TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.25.1.1









Invertebrate innexin, (gap junction protein), INX3
Eukaryota
Metazoa
INX3 of C. elegans
*1.A.25.1.2









Invertebrate innexin, UNC-7
Eukaryota
Metazoa
UNC-7 of C. elegans
*1.A.25.1.3









Invertebrate innexin, Ogre
Eukaryota
Metazoa
Ogre of Drosophila melanogaster
*1.A.25.1.4









Invertebrate innexin, passover protein (shaking B locus)
Eukaryota
Metazoa
Passover protein of Drosophila melanogaster
*1.A.25.1.5









Invertebrate innexin, NSY-5 (INX-19) (Chuang et al., 2007) (establishes left-right neuronal asymmetry) (Oviedo and Levin, 2007)
Eukaryota
Metazoa
NSY-5 (INX-19) of Caenorhabditis elegans (NP_490983)
*1.A.25.1.6









Innexin-14 (Protein Opu-14)

Eukaryota
Metazoa
Inx-14 of Caenorhabditis elegans
*1.A.25.1.7









Innexin-6 protein, Inx-6 or Opu-6, of 389 aas and 4 TMSs. A single INX-6 gap junction channel consists of 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which consist of 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26 (Oshima et al. 2016). Nevertheless, the arrangements of the transmembrane helices and extracellular loops of the INX-6 monomer are highly similar to those of connexin-26 (Cx26). The INX-6 gap junction channel comprises hexadecameric subunits but reveals an N-terminal pore funnel consistent with Cx26. The helix-rich cytoplasmic loop and C-terminus are intercalated through an octameric hemichannel, forming a dome-like entrance that interacts with N-terminal loops in the pore (Oshima et al. 2016).

Eukaryota
Metazoa
Inx-6 of Caenorhabditis elegans
*1.A.25.1.8









Innexin Inx4 (Innexin-4) (Protein zero population growth)

Eukaryota
Metazoa
Zpg of Drosophila melanogaster
*1.A.25.1.9









Eukaryota
Metazoa
Inx6 of Hirudo verbana
*1.A.25.1.10









Eukaryota
Metazoa
Inx2 of Hirudo verbana
*1.A.25.1.11









Duplicated innexin of 801 aas and 8 TMSs.

Eukaryota
Metazoa
Innexin of Ascaris suum
*1.A.25.1.12









Duplicated innexin protein of 813 aas and 8 TMSs.

Eukaryota
Metazoa
Duplicated innexin of Trichinella spiralis (Trichina worm)
*1.A.25.1.13









Innexin2, Inx2 of 359 aas and 4 TMSs. N-terminally elongated domains in innexins may act to plug or manipulate hemichannel closure and provide a mechanism connecting the effect of hemichannel closure directly to apoptotic signaling transduction (Chen et al. 2016).

Eukaryota
Metazoa
Inx2 of Spodoptera litura (Asian cotton leafworm)
*1.A.25.2.1









Pannexin-1 (reported to form functional, single membrane, cell surface channels (Penuela et al., 2007)). Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex (Locovei et al., 2007). It can catalyze ATP release from cells (Huang and Roper, 2010) and promote ATP signalling in mice (Suadicani et al. 2012). It also promotes acetaminophen liver toxicity by allowing it to enter the cell (Maes et al. 2016).  Pannexin1 and pannexin2 channels show quaternary similarities to connexons but different oligomerization numbers (Ambrosi et al., 2010). Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes (Kienitz et al., 2011). Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) underlie channel function in neurons and contribute to ischemic brain damage (Bargiotas et al., 2011). Single cysteines in the extracellular and transmembrane regions modulate pannexin 1 channel function (Bunse et al., 2011).  Spreading depression triggers migraine headaches by activating neuronal pannexin1 (panx1) channels  (Karatas et al. 2013).  The channel in the mouse orthologue opens upon apoptosis (Spagnol et al. 2014). Transports ATP out of the cell since L-carbenoxolone (a Panx1 channel blocker) inhibits ATP release from the nasal mucosa, but flufenamic acid (a connexin channel blocker) and gadolinium (a stretch-activated channel blocker) do not (Ohbuchi et al. 2014). CALHM1 (TC#1.N.1.1.1) and PANX1 both play roles in ATP release and downstream ciliary beat frequency modulation following a mechanical stimulus in airway epithelial cells (Workman et al. 2017).

Eukaryota
Metazoa
Pannexin-1 of Homo sapiens (gi39995064)
*1.A.25.2.2









Pannexin1 and pannexin2 channels show quaternary similarities to connexons but different oligomerization numbers (Ambrosi et al., 2010). Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) underlie channel function in neurons and contribute to ischemic brain damage (Bargiotas et al., 2011).

Eukaryota
Metazoa
Pannexin-2 of Homo sapiens (Q96RD6)
*1.A.25.2.3









Pannexin-3 is reported to form functional, single membrane, cell surface channels (Penuela et al., 2007)). It functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation (Ishikawa et al., 2011).

Eukaryota
Metazoa
Pannexin-3 of Homo sapiens (gi16418453)
*1.A.25.3.1









The volume-regulated Anion Channel, VRAC, or volume-sensitive outward rectifying anion channel, VSOR.  It consists of the leucine-rich repeat-containing protein 8A with N-terminal pannexin-like domain, LRRC8A, together with other LRRC8 subunits (B, C, D and E). The first two TMSs of the 4 TMS LRRC8 proteins appear as DUF3733 in CDD (Abascal and Zardoya, 2012). The C-terminal soluble domain shows sequence similarity to the heme-binding protein, Shv, and pollen-specific leucine-rich repeat extension-like proteins (3.A.20.1.1).  The volume-regulated anion channel, VRAC, has LRRC8A as a VRAC component. It forms heteromers with other LRRC8 membrane proteins (Voss et al. 2014). Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A cotransfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined the VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Thus, VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents (Voss et al. 2014).  Point mutations in two amino-acyl residues (Lys98 and Asp100 in LRRC8A and equivalent residues in LRRC8C and -E) which upon charge reversal alter the kinetics and voltage- dependence of inactivation (Ullrich et al. 2016).

Eukaryota
Metazoa
The VRAC channel consisting of LRRC8A together with one or two of the subunits, LRRC8B, LRRC8C, LRRC8D and/or LRRC8E of Homo sapiens (Q8IWT6)
*1.A.25.3.2









The LRRC8B homologue of 480 aas

Eukaryota
Metazoa
LRRC8B of Ciona intestinalis (Transparent sea squirt) (Ascidia intestinalis)
*1.A.25.3.3









Uncharacterized protein of 467 aas

Eukaryota
Metazoa
UP of Branchiostoma floridae (Florida lancelet) (Amphioxus)
*1.A.25.3.4









Uncharacterized ADP-binding protein of 1311 aas and 2 TMSs.  May be involved in defense responses.

Eukaryota
Viridiplantae
UP of Oryza sativa