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Q80WG5 (LRC8A_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Volume-regulated anion channel subunit LRRC8A
Alternative name(s):
Leucine-rich repeat-containing protein 8A
Gene names
Name:Lrrc8a
Synonyms:Lrrc8
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length810 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.4 Ref.7

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Ubiquitously expressed. High levels detected in the bone marrow; lower levels found in peripheral blood cells. Ref.4 Ref.5 Ref.6 Ref.7

Post-translational modification

N-glycosylated By similarity.

Disruption phenotype

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. Ref.7

Sequence similarities

Belongs to the LRRC8 family.

Contains 17 LRR (leucine-rich) repeats.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 810810Volume-regulated anion channel subunit LRRC8A
PRO_0000084500

Regions

Topological domain1 – 2525Cytoplasmic Potential
Transmembrane26 – 4520Helical; Potential
Topological domain46 – 12378Extracellular Potential
Transmembrane124 – 14623Helical; Potential
Topological domain147 – 262116Cytoplasmic Potential
Transmembrane263 – 28523Helical; Potential
Topological domain286 – 31934Extracellular Potential
Transmembrane320 – 34223Helical; Potential
Topological domain343 – 810468Cytoplasmic Potential
Repeat373 – 40129LRR 1
Repeat402 – 42423LRR 2
Repeat425 – 44723LRR 3
Repeat448 – 47023LRR 4
Repeat471 – 49424LRR 5
Repeat495 – 51824LRR 6
Repeat519 – 54527LRR 7
Repeat546 – 56823LRR 8
Repeat569 – 59224LRR 9
Repeat593 – 61523LRR 10
Repeat616 – 64025LRR 11
Repeat641 – 66323LRR 12
Repeat664 – 68623LRR 13
Repeat687 – 70620LRR 14
Repeat707 – 73226LRR 15
Repeat733 – 75523LRR 16
Repeat756 – 77722LRR 17

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue2171Phosphoserine By similarity
Glycosylation661N-linked (GlcNAc...) Potential
Glycosylation831N-linked (GlcNAc...) Potential

Sequences

Sequence LengthMass (Da)Tools
Q80WG5 [UniParc].

Last modified June 1, 2003. Version 1.
Checksum: E3B125BC9977DBB0

FASTA81094,120
        10         20         30         40         50         60 
MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD KMICLPCKWV 

        70         80         90        100        110        120 
TKDSCNDSFR GWAASSPEPT YPNSTVLPTP DTGPTGIKYD LDRHQYNYVD AVCYENRLHW 

       130        140        150        160        170        180 
FAKYFPYLVL LHTLIFLACS NFWFKFPRTS SKLEHFVSIL LKCFDSPWTT RALSETVVEE 

       190        200        210        220        230        240 
SDPKPAFSKM NGSMDKKSST VSEDVEATVP MLQRTKSRIE QGIVDRSETG VLDKKEGEQA 

       250        260        270        280        290        300 
KALFEKVKKF RTHVEEGDIV YRLYMRQTII KVIKFALIIC YTVYYVHNIK FDVDCTVDIE 

       310        320        330        340        350        360 
SLTGYRTYRC AHPLATLFKI LASFYISLVI FYGLICMYTL WWMLRRSLKK YSFESIREES 

       370        380        390        400        410        420 
SYSDIPDVKN DFAFMLHLID QYDPLYSKRF AVFLSEVSEN KLRQLNLNNE WTLDKLRQRL 

       430        440        450        460        470        480 
TKNAQDKLEL HLFMLSGIPD TVFDLVELEV LKLELIPDVT IPPSIAQLTG LKELWLYHTA 

       490        500        510        520        530        540 
AKIEAPALAF LRENLRALHI KFTDIKEIPL WIYSLKTLEE LHLTGNLSAE NNRYIVIDGL 

       550        560        570        580        590        600 
RELKRLKVLR LKSNLSKLPQ VVTDVGVHLQ KLSINNEGTK LIVLNSLKKM VNLTELELIR 

       610        620        630        640        650        660 
CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH IAYIPIQIGN 

       670        680        690        700        710        720 
LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTFL PADIGLLQNL QNLAVTANRI 

       730        740        750        760        770        780 
EALPPELFQC RKLRALHLGN NVLQSLPSRV GELTNLTQIE LRGNRLECLP VELGECPLLK 

       790        800        810 
RSGLVVEEDL FSTLPPEVKE RLWRADKEQA 

« Hide

References

« Hide 'large scale' references
[1]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
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]"A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans."
Sawada A., Takihara Y., Kim J.Y., Matsuda-Hashii Y., Tokimasa S., Fujisaki H., Kubota K., Endo H., Onodera T., Ohta H., Ozono K., Hara J.
J. Clin. Invest. 112:1707-1713(2003) [PubMed] [Europe PMC] [Abstract]
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AL845258 Genomic DNA. Translation: CAM20568.1.
CH466542 Genomic DNA. Translation: EDL08450.1.
BC048152 mRNA. No translation available.
CCDSCCDS15875.1.
RefSeqNP_808393.1. NM_177725.4.
UniGeneMm.389232.
Mm.475219.

3D structure databases

ProteinModelPortalQ80WG5.
SMRQ80WG5. Positions 331-802.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ80WG5.

Proteomic databases

PaxDbQ80WG5.
PRIDEQ80WG5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000095078; ENSMUSP00000092690; ENSMUSG00000007476.
ENSMUST00000113654; ENSMUSP00000109284; ENSMUSG00000007476.
ENSMUST00000139454; ENSMUSP00000139038; ENSMUSG00000099041.
GeneID241296.
KEGGmmu:241296.
UCSCuc008jbu.2. mouse.

Organism-specific databases

CTD56262.
MGIMGI:2652847. Lrrc8a.

Phylogenomic databases

eggNOGCOG4886.
GeneTreeENSGT00600000084236.
HOGENOMHOG000231806.
HOVERGENHBG052360.
InParanoidA2AQZ0.
OMAHIAYIPM.
OrthoDBEOG7Z3F3T.
PhylomeDBQ80WG5.
TreeFamTF331443.

Gene expression databases

BgeeQ80WG5.
GenevestigatorQ80WG5.

Family and domain databases

InterProIPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRR_protein-8_N.
[Graphical view]
PfamPF12534. DUF3733. 2 hits.
PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 2 hits.
[Graphical view]
SMARTSM00369. LRR_TYP. 2 hits.
[Graphical view]
PROSITEPS51450. LRR. 11 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSLRRC8A. mouse.
NextBio384965.
PROQ80WG5.
SOURCESearch...

Entry information

Entry nameLRC8A_MOUSE
AccessionPrimary (citable) accession number: Q80WG5
Secondary accession number(s): A2AQZ0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: June 1, 2003
Last modified: July 9, 2014
This is version 93 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot