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Protein

Volume-regulated anion channel subunit LRRC8A

Gene

Lrrc8a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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. It is unclear whether LRRC8A constitutes a pore-forming subunit or whether it is closely associated with the pore and mediates channel properties such as ion selectivity (By similarity). Involved in B-cell development: required for the pro-B cell to pre-B cell transition. Also required for T-cell development.By similarity2 Publications

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
ProteomesiUP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2652847. Lrrc8a.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2525CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei26 – 4520HelicalSequence AnalysisAdd
BLAST
Topological domaini46 – 12378ExtracellularSequence AnalysisAdd
BLAST
Transmembranei124 – 14623HelicalSequence AnalysisAdd
BLAST
Topological domaini147 – 262116CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei263 – 28523HelicalSequence AnalysisAdd
BLAST
Topological domaini286 – 31934ExtracellularSequence AnalysisAdd
BLAST
Transmembranei320 – 34223HelicalSequence AnalysisAdd
BLAST
Topological domaini343 – 810468CytoplasmicSequence AnalysisAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 810810Volume-regulated anion channel subunit LRRC8APRO_0000084500Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Glycosylationi66 – 661N-linked (GlcNAc...)Sequence Analysis
Glycosylationi83 – 831N-linked (GlcNAc...)Sequence Analysis
Modified residuei217 – 2171PhosphoserineBy similarity

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ80WG5.
PaxDbiQ80WG5.
PRIDEiQ80WG5.

PTM databases

PhosphoSiteiQ80WG5.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ80WG5.
GenevisibleiQ80WG5. MM.

Interactioni

Subunit structurei

Heterooligomer; heterooligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E), possibly to form a heterohexamer.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092690.

Structurei

3D structure databases

ProteinModelPortaliQ80WG5.
SMRiQ80WG5. Positions 331-802.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati373 – 40129LRR 1Add
BLAST
Repeati402 – 42423LRR 2Add
BLAST
Repeati425 – 44723LRR 3Add
BLAST
Repeati448 – 47023LRR 4Add
BLAST
Repeati471 – 49424LRR 5Add
BLAST
Repeati495 – 51824LRR 6Add
BLAST
Repeati519 – 54527LRR 7Add
BLAST
Repeati546 – 56823LRR 8Add
BLAST
Repeati569 – 59224LRR 9Add
BLAST
Repeati593 – 61523LRR 10Add
BLAST
Repeati616 – 64025LRR 11Add
BLAST
Repeati641 – 66323LRR 12Add
BLAST
Repeati664 – 68623LRR 13Add
BLAST
Repeati687 – 70620LRR 14Add
BLAST
Repeati707 – 73226LRR 15Add
BLAST
Repeati733 – 75523LRR 16Add
BLAST
Repeati756 – 77722LRR 17Add
BLAST

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

eggNOGiCOG4886.
GeneTreeiENSGT00800000124020.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ80WG5.
OMAiHIAYIPM.
OrthoDBiEOG7Z3F3T.
PhylomeDBiQ80WG5.
TreeFamiTF331443.

Family and domain databases

InterProiIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRR_protein-8_N.
[Graphical view]
PfamiPF12534. DUF3733. 2 hits.
PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 2 hits.
[Graphical view]
SMARTiSM00369. LRR_TYP. 2 hits.
[Graphical view]
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.
SMRiQ80WG5. Positions 331-802.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000092690.

PTM databases

PhosphoSiteiQ80WG5.

Proteomic databases

MaxQBiQ80WG5.
PaxDbiQ80WG5.
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

eggNOGiCOG4886.
GeneTreeiENSGT00800000124020.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ80WG5.
OMAiHIAYIPM.
OrthoDBiEOG7Z3F3T.
PhylomeDBiQ80WG5.
TreeFamiTF331443.

Miscellaneous databases

NextBioi384965.
PROiQ80WG5.
SOURCEiSearch...

Gene expression databases

BgeeiQ80WG5.
GenevisibleiQ80WG5. MM.

Family and domain databases

InterProiIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRR_protein-8_N.
[Graphical view]
PfamiPF12534. DUF3733. 2 hits.
PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 2 hits.
[Graphical view]
SMARTiSM00369. LRR_TYP. 2 hits.
[Graphical view]
PROSITEiPS51450. LRR. 11 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  4. Cited for: FUNCTION, TISSUE SPECIFICITY.
  5. "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins."
    Kubota K., Kim J.Y., Sawada A., Tokimasa S., Fujisaki H., Matsuda-Hashii Y., Ozono K., Hara J.
    FEBS Lett. 564:147-152(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  6. "SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel."
    Qiu Z., Dubin A.E., Mathur J., Tu B., Reddy K., Miraglia L.J., Reinhardt J., Orth A.P., Patapoutian A.
    Cell 157:447-458(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  7. "Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function."
    Kumar L., Chou J., Yee C.S., Borzutzky A., Vollmann E.H., von Andrian U.H., Park S.Y., Hollander G., Manis J.P., Poliani P.L., Geha R.S.
    J. Exp. Med. 211:929-942(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.

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: July 22, 2015
This is version 102 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

External Data

Dasty 3

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 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.