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Protein

Volume-regulated anion channel subunit LRRC8A

Gene

Lrrc8a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). Required for channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition. Can form functional channels by itself (in vitro) (By similarity). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746, PubMed:24752297). Also required for T-cell development (PubMed:24752297).By similarity3 Publications

GO - Molecular functioni

  • identical protein binding Source: MGI
  • volume-sensitive anion channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processDifferentiation, Ion transport, Transport

Enzyme and pathway databases

ReactomeiR-MMU-5223345 Miscellaneous transport and binding events

Names & Taxonomyi

Protein namesi
Recommended name:
Volume-regulated anion channel subunit LRRC8A
Alternative name(s):
Leucine-rich repeat-containing protein 8A
Gene namesi
Name:Lrrc8a
Synonyms:Lrrc8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2652847 Lrrc8a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22Cytoplasmic1 PublicationAdd BLAST22
Transmembranei23 – 45Helical1 PublicationAdd BLAST23
Topological domaini46 – 123Extracellular1 PublicationAdd BLAST78
Transmembranei124 – 146Helical1 PublicationAdd BLAST23
Topological domaini147 – 262Cytoplasmic1 PublicationAdd BLAST116
Transmembranei263 – 285Helical1 PublicationAdd BLAST23
Topological domaini286 – 319Extracellular1 PublicationAdd BLAST34
Transmembranei320 – 342Helical1 PublicationAdd BLAST23
Topological domaini343 – 810Cytoplasmic1 PublicationAdd BLAST468

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities. B-cell development is slightly impaired, without affecting B-cell function. Mice however show a cell-autonomous early block in thymocyte development and impairs peripheral T-cell expansion and function.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi103R → A: No effect on anion channel activity. Impairs channel selectivity, so that the channel is also permeable to Na(+) ions. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000845001 – 810Volume-regulated anion channel subunit LRRC8AAdd BLAST810

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Disulfide bondi54 ↔ 310Combined sources1 Publication
Disulfide bondi57 ↔ 65Combined sources1 Publication
Glycosylationi66N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi113 ↔ 295Combined sources1 Publication
Modified residuei200PhosphothreonineCombined sources1
Modified residuei202PhosphoserineCombined sources1
Modified residuei215PhosphothreonineBy similarity1
Modified residuei217PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ80WG5
PaxDbiQ80WG5
PeptideAtlasiQ80WG5
PRIDEiQ80WG5

PTM databases

iPTMnetiQ80WG5
PhosphoSitePlusiQ80WG5

Expressioni

Tissue specificityi

Ubiquitously expressed. High levels detected in the bone marrow; lower levels found in peripheral blood cells.4 Publications

Gene expression databases

BgeeiENSMUSG00000007476 Expressed in 290 organ(s), highest expression level in umbilical cord
GenevisibleiQ80WG5 MM

Interactioni

Subunit structurei

Hexamer (PubMed:29769723). Heterohexamer; oligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723). Can form homohexamers in vitro, but these have lower conductance than heterohexamers (PubMed:29769723). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable).By similarityCurated2 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092690

Structurei

Secondary structure

1810
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ80WG5
SMRiQ80WG5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati399 – 422LRR 1Sequence analysisAdd BLAST24
Repeati423 – 445LRR 2Sequence analysis1 PublicationAdd BLAST23
Repeati447 – 468LRR 3Sequence analysis1 PublicationAdd BLAST22
Repeati469 – 492LRR 4Sequence analysis1 PublicationAdd BLAST24
Repeati493 – 515LRR 5Sequence analysis1 PublicationAdd BLAST23
Repeati518 – 542LRR 6Sequence analysis1 PublicationAdd BLAST25
Repeati543 – 565LRR 7Sequence analysis1 PublicationAdd BLAST23
Repeati567 – 589LRR 8Sequence analysis1 PublicationAdd BLAST23
Repeati590 – 613LRR 9Sequence analysis1 PublicationAdd BLAST24
Repeati614 – 637LRR 10Sequence analysis1 PublicationAdd BLAST24
Repeati639 – 661LRR 11Sequence analysis1 PublicationAdd BLAST23
Repeati662 – 684LRR 12Sequence analysis1 PublicationAdd BLAST23
Repeati686 – 707LRR 13Sequence analysis1 PublicationAdd BLAST22
Repeati708 – 730LRR 14Sequence analysis1 PublicationAdd BLAST23
Repeati732 – 753LRR 15Sequence analysis1 PublicationAdd BLAST22
Repeati754 – 776LRR 16Sequence analysis1 PublicationAdd BLAST23
Repeati778 – 801LRR 17Sequence analysis1 PublicationAdd BLAST24

Sequence similaritiesi

Belongs to the LRRC8 family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00930000150868
HOGENOMiHOG000231806
HOVERGENiHBG052360
InParanoidiQ80WG5
KOiK22038
OMAiVDTQPAY
OrthoDBiEOG091G01ER
PhylomeDBiQ80WG5
TreeFamiTF331443

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR038960 LRRC8
IPR021040 LRRC8_Pannexin-like
PANTHERiPTHR43945 PTHR43945, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 3 hits
PF12534 Pannexin_like, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 8 hits
PROSITEiView protein in PROSITE
PS51450 LRR, 11 hits

Sequencei

Sequence statusi: Complete.

Q80WG5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD
60 70 80 90 100
KMICLPCKWV TKDSCNDSFR GWAASSPEPT YPNSTVLPTP DTGPTGIKYD
110 120 130 140 150
LDRHQYNYVD AVCYENRLHW FAKYFPYLVL LHTLIFLACS NFWFKFPRTS
160 170 180 190 200
SKLEHFVSIL LKCFDSPWTT RALSETVVEE SDPKPAFSKM NGSMDKKSST
210 220 230 240 250
VSEDVEATVP MLQRTKSRIE QGIVDRSETG VLDKKEGEQA KALFEKVKKF
260 270 280 290 300
RTHVEEGDIV YRLYMRQTII KVIKFALIIC YTVYYVHNIK FDVDCTVDIE
310 320 330 340 350
SLTGYRTYRC AHPLATLFKI LASFYISLVI FYGLICMYTL WWMLRRSLKK
360 370 380 390 400
YSFESIREES SYSDIPDVKN DFAFMLHLID QYDPLYSKRF AVFLSEVSEN
410 420 430 440 450
KLRQLNLNNE WTLDKLRQRL TKNAQDKLEL HLFMLSGIPD TVFDLVELEV
460 470 480 490 500
LKLELIPDVT IPPSIAQLTG LKELWLYHTA AKIEAPALAF LRENLRALHI
510 520 530 540 550
KFTDIKEIPL WIYSLKTLEE LHLTGNLSAE NNRYIVIDGL RELKRLKVLR
560 570 580 590 600
LKSNLSKLPQ VVTDVGVHLQ KLSINNEGTK LIVLNSLKKM VNLTELELIR
610 620 630 640 650
CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH
660 670 680 690 700
IAYIPIQIGN LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTFL
710 720 730 740 750
PADIGLLQNL QNLAVTANRI EALPPELFQC RKLRALHLGN NVLQSLPSRV
760 770 780 790 800
GELTNLTQIE LRGNRLECLP VELGECPLLK RSGLVVEEDL FSTLPPEVKE
810
RLWRADKEQA
Length:810
Mass (Da):94,120
Last modified:June 1, 2003 - v1
Checksum:iE3B125BC9977DBB0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL845258 Genomic DNA Translation: CAM20568.1
CH466542 Genomic DNA Translation: EDL08450.1
BC048152 mRNA No translation available.
CCDSiCCDS15875.1
RefSeqiNP_808393.1, NM_177725.4
UniGeneiMm.389232
Mm.475219

Genome annotation databases

EnsembliENSMUST00000095078; ENSMUSP00000092690; ENSMUSG00000007476
ENSMUST00000113654; ENSMUSP00000109284; ENSMUSG00000007476
ENSMUST00000139454; ENSMUSP00000139038; ENSMUSG00000099041
GeneIDi241296
KEGGimmu:241296
UCSCiuc008jbu.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL845258 Genomic DNA Translation: CAM20568.1
CH466542 Genomic DNA Translation: EDL08450.1
BC048152 mRNA No translation available.
CCDSiCCDS15875.1
RefSeqiNP_808393.1, NM_177725.4
UniGeneiMm.389232
Mm.475219

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
6FNWX-ray1.80A398-810[»]
6G8Zelectron microscopy3.66A/B/C/D/E/F1-810[»]
6G9Lelectron microscopy5.01A/B/C/D/E/F1-810[»]
6G9Oelectron microscopy4.25A/B/C/D/E/F1-810[»]
ProteinModelPortaliQ80WG5
SMRiQ80WG5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092690

PTM databases

iPTMnetiQ80WG5
PhosphoSitePlusiQ80WG5

Proteomic databases

MaxQBiQ80WG5
PaxDbiQ80WG5
PeptideAtlasiQ80WG5
PRIDEiQ80WG5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000095078; ENSMUSP00000092690; ENSMUSG00000007476
ENSMUST00000113654; ENSMUSP00000109284; ENSMUSG00000007476
ENSMUST00000139454; ENSMUSP00000139038; ENSMUSG00000099041
GeneIDi241296
KEGGimmu:241296
UCSCiuc008jbu.2 mouse

Organism-specific databases

CTDi56262
MGIiMGI:2652847 Lrrc8a

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00930000150868
HOGENOMiHOG000231806
HOVERGENiHBG052360
InParanoidiQ80WG5
KOiK22038
OMAiVDTQPAY
OrthoDBiEOG091G01ER
PhylomeDBiQ80WG5
TreeFamiTF331443

Enzyme and pathway databases

ReactomeiR-MMU-5223345 Miscellaneous transport and binding events

Miscellaneous databases

ChiTaRSiLrrc8a mouse
PROiPR:Q80WG5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000007476 Expressed in 290 organ(s), highest expression level in umbilical cord
GenevisibleiQ80WG5 MM

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR038960 LRRC8
IPR021040 LRRC8_Pannexin-like
PANTHERiPTHR43945 PTHR43945, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 3 hits
PF12534 Pannexin_like, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 8 hits
PROSITEiView protein in PROSITE
PS51450 LRR, 11 hits
ProtoNetiSearch...

Entry informationi

Entry nameiLRC8A_MOUSE
AccessioniPrimary (citable) accession number: Q80WG5
Secondary accession number(s): A2AQZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: June 1, 2003
Last modified: November 7, 2018
This is version 130 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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