LRC8E_XENTR
ID LRC8E_XENTR Reviewed; 806 AA.
AC Q68F79; Q28BV4;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8E {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8E {ECO:0000250|UniProtKB:Q6NSJ5};
GN Name=lrrc8e {ECO:0000250|UniProtKB:Q6NSJ5};
GN ORFNames=TNeu081m12.1 {ECO:0000303|Ref.1};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Neurula;
RG Sanger Xenopus tropicalis EST/cDNA project;
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
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. The VRAC channel conducts iodide better than chloride
CC and can also conduct organic osmolytes like taurine. Mediates efflux of
CC amino acids, such as aspartate, in response to osmotic stress. 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. Channel activity requires lrrc8a plus at least
CC one other family member (lrrc8b, lrrc8c, lrrc8d or lrrc8e); channel
CC characteristics depend on the precise subunit composition. Also plays a
CC role in lysosome homeostasis by forming functional lysosomal VRAC
CC channels in response to low cytoplasmic ionic strength condition:
CC lysosomal VRAC channels are necessary for the formation of large
CC lysosome-derived vacuoles, which store and then expel excess water to
CC maintain cytosolic water homeostasis. {ECO:0000250|UniProtKB:Q6NSJ5}.
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:0000250|UniProtKB:Q6NSJ5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66321;
CC Evidence={ECO:0000250|UniProtKB:Q6NSJ5};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66322;
CC Evidence={ECO:0000250|UniProtKB:Q6NSJ5};
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 -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
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DR EMBL; CR942616; CAJ82818.1; -; mRNA.
DR EMBL; BC079964; AAH79964.1; -; mRNA.
DR RefSeq; NP_001007863.1; NM_001007862.1.
DR RefSeq; XP_012808517.1; XM_012953063.2.
DR AlphaFoldDB; Q68F79; -.
DR SMR; Q68F79; -.
DR STRING; 8364.ENSXETP00000049449; -.
DR PaxDb; Q68F79; -.
DR DNASU; 493249; -.
DR Ensembl; ENSXETT00000049449; ENSXETP00000049449; ENSXETG00000022859.
DR GeneID; 493249; -.
DR KEGG; xtr:493249; -.
DR CTD; 80131; -.
DR Xenbase; XB-GENE-6041092; lrrc8e.
DR eggNOG; KOG0619; Eukaryota.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q68F79; -.
DR OMA; TGCELER; -.
DR OrthoDB; 192398at2759; -.
DR PhylomeDB; Q68F79; -.
DR TreeFam; TF331443; -.
DR Reactome; R-XTR-5223345; Miscellaneous transport and binding events.
DR Proteomes; UP000008143; Chromosome 3.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000022859; Expressed in gastrula and 11 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
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; 3.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 6.
DR PROSITE; PS51450; LRR; 7.
PE 2: Evidence at transcript 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..806
FT /note="Volume-regulated anion channel subunit LRRC8E"
FT /id="PRO_0000076254"
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..130
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 131..151
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 152..275
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 276..296
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 297..323
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 324..344
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 345..806
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 544..566
FT /note="LRR 1"
FT REPEAT 569..589
FT /note="LRR 2"
FT REPEAT 593..614
FT /note="LRR 3"
FT REPEAT 616..637
FT /note="LRR 4"
FT REPEAT 641..662
FT /note="LRR 5"
FT REPEAT 664..685
FT /note="LRR 6"
FT REPEAT 687..708
FT /note="LRR 7"
FT REPEAT 710..731
FT /note="LRR 8"
FT REPEAT 733..754
FT /note="LRR 9"
FT REPEAT 756..777
FT /note="LRR 10"
FT REGION 72..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..213
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 72..90
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..206
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 57
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..311
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
SQ SEQUENCE 806 AA; 92205 MW; 0E4736D9BE6F6123 CRC64;
MIPVAEFKQF TEQQPAFKVL KPWWDVLAEY ITYAMLMIGV FGCTLQVTQD KIICLPNHTS
ADVVSQITCQ EYDQQSPPSN DSDLETTIPP PTATSSPPRE MSGLRNNLDL QQYSFINQMC
YETALHWYAK YFPYLVVIHT LIFIICGNFW FKFPGTSSKI EHFISILGKC FDSPWTTRAL
SEVSGESSQE KPSQERSIDR ELSKPNFEEG SPATADLPIA EKLVAETSSA SVLDKKEGEQ
AKALFEKVKK FRHHVEEGDL LYSMYMRQTV LKVCKFVLIT IYNAVLVGKI HFIVPCSVHT
EDMTGYNSFC CNHTKAHLFS KLAITYLCFL GVYGLTCLYT LYWLFRRPLK EYSFRSVREE
TGIGDIPDVK NDFAFVLHLV DQYDSLYSKR FAVFLSEVSE SRLRQLNLNH EWPADKLRQK
LQHTPEGRLE LHLFKLPGLP DTVFEVAEME SLKLEMVNEA LIPPLVSKLV RLEELSLINC
TAKVQHASLA YLRDHLRILQ VKFDDIKEIP LWIFSLRALE ELHLFGWLSQ DLSKNPALES
LRELKSLKVL TIKSNLSKIP ATVADVAGHL QKFSIHNDGT KLLTLNALKR LALVKELELV
RCELERIPHA VFSLTNLQVL DLKENTLHTI EEIISLQHCR KLSVLRLWHN QIAYIPEHIR
KLKGLEELSL NRNKILVIPS QLFLCNKLRH LDLSNNEIRE LPPEIGVLQL LQYLGLSGNF
LEDLPNELFF CQKLKTLKLG QNRLGNLSPK VGSLVCLVKL ELKGNRMDTL PPELGNCVSL
KRSGLTVEPS LFETLPVEVR DKLKED
