MKS-1 (also known as XBX-7) is a B9 domain-containing protein that localizes to the ciliary transition zone in C. elegans sensory neurons. It is the ortholog of human MKS1, which is mutated in Meckel-Gruber syndrome. MKS-1 is a component of the MKS complex (also called the MKS module), which works together with the NPHP complex to establish and maintain the ciliary gate at the transition zone. The B9 domain is structurally related to C2 domains and may be involved in membrane association. MKS-1 functions redundantly with other B9 proteins (MKSR-1/TZA-1 and MKSR-2/TZA-2) and the nephrocystins (NPH-1, NPH-4). Single mutants show no overt ciliary defects, but combined mutations with nphp genes result in severe ciliogenesis and dendrite formation defects in amphid and phasmid neurons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0036038 MKS complex | IBA GO_REF:0000033 | ACCEPT | Summary: MKS-1 is a well-established component of the MKS complex (MKS module) at the ciliary transition zone. The C. elegans B9 proteins (MKS-1, MKSR-1, MKSR-2) form a complex that localizes to the base of cilia (PMID:18337471). Williams et al. (2011) demonstrated that MKS-1 functions as part of the MKS module together with MKSR-1, MKSR-2, MKS-3, MKS-5, and MKS-6 (PMID:21422230). This annotation is phylogenetically inferred from multiple orthologs including mouse and human MKS1. Reason: The annotation is strongly supported by multiple studies demonstrating that MKS-1 is a bona fide component of the MKS complex at the transition zone. The IBA annotation is based on phylogenetic inference from well- characterized orthologs and is consistent with experimental data from C. elegans. Supporting Evidence: PMID:18337471 the C. elegans B9 proteins form a complex that localizes to the base of cilia PMID:21422230 the conserved C. elegans B9 domain (MKS-1, MKSR-1, and MKSR-2), MKS-3/TMEM67, MKS-5/RPGRIP1L, MKS-6/CC2D2A, NPHP-1, and NPHP-4 proteins exhibit essential, collective functions at the transition zone (TZ) PMID:19208769 All Caenorhabditis elegans B9-domain-containing proteins, MKS-1 and MKS-1-related proteins 1 and 2 (MKSR-1, MKSR-2), localize to transition zones/basal bodies of sensory cilia file:worm/mks-1/mks-1-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: MKS-1 is involved in cilium assembly, though in a functionally redundant manner with other B9 proteins and nephrocystins. Single mks-1 mutants do not show overt ciliogenesis defects, but combined mutations with nphp genes result in severe cilium formation defects (PMID:18337471, PMID:21422230). The MKS module works with the NPHP module to establish basal body/transition zone membrane associations during early ciliogenesis. Reason: The IBA annotation is appropriate. MKS-1 does contribute to cilium assembly as part of the MKS module, even though this function is redundant with other proteins. The combined evidence shows that MKS proteins are required for normal ciliogenesis when NPHP function is compromised. Supporting Evidence: PMID:18337471 the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons PMID:21422230 Specifically, MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport-dependent axoneme extension |
| GO:0005929 cilium | IEA GO_REF:0000117 | MODIFY | Summary: This IEA annotation states MKS-1 is located in the cilium. However, the protein specifically localizes to the transition zone at the base of cilia, not throughout the cilium. A more specific cellular component term would be more accurate. Reason: The annotation is not incorrect since the transition zone is part of the cilium, but it is too general. MKS-1 specifically localizes to the ciliary transition zone, which is a distinct subcompartment. The GO:0035869 (ciliary transition zone) term would be more informative and accurate. Additionally, the MKS complex annotation (GO:0036038) already captures the localization since the MKS complex is by definition located at the transition zone. Proposed replacements: ciliary transition zone Supporting Evidence: PMID:19208769 All Caenorhabditis elegans B9-domain-containing proteins, MKS-1 and MKS-1-related proteins 1 and 2 (MKSR-1, MKSR-2), localize to transition zones/basal bodies of sensory cilia PMID:21422230 MKS-1::YFP localization to the TZ in relation to the CHE-13 IFT protein |
| GO:0030030 cell projection organization | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This IEA annotation was inferred from the UniProtKB keyword mapping for 'Cell projection'. While not incorrect, it is very general and less informative than the cilium assembly annotation already present. Reason: This term is too general. The more specific GO:0060271 (cilium assembly) annotation is already present and better captures the actual function of MKS-1. Cell projection organization is a parent term that adds no additional information beyond what cilium assembly provides. Retaining both is redundant. Supporting Evidence: PMID:18337471 the B9 proteins function redundantly with the nephrocystins to regulate the formation and/or maintenance of cilia and dendrites in the amphid and phasmid ciliated sensory neurons |
| GO:0035869 ciliary transition zone | IDA PMID:19208769 Functional interactions between the ciliopathy-associated Me... | NEW | Summary: MKS-1 localizes specifically to the ciliary transition zone as demonstrated by fluorescence microscopy studies. This annotation should be added based on direct experimental evidence. Reason: Multiple publications directly demonstrate that MKS-1 localizes to the transition zone in C. elegans sensory neurons. This is a core annotation that accurately describes the subcellular localization of the protein. Supporting Evidence: PMID:19208769 All Caenorhabditis elegans B9-domain-containing proteins, MKS-1 and MKS-1-related proteins 1 and 2 (MKSR-1, MKSR-2), localize to transition zones/basal bodies of sensory cilia PMID:21422230 MKS-1::YFP localization to the TZ in relation to the CHE-13 IFT protein 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:1905349 ciliary transition zone assembly | IMP PMID:21422230 MKS and NPHP modules cooperate to establish basal body/trans... | NEW | Summary: The MKS module including MKS-1 is required for proper transition zone assembly and Y-link formation. Combined mutations affecting MKS and NPHP modules result in defective Y-link structures at the transition zone. Reason: MKS-1 contributes to transition zone assembly as part of the MKS module. The function is only revealed in combination with NPHP mutations due to redundancy, but the process-level annotation is supported by the evidence. Supporting Evidence: PMID:21422230 Specifically, MKS/MKSR/NPHP proteins establish basal body/TZ membrane attachments before or coinciding with intraflagellar transport-dependent axoneme extension PMID:26595381 TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors |
| GO:0005515 protein binding | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
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