ID LRC8B_HUMAN Reviewed; 803 AA.
AC Q6P9F7; D3DT28; Q6UY21; Q8N106; Q92627;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 2.
DT 27-MAR-2024, entry version 167.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8B {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8B {ECO:0000303|PubMed:22532330};
DE AltName: Full=T-cell activation leucine repeat-rich protein {ECO:0000303|Ref.1};
DE Short=TA-LRRP {ECO:0000303|Ref.1};
GN Name=LRRC8B {ECO:0000303|PubMed:22532330, ECO:0000312|HGNC:HGNC:30692};
GN Synonyms=KIAA0231 {ECO:0000303|PubMed:9039502};
GN ORFNames=UNQ6413/PRO21207 {ECO:0000303|PubMed:12975309};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Mao M., Biery M.C., Kobayashi S.V., Schimmack G.A., Ward T.R.,
RA Schelter J.M., Burchard J., He Y.D., Dai H., Leonardson A., Coffey E.,
RA Stoughton R., Linsley P.S.;
RT "T lymphocyte activation gene discovery using ink-jet microarrays.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-419.
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION.
RX PubMed=22532330; DOI=10.1002/bies.201100173;
RA Abascal F., Zardoya R.;
RT "LRRC8 proteins share a common ancestor with pannexins, and may form
RT hexameric channels involved in cell-cell communication.";
RL Bioessays 34:551-560(2012).
RN [7]
RP FUNCTION, TRANSPORTER ACTIVITY, INTERACTION WITH LRRC8A, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24790029; DOI=10.1126/science.1252826;
RA Voss F.K., Ullrich F., Muench J., Lazarow K., Lutter D., Mah N.,
RA Andrade-Navarro M.A., von Kries J.P., Stauber T., Jentsch T.J.;
RT "Identification of LRRC8 heteromers as an essential component of the
RT volume-regulated anion channel VRAC.";
RL Science 344:634-638(2014).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=26824658; DOI=10.1016/j.cell.2015.12.031;
RA Syeda R., Qiu Z., Dubin A.E., Murthy S.E., Florendo M.N., Mason D.E.,
RA Mathur J., Cahalan S.M., Peters E.C., Montal M., Patapoutian A.;
RT "LRRC8 proteins form volume-regulated anion channels that sense ionic
RT strength.";
RL Cell 164:499-511(2016).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=28193731; DOI=10.1242/jcs.196253;
RA Lutter D., Ullrich F., Lueck J.C., Kempa S., Jentsch T.J.;
RT "Selective transport of neurotransmitters and modulators by distinct
RT volume-regulated LRRC8 anion channels.";
RL J. Cell Sci. 130:1122-1133(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:24790029, PubMed:26824658, PubMed:28193731).
CC The VRAC channel conducts iodide better than chloride and can also
CC conduct organic osmolytes like taurine. 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 (PubMed:24790029, PubMed:26824658, PubMed:28193731).
CC {ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26824658,
CC ECO:0000269|PubMed:28193731}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000305|PubMed:24790029};
CC -!- SUBUNIT: Heterohexamer (Probable). Oligomerizes with other LRRC8
CC proteins (LRRC8A, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer
CC (PubMed:24790029, PubMed:26824658, PubMed:28193731). 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 (Probable).
CC {ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26824658,
CC ECO:0000269|PubMed:28193731, ECO:0000305}.
CC -!- INTERACTION:
CC Q6P9F7; Q8IWT6: LRRC8A; NbExp=3; IntAct=EBI-9477617, EBI-10970086;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24790029,
CC ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731}; Multi-pass
CC membrane protein {ECO:0000305}. Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:24790029}. Note=In the absence of LRRC8A, resides
CC primarily in a cytoplasmic compartment, probably the endoplasmic
CC reticulum. Requires LRRC8A for expression at the cell membrane.
CC {ECO:0000269|PubMed:24790029}.
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=BAA13220.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF385436; AAM43837.1; -; mRNA.
DR EMBL; D86984; BAA13220.2; ALT_INIT; mRNA.
DR EMBL; AY358112; AAQ88479.1; -; mRNA.
DR EMBL; CH471097; EAW73137.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73138.1; -; Genomic_DNA.
DR EMBL; BC030607; AAH30607.1; -; mRNA.
DR EMBL; BC060782; AAH60782.1; -; mRNA.
DR CCDS; CCDS724.1; -.
DR RefSeq; NP_001127948.1; NM_001134476.1.
DR RefSeq; NP_056165.1; NM_015350.2.
DR RefSeq; XP_005270758.1; XM_005270701.4.
DR RefSeq; XP_005270759.1; XM_005270702.4.
DR RefSeq; XP_005270760.1; XM_005270703.4.
DR RefSeq; XP_011539445.1; XM_011541143.2.
DR RefSeq; XP_011539446.1; XM_011541144.2.
DR RefSeq; XP_011539447.1; XM_011541145.2.
DR RefSeq; XP_011539448.1; XM_011541146.2.
DR RefSeq; XP_016856372.1; XM_017000883.1.
DR RefSeq; XP_016856373.1; XM_017000884.1.
DR RefSeq; XP_016856374.1; XM_017000885.1.
DR AlphaFoldDB; Q6P9F7; -.
DR SMR; Q6P9F7; -.
DR BioGRID; 117054; 34.
DR CORUM; Q6P9F7; -.
DR DIP; DIP-61361N; -.
DR IntAct; Q6P9F7; 21.
DR STRING; 9606.ENSP00000491377; -.
DR TCDB; 1.A.25.3.1; the gap junction-forming innexin (innexin) family.
DR GlyCosmos; Q6P9F7; 1 site, No reported glycans.
DR GlyGen; Q6P9F7; 2 sites.
DR iPTMnet; Q6P9F7; -.
DR PhosphoSitePlus; Q6P9F7; -.
DR BioMuta; LRRC8B; -.
DR DMDM; 88911355; -.
DR EPD; Q6P9F7; -.
DR jPOST; Q6P9F7; -.
DR MassIVE; Q6P9F7; -.
DR MaxQB; Q6P9F7; -.
DR PaxDb; 9606-ENSP00000332674; -.
DR PeptideAtlas; Q6P9F7; -.
DR ProteomicsDB; 67042; -.
DR Antibodypedia; 19852; 138 antibodies from 15 providers.
DR DNASU; 23507; -.
DR Ensembl; ENST00000330947.7; ENSP00000332674.2; ENSG00000197147.15.
DR Ensembl; ENST00000639264.1; ENSP00000492151.1; ENSG00000197147.15.
DR Ensembl; ENST00000640258.1; ENSP00000491377.1; ENSG00000197147.15.
DR GeneID; 23507; -.
DR KEGG; hsa:23507; -.
DR MANE-Select; ENST00000330947.7; ENSP00000332674.2; NM_001369817.2; NP_001356746.1.
DR UCSC; uc057ieo.1; human.
DR AGR; HGNC:30692; -.
DR CTD; 23507; -.
DR GeneCards; LRRC8B; -.
DR HGNC; HGNC:30692; LRRC8B.
DR HPA; ENSG00000197147; Tissue enhanced (brain).
DR MIM; 612888; gene.
DR neXtProt; NX_Q6P9F7; -.
DR OpenTargets; ENSG00000197147; -.
DR PharmGKB; PA142671535; -.
DR VEuPathDB; HostDB:ENSG00000197147; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000160703; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q6P9F7; -.
DR OMA; CYERELH; -.
DR OrthoDB; 55205at2759; -.
DR PhylomeDB; Q6P9F7; -.
DR TreeFam; TF331443; -.
DR PathwayCommons; Q6P9F7; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; Q6P9F7; -.
DR BioGRID-ORCS; 23507; 9 hits in 1153 CRISPR screens.
DR ChiTaRS; LRRC8B; human.
DR GenomeRNAi; 23507; -.
DR Pharos; Q6P9F7; Tbio.
DR PRO; PR:Q6P9F7; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6P9F7; Protein.
DR Bgee; ENSG00000197147; Expressed in Brodmann (1909) area 23 and 178 other cell types or tissues.
DR ExpressionAtlas; Q6P9F7; baseline and differential.
DR Genevisible; Q6P9F7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034702; C:monoatomic ion channel complex; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098656; P:monoatomic anion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 3.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR021040; LRRC8_Pannexin-like.
DR PANTHER; PTHR48051; -; 1.
DR PANTHER; PTHR48051:SF36; LEUCINE RICH REPEAT CONTAINING 8 VRAC SUBUNIT B; 1.
DR Pfam; PF13306; LRR_5; 2.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 8.
DR SUPFAM; SSF52047; RNI-like; 1.
DR PROSITE; PS51450; LRR; 9.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Ion channel; Ion transport; Leucine-rich repeat; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..803
FT /note="Volume-regulated anion channel subunit LRRC8B"
FT /id="PRO_0000076245"
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 464..486
FT /note="LRR 1"
FT REPEAT 488..509
FT /note="LRR 2"
FT REPEAT 511..532
FT /note="LRR 3"
FT REPEAT 539..559
FT /note="LRR 4"
FT REPEAT 562..582
FT /note="LRR 5"
FT REPEAT 586..607
FT /note="LRR 6"
FT REPEAT 609..630
FT /note="LRR 7"
FT REPEAT 634..655
FT /note="LRR 8"
FT REPEAT 657..678
FT /note="LRR 9"
FT REPEAT 680..701
FT /note="LRR 10"
FT REPEAT 703..724
FT /note="LRR 11"
FT REPEAT 726..747
FT /note="LRR 12"
FT REPEAT 749..771
FT /note="LRR 13"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DU41"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5DU41"
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 VARIANT 288
FT /note="D -> N (in dbSNP:rs17131746)"
FT /id="VAR_051126"
FT VARIANT 419
FT /note="Q -> K (in dbSNP:rs17855025)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025275"
FT VARIANT 469
FT /note="R -> H (in dbSNP:rs3795832)"
FT /id="VAR_051127"
FT VARIANT 689
FT /note="N -> S (in dbSNP:rs12747447)"
FT /id="VAR_051128"
FT CONFLICT 225
FT /note="V -> G (in Ref. 3; AAQ88479)"
FT /evidence="ECO:0000305"
FT CONFLICT 626
FT /note="Missing (in Ref. 3; AAQ88479)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 803 AA; 92390 MW; 9006CE628F427EB9 CRC64;
MITLTELKCL ADAQSSYHIL KPWWDVFWYY ITLIMLLVAV LAGALQLTQS RVLCCLPCKV
EFDNHCAVPW DILKASMNTS SNPGTPLPLP LRIQNDLHRQ QYSYIDAVCY EKQLHWFAKF
FPYLVLLHTL IFAACSNFWL HYPSTSSRLE HFVAILHKCF DSPWTTRALS ETVAEQSVRP
LKLSKSKILL SSSGCSADID SGKQSLPYPQ PGLESAGIES PTSSVLDKKE GEQAKAIFEK
VKRFRMHVEQ KDIIYRVYLK QIIVKVILFV LIITYVPYFL THITLEIDCS VDVQAFTGYK
RYQCVYSLAE IFKVLASFYV ILVILYGLTS SYSLWWMLRS SLKQYSFEAL REKSNYSDIP
DVKNDFAFIL HLADQYDPLY SKRFSIFLSE VSENKLKQIN LNNEWTVEKL KSKLVKNAQD
KIELHLFMLN GLPDNVFELT EMEVLSLELI PEVKLPSAVS QLVNLKELRV YHSSLVVDHP
ALAFLEENLK ILRLKFTEMG KIPRWVFHLK NLKELYLSGC VLPEQLSTMQ LEGFQDLKNL
RTLYLKSSLS RIPQVVTDLL PSLQKLSLDN EGSKLVVLNN LKKMVNLKSL ELISCDLERI
PHSIFSLNNL HELDLRENNL KTVEEIISFQ HLQNLSCLKL WHNNIAYIPA QIGALSNLEQ
LSLDHNNIEN LPLQLFLCTK LHYLDLSYNH LTFIPEEIQY LSNLQYFAVT NNNIEMLPDG
LFQCKKLQCL LLGKNSLMNL SPHVGELSNL THLELIGNYL ETLPPELEGC QSLKRNCLIV
EENLLNTLPL PVTERLQTCL DKC
//
