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Protein

Volume-regulated anion channel subunit LRRC8A

Gene

Lrrc8a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. The VRAC channel conducts iodide better than chloride and may also conduct organic osmolytes like taurine. 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 similarity2 Publications

GO - Molecular functioni

GO - Biological processi

  • anion transport Source: UniProtKB
  • cell volume homeostasis Source: UniProtKB
  • pre-B cell differentiation Source: UniProtKB
  • response to osmotic stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Differentiation, Ion transport, Transport

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2652847. Lrrc8a.

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity

  • Note: The leucine-rich repeat (LRR) domain is on the cytoplasmic side of the cell membrane.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 25CytoplasmicSequence analysisAdd BLAST25
Transmembranei26 – 45HelicalSequence analysisAdd BLAST20
Topological domaini46 – 123ExtracellularSequence analysisAdd BLAST78
Transmembranei124 – 146HelicalSequence analysisAdd BLAST23
Topological domaini147 – 262CytoplasmicSequence analysisAdd BLAST116
Transmembranei263 – 285HelicalSequence analysisAdd BLAST23
Topological domaini286 – 319ExtracellularSequence analysisAdd BLAST34
Transmembranei320 – 342HelicalSequence analysisAdd BLAST23
Topological domaini343 – 810CytoplasmicSequence analysisAdd BLAST468

GO - Cellular componenti

Complete GO annotation...

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

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
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Modified residuei200PhosphothreonineCombined sources1
Modified residuei202PhosphoserineCombined sources1
Modified residuei215PhosphothreonineBy similarity1
Modified residuei217PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Acetylation, 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.
GenevisibleiQ80WG5. MM.

Interactioni

Subunit structurei

Heterooligomer; heterooligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E), possibly to form a heterohexamer (PubMed:24782309). 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).Curated1 Publication

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092690.

Structurei

3D structure databases

ProteinModelPortaliQ80WG5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati373 – 401LRR 1Add BLAST29
Repeati402 – 424LRR 2Add BLAST23
Repeati425 – 447LRR 3Add BLAST23
Repeati448 – 470LRR 4Add BLAST23
Repeati471 – 494LRR 5Add BLAST24
Repeati495 – 518LRR 6Add BLAST24
Repeati519 – 545LRR 7Add BLAST27
Repeati546 – 568LRR 8Add BLAST23
Repeati569 – 592LRR 9Add BLAST24
Repeati593 – 615LRR 10Add BLAST23
Repeati616 – 640LRR 11Add BLAST25
Repeati641 – 663LRR 12Add BLAST23
Repeati664 – 686LRR 13Add BLAST23
Repeati687 – 706LRR 14Add BLAST20
Repeati707 – 732LRR 15Add BLAST26
Repeati733 – 755LRR 16Add BLAST23
Repeati756 – 777LRR 17Add BLAST22

Sequence similaritiesi

Belongs to the LRRC8 family.Curated
Contains 17 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ80WG5.
OMAiHIAYIPM.
OrthoDBiEOG091G01ER.
PhylomeDBiQ80WG5.
TreeFamiTF331443.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13855. LRR_8. 3 hits.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
[Graphical view]

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.

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

ProteinModelPortaliQ80WG5.
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.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ80WG5.
OMAiHIAYIPM.
OrthoDBiEOG091G01ER.
PhylomeDBiQ80WG5.
TreeFamiTF331443.

Miscellaneous databases

PROiQ80WG5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000007476.
GenevisibleiQ80WG5. MM.

Family and domain databases

Gene3Di3.80.10.10. 3 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13855. LRR_8. 3 hits.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRC8A_MOUSE
AccessioniPrimary (citable) accession number: Q80WG5
Secondary accession number(s): A2AQZ0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: June 1, 2003
Last modified: November 30, 2016
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.