PARD6A

Partitioning defective 6 homolog alpha is a protein that in humans is encoded by the PARD6A gene.[5][6][7]

PARD6A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1WMH
Identifiers
Aliases	PARD6A, PAR-6A, PAR6, PAR6C, PAR6alpha, TAX40, TIP-40, par-6 family cell polarity regulator alpha
External IDs	OMIM: 607484 MGI: 1927223 HomoloGene: 9661 GeneCards: PARD6A
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q22.1 Start 67,660,946 bp[1] End 67,662,778 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 D3 Start 105,701,148 bp[2] End 105,703,496 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transcription factor binding • GTP-dependent protein binding • GO:0001948 protein binding • Rho GTPase binding • protein kinase C binding Cellular component • cytosol • cell projection • membrane • bicellular tight junction • ruffle • cell membrane • cell cortex • cell nucleus • cytoplasm • centrosome • microtubule organizing center • cytoskeleton • cell junction • centriolar satellite • macromolecular complex • apical plasma membrane Biological process • negative regulation of protein phosphorylation • cell division • cell-cell junction maintenance • bicellular tight junction assembly • cell cycle • GO:0022415 viral process • transforming growth factor beta receptor signaling pathway • Wnt signaling pathway, planar cell polarity pathway • positive regulation of protein localization to centrosome • centrosome cycle • establishment or maintenance of cell polarity • regulation of cellular localization • positive regulation of protein secretion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	50855	56513
Ensembl	ENSG00000102981	ENSMUSG00000005699
UniProt	Q9NPB6	Q9Z101
RefSeq (mRNA)	NM_001037281 NM_016948	NM_001047435 NM_001047436 NM_001286344 NM_001286345 NM_019695
RefSeq (protein)	NP_001032358 NP_058644	NP_001040900 NP_001040901 NP_001273273 NP_001273274 NP_062669
Location (UCSC)	Chr 16: 67.66 – 67.66 Mb	Chr 8: 105.7 – 105.7 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[7]

A recent study shows that Par6 associates with PKC-ι but not with PKC-zeta in melanoma. Oncogenic PKC-iota can promote melanoma cell invasion by up-regulating PKC-ι/Par6 pathway during EMT. PKC-ι inhibition or knockdown resulted an increase E-cadherin and RhoA levels while decreasing total Vimentin, phophorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma.[8]

Interactions

PARD6A has been shown to interact with:

• CDC42,[6][9][10]
• ECT2[11]
• Protein kinase Mζ,[6][11][12] and
• RAC1.[6][10]
• Protein kinase C-ι.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000102981 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000005699 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Rousset R, Fabre S, Desbois C, Bantignies F, Jalinot P (March 1998). "The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins". Oncogene. 16 (5): 643–54. doi:10.1038/sj.onc.1201567. PMID 9482110.
6. Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (March 2001). "Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C". Genes Cells. 6 (2): 107–19. doi:10.1046/j.1365-2443.2001.00404.x. PMID 11260256.
7. "Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)".
8. Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M (2017). "Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis". Int. J. Oncol. 51 (5): 1370–1382. doi:10.3892/ijo.2017.4131. PMC 5642393. PMID 29048609.
9. Joberty G, Petersen C, Gao L, Macara IG (August 2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42". Nat. Cell Biol. 2 (8): 531–9. doi:10.1038/35019573. PMID 10934474.
10. Qiu RG, Abo A, Steven Martin G (June 2000). "A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation". Curr. Biol. 10 (12): 697–707. doi:10.1016/s0960-9822(00)00535-2. PMID 10873802.
11. Liu XF, Ishida H, Raziuddin R, Miki T (August 2004). "Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity". Mol. Cell. Biol. 24 (15): 6665–75. doi:10.1128/MCB.24.15.6665-6675.2004. PMC 444862. PMID 15254234.
12. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.

Further reading

• Solecki DJ, Govek EE, Hatten ME (2006). "mPar6 alpha controls neuronal migration". J. Neurosci. 26 (42): 10624–5. doi:10.1523/JNEUROSCI.4060-06.2006. PMID 17050699.
• Qiu RG, Abo A, Steven Martin G (2000). "A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation". Curr. Biol. 10 (12): 697–707. doi:10.1016/S0960-9822(00)00535-2. PMID 10873802.
• Joberty G, Petersen C, Gao L, Macara IG (2000). "The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42". Nat. Cell Biol. 2 (8): 531–9. doi:10.1038/35019573. PMID 10934474.
• Johansson A, Driessens M, Aspenström P (2000). "The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1". J. Cell Sci. 113 (18): 3267–75. PMID 10954424.
• Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, Akimoto K, Izumi Y, Ohnishi T, Ohno S (2001). "Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures". J. Cell Biol. 152 (6): 1183–96. doi:10.1083/jcb.152.6.1183. PMC 2199212. PMID 11257119.
• Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H (2003). "PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions". Biochem. Biophys. Res. Commun. 299 (4): 641–6. doi:10.1016/S0006-291X(02)02698-0. PMID 12459187.
• Hurd TW, Gao L, Roh MH, Macara IG, Margolis B (2003). "Direct interaction of two polarity complexes implicated in epithelial tight junction assembly". Nat. Cell Biol. 5 (2): 137–42. doi:10.1038/ncb923. PMID 12545177.
• Brajenovic M, Joberty G, Küster B, Bouwmeester T, Drewes G (2004). "Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network". J. Biol. Chem. 279 (13): 12804–11. doi:10.1074/jbc.M312171200. PMID 14676191.
• Lemmers C, Michel D, Lane-Guermonprez L, Delgrossi MH, Médina E, Arsanto JP, Le Bivic A (2004). "CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells". Mol. Biol. Cell. 15 (3): 1324–33. doi:10.1091/mbc.E03-04-0235. PMC 363137. PMID 14718572.
• Weyrich P, Kapp K, Niederfellner G, Melzer M, Lehmann R, Häring HU, Lammers R (2005). "Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis via atypical protein kinase C." Mol. Endocrinol. 18 (5): 1287–300. doi:10.1210/me.2003-0253. PMID 14976222.
• Liu XF, Ishida H, Raziuddin R, Miki T (2004). "Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity". Mol. Cell. Biol. 24 (15): 6665–75. doi:10.1128/MCB.24.15.6665-6675.2004. PMC 444862. PMID 15254234.
• Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell. Proteomics. 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
• Hirano Y, Yoshinaga S, Takeya R, Suzuki NN, Horiuchi M, Kohjima M, Sumimoto H, Inagaki F (2005). "Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains". J. Biol. Chem. 280 (10): 9653–61. doi:10.1074/jbc.M409823200. PMID 15590654.
• Weyrich P, Lammers R, Fritsche A, Machicao F, Häring HU, Stefan N (2005). "A novel functional polymorphism (-336A/G) in the promoter of the partitioning-defective protein-6alpha gene is associated with increased glucose tolerance and lower concentrations of serum non-esterified fatty acids". Diabetologia. 48 (4): 669–74. doi:10.1007/s00125-005-1688-4. PMID 15744531.
• Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL (2005). "Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity". Science. 307 (5715): 1603–9. doi:10.1126/science.1105718. PMID 15761148.
• Barrios-Rodiles M, Brown KR, Ozdamar B, Bose R, Liu Z, Donovan RS, Shinjo F, Liu Y, Dembowy J, Taylor IW, Luga V, Przulj N, Robinson M, Suzuki H, Hayashizaki Y, Jurisica I, Wrana JL (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153.