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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Partitioning defective 6 homolog alpha''' is a [[protein]] that in humans is encoded by the ''PARD6A'' [[gene]].<ref name="pmid9482110">{{cite journal | vauthors = Rousset R, Fabre S, Desbois C, Bantignies F, Jalinot P | title = The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins | journal = Oncogene | volume = 16 | issue = 5 | pages = 643–54 | date = March 1998 | pmid = 9482110 | pmc =  | doi = 10.1038/sj.onc.1201567 }}</ref><ref name="pmid11260256">{{cite journal | vauthors = Noda Y, Takeya R, Ohno S, Naito S, Ito T, Sumimoto H | title = 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 | journal = Genes Cells | volume = 6 | issue = 2 | pages = 107–19 | date = March 2001 | pmid = 11260256 | pmc =  | doi = 10.1046/j.1365-2443.2001.00404.x }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50855| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_PARD6A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1wmh.
| PDB = {{PDB2|1wmh}}
| Name = Par-6 partitioning defective 6 homolog alpha (C. elegans)
| HGNCid = 15943
| Symbol = PARD6A
| AltSymbols =; PAR-6A; PAR6; PAR6C; PAR6alpha; TAX40; TIP-40
| OMIM = 607484
| ECnumber = 
| Homologene = 9661
| MGIid = 1927223
| GeneAtlas_image1 = PBB_GE_PARD6A_205245_at_tn.png
| Function = {{GNF_GO|id=GO:0008134 |text = transcription factor binding}} {{GNF_GO|id=GO:0017048 |text = Rho GTPase binding}} {{GNF_GO|id=GO:0030742 |text = GTP-dependent protein binding}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005923 |text = tight junction}} {{GNF_GO|id=GO:0005938 |text = cell cortex}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0007049 |text = cell cycle}} {{GNF_GO|id=GO:0016032 |text = viral reproduction}} {{GNF_GO|id=GO:0030010 |text = establishment of cell polarity}} {{GNF_GO|id=GO:0045217 |text = intercellular junction maintenance}} {{GNF_GO|id=GO:0051301 |text = cell division}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 50855
    | Hs_Ensembl = ENSG00000102981
    | Hs_RefseqProtein = NP_001032358
    | Hs_RefseqmRNA = NM_001037281
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 16
    | Hs_GenLoc_start = 66252352
    | Hs_GenLoc_end = 66254181
    | Hs_Uniprot = Q9NPB6
    | Mm_EntrezGene = 56513
    | Mm_Ensembl = ENSMUSG00000005699
    | Mm_RefseqmRNA = NM_001047435
    | Mm_RefseqProtein = NP_001040900
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 108590812
    | Mm_GenLoc_end = 108592594
    | Mm_Uniprot = Q3TY70
  }}
}}
'''Par-6 partitioning defective 6 homolog alpha (C. elegans)''', also known as '''PARD6A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50855| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50855| accessdate = }}</ref>
}}


==References==
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.<ref name = pmid29048609>{{cite journal |vauthors=Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M | title = Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis | journal = Int. J. Oncol. | volume = 51 | issue = 5 | pages = 1370-1382 | year = 2017 | pmid = 29048609 | doi = 10.3892/ijo.2017.4131 }}</ref>
{{reflist|2}}
{{Div col end}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Solecki DJ, Govek EE, Hatten ME |title=mPar6 alpha controls neuronal migration. |journal=J. Neurosci. |volume=26 |issue= 42 |pages= 10624-5 |year= 2006 |pmid= 17050699 |doi= 10.1523/JNEUROSCI.4060-06.2006 }}
*{{cite journal  | author=Rousset R, Fabre S, Desbois C, ''et al.'' |title=The C-terminus of the HTLV-1 Tax oncoprotein mediates interaction with the PDZ domain of cellular proteins. |journal=Oncogene |volume=16 |issue= 5 |pages= 643-54 |year= 1998 |pmid= 9482110 |doi= 10.1038/sj.onc.1201567 }}
*{{cite journal  | author=Qiu RG, Abo A, Steven Martin G |title=A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. |journal=Curr. Biol. |volume=10 |issue= 12 |pages= 697-707 |year= 2000 |pmid= 10873802 |doi=  }}
*{{cite journal  | author=Joberty G, Petersen C, Gao L, Macara IG |title=The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. |journal=Nat. Cell Biol. |volume=2 |issue= 8 |pages= 531-9 |year= 2000 |pmid= 10934474 |doi= 10.1038/35019573 }}
*{{cite journal  | author=Johansson A, Driessens M, Aspenström P |title=The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. |journal=J. Cell. Sci. |volume=113 ( Pt 18) |issue=  |pages= 3267-75 |year= 2000 |pmid= 10954424 |doi=  }}
*{{cite journal  | author=Suzuki A, Yamanaka T, Hirose T, ''et al.'' |title=Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. |journal=J. Cell Biol. |volume=152 |issue= 6 |pages= 1183-96 |year= 2001 |pmid= 11257119 |doi=  }}
*{{cite journal | author=Noda Y, Takeya R, Ohno S, ''et al.'' |title=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. |journal=Genes Cells |volume=6 |issue= 2 |pages= 107-19 |year= 2001 |pmid= 11260256 |doi=  }}
*{{cite journal  | author=Kohjima M, Noda Y, Takeya R, ''et al.'' |title=PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions. |journal=Biochem. Biophys. Res. Commun. |volume=299 |issue= 4 |pages= 641-6 |year= 2003 |pmid= 12459187 |doi=  }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Hurd TW, Gao L, Roh MH, ''et al.'' |title=Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. |journal=Nat. Cell Biol. |volume=5 |issue= 2 |pages= 137-42 |year= 2003 |pmid= 12545177 |doi= 10.1038/ncb923 }}
*{{cite journal  | author=Brajenovic M, Joberty G, Küster B, ''et al.'' |title=Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. |journal=J. Biol. Chem. |volume=279 |issue= 13 |pages= 12804-11 |year= 2004 |pmid= 14676191 |doi= 10.1074/jbc.M312171200 }}
*{{cite journal  | author=Lemmers C, Michel D, Lane-Guermonprez L, ''et al.'' |title=CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. |journal=Mol. Biol. Cell |volume=15 |issue= 3 |pages= 1324-33 |year= 2004 |pmid= 14718572 |doi= 10.1091/mbc.E03-04-0235 }}
*{{cite journal  | author=Weyrich P, Kapp K, Niederfellner G, ''et al.'' |title=Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis via atypical protein kinase C. |journal=Mol. Endocrinol. |volume=18 |issue= 5 |pages= 1287-300 |year= 2005 |pmid= 14976222 |doi= 10.1210/me.2003-0253 }}
*{{cite journal  | author=Liu XF, Ishida H, Raziuddin R, Miki T |title=Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity. |journal=Mol. Cell. Biol. |volume=24 |issue= 15 |pages= 6665-75 |year= 2004 |pmid= 15254234 |doi= 10.1128/MCB.24.15.6665-6675.2004 }}
*{{cite journal  | author=Ballif BA, Villén J, Beausoleil SA, ''et al.'' |title=Phosphoproteomic analysis of the developing mouse brain. |journal=Mol. Cell Proteomics |volume=3 |issue= 11 |pages= 1093-101 |year= 2005 |pmid= 15345747 |doi= 10.1074/mcp.M400085-MCP200 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Hirano Y, Yoshinaga S, Takeya R, ''et al.'' |title=Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. |journal=J. Biol. Chem. |volume=280 |issue= 10 |pages= 9653-61 |year= 2005 |pmid= 15590654 |doi= 10.1074/jbc.M409823200 }}
*{{cite journal  | author=Weyrich P, Lammers R, Fritsche A, ''et al.'' |title=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. |journal=Diabetologia |volume=48 |issue= 4 |pages= 669-74 |year= 2005 |pmid= 15744531 |doi= 10.1007/s00125-005-1688-4 }}
*{{cite journal  | author=Ozdamar B, Bose R, Barrios-Rodiles M, ''et al.'' |title=Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. |journal=Science |volume=307 |issue= 5715 |pages= 1603-9 |year= 2005 |pmid= 15761148 |doi= 10.1126/science.1105718 }}
*{{cite journal  | author=Barrios-Rodiles M, Brown KR, Ozdamar B, ''et al.'' |title=High-throughput mapping of a dynamic signaling network in mammalian cells. |journal=Science |volume=307 |issue= 5715 |pages= 1621-5 |year= 2005 |pmid= 15761153 |doi= 10.1126/science.1105776 }}
}}
{{refend}}


{{protein-stub}}
== Interactions ==
{{WikiDoc Sources}}
 
PARD6A has been shown to [[Protein-protein interaction|interact]] with:
* [[CDC42]],<ref name = pmid11260256 /><ref name = pmid10934474>{{cite journal | vauthors = Joberty G, Petersen C, Gao L, Macara IG | title = The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42 | journal = Nat. Cell Biol. | volume = 2 | issue = 8 | pages = 531–9 | date = August 2000 | pmid = 10934474 | doi = 10.1038/35019573 }}</ref><ref name = pmid10873802>{{cite journal | vauthors = Qiu RG, Abo A, Steven Martin G | title = A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation | journal = Curr. Biol. | volume = 10 | issue = 12 | pages = 697–707 | date = June 2000 | pmid = 10873802 | doi =  10.1016/s0960-9822(00)00535-2}}</ref>
* [[ECT2]]<ref name = pmid15254234>{{cite journal | vauthors = Liu XF, Ishida H, Raziuddin R, Miki T | title = Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity | journal = Mol. Cell. Biol. | volume = 24 | issue = 15 | pages = 6665–75 | date = August 2004 | pmid = 15254234 | pmc = 444862 | doi = 10.1128/MCB.24.15.6665-6675.2004 }}</ref>
* [[Protein kinase Mζ]],<ref name = pmid11260256/><ref name = pmid15254234/><ref name = pmid16189514>{{cite journal | vauthors = 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 | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}</ref> and
* [[RAC1]].<ref name = pmid11260256/><ref name = pmid10873802/>
* [[Protein kinase C-ι]].<ref name = pmid29048609>{{cite journal |vauthors=Ratnayake WS, Apostolatos AH, Ostrov DA, Acevedo-Duncan M | title = Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis | journal = Int. J. Oncol. | volume = 51 | issue = 5 | pages = 1370-1382 | year = 2017 | pmid = 29048609 | doi = 10.3892/ijo.2017.4131 }}</ref>
{{Div col end}}
 
== References ==
{{Reflist}}
{{Clear}}
 
== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Solecki DJ, Govek EE, Hatten ME | title = mPar6 alpha controls neuronal migration. | journal = J. Neurosci. | volume = 26 | issue = 42 | pages = 10624–5 | year = 2006 | pmid = 17050699 | doi = 10.1523/JNEUROSCI.4060-06.2006 }}
* {{cite journal | vauthors = Qiu RG, Abo A, Steven Martin G | title = A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation. | journal = Curr. Biol. | volume = 10 | issue = 12 | pages = 697–707 | year = 2000 | pmid = 10873802 | doi = 10.1016/S0960-9822(00)00535-2 }}
* {{cite journal | vauthors = Joberty G, Petersen C, Gao L, Macara IG | title = The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42. | journal = Nat. Cell Biol. | volume = 2 | issue = 8 | pages = 531–9 | year = 2000 | pmid = 10934474 | doi = 10.1038/35019573 }}
* {{cite journal | vauthors = Johansson A, Driessens M, Aspenström P | title = The mammalian homologue of the Caenorhabditis elegans polarity protein PAR-6 is a binding partner for the Rho GTPases Cdc42 and Rac1. | journal = J. Cell Sci. | volume = 113 | issue = 18 | pages = 3267–75 | year = 2000 | pmid = 10954424 | doi =  }}
* {{cite journal | vauthors = Suzuki A, Yamanaka T, Hirose T, Manabe N, Mizuno K, Shimizu M, Akimoto K, Izumi Y, Ohnishi T, Ohno S | title = Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. | journal = J. Cell Biol. | volume = 152 | issue = 6 | pages = 1183–96 | year = 2001 | pmid = 11257119 | pmc = 2199212 | doi = 10.1083/jcb.152.6.1183 }}
* {{cite journal | vauthors = Kohjima M, Noda Y, Takeya R, Saito N, Takeuchi K, Sumimoto H | title = PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions. | journal = Biochem. Biophys. Res. Commun. | volume = 299 | issue = 4 | pages = 641–6 | year = 2003 | pmid = 12459187 | doi = 10.1016/S0006-291X(02)02698-0 }}
* {{cite journal | vauthors = Hurd TW, Gao L, Roh MH, Macara IG, Margolis B | title = Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. | journal = Nat. Cell Biol. | volume = 5 | issue = 2 | pages = 137–42 | year = 2003 | pmid = 12545177 | doi = 10.1038/ncb923 }}
* {{cite journal | vauthors = Brajenovic M, Joberty G, Küster B, Bouwmeester T, Drewes G | title = Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. | journal = J. Biol. Chem. | volume = 279 | issue = 13 | pages = 12804–11 | year = 2004 | pmid = 14676191 | doi = 10.1074/jbc.M312171200 }}
* {{cite journal | vauthors = Lemmers C, Michel D, Lane-Guermonprez L, Delgrossi MH, Médina E, Arsanto JP, Le Bivic A | title = CRB3 binds directly to Par6 and regulates the morphogenesis of the tight junctions in mammalian epithelial cells. | journal = Mol. Biol. Cell | volume = 15 | issue = 3 | pages = 1324–33 | year = 2004 | pmid = 14718572 | pmc = 363137 | doi = 10.1091/mbc.E03-04-0235 }}
* {{cite journal | vauthors = Weyrich P, Kapp K, Niederfellner G, Melzer M, Lehmann R, Häring HU, Lammers R | title = Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis via atypical protein kinase C. | journal = Mol. Endocrinol. | volume = 18 | issue = 5 | pages = 1287–300 | year = 2005 | pmid = 14976222 | doi = 10.1210/me.2003-0253 }}
* {{cite journal | vauthors = Liu XF, Ishida H, Raziuddin R, Miki T | title = Nucleotide exchange factor ECT2 interacts with the polarity protein complex Par6/Par3/protein kinase Czeta (PKCzeta) and regulates PKCzeta activity. | journal = Mol. Cell. Biol. | volume = 24 | issue = 15 | pages = 6665–75 | year = 2004 | pmid = 15254234 | pmc = 444862 | doi = 10.1128/MCB.24.15.6665-6675.2004 }}
* {{cite journal | vauthors = Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP | title = Phosphoproteomic analysis of the developing mouse brain. | journal = Mol. Cell. Proteomics | volume = 3 | issue = 11 | pages = 1093–101 | year = 2005 | pmid = 15345747 | doi = 10.1074/mcp.M400085-MCP200 }}
* {{cite journal | vauthors = Hirano Y, Yoshinaga S, Takeya R, Suzuki NN, Horiuchi M, Kohjima M, Sumimoto H, Inagaki F | title = Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains. | journal = J. Biol. Chem. | volume = 280 | issue = 10 | pages = 9653–61 | year = 2005 | pmid = 15590654 | doi = 10.1074/jbc.M409823200 }}
* {{cite journal | vauthors = Weyrich P, Lammers R, Fritsche A, Machicao F, Häring HU, Stefan N | title = 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. | journal = Diabetologia | volume = 48 | issue = 4 | pages = 669–74 | year = 2005 | pmid = 15744531 | doi = 10.1007/s00125-005-1688-4 }}
* {{cite journal | vauthors = Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL | title = Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. | journal = Science | volume = 307 | issue = 5715 | pages = 1603–9 | year = 2005 | pmid = 15761148 | doi = 10.1126/science.1105718 }}
* {{cite journal | vauthors = 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 | title = High-throughput mapping of a dynamic signaling network in mammalian cells. | journal = Science | volume = 307 | issue = 5715 | pages = 1621–5 | year = 2005 | pmid = 15761153 | doi = 10.1126/science.1105776 }}
{{Refend}}
 
{{PDB Gallery|geneid=50855}}
 
 
{{Gene-16-stub}}

Latest revision as of 09:14, 10 January 2019

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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]

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.[4]

Interactions

PARD6A has been shown to interact with:

References

  1. ↑ 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. ↑ 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. ↑ 3.0 3.1 "Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)".
  4. ↑ 4.0 4.1 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. PMID 29048609.
  5. ↑ 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.
  6. ↑ 6.0 6.1 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.
  7. ↑ 7.0 7.1 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.
  8. ↑ 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


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