B9D2 (B9 domain-containing protein 2; MKSR2/MKS10) is a small soluble protein with a C2-like B9 domain. It forms the B9 complex with MKS1 and B9D1 (arranged MKS1-B9D2-B9D1), part of the MKS module at the ciliary transition zone. The B9 complex anchors the transmembrane protein TMEM67, and the module acts as a diffusion barrier that keeps the ciliary membrane composition distinct from the plasma membrane; for example, B9D2-knockout cells lose GPR161 from the ciliary membrane. The B9-TMEM67 module also sustains post-translational modification of axonemal microtubules. Earlier, at the mother centriole, B9 proteins promote vesicle docking and CP110 removal to initiate ciliogenesis. B9D2 is not essential for ciliogenesis, but its loss reduces cilium formation and length. Biallelic B9D2 variants cause Meckel syndrome (MKS10) and Joubert syndrome (JBTS34).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:21602787 Nephrocystins and MKS proteins interact with IFT particle an... | REMOVE | Summary: Protein binding (IPI) with IFT70B, from a study of nephrocystin/MKS-IFT interactions. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:21602787 Nephrocystins and MKS proteins interact with IFT particle an... | REMOVE | Summary: Protein binding (IPI) with INVS, from a study of nephrocystin/MKS-IFT interactions. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | REMOVE | Summary: Protein binding (IPI) with MKS1, from a centrosome-cilium interface interaction map. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | REMOVE | Summary: Protein binding (IPI) with B9D1, from a centrosome-cilium interface interaction map. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:27173435 An organelle-specific protein landscape identifies novel dis... | REMOVE | Summary: Protein binding (IPI) with B9D1, from a cilium organelle-specific protein landscape. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TLX3, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with QARS1, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with PLEKHA7, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with P4HA3, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SAXO4, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SPAG8, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with VPS25, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with ALKBH7, from the HuRI binary interactome. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32726168 Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is... | REMOVE | Summary: Protein binding (IPI) with MKS1, from the MKS1-B9D2-B9D1 complex study. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:32726168 Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is... | REMOVE | Summary: Protein binding (IPI) with B9D1, from the MKS1-B9D2-B9D1 complex study. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with MKS1, from the BioPlex network. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with B9D1, from the BioPlex network. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Protein binding (IPI) with MKS1, from a multimodal cell map. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Protein binding (IPI) with B9D1, from a multimodal cell map. MKS1 and B9D1 are its partners in the B9 complex, which is captured by the MKS complex (GO:0036038) rows. Generic protein binding is uninformative; removed under policy. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nucleus (IEA). This comes from UniProt's nucleus location, which is by similarity (ECO:0000250) only, with no experimental data for human B9D2. Kept as non-core. Reason: [file:human/B9D2/B9D2-uniprot.txt "CC {ECO:0000269|PubMed:19208769}. Nucleus {ECO:0000250}."] Supporting Evidence: file:human/B9D2/B9D2-uniprot.txt CC {ECO:0000269|PubMed:19208769}. Nucleus {ECO:0000250}. |
| GO:0005813 centrosome | IDA PMID:19208769 Functional interactions between the ciliopathy-associated Me... | ACCEPT | Summary: Centrosome (IDA). Before ciliogenesis, B9 proteins localize to the mother centriole of the centrosome. There they help dock membrane vesicles to the distal appendages and promote removal of CP110, which initiates cilium assembly. This is a functional pre-ciliary role, distinct from the later transition-zone role. Accepted. Reason: [PMID:41165761 "During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly."] [PMID:19208769 "This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia."] Supporting Evidence: PMID:41165761 During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly. PMID:19208769 This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141409 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Mad1 binds kinetochore', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141422 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'MAD2 converted to an inhibitory state via interaction with Mad1', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141431 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'MAD2 associates with the Mad1 kinetochore complex', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-141439 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Release of activated MAD2 from kinetochores', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638803 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Phosphorylation of cohesin by PLK1 at centromeres', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1638821 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'PP2A-B56 dephosphorylates centromeric cohesin', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467809 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'ESPL1 (Separase) cleaves centromeric cohesin', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2467811 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Separation of sister chromatids', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2468287 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'CDK1 phosphorylates CDCA5 (Sororin) at centromeres', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2484822 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Kinetochore assembly', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-375302 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Kinetochore capture of astral microtubules', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'RAB3IP stimulates nucleotide exchange on RAB8A', which is a ciliary-trafficking/transition-zone event. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Recruitment of transition zone proteins', which is a ciliary-trafficking/transition-zone event. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'CEP164 recruits RAB3IP-carrying Golgi-derived vesicles to the basal body', which is a ciliary-trafficking/transition-zone event. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666129 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'CDC42:GTP recruits DIAPH2-2 to kinetochores', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666160 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'AURKB phosphorylates DIAPH2-2 at kinetochores', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5666169 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9648114 | KEEP AS NON CORE | Summary: Cytosol (TAS, Reactome). Reactome event: 'EML4 recruits NUDC to mitotic spindle', which is a mitotic kinetochore event, in which Reactome lists B9D2 as a component of its 'Kinetochore [cytosol]' complex without a literature reference. B9D2 is soluble and cytoplasmic before it is recruited to the transition zone, so cytosol is plausible but not its functional site. Kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0005929 cilium | IEA GO_REF:0000117 | ACCEPT | Summary: Cilium (IEA, ARBA). B9D2 is a ciliary transition-zone protein. Accepted. Reason: [PMID:19208769 "This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] Supporting Evidence: PMID:19208769 This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. |
| GO:0005930 axoneme | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Axoneme (IEA, UniProt subcellular location). The 2009 study reports human B9 orthologs at basal bodies as well as cilia. B9D2's defined site is the transition zone at the base of the axoneme. It regulates axonemal microtubule post-translational modifications from there, through the B9-TMEM67 module controlling tubulin-modifying enzymes, rather than by residing along the axoneme. Kept as non-core. Reason: [PMID:19208769 "This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia."] [file:human/B9D2/B9D2-uniprot.txt "CC {ECO:0000269|PubMed:19208769}. Cytoplasm, cytoskeleton, cilium axoneme"] [PMID:41165761 "Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia."] Supporting Evidence: PMID:19208769 This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. file:human/B9D2/B9D2-uniprot.txt CC {ECO:0000269|PubMed:19208769}. Cytoplasm, cytoskeleton, cilium axoneme PMID:41165761 Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia. |
| GO:0016020 membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Membrane (IEA, from mouse). B9D2 is a soluble B9/C2-domain protein with no transmembrane segment. It associates with the transition-zone membrane through the MKS module: the B9 complex binds and anchors the transmembrane protein TMEM67 to the TZ membrane. Peripheral, not integral; kept as non-core. Reason: [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:41165761 "We also found that the B9 complex interacts with and anchors TMEM67 to the TZ membrane, thereby stabilizing the MKS module and maintaining the integrity of the TZ diffusion barrier."] [PMID:41165761 "Co-IP experiments using FLAG-TMEM67 as bait confirmed interactions between TMEM67, B9D2, and MKS1 (Figure 2B)."] Supporting Evidence: PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:41165761 We also found that the B9 complex interacts with and anchors TMEM67 to the TZ membrane, thereby stabilizing the MKS module and maintaining the integrity of the TZ diffusion barrier. PMID:41165761 Co-IP experiments using FLAG-TMEM67 as bait confirmed interactions between TMEM67, B9D2, and MKS1 (Figure 2B). |
| GO:0035869 ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: Ciliary transition zone (NAS). B9D2 is a soluble transition-zone protein of the MKS module and localizes there interdependently with MKS1 and B9D1. Core location. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:22179047 "Using RNAi screening, proteomics, cell biological and mouse genetics approaches, we have identified a complex of nine proteins, seven of which are disrupted in human ciliopathies."] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:22179047 Using RNAi screening, proteomics, cell biological and mouse genetics approaches, we have identified a complex of nine proteins, seven of which are disrupted in human ciliopathies. |
| GO:0036038 MKS complex | IBA GO_REF:0000033 | ACCEPT | Summary: MKS complex (IBA). B9D2 is one of the three soluble B9-domain proteins of the MKS module at the ciliary transition zone. It bridges MKS1 and B9D1 (MKS1-B9D2-B9D1), and the three localize interdependently. Core. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:21763481 "With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized"] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000311628 SUPPORTS TRANSFER B9-domain family node (MKS1/B9D1/B9D2 across metazoa and trypanosomes). Transition-zone complex membership and ciliogenesis roles are conserved. Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. file:human/B9D2/B9D2-uniprot.txt CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized |
| GO:0036038 MKS complex | IEA GO_REF:0000107 | ACCEPT | Summary: MKS complex (IEA). B9D2 is one of the three soluble B9-domain proteins of the MKS module at the ciliary transition zone. It bridges MKS1 and B9D1 (MKS1-B9D2-B9D1), and the three localize interdependently. Core. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:21763481 "With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized"] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. file:human/B9D2/B9D2-uniprot.txt CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized |
| GO:0036038 MKS complex | ISS GO_REF:0000024 | ACCEPT | Summary: MKS complex (ISS). B9D2 is one of the three soluble B9-domain proteins of the MKS module at the ciliary transition zone. It bridges MKS1 and B9D1 (MKS1-B9D2-B9D1), and the three localize interdependently. Core. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:21763481 "With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized"] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. file:human/B9D2/B9D2-uniprot.txt CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized |
| GO:0036038 MKS complex | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: MKS complex (NAS). B9D2 is one of the three soluble B9-domain proteins of the MKS module at the ciliary transition zone. It bridges MKS1 and B9D1 (MKS1-B9D2-B9D1), and the three localize interdependently. Core. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:32726168 "Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common."] [PMID:21763481 "With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized"] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:32726168 Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. file:human/B9D2/B9D2-uniprot.txt CC -!- FUNCTION: Component of the tectonic-like complex, a complex localized |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: Ciliary basal body (IDA). Human B9D2 localizes to basal bodies, as do the C. elegans orthologs at transition zones/basal bodies. The transition zone lies immediately distal to the basal body. Accepted. Reason: [PMID:19208769 "This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:19208769 This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0036064 ciliary basal body | IDA PMID:19208769 Functional interactions between the ciliopathy-associated Me... | ACCEPT | Summary: Ciliary basal body (IDA). Human B9D2 localizes to basal bodies, as do the C. elegans orthologs at transition zones/basal bodies. The transition zone lies immediately distal to the basal body. Accepted. Reason: [PMID:19208769 "This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia."] [file:human/B9D2/B9D2-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body"] Supporting Evidence: PMID:19208769 This localization is evolutionarily conserved, because the human orthologues also localize to basal bodies, as well as cilia. file:human/B9D2/B9D2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body |
| GO:0043015 gamma-tubulin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Gamma-tubulin binding (IEA, from mouse B9d2/Stumpy). UniProt records the TUBG1 interaction only by similarity. No human data are cited, and the functional role of B9D2 is in the transition-zone complex. Kept as non-core. Reason: [file:human/B9D2/B9D2-uniprot.txt "CC Interacts with TUBG1 (By similarity). {ECO:0000250}."] Supporting Evidence: file:human/B9D2/B9D2-uniprot.txt CC Interacts with TUBG1 (By similarity). {ECO:0000250}. |
| GO:0043015 gamma-tubulin binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Gamma-tubulin binding (ISS, from mouse B9d2/Stumpy). UniProt records the TUBG1 interaction only by similarity. No human data are cited, and the functional role of B9D2 is in the transition-zone complex. Kept as non-core. Reason: [file:human/B9D2/B9D2-uniprot.txt "CC Interacts with TUBG1 (By similarity). {ECO:0000250}."] Supporting Evidence: file:human/B9D2/B9D2-uniprot.txt CC Interacts with TUBG1 (By similarity). {ECO:0000250}. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Cilium assembly (IBA). B9D2-knockout RPE1 cells have moderately reduced ciliogenesis efficiency and shorter cilia. Before ciliogenesis, B9 proteins at the mother centriole promote vesicle docking and CP110 removal. Mouse B9d2 (Stumpy) mutants compromise ciliogenesis, and a B9D2 missense allele causes Meckel syndrome. B9D2 contributes to, but is not essential for, cilium formation. Accepted. Reason: [PMID:32726168 "Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis."] [PMID:41165761 "During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly."] [PMID:21763481 "Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS."] [PMID:21763481 "We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000311628 SUPPORTS TRANSFER B9-domain family node (MKS1/B9D1/B9D2 across metazoa and trypanosomes). Transition-zone complex membership and ciliogenesis roles are conserved. Supporting Evidence: PMID:32726168 Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis. PMID:41165761 During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly. PMID:21763481 Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. PMID:21763481 We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Cilium assembly (IEA). B9D2-knockout RPE1 cells have moderately reduced ciliogenesis efficiency and shorter cilia. Before ciliogenesis, B9 proteins at the mother centriole promote vesicle docking and CP110 removal. Mouse B9d2 (Stumpy) mutants compromise ciliogenesis, and a B9D2 missense allele causes Meckel syndrome. B9D2 contributes to, but is not essential for, cilium formation. Accepted. Reason: [PMID:32726168 "Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis."] [PMID:41165761 "During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly."] [PMID:21763481 "Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS."] [PMID:21763481 "We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls."] Supporting Evidence: PMID:32726168 Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis. PMID:41165761 During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly. PMID:21763481 Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. PMID:21763481 We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Cilium assembly (ISS). B9D2-knockout RPE1 cells have moderately reduced ciliogenesis efficiency and shorter cilia. Before ciliogenesis, B9 proteins at the mother centriole promote vesicle docking and CP110 removal. Mouse B9d2 (Stumpy) mutants compromise ciliogenesis, and a B9D2 missense allele causes Meckel syndrome. B9D2 contributes to, but is not essential for, cilium formation. Accepted. Reason: [PMID:32726168 "Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis."] [PMID:41165761 "During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly."] [PMID:21763481 "Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS."] [PMID:21763481 "We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls."] Supporting Evidence: PMID:32726168 Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis. PMID:41165761 During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly. PMID:21763481 Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. PMID:21763481 We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Cilium assembly (ISS). B9D2-knockout RPE1 cells have moderately reduced ciliogenesis efficiency and shorter cilia. Before ciliogenesis, B9 proteins at the mother centriole promote vesicle docking and CP110 removal. Mouse B9d2 (Stumpy) mutants compromise ciliogenesis, and a B9D2 missense allele causes Meckel syndrome. B9D2 contributes to, but is not essential for, cilium formation. Accepted. Reason: [PMID:32726168 "Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis."] [PMID:41165761 "During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly."] [PMID:21763481 "Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS."] [PMID:21763481 "We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls."] Supporting Evidence: PMID:32726168 Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis. PMID:41165761 During ciliogenesis, B9 proteins localize to the mother centriole, facilitate the docking of membrane vesicles to the distal appendages, and promote the removal of CP110 from the mother centriole, thus initiating cilia assembly. PMID:21763481 Mouse mutations in either Mks1 or B9d2 compromise ciliogenesis and result in phenotypes similar to those of MKS. PMID:21763481 We identified a homozygous c.301A>C (p.Ser101Arg) B9D2 mutation that segregates with MKS, affects an evolutionarily conserved residue, and is absent from controls. |
| GO:1904491 protein localization to ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: Protein localization to ciliary transition zone (NAS). The B9 proteins localize to the transition zone interdependently, so B9D2 is needed for MKS1 and B9D1 to be targeted there and vice versa. The MKS module as a whole is required to localize other TZ components. Accepted. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:22179047 "Using RNAi screening, proteomics, cell biological and mouse genetics approaches, we have identified a complex of nine proteins, seven of which are disrupted in human ciliopathies."] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:22179047 Using RNAi screening, proteomics, cell biological and mouse genetics approaches, we have identified a complex of nine proteins, seven of which are disrupted in human ciliopathies. |
| GO:0030674 protein-macromolecule adaptor activity | IDA PMID:32726168 Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is... | NEW | Summary: Protein-macromolecule adaptor activity (NEW, IDA). The B9 proteins assemble as MKS1-B9D2-B9D1, so B9D2 is the central subunit that brings MKS1 and B9D1 together, and the three localize to the TZ interdependently. The complex in turn binds and anchors TMEM67 at the TZ membrane, stabilizing the MKS module. This fits GO's definition of an adaptor that brings macromolecules into contact so they function together. Affinage proposed the parent, GO:0060090; the more specific protein-macromolecule child is used. MKS1 and B9D1, the end members of the chain, carry only protein binding in GOA. The adaptor role is specific to B9D2's bridging position. Reason: [PMID:32726168 "We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ."] [PMID:41165761 "We also found that the B9 complex interacts with and anchors TMEM67 to the TZ membrane, thereby stabilizing the MKS module and maintaining the integrity of the TZ diffusion barrier."] [PMID:41165761 "Co-IP experiments using FLAG-TMEM67 as bait confirmed interactions between TMEM67, B9D2, and MKS1 (Figure 2B)."] Supporting Evidence: PMID:32726168 We here demonstrate the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrate their interdependent localization to the TZ. PMID:41165761 We also found that the B9 complex interacts with and anchors TMEM67 to the TZ membrane, thereby stabilizing the MKS module and maintaining the integrity of the TZ diffusion barrier. PMID:41165761 Co-IP experiments using FLAG-TMEM67 as bait confirmed interactions between TMEM67, B9D2, and MKS1 (Figure 2B). PMID:21763481 With coimmunoprecipitation and mass spectrometric analyses, we found that Mks1, B9d1, and B9d2 interact physically, but that the p.Ser101Arg mutation abrogates the ability of B9d2 to interact with Mks1, further suggesting that the mutation compromises B9d2 function. |
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Download this section (compressed HTML)Q: Does the B9D2 B9 (C2-like) domain bind membrane lipids at the transition zone, and is that required for the diffusion barrier?
Experiment: Test purified B9 complex (MKS1-B9D2-B9D1) for liposome binding, and rescue B9D2-KO RPE1 cells with B9-domain lipid-binding mutants, scoring GPR161 ciliary retention and membrane-protein diffusion (FRAP).
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: How the soluble B9 complex contributes to the transition-zone diffusion barrier at the molecular level is unknown. It may bind membrane lipids through its C2-like B9 domains or scaffold the transmembrane MKS-module proteins.
OPEN BIOLOGY
What is known: Established: B9D2 bridges MKS1 and B9D1 and localizes interdependently with them at the transition zone (PMID:32726168). The B9 complex binds and anchors TMEM67 at the TZ membrane (PMID:41165761). B9D2 is needed for ciliary membrane composition (GPR161 retention). Not established: direct lipid or membrane binding by the B9 (C2-like) domains, and the structural basis of the barrier.
Provenance (the field's own admissions):
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