SCLT1 (sodium channel and clathrin linker 1) is a coiled-coil component of the distal appendages (ciliary transition fibers) of the mother centriole. Recruited by CEP83, it forms part of the appendage blade backbone and is required to recruit the more distal appendage components FBF1 and CEP164, as well as LRRC45. Through this scaffolding role SCLT1 is essential for docking of the mother centriole to membranes and for primary cilium assembly. Sclt1-null mice show ciliopathy phenotypes (cystic kidney, cleft palate, polydactyly), and SCLT1 variants are associated with oral-facial-digital syndrome. The rat orthologue (CAP-1A) was first described as an adaptor that binds the Nav1.8 sodium channel and clathrin and lowers Nav1.8 current density in sensory neurons, a role not yet examined in human cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005813 centrosome | IDA PMID:21399614 Novel asymmetrically localizing components of human centroso... | ACCEPT | Summary: IDA from the Jakobsen et al. centrosome proteomics/HPA antibody screen. Reason: The specific SCLT1 image is in the paper's supplementary data, which is not in the cache, but centrosomal localization is independently and robustly established: SCLT1 is a distal appendage component of the mother centriole. Accepted, deferring to the curator. Supporting Evidence: PMID:21399614 An antibody screen covering 4000 genes revealed an additional 113 candidates. PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0005814 centriole | IBA GO_REF:0000033 | ACCEPT | Summary: IBA centriole location; SCLT1 is among the experimental sources. Reason: SCLT1 is part of the distal appendage blade backbone on the mother centriole. Supporting Evidence: PMID:29789620 CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. |
| GO:0005814 centriole | IDA PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IDA: SCLT1 identified as a distal appendage component of the mother centriole. Reason: Direct localization evidence. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0005814 centriole | IEA GO_REF:0000120 | ACCEPT | Summary: IEA centriole location transferred from mouse/UniProt subcellular location. Reason: Consistent with direct human evidence. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626223 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626227 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626228 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626699 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | KEEP AS NON CORE | Summary: Reactome places this distal appendage protein in its 'cytosol' compartment for a ciliogenesis reaction; Reactome has no centriole/distal-appendage compartment, so centrosomal reactions are modelled in cytosol. Reason: This TAS row reflects a Reactome compartment convention rather than an independent localization experiment. The protein is a structural component of the centriolar distal appendages (ciliary transition fibers), which are part of the centrosome in the cytoplasm rather than the soluble cytosol. The location is broadly compatible (the centrosome lies in the cytoplasm and is not membrane-bounded) but uninformative, so it is retained only as non-core; the informative location is ciliary transition fiber. |
| GO:0017080 sodium channel regulator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA from rat Sclt1 (CAP-1A), which links Nav1.8 to clathrin and reduces Nav1.8 current density in DRG neurons. Reason: A single rat study supports a role in limiting Nav1.8 surface density, probably via clathrin-dependent internalization. This has not been tested for human SCLT1 and is unrelated to its well-established distal appendage role, which is the function supported by human genetics and cell biology. Retained as a non-core, ortholog-based activity. Supporting Evidence: PMID:15797711 We have identified a novel protein, clathrin-associated protein-1A (CAP-1A), which contains distinct domains that bind Na(v)1.8 and clathrin. PMID:15797711 Coexpression of CAP-1A and Na(v)1.8 in DRG neurons reduces Na(v)1.8 current density by approximately 50% without affecting the endogenous or recombinant tetrodotoxin-sensitive currents. |
| GO:0030276 clathrin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IEA clathrin binding transferred from rat CAP-1A. Reason: The rat orthologue contains a clathrin-binding domain. Plausible but untested in human, and peripheral to the centriolar role. Supporting Evidence: PMID:15797711 We have identified a novel protein, clathrin-associated protein-1A (CAP-1A), which contains distinct domains that bind Na(v)1.8 and clathrin. |
| GO:0036064 ciliary basal body | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence (GO_REF:0000052) places SCLT1 at the basal body (HPA grade Supported). Reason: Consistent with SCLT1 being a distal appendage protein; distal appendages become transition fibers on the basal body of ciliated cells. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins |
| GO:0045162 clustering of voltage-gated sodium channels | IEA GO_REF:0000120 | REMOVE | Summary: IEA (ortholog/InterPro mapping) to clustering of voltage-gated sodium channels. Reason: The only functional data (rat CAP-1A) show that SCLT1 reduces Nav1.8 current density, consistent with removal of channels from the surface, not with clustering of channels at specific membrane domains such as nodes of Ranvier. No evidence supports a clustering role, so this mapping is not supported. Supporting Evidence: PMID:15797711 Coexpression of CAP-1A and Na(v)1.8 in DRG neurons reduces Na(v)1.8 current density by approximately 50% without affecting the endogenous or recombinant tetrodotoxin-sensitive currents. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: IBA cilium assembly; SCLT1 among the sources. Reason: SCLT1 is required for ciliogenesis as a distal appendage component that recruits FBF1 and CEP164. Supporting Evidence: PMID:23348840 All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. PMID:23348840 CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. |
| GO:0060271 cilium assembly | IMP PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IMP: SCLT1 depletion abolishes ciliogenesis. Reason: SCLT1 is a structural distal appendage component that recruits FBF1 and CEP164, so it participates in the docking step that initiates cilium assembly. Supporting Evidence: PMID:23348840 All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. PMID:23348840 CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. |
| GO:0060271 cilium assembly | IMP PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IMP: SCLT1 depletion abolishes ciliogenesis (involved_in row). Reason: As above; corroborated by ciliopathy phenotypes in Sclt1-null mice. Supporting Evidence: PMID:23348840 All five DAP components are essential for ciliogenesis; loss of CEP83 specifically blocks centriole-to-membrane docking. PMID:28486600 The Sclt1-/- mice exhibit typical ciliopathy phenotypes, including cystic kidney, cleft palate and polydactyly. |
| GO:0071439 clathrin complex | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: IEA part_of clathrin complex transferred from rat CAP-1A. Reason: The rat study shows CAP-1A can form a multiprotein complex with Nav1.8 and clathrin, i.e. it is a clathrin-binding adaptor. That does not make it a subunit of the clathrin complex (the triskelion of heavy and light chains). The clathrin binding annotation already captures the claim. Supporting Evidence: PMID:15797711 CAP-1A is abundantly expressed in DRG neurons and colocalizes with Na(v)1.8 and can form a multiprotein complex with Na(v)1.8 and clathrin. |
| GO:0097539 ciliary transition fiber | IDA PMID:23348840 Centriole distal appendages promote membrane docking, leadin... | ACCEPT | Summary: IDA: SCLT1 is one of five distal appendage (transition fiber) components. Reason: Defining location of SCLT1; super-resolution mapping places it in the blade backbone. Supporting Evidence: PMID:23348840 we identified five DAP components, including one previously described (CEP164), one partially characterized (CEP89 [ccdc123]), and three novel (CEP83 [ccdc41], SCLT1, and FBF1) DAP proteins PMID:29789620 CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. |
| GO:0005198 structural molecule activity | IDA PMID:29789620 Super-resolution architecture of mammalian centriole distal ... | NEW | Summary: Proposed: SCLT1 contributes to the structural integrity of the distal appendage (ciliary transition fiber) blade, as one of the four proteins forming the blade backbone. Reason: Super-resolution mapping shows the protein forms part of the backbone of the distal appendage blades, and loss-of-function abolishes recruitment of downstream appendage components. No enzymatic or specific binding activity is known, so structural molecule activity is the most accurate available MF term. This is a molecular-function proposal, not a process term. Supporting Evidence: PMID:29789620 CEP83, CEP89, SCLT1, and CEP164 form the backbone of pinwheel blades, with CEP83 confined at the root and CEP164 extending to the tip near the membrane-docking site. PMID:23348840 CEP83 recruits both SCLT1 and CEP89 to centrioles. Subsequent recruitment of FBF1 and CEP164 is independent of CEP89 but mediated by SCLT1. |
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Download this section (compressed HTML)Q: Is the rat CAP-1A role in limiting Nav1.8 surface density conserved for human SCLT1, and is it carried out by a non-centrosomal pool or by an alternative isoform?
Q: Does SCLT1 bind FBF1 and CEP164 directly, or does it recruit them through intermediates such as LRRC45?
Experiment: Express human SCLT1 isoforms with Nav1.8 in human iPSC-derived sensory neurons and measure surface channel density and clathrin-dependent internalization, comparing with SCLT1-knockout cells, to test whether the rat linker function is conserved.
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