TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*1.A.5.1.1









Polycystin 1 (PKD1 or PC1) assembles with TRPP2 (Q86VP3) in a stoichiometry of 3TRPP2: 1PKD1, forming the receptor/ion channel complex (Yu et al., 2009). The C-terminal coiled-coil complex is critical for proper assembly (Zhu et al., 2011).  Missense mutations have been identified that affect membrane topogenesis (Nims et al. 2011). Biomarkers for polycystic kidney diseases have been identified (Hogan et al. 2015).  Extracellular divalent ions, including Ca2+, inhibit permeation of monovalent ions by directly blocking the TRPP2 channel pore. D643, a negatively charged amino acid in the pore, is crucial for channel permeability (Arif Pavel et al. 2016). Polycystin (TRPP/PKD) complexes, made of transient receptor potential channel polycystin (TRPP)4 and polycystic kidney disease (PKD) proteins, play key roles in coupling extracellular stimuli with intracellular Ca2+ signals.

Eukaryota
Metazoa
Polycystin 1 of Homo sapiens
*1.A.5.1.2









Polycystic kidney disease protein 1-like 3 (PC1-like 3 protein or PKD1L3) (Polycystin-1L3).  May particpate in formation of the TRP sour taste receptor (see 1.A.5.2.2) (Ishimaru et al. 2010). Mediates Ca2+ influx-operated Ca2+ entry that generates pronounced Ca2+ spikes. Triggered by rapid onset/offset of Ca2+, voltage, or acid stimuli, Ca2+-dependent activation amplifies a small Ca2+ influx via the channel which concurrently drives self-limiting negative feedback inactivation that is regulated by the Ca2+-binding EF hands of its partner protein, PKD2-L1 (Hu et al. 2015).

Eukaryota
Metazoa
PKD1L3 of Homo sapiens
*1.A.5.1.3









Heteromeric polycystic kidney disease proteins 1 and 2-like 1 (PKD1L1/PKD2L1) cation (calcium) channel of kidney primary cilia (DeCaen et al. 2013).  PKD2L1 is probably orthologous to mouse TC# 1.A.5.2.2.

Eukaryota
Metazoa
PKD1L1/PKD2L1 of Homo sapiens
*1.A.5.1.4









One of 10 receptors for the egg jelly ligands (REJ, REJ1 or PKD-REJ1) inducing the acrosome reaction in sea urchin eggs. Could be a regulator of sperm ion channels (Gunaratne et al. 2007).

Eukaryota
Metazoa
REJ of Strongylocentrotus purpuratus (Purple sea urchin)
*1.A.5.1.5









PKD-REJ4 of 2829 aas and 2 TMSs, one N-terminal and one C-terminal (Gunaratne et al. 2007). Shows homology with hydrophilic domains in human PKDs.

Eukaryota
Metazoa
REJ4 of Strongylocentrotus purpuratus (Purple sea urchin)
*1.A.5.1.6









PKD-REJ3 of 2681 aas (Gunaratne et al. 2007).

Eukaryota
Metazoa
REJ3 of Strongylocentrotus purpuratus (Purple sea urchin)
*1.A.5.2.1









Polycystin 2 (PKD2 or PC2) (Anyatonwu and Ehrlich, 2005). Regulated by α-actinin (AAC17470) by direct binding (Li et al., 2007). Regulated by diaphanous-related formin 1 (mDia1) (Bai et al., 2008). Has 6 TMSs with N- and C- termini inside (Hoffmeister et al., 2010).  PC2 interacts with the inositol 1,4,5-trisphosphate receptor (IP(3)R) to modulate Ca2+ signaling (Li et al. 2009). The PKD2 voltage- sensor domain retains two of four gating charges commonly found in voltage-gated ion channels. The PKD2 ion permeation pathway is constricted at the selectivity filter near the cytoplasmic end of S6, suggesting that two gates regulate ion conduction (Shen et al. 2016). 15% of cases of polycystic kidney disease are in this protein, while 85% are in PKD1 (Ghata and Cowley 2017).

Eukaryota
Metazoa
Polycystin 2 of Homo sapiens (Q13563)
*1.A.5.2.2









Polycystic kidney disease Z-like protein, TrpP3 or PKD2L1 (50% identical to Polycystin 2 (1.A.5.2.1); regulated by α-actinin (AAC17470) by direct binding; Li et al, 2007). May form a heterodimeric complex with PKD1L3 (1.A.5.1.2) to form the TRP sour taste channel receptor (Ishimaru et al., 2006; Ishimaru et al. 2010).  Polycystic kidney disease (PKD) protein 2 Like 1 (PKD2L1) is also called transient receptor potential polycystin-3 (TRPP3).  It regulates Ca2+-dependent hedgehog signalling in primary cilia, intestinal development and sour taste. Two intra-membrane residues, aspartic acid 349 (D349) and glutamic acid 356 (E356) in the third TMS are critical for PKD2L1 channel function which may itself sense acids (Hussein et al. 2015). Extracellular loops are involved in assemby of the complex (Salehi-Najafabadi et al. 2017).

Eukaryota
Metazoa
TrpP3 of Mus musculus (Q14B55)
*1.A.5.2.3









PKD2 or PKD-REJ2 of 907 aas (Gunaratne et al. 2007).

Eukaryota
Metazoa
REJ2 of Strongylocentrotus purpuratus (Purple sea urchin)
*1.A.5.2.4









Polycystin-2 (CePc2) (Polycystic kidney disease 2 protein homologue)

Eukaryota
Metazoa
Pkd-2 of Caenorhabditis elegans
*1.A.5.3.1









The lysosomal monovalent cation/Ca2+ channel, TRP-ML1 (Mucolipin-1) (associated with the human lipid storage disorder, mucolipidosis type IV (MLIV)) (Kiselyov et al., 2005; Luzio et al., 2007). TRPML1 is an endolysosomal iron release channel (Dong et al., 2008).  Interacts with TMEM163, a CDF heavy metal transporter (TC# 2.A.4.8.3).  Together these proteins function in Zn2+ homeostasis, possibly by exporting Zn2+ (Cuajungco et al. 2014).  The MLIV disease could result from Zn2+ overload.  Probably involved in Zn2+ uptake into lysosomes (Cuajungco and Kiselyov 2017).

Eukaryota
Metazoa
TRP-ML1 (Mucolipin-1) of Homo sapiens (Q9GZU1)
*1.A.5.3.2









The TRP-ML3 or TRPML3 or Mcoln3 (Mucolipin-3) inward rectifying cation channel; associated with the mouse Viartini-Waddler phenotype when mutant (A419P) (Kim et al., 2007; Cuajungco and Samie 2008). H+-regulated Ca2+ channel that shuttles between intracellular vesicular compartments and the plasma membrane (Kim et al., 2010).

Eukaryota
Metazoa
Trp-ML3 of Mus musculus
(Q8R4F0)
*1.A.5.3.3









Mucolipin-2 (TRPML2) non-selective plasma membrane cation channel (Ca2+ permeable). Shows inward rectification like TRPML1 and TRPML3 (Lev et al., 2010). Induces cell degeneration. Causes embryonic lethality, pigmentation defects and deafness, and regulates the acidification of early endosomes (Noben-Trauth, 2011). Found in the plasma membrane and early- and late-endosomes as well as lysosomes.  Activated by a transient reduction of extracellular sodium followed by sodium replenishment, by small chemicals related to sulfonamides, and by PI(3,5)P2, a rare phosphoinositide that naturally accumulates in the membranes of endosomes and lysosomes, and thus could act as a physiologically relevant agonist (García-Añoveros and Wiwatpanit 2014).  TRPML2 can form heteromultimers with TRPML1 and TRPML3; in B-lymphocytes, TRPML2 and TRPML1 may play redundant roles.  TRPML2 may play a role in immune cell development and inflammatory responses (Cuajungco et al. 2015).

Eukaryota
Metazoa
TRPML2 of Homo sapiens (Q8IZK6)
*1.A.5.3.4









Mucolipin-3 (Mcoln3, TRPML3). Orthologue of 1.A.5.3.2.

Eukaryota
Metazoa
TRPML3 of Homo sapiens
*1.A.5.4.1









The algal PDK2 cation channel in Chlamydomonas reinhardii, involved in coupling flagellar adhesion at the beginning of mating to the increase in flagellar calcium required for subsequent steps in mating (Huang et al., 2007). (Residues 1278-1346 (the PKD domain) are 25% identical, 54% similar to residues 107-176 in CcaA (TC# 1.A.1.14.2))
Eukaryota
Viridiplantae
PDK2 of Chlamydomonas reinhardii (A9LE42)