LRRC8C

Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene.[5] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel.[6] Volume-Regulated Anion Channels (VRACs) are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane,[7] and that is not the only function these channels have been linked to.

LRRC8C
Identifiers
Aliases	LRRC8C, AD158, FAD158, leucine-rich repeat containing 8 family member C, leucine rich repeat containing 8 family member C, leucine rich repeat containing 8 VRAC subunit C
External IDs	OMIM: 612889 MGI: 2140839 HomoloGene: 12997 GeneCards: LRRC8C
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p22.2 Start 89,633,072 bp[1] End 89,769,903 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 E5 Start 105,519,388 bp[2] End 105,613,018 bp[2]
Gene ontology Molecular function • GO:0001948 protein binding • volume-sensitive anion channel activity Cellular component • cytoplasm • integral component of membrane • integral component of plasma membrane • endoplasmic reticulum membrane • membrane • endoplasmic reticulum • ion channel complex • cell membrane Biological process • anion transmembrane transport • ion transport • fat cell differentiation • regulation of anion transport • signal transduction • transmembrane transport • transport • cell volume homeostasis • inorganic anion transport • taurine transport • aspartate transport • protein hexamerization • cellular response to osmotic stress Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	84230	100604
Ensembl	ENSG00000171488	ENSMUSG00000054720
UniProt	Q8TDW0	Q8R502
RefSeq (mRNA)	NM_032270	NM_133897
RefSeq (protein)	NP_115646	NP_598658
Location (UCSC)	Chr 1: 89.63 – 89.77 Mb	Chr 5: 105.52 – 105.61 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

While LRRC8C is one of many proteins that can be part of VRAC, research has found that it is not as crucial to the activity of the channel in comparison to LRRC8A and LRRC8D.[8][9][10] However, while we know that LRRC8A and LRRC8D are necessary for VRAC function, other studies have found that they are not sufficient for the full range of usual VRAC activity.[11] This is where the other LRRC8 proteins come in, such as LRRC8C, as the different composition of these subunits affects the range of specificity for VRACs.[12][10]

In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5.[13]

References

1. GRCh38: Ensembl release 89: ENSG00000171488 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000054720 - Ensembl, 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. "Entrez Gene: LRRC8A leucine rich repeat containing 8 family, member A".
6. Voss, Felizia; Ullrich, Florian; Münch, Jonas (2014-05-09). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC" (PDF). Science (Submitted manuscript). 344 (6184): 634–8. Bibcode:2014Sci...344..634V. doi:10.1126/science.1252826. PMID 24790029.
7. Jentsch, Thomas J. (2016-05-17). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (2): 293–3017. doi:10.1038/nrm.2016.29. ISSN 1471-0072. PMID 27033257.
8. Hyzinski-García, María C; Rudkouskaya, Alena; Mongin, Alexander (2014-11-15). "LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes". The Journal of Physiology. 592 (22): 4855–62. doi:10.1113/jphysiol.2014.278887. PMC 4259531. PMID 25172945.
9. Yamada, Toshiki; Wondergem, Robert; Morrison, Rebecca (2016-10-04). "Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl⁻ currents and embryonic development in zebrafish". Physiological Reports. 4 (19): e12940. doi:10.14814/phy2.12940. PMC 5064130. PMID 27688432.
10. Planells‐Cases, Rosa; Lutter, Darius; Guyader, Charlotte (2015-12-14). "Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt‐based anti‐cancer drugs". EMBO Journal. 34 (24): 2993–3008. doi:10.15252/embj.201592409. PMC 4687416. PMID 26530471.
11. Okada, T; Islam, MR; Tsiferova, NA (2016-10-20). "Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)". Channels. 11 (2): 109–120. doi:10.1080/19336950.2016.1247133. PMC 5398601. PMID 27764579.
12. Lutter, D; Ullrich, F; Lueck, JC (2017-03-15). "Selective transport of neurotransmitters and –modulators by distinct volume-regulated LRRC8 anion channels". Journal of Cell Science. 130 (6): 1122–1133. doi:10.1242/jcs.196253. PMID 28193731.
13. Sawada, A; Takihara, Y; Kim, JY (December 2003). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". Journal of Clinical Investigation. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC 281644. PMID 14660746.

Further reading

• Jentsch Thomas J (2016). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (2): 293–307. doi:10.1038/nrm.2016.29. PMID 27033257.
• Eggermont D, Trouet I, Carton I, et al. (2001). "Cellular function and control of volume-regulated anion channels". Cell Biochemistry and Biophysics. 35 (3): 263–74. doi:10.1385/CBB:35:3:263. PMID 11894846.
• Mongin Alexander (2016). "Volume-regulated anion channel – a frenemy within the brain". Pflügers Archiv. 468 (3): 421–441. doi:10.1007/s00424-015-1765-6. PMC 4752865. PMID 26620797.
• Nagase T, Kikuno R, Ishikawa KI, et al. (2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Sawada A, Takihara Y, Kim JY, et al. (2004). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". J. Clin. Invest. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC 281644. PMID 14660746.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Kubota K, Kim JY, Sawada A, et al. (2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Lett. 564 (1–2): 147–52. doi:10.1016/S0014-5793(04)00332-1. PMID 15094057.
• Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9". Nature. 429 (6990): 369–74. Bibcode:2004Natur.429..369H. doi:10.1038/nature02465. PMC 2734081. PMID 15164053.
• Smits G, Kajava AV (2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Mol. Immunol. 41 (5): 561–2. doi:10.1016/j.molimm.2004.04.001. PMID 15183935.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.