1.A.36 The Intracellular Chloride Channel (ICC) Family

Mammals possess an intracellular (endoplasmic reticular, Golgi and nuclear membrane) protein which in humans is 551 aas long and exhibits 3 - 5 TMSs. Homologues have been identified in rodents and frogs (see 1.A.36.1.5), but not in C. elegans or D. melanogaster. The protein has been shown to exhibit anion-selective channel activity (Nagasawa et al., 2001). Although it was isolated using a yeast MID1 gene mutant (see TC # 1.A.16), it does not exhibit appreciable sequence similarity to the yeast Mid1 protein. Of the 4 putative TMSs, TMSs 1 and 4 are strongly hydrophobic while TMSs 2 and 3 are only weakly hydrophobic. None is strongly amphipathic when the angle is set at 100° as is appropriate for an α-helix.

This family belongs to the Tetraspan Junctional Complex Protein or MARVEL (4JC) Superfamily.



Al Khamici, H., L.J. Brown, K.R. Hossain, A.L. Hudson, A.A. Sinclair-Burton, J.P. Ng, E.L. Daniel, J.E. Hare, B.A. Cornell, P.M. Curmi, M.W. Davey, and S.M. Valenzuela. (2015). Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity. PLoS One 10: e115699.

Basham, S.E. and L.S. Rose. (1999). Mutations in ooc-5 and ooc-3 disrupt oocyte formation and the reestablishment of asymmetric PAR protein localization in two-cell Caenorhabditis elegans embryos. Dev Biol 215: 253-263.

Giannotta, M., G. Fragassi, A. Tamburro, C. Vanessa, A. Luini, and M. Sallese. (2015). Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling. Biomed Res Int 2015: 319454.

Jia, Y., T.J. Jucius, S.A. Cook, and S.L. Ackerman. (2015). Loss of Clcc1 Results in ER Stress, Misfolded Protein Accumulation, and Neurodegeneration. J. Neurosci. 35: 3001-3009.

Leanza, L., L. Biasutto, A. Managò, E. Gulbins, M. Zoratti, and I. Szabò. (2013). Intracellular ion channels and cancer. Front Physiol 4: 227.

Nagasawa, M., M. Kanzaki, Y. Iino, Y. Morishita, and I. Kojima. (2001). Identification of a novel chloride channel expressed in the endoplasmic reticulum, Golgi apparatus, and nucleus. J. Biol. Chem. 276: 20413-20418.

Pichler, S., P. Gönczy, H. Schnabel, A. Pozniakowski, A. Ashford, R. Schnabel, and A.A. Hyman. (2000). OOC-3, a novel putative transmembrane protein required for establishment of cortical domains and spindle orientation in the P(1) blastomere of C. elegans embryos. Development 127: 2063-2073.


TC#NameOrganismal TypeExample

The intracellular chloride channel, CLIC-like, Clcc1 (Mid1-related chloride [anion] channel, MCLC), of 551 aas. Its loss results in endoplasmic reticular (ER) stress, misfolded protein accumulation, and neurodegeneration (Jia et al. 2015).


MCLC of Homo sapiens


CLIC- homologue


CLIC homologue of Nematostella vectensis


Clic-like Chloride channel protein 1


Clic-like protein of Acromyrmex echinatior (Panamanian leafcutter ant) (Acromyrmex octospinosus echinatior)


Putative chloride channel


Chloride channel of Abalone herpesvirus Victorial


Chloride channel, CLIC-like protein 1 of 508 aas.


CLIC of Xenopus laevis (African clawed frog)


TC#NameOrganismal TypeExample

OOC-3 protein, isoform B.  Required for establishment of cortical domains in C. elegans embryos (Basham and Rose 1999; Pichler et al. 2000).


OOC-3 of Caenorhabditis elegans


Uncharacterized protein


Uncharacterized protein of Loa loa


TC#NameOrganismal TypeExample