TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.78.1.1









Endosomal/Lysosomal K+ channel of 504 aas and 12 TMSs with two 6 TMS repeat units, KEL or TMEM175 (Cang et al. 2015).  A mutation in the encoding gene was associated with Parkinson's disease (Jing et al. 2015). TMEM175 plays a direct and critical role in lysosomal and mitochondrial function as well as Parkinson's Disease (PD) pathogenesis (Jinn et al. 2017).

Eukaryota
Metazoa
KEL or TMEM175 of Homo sapiens
*1.A.78.1.2









TMEM175 of 506 aas and 12 TMSs

Eukaryota
Metazoa
TMEM175 of Takifugu rubripes (Japanese pufferfish) (Fugu rubripes)
*1.A.78.1.3









TMEM175 of 598 aas and 12 TMSs.

Eukaryota
Choanoflagellida
TMEM175 of Salpingoeca rosetta
*1.A.78.2.1









DUF211/TMEM175 of 206 aas and 6 TMSs.

Bacteria
Bacteroidetes/Chlorobi group
TMEM175 of Fibrella aestuarina
*1.A.78.2.2









PF06736/TMEM175 of 198 aas and 6 TMSs.

Bacteria
Spirochaetes
TMEM175 of Leptospira inadai
*1.A.78.2.3









TMEM175 of 206 aas and 5 TMSs

Bacteria
Actinobacteria
TMEM175 of Streptomyces collinus
*1.A.78.2.4









Uncharacterized protein of 216 aas and 6 TMSs

Bacteria
Deinococcus-Thermus
UP of Deinococcus radiodurans
*1.A.78.2.5









DUF1211/TMEM175 of 235 aas and 5 or 6 TMSs

Bacteria
Proteobacteria
TMEM175 of Azospirillum brasilense
*1.A.78.2.6









DUF1211 family member of 205 aas and 5 TMSs

Archaea
Euryarchaeota
DUF1211 protein of Methanobacterium lacus
*1.A.78.2.7









Uncharacterized protein of 210 aas and 6 TMSs

Archaea
Euryarchaeota
UP of Methanospirillum hungatei
*1.A.78.2.8









Uncharacterized protein of 195 aas and 6 TMSs.

Bacteria
Firmicutes
UP of Catellicoccus marimammalium
*1.A.78.2.9









TMEM175 homologue of 197 aas and 5 or 6 TMSs. It is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability of lysosomes. It contains two homologous copies of a 6 TMS domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels (Lee et al. 2017). The architecture represents a completely different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TMS1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TMS1 form a bottleneck along the ion conduction pathway and serve as the selectivity filter. Mutagenesis analyses suggested that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family (Lee et al. 2017).

TMEM175 homologue of Chamaesiphon minutus
*1.A.78.2.10









TMEM175 lysosomal K+ channel of 203 aas and 6 TMSs. It's 3-d structure reveals a novel tetrameric arrangement (Lee et al. 2017). All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TM1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TM1 helices form a bottleneck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity (Lee et al. 2017).

Bacteria
Cyanobacteria
TMEM175 of Chamaesiphon minutus