PARD6A

Protein PARD6A

Identifiers
par-6 partitioning defective 6 homolog alpha (C. elegans)
HUGO:PARD6A, HGNC:15943, ENTREZ:50855, GENECARDS:GC16P067696, UNIPROT:Q9NPB6

Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / CELL_CELL_ADHESIONS
EMT Senescence / TIGHT_JUNCTIONS
EMT Senescence / CYTOSKELETON_POLARITY

References
PMID:15761148
PARD6A is a regulator of epithelial cell polarity and tight-junction assembly
TGFBRI is localized to tight junctions where PARD6A is also found. TGFBR1 binds to PARD6A and localizes to tight junctions irrespective of TGF-beta stimulation.
The N-terminus of PARD6A, containing a PB1 domain necessary for binding to TGFBR1
TGFB stimulation induces redistribution of TGFBRII into tight junctions.
PARD6A interacts with TGFB receptors and is phsophorylated by TGFBRIII.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation controls the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBRI binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBRII phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.

PARD6A@Cytosol

References
em_emtc_emtc_re340( EMT Senescence ):
PMID:15761153
Occludin is a structural component of tight junctions that is associated with the cell polarity network.
Occludin regulates TGFBR1 localization for efficient TGFB-dependent dissolution of tight junctions during EMT
Interaction of endogenous OCLN with endogenous TGFBR1 was not modulated by TGFB
but its association with the TGFBR2 increased in a TGFB-dependent manner
PMID:15761148
TGFBR1 localizes with ZO-1 on the cellular apical aspect together with PARD6A and they are situated apically to endogenous E-cadherin
After stimulation by TGFB, TGFBR2 is redistributed to the tight junctions, where it localizes with both TGFBR1 and ZO-1.

PARD6A|S345_pho|active@Cytosol

References
em_emtc_emtc_re343( EMT Senescence ):
PMID:21572392
SMURF1 is an homologous to E6AP C-ter (HECT)-type E3 ubiquitin ligase
SMURF1 performs a crucial role in the regulation of the BMP signalling pathway in both embryonic development and bone remodelling.
PMID:15761148
PARD6A interacts with TGFB receptors and is phsophorylated by TGFBRIII.
Phosphorylation of Par6 is required for TGFB-dependent EMT in mammary gland epithelial cells
This phosphorylation controls the interaction of PARD6A with the E3 ubiquitin ligase Smurf1.
Smurf1, in turn, targets GTPase RhoA for degradation, thereby leading to a loss of tight junctions.
PMID:22949611
Signaling molecules act directly on polarity proteins, bypassing transcription factors such as Snail and Zeb1:
TGFBRI binds to the tight junction protein Occludin and locally assembles into a complex containing Par6.
Activated TGFBRII phosphorylates Par6, which binds to Smurf1 and causes RhoA ubiquitylation and the dissolution of junctions.

Modifications:
In compartment: Cytosol

PARD6A@Cytosol
PARD6A|S345_pho|active@Cytosol

Participates in complexes:
In compartment: Cytosol

Participates in reactions:
As Reactant or Product:

As Catalyser: