PARD6A

Last updated
PARD6A
Protein PARD6A PDB 1wmh.png
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001037281
NM_016948

NM_001047435
NM_001047436
NM_001286344
NM_001286345
NM_019695

Contents

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: 106.43 – 106.43 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

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:

Related Research Articles

In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades.

The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal cells that can differentiate into a variety of cell types. EMT is essential for numerous developmental processes including mesoderm formation and neural tube formation. EMT has also been shown to occur in wound healing, in organ fibrosis and in the initiation of metastasis in cancer progression.

<span class="mw-page-title-main">Protein kinase C zeta type</span>

Protein kinase C, zeta (PKCζ), also known as PRKCZ, is a protein in humans that is encoded by the PRKCZ gene. The PRKCZ gene encodes at least two alternative transcripts, the full-length PKCζ and an N-terminal truncated form PKMζ. PKMζ is thought to be responsible for maintaining long-term memories in the brain. The importance of PKCζ in the creation and maintenance of long-term potentiation was first described by Todd Sacktor and his colleagues at the SUNY Downstate Medical Center in 1993.

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog, also known as Cdc42, is a protein involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">FGD1</span> Protein-coding gene in the species Homo sapiens

FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in the species Homo sapiens

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

<span class="mw-page-title-main">Sequestosome 1</span> Protein-coding gene in the species Homo sapiens

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype.

<span class="mw-page-title-main">PRKCI</span>

Protein kinase C iota type is an enzyme that in humans is encoded by the PRKCI gene.

<span class="mw-page-title-main">PARD3</span> Protein-coding gene in the species Homo sapiens

Partitioning defective 3 homolog is a protein that in humans is encoded by the PARD3 gene.

<span class="mw-page-title-main">MARK2</span>

Serine/threonine-protein kinase MARK2 is an enzyme that in humans is encoded by the MARK2 gene.

<span class="mw-page-title-main">ECT2</span> Gene of the species Homo sapiens

Protein ECT2 is a protein that in humans is encoded by the ECT2 gene.

<span class="mw-page-title-main">RHOQ</span>

Rho-related GTP-binding protein RhoQ is a protein that in humans is encoded by the RHOQ gene.

<span class="mw-page-title-main">MARK3</span>

MAP/microtubule affinity-regulating kinase 3 is an enzyme that in humans is encoded by the MARK3 gene.

<span class="mw-page-title-main">LLGL1</span> Protein-coding gene in the species Homo sapiens

Lethal(2) giant larvae protein homolog 1 is a protein that in humans is encoded by the LLGL1 gene.

<span class="mw-page-title-main">PARD6B</span> Protein-coding gene in the species Homo sapiens

Partitioning defective 6 homolog beta is a protein that in humans is encoded by the PARD6B gene.

<span class="mw-page-title-main">Phosphoinositide-dependent kinase-1</span> Protein-coding gene in the species Homo sapiens

In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the PDPK1 gene in humans. It is implicated in the development and progression of melanomas.

<span class="mw-page-title-main">Cell polarity</span>

Cell polarity refers to spatial differences in shape, structure, and function within a cell. Almost all cell types exhibit some form of polarity, which enables them to carry out specialized functions. Classical examples of polarized cells are described below, including epithelial cells with apical-basal polarity, neurons in which signals propagate in one direction from dendrites to axons, and migrating cells. Furthermore, cell polarity is important during many types of asymmetric cell division to set up functional asymmetries between daughter cells.

Epithelial polarity is one example of the cell polarity that is a fundamental feature of many types of cells. Epithelial cells feature distinct 'apical', 'lateral' and 'basal' plasma membrane domains. Epithelial cells connect to one another via their lateral membranes to form epithelial sheets that line cavities and surfaces throughout the animal body. Each plasma membrane domain has a distinct protein composition, giving them distinct properties and allowing directional transport of molecules across the epithelial sheet. How epithelial cells generate and maintain polarity remains unclear, but certain molecules have been found to play a key role.

Shigeo Ohno is a Japanese molecular biologist known for his pioneer research on Protein Kinase C (PKC) and Cell Polarity. His works led to the fundamental understanding of cell polarity in response to cell signaling.

Barry James Thompson is an Australian and British developmental biologist and cancer biologist. He is a professor of the John Curtin School of Medical Research at the Australian National University in Canberra. Thompson is known for identifying genes, proteins and mechanisms involved in epithelial polarity, morphogenesis and cell signaling via the Wnt and Hippo signaling pathways, which have key roles in human cancer.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102981 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 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. 1 2 "Entrez Gene: PARD6A par-6 partitioning defective 6 homolog alpha (C. elegans)".
  8. 1 2 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. 1 2 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. 1 2 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.

Further reading