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FLASH GENE

Symbol

PARD3

contributors: mct/npt/pgu - updated : 07-09-2016

HGNC name	par-3 partitioning defective 3 homolog (C. elegans)
HGNC id	16051

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_019619 25 - 4071 NP_062565 - 1356 - 2015 26116754 NM_001184791 21 - 5677 NP_001171720 - 1244 - 2015 26116754 NM_001184789 24 - 5764 NP_001171718 - 1273 - 2015 26116754 NM_001184787 24 - 5902 NP_001171716 - 1319 - 2015 26116754 NM_001184790 23 - 5743 NP_001171719 - 1266 - 2015 26116754 NM_001184788 24 - 5875 NP_001171717 - 1310 - 2015 26116754 NM_001184786 24 - 5965 NP_001171715 - 1340 - 2015 26116754 NM_001184785 25 - 6004 NP_001171714 - 1353 - 2015 26116754 NM_001184793 21 - 3427 NP_001171722 - 1000 - 2015 26116754 NM_001184794 20 - 3391 NP_001171723 - 988 - 2015 26116754 NM_001184792 21 - 3520 NP_001171721 - 1031 - 2015 26116754

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial

cells

System Cell Pubmed Species Stage Rna symbol Nervous Schwann cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

three PDZ domains (the first PDZ domain interacts with PARD6 family), and PDZ domains interact with the negatively charged phospholipid phosphatidic acid immobilized on solid substrates or in liposomes

HOMOLOGY

interspecies	homolog to murine Pard3 (91.2pc)
	homolog to rattus Pard3 (90.9pc)

Homologene

FAMILY

PAR3 family

CATEGORY

adaptor , adhesion , structural protein

SUBCELLULAR LOCALIZATION	plasma membrane,junction,tight
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton
text	colocalized with the tight protein Z01 (TJP1)
	localized asymmetrically in Schwann cells at the axon-glial junction
	in epithelial cells, PARD3 is localised to the cell-cell adhesion complex

basic FUNCTION	involved in the establishment of cell polarity and in the asymmetric cytokinesis
	playing a role in tight junctions at epithelial cell-cell contacts
	PARD3, PARD3B, atypical protein kinase C (aPKC) and PARD6A, PARD6B critically regulate the apical membrane development required for epithelial organ development
	may be playing an important role in radiation-induced carcinogenesis of retinal pigment epithelium cells
	preventing tight junction assembly via its interaction with PARD6B
	mediating the inhibition of LIMK2 to regulate cofilin phosphorylation and tight junction assembly
	binds SPTLC1 and modulates monocyte serine palmitoyltransferase activity and chemotaxis
	FRMD6 and PARD3, cooperatively regulate ROCK1-dependent apical constriction
	conserved polarity regulator that organizes molecular networks in a wide range of cell types
	PARD3 polarity landmarks may be conglomerates of proteins and plasma membrane lipids that modify each other activities for an integrated effect on cell polarity
	is important in the definition of apicobasal polarity
	novel role of PARD3 during neural crest migration, which is likely to be conserved in other processes that involve contact inhibition of locomotion (CIL) such as cancer invasion or cell dispersion
	mediates contact inhibition between neural crest cells and promotes timely myelin gene expression but is not essential for neural crest migration or myelination
	plays an important role in the modulation of intestinal barrier function by regulating delivery of occludin as well as suppression of MYL1 phosphorylation
	inducing TAZ activation and cell growth by promoting LATS1 and PPP1CA interaction
	PARD3 function is either dispensable for slit diaphragm integrity, or compensatory mechanisms and a high redundancy of the different polarity proteins, including PARD3B, or PALS1, maintain the function of the glomerular filtration barrier, even in the absence of PARD3

CELLULAR PROCESS	cell cycle, division
	cell life, proliferation/growth
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

nervous system

text	axonogenesis

PATHWAY

metabolism

signaling

SIAH1-PARD3 signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche

a component	forming a quaternary complex with protein kinease C-zeta (PRKCZ), PARD6 family and CDC42 or ALS2CR19
	also forming a complex (with NGFR) neccessary for myelination
	FRMD6/PARD3-PRKCI-ROCK1 pathway that controls epithelial apical morphology
	PAR polarity complex of PARD3, PARD6A, and an atypical protein kinase C (PRKCI) regulate several aspects of neuronal migration

INTERACTION

DNA

RNA

small molecule

protein	interacting with PARD6B
	PNMA1, PARD6A
	associating with NGFR
	binding to TIAM1
	PARD3 acts as a cortical factor that tethers Microtubules through its association with DYNC1I2
	protein-protein interaction between SPTLC1 and PARD3 (is able to associate with the SPTLC1/2 holoenzyme by binding the C-terminal SPTLC1 PDZ motif)
	interacting with AURKA (interacts directly with the atypical protein kinase C binding domain of PARD3 and phosphorylates it at serine 962, phosphorylation that contributes to its function in the establishment of neuronal polarity)
	PARD3 regulates RAC1 activation by BDNF but not by NRG1-Type III in Schwann cells, although both ligands activate RAC1
	nuclear movement during myotube formation is microtubule and dynein dependent and is regulated by CDC42, PARD6A and PARD3
	GAB1 brings MARK2 and PARD3 into a transient complex, stimulating PARD3 phosphorylation by MARK2
	GAB1 and PARD6A bind the PARD3 PDZ1 domain and thereby compete for PARD3 binding
	RAC1 exchange factor TIAM1 participates in polarized cell migration with the PAR complex of PARD3, PARD6A, and PRKCI
	BAI1 interacts with PARD3/TIAM1 and recruits these proteins to synaptic sites
	CLASP2 directly interacted with PARD3 and was phosphorylated by PRKCI
	LRRC4 binds to the PDZ domain of PARD6A, and interacts with PARD3
	PARD3 physically interacts with CCDC88A, and together with GNAI3, CCDC88A controls tight junction formation, apical domain development and actin organization downstream of PARD3
	PARD3 promotes the interaction between PPP1CA and LATS1 to induce LATS1 dephosphorylation and inactivation, therefore leading to dephosphorylation and activation of TAZ
	biological activity of CDH5 in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins PALS1 and PARD3

cell & other

REGULATION

Phosphorylated by

MAPK1, that phosphorylates PARD3 and inhibits its binding with KIF3A, thereby controlling PARD3 transport and neuronal polarity

Other

phosphorylated by PRKCZ

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   reduced expression in esophageal squamous cell carcinoma associated with positive lymph node metastasis and poor differentiation

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS