TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.6.1.1









Epithelial Na+ channel, ENaC (regulates salt and fluid homeostasis and blood pressure; regulated by Nedd4 isoforms and SGK1, 2 and 3 kinases) (Henry et al., 2003; Pao 2012).  Cd2+ inhibits α-ENaC by binding to the internal pore where it interacts with residues in TMS2 (Takeda et al., 2007).  The channel is regulated by palmitoylation of the beta subunit which modulates gating (Mueller et al. 2010).  Plays a role in chronic obstructive pulmonary diseases (COPD) (Zhao et al. 2014). The hetrodimeric complex can consist of αβγ or δβγ subunits, depending on the tissue (Giraldez et al. 2012).  The α- and γ-subunits of the epithelial Na+ channel interact directly with the Na+:Cl- cotransporter, NCC, in the renal distal tubule with functional cosequences, and together they determine bodily salt balance and blood pressure (Mistry et al. 2016).  Regulated by syntaxins (Saxena et al. 2006).

Eukaryota
Metazoa
αβγ- or δβγ-ENaC heterotrimeric epithelial Na+ channel of Homo sapiens
*1.A.6.1.2









Amiloride-sensitive cation channel, ASIC1/ASIC3 (also called BNC1 or MDEG), which is an acid-sensitive (proton-gated) homo- or hetero-oligomeric cation (Na+ (high affinity), Ca2+, K+) channel. It associates with DRASIC and mediates touch sensation, being a mechanosensor (lead inhibited) channel (Wang et al., 2006). In pulmonary tissue (lung epithelial cells) it and CFTR interregulate each other (Su et al., 2006). ASIC3 is a sensor of acidic and primary inflammatory pain (Deval et al., 2008).  Acid sensing ion channel-1b (ASIC1b), virtually identical to  the rat and human orthologs, is stimulated by hypotonic stimuli  (Ugawa et al., 2007; Deval et al., 2008).

Eukaryota
Metazoa
αβγENaC of Rattus norvegicus.
DRASIC (O35240)
ASIC3 (O55163)
ASIC1 (P55926)
*1.A.6.1.3









The epithelial Na+ channel, EnaC5 (involved in fluid and electrolyte homeostasis). The C-terminus of each subunit (α, β, and γ) contains a PPXY motif for interaction with the WW domains of the ubiquitin-protein ligases, Nedd4 and Nedd4-2. Disruption of this interaction, as in Liddle's syndrome where mutations delete or alter the PPXY motif of either the β or γ subunits, has been shown to result in increased ENaC activity and arterial hypertension. N4WBP5A (Nedd4-family interacting protein-2) plays a role (see 8.A.30; Konstas et al., 2002). Wiemuth & Grunder (2010) showed that an unknown ligand, interacting with an amino acyl residue in the extracellular domain, tunes Ca2+ inhibition in the rat protein, but not the mouse orthologue.

Eukaryota
Metazoa
ENaC5 of Rattus norvegicus (Q9R0W5)
*1.A.6.1.4









ACD-1 (degenerin-like glial acid-sensitive channel) is constitutively open and impermeable to Ca2+, yet is required with neuronal DEG/ENaC channel, DEG-1 (1.A.6.2.1) for acid avoidance and chemotaxis to the amino acid lysine (Wang et al. 2008).
Eukaryota
Metazoa
ACD-1 of Caenorhabditis elegans (P91102)
*1.A.6.1.5









Neuronal acid-sensing cation channel-1, ASIC1 (>90% identical to ASIC1 of Rat (TC#1.A.6.1.2)). 3D structure (1.9Å resolution) has been solved (Jasti et al., 2007). Regulated by the glucocorticoid-induced kinase-1 isoform 1 (SGK1.1) (Arteaga et al., 2008). Residues in the second transmembrane domain of the ASIC1a that contribute to ion selectivity have been defined (Carattino and Della Vecchia, 2012). Outlines of the pore in open and closed conformations describe the gating mechanism (Li et al., 2011). Interactions between two extracellular linker regions control sustained channel opening (Springauf et al., 2011).  Can form monomers, trimers and tetramers, but the tetramer may be the predominant species in the plasma membrane (van Bemmelen et al. 2015).

Eukaryota
Metazoa
ASIC-1 of Gallus gallus (Q1XA76)
*1.A.6.1.6









Acid sensing cation channel ASIC4.1 (senses and gated by extracellular pH) (forms homomers and heteromers with ASIC4.2) (Chen et al., 2007)
Eukaryota
Metazoa
ASIC4.1 of Danio rerio (Q708S4)
*1.A.6.1.7









Acid sensing cation channel ASIC4.2 (does not sense extracellular pH) (forms homomers and heteromers with ASIC4.1) (Chen et al., 2007).
Eukaryota
Metazoa
ASIC4.2 of Danio rerio (Q708S3)
*1.A.6.1.8









Amiloride and acid-sensitive cation channels, ASCI2a and ASIC2b are splice variants of the same gene (ACCN1) product.  Regions involved in acid (proton) sensing and confering tachyphylasis have been identified (Schuhmacher et al. 2015).  ASIC2 isoforms have different subcellular distribution: ASIC2a targets the cell surface while ASIC2b resides in the ER. TMS1 and the proximal post-TMS1 domain (17 amino acids) of ASIC2a are critical for membrane targeting, and replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b (Kweon et al. 2016).

Eukaryota
Metazoa
ASIC1b of Mus musculus
*1.A.6.1.9









Acid-sensing ion channel 2, ASIC2, of 520 aas and 2 TMSs.

Eukaryota
Metazoa
ASIC2 of Petromyzon marinus (Sea lamprey)
*1.A.6.1.10









Acid-sensing ion channel 1, ACCN2 of 514 aas and 2 TMSs.

Eukaryota
Metazoa
ACCN2 of Lampetra fluviatilis (European river lamprey) (Petromyzon fluviatilis)
*1.A.6.1.11









(Bile) acid-sensitive ion channel, BASIC (ASIC, ACCN5, HINAC), of 505 aas. Cation channel that gives rise to very low constitutive currents in the absence of activation. The activated channel exhibits selectivity for sodium, and is inhibited by amiloride (Schaefer et al. 2000).  A cytoplasmic amphipathic α-helix controls activity (Schmidt et al. 2016).

BASIC of Homo sapiens
*1.A.6.2.1









Degenerin-1
Eukaryota
Metazoa
Degenerin-1 of Caenorhabditis elegans (P24585)
*1.A.6.2.2









Touch-responsive mechanosensitive degenerin channel complex (Mec-4/Mec-10 form the channel; Mec-2 and Mec-6 activate) (Bianchi, 2007; Chelur et al., 2002).  Mec-10 plays a role in the response to mechanical forces such as laminar shear stress (Shi et al. 2016).

Eukaryota
Metazoa
Mec-2, 4, 6, 10 mechanosensitive degenerin channel complex in Caenorhabditis elegans
Mec-4
Mec-10
Mec-6
Mec-2
*1.A.6.2.3









Degenerin channel, UNC-105. (Activated by degeneration or hypercontraction-causing mutations) (Bianchi, 2007; García-Añoveros et al., 1998)
Eukaryota
Metazoa
UNC-105 of Caenorhabditis elegans (Q09274)
*1.A.6.2.4









Motility and anesthetic-sensitive degenerin, UNC-8 (Uncoordinated protein-8) Na+ channel (regulated by UNC-1 (a mammalian stomatin homologue)). UNC-1 and UNC-8 are found in cholesterol/sphingolipid rafts together with UNC-24 (Bianchi, 2007; Sedensky et al., 2004)
Eukaryota
Metazoa
UNC-8 of Caenorhaditis elegans (Q21974)
*1.A.6.2.5









Mechanotransduction degenerin, DEL-1 (Bianchi, 2007).

Eukaryota
Metazoa
DEL-1 of Caenorhabditis elegans (Q19038)
*1.A.6.2.6









Serum paraoxonase/arylesterase 1, PON 1 (Aromatic esterase 1) (A-esterase 1) (Serum aryldialkylphosphatase 1)

Eukaryota
Metazoa
PON1 of Homo sapiens
*1.A.6.3.1









Peptide neurotransmitter-gated ionotropic receptor
Eukaryota
Metazoa
Phe-Met-Arg-Phe-NH2-activated Na+ channel of Helix aspersa
*1.A.6.3.2









FMRFamide (peptide)-gated  sodium channel, FaNaC.  The charge on aspartate-552 in TMS2 influcences the gating properties and potency of the channel (Kodani and Furukawa 2010; Kodani and Furukawa 2014).  The FMRFamide-evoked current through AkFaNaC was depressed 2-3-fold by millimolar (1.8 mM) Ca2+ (Fujimoto et al. 2017). Both D552 and D556 were indispensable for the sensitivity of FaNaC to millimolar Ca2+. The Ca2+-sensitive gating was recapitulated by an allosteric model in which Ca2+-bound channels are more difficult to open. The desensitization of FaNaC was also inhibited by Ca2+ (Fujimoto et al. 2017).

Eukaryota
Metazoa
FaNaC of Aplysia kurodai
*1.A.6.4.1









Ripped pocket (Rpk) fly gonad-specific Na+ channel (amiloride-sensitive) (Adams et al., 1998).

Eukaryota
Metazoa
Rpk of Drosophila melanogaster
*1.A.6.4.2









Eukaryota
Metazoa
Pickpocket of Drosophila melanogaster (Q7KT94)
*1.A.6.4.3









Putative Na+ channel 

Eukaryota
Metazoa
Putative Na+ channel of Drosophila melanogaster (O61365)
*1.A.6.5.1









FMRFamide (peptide)-gated ionotropic receptor Na+ channel, NaC2-4 or NaC2, 3 and 5 (gated by neuropeptides Hydra-RFamides I and II; present in tentacles) (Golubovic et al. 2007). Three homologous subunits, NaC2, 3 and 5, assemble to form a more typical high affinity peptide-gated ion channel (Durrnagel et al., 2010).

Eukaryota
Metazoa
NaC2-5 of Hydra magnipapillata:
NaC2 - A8DZR6
NaC3 - A8DZR7
NaC4 - A8DZR8
NaC5 - D3UD58