PARD6A encodes Partitioning defective 6 homolog alpha (PAR-6A), a key adaptor protein in the evolutionarily conserved PAR polarity complex. The protein contains an N-terminal PB1 domain that heterodimerizes with atypical PKC (aPKC/PRKCI/PRKCZ), a semi-CRIB motif that binds GTP-bound CDC42/RAC1, and a C-terminal PDZ domain that recognizes polarity partners including CRB3/PALS1 and PAR-3. PARD6A functions as a scaffold/adaptor that recruits and regulates aPKC activity at the apical cortex to establish apical-basal polarity in epithelial cells. Through its multi-domain architecture, PARD6A integrates inputs from CDC42-GTP and PDZ ligands to modulate aPKC autoinhibition and substrate access, controlling phosphorylation of basolateral determinants like LGL. PARD6A also has a distinct role at centrosomes where it interacts with p150Glued to regulate centrosomal protein recruitment and microtubule organization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0060341 regulation of cellular localization | IBA GO_REF:0000033 | ACCEPT | Summary: PARD6A regulates the localization of multiple proteins including controlling recruitment of centrosomal proteins via p150Glued interaction (PMID:20719959), and regulating the subcellular distribution of aPKC and polarity substrates (deep research, Vargas 2023). Reason: The IBA annotation is well-supported. PARD6A functions as an adaptor that regulates localization of multiple proteins. PMID:20719959 demonstrates "Par6alpha-mediated centrosome regulation involves the binding of Par6alpha to p150Glued" and shows "depletion of Par6alpha caused the mislocalization of p150Glued and centrosomal components." This is a core function. Supporting Evidence: PMID:20719959 Depletion of Par6alpha caused the mislocalization of p150(Glued) and centrosomal components that are critical for microtubule anchoring at the centrosome. file:human/PARD6A/PARD6A-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0007163 establishment or maintenance of cell polarity | IBA GO_REF:0000033 | ACCEPT | Summary: PARD6A is a core component of the PAR polarity complex essential for establishing and maintaining cell polarity. Multiple primary studies confirm this central role (PMID:10934474, PMID:11257119, PMID:11260256). Reason: This is a core function of PARD6A. PMID:10934474 states "Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3" and is "implicated in the formation of normal tight junctions." PMID:11257119 shows the aPKC-ASIP/PAR-3-PAR-6 complex "plays critical roles in the development of the junctional structures and apico-basal polarization of mammalian epithelial cells." Supporting Evidence: PMID:10934474 Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3. 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: PARD6A localizes to the cell cortex as part of the PAR complex, particularly at the apical cortex where it recruits aPKC for polarity establishment. Reason: Deep research confirms "PAR-6alpha localizes to the apical cortex, tight junctional regions, and polarity organizing centers." The IBA annotation is consistent with established PAR complex biology. Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAR-6 has been detected in the nucleus in addition to its membrane/junctional localization (PMID:10954424). Reason: PMID:10954424 reports "PAR-6 was also detected in the cell nucleus" in MDCK cells. This appears to be a secondary localization, not the primary site of function for polarity regulation. Supporting Evidence: PMID:10954424 PAR-6 was also detected in the cell nucleus. |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PARD6A localizes to the apical plasma membrane as part of the apical PAR complex that defines apical identity in epithelial cells. Reason: This is a well-established core localization. Deep research indicates "PAR-6alpha localizes to the apical cortex" and PMID:11257119 shows "mammalian PAR-6 localizes to the apical junctional region." Supporting Evidence: PMID:11257119 mammalian PAR-6 localizes to the apical junctional region together with aPKC and ASIP/PAR-3. |
| GO:0007098 centrosome cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PARD6A plays a role in centrosome organization and the centrosome cycle through its interaction with p150Glued and PCM-1 (PMID:20719959). Reason: PMID:20719959 provides experimental evidence for Par6alpha's role in centrosome organization: "RNAi-mediated depletion of this protein caused the mislocalization of specific centrosomal proteins" and "in the absence of Par6alpha, there were defects in microtubule organization in interphase, but also in mitosis, which affected cell cycle progression." Supporting Evidence: PMID:20719959 in the absence of Par6alpha, there were defects in microtubule organization in interphase, but also in mitosis, which affected cell cycle progression. |
| GO:0001726 ruffle | IEA GO_REF:0000044 | ACCEPT | Summary: Par6 proteins colocalize with aPKC at membrane ruffles when expressed with constitutively active Rac (PMID:11260256). Reason: PMID:11260256 states "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, which are known to occur at the leading edge of polarized cells during cell movement." This is consistent with Par6's role in polarity. 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, which are known to occur at the leading edge of polarized cells during cell movement. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: PARD6A is present in the cytoplasm in addition to its membrane localizations. Reason: General cytoplasmic localization is consistent with the protein's function as an adaptor that can shuttle between cytosol and membrane compartments. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | ACCEPT | Summary: PARD6A localizes to the centrosome where it regulates centrosomal protein recruitment (PMID:20719959). Reason: PMID:20719959 provides direct experimental evidence: "We detected Par6alpha at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150(Glued)." Supporting Evidence: PMID:20719959 We detected Par6alpha at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150(Glued). |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: PARD6A localizes to the plasma membrane as part of its polarity function. Reason: Plasma membrane localization is well-established for Par6 proteins at cell-cell contacts and tight junctions. |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000120 | ACCEPT | Summary: PARD6A localizes to tight junctions as part of the PAR polarity complex (PMID:10954424, PMID:11257119). Reason: PMID:10954424 states "In epithelial MDCK cells, endogenous PAR-6 was present in the tight junctions, as judged from its co-localisation with the tight junction protein ZO-1." This is a core localization for polarity function. Supporting Evidence: PMID:10954424 We found that, in epithelial Madin-Darby canine kidney cells (MDCK), endogenous PAR-6 was present in the tight junctions, as judged from its co-localisation with the tight junction protein ZO-1, however, PAR-6 was also detected in the cell nucleus |
| GO:0034451 centriolar satellite | IEA GO_REF:0000044 | ACCEPT | Summary: PARD6A localizes to centriolar satellites where it interacts with PCM-1 (PMID:20719959). Reason: PMID:20719959 provides direct evidence: "We detected Par6alpha at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1." Supporting Evidence: PMID:20719959 We detected Par6Ξ± at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150(Glued) |
| GO:0051301 cell division | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: PARD6A depletion affects cell division through its role in centrosome organization and microtubule dynamics (PMID:20719959). Reason: PMID:20719959 shows "cell division was blocked" in the absence of Par6alpha due to mitotic defects. While this is a documented consequence of Par6alpha function, cell division is not the primary/core function of PARD6A. Supporting Evidence: PMID:20719959 cell division was blocked. |
| GO:0005515 protein binding | IPI PMID:10934474 The cell-polarity protein Par6 links Par3 and atypical prote... | REMOVE | Summary: This annotation documents interaction with CDC42 (UniProtKB:P60953). However, GO:0005515 is uninformative. Reason: While PMID:10934474 demonstrates specific CDC42 binding, the term "protein binding" (GO:0005515) is uninformative and does not capture the functional nature of this interaction. More specific terms like "small GTPase binding" or "GTP-dependent protein binding" are already annotated and are more appropriate. Supporting Evidence: PMID:10934474 The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. |
| GO:0005515 protein binding | IPI PMID:11257119 Atypical protein kinase C is involved in the evolutionarily ... | REMOVE | Summary: This annotation documents interaction with aPKC (UniProtKB:P41743) and PAR-3 (UniProtKB:Q8TEW0). Reason: GO:0005515 is uninformative. The specific adaptor function linking aPKC, PAR-3, and CDC42 is better captured by GO:0030674 (protein-macromolecule adaptor activity) which is already annotated for this gene. Supporting Evidence: PMID:11257119 Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. |
| GO:0005515 protein binding | IPI PMID:11260256 Human homologues of the Caenorhabditis elegans cell polarity... | REMOVE | Summary: Documents interactions with aPKC, CDC42, RAC1. These are adaptor-mediated interactions central to polarity function. Reason: GO:0005515 is uninformative. The specific interactions are better captured by GO:0030674 (protein-macromolecule adaptor activity), GO:0031267 (small GTPase binding), and GO:0030742 (GTP-dependent protein binding). 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: Large-scale proteomic analysis of Par protein complexes documenting multiple interactions. Reason: GO:0005515 is uninformative for functional annotation. More specific molecular function terms should be used. 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:15590654 Structure of a cell polarity regulator, a complex between at... | REMOVE | Summary: Documents the PB1-PB1 domain interaction between Par6alpha and PKCiota. Crystal structure at 1.5 A resolution. Reason: While this is excellent structural evidence for the PB1-PB1 interaction, GO:0005515 is uninformative. The adaptor activity (GO:0030674) already captures this functional relationship. Supporting Evidence: PMID:15590654 2004 Dec 7. Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. |
| GO:0005515 protein binding | IPI PMID:15782111 G-protein-activated phospholipase C-beta, new partners for c... | REMOVE | Summary: Documents interaction with phospholipase C-beta proteins. Reason: GO:0005515 is uninformative and should not be used for GO annotation. Supporting Evidence: PMID:15782111 G-protein-activated phospholipase C-beta, new partners for cell polarity proteins Par3 and Par6. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | REMOVE | Summary: High-throughput interactome mapping study. Reason: GO:0005515 is uninformative. High-throughput studies documenting protein-protein interactions should use more specific MF terms. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network. |
| GO:0005515 protein binding | IPI PMID:17057644 A distinct PAR complex associates physically with VE-cadheri... | REMOVE | Summary: Documents Par complex association with VE-cadherin in endothelial cells. Reason: GO:0005515 is uninformative and does not convey the functional significance of this interaction in endothelial cell polarity. Supporting Evidence: PMID:17057644 A distinct PAR complex associates physically with VE-cadherin in vertebrate endothelial cells. |
| GO:0005515 protein binding | IPI PMID:17350623 PKCzetaII is a target for degradation through the tumour sup... | REMOVE | Summary: Documents interaction with PKCzeta/aPKC related to VHL tumor suppressor. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:17350623 Epub 2007 Mar 5. PKCzetaII is a target for degradation through the tumour suppressor protein pVHL. |
| GO:0005515 protein binding | IPI PMID:21516116 Next-generation sequencing to generate interactome datasets. | REMOVE | Summary: Next-generation sequencing interactome study. Reason: GO:0005515 is uninformative for functional annotation. Supporting Evidence: PMID:21516116 Next-generation sequencing to generate interactome datasets. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Proteome-scale interactome mapping study. Reason: GO:0005515 is uninformative. 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: Kinase network analysis in TRAIL-induced apoptosis. Reason: GO:0005515 is uninformative. 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: Quantitative interactome study. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Dual proteome-scale network study. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005634 nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ortholog-based transfer from mouse, consistent with experimental observation in PMID:10954424. Reason: Nuclear localization is documented but represents a secondary localization, not the primary site of polarity function. |
| GO:0005938 cell cortex | IEA GO_REF:0000107 | ACCEPT | Summary: Ortholog-based transfer consistent with experimental evidence. Reason: Cell cortex localization is a core aspect of PARD6A function in polarity. |
| GO:0030742 GTP-dependent protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: PARD6A binds specifically to GTP-bound forms of CDC42 and RAC1 via its CRIB motif (PMID:10934474, PMID:11260256). Reason: This is a core molecular function. PMID:10934474 states "Par6 forms a complex with Cdc42-GTP." PMID:11260256 confirms "PAR6 proteins directly interact with GTP-bound Rac and Cdc42 via this motif." 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 and with the aPKC isoforms PKCiota/lambda and PKCzeta via the N-terminal head-to-head association |
| GO:0031267 small GTPase binding | IEA GO_REF:0000107 | ACCEPT | Summary: PARD6A binds small GTPases CDC42 and RAC1 through its CRIB motif (PMID:10934474, PMID:10954424, PMID:11260256). Reason: Core molecular function. Multiple studies demonstrate CRIB-mediated binding to CDC42 and RAC1. Supporting Evidence: PMID:10954424 PAR-6 interacted with Cdc42 and Rac1 both in the yeast two-hybrid system and in in vitro binding assays. |
| GO:0045217 cell-cell junction maintenance | IEA GO_REF:0000107 | ACCEPT | Summary: PARD6A is involved in tight junction formation and maintenance as part of the PAR complex (PMID:11257119, PMID:14718572). Reason: Core function. PMID:11257119 shows aPKCkn expression "severely affected" tight junction biogenesis. PMID:14718572 demonstrates CRB3-Par6 interaction "regulates the morphogenesis of the tight junctions." Supporting Evidence: PMID:14718572 CRB3, through its cytoplasmic domain and its interactors, plays a role in apical membrane morphogenesis and tight junction regulation. |
| GO:0050714 positive regulation of protein secretion | IEA GO_REF:0000107 | UNDECIDED | Summary: Ortholog-based transfer. The functional connection to PARD6A's core polarity functions is not clear from the primary literature reviewed. Reason: Unable to find direct literature support in publications reviewed. This may be a secondary effect of polarity function in secretory cells, but cannot confirm based on available evidence. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence data supporting cytosolic localization. Reason: Cytosolic localization is consistent with PARD6A's role as a scaffold/adaptor that can shuttle between cytosol and membrane. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence data supporting plasma membrane localization. Reason: Plasma membrane localization is well-established for Par6 at tight junctions and cell-cell contacts. |
| GO:0030054 cell junction | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence data supporting cell junction localization. Reason: Cell junction localization is a core aspect of PARD6A function, particularly at tight junctions. |
| GO:0045197 establishment or maintenance of epithelial cell apical/basal polarity | IDA PMID:11257119 Atypical protein kinase C is involved in the evolutionarily ... | ACCEPT | Summary: PMID:11257119 directly demonstrates that aPKC-PAR-3-PAR-6 complex is required for epithelial cell polarity. Reason: Core function. PMID:11257119 shows "epithelial cell surface polarity is severely impaired" when aPKC function is disrupted, and demonstrates the aPKC-ASIP/PAR-3-PAR-6 ternary complex "plays critical roles in the development of the junctional structures and apico-basal polarization." 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. |
| GO:0070160 tight junction | NAS PMID:11257119 Atypical protein kinase C is involved in the evolutionarily ... | ACCEPT | Summary: PMID:11257119 demonstrates PAR-6 localization to tight junctions. Reason: Well-supported localization. Multiple studies confirm tight junction localization (PMID:10954424, PMID:11257119). Supporting Evidence: PMID:10954424 We found that, in epithelial Madin-Darby canine kidney cells (MDCK), endogenous PAR-6 was present in the tight junctions, as judged from its co-localisation with the tight junction protein ZO-1, however, PAR-6 was also detected in the cell nucleus PMID:11257119 Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. |
| GO:0030674 protein-macromolecule adaptor activity | IPI PMID:14718572 CRB3 binds directly to Par6 and regulates the morphogenesis ... | ACCEPT | Summary: PARD6A functions as an adaptor linking CRB3, aPKC, CDC42, and PAR-3 in the polarity complex. This annotation captures the key molecular function. Reason: Core molecular function. PMID:14718572 demonstrates direct CRB3-Par6 interaction. PMID:10934474 states "Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3." PMID:11260256 confirms PAR6 proteins function "as an adaptor protein that links activated Rac and Cdc42 to aPKC signalling." Supporting Evidence: PMID:10934474 Par6 is a key adaptor that links Cdc42 and atypical PKCs to Par3. 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:14718572 Jan 12. CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. |
| GO:0005515 protein binding | IPI PMID:20719959 Par6 alpha interacts with the dynactin subunit p150 Glued an... | REMOVE | Summary: Documents interaction with p150Glued (DCTN1) and PCM-1 at centrosomes. Reason: GO:0005515 is uninformative. The specific interactions at centrosomes are functionally important but should be captured by more specific terms if available. Supporting Evidence: PMID:20719959 2010 Aug 18. Par6 alpha interacts with the dynactin subunit p150 Glued and is a critical regulator of centrosomal protein recruitment. |
| GO:0005813 centrosome | IDA PMID:20719959 Par6 alpha interacts with the dynactin subunit p150 Glued an... | ACCEPT | Summary: Direct experimental evidence for centrosome localization. Reason: PMID:20719959 provides direct evidence: "We detected Par6alpha at the centrosome and centriolar satellites." Supporting Evidence: PMID:20719959 We detected Par6Ξ± at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150(Glued) |
| GO:0007098 centrosome cycle | IMP PMID:20719959 Par6 alpha interacts with the dynactin subunit p150 Glued an... | ACCEPT | Summary: Experimental evidence from Par6alpha depletion studies showing centrosome organization defects. Reason: PMID:20719959 demonstrates "RNAi-mediated depletion of this protein caused the mislocalization of specific centrosomal proteins" and "cell division was blocked." Supporting Evidence: PMID:20719959 RNAi-mediated depletion of this protein caused the mislocalization of specific centrosomal proteins, including regulators of microtubule anchoring. |
| GO:0034451 centriolar satellite | IDA PMID:20719959 Par6 alpha interacts with the dynactin subunit p150 Glued an... | ACCEPT | Summary: Direct experimental evidence for centriolar satellite localization. Reason: PMID:20719959 states "We detected Par6alpha at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1." Supporting Evidence: PMID:20719959 We detected Par6Ξ± at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150(Glued) |
| GO:1904781 positive regulation of protein localization to centrosome | IMP PMID:20719959 Par6 alpha interacts with the dynactin subunit p150 Glued an... | ACCEPT | Summary: Par6alpha depletion causes mislocalization of centrosomal proteins, indicating it positively regulates their centrosome recruitment. Reason: PMID:20719959 demonstrates "Depletion of Par6alpha caused the mislocalization of p150(Glued) and centrosomal components that are critical for microtubule anchoring at the centrosome." Supporting Evidence: PMID:20719959 Depletion of Par6alpha caused the mislocalization of p150(Glued) and centrosomal components that are critical for microtubule anchoring at the centrosome. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-419981 | ACCEPT | Summary: Reactome pathway annotation for PAR-3:PAR-6:aPKC complex recruitment. Reason: Cytosolic localization is consistent with adaptor function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4608825 | ACCEPT | Summary: Reactome pathway annotation for WNT5A signaling. Reason: Consistent with known localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4608852 | ACCEPT | Summary: Reactome pathway annotation for SMURF1/2 ubiquitination pathway. Reason: Consistent with known localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-4608854 | ACCEPT | Summary: Reactome pathway annotation for SMURF recruitment. Reason: Consistent with known localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013145 | ACCEPT | Summary: Reactome pathway annotation for RAC1 effector binding. Reason: Consistent with known localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9013157 | ACCEPT | Summary: Reactome pathway annotation for CDC42 effector binding. Reason: Consistent with PARD6A as a CDC42 effector binding partner. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9018766 | ACCEPT | Summary: Reactome pathway annotation for RHOU effector binding. Reason: Consistent with known localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-419981 | ACCEPT | Summary: Reactome pathway for PAR complex recruitment to tight junctions. Reason: Plasma membrane localization at tight junctions is well-established. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2160931 | ACCEPT | Summary: Reactome pathway for tight junction disassembly during EMT. Reason: Consistent with PARD6A role in TGFbeta-induced EMT (PMID:15761148). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2160932 | ACCEPT | Summary: Reactome pathway for SMURF1 binding to phosphorylated PARD6A. Reason: PMID:15761148 shows Par6 phosphorylation by TGFbeta receptor leads to SMURF1 interaction at the plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2160935 | ACCEPT | Summary: Reactome pathway for SMURF1-mediated RHOA ubiquitination. Reason: Part of the EMT pathway involving PARD6A at plasma membrane. |
| GO:0005515 protein binding | IPI PMID:15761148 Regulation of the polarity protein Par6 by TGFbeta receptors... | REMOVE | Summary: Documents interaction with TGFbeta receptor TbetaRII. Reason: GO:0005515 is uninformative. The TGFbeta receptor interaction leading to Par6 phosphorylation is functionally significant but should use more specific terms. Supporting Evidence: PMID:15761148 Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. |
| GO:0005515 protein binding | IPI PMID:19617897 Ect2 links the PKCiota-Par6alpha complex to Rac1 activation ... | REMOVE | Summary: Documents interaction with PKCiota and ECT2. Reason: GO:0005515 is uninformative. Supporting Evidence: PMID:19617897 Jul 20. Ect2 links the PKCiota-Par6alpha complex to Rac1 activation and cellular transformation. |
| GO:0005515 protein binding | IPI PMID:10954424 The mammalian homologue of the Caenorhabditis elegans polari... | REMOVE | Summary: Documents interaction with CDC42 (UniProtKB:P60766). Reason: GO:0005515 is uninformative. The CDC42 binding is better captured by GO:0031267 (small GTPase binding) and GO:0030742 (GTP-dependent protein binding). Supporting Evidence: PMID:10954424 The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. |
| GO:0016032 viral process | TAS PMID:9482110 The C-terminus of the HTLV-1 Tax oncoprotein mediates intera... | KEEP AS NON CORE | Summary: PMID:9482110 shows HTLV-1 Tax protein interacts with PDZ domain proteins including Par6. This is about viral exploitation of host proteins. Reason: PMID:9482110 demonstrates "The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins." The viral process involvement is a consequence of having a PDZ domain, not a core cellular function. Supporting Evidence: PMID:9482110 Tax could perturb the normal function of targeted cellular proteins by strongly interacting with their PDZ domains. |
| GO:0031267 small GTPase binding | ISS GO_REF:0000024 | ACCEPT | Summary: PARD6A binds small GTPases CDC42 and RAC1 via its CRIB motif. Reason: Core molecular function well-supported by multiple studies (PMID:10934474, PMID:10954424, PMID:11260256). Supporting Evidence: PMID:10954424 PAR-6 interacted with Cdc42 and Rac1 both in the yeast two-hybrid system and in in vitro binding assays. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Ortholog-based annotation consistent with experimental evidence. Reason: Nuclear localization is documented but secondary to membrane/cortical functions. |
| GO:0005923 bicellular tight junction | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based annotation consistent with experimental evidence. Reason: Tight junction localization is core to PARD6A polarity function. |
| GO:0030742 GTP-dependent protein binding | ISS GO_REF:0000024 | ACCEPT | Summary: PARD6A preferentially binds GTP-bound CDC42/RAC1 via CRIB motif. Reason: Core molecular function. PMID:10934474 states "Par6 forms a complex with Cdc42-GTP." PMID:11260256 confirms binding to "GTP-bound Rac and Cdc42." Supporting Evidence: PMID:10934474 Par6 forms a complex with Cdc42-GTP, with a human homologue of the multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein kinase C (PKC) proteins |
| GO:0045217 cell-cell junction maintenance | ISS GO_REF:0000024 | ACCEPT | Summary: Ortholog-based annotation for junction maintenance function. Reason: Core function well-supported by multiple studies showing Par6 role in tight junction formation and maintenance. |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Does PARD6A have distinct functions compared to PARD6B and PARD6G in different cell types or developmental contexts?
Q: What is the physiological significance of nuclear PARD6A localization?
Q: How is the balance between PARD6A's polarity function and centrosome function regulated?
Experiment: Systematic comparison of PARD6A, PARD6B, and PARD6G isoform-specific functions using isoform-specific knockouts
Experiment: Live-cell imaging to understand dynamic shuttling of PARD6A between different subcellular compartments
Experiment: Structure-function analysis of PARD6A domain contributions to different cellular functions
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)