PARD6A

Par-6 family cell polarity regulator alpha

PDB rendering based on 1wmh.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1WMH

Identifiers

Symbols

PARD6A ; PAR-6A; PAR6; PAR6C; PAR6alpha; TAX40; TIP-40

External IDs

OMIM: 607484 MGI: 1927223 HomoloGene: 9661 GeneCards: PARD6A Gene

Gene ontology
Molecular function	• protein kinase C binding • protein binding • transcription factor binding • Rho GTPase binding • GTP-dependent protein binding
Cellular component	• ruffle • nucleus • cytosol • plasma membrane • tight junction • cell cortex • protein complex • apical part of cell
Biological process	• cell cycle • transforming growth factor beta receptor signaling pathway • viral process • cell junction assembly • cell-cell junction organization • cell-cell junction maintenance • cell division • tight junction assembly
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 16:
67.69 – 67.7 Mb

Chr 8:
105.7 – 105.7 Mb

PubMed search

Partitioning defective 6 homolog alpha is a protein that in humans is encoded by the PARD6A gene.^[1]^[2]^[3]

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.^[3]

Interactions

PARD6A has been shown to interact with:

CDC42,^[2]^[4]^[5]
ECT2^[6]
Protein kinase Mζ,^[2]^[6]^[7] and
RAC1.^[2]^[5]

References

↑ 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.
↑ 2.0 2.1 2.2 2.3 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.
↑ 3.0 3.1 "Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)".
↑ 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.
↑ 5.0 5.1 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.
↑ 6.0 6.1 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.
↑ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (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.

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. Vancouver style error (help)
Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M et al. (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. Vancouver style error (help)
Lemmers C, Michel D, Lane-Guermonprez L, Delgrossi MH, Médina E, Arsanto JP et al. (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. Vancouver style error (help)
Weyrich P, Kapp K, Niederfellner G, Melzer M, Lehmann R, Häring HU et al. (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. Vancouver style error (help)
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. Vancouver style error (help)
Hirano Y, Yoshinaga S, Takeya R, Suzuki NN, Horiuchi M, Kohjima M et al. (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. Vancouver style error (help)
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 et al. (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells.". Science 307 (5715): 1621–5. doi:10.1126/science.1105776. PMID 15761153.

PDB gallery

1wmh: Crystal structure of a PB1 domain complex of Protein kinase c iota and Par6 alpha

PARD6A

Function

Interactions

References

Further reading