TCTN1 (tectonic-1) is a conserved signal-peptide protein of the tectonic family. It is a component of the MKS (tectonic-like) complex at the ciliary transition zone, together with TCTN2, TCTN3, MKS1, TMEM216, TMEM67, B9D1, CC2D2A and CEP290. This membrane-spanning assembly acts as a diffusion barrier that keeps the ciliary membrane a distinct signaling compartment. TCTN1 is required for MKS1 and TMEM67 to reach the transition zone, for ciliogenesis in some tissues such as the embryonic node and neural tube, and for ciliary localization of membrane-associated proteins such as ARL13B, adenylyl cyclase 3, Smoothened and PKD2. Through these ciliary roles it is needed for full Hedgehog pathway activation and repression in the neural tube and limb, acting downstream of Smoothened and RAB23. A TCTN1 mutation causes Joubert syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: UniProt subcellular-location mapping (Secreted, by curator inference from the signal peptide) to extracellular region. Reason: TCTN1 has an N-terminal signal peptide. The founding Tectonic paper described the family as secreted and transmembrane proteins. However, UniProt notes that the full-length protein might not be secreted. Endogenous and tagged TCTN1 concentrates at the ciliary transition zone as part of a membrane-spanning MKS/tectonic complex. Secretion of native full-length TCTN1 has not been demonstrated, so extracellular region overstates the evidence. Supporting Evidence: PMID:21725307 Tctn1 belongs to a family of signal sequence-containing proteins conserved among eukaryotes that generate cilia or flagella. PMID:16357211 This protein, named Tectonic, is the founding member of a previously undescribed family of evolutionarily conserved secreted and transmembrane proteins. PMID:21725307 We demonstrate that Tctn1 forms a membrane-spanning transition zone complex with JBTS and MKS proteins, and identify human TCTN1 as a novel JBTS gene. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5617816 | MARK AS OVER ANNOTATED | Summary: Reactome places TCTN1 in the cytosol in the RAB3IP/RAB8A ciliary-vesicle step. Reason: TCTN1 is a signal-peptide protein that enters the secretory pathway. In the transition-zone complex it is expected to face the lumen or the extracellular side of the membrane, not the cytosol. Cytosol is a modelling convenience in Reactome and is unlikely to reflect where TCTN1 actually resides. Supporting Evidence: PMID:21725307 Tctn1 belongs to a family of signal sequence-containing proteins conserved among eukaryotes that generate cilia or flagella. PMID:21725307 We demonstrate that Tctn1 forms a membrane-spanning transition zone complex with JBTS and MKS proteins, and identify human TCTN1 as a novel JBTS gene. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5626681 | MARK AS OVER ANNOTATED | Summary: Reactome places TCTN1 in the cytosol for the 'Recruitment of transition zone proteins' event. Reason: As above, a signal-peptide protein of a membrane-spanning transition-zone complex is not expected to be cytosolic. Supporting Evidence: PMID:21725307 Tctn1 belongs to a family of signal sequence-containing proteins conserved among eukaryotes that generate cilia or flagella. PMID:21725307 We demonstrate that Tctn1 forms a membrane-spanning transition zone complex with JBTS and MKS proteins, and identify human TCTN1 as a novel JBTS gene. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5638009 | MARK AS OVER ANNOTATED | Summary: Reactome places TCTN1 in the cytosol for CEP164-dependent vesicle recruitment. Reason: As above. Supporting Evidence: PMID:21725307 Tctn1 belongs to a family of signal sequence-containing proteins conserved among eukaryotes that generate cilia or flagella. |
| GO:0016020 membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCTN1 to membrane. Reason: TCTN1 is a signal-peptide protein in a membrane-spanning transition-zone complex with the transmembrane proteins TMEM216, TMEM67 and TCTN2. Membrane association is acceptable as a general location. Supporting Evidence: PMID:21725307 We demonstrate that Tctn1 forms a membrane-spanning transition zone complex with JBTS and MKS proteins, and identify human TCTN1 as a novel JBTS gene. |
| GO:0035869 ciliary transition zone | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCTN1 to the ciliary transition zone. Reason: TCTN1 localizes to the transition zone in human RPE1 cells. This is the core location. Supporting Evidence: PMID:21725307 In hTERT-RPE1 cells, Tctn1 localized to the transition zone, between the ciliary axoneme and basal body |
| GO:0035869 ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: A curator statement placing TCTN1 at the transition zone, citing the TMEM231/B9D1 ciliopathy complex paper. Reason: This is correct. The cached abstract does not name TCTN1, but the curator read the full text, which includes the tectonic proteins among the nine-protein complex. Transition-zone localization of TCTN1 is directly shown in PMID:21725307. Supporting Evidence: PMID:22179047 acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle PMID:21725307 In hTERT-RPE1 cells, Tctn1 localized to the transition zone, between the ciliary axoneme and basal body |
| GO:0036038 MKS complex | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference that TCTN1 is part of the MKS complex. Reason: This is well supported. Tctn1 purifications recover MKS1, TMEM216, TMEM67, CEP290, B9D1, TCTN2, TCTN3 and CC2D2A. Supporting Evidence: PMID:21725307 Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. PMID:21725307 The two strongest Tctn1 interactors were Tctn2 and Tctn3, indicating that the three Tectonics are part of the same complex. |
| GO:0036038 MKS complex | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCTN1 to the MKS complex. Reason: This is correct. Supporting Evidence: PMID:21725307 Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. |
| GO:0036038 MKS complex | ISS GO_REF:0000024 | ACCEPT | Summary: Transfer from mouse Tctn1 of MKS complex membership. Reason: This is correct and directly supported by the mouse proteomics. Supporting Evidence: PMID:21725307 Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. |
| GO:0036038 MKS complex | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: A curator statement of MKS complex membership. Reason: This is correct. Supporting Evidence: PMID:22179047 acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle PMID:21725307 Tctn1 forms a complex with multiple ciliopathy proteins associated with Meckel and Joubert syndromes, including Mks1, Tmem216, Tmem67, Cep290, B9d1, Tctn2 and Cc2d2a. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference that TCTN1 acts in cilium assembly. Reason: Tctn1 is essential for ciliogenesis in the mouse node and neural tube, where basal bodies dock but fail to extend axonemes. It is dispensable in some other tissues. The process is accepted, with the caveat that the requirement is tissue-specific. Supporting Evidence: PMID:21725307 we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. PMID:21725307 transmission electron microscopy (TEM) demonstrated that basal bodies of mutant node cells attach to the plasma membrane but fail to extend axonemes |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCTN1 to cilium assembly. Reason: This is correct. Supporting Evidence: PMID:21725307 we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Transfer from mouse Tctn1 of a role in cilium assembly. Reason: This is correct. Supporting Evidence: PMID:21725307 we investigated Tectonic1 (Tctn1), a regulator of mouse Hedgehog signaling, and found that it is essential for ciliogenesis in some, but not all, tissues. PMID:21725307 transmission electron microscopy (TEM) demonstrated that basal bodies of mutant node cells attach to the plasma membrane but fail to extend axonemes |
| GO:1904491 protein localization to ciliary transition zone | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference that TCTN1 acts in protein localization to the ciliary transition zone. Reason: Tctn1-null MEFs have reduced MKS1 and TMEM67 at the transition zone, so TCTN1 is required to localize a subset of MKS-complex proteins. This is a core function. Supporting Evidence: PMID:21725307 In contrast, Tctn1−/− MEFs exhibited decreased Mks1 and Tmem67 localization to the transition zone PMID:21725307 These results reveal that Tctn1 is required for transition zone localization of a subset of interacting proteins. |
| GO:1904491 protein localization to ciliary transition zone | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCTN1 to protein localization to the ciliary transition zone. Reason: This is correct. Supporting Evidence: PMID:21725307 In contrast, Tctn1−/− MEFs exhibited decreased Mks1 and Tmem67 localization to the transition zone |
| GO:1904491 protein localization to ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: A curator statement of a role in protein localization to the ciliary transition zone. Reason: This is consistent with the direct mouse data and with the interdependent localization of MKS-complex components. Supporting Evidence: PMID:21725307 These results reveal that Tctn1 is required for transition zone localization of a subset of interacting proteins. PMID:22179047 acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle |
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Download this section (compressed HTML)Q: What is the topology of TCTN1 at the transition zone? Is it held at the extracellular or lumenal face by binding to TCTN2/TMEM216/TMEM67, and is any of it secreted in vivo?
Q: Is the Hedgehog phenotype of Tctn1 mutants entirely explained by loss of ciliary Smoothened and ARL13B, or does TCTN1 have a separate signaling role?
Experiment: Map TCTN1 topology at the transition zone with protease-protection and surface-labelling assays on non-permeabilized ciliated cells, and test for secreted TCTN1 in conditioned medium from cells expressing untagged endogenous protein.
Experiment: Combine domain-deletion rescue of Tctn1-null MEFs with assays for MKS1/TMEM67 recruitment and ciliary Smoothened entry to map the parts of TCTN1 needed for complex assembly versus gate function.
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