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{{Short description|Protein-coding gene in the species Homo sapiens}}
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'''Leucine-rich repeat-containing protein 8D''' is a [[protein]] that in humans is encoded by the ''LRRC8D'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: LRRC8A leucine rich repeat containing 8 family, member A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56262}}</ref> Researchers have found out that this protein, along with the other LRRC8 proteins [[LRRC8A]], [[LRRC8B]], [[LRRC8C]], and [[LRRC8E]], is a subunit of the heteromer protein [[Volume-regulated anion channel|Volume-Regulated Anion Channel]].<ref name="Voss_2014">{{cite journal | vauthors = Voss FK, Ullrich F, Münch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ | title = Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC | journal = Science | volume = 344 | issue = 6184 | pages = 634–8 | date = May 2014 | pmid = 24790029 | doi = 10.1126/science.1252826 | bibcode = 2014Sci...344..634V | s2cid = 24709412 | url = http://edoc.mdc-berlin.de/14008/1/14008oa.pdf }}</ref> 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,<ref name ="Jentsch_2016">{{cite journal | vauthors = Jentsch TJ | title = VRACs and other ion channels and transporters in the regulation of cell volume and beyond | journal = Nature Reviews Molecular Cell Biology | volume = 17 | issue = 5 | pages = 293–307 | date = May 2016 | pmid = 27033257 | doi = 10.1038/nrm.2016.29 | s2cid = 40565653 }}</ref> and that is not the only function these channels have been linked to.
<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Leucine rich repeat containing 8 family, member D
| HGNCid = 16992
| Symbol = LRRC8D
| AltSymbols =; FLJ10470; FLJ20403; LRRC5
| OMIM =
| ECnumber =
| Homologene = 10004
| MGIid = 1922368
| GeneAtlas_image1 = PBB_GE_LRRC8D_218684_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process =
| Orthologs = {{GNF_Ortholog_box
| Hs_EntrezGene = 55144
| Hs_Ensembl = ENSG00000171492
| Hs_RefseqProtein = NP_060573
| Hs_RefseqmRNA = NM_018103
| Hs_GenLoc_db =
| Hs_GenLoc_chr = 1
| Hs_GenLoc_start = 90059192
| Hs_GenLoc_end = 90174147
| Hs_Uniprot = Q7L1W4
| Mm_EntrezGene = 231549
| Mm_Ensembl = ENSMUSG00000046079
| Mm_RefseqmRNA = NM_178701
| Mm_RefseqProtein = NP_848816
| Mm_GenLoc_db =
| Mm_GenLoc_chr = 5
| Mm_GenLoc_start = 105940338
| Mm_GenLoc_end = 106055354
| Mm_Uniprot = Q3TI70
}}
}}
'''Leucine rich repeat containing 8 family, member D''', also known as '''LRRC8D''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: LRRC8D leucine rich repeat containing 8 family, member D| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=55144| accessdate = }}</ref>


While LRRC8D is one of many proteins that can be part of VRAC, it is in fact one of the most important subunits for the channel’s ability to function; the other protein of importance is [[LRRC8A]].<ref name ="Hyzinski-García_2014">{{cite journal | vauthors = Hyzinski-García MC, Rudkouskaya A, Mongin AA | title = LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes | journal = The Journal of Physiology | volume = 592 | issue = 22 | pages = 4855–62 | date = November 2014 | pmid = 25172945 | pmc = 4259531 | doi = 10.1113/jphysiol.2014.278887 }}</ref><ref name ="Yamada_2016">{{cite journal | vauthors = Yamada T, Wondergem R, Morrison R, Yin VP, Strange K | title = Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish | journal = Physiological Reports | volume = 4 | issue = 19 | date = October 2016 | pmid = 27688432 | pmc = 5064130 | doi = 10.14814/phy2.12940 | page=e12940}}</ref> However, while we know it is necessary for specific VRAC function, other studies have found that it is not sufficient for the full range of usual VRAC activity.<ref name ="Okada_2017">{{cite journal | vauthors = Okada T, Islam MR, Tsiferova NA, Okada Y, Sabirov RZ | title = Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR) | journal = Channels | volume = 11 | issue = 2 | pages = 109–120 | date = March 2017 | pmid = 27764579 | doi = 10.1080/19336950.2016.1247133 | pmc=5398601}}</ref> This is where the other LRRC8 proteins come in, as the different composition of these subunits affects the range of specificity for VRACs.<ref name ="Lutter_2017">{{cite journal | vauthors = Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ | title = Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels | journal = Journal of Cell Science | volume = 130 | issue = 6 | pages = 1122–1133 | date = March 2017 | pmid = 28193731 | doi = 10.1242/jcs.196253 | doi-access = free }}</ref><ref name="Planells-Cases_2015">{{cite journal | vauthors = 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 | title = Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs | journal = The EMBO Journal | volume = 34 | issue = 24 | pages = 2993–3008 | date = December 2015 | pmid = 26530471 | pmc = 4687416 | doi = 10.15252/embj.201592409 }}</ref>
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In addition to its role in VRACs, the LRRC8 protein family is also associated with [[agammaglobulinemia]]-5.<ref name="Sawada_2003">{{cite journal | vauthors = 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 | title = A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans | journal = The Journal of Clinical Investigation | volume = 112 | issue = 11 | pages = 1707–13 | date = December 2003 | pmid = 14660746 | doi = 10.1172/JCI18937 | pmc=281644}}</ref>
⚫
==References==

⚫
== References ==
{{reflist}}
{{reflist}}

==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin | 30em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Eggermont J, Trouet D, Carton I, Nilius B | title = Cellular function and control of volume-regulated anion channels | journal = [[Cell Biochemistry and Biophysics]] | volume = 35 | issue = 3 | pages = 263–74 | year = 2001 | pmid = 11894846 | doi = 10.1385/CBB:35:3:263 | s2cid = 31821726 }}
| citations =
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Mongin AA | title = Volume-regulated anion channel--a frenemy within the brain | journal = Pflügers Archiv | volume = 468 | issue = 3 | pages = 421–41 | date = March 2016 | pmid = 26620797 | pmc = 4752865 | doi = 10.1007/s00424-015-1765-6}}
*{{cite journal | author=Andersson B, Wentland MA, Ricafrente JY, ''et al.'' |title=A "double adaptor" method for improved shotgun library construction. |journal=Anal. Biochem. |volume=236 |issue= 1 |pages= 107–13 |year= 1996 |pmid= 8619474 |doi= 10.1006/abio.1996.0138 }}
* {{cite journal | vauthors = Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O | title = 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 | journal = DNA Research | volume = 7 | issue = 1 | pages = 65–73 | date = February 2000 | pmid = 10718198 | doi = 10.1093/dnares/7.1.65 | doi-access = free }}
*{{cite journal | author=Yu W, Andersson B, Worley KC, ''et al.'' |title=Large-scale concatenation cDNA sequencing. |journal=Genome Res. |volume=7 |issue= 4 |pages= 353–8 |year= 1997 |pmid= 9110174 |doi= }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–13 | date = April 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–8 | date = April 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
*{{cite journal | author=Clark HF, Gurney AL, Abaya E, ''et al.'' |title=The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. |journal=Genome Res. |volume=13 |issue= 10 |pages= 2265–70 |year= 2003 |pmid= 12975309 |doi= 10.1101/gr.1293003 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{cite journal | vauthors = Lehner B, Sanderson CM | title = A protein interaction framework for human mRNA degradation | journal = Genome Research | volume = 14 | issue = 7 | pages = 1315–23 | date = July 2004 | pmid = 15231747 | pmc = 442147 | doi = 10.1101/gr.2122004 }}
* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}
*{{cite journal | author=Kubota K, Kim JY, Sawada A, ''et al.'' |title=LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins. |journal=FEBS Lett. |volume=564 |issue= 1-2 |pages= 147–52 |year= 2004 |pmid= 15094057 |doi= 10.1016/S0014-5793(04)00332-1 }}
*{{cite journal | author=Lehner B, Sanderson CM |title=A protein interaction framework for human mRNA degradation. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1315–23 |year= 2004 |pmid= 15231747 |doi= 10.1101/gr.2122004 }}
* {{cite journal | vauthors = Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, Ozono K, Hara J | title = LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins | journal = FEBS Letters | volume = 564 | issue = 1–2 | pages = 147–52 | date = April 2004 | pmid = 15094057 | doi = 10.1016/S0014-5793(04)00332-1 | doi-access = free }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Smits G, Kajava AV | title = LRRC8 extracellular domain is composed of 17 leucine-rich repeats | journal = Molecular Immunology | volume = 41 | issue = 5 | pages = 561–2 | date = July 2004 | pmid = 15183935 | doi = 10.1016/j.molimm.2004.04.001 }}
* {{cite journal | vauthors = 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 | title = Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries | journal = DNA Research | volume = 12 | issue = 2 | pages = 117–26 | year = 2007 | pmid = 16303743 | doi = 10.1093/dnares/12.2.117 | doi-access = free }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal | author=Gregory SG, Barlow KF, McLay KE, ''et al.'' |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = November 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
}}
{{refend}}
{{refend}}

[[Category:LRR proteins]]



{{gene-1-stub}}
{{gene-1-stub}}

Latest revision as of 02:12, 8 April 2022

LRRC8D
Identifiers
AliasesLRRC8D, LRRC5, leucine-rich repeat containing 8 family member D, leucine rich repeat containing 8 family member D, leucine rich repeat containing 8 VRAC subunit D, HsLRRC8D
External IDsOMIM: 612890; MGI: 1922368; HomoloGene: 10004; GeneCards: LRRC8D; OMA:LRRC8D - orthologs
Orthologs
SpeciesHumanMouse
Entrez

55144

231549

Ensembl

ENSG00000171492

ENSMUSG00000046079

UniProt

Q7L1W4

Q8BGR2

RefSeq (mRNA)

NM_001134479
NM_018103

NM_001122768
NM_178701

RefSeq (protein)

NP_001127951
NP_060573

NP_001116240
NP_848816

Location (UCSC)Chr 1: 89.82 – 89.94 MbChr 5: 105.85 – 105.98 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

While LRRC8D is one of many proteins that can be part of VRAC, it is in fact one of the most important subunits for the channel’s ability to function; the other protein of importance is LRRC8A.[8][9] However, while we know it is necessary for specific VRAC function, other studies have found that it is not sufficient for the full range of usual VRAC activity.[10] This is where the other LRRC8 proteins come in, as the different composition of these subunits affects the range of specificity for VRACs.[11][12]

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

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171492 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046079 – 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. Bibcode:2014Sci...344..634V. doi:10.1126/science.1252826. PMID 24790029. S2CID 24709412.
  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. S2CID 40565653.
  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". Physiological Reports. 4 (19): e12940. doi:10.14814/phy2.12940. PMC 5064130. PMID 27688432.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  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.

Further reading

[edit]


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