| Written | 2009-07 | Velayuthan C Padmakumar, Stuart H Yuspa |
| Laboratory of Cancer Biology, Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA |
| Identity |
| Alias (NCBI) | MTCLIC | P64H1 | CLIC4L | H1 | huH1 |
| HGNC (Hugo) | CLIC4 |
| HGNC Alias symb | DKFZP566G223 | CLIC4L | P64H1 | H1 | huH1 | p64H1 |
| LocusID (NCBI) | 25932 |
| Atlas_Id | 40102 |
| Location | 1p36.11 [Link to chromosome band 1p36] |
| Location_base_pair | Starts at 24745447 and ends at 24844319 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping CLIC4.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| CACHD1 (1p31.3)::CLIC4 (1p36.11) | CLIC4 (1p36.11)::GRHL3 (1p36.11) | CLIC4 (1p36.11)::PLOD1 (1p36.22) | |
| CLIC4 (1p36.11)::RPS25 (11q23.3) | CLIC4 (1p36.11)::SRRM1 (1p36.11) | COL2A1 (12q13.11)::CLIC4 (1p36.11) | |
| HERC1 (15q22.31)::CLIC4 (1p36.11) |
| 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. |
| Protein |
 | |
| 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. |
| Expression | Ubiquitous and induced by p53, TNF-alpha and c-myc. |
| 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. |
| Homology | CLIC1, CLIC2, CLIC3, CLIC5 and CLIC6. |
| Implicated in |
| Note | |
| Entity | 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. |
| Bibliography |
| mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA damage and participates in the apoptotic response to p53. |
| Fernandez-Salas E, Suh KS, Speransky VV, Bowers WL, Levy JM, Adams T, Pathak KR, Edwards LE, Hayes DD, Cheng C, Steven AC, Weinberg WC, Yuspa SH. |
| Mol Cell Biol. 2002 Jun;22(11):3610-20. |
| PMID 11997498 |
| Overexpressed chloride intracellular channel protein CLIC4 (p64H1) is an essential component of novel plasma membrane anion channels. |
| Proutski I, Karoulias N, Ashley RH. |
| Biochem Biophys Res Commun. 2002 Sep 20;297(2):317-22. |
| PMID 12237120 |
| Differential expression of a chloride intracellular channel gene, CLIC4, in transforming growth factor-beta1-mediated conversion of fibroblasts to myofibroblasts. |
| Ronnov-Jessen L, Villadsen R, Edwards JC, Petersen OW. |
| Am J Pathol. 2002 Aug;161(2):471-80. |
| PMID 12163372 |
| Quantitative proteomic analysis of myc-induced apoptosis: a direct role for Myc induction of the mitochondrial chloride ion channel, mtCLIC/CLIC4. |
| Shiio Y, Suh KS, Lee H, Yuspa SH, Eisenman RN, Aebersold R. |
| J Biol Chem. 2006 Feb 3;281(5):2750-6. Epub 2005 Nov 29. |
| PMID 16316993 |
| TGF-beta signalling is regulated by Schnurri-2-dependent nuclear translocation of CLIC4 and consequent stabilization of phospho-Smad2 and 3. |
| Shukla A, Malik M, Cataisson C, Ho Y, Friesen T, Suh KS, Yuspa SH. |
| Nat Cell Biol. 2009 Jun;11(6):777-84. Epub 2009 May 17. |
| PMID 19448624 |
| 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, Karoulias N, Aitken A, Ashley RH. |
| Biochem J. 2001 Oct 1;359(Pt 1):55-64. |
| PMID 11563969 |
| Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers. |
| Suh KS, Crutchley JM, Koochek A, Ryscavage A, Bhat K, Tanaka T, Oshima A, Fitzgerald P, Yuspa SH. |
| Clin Cancer Res. 2007 Jan 1;13(1):121-31. |
| PMID 17200346 |
| The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis. |
| Suh KS, Mutoh M, Nagashima K, Fernandez-Salas E, Edwards LE, Hayes DD, Crutchley JM, Marin KG, Dumont RA, Levy JM, Cheng C, Garfield S, Yuspa SH. |
| J Biol Chem. 2004 Feb 6;279(6):4632-41. Epub 2003 Nov 10. |
| PMID 14610078 |
| Chloride intracellular channel protein-4 functions in angiogenesis by supporting acidification of vacuoles along the intracellular tubulogenic pathway. |
| Ulmasov B, Bruno J, Gordon N, Hartnett ME, Edwards JC. |
| Am J Pathol. 2009 Mar;174(3):1084-96. Epub 2009 Feb 5. |
| PMID 19197003 |
| Citation |
| This paper should be referenced as such : |
| Padmakumar, VC ; Yuspa, SH |
| CLIC4 (chloride intracellular channel 4) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(6):536-537. |
| Free journal version : [ pdf ] [ DOI ] |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Oct 8 21:15:13 CEST 2021 |
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