LRC8B_MOUSE
ID LRC8B_MOUSE Reviewed; 803 AA.
AC Q5DU41; B2RSI6;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8B {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8B {ECO:0000303|PubMed:24782309};
GN Name=Lrrc8b {ECO:0000303|PubMed:24782309, ECO:0000312|MGI:MGI:2141353};
GN Synonyms=Kiaa0231 {ECO:0000303|Ref.1};
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 MRNA] (ISOFORM 2).
RC TISSUE=Fetal brain;
RA Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene. The
RT complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by
RT screening of terminal sequences of cDNA clones randomly sampled from size-
RT fractionated libraries.";
RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND SER-196, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUBUNIT, AND INTERACTION WITH LRRC8A; LRRC8C AND LRRC8D.
RX PubMed=24782309; DOI=10.1074/jbc.m114.571257;
RA Lee C.C., Freinkman E., Sabatini D.M., Ploegh H.L.;
RT "The protein synthesis inhibitor blasticidin S enters mammalian cells via
RT leucine-rich repeat-containing protein 8D.";
RL J. Biol. Chem. 289:17124-17131(2014).
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. Channel activity
CC requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C,
CC LRRC8D or LRRC8E); channel characteristics depend on the precise
CC subunit composition. {ECO:0000250|UniProtKB:Q6P9F7}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q6P9F7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000250|UniProtKB:Q6P9F7};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000250|UniProtKB:Q6P9F7};
CC -!- SUBUNIT: Heterohexamer. Oligomerizes with other LRRC8 proteins (LRRC8A,
CC LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer
CC (PubMed:24782309). In vivo, the subunit composition may depend
CC primarily on expression levels, and heterooligomeric channels
CC containing various proportions of the different LRRC8 proteins may
CC coexist (Probable). {ECO:0000269|PubMed:24782309, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6P9F7};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q6P9F7}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q6P9F7}. Note=In the absence
CC of LRRC8A, resides primarily in a cytoplasmic compartment, probably the
CC endoplasmic reticulum. Requires LRRC8A for expression at the cell
CC membrane. {ECO:0000250|UniProtKB:Q6P9F7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5DU41-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5DU41-2; Sequence=VSP_055395;
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD90398.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK220329; BAD90398.1; ALT_INIT; mRNA.
DR EMBL; AC113980; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466529; EDL20199.1; -; Genomic_DNA.
DR EMBL; BC138877; AAI38878.1; -; mRNA.
DR EMBL; BC138878; AAI38879.1; -; mRNA.
DR CCDS; CCDS39193.1; -. [Q5DU41-1]
DR RefSeq; NP_001028722.1; NM_001033550.2. [Q5DU41-1]
DR RefSeq; XP_011247810.1; XM_011249508.2. [Q5DU41-1]
DR AlphaFoldDB; Q5DU41; -.
DR SMR; Q5DU41; -.
DR BioGRID; 241505; 2.
DR IntAct; Q5DU41; 1.
DR MINT; Q5DU41; -.
DR STRING; 10090.ENSMUSP00000108327; -.
DR GlyGen; Q5DU41; 1 site.
DR iPTMnet; Q5DU41; -.
DR PhosphoSitePlus; Q5DU41; -.
DR SwissPalm; Q5DU41; -.
DR EPD; Q5DU41; -.
DR MaxQB; Q5DU41; -.
DR PaxDb; Q5DU41; -.
DR PeptideAtlas; Q5DU41; -.
DR PRIDE; Q5DU41; -.
DR ProteomicsDB; 252513; -. [Q5DU41-1]
DR ProteomicsDB; 252514; -. [Q5DU41-2]
DR Antibodypedia; 19852; 123 antibodies from 15 providers.
DR DNASU; 433926; -.
DR Ensembl; ENSMUST00000112707; ENSMUSP00000108327; ENSMUSG00000070639. [Q5DU41-1]
DR GeneID; 433926; -.
DR KEGG; mmu:433926; -.
DR UCSC; uc008yle.1; mouse. [Q5DU41-1]
DR CTD; 23507; -.
DR MGI; MGI:2141353; Lrrc8b.
DR VEuPathDB; HostDB:ENSMUSG00000070639; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160703; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q5DU41; -.
DR OMA; DHHNSIY; -.
DR OrthoDB; 298712at2759; -.
DR PhylomeDB; Q5DU41; -.
DR TreeFam; TF331443; -.
DR Reactome; R-MMU-5223345; Miscellaneous transport and binding events.
DR BioGRID-ORCS; 433926; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Lrrc8b; mouse.
DR PRO; PR:Q5DU41; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q5DU41; protein.
DR Bgee; ENSMUSG00000070639; Expressed in dorsal pancreas and 213 other tissues.
DR Genevisible; Q5DU41; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; ISO:MGI.
DR GO; GO:0005225; F:volume-sensitive anion channel activity; ISO:MGI.
DR GO; GO:0098656; P:anion transmembrane transport; ISS: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; 2.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 10.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Ion channel; Ion transport; Leucine-rich repeat; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..803
FT /note="Volume-regulated anion channel subunit LRRC8B"
FT /id="PRO_0000076246"
FT TOPO_DOM 1..25
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 47..119
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 141..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..307
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..803
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 415..439
FT /note="LRR 1"
FT REPEAT 440..462
FT /note="LRR 2"
FT REPEAT 464..486
FT /note="LRR 3"
FT REPEAT 488..509
FT /note="LRR 4"
FT REPEAT 511..532
FT /note="LRR 5"
FT REPEAT 539..559
FT /note="LRR 6"
FT REPEAT 562..582
FT /note="LRR 7"
FT REPEAT 586..607
FT /note="LRR 8"
FT REPEAT 609..630
FT /note="LRR 9"
FT REPEAT 634..655
FT /note="LRR 10"
FT REPEAT 657..678
FT /note="LRR 11"
FT REPEAT 680..701
FT /note="LRR 12"
FT REPEAT 703..724
FT /note="LRR 13"
FT REPEAT 726..747
FT /note="LRR 14"
FT REPEAT 749..771
FT /note="LRR 15"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 55..304
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT DISULFID 109..289
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT VAR_SEQ 169..180
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_055395"
SQ SEQUENCE 803 AA; 92186 MW; 5E6E4DE4A5136613 CRC64;
MITLTELKCL ADAQSSYHIL KPWWDVFWYY ITLIMLLVAV LAGALQLTQS RVLCCLPCKV
EFDNQCAVPW DLLKGSENAS SNSGLLLPLP LRIQNDLHRQ QYSYIDAVCY EKQLHWFAKF
FPYLVLLHTL IFAACSNFWL HYPSTSSRLE HFVSILHKCF DSPWTTRALS ETVAEQSVRP
LKLSKSKTLL STSGGSADID ASKQSLPYPQ PGLESPGIES PTSSVLDKKE GEQAKAIFEK
VKRFRLHVEQ RDIIYRVYLK QIIVKVILFV LIITYVPYFL SYITLEIDCS IDVQAFTGYK
RYQCVYSLAE IFKVLASFYV ILVMLYGLTS SYSLWWMLRS SLKQYSFEAL REKSNYSDIP
DVKNDFAFIL HLADQYDPLY SKRFSIFLSE VSENKLKQIN LNNEWTVERL KSKLVKNSQD
KVELHLFMLN GLPDNVFELT EMEVLSLELI PEVKLPAAVA QLVNLRELHV YHSSLVVDHP
ALAFLEENLR ILRLKFTEMG KIPRWVFHLK NLKELYLSGC VLPEQLSSLH LEGFQDLKNL
RTLYLKSSLS RIPQVVTDLL PSLQKLSLDN EGSKLVVLNN LKKMVNLKSL ELLSCDLERI
PHSIFSLNNL HELDLKENNL KTVEEIISFQ HLPSLSCLKL WHNNIAYIPA QIGALSNLEQ
LFLGHNNIES LPLQLFLCTK LHYLDLSYNH LTFIPEEIQY LTNLQYFAVT NNNIEMLPDG
LFQCKKLQCL LLGRNSLTDL SPLVGELSNL THLELTGNYL ETLPVELEGC QSLKRSCLIV
EDSLLNSLPL PVAERLQTCL DKC
