CLIC4 (chloride intracellular channel 4)
2009-07-01 Velayuthan C Padmakumar , Stuart H Yuspa AffiliationLaboratory of Cancer Biology, Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Identity
HGNC
LOCATION
1p36.11
LOCUSID
ALIAS
CLIC4L,H1,MTCLIC,huH1,p64H1
FUSION GENES
DNA/RNA
CLIC4 gene consists of 6 exons. The number between the exons indicate the length in kilo bases of intervening introns.
Description
CLIC4 gene comprises of 6 exons spanning a region of about 99 kb on human chromosome 1p36.
Transcription
CLIC4 gene codes for a protein of 253 amino acids length corresponding to molecular weight of about 29 kDa. No alternative isoforms of CLIC4 has been reported.
Proteins
Domain organisation of CLIC4. TM indicates transmembrane domain and NLS represents nuclear localisation signal.
Description
CLIC4 is a putative chloride channel for intracellular organelles. The human protein consists of 253 amino acids with an N-terminal transmembrane domain and C-terminal nuclear localisation signal.
Localisation
It is localised in cytoplasm and mitochondria in primary keratinocytes and translocated to nucleus upon cellular stress.
Function
CLIC4 has been shown to regulate TGF-beta signaling. It has been shown to translocate to the nucleus in a Schnurri-2 dependent manner and nuclear CLIC4 has been shown to subsequently stabilise phospho- Smad2 and Smad3.
CLIC4 has been implicated in angiogenesis. It has been shown to be involved in acidification of vacuoles along the cell hollowing tubulogenic pathway.
CLIC4 has been shown to be expressed in myofibroblasts and inhibit motility of MEF/3T3 cells.
CLIC4 has been implicated in Myc-induced apoptosis. It was identified as a candidate gene after protein expression analysis during Myc-induced apoptosis. Myc has been shown to bind to CLIC4 promotor and activate its transcription.
CLIC4 has been implicated in angiogenesis. It has been shown to be involved in acidification of vacuoles along the cell hollowing tubulogenic pathway.
CLIC4 has been shown to be expressed in myofibroblasts and inhibit motility of MEF/3T3 cells.
CLIC4 has been implicated in Myc-induced apoptosis. It was identified as a candidate gene after protein expression analysis during Myc-induced apoptosis. Myc has been shown to bind to CLIC4 promotor and activate its transcription.
Homology
CLIC1, CLIC2, CLIC3, CLIC5 and CLIC6.
Implicated in
Entity name
Various cancer
Note
Expression analysis on a human tumour array has shown that CLIC4 expression is dimished in several tumour types including breast, ovary and kidney. CLIC4 expression has also been shown to be upregulated in some tumours.
In matched tissue arrays, CLIC4 was predominantly nuclear in normal epithelial tissues but not cancers. As tumours progressed CLIC4 expression became undetectable in tumour cells but increased in stromal cells.
Sequence analysis of CLIC4 cDNA of 60 human cancer cell lines (NCI60) and EST database analysis failed to reveal mutations in CLIC4 gene.
In matched tissue arrays, CLIC4 was predominantly nuclear in normal epithelial tissues but not cancers. As tumours progressed CLIC4 expression became undetectable in tumour cells but increased in stromal cells.
Sequence analysis of CLIC4 cDNA of 60 human cancer cell lines (NCI60) and EST database analysis failed to reveal mutations in CLIC4 gene.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11997498 | 2002 | mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA damage and participates in the apoptotic response to p53. | Fernández-Salas E et al |
| 12237120 | 2002 | Overexpressed chloride intracellular channel protein CLIC4 (p64H1) is an essential component of novel plasma membrane anion channels. | Proutski I et al |
| 12163372 | 2002 | Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts. | Rønnov-Jessen L et al |
| 16316993 | 2006 | Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4. | Shiio Y et al |
| 19448624 | 2009 | TGF-beta signalling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3. | Shukla A et al |
| 11563969 | 2001 | Chloride intracellular channel protein CLIC4 (p64H1) binds directly to brain dynamin I in a complex containing actin, tubulin and 14-3-3 isoforms. | Suginta W et al |
| 17200346 | 2007 | Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers. | Suh KS et al |
| 14610078 | 2004 | The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis. | Suh KS et al |
| 19197003 | 2009 | Chloride intracellular channel protein-4 functions in angiogenesis by supporting acidification of vacuoles along the intracellular tubulogenic pathway. | Ulmasov B et al |
Other Information
Locus ID:
NCBI: 25932
MIM: 606536
HGNC: 13518
Ensembl: ENSG00000169504
Variants:
dbSNP: 25932
ClinVar: 25932
TCGA: ENSG00000169504
COSMIC: CLIC4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000169504 | ENST00000374379 | Q9Y696 |
| ENSG00000169504 | ENST00000374379 | Q6FIC5 |
| ENSG00000169504 | ENST00000488683 | Q9Y696 |
| ENSG00000169504 | ENST00000488683 | Q6FIC5 |
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38727794 | 2024 | CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions. | 0 |
| 38727794 | 2024 | CLIC4 Function in the Epithelial-Mesenchymal Transition of Epithelial Odontogenic Lesions. | 0 |
| 37026609 | 2023 | The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma. | 1 |
| 37317855 | 2023 | CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA. | 0 |
| 37026609 | 2023 | The stromal immunoexpression of CLIC4 may be related to the difference in the biological behavior between oral squamous cell carcinoma and oral verrucous carcinoma. | 1 |
| 37317855 | 2023 | CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA. | 0 |
| 35078024 | 2022 | Characterization of chloride intracellular channel 4 in the regulation of human trophoblast function. | 1 |
| 35081862 | 2022 | Circular RNA_0033596 aggravates endothelial cell injury induced by oxidized low-density lipoprotein via microRNA-217-5p /chloride intracellular channel 4 axis. | 5 |
| 35159339 | 2022 | Induction of Pro-Fibrotic CLIC4 in Dermal Fibroblasts by TGF-β/Wnt3a Is Mediated by GLI2 Upregulation. | 4 |
| 35727842 | 2022 | Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence. | 2 |
| 35732323 | 2022 | Requirement of CLIC4 Expression in Human Colorectal Cancer Cells for Sensitivity to Growth Inhibition by Fucoxanthinol. | 1 |
| 35078024 | 2022 | Characterization of chloride intracellular channel 4 in the regulation of human trophoblast function. | 1 |
| 35081862 | 2022 | Circular RNA_0033596 aggravates endothelial cell injury induced by oxidized low-density lipoprotein via microRNA-217-5p /chloride intracellular channel 4 axis. | 5 |
| 35159339 | 2022 | Induction of Pro-Fibrotic CLIC4 in Dermal Fibroblasts by TGF-β/Wnt3a Is Mediated by GLI2 Upregulation. | 4 |
| 35727842 | 2022 | Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence. | 2 |
Citation
Velayuthan C Padmakumar ; Stuart H Yuspa
CLIC4 (chloride intracellular channel 4)
Atlas Genet Cytogenet Oncol Haematol. 2009-07-01
Online version: http://atlasgeneticsoncology.org/gene/40102/clic4-(chloride-intracellular-channel-4)
