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FLASH GENE

Symbol

CLIC4

contributors: mct/npt - updated : 30-09-2015

HGNC name	chloride intracellular channel 4
HGNC id	13518

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	1p36.11      Physical location : 25.071.759 - 25.170.815
Synonym name	intracellular chloride ion channel protein p64H1
Synonym symbol(s)	H1, huH1, P64H1, CLIC4L, FLJ38640, MTCLIC, DKFZP566G223

DNA

TYPE	functioning gene
SPECIAL FEATURE	head to head
STRUCTURE	99.56 kb     6 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_013943 6 - 4452 NP_039234 28.8 253 - Singh (2007)

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Reproductive female system breast         female system uterus     highly Respiratory respiratory tract trachea     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone     highly Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage Mus musculus Fetal Skin/Tegument keratinocyte

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies

homolog to murine Clic4

Homologene

FAMILY

CLIC family of chloride channel

CATEGORY

chaperone/stress , regulatory , transport channel

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,nucleus
	intracellular,nuclear envelope
text	trans-golgi network vesicles
	nuclear CLIC4, possibly by altering the Cl(-) and pH of the nucleus, contributes to cell cycle arrest and the specific gene expression program associated with keratinocyte terminal differentiation (Suh 2007)
	in keratinocytes, resides in the mitochondria and cytoplasm (Suh 2007)
	nuclear translocation of cytosolic CLIC4 is an essential feature of its proapoptotic and prodifferentiation functions
	localizes to mitochondria, endoplasmic reticulum (ER), nucleus and cytoplasm, and participates in the apoptotic response to stress

basic FUNCTION	involved in cell membrane remodelling, control of cell shape, anion channel activity
	actin-regulated membrane protein that could modify solute transport at key stages during cellular events such as apoptosis, cell and organelle division and fusion, cell-volume regulation, and cell movement
	mediates and is required for Ca2+-induced keratinocyte differentiation
	may play a role in maintaining apical-basolateral membrane polarity during mitosis and cytokinesis, and may be important for regulating cytoskeletal organization during the cell cycle
	chaperon component of a GPCR trafficking machinery that operates at some location along the exocytic pathway where heterotrimeric G protein assembly takes place
	functions to promote endothelial cell proliferation and to regulate endothelial morphogenesis
	a multifunctional protein that traffics between the cytoplasm and nucleus
	plays an important role in RPE-photoreceptor adhesion, perhaps by modulating the activity of cell surface channels/transportersv
	is a bacterial lipopolysaccharide (LPS)-induced product that can serve as a positive regulator of LPS signaling
	role for CLIC4 in innate immunity
	importance of nuclear CLIC4 for deactivation of proinflammatory macrophages
	CLIC4 nuclear translocation is an integral part of the cellular response to starvation
	regulates vasculogenesis through endothelial tube formation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	dynamin 1, alpha-tubulin, beta-actin
	interacting with AKAP9 (CLIC4 and AKAP9 colocalize at the centrosome)
	interacts with HIVEP2 (HIVEP2 and CLIC4 are modifiers of TGF-beta signalling through their stabilization of p-Smad2 and 3 in the nucleus)
	overexpression of nuclear-targeted CLIC4 down-regulates IL1B in stimulated macrophages
	CLIC4 is a regulator of RAB35 activity and serum- and LPA-dependent integrin trafficking

cell & other

REGULATION

induced by

induced concurrently with inducible nitric oxide synthase (iNOS) and S-nitrosylated in proinflammatory peritoneal macrophages

Other

regulated by RHOA to be targeted to the plasma membrane, where it may function not as an inducible chloride channel but rather by displaying Cys-dependent transferase activity toward a yet unknown substrate

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in tumor stromal cells stimulates tumor growth (Suh 2007) constitutional     --other   aberrant CLIC4 expression may contribute to the vascular pathology of pulmonary arterial hypertension constitutional     --over   is an early manifestation and mediator of endothelial dysfunction in pulmonary hypertension constitutional     --low   enhances autophagy and contributes to mitochondrial and ER stress-induced apoptosis under starvation tumoral     --over   of CLIC3, CLIC4 in malignant pleural mesothelioma (MPM) as compared to controls

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target	participates in normal and pathological processes and may serve as a useful target for therapies in disturbances of homeostasis and neoplastic transformation (Suh 2007)

ANIMAL & CELL MODELS