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Q80WG5

- LRC8A_MOUSE

UniProt

Q80WG5 - LRC8A_MOUSE

Protein

Volume-regulated anion channel subunit LRRC8A

Gene

Lrrc8a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 1 (01 Jun 2003)
      Previous versions | rss
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    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

    1. anion transport Source: UniProtKB
    2. cell volume homeostasis Source: UniProtKB
    3. pre-B cell differentiation Source: UniProtKB
    4. response to osmotic stress Source: UniProtKB

    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: Chromosome 2

    Organism-specific databases

    MGIiMGI:2652847. Lrrc8a.

    Subcellular locationi

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

    GO - Cellular componenti

    1. ion channel complex Source: UniProtKB
    2. plasma membrane Source: UniProtKB

    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

    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.
    GenevestigatoriQ80WG5.

    Interactioni

    Subunit structurei

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

    Structurei

    3D structure databases

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

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2525CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini46 – 12378ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini147 – 262116CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini286 – 31934ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini343 – 810468CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei26 – 4520HelicalSequence AnalysisAdd
    BLAST
    Transmembranei124 – 14623HelicalSequence AnalysisAdd
    BLAST
    Transmembranei263 – 28523HelicalSequence AnalysisAdd
    BLAST
    Transmembranei320 – 34223HelicalSequence AnalysisAdd
    BLAST

    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.
    GeneTreeiENSGT00600000084236.
    HOGENOMiHOG000231806.
    HOVERGENiHBG052360.
    InParanoidiA2AQZ0.
    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

    MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD    50
    KMICLPCKWV TKDSCNDSFR GWAASSPEPT YPNSTVLPTP DTGPTGIKYD 100
    LDRHQYNYVD AVCYENRLHW FAKYFPYLVL LHTLIFLACS NFWFKFPRTS 150
    SKLEHFVSIL LKCFDSPWTT RALSETVVEE SDPKPAFSKM NGSMDKKSST 200
    VSEDVEATVP MLQRTKSRIE QGIVDRSETG VLDKKEGEQA KALFEKVKKF 250
    RTHVEEGDIV YRLYMRQTII KVIKFALIIC YTVYYVHNIK FDVDCTVDIE 300
    SLTGYRTYRC AHPLATLFKI LASFYISLVI FYGLICMYTL WWMLRRSLKK 350
    YSFESIREES SYSDIPDVKN DFAFMLHLID QYDPLYSKRF AVFLSEVSEN 400
    KLRQLNLNNE WTLDKLRQRL TKNAQDKLEL HLFMLSGIPD TVFDLVELEV 450
    LKLELIPDVT IPPSIAQLTG LKELWLYHTA AKIEAPALAF LRENLRALHI 500
    KFTDIKEIPL WIYSLKTLEE LHLTGNLSAE NNRYIVIDGL RELKRLKVLR 550
    LKSNLSKLPQ VVTDVGVHLQ KLSINNEGTK LIVLNSLKKM VNLTELELIR 600
    CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH 650
    IAYIPIQIGN LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTFL 700
    PADIGLLQNL QNLAVTANRI EALPPELFQC RKLRALHLGN NVLQSLPSRV 750
    GELTNLTQIE LRGNRLECLP VELGECPLLK RSGLVVEEDL FSTLPPEVKE 800
    RLWRADKEQA 810
    Length:810
    Mass (Da):94,120
    Last modified:June 1, 2003 - v1
    Checksum:iE3B125BC9977DBB0
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AL845258 Genomic DNA. Translation: CAM20568.1 .
    CH466542 Genomic DNA. Translation: EDL08450.1 .
    BC048152 mRNA. No translation available.
    CCDSi CCDS15875.1.
    RefSeqi NP_808393.1. NM_177725.4.
    UniGenei Mm.389232.
    Mm.475219.

    3D structure databases

    ProteinModelPortali Q80WG5.
    SMRi Q80WG5. Positions 331-802.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei Q80WG5.

    Proteomic databases

    PaxDbi Q80WG5.
    PRIDEi Q80WG5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000095078 ; ENSMUSP00000092690 ; ENSMUSG00000007476 .
    ENSMUST00000113654 ; ENSMUSP00000109284 ; ENSMUSG00000007476 .
    ENSMUST00000139454 ; ENSMUSP00000139038 ; ENSMUSG00000099041 .
    GeneIDi 241296.
    KEGGi mmu:241296.
    UCSCi uc008jbu.2. mouse.

    Organism-specific databases

    CTDi 56262.
    MGIi MGI:2652847. Lrrc8a.

    Phylogenomic databases

    eggNOGi COG4886.
    GeneTreei ENSGT00600000084236.
    HOGENOMi HOG000231806.
    HOVERGENi HBG052360.
    InParanoidi A2AQZ0.
    OMAi HIAYIPM.
    OrthoDBi EOG7Z3F3T.
    PhylomeDBi Q80WG5.
    TreeFami TF331443.

    Miscellaneous databases

    ChiTaRSi LRRC8A. mouse.
    NextBioi 384965.
    PROi Q80WG5.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q80WG5.
    Genevestigatori Q80WG5.

    Family and domain databases

    InterProi IPR001611. Leu-rich_rpt.
    IPR025875. Leu-rich_rpt_4.
    IPR003591. Leu-rich_rpt_typical-subtyp.
    IPR021040. LRR_protein-8_N.
    [Graphical view ]
    Pfami PF12534. DUF3733. 2 hits.
    PF12799. LRR_4. 1 hit.
    PF13855. LRR_8. 2 hits.
    [Graphical view ]
    SMARTi SM00369. LRR_TYP. 2 hits.
    [Graphical view ]
    PROSITEi PS51450. LRR. 11 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 94 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