MKS1 is a B9/C2-domain protein of the ciliary transition zone and a core subunit of the MKS (Meckel syndrome) module. Together with B9D2 and B9D1 it forms a soluble heterotrimeric B9-domain complex. The complex localizes to the distal transition zone at the level of the Y-links, between the axonemal microtubules and the ciliary membrane. There it is needed for the diffusion barrier that keeps the ciliary membrane's protein composition distinct from the plasma membrane. MKS1 is also needed for normal ciliogenesis and the control of centrosome number in some cell types. Loss-of-function mutations cause Meckel-Gruber syndrome and Joubert syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:17185389 The Meckel-Gruber Syndrome proteins MKS1 and meckelin intera... | REMOVE | Summary: MKS1 interaction with TMEM67 (meckelin). Co-immunoprecipitation of MKS1 with meckelin in ciliated cells. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. Supporting Evidence: PMID:17185389 Co-immunoprecipitation experiments show that wild-type meckelin and MKS1 interact |
| GO:0005515 protein binding | IPI PMID:19515853 Ciliary and centrosomal defects associated with mutation and... | REMOVE | Summary: MKS1 interaction with TMEM67 (meckelin). Interaction re-reported in the MKS1/MKS3 rat and patient study; both proteins are MKS-module transition-zone components. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. |
| GO:0005515 protein binding | IPI PMID:26595381 TMEM107 recruits ciliopathy proteins to subdomains of the ci... | REMOVE | Summary: MKS1 interaction with TMEM107. TMEM107 organizes recruitment of MKS module proteins including MKS-1 in C. elegans; the human interaction assay supports physical association within the MKS module. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. Supporting Evidence: PMID:26595381 nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237) |
| GO:0005515 protein binding | IPI PMID:26638075 A Dynamic Protein Interaction Landscape of the Human Centros... | REMOVE | Summary: MKS1 interaction with B9D2. Proximity labelling (BioID) hit in the centrosome-cilium interface map; B9D2 is MKS1's direct B9-domain partner. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. |
| GO:0005515 protein binding | IPI PMID:32726168 Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is... | REMOVE | Summary: MKS1 interaction with B9D2. MKS1 binds B9D2 directly, forming the linear MKS1-B9D2-B9D1 B9-domain complex required for TZ localization. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. 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 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: MKS1 interaction with B9D2. High-throughput binary interactome screen; consistent with the established MKS1-B9D2 module. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: MKS1 interaction with B9D2. Multimodal proteome map; consistent with the established MKS1-B9D2 interaction. Reason: GO:0005515 protein binding records that an interaction was detected but says nothing about what MKS1 does. The interaction itself is credible and is captured biologically by the MKS complex (GO:0036038) part_of annotations and by ciliary transition zone localization. Removal of the generic binding term does not mean the interaction is false; no more informative molecular-function term is supported by the assay. |
| GO:0005737 cytoplasm | IDA PMID:17185389 The Meckel-Gruber Syndrome proteins MKS1 and meckelin intera... | KEEP AS NON CORE | Summary: Cytoplasmic signal for MKS1 in cultured cells. Reason: MKS1 is a soluble protein, so a cytoplasmic pool is plausible, but its functionally relevant location is the basal body/transition zone. Cytoplasm is retained as a broad, non-core location. Supporting Evidence: PMID:17185389 MKS1 localized to basal bodies |
| GO:0005813 centrosome | IDA PMID:19208769 Functional interactions between the ciliopathy-associated Me... | ACCEPT | Summary: MKS1 localizes to the basal body/centrosome of ciliated and non-ciliated cells. Reason: Human MKS1 is detected at basal bodies (the centrosome-derived structure) and in cilia; patient cells show centrosome-number defects. Centrosome is an accurate if less specific location than ciliary transition zone. Supporting Evidence: PMID:19208769 the human orthologues also localize to basal bodies, as well as cilia |
| GO:0005813 centrosome | IDA PMID:19515853 Ciliary and centrosomal defects associated with mutation and... | ACCEPT | Summary: MKS1 at centrosomes in IMCD3 and patient-derived cells. Reason: Localization and centrosome-number phenotypes support a centrosome/basal-body location. Supporting Evidence: PMID:19515853 Kidney tissue and cells from MKS1 and MKS3 patients showed defects in centrosome and cilia number PMID:19515853 MKS1 and MKS3 functions are required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication |
| GO:0005813 centrosome | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic transfer of centrosome location from mouse Mks1 and UniProt subcellular location. Reason: Consistent with the human experimental centrosome/basal body localizations. Supporting Evidence: PMID:19208769 the human orthologues also localize to basal bodies, as well as cilia |
| GO:0005814 centriole | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer of centriole location from mouse. Reason: MKS1 sits at the distal end of the basal body (mother centriole) and in the adjoining transition zone; the centriole term is compatible but less informative than ciliary transition zone. Supporting Evidence: PMID:28401750 components of the MKS complex (MKS1, MKS1-R1/B9D1, MKS1-R2/B9D2), localize to the distal half of the TZ corresponding to the region containing y-links |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Reactome places the MKS complex in the cytosol in the RAB8A nucleotide exchange event. Reason: Broad compartment assigned to participants of the event; the GEF activity belongs to RAB3IP, not MKS1. Supporting Evidence: Reactome:R-HSA-5617816 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Reactome cytosol location in the recruitment of transition zone proteins event. Reason: The event is biologically apt for MKS1 (transition zone recruitment), but cytosol is a broad compartment; the informative location is ciliary transition zone. Supporting Evidence: Reactome:R-HSA-5626681 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Reactome cytosol location in CEP164-mediated recruitment of RAB3IP vesicles. Reason: Broad compartment from a pathway event whose activities belong to other participants. Supporting Evidence: Reactome:R-HSA-5638009 |
| GO:0005929 cilium | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of cilium localization. Reason: Correct: the transition zone is part of the cilium and human MKS1 is also detected in cilia. Supporting Evidence: PMID:19208769 the human orthologues also localize to basal bodies, as well as cilia |
| GO:0016020 membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer of membrane location from mouse Mks1. Reason: MKS1 is a soluble B9-domain protein that lies between axonemal microtubules and the ciliary membrane at the transition zone; association with membrane is plausible as peripheral association within the MKS module, but MKS1 is not an integral membrane protein. Retained as broad, non-core. 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:28401750 components of the MKS complex (MKS1, MKS1-R1/B9D1, MKS1-R2/B9D2), localize to the distal half of the TZ corresponding to the region containing y-links |
| GO:0035869 ciliary transition zone | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of ciliary transition zone location from mouse Mks1. Reason: Core location; human MKS1 localizes to the TZ interdependently with B9D1 and B9D2. 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 |
| GO:0035869 ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: MKS1 is part of the transition-zone ciliopathy complex. Reason: Core location; supported by the curator statement and by direct human TZ localization data. Supporting Evidence: PMID:22179047 The complex that we have described is essential for normal cilia function and acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle 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 |
| GO:0036038 MKS complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference that MKS1 is part of the MKS complex. Reason: MKS1 is a defining member of the MKS module from worms to mammals; the IBA node placement is sound. 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:28401750 components of the MKS complex (MKS1, MKS1-R1/B9D1, MKS1-R2/B9D2), localize to the distal half of the TZ corresponding to the region containing y-links |
| GO:0036038 MKS complex | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of MKS complex membership from mouse Mks1. Reason: Consistent with human biochemical and localization data. 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 |
| GO:0036038 MKS complex | ISS GO_REF:0000024 | ACCEPT | Summary: Manual ortholog transfer of MKS complex membership from mouse Mks1. Reason: Consistent with human biochemical and localization data. 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 |
| GO:0036038 MKS complex | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: MKS1 is part of the transition-zone MKS complex described by Chih et al. Reason: Core complex membership. Supporting Evidence: PMID:22179047 The complex that we have described is essential for normal cilia function and acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence curation (HPA-type) of MKS1 at the ciliary basal body. Reason: Consistent with the published human basal-body localization. Supporting Evidence: PMID:19208769 the human orthologues also localize to basal bodies, as well as cilia |
| GO:0036064 ciliary basal body | IDA PMID:19208769 Functional interactions between the ciliopathy-associated Me... | ACCEPT | Summary: Human MKS1 localizes to basal bodies and cilia. Reason: Direct localization evidence in human cells. Supporting Evidence: PMID:19208769 the human orthologues also localize to basal bodies, as well as cilia |
| GO:0036064 ciliary basal body | IDA PMID:19515853 Ciliary and centrosomal defects associated with mutation and... | ACCEPT | Summary: MKS1 at basal bodies in IMCD3/patient cells. Reason: Basal body localization consistent with other studies. Supporting Evidence: PMID:17185389 MKS1 localized to basal bodies |
| GO:0048754 branching morphogenesis of an epithelial tube | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer of branching morphogenesis of an epithelial tube from mouse. Reason: Epithelial branching defects in 3D culture after MKS1/MKS3 depletion are a downstream developmental consequence of defective ciliogenesis, not a process MKS1 executes directly. Supporting Evidence: PMID:17185389 epithelial branching morphogenesis was severely impaired |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of cilium assembly for the MKS1 family. Reason: MKS1 is required for normal cilium formation in mammalian cells, although the B9D complex is 'involved in, although not essential for' ciliogenesis in RPE1 cells; its central role is TZ gating. Accepted at this level. Supporting Evidence: PMID:32726168 the B9D proteins are involved in, although not essential for, normal cilia biogenesis PMID:17185389 siRNA-mediated reduction of Mks1 and Mks3 expression in a ciliated epithelial cell-line blocked centriole migration to the apical membrane and consequent formation of the primary cilium |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer of cilium assembly from mouse Mks1. Reason: Consistent with mammalian knockdown and knockout phenotypes. Supporting Evidence: PMID:32726168 the B9D proteins are involved in, although not essential for, normal cilia biogenesis |
| GO:0060271 cilium assembly | IMP PMID:19515853 Ciliary and centrosomal defects associated with mutation and... | ACCEPT | Summary: Mks1 knockdown in IMCD3 cells and patient tissue show ciliary structure/number defects. Reason: Experimental support for a requirement in cilium assembly. Supporting Evidence: PMID:19515853 MKS1 and MKS3 functions are required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Manual ortholog transfer of cilium assembly from mouse Mks1. Reason: Consistent with human and mouse data. Supporting Evidence: PMID:17185389 siRNA-mediated reduction of Mks1 and Mks3 expression in a ciliated epithelial cell-line blocked centriole migration to the apical membrane and consequent formation of the primary cilium |
| GO:1904491 protein localization to ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: MKS1 participates in localizing MKS-module proteins to the transition zone. Reason: MKS1, B9D2 and B9D1 localize interdependently to the TZ and an MKS1 mutant unable to bind B9D2 fails to localize or restore ARL13B ciliary localization, showing MKS1 contributes structurally to assembling the TZ module. 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 By contrast, EGFP-fused MKS1(1–492), which lacks the ability to interact with B9D2 (Figure 1, C and D), did not localize to the TZ or restore ARL13B localization in MKS1-KO cells (Figure 5C). |
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Download this section (compressed HTML)Q: Does the MKS1 B9/C2 domain bind membrane lipids directly, and does that binding position the MKS module between the axoneme and the ciliary membrane?
Experiment: Liposome flotation/co-sedimentation of purified MKS1-B9D2-B9D1 complex to test direct lipid binding by the B9 domains, combined with TZ-localization rescue by lipid-binding-deficient mutants in MKS1-KO RPE1 cells.
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