LRC8E_MOUSE
ID LRC8E_MOUSE Reviewed; 795 AA.
AC Q66JT1; E9QNV5;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8E {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8E {ECO:0000303|PubMed:32277911};
GN Name=Lrrc8e {ECO:0000303|PubMed:32277911, ECO:0000312|MGI:MGI:1919517};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=32277911; DOI=10.1016/j.immuni.2020.03.016;
RA Zhou C., Chen X., Planells-Cases R., Chu J., Wang L., Cao L., Li Z.,
RA Lopez-Cayuqueo K.I., Xie Y., Ye S., Wang X., Ullrich F., Ma S., Fang Y.,
RA Zhang X., Qian Z., Liang X., Cai S.Q., Jiang Z., Zhou D., Leng Q.,
RA Xiao T.S., Lan K., Yang J., Li H., Peng C., Qiu Z., Jentsch T.J., Xiao H.;
RT "Transfer of cgamp into bystander cells via LRRC8 volume-regulated anion
RT channels augments STING-mediated interferon responses and anti-viral
RT immunity.";
RL Immunity 52:767-781(2020).
CC -!- FUNCTION: Non-essential component of the volume-regulated anion channel
CC (VRAC, also named VSOAC channel), an anion channel required to maintain
CC a constant cell volume in response to extracellular or intracellular
CC osmotic changes (By similarity). The VRAC channel conducts iodide
CC better than chloride and can also conduct organic osmolytes like
CC taurine (By similarity). Mediates efflux of amino acids, such as
CC aspartate, in response to osmotic stress (By similarity). The VRAC
CC channel also mediates transport of immunoreactive cyclic dinucleotide
CC GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA
CC virus in the cytosol (PubMed:32277911). Channel activity requires
CC LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or
CC LRRC8E); channel characteristics depend on the precise subunit
CC composition (By similarity). Also plays a role in lysosome homeostasis
CC by forming functional lysosomal VRAC channels in response to low
CC cytoplasmic ionic strength condition: lysosomal VRAC channels are
CC necessary for the formation of large lysosome-derived vacuoles, which
CC store and then expel excess water to maintain cytosolic water
CC homeostasis (By similarity). {ECO:0000250|UniProtKB:Q6NSJ5,
CC ECO:0000269|PubMed:32277911}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q6NSJ5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000250|UniProtKB:Q6NSJ5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000250|UniProtKB:Q6NSJ5};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cGAMP(out) = 2',3'-cGAMP(in); Xref=Rhea:RHEA:66320,
CC ChEBI:CHEBI:143093; Evidence={ECO:0000305|PubMed:32277911};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66321;
CC Evidence={ECO:0000305|PubMed:32277911};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66322;
CC Evidence={ECO:0000305|PubMed:32277911};
CC -!- SUBUNIT: Heterohexamer. Oligomerizes with other LRRC8 proteins (LRRC8A,
CC LRRC8C, LRRC8D and/or LRRC8B) to form a heterohexamer. Detected in a
CC channel complex that contains LRRC8A, LRRC8C and LRRC8E. In vivo, the
CC subunit composition may depend primarily on expression levels, and
CC heterooligomeric channels containing various proportions of the
CC different LRRC8 proteins may coexist. {ECO:0000250|UniProtKB:Q6NSJ5}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6NSJ5};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q6NSJ5}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q6NSJ5}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q6NSJ5}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q6NSJ5}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q6NSJ5}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q6NSJ5}. Note=In the absence of LRRC8A, resides
CC primarily in the endoplasmic reticulum. Requires LRRC8A for
CC localization at the cell membrane or lysosome membrane.
CC {ECO:0000250|UniProtKB:Q6NSJ5}.
CC -!- DOMAIN: The volume-regulated anion channel (VRAC) channel forms a
CC trimer of dimers, with symmetry mismatch between the pore-forming
CC domain and the cytosolic LRR repeats, a topology similar to gap
CC junction proteins. {ECO:0000250|UniProtKB:Q8IWT6}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype in normal conditions
CC (PubMed:32277911). Impaired response to herpes simplex virus 1 (HSV-1)
CC infection, caused by decreased ability to transport 2'-3'-cGAMP
CC (PubMed:32277911). {ECO:0000269|PubMed:32277911}.
CC -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC123029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC080783; AAH80783.1; -; mRNA.
DR CCDS; CCDS22079.1; -.
DR RefSeq; NP_082451.2; NM_028175.2.
DR RefSeq; XP_006508969.1; XM_006508906.3.
DR RefSeq; XP_006508970.1; XM_006508907.3.
DR RefSeq; XP_011240388.1; XM_011242086.2.
DR AlphaFoldDB; Q66JT1; -.
DR SMR; Q66JT1; -.
DR STRING; 10090.ENSMUSP00000052055; -.
DR GlyGen; Q66JT1; 2 sites.
DR iPTMnet; Q66JT1; -.
DR PhosphoSitePlus; Q66JT1; -.
DR MaxQB; Q66JT1; -.
DR PaxDb; Q66JT1; -.
DR PeptideAtlas; Q66JT1; -.
DR PRIDE; Q66JT1; -.
DR ProteomicsDB; 290160; -.
DR Antibodypedia; 12282; 59 antibodies from 15 providers.
DR DNASU; 72267; -.
DR Ensembl; ENSMUST00000053035; ENSMUSP00000052055; ENSMUSG00000046589.
DR GeneID; 72267; -.
DR KEGG; mmu:72267; -.
DR UCSC; uc009kth.2; mouse.
DR CTD; 80131; -.
DR MGI; MGI:1919517; Lrrc8e.
DR VEuPathDB; HostDB:ENSMUSG00000046589; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159311; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q66JT1; -.
DR OMA; EYSFEQV; -.
DR OrthoDB; 192398at2759; -.
DR PhylomeDB; Q66JT1; -.
DR TreeFam; TF331443; -.
DR Reactome; R-MMU-5223345; Miscellaneous transport and binding events.
DR BioGRID-ORCS; 72267; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Lrrc8e; mouse.
DR PRO; PR:Q66JT1; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q66JT1; protein.
DR Bgee; ENSMUSG00000046589; Expressed in primary oocyte and 74 other tissues.
DR ExpressionAtlas; Q66JT1; baseline and differential.
DR Genevisible; Q66JT1; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0034702; C:ion channel complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005225; F:volume-sensitive anion channel activity; ISS:UniProtKB.
DR GO; GO:0098656; P:anion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015810; P:aspartate transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006884; P:cell volume homeostasis; ISS:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; ISS:UniProtKB.
DR GO; GO:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 2.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR021040; LRRC8_Pannexin-like.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 8.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Ion channel; Ion transport; Leucine-rich repeat; Lysosome; Membrane;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..795
FT /note="Volume-regulated anion channel subunit LRRC8E"
FT /id="PRO_0000076251"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..116
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..264
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..312
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..333
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 334..795
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 535..556
FT /note="LRR 1"
FT REPEAT 558..578
FT /note="LRR 2"
FT REPEAT 582..603
FT /note="LRR 3"
FT REPEAT 605..626
FT /note="LRR 4"
FT REPEAT 630..651
FT /note="LRR 5"
FT REPEAT 653..674
FT /note="LRR 6"
FT REPEAT 676..697
FT /note="LRR 7"
FT REPEAT 699..720
FT /note="LRR 8"
FT REPEAT 722..744
FT /note="LRR 9"
FT REPEAT 745..766
FT /note="LRR 10"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..300
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT CONFLICT 33
FT /note="V -> M (in Ref. 2; AAH80783)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="N -> D (in Ref. 2; AAH80783)"
FT /evidence="ECO:0000305"
FT CONFLICT 750
FT /note="E -> G (in Ref. 2; AAH80783)"
FT /evidence="ECO:0000305"
FT CONFLICT 776
FT /note="V -> A (in Ref. 2; AAH80783)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 795 AA; 90501 MW; CC78623A3FC75DB7 CRC64;
MIPVAEFKQF TEQQPAFKVL KPWWDVLAEY LTVAMLMIGV FGCTLQVTQD KIICLPSHES
RENISGAPCQ QLLPQGISEQ MGGLRELSGL KNNLDLQQYS FINQLCYETA LHWYAKYFPY
LVVIHTLIFM VCTSFWFKFP GTSSKIEHFI SILGKCFDSP WTTRALSEVS GENHKGPASG
RAMVTTVTTT GAGSGKVGEG EKEKVLIEPE KVVSEPPVVT LLDKKEGEQA KALFEKVKKF
RVHVEEGDIL YSMYIRQTVL KVCKFFAILV YNLIYVEKIS FLVACRVETS EITGYASFCC
NHTKAHLFSK LAFCYISFVC VYGITCLYTL YWLFHRPLKE YSFRSVREET GMNDIPDVKN
DFAFMLHLID QYDSLYSKRF AVFLSEVSES RLKQLNLNHE WTPEKLRQKL QRNMRGRLEL
SLCMLPGLPD TVFELSEVEA LRLEAICDIS FPPGLSQLVN LQELSLLHSP ARLPFSSQIF
LRDRLKVICV KFEELREVPL WVFGLRGLEE LHLEGLFPPE MARGATLESL RELKQLKVLS
LRSNAGKVPA SVTDVAGHLQ RLSLHNDGAR LLALNSLKKL AVLRELELVA CGLERIPHAI
FSLGALQELD LKDNHLRSIE EILSFQHCRK LVTLRLWHNQ IAYVPEHVRK LRSLEQLYLS
HNKLETLPTQ LGQCFGLRLL DLSHNGLRSL PPELGLLQSL QHLALSYNAL ESLPDELFFC
HKLRTLLLGY NHLTQLSPDV AALQALSRLE LKGNRLETLP EELGDCKGLK KSGLLVEDTL
YEGLPAEVRE KMEEE
