ZAC | ZAC | IUPHAR/BPS Guide to PHARMACOLOGY

ZAC

Target id: 587

Nomenclature: ZAC

Family: ZAC

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for ZAC in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 412 17q25.3 ZACN zinc activated ion channel 1-2
Previous and Unofficial Names
ZAC1 | LGICZ1 | L2 | LGICZ | zinc activated ligand-gated ion channel
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Functional Characteristics
Outwardly rectifying current (both constitutive and evoked by Zn2+)
Ion Selectivity and Conductance Comments
ZAC is cation-selective [1]
Natural/Endogenous Ligands
Zn2+

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
H+ Hs Agonist 5.6 pEC50 3
pEC50 5.6 [3]
Cu2+ Hs Agonist 5.4 pEC50 3
pEC50 5.4 [3]
Zn2+ Hs Agonist 3.3 – 3.7 pEC50 1,3
pEC50 3.3 – 3.7 [1,3]
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 Affinity Units Reference
tubocurarine Hs Antagonist 5.2 pIC50 1
pIC50 5.2 (IC50 6.3x10-6 M) [1]
Ca2+ Hs Antagonist 2.0 pIC50 3
pIC50 2.0 [3]
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.
Tissue Distribution
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+ [3]. The concentration response relationship to Cu2+ is biphasic, with concentrations exceeding 30 μM being associated with reduced activation [3].

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. 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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How to cite this page

Tim G. Hales, John A. Peters.
ZAC: ZAC . Last modified on 06/07/2016. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=587.