PARD6A

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

PARD6A
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPARD6A, PAR-6A, PAR6, PAR6C, PAR6alpha, TAX40, TIP-40, par-6 family cell polarity regulator alpha
External IDsOMIM: 607484 MGI: 1927223 HomoloGene: 9661 GeneCards: PARD6A
Gene location (Human)
Chr.Chromosome 16 (human)[1]
Band16q22.1Start67,660,946 bp[1]
End67,662,778 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 8: 105.7 – 105.7 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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:

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. S2CID 8789941.
  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. S2CID 27139234.
  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. S2CID 14825707.
  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. S2CID 4427026.

Further reading


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