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CLIC4 Membrane Protein Introduction

Introduction of CLIC4

Chloride intracellular channel 4 (CLIC4) protein is encoded by the CLIC4 gene, which is a member of the p64 family and found in many tissues. The CLIC4 gene exhibits an intracellular vesicular pattern in PANC-1 cells (pancreatic cancer cells). Gene ontology annotations associated with this gene include chloride channel activity and voltage-gated chloride channel activity. An important paralog of this gene is CLIC5. Chloride channels are a diverse group of proteins which regulate basic cellular processes. Chloride channels stabilize cell membrane potential, transepithelial transport, maintain intracellular pH and regulate cell volume. Related pathways of CLIC4 include hepatic ABC transporters and activation of cAMP-dependent PKA.

Basic Information of CLIC4
Protein Name Chloride intracellular channel protein 4
Gene Name CLIC4
Aliases Intracellular chloride ion channel protein p64H1
Organism Homo sapiens (Human)
UniProt ID Q9Y696
Transmembrane Times 1
Length (aa) 253
Sequence MALSMPLNGLKEEDKEPLIELFVKAGSDGESIGNCPFSQRLFMILWLKGVVFSVTTVDLKRKPADLQNLAPGTHPPFITFNSEVKTDVNKIEEFLEEVLCPPKYLKLSPKHPESNTAGMDIFAKFSAYIKNSRPEANEALERGLLKTLQKLDEYLNSPLPDEIDENSMEDIKFSTRKFLDGNEMTLADCNLLPKLHIVKVVAKKYRNFDIPKEMTGIWRYLTNAYSRDEFTNTCPSDKEVEIAYSDVAKRLTK

Function of CLIC4 Membrane Protein

High cell proliferation rate, migration, and invasiveness are specific properties of tumorigenesis, which involves chloride channels. CLIC4 is present in the mitochondrial membrane, cytoplasm, and nucleus as a soluble protein. CLIC4 is expressed in the mitochondria and regulates intracellular pH and cell volume. Under normal physiological conditions, CLIC4 is localized in the nucleus through the nuclear localization signal (NLS). The functional activity of CLIC4 is determined by its redox state: oxidant conditions enhance its membrane binding capacity and channel activity. CLIC4 is also involved in multiple cellular processes such as apoptosis, inflammation and endothelial tubulogenesis. However, CLIC4 is almost absent in normal stromal tissues and highly expressed in cancer tissues and tumor-related stromal fibroblasts. CLIC4 may be a potential target for certain cancers.

CLIC4 Membrane Protein IntroductionFig.1 Structure of the CLIC4 protein.

Application of CLIC4 Membrane Protein in Literature

  1. Yu Q.Y., et al. SiRNA-mediated down-regulation of CLIC4 gene inhibits cell proliferation and accelerates cell apoptosis of mouse liver cancer Hca-F and Hca-P cells. J Cell Biochem. 2018, 119(1): 659-668. PubMed ID: 28636115

    The article reveals that siRNA-induced down-regulation of CLIC4 could enhance proliferation, while in turn promoting apoptosis of mouse liver cancer Hca-F and Hca-P cells.

  2. Zou Q., et al. Association of chloride intracellular channel 4 and Indian hedgehog proteins with survival of patients with pancreatic ductal adenocarcinoma. Int J Exp Pathol. 2016, 97(6): 422-429. PubMed ID: 28205343

    The article indicates that CLIC4 and Ihh can be used as biomarkers for the diagnostic of pancreatic ductal adenocarcinoma, including progression, metastasis, and invasiveness.

  3. Lucitti J.L., et al. Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation. Am J Physiol Heart Circ Physiol. 2015, 309(7): H1141-50. PubMed ID: 26276819

    Authors in this group demonstrated that CLIC4 is not essential for collaterogenesis but is required for perinatal maturation of nascent collaterals.

  4. Argenzio E., et al. CLIC4 regulates cell adhesion and β1 integrin trafficking. J Cell Sci. 2014, 127(Pt 24): 5189-203. PubMed ID: 22891322

    This article focuses on the possible role of CLIC4 in cell adhesion and β1 integrin trafficking. CLIC4 was defined as a modulator of Rab35 activity and serum- and LPA-dependent integrin trafficking.

  5. Padmakumar V., et al. Detection of differential fetal and adult expression of chloride intracellular channel 4 (CLIC4) protein by analysis of a green fluorescent protein knock-in mouse line. BMC Dev Biol. 2014, 14: 24. PubMed ID: 24886590

    This article reports that CLIC4 expression is regulated particularly in fetal liver, thymus, kidney, brain, and heart, as well as developing brown adipose tissue and stratifying epidermis during the second and third trimesters.

CLIC4 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Besides, aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CLIC4 antibody development services.


As a leading service provider, Creative Biolabs is proud to present our professional service in membrane protein preparation and help you with the research of membrane proteins. Please do not hesitate to inquire us for more details.

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