PARD3
Domain
Contains a conserved N-terminal oligomerization domain (NTD) that is involved in oligomerization and is essential for proper subapical membrane localization.
The second PDZ domain mediates interaction with membranes containing phosphoinositol lipids.
Function
Adapter protein involved in asymmetrical cell division and cell polarization processes (PubMed:10954424, PubMed:27925688). Seems to play a central role in the formation of epithelial tight junctions (PubMed:27925688). Targets the phosphatase PTEN to cell junctions (By similarity). Involved in Schwann cell peripheral myelination (By similarity). Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly (By similarity). The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins (PubMed:10934474). Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (PubMed:19812038, PubMed:27925688).
Involvement in disease
Neural tube defects
NTD
Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy. Failure of neural tube closure can occur at any level of the embryonic axis. Common NTD forms include anencephaly, myelomeningocele and spina bifida, which result from the failure of fusion in the cranial and spinal region of the neural tube. NTDs have a multifactorial etiology encompassing both genetic and environmental components.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
Acetylated. Deacetylated by SIRT2, thereby inhibiting Schwann cell peripheral myelination.
Phosphorylation at Ser-827 by PRKCZ and PRKCI occurs at the most apical tip of epithelial cell-cell contacts during the initial phase of tight junction formation and may promote dissociation of the complex with PARD6. EGF-induced Tyr-1127 phosphorylation mediates dissociation from LIMK2 (By similarity). Phosphorylation by AURKA at Ser-962 is required for the normal establishment of neuronal polarity (PubMed:19812038).
Sequence Similarities
Belongs to the PAR3 family.
Tissue Specificity
Widely expressed.
Cellular localization
- Cytoplasm
- Endomembrane system
- Cell junction
- Cell junction
- Tight junction
- Cell junction
- Adherens junction
- Cell membrane
- Cytoplasm
- Cell cortex
- Cytoplasm
- Cytoskeleton
- Localized along the cell-cell contact region. Colocalizes with PARD6A and PRKCI at epithelial tight junctions. Colocalizes with the cortical actin that overlays the meiotic spindle during metaphase I and metaphase II. Colocalized with SIRT2 in internode region of myelin sheath (By similarity). Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction.
Alternative names
PAR3, PAR3A, PARD3, Partitioning defective 3 homolog, PAR-3, PARD-3, Atypical PKC isotype-specific-interacting protein, CTCL tumor antigen se2-5, PAR3-alpha, ASIP