The zinc-activated ligand-gated ion channel (ZACN) belongs to the Cys-loop receptor superfamily which also includes the nicotinic acetylcholine (nACh), 5-hydroxytryptamine type-3 (5-HT3), γ-aminobutyric acid type A (GABAA) and glycine receptors. The protein is encoded by the ZACN gene which is present in humans and dogs, but no ortholog is thought to exist in the rat or mouse genomes. The superfamily proteins consist of three domains. First, an extracellular domain with 200 residues binds the agonist and largely consists of a β-sheet structure. Second, a transmembrane domain containing four α-helices arranged as a four-helix bundle (M1-M4), in which M1/M2 and M2/M3 are separated by short loops. Third, there is a long intracellular loop between M3 and M4.
Basic Information of ZACN | |
Protein Name | Zinc-activated ligand-gated ion channel |
Gene Name | ZACN, L2, LGICZ, LGICZ1, ZAC |
Aliases | Ligand-gated ion channel zinc-activated 1, Ligand-gated ion-channel receptor L2 |
Organism | Homo sapiens (Human) |
UniProt ID | Q401N2 |
Transmembrane Times | 4 |
Length (aa) | 412 |
Sequence | MMALWSLLHLTFLGFSITLLLVHGQGFQGTAAIWPSLFNVNLSKKVQESIQIPNNGSAPLLVDVRVFVSNVFNVDILRYTMSSMLLLRLSWLDTRLAWNTSAHPRHAITLPWESLWTPRLTILEALWVDWRDQSPQARVDQDGHVKLNLALATETNCNFELLHFPRDHSNCSLSFYALSNTAMELEFQAHVVNEIVSVKREYVVYDLKTQVPPQQLVPCFQVTLRLKNTALKSIIALLVPAEALLLADVCGGLLPLRAIERIGYKVTLLLSYLVLHSSLVQALPSSSSCNPLLIYYFTILLLLLFLSTIETVLLAGLLARGNLGAKSGPSPAPRGEQREHGNPGPHPAEEPSRGVKGSQRSWPETADRIFFLVYVVGVLCTQFVFAGIWMWAACKSDAAPGEAAPHGRRPRL |
Expression studies have detected ZACN mRNA in the human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach. Zn2+ causes a concentration-dependent activation of ZACN. Zn2+ may activate ZACN through an action at the putative N-terminal B ligand-binding domain. ZACN forms an ion channel gated by Zn2+, Cu2+, and H+ and is non-selectively permeable to monovalent cations. The function of spontaneous ZACN activation is unknown. These classical members of Cys-loop receptor superfamily play important roles in physiology and pathology and thus constitute interesting drug targets in a wide range of disorders.
Fig.1 The structure of a Cys-loop ligand-gated ion channel.
This article finds the presence of L2 orthologs in several kinds of mammalian species other than humans and dogs.
This article suggests that ZACN forms an ion channel gated by Zn2+, Cu2+, and H+ and is non-selectively permeable to monovalent cations.
This article suggests that Zn2+ behaves as an agonist and TC as an inhibitor of spontaneous gating, these agents will be useful tools for characterizing the properties of native ZACN receptors in tissues from human and other non-rodent species.
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