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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
Location 10p11.21      Physical location : 34.398.487 - 35.104.253
Synonym name
  • three-PDZ containing protein similar to C. elegans PAR3 (partitioning defect)
  • atypical PKC isotype-specific interacting protein
  • CTCL tumor antigen se2-5
  • Synonym symbol(s) Baz, ASIP, PAR3, PARD3A, Bazooka, SE2-5T2, FLJ21015, SE2-5L16, SE2-5LT1, PAR3alpha, PPP1R118
    DNA
    TYPE functioning gene
    STRUCTURE 705.77 kb     25 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    FLJ10486 10p12.1 hypothetical protein FLJ10486 LOC389946 10 similar to G1/S-specific cyclin D3 MAP3K8 10p11.2 mitogen-activated protein kinase kinase kinase 8 LOC119180 10p11.23 lysozyme 2 LOC143110 10p11.23 similar to supervillin isoform 2; membrane-associated F-actin binding protein p205; archvillin LOC387648 10 similar to supervillin isoform 2; membrane-associated F-actin binding protein p205; archvillin LOC220929 10p11.23 hypothetical protein LOC220929 TCF8 10p11.2 transcription factor 8 (represses interleukin 2 expression) LOC387649 10 LOC387649 ARHGAP12 10pter-cen Rho GTPase activating protein 12 KIF5B 10p11.2 kinesin family member 5B LOC387650 10 hypothetical gene supported by BC000689; NM_021130; NR_000030 EPC1 10p11 enhancer of polycomb homolog 1, (Drosophila) FLJ32762 FLJ13031 ITGB1 10p11.2 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12) LOC340933 10p11.23 similar to 60S ribosomal protein L7a (Surfeit locus protein 3) (PLA-X polypeptide) NRP1 10p12 neuropilin 1 PARD3 10p11.23 par-3 partitioning defective 3 homolog (C. elegans) CUL2 10p11.2-p11.1 cullin 2 CREM 10p12.1-p11.1 cAMP responsive element modulator C10orf9 10p11.22 chromosome 10 open reading frame 9 CX40.1 10p11.22 connexin40.1 FZD8 10p11.22 frizzled homolog 8 (Drosophila) LOC389947 10 similar to ribosomal protein L7 LOC387651 10 similar to Pre-B cell enhancing factor precursor LOC389948 10 similar to MAP kinase-interacting serine/threonine kinase 1; MAP kinase interacting kinase 1 NY-BR-1 10p11.21 breast cancer antigen NY-BR-1 LOC387652 10 similar to hypothetical protein MGC33214 LOC219752 10p11.21 similar to TACC1 protein LOC387653 10 similar to tousled-like kinase 2; serine/threonine kinase; tousled-like kinase ZNF248 10p11.2 zinc finger protein 248 LOC387654 10 LOC387654 BA775A3.1 10p11 KRAB box zinc finger protein pseudogene LOC389949 10 similar to zinc finger protein 11b (KOX 2) ZNF25 10p11.2 zinc finger protein 25 (KOX 19) ZNF33A 10p11.2 zinc finger protein 33a (KOX 31)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    25 - 4071 - 1356 - 2015 26116754
    21 - 5677 - 1244 - 2015 26116754
    24 - 5764 - 1273 - 2015 26116754
    24 - 5902 - 1319 - 2015 26116754
    23 - 5743 - 1266 - 2015 26116754
    24 - 5875 - 1310 - 2015 26116754
    24 - 5965 - 1340 - 2015 26116754
    25 - 6004 - 1353 - 2015 26116754
    21 - 3427 - 1000 - 2015 26116754
    20 - 3391 - 988 - 2015 26116754
    21 - 3520 - 1031 - 2015 26116754
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelial    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    NervousSchwann 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
  • 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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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