PARD6B: Partitioning Defective 6 Homolog Beta in Human (Par-6β) OpenAI o3-deep-research-2025-06-26 137 citations 2025-12-27T18:01:07.327187

PARD6B: Partitioning Defective 6 Homolog Beta in Human (Par-6β)

Gene and Protein Overview

PARD6B (Par-6 beta) is a human gene encoding the polarity protein Par-6 homolog beta (also known as PAR6B). It belongs to the Par6 family of evolutionarily conserved cell-polarity regulators originally identified in C. elegans (the “partitioning defective” genes) (pmc.ncbi.nlm.nih.gov) (www.sciencedirect.com). Humans have three Par6 isoforms – Par6α (PARD6A), Par6β (PARD6B), and Par6γ (PARD6G) – which share common domain architecture and functions in polarity control (www.sciencedirect.com). Par6 proteins are adapter/scaffold molecules that form multi-protein complexes essential for asymmetric cell division and the establishment of cell polarity in many contexts (www.genecards.org) (www.genecards.org). Notably, Par6β is a cytoplasmic protein that translocates to specific cortical sites in cells to execute its function in coordination with other Par proteins (www.genecards.org).

Conservation and Importance: The Par6 family is highly conserved across species. The C. elegans par-6 gene is required for embryonic asymmetry, and homologs in flies and mammals perform analogous roles in organizing cell polarity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The critical role of PARD6B in development is underscored by mouse studies showing that Par6B is essential for forming the first polarized epithelium (trophectoderm) in the early embryo – loss of Pard6b disrupts blastocyst trophectoderm differentiation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Thus, PARD6B encodes a fundamental polarity regulator whose absence can lead to severe developmental defects, reflecting its indispensable role in cell organization.

Structure and Domain Features

PARD6B’s protein product Par-6β is defined by several conserved domains that mediate its interactions (Figure 1). It contains an N-terminal PB1 (Phox/Bem1) domain – also referred to as an OPR domain – which enables heterodimerization with other PB1-domain proteins (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, the PB1 of Par6β binds directly to the PB1 domain of atypical Protein Kinase C (aPKC), forming a Par6–aPKC complex (pmc.ncbi.nlm.nih.gov). Par6β also has a PDZ (PSD95/Discs-large/ZO-1) domain, a common protein–protein interaction module that in Par6 binds specific partner proteins at cell junctions (www.sciencedirect.com) (pmc.ncbi.nlm.nih.gov). Uniquely, Par6 proteins possess a semi-CRIB (Cdc42/Rac Interactive Binding) motif adjacent to the PDZ domain, which allows Par6β to bind the active (GTP-bound) forms of small Rho-family GTPases like Cdc42 and Rac1 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). An IQ motif (a calmodulin-binding sequence) is present as well, suggesting additional regulatory interactions (for example, binding myosin light chain) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These domains collectively define Par6β’s role as a modular scaffold: the PB1 domain tethers aPKC, the PDZ domain connects to polarity proteins (such as Par3 or Crumbs), and the CRIB-like region docks Cdc42/Rac1, integrating signaling inputs (www.sciencedirect.com) (pmc.ncbi.nlm.nih.gov). The “Par6 homology” motif encompasses this arrangement (PB1–PDZ–CRIB) characteristic of all Par6 family members (www.genecards.org).

Key Interactions: Through its PDZ domain, Par6β directly interacts with PARD3 (Par3), another PDZ-domain polarity protein, forming the Par6–Par3 complex (www.genecards.org) (pmc.ncbi.nlm.nih.gov). Par6’s PDZ can also bind the C-terminal PDZ-binding motifs of transmembrane polarity proteins like CRB3 (Crumbs3) (pmc.ncbi.nlm.nih.gov) and the N-terminal region of LGL (lethal giant larvae tumor suppressor) (pmc.ncbi.nlm.nih.gov). These interactions localize Par6/aPKC to specific membrane sites. The CRIB-like region binds GTP-loaded Cdc42 or Rac1, which allosterically increases Par6’s affinity for partners like Par3 (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In essence, active Cdc42 “recruits” Par6β to the cell cortex and enhances Par6’s binding to Par3 and other PDZ targets, aiding assembly of the polarity complex (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The PB1 domain binding to aPKC not only sequesters the kinase at the correct location but also can relieve aPKC’s autoinhibition, contributing to aPKC activation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Indeed, the binding of GTP-Cdc42 to Par6 is known to activate aPKC as part of the polarity signaling cascade (pmc.ncbi.nlm.nih.gov). Par6β itself is regulated by phosphorylation: for example, Par6 proteins can be phosphorylated by kinases like Aurora A or TGF-β receptor, which modulates their interactions (discussed below) (pmc.ncbi.nlm.nih.gov) (www.sciencedirect.com). Together, the domain structure of Par6β enables it to act as a central scaffold node linking small GTPases to aPKC and other polarity proteins (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This scaffold function is crucial for the downstream events that establish cell polarity.

Role in Cell Polarity and Asymmetric Division

Par6β is a core component of the polarity complex that establishes apical–basal polarity in epithelial cells and other cell types. It functions in partnership with Par3 and aPKC (often called the Par3–Par6–aPKC complex, or Par complex) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This complex localizes to the apical side of polarized cells, especially at the tight junctions that demarcate apical and basolateral membranes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In cultured human epithelial cells, PARD6B is required for proper tight junction assembly: knockdown of PARD6B impairs the formation of epithelial tight junctions and disrupts apical–basal polarity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, silencing PARD6B in MCF7 breast epithelial cells causes loss of the tight junction network and mislocalization of aPKCζ from the membrane (pmc.ncbi.nlm.nih.gov). This indicates that Par6β is essential to recruit/activate aPKC at cell–cell contacts, which in turn signals the maturation of tight junctions (pmc.ncbi.nlm.nih.gov). Consistently, cells lacking Par6β or aPKC phenocopy the effects of losing Cdc42 – they fail to orient their polarity correctly (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In a 3D morphogenesis model (Caco-2 cell cysts), depletion of Par6B was shown to mimic Cdc42 loss, leading to misoriented mitotic spindles, mispositioned apical surfaces, and aberrant multi-lumen cysts (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Par6β localizes to the apical surface of developing cysts and recruits aPKC to that site, helping define a single lumen; conversely, aPKC stabilizes Par6β (protecting it from degradation) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This interdependence ensures that the Par6–aPKC module is positioned at the nascent apical cortex to direct polarized cell division (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In broader terms, Par6β and its partners govern the orientation of cell division and the segregation of cell-fate determinants during asymmetric cell division. In polarized neuroepithelial stem cells, for instance, Par complexes remain apically localized in the dividing cell, thereby biasing the distribution of fate determinants and influencing whether the division is symmetric or asymmetric (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Localization of Par6 (along with Par3 and aPKC) at the apical cortex of a dividing progenitor can ensure one daughter cell inherits the apical complex (maintaining a progenitor character) while the other does not, contributing to differentiation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, regulatory mechanisms link cell-cycle machinery to Par6 activity during division: in Drosophila, the mitotic kinase Aurora-A phosphorylates Par6, leading to activation of aPKC, phosphorylation of Lgl, and the polarized localization of cell fate determinant Numb to one daughter cell (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Similar principles apply in mammals – Par6β–aPKC phosphorylates targets like Lgl to release their inhibition on Par3 and to exclude certain proteins from the apical domain (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Through such actions, Par6β helps define distinct cortical domains in daughter cells. In summary, PARD6B plays a central role in establishing cell polarity axes, from guiding tight junction formation and apical domain identity in epithelia (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov) to coordinating mitotic spindle orientation and asymmetric outcome of divisions in development (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These functions are tightly linked to its ability to integrate signals from cell–cell contacts and Rho GTPases and translate them into spatially organized aPKC activity.

Mechanistic insight – Par6β, Par3, and junction assembly: Par6β’s association with Par3 is thought to regulate the timing of tight junction assembly. Par3 can bind directly to junctional adhesion molecules like JAM-A (F11R) at nascent cell contacts; interestingly, when Par6 (PARD6B) binds Par3, it can prevent Par3’s interaction with JAM-A, thereby transiently preventing tight junction assembly (www.genecards.org). This suggests a regulatory mechanism where the Par6–Par3 complex must dissociate or rearrange to allow Par3 to engage JAM-A and finalize the tight junction. In early polarization, Par6–Par3–aPKC complexes accumulate at contacts, but Par6β-bound Par3 may hold off tight junction sealing until other polarity cues are aligned (www.genecards.org). Once conditions are appropriate, Par3 is released (possibly after aPKC phosphorylates Par3), freeing JAM-A and other components to form a mature tight junction. Thus, Par6β helps orchestrate junction assembly in a temporally controlled manner** by modulating Par3’s availability to junctional sites (www.genecards.org). This nuance exemplifies how Par6β not only initiates polarity signaling but also fine-tunes the formation of structural polarity features (like junctions) through its protein–protein interactions.

Integration into Signaling Pathways

Beyond its architectural role, Par6β participates in multiple signaling pathways that link cell polarity to changes in cell behavior. One well-studied pathway is TGF-β (transforming growth factor beta) signaling during epithelial–mesenchymal transition (EMT). In response to TGF-β, Par6 (likely including Par6β) becomes phosphorylated by the Type I TGF-β receptor at a conserved Ser/Thr site (pmc.ncbi.nlm.nih.gov) (www.sciencedirect.com). This phosphorylation enables Par6 to recruit an ubiquitin ligase, Smurf1, to the complex (pmc.ncbi.nlm.nih.gov). Smurf1, via Par6, then targets the small GTPase RhoA for ubiquitin-mediated degradation, leading to a loss of RhoA activity (www.sciencedirect.com). Since RhoA drives actin stress fiber formation and junctional tension, its downregulation causes dissolution of tight junctions and loss of polarity – early steps in EMT. In fact, a seminal study showed that TGF-β-induced phosphorylation of Par6 triggers RhoA degradation and breakup of epithelial junctions, promoting cell migration and invasiveness (www.sciencedirect.com). Thus, Par6β serves as a key node where extracellular TGF-β signals hijack the polarity machinery to induce phenotypic transformation. This mechanism connects polarity loss to cancer progression: by driving RhoA inactivation and junction disassembly, Par6 phosphorylation facilitates EMT and metastasis (www.sciencedirect.com).

Par6β also cross-talks with other major pathways that coordinate cell polarity and proliferation. For example, the Par6–aPKC complex can interface with the PI3K/Akt pathway and the MAPK/ERK pathway (www.sciencedirect.com). In certain contexts, Par6 proteins have been reported to interact with components of these signaling cascades, thereby influencing cell survival and growth in parallel to polarity. A recent review highlights that Par6 engages multiple signaling axes – including Wnt signaling and the Hippo pathway – in cancer cells, collectively promoting the loss of polarity and malignant progression (www.sciencedirect.com). One instance of cross-talk: Par6 (with Par3) can form a complex with phospholipase C-β (PLCβ) via their PDZ domains, stimulating PLCβ activity and downstream second messengers (DAG and IP3) that can affect cell dynamics (pmc.ncbi.nlm.nih.gov). Additionally, Par6–aPKC can inhibit RhoA signaling through alternative mechanisms: in neurons, Par6–aPKC activates p190 RhoGAP, thereby inactivating RhoA to promote dendritic spine development (pmc.ncbi.nlm.nih.gov). These interactions illustrate that Par6β is not an isolated polarity factor but an integrative hub connecting polarity with signaling networks. Through phosphorylation events and binding partnerships, Par6β influences pathways that govern cytoskeletal dynamics, cell cycle, and cell migration.

It is important to note that the Par6–aPKC complex’s activity is tightly regulated. Upstream signals (like Cdc42 activation or PIP₃ accumulation at the membrane) recruit and activate the complex (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), while other inputs (like Aurora-A kinase during mitosis or Rho-kinase via Par3 phosphorylation) modulate it to achieve specific outcomes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Furthermore, feedback loops exist: Par complex activity can feed back to activate or inhibit small GTPases and other signaling effectors (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For instance, Par3–Par6–aPKC can activate Rac1 by recruiting guanine-nucleotide exchange factors, creating a positive feedback that reinforces polarized signaling (pmc.ncbi.nlm.nih.gov). Overall, PARD6B is a central player in a network of signaling pathways that ensure polarity cues are coordinated with cell growth and motility signals. Its ability to link extracellular signals (TGF-β, Wnt) and intracellular signaling (Rho GTPases, kinases) to the polarity apparatus is a cornerstone of how cells translate polarity changes into broader biological responses.

Subcellular Localization and Dynamics

Par6β is predominantly found at the cell cortex in polarized cells, reflecting its role at the interface of cell–cell contacts. While the protein can diffuse in the cytoplasm, it becomes enriched at specific sites upon receiving polarity cues. During epithelial polarization, Par6β concentrates at the apical membrane and tight junction region – the boundary between apical and lateral surfaces (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). For example, in 3D cysts of Caco-2 cells, Par6B is observed localizing to the developing apical surface, precisely where the lumen will form (pmc.ncbi.nlm.nih.gov). This apical recruitment depends on Par6β binding to active Cdc42 at the cortex and to Par3 and aPKC that are also targeted to nascent junctions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). If Par6β is depleted, aPKC fails to localize apically and tight junction scaffolding is lost, underscoring that Par6β is required to anchor aPKC at the membrane (pmc.ncbi.nlm.nih.gov). Par6β can also localize to the leading edge or other polarized structures in migrating cells, in line with regions of active Cdc42. In neurons, Par6 (including Par6β isoform) localizes to the nascent axon tip, helping establish axon identity versus dendrites (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

Intracellularly, Par6β’s localization is dynamic: it cycles between the cytosol and cortical sites. Protein–protein interactions largely dictate Par6β positioning. When Par6β binds aPKC, the complex often associates with membranes (since aPKC has partial lipid-binding capacity and partners like Par3 can attach to membranes via lipid-binding domains) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Additionally, transmembrane proteins like Crumbs3 that bind Par6 can recruit the Par6β–aPKC complex directly to the plasma membrane (pmc.ncbi.nlm.nih.gov). On the other hand, if aPKC is inhibited or Par6β is unbound, Par6β may remain in the cytoplasm. Par6β has also been detected at the centrosome in some cell types, potentially linked to its role in spindle orientation (since the Par complex can influence centrosome positioning) (pmc.ncbi.nlm.nih.gov). However, its primary functional locale is the cell cortex at polarity sites: apical junctions in epithelia, the apical endfoot of neural progenitors, the “front” of migrating cells, or the cytokinetic cleavage plane in dividing polarized cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This spatially restricted localization allows Par6β to serve as a platform where specific enzymes (like aPKC) and small GTPases converge, ensuring that downstream phosphorylation events occur in the right place to define cellular asymmetry.

Clinical Significance and Recent Research Developments

Given its fundamental role in cell polarity, PARD6B has drawn attention in disease contexts, especially cancer. Loss of polarity is a hallmark of carcinoma progression, and polarity proteins like Par6β are often dysregulated in tumors (www.sciencedirect.com). Notably, PARD6B is located on chromosome 20, a region frequently amplified in cancers such as breast and colorectal carcinomas (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). A 2012 study reported that PARD6B is amplified and overexpressed in a subset of breast cancers (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In an analysis of 11 breast cancer cell lines, 5 lines harbored a PARD6B gene amplification (at 20q13.13), with copy-number increases up to 7–27 copies per cell (pmc.ncbi.nlm.nih.gov). This genomic amplification correlated with elevated Par6B mRNA and protein levels in those cells (pmc.ncbi.nlm.nih.gov). Functional experiments in the same study showed that Par6B overexpression was associated with robust tight junction structures in cultured monolayers, whereas Par6B silencing led to junctional defects, as mentioned earlier (pmc.ncbi.nlm.nih.gov). Immunohistochemistry on breast tumor samples further found Par6β to be expressed specifically in epithelial tumor cells (absent in stroma), although staining intensity varied and only subtle quantitative differences were noted between tumors (pmc.ncbi.nlm.nih.gov). These findings suggest that some cancers select for increased Par6B, potentially to exploit its polarity-regulating functions. Interestingly, maintaining some aspects of cell polarity via Par6B might confer advantages to tumor cells in certain microenvironments (for example, organizing invasive fronts or sustaining growth in epithelioid clusters).

Recent research has uncovered a direct pro-tumor role for PARD6B in colorectal cancer (CRC). A 2025 study (Park et al., published in Cancer Science) showed that PARD6B is frequently upregulated in CRC and promotes tumor growth by modulating oncogenic signaling (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). The PARD6B gene lies in a region of chromosome 20 often gained in CRC, and its mRNA expression was found to be significantly higher in colorectal tumors than in normal tissue, correlating with DNA copy-number gain (pubmed.ncbi.nlm.nih.gov). High PARD6B expression was associated with advanced disease and poorer patient prognosis (pubmed.ncbi.nlm.nih.gov). Functionally, elevated Par6B drives proliferation of CRC cells: in vitro and in vivo experiments demonstrated that PARD6B positively regulates cancer cell proliferation and cell-cycle progression (pubmed.ncbi.nlm.nih.gov). Mechanistically, Par6B overexpression in CRC was shown to upregulate the oncogene MYC by suppressing a tumor-suppressor microRNA (miR-34c) (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). miR-34c normally would repress MYC; thus, Par6B creates a permissive environment for MYC overexpression, fueling cell growth. This PARD6B–miR-34c–MYC axis represents a novel connection between a polarity protein and the core proliferation machinery (pmc.ncbi.nlm.nih.gov). The same study noted that PARD6B mRNA overexpression is a poor prognostic factor in multiple cancer types, and it proposed PARD6B as a promising prognostic biomarker and potential therapeutic target in CRC (pubmed.ncbi.nlm.nih.gov). Targeting Par6B or its downstream interactions (for instance, disrupting Par6–aPKC or Par6–Cdc42 binding) could be explored as a strategy to impair tumor cell polarity signals that are supporting growth and survival. While no Par6-specific inhibitors exist yet, the identification of Par6B’s impact on pathways like MYC suggests that patients with PARD6B-high tumors might benefit from therapies targeting those downstream oncogenic pathways (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).

More broadly, emerging data indicate that different Par6 isoforms may have context-specific roles in cancer. According to a 2025 comprehensive review, Par6 family proteins show tumor-type-specific expression patterns and clinical implications (www.sciencedirect.com). For example, PARD6A (Par6α) was recently implicated in ovarian cancer cell invasion via EMT pathways, whereas PARD6B (Par6β) appears more prominently in breast and colorectal cancers (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Despite these differences, a common theme is that overexpression or dysregulation of Par6 proteins can contribute to loss of cell polarity, enhanced migration, and uncontrolled proliferation in tumors (www.sciencedirect.com). Par6-mediated polarity signaling intersects with oncogenic pathways (TGF-β, PI3K/Akt, Wnt, etc.), meaning that aberrant Par6 activity can tip the balance toward tumor progression (www.sciencedirect.com). Clinically, this makes components of the Par complex interesting as biomarkers: high Par6 expression might indicate an aggressive tumor phenotype or specific vulnerabilities. For instance, the CRC study suggests monitoring PARD6B levels could inform prognosis, and combining Par6B status with other molecular data might refine patient stratification (pubmed.ncbi.nlm.nih.gov). There is also interest in whether Par6β could be therapeutically targeted. While directly drugging a scaffold protein is challenging, disrupting its critical interactions (like Par6–aPKC) or downstream effects (like the Par6→RhoA or Par6→MYC pathways) could yield new anti-cancer strategies. Additional research is ongoing to map all interaction partners of Par6β and how they contribute to oncogenic processes.

Expert Perspectives and Future Directions

Cell polarity regulators like Par6β are now recognized as more than just “housekeeping” proteins – experts consider them key orchestrators of complex cellular behaviors. A recent authoritative review (Cell Signalling, 2025) emphasizes that Par6 “plays a crucial role in controlling cell polarity,” with its PDZ, CRIB, and PB1 domains enabling diverse signaling interactions that establish polarity (www.sciencedirect.com). Researchers Vargas et al. (2025) highlight that Par6’s functional versatility allows it to coordinate structural polarity with signaling pathways involved in cell proliferation and survival (www.sciencedirect.com). They note that Par6 (including Par6β) lies at a crossroads of pathways – citing its involvement in TGF-β-driven EMT, and its ability to engage PI3K/Akt, MAPK/ERK, and Wnt signaling – thereby integrating polarity loss with malignant transformation (www.sciencedirect.com). Such expert analyses suggest that PARD6B is not only central to normal epithelial biology but also to pathological processes like cancer metastasis. There is a growing consensus that studying polarity proteins can yield insights into disease mechanisms: for example, how a tumor cell loses organized structure and gains invasive capacity.

Going forward, key questions remain about PARD6B’s regulation and potential as a drug target. Post-translational modifications (phosphorylation by various kinases, ubiquitination, etc.) of Par6β are an active research area, as these modifications dictate Par6β’s activity and localization. Understanding these regulatory layers could open opportunities to modulate Par6β function pharmacologically. Another area of interest is the isoform-specific functions of Par6 proteins: why do mammals have three Par6 genes and do they have non-redundant roles? Some studies hint that Par6β might be specialized for certain tissues or signals – for instance, it may preferentially partner with aPKCζ versus aPKCλ, or have distinct affinities for Cdc42 vs Rac1 compared to Par6α (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Deciphering these nuances could inform tissue-specific interventions (e.g. targeting Par6β in cancers where it is the dominant isoform).

In summary, PARD6B (Par-6β) is a pivotal cell polarity regulator with a well-defined role in organizing the Par polarity complex at the cell cortex. Its scaffold function links GTPases like Cdc42 to the activation and localization of aPKC, driving the assembly of polarity structures such as tight junctions (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). By controlling cell polarity and asymmetric division, Par6β ensures normal tissue architecture and development. Simultaneously, it serves as a conduit for signaling pathways (TGF-β, PI3K, etc.) that can repurpose the polarity machinery to influence cell migration and proliferation (www.sciencedirect.com). Recent research underscores Par6β’s clinical relevance, implicating it in cancer progression where its overexpression can promote tumor growth and metastasis (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). As our understanding of PARD6B deepens, it stands out as both a fundamental piece of the cell polarity puzzle and a potential bridge between loss of polarity and disease, making it a compelling subject for continued investigation in cell biology and oncology.

Figures: Diagrammatic representation of Par6B domain structure and the Par6–Par3–aPKC complex localization in a polarized epithelial cell (with Par6B at the apical junction, interacting with Cdc42 and aPKC). (Refer to sources such as Joberty 2000 (pmc.ncbi.nlm.nih.gov) and Lin 2000 (pmc.ncbi.nlm.nih.gov) for original discovery of Par6 interactions.)

Citations

  1. AnnotationURLCitation(end_index=504, start_index=373, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=JR%2C%20Kemphues%20KJ%20%281996%29%20par,Google')
  2. AnnotationURLCitation(end_index=678, start_index=505, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20plays%20a%20crucial%20role,The%20PDZ%2C%20CRIB%20%28Cdc42%2FRac')
  3. AnnotationURLCitation(end_index=1013, start_index=840, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20plays%20a%20crucial%20role,The%20PDZ%2C%20CRIB%20%28Cdc42%2FRac')
  4. AnnotationURLCitation(end_index=1360, start_index=1193, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=Adapter%20protein%20involved%20in%20asymmetrical,PARD3%20complex%20links%20GTP')
  5. AnnotationURLCitation(end_index=1490, start_index=1361, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=This%20gene%20is%20a%20member,See%20more')
  6. AnnotationURLCitation(end_index=1783, start_index=1654, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=This%20gene%20is%20a%20member,See%20more')
  7. AnnotationURLCitation(end_index=2154, start_index=2023, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=JR%2C%20Kemphues%20KJ%20%281996%29%20par,Google')
  8. AnnotationURLCitation(end_index=2334, start_index=2155, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=Proper%20neurodevelopment%20is%20regulated%20by,chromosome%20location%20of%20these%20homologous')
  9. AnnotationURLCitation(end_index=2733, start_index=2593, title='Cell Polarity Regulator PARD6B Is Essential for Trophectoderm Formation in the Preimplantation Mouse Embryo - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2924801/#:~:text=Cell%20Polarity%20Regulator%20PARD6B%20Is,%28n%20%3D%203')
  10. AnnotationURLCitation(end_index=2869, start_index=2734, title='Cell Polarity Regulator PARD6B Is Essential for Trophectoderm Formation in the Preimplantation Mouse Embryo - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2924801/#:~:text=PMCID%3A%20PMC2924801%C2%A0%C2%A0PMID%3A%2020505164')
  11. AnnotationURLCitation(end_index=3462, start_index=3343, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L296%20calmodulin,2005')
  12. AnnotationURLCitation(end_index=3561, start_index=3463, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PB1%20%20,2005')
  13. AnnotationURLCitation(end_index=3785, start_index=3687, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PB1%20%20,2005')
  14. AnnotationURLCitation(end_index=4125, start_index=3952, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20plays%20a%20crucial%20role,The%20PDZ%2C%20CRIB%20%28Cdc42%2FRac')
  15. AnnotationURLCitation(end_index=4224, start_index=4126, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PDZ%20%20,2003')
  16. AnnotationURLCitation(end_index=4571, start_index=4452, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L296%20calmodulin,2005')
  17. AnnotationURLCitation(end_index=4731, start_index=4572, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  18. AnnotationURLCitation(end_index=5008, start_index=4889, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L296%20calmodulin,2005')
  19. AnnotationURLCitation(end_index=5127, start_index=5009, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=Par6%27s%20N%20terminus%20%20,2009')
  20. AnnotationURLCitation(end_index=5556, start_index=5383, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20plays%20a%20crucial%20role,The%20PDZ%2C%20CRIB%20%28Cdc42%2FRac')
  21. AnnotationURLCitation(end_index=5716, start_index=5557, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  22. AnnotationURLCitation(end_index=5959, start_index=5830, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=This%20gene%20is%20a%20member,See%20more')
  23. AnnotationURLCitation(end_index=6290, start_index=6123, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=Adapter%20protein%20involved%20in%20asymmetrical,PARD3%20complex%20links%20GTP')
  24. AnnotationURLCitation(end_index=6390, start_index=6291, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PDZ1%20%20,2005')
  25. AnnotationURLCitation(end_index=6632, start_index=6510, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=at%20the%20apical%20side,Yamanaka%20et')
  26. AnnotationURLCitation(end_index=6835, start_index=6709, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L517%20at%20the,Yamanaka%20et')
  27. AnnotationURLCitation(end_index=7189, start_index=7030, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  28. AnnotationURLCitation(end_index=7340, start_index=7190, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=The%20binding%20of%20GTP,conformational%20changes%20in%20Par6%20to')
  29. AnnotationURLCitation(end_index=7665, start_index=7506, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  30. AnnotationURLCitation(end_index=7788, start_index=7666, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=at%20the%20apical%20side,Yamanaka%20et')
  31. AnnotationURLCitation(end_index=8054, start_index=7956, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PB1%20%20,2005')
  32. AnnotationURLCitation(end_index=8237, start_index=8055, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=their%20pleckstrin%20homology%20domains%20to,complexes%2C%20making%20Par%20complexes%20integration')
  33. AnnotationURLCitation(end_index=8534, start_index=8352, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=their%20pleckstrin%20homology%20domains%20to,complexes%2C%20making%20Par%20complexes%20integration')
  34. AnnotationURLCitation(end_index=8889, start_index=8732, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=asymmetric%20cell%20division,specificity%20of%20aPKC%20and%20consequently')
  35. AnnotationURLCitation(end_index=9077, start_index=8890, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  36. AnnotationURLCitation(end_index=9385, start_index=9226, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  37. AnnotationURLCitation(end_index=9568, start_index=9386, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=their%20pleckstrin%20homology%20domains%20to,complexes%2C%20making%20Par%20complexes%20integration')
  38. AnnotationURLCitation(end_index=10121, start_index=9952, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L107%20Par3%2C%20Par6%2C,to%20these%20protein%20complexes%20collectively')
  39. AnnotationURLCitation(end_index=10221, start_index=10122, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PDZ1%20%20,2005')
  40. AnnotationURLCitation(end_index=10518, start_index=10371, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=Dysregulation%20of%20mechanisms%20that%20govern,Expression%20of')
  41. AnnotationURLCitation(end_index=10691, start_index=10519, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  42. AnnotationURLCitation(end_index=11044, start_index=10897, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=Dysregulation%20of%20mechanisms%20that%20govern,Expression%20of')
  43. AnnotationURLCitation(end_index=11221, start_index=11045, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  44. AnnotationURLCitation(end_index=11550, start_index=11374, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  45. AnnotationURLCitation(end_index=11871, start_index=11695, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  46. AnnotationURLCitation(end_index=12178, start_index=12004, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=reported%20that%20Cdc42%20controls%20mitotic,and%20aPKC%20function%20interdependently%20in')
  47. AnnotationURLCitation(end_index=12351, start_index=12179, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  48. AnnotationURLCitation(end_index=12733, start_index=12559, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=reported%20that%20Cdc42%20controls%20mitotic,and%20aPKC%20function%20interdependently%20in')
  49. AnnotationURLCitation(end_index=12906, start_index=12734, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  50. AnnotationURLCitation(end_index=13279, start_index=13100, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=Cdc42%2C%20inducing%20misorientation%20of%20the,different%20thresholds%20of%20aPKC%20expression')
  51. AnnotationURLCitation(end_index=13432, start_index=13280, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=multiple%20lumens,spindle%20orientation%20in%20polarized%20epithelia')
  52. AnnotationURLCitation(end_index=13738, start_index=13566, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  53. AnnotationURLCitation(end_index=13891, start_index=13739, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=multiple%20lumens,spindle%20orientation%20in%20polarized%20epithelia')
  54. AnnotationURLCitation(end_index=14471, start_index=14295, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=divisions%2C%20whereas%20asymmetric%20divisions%20produce,a%20basal%20daughter%20cell%20that')
  55. AnnotationURLCitation(end_index=14642, start_index=14472, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=spatiotemporal%20manners%20%28Liu%20et%20al,supported%20by%20studies%20of%20asymmetric')
  56. AnnotationURLCitation(end_index=15057, start_index=14890, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L710%20asymmetrically%20depends,all%20regulated%20by%20Par%20complexes')
  57. AnnotationURLCitation(end_index=15228, start_index=15058, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=spatiotemporal%20manners%20%28Liu%20et%20al,supported%20by%20studies%20of%20asymmetric')
  58. AnnotationURLCitation(end_index=15681, start_index=15524, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=asymmetric%20cell%20division,specificity%20of%20aPKC%20and%20consequently')
  59. AnnotationURLCitation(end_index=15848, start_index=15682, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=phosphorylates%20and%20activates%20DmPar,promote%20its%20basal%20localization%20in')
  60. AnnotationURLCitation(end_index=16183, start_index=16026, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=asymmetric%20cell%20division,specificity%20of%20aPKC%20and%20consequently')
  61. AnnotationURLCitation(end_index=16310, start_index=16184, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L517%20at%20the,Yamanaka%20et')
  62. AnnotationURLCitation(end_index=16707, start_index=16560, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=Dysregulation%20of%20mechanisms%20that%20govern,Expression%20of')
  63. AnnotationURLCitation(end_index=16884, start_index=16708, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  64. AnnotationURLCitation(end_index=17156, start_index=16984, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  65. AnnotationURLCitation(end_index=17336, start_index=17157, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=Cdc42%2C%20inducing%20misorientation%20of%20the,different%20thresholds%20of%20aPKC%20expression')
  66. AnnotationURLCitation(end_index=18083, start_index=17916, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=Adapter%20protein%20involved%20in%20asymmetrical,PARD3%20complex%20links%20GTP')
  67. AnnotationURLCitation(end_index=18576, start_index=18409, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=Adapter%20protein%20involved%20in%20asymmetrical,PARD3%20complex%20links%20GTP')
  68. AnnotationURLCitation(end_index=19046, start_index=18879, title='PARD6B Gene - GeneCards | PAR6B Protein | PAR6B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=PARD6B#:~:text=Adapter%20protein%20involved%20in%20asymmetrical,PARD3%20complex%20links%20GTP')
  69. AnnotationURLCitation(end_index=19785, start_index=19687, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PB1%20%20,2005')
  70. AnnotationURLCitation(end_index=19973, start_index=19786, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  71. AnnotationURLCitation(end_index=20235, start_index=20068, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L1981%20Rho%20GTPases,Molecular%20characterization%20of%20CDC42%2C%20a')
  72. AnnotationURLCitation(end_index=20552, start_index=20365, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  73. AnnotationURLCitation(end_index=21092, start_index=20905, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  74. AnnotationURLCitation(end_index=21591, start_index=21404, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  75. AnnotationURLCitation(end_index=21986, start_index=21805, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=interactions%20of%20PAR6%20in%20tumor,the%20Par6%20complex%20by%20phosphatases')
  76. AnnotationURLCitation(end_index=22560, start_index=22379, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=interactions%20of%20PAR6%20in%20tumor,the%20Par6%20complex%20by%20phosphatases')
  77. AnnotationURLCitation(end_index=22934, start_index=22786, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L605%20G,signaling%20plays%20important%20roles%20in')
  78. AnnotationURLCitation(end_index=23264, start_index=23133, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=that%20the%20loss%20of%20Cdc42%2C,In%20addition')
  79. AnnotationURLCitation(end_index=23915, start_index=23765, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=The%20binding%20of%20GTP,conformational%20changes%20in%20Par6%20to')
  80. AnnotationURLCitation(end_index=24098, start_index=23916, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=their%20pleckstrin%20homology%20domains%20to,complexes%2C%20making%20Par%20complexes%20integration')
  81. AnnotationURLCitation(end_index=24402, start_index=24245, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=asymmetric%20cell%20division,specificity%20of%20aPKC%20and%20consequently')
  82. AnnotationURLCitation(end_index=24568, start_index=24403, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=neurons%20by%20activating%20p190%20RhoGAP,and%20downstream%20of%20Par%20complexes')
  83. AnnotationURLCitation(end_index=24849, start_index=24707, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=activate%20aPKC%20%28Yamanaka%20et%20al,Pard3%20can%20also')
  84. AnnotationURLCitation(end_index=25015, start_index=24850, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=neurons%20by%20activating%20p190%20RhoGAP,and%20downstream%20of%20Par%20complexes')
  85. AnnotationURLCitation(end_index=25322, start_index=25180, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=activate%20aPKC%20%28Yamanaka%20et%20al,Pard3%20can%20also')
  86. AnnotationURLCitation(end_index=26330, start_index=26151, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=Cdc42%2C%20inducing%20misorientation%20of%20the,different%20thresholds%20of%20aPKC%20expression')
  87. AnnotationURLCitation(end_index=26507, start_index=26331, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  88. AnnotationURLCitation(end_index=26829, start_index=26650, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=Cdc42%2C%20inducing%20misorientation%20of%20the,different%20thresholds%20of%20aPKC%20expression')
  89. AnnotationURLCitation(end_index=27134, start_index=26975, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L400%20The%20binding,conformational%20changes%20in%20Par6%20to')
  90. AnnotationURLCitation(end_index=27314, start_index=27135, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=Cdc42%2C%20inducing%20misorientation%20of%20the,different%20thresholds%20of%20aPKC%20expression')
  91. AnnotationURLCitation(end_index=27657, start_index=27481, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  92. AnnotationURLCitation(end_index=28050, start_index=27918, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=match%20at%20L405%20Cdc42%20distributes,lymphoma')
  93. AnnotationURLCitation(end_index=28214, start_index=28051, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=aPKC%CE%B6%20can%20be%20activated%20to,mediated%20aPKC%CE%B6%20activation%20for')
  94. AnnotationURLCitation(end_index=28734, start_index=28574, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=1988%2C%201995%3B%20Steinberg%2C%202008%29,by%20contrast%2C%20aPKC%20require')
  95. AnnotationURLCitation(end_index=28914, start_index=28735, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=and%20activation%20of%20Par%20complexes,from%20nonspecific%20electrostatic%20interactions%20and')
  96. AnnotationURLCitation(end_index=29146, start_index=29048, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PDZ%20%20,2004')
  97. AnnotationURLCitation(end_index=29600, start_index=29426, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=reported%20that%20Cdc42%20controls%20mitotic,and%20aPKC%20function%20interdependently%20in')
  98. AnnotationURLCitation(end_index=30026, start_index=29850, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=divisions%2C%20whereas%20asymmetric%20divisions%20produce,a%20basal%20daughter%20cell%20that')
  99. AnnotationURLCitation(end_index=30199, start_index=30027, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=partner%2C%20atypical%20protein%20kinase%20C,induces%20robust%20apoptotic%20cell%20death')
  100. AnnotationURLCitation(end_index=30929, start_index=30742, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  101. AnnotationURLCitation(end_index=31180, start_index=31062, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=apico,aPKC%29%2C%20but%20did%20not')
  102. AnnotationURLCitation(end_index=31342, start_index=31181, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=which%20is%20frequently%20amplified%20in,unlike%20other%20polarity%20gene%20groups')
  103. AnnotationURLCitation(end_index=31590, start_index=31443, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=Dysregulation%20of%20mechanisms%20that%20govern,Expression%20of')
  104. AnnotationURLCitation(end_index=31709, start_index=31591, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=apico,aPKC%29%2C%20but%20did%20not')
  105. AnnotationURLCitation(end_index=32030, start_index=31874, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=In%20this%20study%20we%20report,TJ%20network%20formation%20in%20cultured')
  106. AnnotationURLCitation(end_index=32247, start_index=32129, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=apico,aPKC%29%2C%20but%20did%20not')
  107. AnnotationURLCitation(end_index=32652, start_index=32476, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  108. AnnotationURLCitation(end_index=33056, start_index=32896, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=cell%20monolayers.%20SiRNA,quantitative%20differences%20in%20staining%20were')
  109. AnnotationURLCitation(end_index=33837, start_index=33682, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12400055/#:~:text=Skip%20to%20main%20content%20Cancer,a%20polarity%20gene%2C%20functions')
  110. AnnotationURLCitation(end_index=33999, start_index=33838, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=highly%20expressed%20PARD6B%20can%20promote,and%20therapeutic%20target%20for%20CRC')
  111. AnnotationURLCitation(end_index=34376, start_index=34215, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=which%20is%20frequently%20amplified%20in,unlike%20other%20polarity%20gene%20groups')
  112. AnnotationURLCitation(end_index=34618, start_index=34467, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=mRNA%20expression%20is%20a%20poor,and%20therapeutic%20target%20for%20CRC')
  113. AnnotationURLCitation(end_index=34955, start_index=34820, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=prognostic%20factor,silico%20and%20in%20vitro%20analyses')
  114. AnnotationURLCitation(end_index=35262, start_index=35100, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12400055/#:~:text=Partitioning%20Defective%206B%20,promising%20therapeutic%20target%20for%20CRC')
  115. AnnotationURLCitation(end_index=35424, start_index=35263, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=highly%20expressed%20PARD6B%20can%20promote,and%20therapeutic%20target%20for%20CRC')
  116. AnnotationURLCitation(end_index=35837, start_index=35675, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12400055/#:~:text=Partitioning%20Defective%206B%20,promising%20therapeutic%20target%20for%20CRC')
  117. AnnotationURLCitation(end_index=36200, start_index=36049, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=mRNA%20expression%20is%20a%20poor,and%20therapeutic%20target%20for%20CRC')
  118. AnnotationURLCitation(end_index=36806, start_index=36644, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12400055/#:~:text=Partitioning%20Defective%206B%20,promising%20therapeutic%20target%20for%20CRC')
  119. AnnotationURLCitation(end_index=36958, start_index=36807, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=mRNA%20expression%20is%20a%20poor,and%20therapeutic%20target%20for%20CRC')
  120. AnnotationURLCitation(end_index=37386, start_index=37212, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20isoforms%20show%20tumor,patterns%20and%20clinical%20significance')
  121. AnnotationURLCitation(end_index=37718, start_index=37571, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=Dysregulation%20of%20mechanisms%20that%20govern,Expression%20of')
  122. AnnotationURLCitation(end_index=37874, start_index=37719, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12400055/#:~:text=Skip%20to%20main%20content%20Cancer,a%20polarity%20gene%2C%20functions')
  123. AnnotationURLCitation(end_index=38268, start_index=38081, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  124. AnnotationURLCitation(end_index=38636, start_index=38449, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  125. AnnotationURLCitation(end_index=39139, start_index=38988, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=mRNA%20expression%20is%20a%20poor,and%20therapeutic%20target%20for%20CRC')
  126. AnnotationURLCitation(end_index=40184, start_index=40011, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=Par6%20plays%20a%20crucial%20role,The%20PDZ%2C%20CRIB%20%28Cdc42%2FRac')
  127. AnnotationURLCitation(end_index=40569, start_index=40382, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  128. AnnotationURLCitation(end_index=41005, start_index=40818, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  129. AnnotationURLCitation(end_index=42249, start_index=42127, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=,the%20requirement%20of%20a%20complete')
  130. AnnotationURLCitation(end_index=42343, start_index=42250, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=CRIB,2000')
  131. AnnotationURLCitation(end_index=42976, start_index=42800, title='PAR6B is required for tight junction formation and activated PKCζ localization in breast cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3433109/#:~:text=related%20isoforms%20PARD6A%20and%20PARD6G,quantitative%20differences%20in%20staining%20were')
  132. AnnotationURLCitation(end_index=43129, start_index=42977, title='Par6B and Atypical PKC Regulate Mitotic Spindle Orientation during Epithelial Morphogenesis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3069449/#:~:text=multiple%20lumens,spindle%20orientation%20in%20polarized%20epithelia')
  133. AnnotationURLCitation(end_index=43600, start_index=43413, title='Polarity protein Par6: Unraveling its mechanisms in tumor development and research advances - ScienceDirect', type='url_citation', url='https://www.sciencedirect.com/science/article/pii/S0898656825005960#:~:text=tumors%20and%20their%20divergent%20clinical,the%20Par6%20complex%20by%20phosphatases')
  134. AnnotationURLCitation(end_index=43921, start_index=43760, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=highly%20expressed%20PARD6B%20can%20promote,and%20therapeutic%20target%20for%20CRC')
  135. AnnotationURLCitation(end_index=44073, start_index=43922, title='Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/40533910/#:~:text=mRNA%20expression%20is%20a%20poor,and%20therapeutic%20target%20for%20CRC')
  136. AnnotationURLCitation(end_index=44691, start_index=44593, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PB1%20%20,2005')
  137. AnnotationURLCitation(end_index=44804, start_index=44705, title='The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC9188383/#:~:text=PDZ1%20%20,2005')