LRRC8E

Leucine-rich repeat-containing protein 8E is a protein that in humans is encoded by the LRRC8E gene.[5] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8C, and LRRC8D, 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.

LRRC8E
Identifiers
Aliases	LRRC8E, leucine rich repeat containing 8 family member E, leucine rich repeat containing 8 VRAC subunit E
External IDs	OMIM: 612891 MGI: 1919517 HomoloGene: 11817 GeneCards: LRRC8E
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 7,888,505 bp[1] End 7,902,021 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 A1.1 Start 4,226,827 bp[2] End 4,237,470 bp[2]
RNA expression pattern More reference expression data
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 • membrane • endoplasmic reticulum membrane • endoplasmic reticulum • cell membrane • ion channel complex Biological process • ion transport • signal transduction • transmembrane transport • inorganic anion transport • cell volume homeostasis • anion transmembrane transport • aspartate transport • cellular response to osmotic stress Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	80131	72267
Ensembl	ENSG00000171017	ENSMUSG00000046589
UniProt	Q6NSJ5	Q66JT1
RefSeq (mRNA)	NM_001268284 NM_001268285 NM_025061	NM_028175
RefSeq (protein)	NP_001255213 NP_001255214 NP_079337	NP_082451
Location (UCSC)	Chr 19: 7.89 – 7.9 Mb	Chr 8: 4.23 – 4.24 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

While LRRC8E 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 LRRC8E, 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]

Specifically for LRRC8E, there has been a recent study that found that this gene was nominally associated with panic disorder.[14]

References

1. GRCh38: Ensembl release 89: ENSG00000171017 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046589 - 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 FK, Ullrich F, Münch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ (May 2014). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC" (PDF). Science. 344 (6184): 634–8. doi:10.1126/science.1252826. PMID 24790029.
7. Jentsch TJ (May 2016). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (5): 293–307. doi:10.1038/nrm.2016.29. PMID 27033257.
8. Hyzinski-García MC, Rudkouskaya A, Mongin AA (November 2014). "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 T, Wondergem R, Morrison R, Yin VP, Strange K (October 2016). "Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish =" [[Change of inulin- and chloride-spaces during acute metabolic acidosis in the rat]]. Physiological Reports. 4 (19): 16–27. doi:10.14814/phy2.12940. PMC 5064130. PMID 27688432.
10. Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, Kucukosmanoglu A, Xu G, Voss FK, Reincke SM, Stauber T, Blomen VA, Vis DJ, Wessels LF, Brummelkamp TR, Borst P, Rottenberg S, Jentsch TJ (December 2015). "Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs". The EMBO Journal. 34 (24): 2993–3008. doi:10.15252/embj.201592409. PMC 4687416. PMID 26530471.
11. Okada T, Islam MR, Tsiferova NA, Okada Y, Sabirov RZ (March 2017). "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, Kempa S, Jentsch TJ (March 2017). "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, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, Kubota K, Endo H, Onodera T, Ohta H, Ozono K, Hara J (December 2003). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". The Journal of Clinical Investigation. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC 281644. PMID 14660746.
14. Gregersen NO, Buttenschøn HN, Hedemand A, Nielsen MN, Dahl HA, Kristensen AS, Johansen O, Woldbye DP, Erhardt A, Kruse TA, Wang AG, Børglum AD, Mors O (December 2016). "Association between genes on chromosome 19p13.2 and panic disorder". Psychiatric Genetics. 26 (6): 287–292. doi:10.1097/YPG.0000000000000147. PMID 27610895.

Further reading

• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Eggermont J, Trouet D, Carton I, Nilius B (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.
• Hsu LY, Kim HJ, Sujansky E, Kousseff B, Hirschhorn K (2016). "Reciprocal translocation versus centric fusion between two No. 13 chromosomes. A case of 46,XX,-13,+t(13;13)(p12;q13) and a case of 46,XY,-13,+t(13;13)(p12;p12)". Cytogenetics and Cell Genetics. 12 (4): 235–44. doi:10.1007/s00424-015-1765-6. PMC 4752865. PMID 4752865.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (February 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 Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, Ozono K, Hara J (April 2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Letters. 564 (1–2): 147–52. doi:10.1016/S0014-5793(04)00332-1. PMID 15094057.
• Smits G, Kajava AV (July 2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Molecular Immunology. 41 (5): 561–2. doi:10.1016/j.molimm.2004.04.001. PMID 15183935.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (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 Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 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.