GJA3 Membrane Protein Introduction

Introduction of GJA3

Gap junction alpha-3 protein (GJA3) is a protein encoded by the GJA3 gene. It is also known as connexin 46 (cx46). Cx46 is a connexin isoform of 46 kDa. One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Basic Information of GJA3
Protein Name	Gap junction alpha-3 protein
Gene Name	GJA3
Aliases	Connexin-46
Organism	Homo sapiens (Human)
UniProt ID	Q9Y6H8
Transmembrane Times	4
Length (aa)	435
Sequence	MGDWSFLGRLLENAQEHSTVIGKVWLTVLFIFRILVLGAAAEDVWGDEQSDFTCNTQQPGCENVCYDRAFPISHIRFWALQIIFVSTPTLIYLGHVLHIVRMEEKKKEREEEEQLKRESPSPKEPPQDNPSSRDDRGRVRMAGALLRTYVFNIIFKTLFEVGFIAGQYFLYGFELKPLYRCDRWPCPNTVDCFISRPTEKTIFIIFMLAVACASLLLNMLEIYHLGWKKLKQGVTSRLGPDASEAPLGTADPPPLPPSSRPPAVAIGFPPYYAHTAAPLGQARAVGYPGAPPPAADFKLLALTEARGKGQSAKLYNGHHHLLMTEQNWANQAAERQPPALKAYPAASTPAAPSPVGSSSPPLAHEAEAGAAPLLLDGSGSSLEGSALAGTPEEEEQAVTTAAQMHQPPLPLGDPGRASKASRASSGRARPEDLAI

Function of GJA3 Membrane Protein

GJA3 is expressed in folliculostellate, TtT/GF and endocrine cells. In the cytoplasm, GJA3 is primarily involved in lysosomes. Different sizes of GJA3 molecules are fully restored in the TtT/GF cell nuclear fraction. It is an intrinsic membrane protein. The localization of the full-length GJA3 molecule in the nucleus is interesting because this process requires the protein to be separated from the membrane in advance and inserted during the synthesis of the ER. So far, either GJA3 or connexin 50 mutations have been associated with congenital cataracts. These proteins are believed to be modified with fiber cell age. However, limited work has been done on specific lens attachment modifications. GJA3 proved to be important in the growth of normal lens and maintenance of lens transparency. Specifically, mutations in the GJA3 gene are involved in the development of cataracts. In addition, disruption of the GJA3 gene led to the development of nuclear cataracts. Cx46 is a phosphorylated protein and truncated in the lens nucleus.

Fig.1 The membrane topology of GJA3. (Beyer, 2013)

Application of GJA3 Membrane Protein in Literature

Slavi N., et al. Connexin 46 (Cx46) Gap Junctions Provide a Pathway for the Delivery of Glutathione to the Lens Nucleus. The Journal of Biological Chemistry. 2014, 289(47):32694-32702. PubMed ID: 25294879

These results indicate that glutathione diffuses from cortical fiber cells to the nucleus via gap junction channels formed by GJA3.
Vitale M.L., et al. Distinctive actions of connexin 46 and connexin 50 in anterior pituitary folliculostellate cells. PLoS ONE. 2017, 12(7):e0182495. PubMed ID: 28759642

The article suggests that GJA3 is associated with cellular activities such as cell growth or proliferation in the anterior pituitary.
Pelletier R., et al. Complementary Expression and Phosphorylation of Cx46 and Cx50 during Development and Following Gene Deletion in Mouse and in Normal and Orchitic Mink Testes. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology. 2015, 309 (3): R255–R276. PubMed ID: 26017495

The data show that expression and phosphorylation of GJA3 and Cx50 are complementary in seminiferous tubules.
Ren Q., et al. Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death. PLoS ONE. 2013, 8(9):e74732. PubMed ID: 24019978

These results suggest that mutation of this highly conserved residue on the cytoplasmic loop domain of GJA3 enhances its interaction with the C-terminus, resulting in a reduction of gap junction channel function, but increased hemichannel function.
Cheng C., et al. Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells. American Journal of Physiology-Cell Physiology. 2015, 308(10):C835-C847. PubMed ID: 25740157

This article indicated that gap junction plaque formation by GJA3 in differentiating lens fiber cells is influenced by the actin-spectrin and beaded intermediate filament networks.

GJA3 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-GJA3 antibody development services.

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Reference

Beyer Eric C. (2013). Connexin Mutants and Cataracts. Frontiers in Pharmacology.4,43.

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