chloride intracellular channel protein 4; intracellular chloride ion channel protein p64H1 (CLIC4)

Function

• can insert into membranes & form poorly selective ion channels that may also transport chloride ions
• channel activity depends on the pH
• membrane insertion seems to be redox-regulated & may occur only under oxidizing conditions
• promotes cell-surface expression of HRH3
• has alternate cellular functions including a potential role in angiogenesis or in maintaining apical-basolateral membrane polarity during mitosis & cytokinesis
• could also promote endothelial cell proliferation & regulate endothelial morphogenesis (tubulogenesis)
• component of a multimeric complex consisting of several cytoskeletal proteins, including actin, ezrin, alpha-actinin, gelsolin, IQGAP1 & CLIC5A
• binds directly to brain dynamin 1 in a complex containing actin, tubulin & 14-3-3 isoforms
• monomer
• interacts with HRH3
• interacts with AKAP9

Structure

• members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane & functions as chloride channel
• a conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion
• belongs to the chloride channel CLIC family
• contains 1 GST C-terminal domain

Compartment

• cytoplasm, cytoskeleton, centrosome
• cytoplasmic vesicle membrane
• single-pass membrane protein (probable)
• nuclear matrix
• cell membrane
• mitochondria
• cell junction
• colocalized with AKAP9 at the centrosome & midbody
• exists both as soluble cytoplasmic protein & as membrane protein with probably a single transmembrane domain
• present in an intracellular vesicular compartment that likely represents trans-Golgi network vesicles

Expression

• detected in epithelial cells from colon, esophagus & kidney (at protein level)
• expression is prominent in heart, kidney, placenta & skeletal muscle
• up-regulated by Ca+2 in differentiating keratinocytes
• up-regulated in myofibroblasts

More general terms

• chloride intracellular channel protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=25932
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:25932
• OMIM: https://mirror.omim.org/entry/606536
• UniProt: http://www.uniprot.org/uniprot/Q9Y696.html