PARD6B encodes PAR-6 beta (partitioning defective 6 homolog beta), an evolutionarily conserved scaffold protein that is a core component of the PAR polarity complex. PAR-6B contains a PB1 domain for interaction with atypical PKC (PRKCI/PRKCZ), a pseudo-CRIB domain for binding activated CDC42/RAC1, and a PDZ domain for interaction with PAR-3 and PALS1. The protein functions as a non-enzymatic adaptor that links small GTPases (CDC42, RAC1) to atypical protein kinase C, thereby coordinating the assembly of the PAR3-PAR6-aPKC polarity complex at tight junctions and the apical membrane of polarized epithelial cells. PARD6B is essential for the establishment and maintenance of apico-basal cell polarity, tight junction formation, and asymmetric cell division. CDC42-GTP binding to PAR-6B conformationally activates aPKC to phosphorylate apical substrates, driving tight junction maturation and apical identity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060341 regulation of cellular localization | IBA GO_REF:0000033 | ACCEPT | Summary: PAR-6B is a polarity scaffold that regulates the subcellular localization of aPKC and other polarity complex components. The PAR3-PAR6-aPKC complex controls apical membrane identity and tight junction localization (PMID:12545177, PMID:11257119). Reason: This annotation captures the regulatory role of PARD6B in controlling subcellular localization of polarity complex components. PMID:12545177 demonstrates that Par6 regulates localization of PALS1 to tight junctions, and PMID:11257119 shows Par6 is required for proper localization of aPKC and PAR-3 at junctional structures. Supporting Evidence: PMID:12545177 overexpression of Par6 in MDCK cells inhibits localization of PALS1 to the tight junction PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3 file:human/PARD6B/PARD6B-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0007163 establishment or maintenance of cell polarity | IBA GO_REF:0000033 | ACCEPT | Summary: PARD6B is a core component of the evolutionarily conserved PAR polarity complex that establishes and maintains cell polarity in epithelia and during asymmetric cell division (PMID:11260256, PMID:11257119). Reason: This is the central biological function of PARD6B. The deep research confirms Par6 proteins play critical roles in cell polarity from C. elegans to mammals. PMID:11260256 explicitly identifies PAR6 proteins as functioning in cell polarization by linking CDC42/RAC1 to aPKC signaling. Supporting Evidence: PMID:11260256 Human PAR6 homologues most likely play an important role in the cell polarization of mammalian cells, by functioning as an adaptor protein that links activated Rac and Cdc42 to aPKC signalling PMID:11257119 aPKC is critically involved in the development of the epithelial junctional structures and controls the cell polarity of mammalian epithelial cells, probably by forming a ternary complex with ASIP/PAR-3 and PAR-6 |
| GO:0005938 cell cortex | IBA GO_REF:0000033 | ACCEPT | Summary: PAR-6B localizes to the cell cortex as part of its role in establishing apico-basal polarity. The PAR complex concentrates at cortical regions during polarity establishment (PMID:11260256). Reason: Cell cortex localization is consistent with PAR-6B function in polarity establishment. PMID:11260256 shows PAR6 proteins co-localize with aPKC at membrane ruffles (cortical regions) when expressed with activated Rac. Supporting Evidence: PMID:11260256 When PAR6 and aPKC are expressed with a constitutively active form of Rac in HeLa or COS-7 cells, these proteins co-localize to membrane ruffles |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Nuclear localization of PAR-6 has been observed in certain contexts, particularly in invasive breast cancer cells, though this may represent altered trafficking in disease states (deep research: Catterall 2021). Reason: Nuclear localization appears to be context-dependent and observed in cancer tissues rather than normal physiological function. The deep research notes that nuclear Par6 appears in invasive cases and not in pre-invasive lesions, suggesting altered trafficking during disease progression rather than a core localization. Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3 |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAR-6B concentrates at the apical plasma membrane as a core component of the PAR polarity complex that defines apical membrane identity (PMID:11257119, PMID:12545177). Reason: Apical plasma membrane localization is a defining characteristic of PAR-6B function. PMID:11257119 demonstrates PAR-6 localizes to the apical junctional region with aPKC and PAR-3, and the deep research confirms Par6 concentrates at the apical membrane and apical-lateral border. Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3 PMID:12545177 Crumbs (Crb)-PALS1 (Stardust)-PATJ (DiscsLost) and Cdc42-Par6-Par3-atypical protein kinase C (aPKC), have been implicated in the assembly of tight junctions and in polarization |
| GO:0007098 centrosome cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAR proteins have been implicated in centrosome positioning during asymmetric cell division, though direct evidence for PARD6B in centrosome cycle regulation is limited. Reason: While PAR proteins are involved in asymmetric cell division which involves centrosome positioning, there is limited direct evidence for PARD6B specifically regulating the centrosome cycle. This is likely a secondary consequence of polarity function rather than a core role. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt annotation indicates cytoplasmic localization for PARD6B, consistent with its scaffold function. Reason: Cytoplasmic localization is accurate - PARD6B is a cytoplasmic scaffold protein that translocates to the plasma membrane/tight junctions upon polarity establishment. UniProt CC states: "SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Cell junction, tight junction." |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: PARD6B localizes to the plasma membrane as part of the PAR polarity complex (PMID:11260256, PMID:11257119). Reason: Plasma membrane localization is well-established for PARD6B. PMID:11260256 shows PAR6 co-localizes with aPKC at membrane ruffles, and PMID:11257119 shows localization to the apical junctional region at the plasma membrane. Supporting Evidence: PMID:11260256 When PAR6 and aPKC are expressed with a constitutively active form of Rac in HeLa or COS-7 cells, these proteins co-localize to membrane ruffles |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000120 | ACCEPT | Summary: PARD6B localizes to tight junctions and is required for tight junction assembly (PMID:12545177, PMID:11257119). Reason: This is strongly supported by experimental evidence. PMID:12545177 demonstrates Par6 interaction with PALS1 is important for tight junction assembly, and PMID:11257119 shows the PAR complex localizes to tight junctions and is required for their formation. Supporting Evidence: PMID:12545177 Two evolutionarily conserved multi-protein complexes, Crumbs (Crb)-PALS1 (Stardust)-PATJ (DiscsLost) and Cdc42-Par6-Par3-atypical protein kinase C (aPKC), have been implicated in the assembly of tight junctions and in polarization of Drosophila melanogaster epithelia PMID:11257119 aPKCkn blocks the completion of tight junction formation after calcium switch |
| GO:0051301 cell division | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PARD6B is involved in asymmetric cell division as part of the PAR polarity complex that controls division plane orientation (PMID:11260256). Reason: While PAR proteins are involved in asymmetric cell division, this is a broader term than the specific role of PARD6B. The primary function is in polarity establishment, which has downstream effects on asymmetric division. This is peripheral rather than a core molecular function. Supporting Evidence: PMID:11260256 Asymmetric cell division in the Caenorhabditis elegans embryos requires products of par (partitioning defective) genes 1-6 |
| GO:0005515 protein binding | IPI PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity... | REMOVE | Summary: This publication demonstrates PAR6 proteins bind to GTP-bound RAC1 and CDC42 via the CRIB-like motif, and to aPKC (PKCiota/lambda and PKCzeta) via N-terminal head-to-head association. Reason: "Protein binding" is uninformative for annotation purposes. The specific interactions demonstrated in PMID:11260256 should be captured with more specific MF terms such as GO:0031267 (small GTPase binding) and GO:0005080 (protein kinase C binding), or preferably GO:0035591 (signaling adaptor activity) which captures the functional role of linking GTPases to aPKC. Supporting Evidence: PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. |
| GO:0005515 protein binding | IPI PMID:14676191 Comprehensive proteomic analysis of human Par protein comple... | REMOVE | Summary: Proteomic analysis of human Par protein complexes identified interactions between PAR6 and other polarity components including PAR3 and aPKC. Reason: "Protein binding" is uninformative. This is a proteomic study that mapped the interconnected PAR protein network. The specific interactions should be captured with GO:0035591 (signaling adaptor activity) or more specific binding terms. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:14676191 2003 Dec 15. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. |
| GO:0005515 protein binding | IPI PMID:20936779 A human MAP kinase interactome. | REMOVE | Summary: High-throughput MAP kinase interactome study. Reason: "Protein binding" from high-throughput interactome studies is uninformative and does not capture the specific functional interactions of PARD6B. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:20936779 A human MAP kinase interactome. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Large-scale proteome-scale map of the human interactome network. Reason: "Protein binding" from high-throughput studies provides no specific information about PARD6B molecular function. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo... | REMOVE | Summary: Integrative analysis of kinase networks in TRAIL-induced apoptosis. Reason: "Protein binding" is uninformative. This high-throughput kinase network study does not specifically characterize PARD6B function. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: Human interactome study organized by stoichiometries and abundances. Reason: "Protein binding" is uninformative for functional annotation. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Pooled-matrix protein interaction screens using Barcode Fusion Genetics. Reason: "Protein binding" from high-throughput screens is uninformative. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusion Genetics. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Architecture of the human interactome defines protein communities. Reason: "Protein binding" is uninformative for annotation. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: EGFR network rewiring study in colorectal cancer cells. Reason: "Protein binding" is uninformative and this appears to be a cancer-context study not directly characterizing core PARD6B function. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Reference map of the human binary protein interactome. Reason: "Protein binding" is uninformative. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: Kinase Interaction Network study. Reason: "Protein binding" is uninformative. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:32707033 2020 Jul 23. Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Dual proteome-scale networks reveal cell-specific remodeling. Reason: "Protein binding" is uninformative. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: OpenCell endogenous tagging for cellular organization cartography. Reason: "Protein binding" is uninformative. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara orthology-based transfer annotation for nuclear localization. Reason: Nuclear localization may occur in some contexts but is not the primary functional localization of PARD6B. The core localization is at tight junctions and apical membrane. |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara orthology-based transfer for cell cortex localization. Reason: Consistent with IBA annotation and experimental evidence that PAR6 localizes to cortical membrane regions. |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara orthology-based transfer for apical plasma membrane. Reason: Consistent with IBA annotation and experimental evidence for apical membrane localization. |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | MODIFY | Summary: PARD6B is part of the PAR polarity complex. Reason: This term is too general. PARD6B is specifically a component of the PAR polarity complex (GO:0120157), which should be used instead. Proposed replacements: PAR polarity complex |
| GO:0045177 apical part of cell | IEA GO_REF:0000107 | ACCEPT | Summary: PARD6B localizes to the apical part of polarized epithelial cells. Reason: Consistent with extensive evidence that PAR6 localizes to the apical domain of polarized cells (PMID:11257119). Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3 |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based annotation showing cytosolic localization for PARD6B. Reason: Cytosolic localization is consistent with PARD6B being a scaffold protein that can exist in the cytosol before membrane recruitment. |
| GO:0070160 tight junction | NAS PMID:11257119 Atypical protein kinase C is involved in the evolutionarily ... | ACCEPT | Summary: PMID:11257119 demonstrates that PAR-6 localizes to tight junctions along with aPKC and PAR-3, and that the PAR complex is required for tight junction formation. Reason: Tight junction localization is a well-established and functionally important localization for PARD6B. PMID:11257119 provides strong evidence. Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3 PMID:11257119 aPKCkn blocks the completion of tight junction formation after calcium switch |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Large-scale proteomics study detected PARD6B in urinary exosomes. Reason: Detection in exosomes from high-throughput proteomics is not necessarily functionally significant. This does not represent a core localization for PARD6B function. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-419981 | ACCEPT | Summary: Reactome pathway annotation for PAR complex recruitment to tight junctions. Reason: Cytosolic localization is consistent with PARD6B scaffold function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-419981 | ACCEPT | Summary: Reactome pathway annotation for recruitment to tight junctions at plasma membrane. Reason: Plasma membrane localization is well-supported by experimental evidence. |
| GO:0005515 protein binding | IPI PMID:12725730 Mammalian Lgl forms a protein complex with PAR-6 and aPKC in... | REMOVE | Summary: This study demonstrates that mammalian Lgl (LLGL1) forms a complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Reason: "Protein binding" is uninformative. The specific interaction with LLGL1 in the context of polarity regulation should be captured with GO:0035591 (signaling adaptor activity). Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:12725730 mammalian Lgl competes for PAR-3 in forming an independent complex with PAR-6/aPKC |
| GO:0005515 protein binding | IPI PMID:15254234 Nucleotide exchange factor ECT2 interacts with the polarity ... | REMOVE | Summary: This study shows ECT2 interacts with the Par6/Par3/PKCzeta polarity complex and regulates PKCzeta activity. Reason: "Protein binding" is uninformative. The ECT2 interaction represents a regulatory input to the PAR complex. Should be captured with more specific terms. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:15254234 ECT2 interacted with Par6 as well as Par3 and PKCzeta |
| GO:0005886 plasma membrane | IDA PMID:12545177 Direct interaction of two polarity complexes implicated in e... | ACCEPT | Summary: PMID:12545177 demonstrates plasma membrane localization of Par6 at tight junctions. Reason: Direct experimental demonstration of plasma membrane localization. Supporting Evidence: PMID:12545177 The transmembrane protein Crb can recruit wild-type Par6, but not Par6 with a mutated PDZ domain, to the cell surface |
| GO:0005923 bicellular tight junction | IDA PMID:12545177 Direct interaction of two polarity complexes implicated in e... | ACCEPT | Summary: PMID:12545177 directly demonstrates Par6 localization to tight junctions and its role in tight junction assembly. Reason: Strong experimental evidence for tight junction localization. The study shows Par6 is essential for proper localization of tight junction components. Supporting Evidence: PMID:12545177 Expression of dominant-negative PALS1-associated tight junction protein (PATJ) in MDCK cells results in mis-localization of PALS1, members of the Par3-Par6-aPKC complex and the tight junction marker, ZO-1 |
| GO:0007043 cell-cell junction assembly | TAS PMID:12545177 Direct interaction of two polarity complexes implicated in e... | ACCEPT | Summary: PMID:12545177 demonstrates Par6 is involved in tight junction assembly linking Crumbs-PALS1 and Par3-Par6-aPKC complexes. Reason: The study provides evidence that Par6 bridges polarity complexes during junction assembly. Supporting Evidence: PMID:12545177 we identify a biochemical and functional link between these two complexes that is mediated by Par6 and PALS1 |
| GO:0007163 establishment or maintenance of cell polarity | TAS PMID:14676191 Comprehensive proteomic analysis of human Par protein comple... | ACCEPT | Summary: Comprehensive proteomic analysis of human Par protein complexes confirms the role of PAR6 in cell polarity establishment. Reason: This proteomic study mapped the interconnected PAR protein network that governs cell polarity, confirming PAR6's central role. Supporting Evidence: PMID:14676191 The PAR proteins, first identified in Caenorhabditis elegans, are common regulators of cell polarity conserved from nematode and flies to man |
| GO:0007409 axonogenesis | TAS PMID:14676191 Comprehensive proteomic analysis of human Par protein comple... | KEEP AS NON CORE | Summary: PAR proteins are implicated in neuronal polarity during axonogenesis. Reason: While PAR proteins are involved in neuronal polarity and axon specification, this represents a tissue-specific developmental function rather than the core molecular function of PARD6B. Supporting Evidence: PMID:14676191 2003 Dec 15. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. |
| GO:0030334 regulation of cell migration | TAS PMID:14676191 Comprehensive proteomic analysis of human Par protein comple... | KEEP AS NON CORE | Summary: PAR proteins are involved in directed cell migration through their role in establishing cell polarity. Reason: Cell migration regulation is a downstream consequence of PARD6B's role in polarity establishment. It is not a core function but a pleiotropic effect. Supporting Evidence: PMID:14676191 2003 Dec 15. Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. |
| GO:0065003 protein-containing complex assembly | IDA PMID:12545177 Direct interaction of two polarity complexes implicated in e... | MODIFY | Summary: PMID:12545177 demonstrates Par6 is involved in assembly of polarity complexes at tight junctions. Reason: This term is too general. The specific function is assembly of the PAR polarity complex. However, this is already captured by the role of PARD6B as a signaling adaptor (GO:0035591) that brings together complex components. Proposed replacements: signaling adaptor activity Supporting Evidence: PMID:12545177 Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. |
| GO:0035591 signaling adaptor activity | IDA PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity... | NEW | Summary: PARD6B functions as an adaptor protein that links activated Rac and Cdc42 to aPKC signaling in the cell polarity pathway (PMID:11260256). Reason: This is the core molecular function of PARD6B. PMID:11260256 explicitly describes PAR6 proteins as functioning as adaptor proteins that link small GTPases to aPKC. The protein brings together CDC42/RAC1 and aPKC in a ternary complex enabling coordinated signaling. Supporting Evidence: PMID:11260256 Human PAR6 homologues most likely play an important role in the cell polarization of mammalian cells, by functioning as an adaptor protein that links activated Rac and Cdc42 to aPKC signalling PMID:11260256 These interactions are not mutually exclusive, thereby allowing the PAR6 proteins to form a ternary complex with the GTPases and aPKC, both in vitro and in vivo |
| GO:0031267 small GTPase binding | IDA PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity... | NEW | Summary: PARD6B directly binds GTP-bound Rac and Cdc42 via its CRIB-like motif (PMID:11260256). Reason: This is a specific molecular function of PARD6B essential for its adaptor role in polarity signaling. More informative than generic "protein binding". Supporting Evidence: PMID:11260256 The PAR6 proteins harbour a PDZ domain and a CRIB-like motif, and directly interact with GTP-bound Rac and Cdc42 via this motif |
| GO:0005080 protein kinase C binding | IDA PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity... | NEW | Summary: PARD6B binds to aPKC isoforms (PKCiota/lambda and PKCzeta) via N-terminal head-to-head association (PMID:11260256). Reason: This is a specific molecular function of PARD6B essential for PAR complex formation and polarity signaling. Supporting Evidence: PMID:11260256 directly interact with GTP-bound Rac and Cdc42 via this motif and with the aPKC isoforms PKCiota/lambda and PKCzeta via the N-terminal head-to-head association |
| GO:0120157 PAR polarity complex | IDA PMID:11257119 Atypical protein kinase C is involved in the evolutionarily ... | NEW | Summary: PARD6B is a core component of the PAR polarity complex along with PAR3 and atypical PKC (PMID:11257119, PMID:12545177). Reason: This cellular component annotation specifically identifies PARD6B as part of the defined PAR polarity complex (GO:0120157: "A protein kinase complex that is required for the establishment of a cell polarity axis"). Supporting Evidence: PMID:11257119 aPKC is critically involved in the development of the epithelial junctional structures and controls the cell polarity of mammalian epithelial cells, probably by forming a ternary complex with ASIP/PAR-3 and PAR-6 PMID:12545177 Two evolutionarily conserved multi-protein complexes, Crumbs (Crb)-PALS1 (Stardust)-PATJ (DiscsLost) and Cdc42-Par6-Par3-atypical protein kinase C (aPKC), have been implicated in the assembly of tight junctions and in polarization of Drosophila melanogaster epithelia |
| GO:0120192 tight junction assembly | IDA PMID:12545177 Direct interaction of two polarity complexes implicated in e... | NEW | Summary: PARD6B is required for tight junction assembly, linking the Crumbs-PALS1 and Par3-Par6-aPKC polarity complexes (PMID:12545177, PMID:11257119). Reason: This biological process annotation is more specific than "cell-cell junction assembly" and directly captures PARD6B's role in tight junction formation. Supporting Evidence: PMID:12545177 Two evolutionarily conserved multi-protein complexes, Crumbs (Crb)-PALS1 (Stardust)-PATJ (DiscsLost) and Cdc42-Par6-Par3-atypical protein kinase C (aPKC), have been implicated in the assembly of tight junctions and in polarization of Drosophila melanogaster epithelia PMID:11257119 aPKCkn blocks the completion of tight junction formation after calcium switch |
Loading supporting content…
Download this section (compressed HTML)Q: What is the specific role of each PARD6 isoform (PARD6A, PARD6B, PARD6G) in different cell types?
Q: How is the transition between PAR3-PAR6-aPKC and Lgl-PAR6-aPKC complexes regulated?
Q: What is the significance of nuclear PAR6 localization observed in invasive breast cancer?
Experiment: Comparative knockdown/knockout of PARD6A vs PARD6B vs PARD6G to determine isoform-specific functions
Hypothesis: Different PARD6 isoforms have distinct tissue-specific or context-specific roles in polarity establishment
Experiment: Live imaging of PAR complex dynamics during tight junction assembly
Hypothesis: PAR6 shows dynamic recruitment and exchange at tight junctions during junction maturation
Experiment: Structural studies of the PAR6-CDC42-aPKC ternary complex
Hypothesis: CDC42-GTP binding induces conformational changes in PAR6 that activate aPKC
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)