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ZAC

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Target not currently curated in GtoImmuPdb

Target id: 587

Nomenclature: ZAC

Family: ZAC

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 412 17q25.1 ZACN zinc activated ion channel 1-2
Previous and Unofficial Names Click here for help
ZAC1 | LGICZ1 | L2 | LGICZ | zinc activated ligand-gated ion channel
Database Links Click here for help
Alphafold
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics Click here for help
Outwardly rectifying current (both constitutive and evoked by Zn2+)
Ion Selectivity and Conductance Comments
ZAC is cation-selective [1]
Natural/Endogenous Ligands Click here for help
Cu2+
H+
Zn2+

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Agonists
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Ligand Sp. Action Value Parameter Reference
H+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 5.6 pEC50 4
pEC50 5.6 [4]
Cu2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 5.4 pEC50 4
pEC50 5.4 [4]
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Agonist 3.3 – 3.7 pEC50 1,4
pEC50 3.3 – 3.7 [1,4]
Agonist Comments
ZAC is spontaneously active and mediates an outwardly rectifying conductance. In whole cell recordings, the spontaneous current increases in magnitude with time [1]. The magnitude of the Zn2+-activated current does not correlate with that of the spontaneous current [1].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tubocurarine Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.2 pIC50 1
pIC50 5.2 (IC50 6.3x10-6 M) [1]
Ca2+ Click here for species-specific activity table Hs Antagonist 2.0 pIC50 4
pIC50 2.0 [4]
Antagonist Comments
(+)-Tubocurarine (100 μM) also blocks spontaneous currents mediated by ZAC [1]. Although tabulated as an antagonist, it remains possible that (+)-tubocurarine acts as a channel blocker.
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Voltage-dependent (mV) Reference
TTFB Small molecule or natural product Hs Antagonist 5.5 pIC50 - no 3
pIC50 5.5 [3]
Not voltage dependent
Tissue Distribution Click here for help
Prostate, thyroid, trachea, fetal whole brain, spinal cord, placenta, stomach.
Species:  Human
Technique:  RT-PCR
References:  1
Adult brain, pancreas, liver, lung, heart, kidney, skeletal muscle.
Species:  Human
Technique:  cDNA PCR amplification
References:  2
General Comments
The ZAC subunit does not appear to exist in the mouse or rat genomes [1]. Although tabulated as an antagonist, it is possible that acts as a channel blocker. Antagonism by Ca2+ is voltage-independent. ZAC is not activated (at 1 mM) by transition metals including Fe2+, Co2+, Ni2+, Cd2+, or Al3+ [4]. The concentration response relationship to Cu2+ is biphasic, with concentrations exceeding 30 μM being associated with reduced activation [4].

References

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1. Davies PA, Wang W, Hales TG, Kirkness EF. (2003) A novel class of ligand-gated ion channel is activated by Zn2+. J Biol Chem, 278 (2): 712-7. [PMID:12381728]

2. Houtani T, Munemoto Y, Kase M, Sakuma S, Tsutsumi T, Sugimoto T. (2005) Cloning and expression of ligand-gated ion-channel receptor L2 in central nervous system. Biochem Biophys Res Commun, 335 (2): 277-85. [PMID:16083862]

3. Madjroh N, Mellou E, Davies PA, Söderhielm PC, Jensen AA. (2021) Discovery and functional characterization of N-(thiazol-2-yl)-benzamide analogs as the first class of selective antagonists of the Zinc-Activated Channel (ZAC). Biochem Pharmacol, 193: 114782. [PMID:34560054]

4. Trattnig SM, Gasiorek A, Deeb TZ, Ortiz EJ, Moss SJ, Jensen AA, Davies PA. (2016) Copper and protons directly activate the zinc-activated channel. Biochem Pharmacol, 103: 109-17. [PMID:26872532]

Contributors

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