Chloride channel CLIC-like 1, also known as CLCC1 is a human gene.[5][6] This protein is vital in the regulation, storage and secretion of lipids[7] and the assembly of nuclear pore complexes (NOCs). It may also be a chloride channel however evidence for this is inconclusive.[8]
It is related in sequence to the MID-1 stretch-activated channel of Saccharomyces cerevisiae. It clusters with lipolysis regulator genes such as ABHD5 and PNPLA2.[6]
Tissue distribution
CLCC1 is located in the membranes of intracellular compartments including endoplasmic reticulum and the Golgi apparatus. It is highly expressed in the testis and moderately in the spleen, liver, kidney, heart, brain, and lung.[6]
Function
CLCC1 has various functions but is vital in two main functions in hepatic cells and nuclear pore complexes (NPCs). In hepatocytes, this protein is a critical regulator of neutral lipid storage and secretion. It mediates membrane fusion which promotes hepatic neutral lipid flux and the assembly of the nuclear pore complex.[8]
Lipid regulation
CLCC1 regulates in lipid homeostasis by regulating the storage and secretion of lipids.[8] It is able to recognize an imbalance in lipids by partnering with TMEM41B. When an imbalance is recognized, lipid scrambling is then promoted. They also support the biogenesis and bulk tranport of lipoproteins (LPs).[7]
NPC assembly
CLCC1 seems to be an essential component in the assembly of the nuclear pore complex in hepatic cells. Disruptions in similar proteins (BRL1 and BRR6) has caused nuclear membrane herniations (nuclear blebs) often being from disruptions in NPC insertion. Because of the similar structure of CLCC1 has to BRL1 and BRR6, it would likely have a similar effect. (Mathiowetz et al. 2026) knocked-out CLCC1 genes from mice cells which resulted in loss of NPCs. This lead to a reduction in transportation between the nucleus and cytoplasm.[8]
Channel protein
The protein encoded by this gene is potentially a chloride channel. However there is no conclusive evidence for this and there seems to be no overall sequence similarity with known protein channel families.[8]
Loss of CLCC1
The loss of CLCC1 leads to a buildup of large lipid droplets (LDs) in hepatoma cells. It also leads to the accumulation of herniations in the nuclear membrane which is accompanied by a reduction in number of nuclear pores. This gene was subjected to knock-out tests on mice. When knocked-out, it causes stress to the endoplasmic reticulum (ER) and neurodegeneration. The loss of this gene also causes liver steatosis.[8]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000121940 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027884 – Ensembl, May 2017
- ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, et al. (October 1998). “Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro”. DNA Research. 5 (5): 277–286. doi:10.1093/dnares/5.5.277. PMID 9872452.
- ^ a b c Nagasawa M, Kanzaki M, Iino Y, Morishita Y, Kojima I (June 2001). “Identification of a novel chloride channel expressed in the endoplasmic reticulum, golgi apparatus, and nucleus”. The Journal of Biological Chemistry. 276 (23): 20413–20418. doi:10.1074/jbc.M100366200. PMID 11279057.
- ^ a b Wu L, Wang J, Wang Y, Yang J, Yao Y, Wang Y, et al. (April 2026). “CLCC1 governs ER bilayer equilibration to maintain lipid homeostasis”. Nature. 652 (8109): 471–480. doi:10.1038/s41586-026-10161-y. PMC 13061606. PMID 41741642.
- ^ a b c d e f Mathiowetz AJ, Meymand ES, Parlakgül G, van Hilten N, Torres EF, Artico LL, et al. (April 2026). “CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly”. Nature. 652 (8109): 462–470. doi:10.1038/s41586-025-10064-4. PMC 13061601. PMID 41741636.
Further reading
- Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, et al. (October 1998). “Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro”. DNA Research. 5 (5): 277–286. doi:10.1093/dnares/5.5.277. PMID 9872452.
{{cite journal}}: CS1 maint: overridden setting (link) - Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). “Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes”. Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
{{cite journal}}: CS1 maint: overridden setting (link) - Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, et al. (September 2004). “Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions”. Genome Research. 14 (9): 1711–1718. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
{{cite journal}}: CS1 maint: overridden setting (link) - Nagasawa M, Kanzaki M, Iino Y, Morishita Y, Kojima I (June 2001). “Identification of a novel chloride channel expressed in the endoplasmic reticulum, golgi apparatus, and nucleus”. The Journal of Biological Chemistry. 276 (23): 20413–20418. doi:10.1074/jbc.M100366200. PMID 11279057.
{{cite journal}}: CS1 maint: overridden setting (link)
External links
- CLCC1 protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CLCC1 genome location and CLCC1 gene details page in the UCSC Genome Browser.