TCTN2 (Tectonic-2) is a single-pass type I transmembrane glycoprotein with a large N-terminal extracellular/luminal tectonic domain and a short cytoplasmic tail. It is a core component of the MKS (tectonic) complex at the ciliary transition zone, where it lies close to the ciliary membrane together with TMEM67, TMEM216, TMEM231, TCTN1/3, CC2D2A, B9D1/2 and MKS1. Within this complex it is required for the transition-zone localization of neighbouring MKS-module proteins such as TMEM67 and MKS1, for the ciliary diffusion barrier that keeps membrane proteins such as ARL13B and Smoothened concentrated in the cilium, and, in a tissue-dependent manner, for ciliogenesis itself. As a result TCTN2 is needed for Hedgehog signal transduction and embryonic patterning; biallelic variants cause Meckel syndrome 8 and Joubert syndrome 24.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007224 smoothened signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: TCTN2 is required for Hedgehog (Smoothened) signal transduction: Tctn2-/- mouse embryos show neural tube patterning defects and Tctn2-/- MEFs fail to induce Ptch1/Gli1 after Smoothened agonist treatment. Reason: Supported by mouse knockout data (Sang et al. 2011). The requirement is indirect: TCTN2 acts at the transition zone to permit ciliary entry/retention of signalling membrane proteins (e.g. Smoothened, ARL13B), and Hedgehog signalling depends on the cilium. TCTN2 is not a signal transducer per se, so this is a downstream consequence of its core gating/ciliogenesis role. Supporting Evidence: PMID:21565611 Thus, Tctn2-/- neural tubes have defects characteristic of altered Hh signal transduction, and Tctn2-/- cells fail to respond to Hh agonists PMID:21565611 Following pathway activation by addition of a Smoothened agonist (SAG) both Ptc1 and Gli1 are induced ∼20-fold in wild-type MEFs, while Tctn2-/- MEFs display negligible responsiveness |
| GO:0007224 smoothened signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: TCTN2 is required for Hedgehog (Smoothened) signal transduction: Tctn2-/- mouse embryos show neural tube patterning defects and Tctn2-/- MEFs fail to induce Ptch1/Gli1 after Smoothened agonist treatment. Reason: Supported by mouse knockout data (Sang et al. 2011). The requirement is indirect: TCTN2 acts at the transition zone to permit ciliary entry/retention of signalling membrane proteins (e.g. Smoothened, ARL13B), and Hedgehog signalling depends on the cilium. TCTN2 is not a signal transducer per se, so this is a downstream consequence of its core gating/ciliogenesis role. Supporting Evidence: PMID:21565611 Thus, Tctn2-/- neural tubes have defects characteristic of altered Hh signal transduction, and Tctn2-/- cells fail to respond to Hh agonists PMID:21565611 Following pathway activation by addition of a Smoothened agonist (SAG) both Ptc1 and Gli1 are induced ∼20-fold in wild-type MEFs, while Tctn2-/- MEFs display negligible responsiveness |
| GO:0007224 smoothened signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: TCTN2 is required for Hedgehog (Smoothened) signal transduction: Tctn2-/- mouse embryos show neural tube patterning defects and Tctn2-/- MEFs fail to induce Ptch1/Gli1 after Smoothened agonist treatment. Reason: Supported by mouse knockout data (Sang et al. 2011). The requirement is indirect: TCTN2 acts at the transition zone to permit ciliary entry/retention of signalling membrane proteins (e.g. Smoothened, ARL13B), and Hedgehog signalling depends on the cilium. TCTN2 is not a signal transducer per se, so this is a downstream consequence of its core gating/ciliogenesis role. Supporting Evidence: PMID:21565611 Thus, Tctn2-/- neural tubes have defects characteristic of altered Hh signal transduction, and Tctn2-/- cells fail to respond to Hh agonists PMID:21565611 Following pathway activation by addition of a Smoothened agonist (SAG) both Ptc1 and Gli1 are induced ∼20-fold in wild-type MEFs, while Tctn2-/- MEFs display negligible responsiveness |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: TCTN2 is a single-pass type I membrane protein (signal peptide plus a C-terminal transmembrane segment). Reason: Correct but uninformative general location; ciliary transition zone / ciliary membrane are the informative locations. Supporting Evidence: PMID:29866362 TMEM67 and TCTN2 are close to the ciliary membrane, whereas MKS1 is likely in between |
| GO:0035869 ciliary transition zone | IEA GO_REF:0000107 | ACCEPT | Summary: TCTN2 localizes to the ciliary transition zone, close to the ciliary membrane, as part of the MKS module. Reason: Core location. Mouse complex members co-localize at the TZ (Garcia-Gonzalo 2011) and super-resolution imaging in human RPE1 cells places TCTN2 at the TZ near the ciliary membrane. Supporting Evidence: PMID:29866362 Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. PMID:21725307 Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. file:human/TCTN2/TCTN2-deep-research-falcon.md The best-supported function of TCTN2 is as a **membrane-associated organizing component of the ciliary transition-zone gate**. |
| GO:0035869 ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: TCTN2 localizes to the ciliary transition zone, close to the ciliary membrane, as part of the MKS module. Reason: Core location. Mouse complex members co-localize at the TZ (Garcia-Gonzalo 2011) and super-resolution imaging in human RPE1 cells places TCTN2 at the TZ near the ciliary membrane. Supporting Evidence: PMID:29866362 Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. PMID:21725307 Components of this complex co-localize at the transition zone, a region between the basal body and ciliary axoneme. file:human/TCTN2/TCTN2-deep-research-falcon.md The best-supported function of TCTN2 is as a **membrane-associated organizing component of the ciliary transition-zone gate**. |
| GO:0036038 MKS complex | IBA GO_REF:0000033 | ACCEPT | Summary: TCTN2 is a component of the MKS (tectonic) complex at the transition zone. Reason: TCTN2 co-purifies with Tctn1, Mks1, Tmem216, Tmem67, Cep290, B9d1 and Cc2d2a, and with Tmem231 in reciprocal purification, defining the MKS module. This is the defining complex membership for TCTN2. 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:25869670 This experiment confirmed the interaction between B9d1 and Tmem231, and revealed that Tmem231 interacts with multiple other components of the MKS complex, including Mks1, Tctn1, Tctn2, Tctn3, Cc2d2a (Mks6), and Tmem17 |
| GO:0036038 MKS complex | IEA GO_REF:0000107 | ACCEPT | Summary: TCTN2 is a component of the MKS (tectonic) complex at the transition zone. Reason: TCTN2 co-purifies with Tctn1, Mks1, Tmem216, Tmem67, Cep290, B9d1 and Cc2d2a, and with Tmem231 in reciprocal purification, defining the MKS module. This is the defining complex membership for TCTN2. 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:25869670 This experiment confirmed the interaction between B9d1 and Tmem231, and revealed that Tmem231 interacts with multiple other components of the MKS complex, including Mks1, Tctn1, Tctn2, Tctn3, Cc2d2a (Mks6), and Tmem17 |
| GO:0036038 MKS complex | ISS GO_REF:0000024 | ACCEPT | Summary: TCTN2 is a component of the MKS (tectonic) complex at the transition zone. Reason: TCTN2 co-purifies with Tctn1, Mks1, Tmem216, Tmem67, Cep290, B9d1 and Cc2d2a, and with Tmem231 in reciprocal purification, defining the MKS module. This is the defining complex membership for TCTN2. 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:25869670 This experiment confirmed the interaction between B9d1 and Tmem231, and revealed that Tmem231 interacts with multiple other components of the MKS complex, including Mks1, Tctn1, Tctn2, Tctn3, Cc2d2a (Mks6), and Tmem17 |
| GO:0036038 MKS complex | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: TCTN2 is a component of the MKS (tectonic) complex at the transition zone. Reason: TCTN2 co-purifies with Tctn1, Mks1, Tmem216, Tmem67, Cep290, B9d1 and Cc2d2a, and with Tmem231 in reciprocal purification, defining the MKS module. This is the defining complex membership for TCTN2. 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:25869670 This experiment confirmed the interaction between B9d1 and Tmem231, and revealed that Tmem231 interacts with multiple other components of the MKS complex, including Mks1, Tctn1, Tctn2, Tctn3, Cc2d2a (Mks6), and Tmem17 |
| GO:0060170 ciliary membrane | TAS Reactome:R-HSA-5617816 | ACCEPT | Summary: Reactome places TCTN2 at the ciliary membrane in the transition-zone recruitment and ciliary vesicle reactions. Reason: TCTN2 is a membrane protein whose transmembrane segment lies in the transition-zone portion of the ciliary membrane, adjacent to the ciliary membrane per super-resolution mapping. The ciliary transition zone term is more precise but ciliary membrane is a fair description of the membrane domain it occupies. Supporting Evidence: PMID:29866362 TMEM67 and TCTN2 are close to the ciliary membrane, whereas MKS1 is likely in between PMID:29866362 Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. |
| GO:0060170 ciliary membrane | TAS Reactome:R-HSA-5626681 | ACCEPT | Summary: Reactome places TCTN2 at the ciliary membrane in the transition-zone recruitment and ciliary vesicle reactions. Reason: TCTN2 is a membrane protein whose transmembrane segment lies in the transition-zone portion of the ciliary membrane, adjacent to the ciliary membrane per super-resolution mapping. The ciliary transition zone term is more precise but ciliary membrane is a fair description of the membrane domain it occupies. Supporting Evidence: PMID:29866362 TMEM67 and TCTN2 are close to the ciliary membrane, whereas MKS1 is likely in between PMID:29866362 Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. |
| GO:0060170 ciliary membrane | TAS Reactome:R-HSA-5638009 | ACCEPT | Summary: Reactome places TCTN2 at the ciliary membrane in the transition-zone recruitment and ciliary vesicle reactions. Reason: TCTN2 is a membrane protein whose transmembrane segment lies in the transition-zone portion of the ciliary membrane, adjacent to the ciliary membrane per super-resolution mapping. The ciliary transition zone term is more precise but ciliary membrane is a fair description of the membrane domain it occupies. Supporting Evidence: PMID:29866362 TMEM67 and TCTN2 are close to the ciliary membrane, whereas MKS1 is likely in between PMID:29866362 Tectonic 2 (TCTN2) is one of the TZ proteins in the vicinity of the ciliary membrane, and its mutation is associated with Meckel syndrome. |
| GO:0060271 cilium assembly | IBA GO_REF:0000033 | ACCEPT | Summary: TCTN2 is required for ciliogenesis in mouse cells and tissues (tissue-specific), and its loss in human RPE1 cells causes partial TZ damage and shortened, curved cilia. Reason: Strong mouse and human cell knockout evidence. Requirement is cell-type dependent (some Tctn2-null MEFs ciliate), consistent with TCTN2 acting as a structural component of the TZ rather than a general axoneme-building factor. Supporting Evidence: PMID:21565611 Tctn2 was required for ciliogenesis in isolated cells and in vivo, consistent with TCTN2 being a ciliopathy gene PMID:21725307 Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. PMID:29866362 We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. |
| GO:0060271 cilium assembly | IEA GO_REF:0000107 | ACCEPT | Summary: TCTN2 is required for ciliogenesis in mouse cells and tissues (tissue-specific), and its loss in human RPE1 cells causes partial TZ damage and shortened, curved cilia. Reason: Strong mouse and human cell knockout evidence. Requirement is cell-type dependent (some Tctn2-null MEFs ciliate), consistent with TCTN2 acting as a structural component of the TZ rather than a general axoneme-building factor. Supporting Evidence: PMID:21565611 Tctn2 was required for ciliogenesis in isolated cells and in vivo, consistent with TCTN2 being a ciliopathy gene PMID:21725307 Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. PMID:29866362 We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | ACCEPT | Summary: TCTN2 is required for ciliogenesis in mouse cells and tissues (tissue-specific), and its loss in human RPE1 cells causes partial TZ damage and shortened, curved cilia. Reason: Strong mouse and human cell knockout evidence. Requirement is cell-type dependent (some Tctn2-null MEFs ciliate), consistent with TCTN2 acting as a structural component of the TZ rather than a general axoneme-building factor. Supporting Evidence: PMID:21565611 Tctn2 was required for ciliogenesis in isolated cells and in vivo, consistent with TCTN2 being a ciliopathy gene PMID:21725307 Like Tctn1, loss of Tctn2, Tmem67 or Cc2d2a causes tissue-specific defects in ciliogenesis and ciliary membrane composition. PMID:29866362 We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. |
| GO:1904491 protein localization to ciliary transition zone | IBA GO_REF:0000033 | ACCEPT | Summary: TCTN2 is required to localize neighbouring MKS module proteins (TMEM67, MKS1) to the transition zone. Reason: In TCTN2-/- RPE1 cells TMEM67 and MKS1 are lost from the ciliary base while NPHP-module proteins and CEP290 remain, showing that TCTN2 participates in assembling/retaining the MKS module at the TZ. The NAS citation (Chih et al.) supports the interdependent localization of MKS complex members. Supporting Evidence: PMID:29866362 Among the ciliated population, TMEM67 and MKS1 were absent in TCTN2 −/− cells, whereas RPGRIP1L, NPHP4, and CEP290 remained in their ciliary base localizations |
| GO:1904491 protein localization to ciliary transition zone | IEA GO_REF:0000107 | ACCEPT | Summary: TCTN2 is required to localize neighbouring MKS module proteins (TMEM67, MKS1) to the transition zone. Reason: In TCTN2-/- RPE1 cells TMEM67 and MKS1 are lost from the ciliary base while NPHP-module proteins and CEP290 remain, showing that TCTN2 participates in assembling/retaining the MKS module at the TZ. The NAS citation (Chih et al.) supports the interdependent localization of MKS complex members. Supporting Evidence: PMID:29866362 Among the ciliated population, TMEM67 and MKS1 were absent in TCTN2 −/− cells, whereas RPGRIP1L, NPHP4, and CEP290 remained in their ciliary base localizations |
| GO:1904491 protein localization to ciliary transition zone | NAS PMID:22179047 A ciliopathy complex at the transition zone protects the cil... | ACCEPT | Summary: TCTN2 is required to localize neighbouring MKS module proteins (TMEM67, MKS1) to the transition zone. Reason: In TCTN2-/- RPE1 cells TMEM67 and MKS1 are lost from the ciliary base while NPHP-module proteins and CEP290 remain, showing that TCTN2 participates in assembling/retaining the MKS module at the TZ. The NAS citation (Chih et al.) supports the interdependent localization of MKS complex members. Supporting Evidence: PMID:29866362 Among the ciliated population, TMEM67 and MKS1 were absent in TCTN2 −/− cells, whereas RPGRIP1L, NPHP4, and CEP290 remained in their ciliary base localizations |
| GO:1905349 ciliary transition zone assembly | IMP PMID:29866362 Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT... | NEW | Summary: TCTN2 knockout in human RPE1 cells causes partial transition-zone damage and loss of TMEM67 and MKS1 from the TZ, indicating that TCTN2 contributes structurally to assembling the MKS part of the transition zone. Reason: Participation test: TCTN2 is itself a structural constituent of the TZ MKS module and is required for the incorporation of its neighbours, i.e. it supplies part of the structure being assembled (scaffold case). The term replaces the obsoleted GO:0097711 and is very sparsely used in GOA (currently CEP290, CCDC66, DZIP1L, RAB3IP), so absence for MKS components reflects a young, under-populated term rather than a convention against annotating structural subunits. The module (primary cilium life cycle, stage 3) assigns this process to the MKS module. Supporting Evidence: PMID:29866362 We found that TCTN2 depletion resulted in partial TZ damage, loss of ciliary membrane proteins, leakage of intraflagellar transport protein IFT88 toward the basal body lumen, and cilium shortening and curving. PMID:29866362 Among the ciliated population, TMEM67 and MKS1 were absent in TCTN2 −/− cells, whereas RPGRIP1L, NPHP4, and CEP290 remained in their ciliary base localizations |
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Download this section (compressed HTML)Q: Is the extracellular/luminal tectonic domain of TCTN2 required for barrier function, or only the transmembrane anchor for MKS-complex incorporation?
Q: Why is TCTN2 dispensable for ciliogenesis in some mouse cell types (e.g. some MEFs) but essential in others, and does the NPHP module compensate?
Experiment: Re-express truncated TCTN2 constructs (luminal-domain deletions, transmembrane swap) in TCTN2-/- RPE1 cells and quantify TMEM67/MKS1 TZ recruitment, ARL13B/SMO ciliary levels and FRAP-based membrane diffusion across the TZ.
Hypothesis: TCTN2 domains have separable roles in MKS-module assembly and diffusion-barrier function.
Type: domain rescue + super-resolution imaging
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