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CLIC5

From Wikipedia, the free encyclopedia
CLIC5
Identifiers
AliasesCLIC5, MST130, MSTP130, DFNB102, DFNB103, chloride intracellular channel 5
External IDsOMIM: 607293; MGI: 1917912; HomoloGene: 987; GeneCards: CLIC5; OMA:CLIC5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001114086
NM_001256023
NM_016929
NM_001370649
NM_001370650

NM_172621

RefSeq (protein)

NP_766209

Location (UCSC)Chr 6: 45.88 – 46.08 MbChr 17: 44.45 – 44.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Chloride intracellular channel protein 5 is a protein that in humans is encoded by the CLIC5 gene.[5][6]

Expression and localization

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CLIC5 exists in two alternative splice variants, a smaller CLIC5A and larger CLIC5B protein.

CLIC5A is expressed chiefly in the renal glomerulus, specifically in podocytes. Within the cell, CLIC5A is localized to the plasma membrane and the cytosol, and associates and is regulated by the actin cytoskeleton.[6] CLIC5A can form ion channels in vitro and its channel activity is regulated by actin, though measurement of its chloride conductance in vitro suggests that CLIC5A is equally selective for cations and anions. Even so, the function of CLICs as bona fide ion channels is controversial and has been disputed.[7][8]

Function

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Although chloride intracellular channel (CLIC) proteins were thought to be involved in ion transport in subcellular compartments, their actual functions suggest their role in diverse cellular and physiological functions including apoptosis and angiogenesis in CLIC1.

CLIC5A, through its interactions with the small GTPase Rac1, induces the phosphorylation of ezrin-moeisin-radixin (ERM) proteins and localized production of the phosphoinositide phosphatidylinositol-4,5-bisphosphate.[9] These two events activate ezrin, enabling it to couple transmembrane proteins to the actin cytoskeleton, which could represent a mechanism by which podocyte foot processes form to enable renal filtration.[10]

Clinical relevance

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Two human families with loss-of-function CLIC5 mutations have been reported, with a total of 5 affected individuals. CLIC5 deficiency results in progressive hearing loss by the second decade, vestibular abnormalities, and kidney dysfunction.[11][12]

CLIC5A deficiency in mouse models potentiates glomerular injury in hypertension. In these mice, podocyte foot processes were also more sparse and disperse than in wild-type mice.[10]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000112782Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023959Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Berryman M, Bretscher A (May 2000). "Identification of a novel member of the chloride intracellular channel gene family (CLIC5) that associates with the actin cytoskeleton of placental microvilli". Molecular Biology of the Cell. 11 (5): 1509–1521. doi:10.1091/mbc.11.5.1509. PMC 14863. PMID 10793131.
  6. ^ a b "Entrez Gene: CLIC5 chloride intracellular channel 5".
  7. ^ Jentsch TJ, Pusch M (July 2018). "CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease" (PDF). Physiological Reviews. 98 (3): 1493–1590. doi:10.1152/physrev.00047.2017. PMID 29845874. S2CID 44165561.
  8. ^ Jentsch TJ (January 2008). "CLC chloride channels and transporters: from genes to protein structure, pathology and physiology". Critical Reviews in Biochemistry and Molecular Biology. 43 (1): 3–36. doi:10.1080/10409230701829110. PMID 18307107. S2CID 86536670.
  9. ^ Al-Momany A, Li L, Alexander RT, Ballermann BJ (December 2014). "Clustered PI(4,5)P₂ accumulation and ezrin phosphorylation in response to CLIC5A". Journal of Cell Science. 127 (Pt 24): 5164–5178. doi:10.1242/jcs.147744. PMID 25344252.
  10. ^ a b Tavasoli M, Li L, Al-Momany A, Zhu LF, Adam BA, Wang Z, Ballermann BJ (April 2016). "The chloride intracellular channel 5A stimulates podocyte Rac1, protecting against hypertension-induced glomerular injury". Kidney International. 89 (4): 833–847. doi:10.1016/j.kint.2016.01.001. PMID 26924049.
  11. ^ Wonkam-Tingang E, Schrauwen I, Esoh KK, Bharadwaj T, Nouel-Saied LM, Acharya A, et al. (October 2020). "Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment". Genes. 11 (11): 1249. doi:10.3390/genes11111249. PMC 7690789. PMID 33114113.
  12. ^ Seco CZ, Oonk AM, Domínguez-Ruiz M, Draaisma JM, Gandía M, Oostrik J, et al. (February 2015). "Progressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5". European Journal of Human Genetics. 23 (2): 189–194. doi:10.1038/ejhg.2014.83. PMC 4297911. PMID 24781754.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.