: Consistent with the experimental ER-membrane localisation of VAPB. Supporting Evidence: Reactome:R-HSA-9956909 CERT1-2 is associated with the cytosolic face of the ER membrane as part of a complex with PPM1L (protein phosphatase 1-like) (Saito et al. 2008) and VAPA or VAPB |
| GO:0005794 Golgi apparatus | IDA PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | KEEP AS NON CORE | Summary: VAPB colocalised with HCV NS5A in the ER and Golgi apparatus in transfected cells. Reason: VAPB is predominantly ER-resident; Golgi signal in overexpression/colocalisation studies is consistent with early reports of VAP on ER and Golgi membranes, but it is peripheral to the ER-anchored function. Keep as non-core. Supporting Evidence: PMID:16227268 NS5A was colocalized with VAP-B in the endoplasmic reticulum and Golgi apparatus. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA from the family root node PTN000087323, seeded by yeast Scs2, Arabidopsis VAP27, fly and fission-yeast members and VAPA. Reason: VAPB is anchored in the ER membrane. Its activity at the cell periphery is exerted from cortical ER at ER-plasma membrane contact sites, where it binds FFAT motifs of plasma-membrane proteins such as Kv2 channels; this is captured by GO:0140268 ER-plasma membrane contact site. No experimental study places human VAPB itself in the plasma membrane, and the donors' plasma membrane annotations largely reflect cortical ER in yeast and plants. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN000087323 SUPPORTS SOURCE BUT NOT TARGET Family root node; VAPB is inside the clade, but the ER-anchored VAP mechanism acts at ER-PM contacts from cortical ER rather than residing in the plasma membrane. The contact-site location is captured by GO:0140268. Supporting Evidence: PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. |
| GO:0006649 phospholipid transfer to membrane | IDA PMID:36853333 ORP9 and ORP10 form a heterocomplex to transfer phosphatidyl... | KEEP AS NON CORE | Summary: Curated IDA from a study of the ORP9-ORP10 PI4P-transfer heterocomplex at ER-TGN contact sites. The lipid transfer itself is carried out by the ORP9/ORP10 ORD domains; VAPB acts as the ER-side FFAT receptor anchoring the transfer proteins. Reason: The cached record is abstract-only and does not mention VAP; the curator saw the full text. VAPB has no lipid-binding or transfer domain, so its contribution is the scaffold/tether case: it supplies the ER docking site the transfer step depends on. Keep as non-core and defer to the curator; the transfer activity belongs to the ORPs. Supporting Evidence: PMID:36853333 ORP9 and ORP10, members of the OSBP/ORPs family, are located at the endoplasmic reticulum (ER)-trans-Golgi network (TGN) membrane contact sites (MCSs). |
| GO:0006874 intracellular calcium ion homeostasis | IMP PMID:22131369 VAPB interacts with the mitochondrial protein PTPIP51 to reg... | KEEP AS NON CORE | Summary: siRNA loss of VAPB or PTPIP51 perturbs ER-to-mitochondria Ca2+ transfer after IP3R-mediated release in human cells. Reason: VAPB affects Ca2+ handling indirectly, by tethering ER to mitochondria through PTPIP51 and thereby supporting Ca2+ transfer at MAMs. It has no channel or transporter activity; this is a downstream consequence of its tethering role and is kept as non-core. Supporting Evidence: PMID:22131369 We also present evidence that both VAPB and PTPIP51 are involved in the regulation of intracellular Ca2+ homeostasis. PMID:22131369 Both VAPB and PTPIP51 knockdown caused a significant delay in mitochondrial Ca2+ uptake |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IMP PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | KEEP AS NON CORE | Summary: IMP from a study in which FFAT expression rescued VAP-induced ER defects; supporting neuronal work shows VAPB is needed for membrane delivery into dendrites. Reason: The abstract of PMID:18713837 reports that overexpression of VAPA, not VAPB, inhibited ER-to-Golgi transport, and the VAPB finding concerns P56S-induced ER aggregation; the curator saw the full text (abstract-only in cache). Independent rat-neuron data (YIF1A) support a VAPB requirement in early secretory traffic. The effect is plausibly indirect (organising ER membrane proteins rather than executing vesicle transport), so keep as non-core. Supporting Evidence: PMID:23736259 These data suggest that both VAPB and YIF1A are important for ER-to-Golgi transport |
| GO:0007029 endoplasmic reticulum organization | IMP PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | KEEP AS NON CORE | Summary: Mutant VAPB-P56S causes large ER aggregates that are resolved by FFAT expression. Reason: The evidence concerns ER restructuring caused by the disease mutant and by overexpression. VAPB contributes to ER membrane organisation, consistent with the family-level IBA for ER membrane organization, but this is not its core activity. Supporting Evidence: PMID:18713837 Overexpression of FFAT restored ER-to-Golgi transport and lateral diffusion of membrane proteins, and resolved the large ER aggregates in VAPB-P56S. |
| GO:0008017 microtubule binding | IDA PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | KEEP AS NON CORE | Summary: Microtubule association of VAP proteins was reported; FFAT peptide disrupted VAP-microtubule association. Reason: The abstract attributes stable microtubule association mainly to VAPA; the curator saw the full text. Microtubule binding is plausible for VAPB but peripheral and possibly indirect; keep as non-core. Supporting Evidence: PMID:18713837 Application of a FFAT peptide restored in vitro ER vesicle budding and disrupted VAP-microtubule association. |
| GO:0008017 microtubule binding | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-derived electronic microtubule binding annotation. Reason: Consistent with the experimental row for the same term, kept as non-core. Supporting Evidence: PMID:18713837 Application of a FFAT peptide restored in vitro ER vesicle budding and disrupted VAP-microtubule association. |
| GO:0019076 viral release from host cell | IEA GO_REF:0000117 | REMOVE | Summary: ARBA-derived electronic annotation to viral release from host cell. Reason: No study shows VAPB acting in release of virions. VAPB's documented virus-related role is in HCV genome replication through binding NS5A/NS5B at replication membranes, captured by the viral genome replication rows. The ARBA rule over-extends the family to a different stage of the viral life cycle. Supporting Evidence: PMID:16227268 These results suggest that VAP-B, in addition to VAP-A, plays an important role in the replication of the HCV genome. |
| GO:0019899 enzyme binding | IPI PMID:17540579 A mutation in human VAP-B--MSP domain, present in ALS patien... | MARK AS OVER ANNOTATED | Summary: GAPDH co-purified with the recombinant VAPB MSP domain in a pulldown, with weaker binding to the P56S mutant. Reason: A single in vitro pulldown of the isolated MSP domain followed by mass spectrometry; no functional consequence or in vivo relevance is established, and GAPDH is a common abundant contaminant. The 'enzyme binding' term says nothing about VAPB's activity. Supporting Evidence: PMID:17540579 Our findings suggest that the P56S mutation may lead to a less stable interaction of this endoplasmic reticulum protein with at least two other proteins: tubulin and GAPDH. |
| GO:0030301 cholesterol transport | IDA PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | KEEP AS NON CORE | Summary: VAPB is the ER-side receptor for the phospho-FFAT of STARD3, which builds ER-endosome contacts where STARD3 transfers cholesterol. The in vitro sterol-transfer reconstitution used VAP-A; VAPB binding to phospho-STARD3 was shown in cells and with recombinant MSP domain. Reason: VAPB does no transfer chemistry; it supplies the membrane docking site that STARD3- and OSBP/ORP-mediated sterol transfer depends on (scaffold case). The role is real but indirect, and the direct reconstitution in PMID:33124732 was done with VAP-A; keep as non-core. Supporting Evidence: PMID:33124732 phosphorylation on the 4th residue switches the motif on and allows its recognition by VAP‐A/VAP‐B/MOSPD2, triggering the formation of ER‐endosome contact and enabling cholesterol transfer (Fig 9). PMID:33124732 Like VAP‐A, VAP‐B bound to wild‐type STARD3, but not with its non‐phosphorylatable mutant STARD3 S209A (Fig 4B). |
| GO:0030301 cholesterol transport | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: VAPB is the ER-side receptor for the phospho-FFAT of STARD3, which builds ER-endosome contacts where STARD3 transfers cholesterol. The in vitro sterol-transfer reconstitution used VAP-A; VAPB binding to phospho-STARD3 was shown in cells and with recombinant MSP domain. Reason: VAPB does no transfer chemistry; it supplies the membrane docking site that STARD3- and OSBP/ORP-mediated sterol transfer depends on (scaffold case). The role is real but indirect, and the direct reconstitution in PMID:33124732 was done with VAP-A; keep as non-core. Supporting Evidence: PMID:33124732 phosphorylation on the 4th residue switches the motif on and allows its recognition by VAP‐A/VAP‐B/MOSPD2, triggering the formation of ER‐endosome contact and enabling cholesterol transfer (Fig 9). PMID:33124732 Like VAP‐A, VAP‐B bound to wild‐type STARD3, but not with its non‐phosphorylatable mutant STARD3 S209A (Fig 4B). |
| GO:0030968 endoplasmic reticulum unfolded protein response | IMP PMID:16891305 Characterization of amyotrophic lateral sclerosis-linked P56... | KEEP AS NON CORE | Summary: Overexpressed VAPB promotes the UPR and VAPB siRNA attenuates UPR to chemical ER stress; P56S abolishes this. Reason: Evidence comes from overexpression and knockdown in cell lines; VAPB is not a UPR sensor or transducer itself. The role is modulatory and peripheral to its FFAT-receptor function. Supporting Evidence: PMID:16891305 small interfering RNA for VAPB attenuates UPR to chemically induced ER stresses, indicating that VAPB is physiologically involved in UPR |
| GO:0033149 FFAT motif binding | IDA PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | ACCEPT | Summary: The VAPB MSP domain binds conventional FFAT and phospho-FFAT motifs of partner proteins. Reason: Core molecular function, shown directly for human VAPB: purified VAPB MSP domain binds FFAT and phospho-FFAT peptides, K43 is required for phospho-FFAT recognition, and FFAT-dependent binding of STARD3/STARD3NL, ORP1 and WDR44 has been shown in cells. Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0033149 FFAT motif binding | IEA GO_REF:0000117 | ACCEPT | Summary: The VAPB MSP domain binds conventional FFAT and phospho-FFAT motifs of partner proteins. Reason: Core molecular function, shown directly for human VAPB: purified VAPB MSP domain binds FFAT and phospho-FFAT peptides, K43 is required for phospho-FFAT recognition, and FFAT-dependent binding of STARD3/STARD3NL, ORP1 and WDR44 has been shown in cells. Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0033149 FFAT motif binding | IMP PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | ACCEPT | Summary: The VAPB MSP domain binds conventional FFAT and phospho-FFAT motifs of partner proteins. Reason: Core molecular function, shown directly for human VAPB: purified VAPB MSP domain binds FFAT and phospho-FFAT peptides, K43 is required for phospho-FFAT recognition, and FFAT-dependent binding of STARD3/STARD3NL, ORP1 and WDR44 has been shown in cells. The IMP row comes from FFAT-motif overexpression rescuing VAPB-P56S ER aggregation, functional evidence that FFAT engagement acts on VAPB. Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0033149 FFAT motif binding | IPI PMID:24105263 STARD3 or STARD3NL and VAP form a novel molecular tether bet... | ACCEPT | Summary: The VAPB MSP domain binds conventional FFAT and phospho-FFAT motifs of partner proteins. Reason: Core molecular function, shown directly for human VAPB: purified VAPB MSP domain binds FFAT and phospho-FFAT peptides, K43 is required for phospho-FFAT recognition, and FFAT-dependent binding of STARD3/STARD3NL, ORP1 and WDR44 has been shown in cells. Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0033149 FFAT motif binding | IPI PMID:24105263 STARD3 or STARD3NL and VAP form a novel molecular tether bet... | ACCEPT | Summary: The VAPB MSP domain binds conventional FFAT and phospho-FFAT motifs of partner proteins. Reason: Core molecular function, shown directly for human VAPB: purified VAPB MSP domain binds FFAT and phospho-FFAT peptides, K43 is required for phospho-FFAT recognition, and FFAT-dependent binding of STARD3/STARD3NL, ORP1 and WDR44 has been shown in cells. Supporting Evidence: PMID:33124732 The FFAT of ORP1 efficiently pulled down VAP‐A and VAP‐B from the whole cell protein extract PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. PMID:24105263 STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. |
| GO:0036498 IRE1-mediated unfolded protein response | IDA PMID:20940299 Characterization of the properties of a novel mutation in VA... | KEEP AS NON CORE | Summary: VAPB potentiates the IRE1/XBP1 branch of the UPR; ALS mutants T46I and P56S lose this property. Reason: Reporter assays with overexpressed VAPB in NSC-34 cells; the mechanism is not defined and VAPB is not a component of the IRE1 signalling machinery. Keep as non-core, consistent with the general UPR row. Supporting Evidence: PMID:20940299 Taken together, these data show that VAPB protein activates the unfolded protein response by acting through the IRE1/XBP1 pathway and that the VAPB protein containing the newly identified T46I mutation lacks this property. |
| GO:0042803 protein homodimerization activity | IPI PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | KEEP AS NON CORE | Summary: VAPB forms homodimers (via transmembrane and MSP domains). Reason: Homodimerisation is well established and the MSP domain dimer is the unit that binds FFAT (affinities in PMID:33124732 are expressed per dimer). It is a structural property supporting the core adaptor function rather than the function itself. Supporting Evidence: PMID:16227268 Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. PMID:33124732 Thus, the concentrations used to determine affinities correspond to those of VAP‐A and VAP‐B homodimers. |
| GO:0042803 protein homodimerization activity | IPI PMID:17540579 A mutation in human VAP-B--MSP domain, present in ALS patien... | KEEP AS NON CORE | Summary: VAPB forms homodimers (via transmembrane and MSP domains). Reason: Homodimerisation is well established and the MSP domain dimer is the unit that binds FFAT (affinities in PMID:33124732 are expressed per dimer). It is a structural property supporting the core adaptor function rather than the function itself. Supporting Evidence: PMID:16227268 Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. PMID:33124732 Thus, the concentrations used to determine affinities correspond to those of VAP‐A and VAP‐B homodimers. |
| GO:0042803 protein homodimerization activity | IPI PMID:9920726 Molecular cloning and characterization of mammalian homologu... | KEEP AS NON CORE | Summary: Early cloning study of human VAP-B; VAPB self-associates as well as heterodimerising with VAPA through the TMD. Reason: Homodimerisation is well established and the MSP domain dimer is the unit that binds FFAT (affinities in PMID:33124732 are expressed per dimer). It is a structural property supporting the core adaptor function rather than the function itself. Supporting Evidence: PMID:9920726 hVAP-A and hVAP-B associated with each other through their respective TMDs. PMID:33124732 Thus, the concentrations used to determine affinities correspond to those of VAP‐A and VAP‐B homodimers. |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: VAPB is an ER membrane-anchored receptor that recruits FFAT-containing cytosolic and organelle-bound proteins to the ER surface, building membrane contact sites. Reason: Core molecular function. The IBA comes from the family root node PTN000087323, consistent with the conserved FFAT-receptor mechanism across VAPA, VAPB and yeast Scs2. The IDA (VAPome BioID) directly characterised human VAPB as an ER tether for FFAT-motif proteins. Supporting Evidence: PMID:33296653 The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0043495 protein-membrane adaptor activity | IDA PMID:33296653 Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane ... | ACCEPT | Summary: VAPB is an ER membrane-anchored receptor that recruits FFAT-containing cytosolic and organelle-bound proteins to the ER surface, building membrane contact sites. Reason: Core molecular function. The IBA comes from the family root node PTN000087323, consistent with the conserved FFAT-receptor mechanism across VAPA, VAPB and yeast Scs2. The IDA (VAPome BioID) directly characterised human VAPB as an ER tether for FFAT-motif proteins. Supporting Evidence: PMID:33296653 The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs. PMID:33124732 VAP‐A, VAP‐B, and MOSPD2 are anchored in the ER membrane by a carboxyl‐terminal transmembrane domain with their MSP domain projecting into the cytosol. |
| GO:0044828 host-mediated suppression of viral genome replication | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation. Experimentally, the short splice isoform VAP-C (O95292-2, MSP N-terminal half only) binds HCV NS5B and inhibits HCV replication when overexpressed, while full-length VAP-B enhances it. Reason: Although the ARBA rule is unvetted, there is gene-specific experimental support: VAP-C, an isoform of this gene, negatively regulates HCV RNA replication by competing for NS5B. This is an isoform-specific, overexpression-based host-virus interaction, so keep as non-core. Supporting Evidence: PMID:19515777 Overexpression of VAP-C impaired the RNA replication of the HCV replicon and the propagation of the HCV JFH1 strain, whereas overexpression of VAP-A and VAP-B enhanced the replication. |
| GO:0044829 host-mediated activation of viral genome replication | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation to host-mediated activation of viral genome replication. Reason: Consistent with experimental data that VAP-B (isoform 1) binds HCV NS5A/NS5B and supports HCV RNA replication; host-virus interaction, non-core. Supporting Evidence: PMID:16227268 Overexpression of VAP-B, but not of a mutant lacking its transmembrane domain, enhanced the expression of NS5A and NS5B and the replication of HCV RNA in Huh-7 cells harboring a subgenomic replicon. |
| GO:0045070 positive regulation of viral genome replication | IMP PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | KEEP AS NON CORE | Summary: VAP-B knockdown/antibody inhibition reduced, and overexpression enhanced, HCV RNA replication. Reason: Well-supported host factor role for HCV replication; VAPB is exploited by the virus to build replication membranes. This is not part of its normal cellular function, so non-core. Supporting Evidence: PMID:16227268 The specific antibody to VAP-B suppressed HCV RNA replication in a cell-free assay. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: VAPB detected among proteins co-purifying with E-cadherin in a quantitative proteomic interactome. Reason: A high-throughput co-purification (HDA) does not show direct binding to cadherin, and VAPB is an ER protein; the E-cadherin link is plausibly through WDR44-dependent export of newly synthesised E-cadherin from the ER/endosomal system rather than cadherin binding. Supporting Evidence: PMID:32344433 Endogenous WDR44 tubules can be described as a subset of tubular endosomes that are closely aligned with the ER via binding to VAPA and VAPB. |
| GO:0046982 protein heterodimerization activity | IPI PMID:16227268 Human VAP-B is involved in hepatitis C virus replication thr... | KEEP AS NON CORE | Summary: VAPB heterodimerises with VAPA through the transmembrane domains. Reason: Well-established structural property of the VAP pair; supports but is not the core adaptor function. Supporting Evidence: PMID:9920726 hVAP-A and hVAP-B associated with each other through their respective TMDs. PMID:16227268 Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. |
| GO:0046982 protein heterodimerization activity | IPI PMID:9920726 Molecular cloning and characterization of mammalian homologu... | KEEP AS NON CORE | Summary: VAPB heterodimerises with VAPA through the transmembrane domains. Reason: Well-established structural property of the VAP pair; supports but is not the core adaptor function. Supporting Evidence: PMID:9920726 hVAP-A and hVAP-B associated with each other through their respective TMDs. PMID:16227268 Immunoprecipitation and mutation analyses revealed that VAP-B binds to both NS5A and NS5B in mammalian cells and forms homo- and heterodimers with VAP-A. |
| GO:0048487 beta-tubulin binding | IDA PMID:17540579 A mutation in human VAP-B--MSP domain, present in ALS patien... | KEEP AS NON CORE | Summary: Tubulin co-purified with the recombinant VAPB MSP domain in vitro, with weaker binding for P56S. Reason: Single in vitro pulldown/MS study; VAP-microtubule association is reported for the family but its direct nature for VAPB is not established. Non-core. Supporting Evidence: PMID:17540579 Our findings suggest that the P56S mutation may lead to a less stable interaction of this endoplasmic reticulum protein with at least two other proteins: tubulin and GAPDH. |
| GO:0070971 endoplasmic reticulum exit site | IDA NOT PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | ACCEPT | Summary: NOT annotation: VAPB was not concentrated at ER exit sites in the cited study, unlike VAPA. Reason: Accept the negative curator assertion (full text not cached). It is consistent with the abstract, which distinguishes VAPA (inhibits cargo segregation into ER vesicles) from VAPB. Supporting Evidence: PMID:18713837 Overexpression of the wild-type A isoform (VAPA) but not the B isoform (VAPB), inhibited ER-to-Golgi transport of membrane proteins. |
| GO:0090114 COPII-coated vesicle budding | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: COPII vesicle budding annotation based on FFAT rescue of in vitro ER vesicle budding in a VAP overexpression context. Reason: VAPB is not a COPII coat component or regulator; the budding defects arose from VAP overexpression (chiefly VAPA) and the same study states that VAPB did not inhibit ER export. Participation in vesicle budding is not established for VAPB. Supporting Evidence: PMID:18713837 Overexpression of the wild-type A isoform (VAPA) but not the B isoform (VAPB), inhibited ER-to-Golgi transport of membrane proteins. |
| GO:0090114 COPII-coated vesicle budding | IMP PMID:18713837 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transpo... | MARK AS OVER ANNOTATED | Summary: COPII vesicle budding annotation based on FFAT rescue of in vitro ER vesicle budding in a VAP overexpression context. Reason: VAPB is not a COPII coat component or regulator; the budding defects arose from VAP overexpression (chiefly VAPA) and the same study states that VAPB did not inhibit ER export. Participation in vesicle budding is not established for VAPB. Supporting Evidence: PMID:18713837 Overexpression of the wild-type A isoform (VAPA) but not the B isoform (VAPB), inhibited ER-to-Golgi transport of membrane proteins. |
| GO:0090158 endoplasmic reticulum membrane organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from family root node PTN000087323, seeded by yeast Scs2 and Scs22, whose loss alters cortical ER organisation. Reason: VAPB is inside the clade carrying the node and VAPB-P56S/overexpression produce ER restructuring, so the inheritance is plausible. It is a consequence of tethering rather than the core activity. Supporting Evidence: PMID:18713837 Overexpression of FFAT restored ER-to-Golgi transport and lateral diffusion of membrane proteins, and resolved the large ER aggregates in VAPB-P56S. |
| GO:0098793 presynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic orthology transfer (Ensembl Compara) of presynapse from rodent Vapb SynGO annotations. Reason: Plausible for an ER protein present in neuronal ER extending into synaptic compartments, and orthology to rodent Vapb is one-to-one in the same PANTHER subfamily (SF12). It is a tissue context rather than the protein's functional location, so non-core. Supporting Evidence: PMID:23736259 VAPB strongly affects the distribution of YIF1A and is required for intracellular membrane trafficking into dendrites and normal dendritic morphology. |
| GO:0098794 postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic orthology transfer (Ensembl Compara) of postsynapse from rodent Vapb SynGO annotations. Reason: Plausible for an ER protein present in neuronal ER extending into synaptic compartments, and orthology to rodent Vapb is one-to-one in the same PANTHER subfamily (SF12). It is a tissue context rather than the protein's functional location, so non-core. Supporting Evidence: PMID:23736259 VAPB strongly affects the distribution of YIF1A and is required for intracellular membrane trafficking into dendrites and normal dendritic morphology. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic orthology transfer (Ensembl Compara) of glutamatergic synapse from rodent Vapb SynGO annotations. Reason: Plausible for an ER protein present in neuronal ER extending into synaptic compartments, and orthology to rodent Vapb is one-to-one in the same PANTHER subfamily (SF12). It is a tissue context rather than the protein's functional location, so non-core. Supporting Evidence: PMID:23736259 VAPB strongly affects the distribution of YIF1A and is required for intracellular membrane trafficking into dendrites and normal dendritic morphology. |
| GO:0140268 endoplasmic reticulum-plasma membrane contact site | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Vapb (same PANTHER subfamily SF12): VAPB binds the FFAT of PITPNM1 at ER-PM contacts. Reason: Mouse Vapb is the one-to-one ortholog in SF12, so the transfer is evolutionarily sound. Human VAPB binds the phospho-FFATs of Kv2.1/Kv2.2 (KCNB1/KCNB2), which build ER-PM junctions. A real but partner-specific contact-site context. Supporting Evidence: file:human/VAPB/VAPB-uniprot.txt Interacts (via MSP) with PITPNM1 (via FFAT motif), the interaction is PMID:33124732 Similarly to VAP‐A K50L, VAP‐B K43L interacted with the conventional FFAT of ORP1, but not with the Phospho‐FFAT of STARD3, while wild‐type VAP‐B interacted equally with the two types of FFAT motifs. |
| GO:0160214 endoplasmic reticulum-plasma membrane adaptor activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Vapb: ER-PM adaptor activity through binding PITPNM1 at ER-PM contacts. Reason: Ortholog transfer within SF12 is sound. The GO definition specifies bridging via membrane lipid binding, whereas VAPB bridges via FFAT motifs of PM-associated proteins (PITPNM1, Kv2 channels), so the term fits imperfectly; the core activity is captured by FFAT motif binding and protein-membrane adaptor activity. Keep as non-core. Supporting Evidence: file:human/VAPB/VAPB-uniprot.txt required for ER-PM membrane contact sites formation (By similarity). |
| GO:0160258 endoplasmic reticulum-trans-Golgi network membrane contact site | IDA PMID:36853333 ORP9 and ORP10 form a heterocomplex to transfer phosphatidyl... | ACCEPT | Summary: VAPB localises to ER-trans-Golgi network contact sites, where it anchors ORP9/ORP10 and related FFAT proteins. Reason: Membrane contact sites are where VAPB's FFAT-receptor activity is exerted, and ER-TGN contacts are one of its best-studied sites (OSBP, CERT, ORP9/10, FAPP1-Sac1). VAP-knockout cells lose Sac1 activity across ER-TGN contacts. Supporting Evidence: PMID:36853333 ORP9 and ORP10, members of the OSBP/ORPs family, are located at the endoplasmic reticulum (ER)-trans-Golgi network (TGN) membrane contact sites (MCSs). PMID:30659099 These include the ER resident proteins VAPA and VAPB |
| GO:1902633 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate metabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS from mouse Vapb: PI(4,5)P2 metabolism via recruitment of the PI transfer protein PITPNM1 at ER-PM contacts. Reason: VAPB has no lipid kinase, phosphatase or transfer activity; PITPNM1 transfers PI to sustain PM PI(4,5)P2. VAPB anchors the transfer protein but does not perform any step of PIP2 metabolism, so involvement in the metabolic process is an over-extension of a tethering role. Supporting Evidence: file:human/VAPB/VAPB-uniprot.txt Interacts (via MSP) with PITPNM1 (via FFAT motif), the interaction is |
| GO:0140474 mitochondrion-endoplasmic reticulum membrane tether activity | IDA PMID:24893131 ER-mitochondria associations are regulated by the VAPB-PTPIP... | NEW | Summary: VAPB in the ER membrane binds the outer mitochondrial membrane protein PTPIP51 (RMDN3) via its FFAT motifs; VAPB knockdown reduces ER-mitochondria associations and overexpression increases them. Reason: VAPB is one half of the VAPB-PTPIP51 tether and does the binding work that holds the two membranes together (it is not a substrate or a mere requirement). Comparator check: the paired tether PTPIP51 and the yeast ERMES-type tethers carry tether MF terms; the GO:0140474 definition explicitly covers an ER protein that binds a mitochondrial outer membrane protein. Human-cell evidence includes reduced contacts on VAPB siRNA. Supporting Evidence: PMID:24893131 Here we show that the ER-resident protein VAPB interacts with the mitochondrial protein tyrosine phosphatase-interacting protein-51 (PTPIP51) to regulate ER-mitochondria associations. PMID:24893131 However, siRNA knockdown of either VAPB or PTPIP51 significantly reduced these values PMID:22131369 Here, we report that the integral ER protein VAPB interacts with the outer mitochondrial membrane protein PTPIP51 and that a proportion of VAPB is present in MAM. |
| GO:0170016 endoplasmic reticulum-endosome tether activity | IDA PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | NEW | Summary: VAPB binds the phospho-FFAT of late-endosomal STARD3 and the FFAT of WDR44 on endosomal tubules, tethering endosomes to the ER. Reason: VAPB is the ER-anchored half of ER-endosome tethers (STARD3, STARD3NL, WDR44): GFP-VAP-B is recruited around endosomes by phospho-STARD3, and endogenous WDR44 tubules align with the ER via VAPA and VAPB. The tether term is more specific than the accepted protein-membrane adaptor activity and matches the VAPA treatment of the same mechanism. Supporting Evidence: PMID:33124732 Akin to VAP‐A, VAP‐B was evenly distributed in the ER when expressed alone, and in the presence of the non‐phosphorylatable STARD3 S209A mutant, while it was recruited around endosomes by wild‐type STARD3 and the phosphomimetic mutant STARD3 S209D/P210A (Fig EV4A–E). PMID:32344433 Endogenous WDR44 tubules can be described as a subset of tubular endosomes that are closely aligned with the ER via binding to VAPA and VAPB. |
| GO:0140284 endoplasmic reticulum-endosome membrane contact site | IDA PMID:33124732 FFAT motif phosphorylation controls formation and lipid tran... | NEW | Summary: VAPB concentrates in ER subdomains contacting endosomes when bound by phospho-STARD3. Reason: Direct imaging of GFP-VAP-B relocalisation to ER-endosome contacts in human HeLa cells. Supporting Evidence: PMID:33124732 Akin to VAP‐A, VAP‐B was evenly distributed in the ER when expressed alone, and in the presence of the non‐phosphorylatable STARD3 S209A mutant, while it was recruited around endosomes by wild‐type STARD3 and the phosphomimetic mutant STARD3 S209D/P210A (Fig EV4A–E). |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IDA PMID:22131369 VAPB interacts with the mitochondrial protein PTPIP51 to reg... | NEW | Summary: Endogenous VAPB is enriched in the MAM fraction of HEK293 cells, and the UniProt record notes MAM localisation. Reason: Subcellular fractionation of human cells showed a prominent VAPB signal in MAM, consistent with its PTPIP51 tethering role. Supporting Evidence: PMID:22131369 All markers were enriched in their respective fractions and a prominent signal for VAPB was obtained in the MAM fraction PMID:22131369 Here, we report that the integral ER protein VAPB interacts with the outer mitochondrial membrane protein PTPIP51 and that a proportion of VAPB is present in MAM. |
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Download this section (compressed HTML)Q: Which FFAT partners are VAPB-selective rather than shared with VAPA, given that the two paralogs sit in sister PANTHER subfamilies (SF12 vs SF155) and bind FFAT peptides with similar affinity?
Q: Is the IRE1/XBP1-potentiating activity of VAPB seen with overexpression a physiological function, or a secondary effect of ER membrane reorganisation?
Q: Should GO:0160214 endoplasmic reticulum-plasma membrane adaptor activity be broadened to cover protein-mediated bridging (FFAT binding of Kv2 channels or PITPNM1), as its definition currently requires membrane lipid binding?
Q: What is the physiological role, if any, of the cleaved and secreted VAPB MSP domain in human serum?
Experiment: Quantitative proximity labelling (TurboID) of endogenously tagged VAPA and VAPB in VAPA/VAPB double-knockout human iPSC-derived motor neurons rescued with each paralog, followed by FFAT-peptide competition, to define paralog-selective partners.
Hypothesis: VAPB and VAPA have partially non-overlapping FFAT partner sets that explain the distinct ALS8 phenotype.
Type: interaction proteomics
Experiment: Measure PTPIP51 phospho-FFAT binding affinity of purified wild-type and P56S MSP domains by SPR, and quantify ER-mitochondria contacts and mitochondrial Ca2+ uptake in knock-in motor neurons.
Hypothesis: VAPB-P56S impairs ER-mitochondria Ca2+ transfer by altering PTPIP51 tethering rather than by loss of FFAT binding.
Type: biochemical and cell imaging
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