LRC8E_RAT
ID LRC8E_RAT Reviewed; 795 AA.
AC Q3KRC6;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8E {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8E {ECO:0000303|PubMed:28833202};
GN Name=Lrrc8e {ECO:0000303|PubMed:28833202, ECO:0000312|RGD:1311979};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=28833202; DOI=10.1113/jp275053;
RA Schober A.L., Wilson C.S., Mongin A.A.;
RT "Molecular composition and heterogeneity of the LRRC8-containing swelling-
RT activated osmolyte channels in primary rat astrocytes.";
RL J. Physiol. (Lond.) 595:6939-6951(2017).
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 (PubMed:28833202). 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 (By similarity). Channel activity requires LRRC8A
CC plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or
CC LRRC8E); channel characteristics depend on the precise subunit
CC composition (PubMed:28833202). Also plays a role in lysosome
CC homeostasis by forming functional lysosomal VRAC channels in response
CC to low cytoplasmic ionic strength condition: lysosomal VRAC channels
CC are necessary for the formation of large lysosome-derived vacuoles,
CC which store and then expel excess water to maintain cytosolic water
CC homeostasis (By similarity). {ECO:0000250|UniProtKB:Q6NSJ5,
CC ECO:0000269|PubMed:28833202}.
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 (Probable). Oligomerizes with other LRRC8
CC proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8B) to form a heterohexamer
CC (PubMed:28833202). Detected in a channel complex that contains LRRC8A,
CC LRRC8C and LRRC8E (By similarity). In vivo, the subunit composition may
CC depend primarily on expression levels, and heterooligomeric channels
CC containing various proportions of the different LRRC8 proteins may
CC coexist (Probable). {ECO:0000250|UniProtKB:Q6NSJ5,
CC ECO:0000269|PubMed:28833202, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28833202};
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; BC105779; AAI05780.1; -; mRNA.
DR RefSeq; NP_001029311.1; NM_001034139.1.
DR RefSeq; XP_006248825.1; XM_006248763.3.
DR RefSeq; XP_006248826.1; XM_006248764.3.
DR RefSeq; XP_008767176.1; XM_008768954.1.
DR AlphaFoldDB; Q3KRC6; -.
DR SMR; Q3KRC6; -.
DR BioGRID; 257792; 1.
DR STRING; 10116.ENSRNOP00000037487; -.
DR GlyGen; Q3KRC6; 2 sites.
DR PhosphoSitePlus; Q3KRC6; -.
DR PaxDb; Q3KRC6; -.
DR PRIDE; Q3KRC6; -.
DR Ensembl; ENSRNOT00000035142; ENSRNOP00000037487; ENSRNOG00000028460.
DR GeneID; 304203; -.
DR KEGG; rno:304203; -.
DR UCSC; RGD:1311979; rat.
DR CTD; 80131; -.
DR RGD; 1311979; Lrrc8e.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159311; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q3KRC6; -.
DR OMA; EYSFEQV; -.
DR OrthoDB; 192398at2759; -.
DR PhylomeDB; Q3KRC6; -.
DR TreeFam; TF331443; -.
DR Reactome; R-RNO-5223345; Miscellaneous transport and binding events.
DR PRO; PR:Q3KRC6; -.
DR Proteomes; UP000002494; Chromosome 12.
DR Bgee; ENSRNOG00000028460; Expressed in stomach and 10 other tissues.
DR Genevisible; Q3KRC6; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
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; -; 3.
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; 2.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 6.
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_0000076252"
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..743
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"
SQ SEQUENCE 795 AA; 90445 MW; 17F6795B243632DC CRC64;
MIPVAEFKQF TEQQPAFKVL KPWWDVLAEY LTVAMLMIGV FGCTLQVTQD KIICLPSHES
RENSSEAPCQ QLLPQGISEQ IGGLRELSGL KNNLDLQQYS FINQLCYETA LHWYAKYFPY
LVVIHTLIFM VCTSFWFKFP GTSSKIEHFI SILGKCFDSP WTTRALSEVS GENHKGPAAG
RATVTTVTTV GTGTGKVGEG EKEKVLIEPE KVVTEPPAVT LLDKKEGEQA KALFEKVKKF
RVHVEEGDIL YSMYIRQTVL KVCKFFAILV YNLVYVEKIS FLVACRVETS EITGYASFCC
NHTKAHLFSK LAFCYISFVC VYGITCLYTL YWLFHRPLKE YSFRSVREET GMNDIPDVRN
DFAFMLHLID QYDSLYSKRF AVFLSEVSES RLKQLNLNHE WTPDKLRQKL QRNARGRLEL
SLCMLPGLPD TVFELSEVEA LRLEAICDIS FPPGLSQLVN LQELSLLHSP ARLPFSSQIF
LRDRLKVICV KFEELREVPL WVFGLRGLEE LHLEGLFPPE MARGATLESL RELKQLKVLS
LRSNAGKVPA SVTDVAGHLQ RLSLHNDGAR LLALNSLKKL AVLRELELVA CGLERIPHAI
FSLGALQELD LKDNHLRSIE EILSFQHCRK LVILRLWHNQ IAYVPEHVRK LRSLEQLYLS
HNKLETLPAQ LGQCFGLRLL DVSHNGLRSL PPELGLLQSL QHLALSYNAL ESLPDELFFC
HKLRTLLLGY NHLTQFSPHV AALQALSRLE LKGNRLEALP EELGDCKGLK KSGLLVEDTL
YEGLPAEVRE KMEEE
