TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.A.12.1.1









Organellar chloride (anion selective) channel, p64 (outwardly rectifying) (437 aas and 1 or 2 TMSs). CLIC5 was the first chloride channel to be identified in the inner mitochondrial membrane, while CLIC4 is located predominantly in the outer mitochondrial membrane. Gururaja Rao et al. 2020 discussed the intracellular chloride channels, their roles in pathologies, such as cardiovascular, cancer, and neurodegenerative diseases, and developments concerning their usage as theraputic targets in humans. The chloride intracellular channel (CLIC) protein family consists of six members in humans (Israeli 2022).  CLICs are unique due to their metamorphic property, displaying both soluble and integral membrane forms. The transmembrane conformation has been shown to give rise to ion-channel activity in vitro. CLICs have been implicated in a growing number of physiological processes in various organ systems and associated with distinct disease states. Indeed, the founding member of the family, CLIC5, was shown to be involved in hereditary deafness and various types of cancer. Ligands that inhibit or activate CLIC5 have been identified, and these may provide tools to modulate its activity,possibly ameliorating CLIC5-related pathologies (Israeli 2022).

Eukaryota
Metazoa, Chordata
CLIC5 or p64 of Bos taurus
1.A.12.1.2









Nuclear chloride channel-27, NCC27 or CLIC1 (Br- > Cl- > I-) (241 aas).  CLIC1 has two charged residues, K37 and R29, in its single TMS which are important for the biophysical properties of the channel (Averaimo et al. 2013).  A putative Lys37-Trp35 cation-pi interaction stabilizes the active dimeric form of the CLIC1 TMS in membranes (Peter et al. 2013).  This channel may play a role in cancer (Peretti et al. 2014).  A positively charged motif at the C-terminus of the single TMS enhances membrane partitioning and insertion via electrostatic contacts.  It also functions as an electrostatic plug to anchor the TMS in membranes and is involved in orientating the TMS with respect to the cis and trans faces of the membrane (Peter et al. 2014).  The CLIC1 protein accumulates in the circulating monocyte membrane during neurodegeneration (Carlini et al. 2020). The involvement of CLIC1 protein functions in physiological and in pathological conditions has been reviewed (Cianci and Verduci 2021).

Eukaryota
Metazoa, Chordata
CLIC1 or NCC27 of Homo sapiens
1.A.12.1.3









Organellar chloride channel, CLIC-5A (251 aas; 2 TMSs; one of six homologous human genes) (95% identical to 1.A.12.1.1 but lacks the N-terminal 185 residues.) It associates with the cortical actin cytoskeleton (Berryman et al., 2004).
Eukaryota
Metazoa, Chordata
CLIC-5A of Homo sapiens (Q53G01)
1.A.12.1.4









Organellar chloride channel CLIC-6 (CLIC6; 704 aas with two peaks of hydrophobicity between residues 440 and 515). The C-terminal half (residues 400-704) resembles a CLIC channel; the N-terminal half (residues 104-356) resembles a repeated C-terminal region of the bovine Na+/Ca2+,K+ exchanger (TC #2.A.19.4.1) as well as several other bacterial and eukaryotic proteins.  This protein inserts into membrane and displays ion conductances with Cl- > Br- > F- > K+.  IAA-94 is a CLIC-specific blocker.  Channel activity is regulated by pH and redox potential (Loyo-Celis et al. 2023).

Eukaryota
Metazoa, Chordata
CLIC-6 of Homo sapiens (Q96NY7)
1.A.12.1.5









The Janus protein, CLIC2. The 3-D structure of its water soluble form has been determined at 1.8 Å resolution (Cromer et al., 2007). CLIC2 interacts with the skeletal ryanodine receptor (RyR1) and modulates its channel activity (Meng et al., 2009).

Eukaryota
Metazoa, Chordata
CLIC2 of Homo sapiens (O15247)
1.A.12.1.6









Chloride intracellular channel protein 4, CLIC4.  Regulates the histamine H3 receptor (Maeda et al., 2008)) Discriminates poorly between anions and cations (Singh and Ashley, 2007). 76% identical to CLIC5; it may play a role in cancer (Peretti et al. 2014). CLIC5 was the first mitochondrial chloride channel to be identified in the inner mitochondrial membrane, while CLIC4 is located predominantly in the outer mitochondrial membrane. Gururaja Rao et al. 2020 discussed the intracellular chloride channels, their roles in pathologies, such as cardiovascular, cancer, and neurodegenerative diseases, and developments concerning their usage as theraputic targets in humans.

Eukaryota
Metazoa, Chordata
CLIC4 of Homo sapiens (Q9Y696)
1.A.12.1.7









Intracellular Cl- channel-3 (CLIC3). The 3-d structure is known (3FY7). This protein is associated with pregnancy disorders (Murthi et al., 2012). 

Eukaryota
Metazoa, Chordata
CLIC3 of Homo sapiens (O95833)
1.A.12.2.1









The plant Cl- intracellular channel protein DHAR1 (glutathione dehydrogenase/dehydroascorbate reductase) (Elter et al., 2007)
Eukaryota
Viridiplantae, Streptophyta
DHAR1 of Arabidopsis thaliana (NP_173387)
1.A.12.2.2









Putative Glutathione S-transferase.  Pore formation has not been demonstrated in prokaryotes.

Bacteria
Spirochaetota
Probable glutathione S-transferase of Leptospira interrogans
1.A.12.3.1









The bacterial CLIC homologue, stringent starvation protein A, SspA (212 aas; 0 TMSs) [N-terminal Trx domain; C-terminal glutathione S-transferase (GST) domain].  May be involved in acid (Hansen et al. 2005) and sodium ion tolerance (Wu et al. 2014).

Bacteria
Pseudomonadota
Stringent starvation protein A of E. coli (P0ACA3)
1.A.12.3.2









Glutathione S-transferase, YfcF of 214 aas.  Pore formation has not been demostrated.

Bacteria
Pseudomonadota
YfcF of E. coli