Q7L1W4 · LRC8D_HUMAN

  • Protein
    Volume-regulated anion channel subunit LRRC8D
  • Gene
    LRRC8D
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Non-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:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:32415200).
The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658, PubMed:28193731).
Plays a redundant role in the efflux of amino acids, such as aspartate, in response to osmotic stress (PubMed:28193731).
LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471).
Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24782309, PubMed:24790029, PubMed:26824658, PubMed:28193731).
Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents, generated in response to hypotonicity- or glucose-induced beta cell swelling, depolarize cells, thereby causing electrical excitation, leading to increase glucose sensitivity and insulin secretion (By similarity).
VRAC channels containing LRRC8D inhibit transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:33171122).
Mediates the import of the antibiotic blasticidin-S into the cell (PubMed:24782309).

Catalytic activity

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Cellular Componentmonoatomic ion channel complex
Cellular Componentplasma membrane
Molecular Functionvolume-sensitive anion channel activity
Biological Processaspartate transmembrane transport
Biological Processcellular response to osmotic stress
Biological Processintracellular glucose homeostasis
Biological Processmonoatomic anion transmembrane transport
Biological Processprotein hexamerization
Biological Processtaurine transmembrane transport

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Volume-regulated anion channel subunit LRRC8D
  • Alternative names
    • Leucine-rich repeat-containing protein 5
    • Leucine-rich repeat-containing protein 8D
      (HsLRRC8D
      )

Gene names

    • Name
      LRRC8D
    • Synonyms
      LRRC5
    • ORF names
      UNQ213/PRO239

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q7L1W4
  • Secondary accessions
    • D3DT29
    • Q6UWB2
    • Q9NVW3

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Endoplasmic reticulum membrane
; Multi-pass membrane protein
Note: In the absence of LRRC8A, resides primarily in a cytoplasmic compartment, probably the endoplasmic reticulum (PubMed:24782309, PubMed:24790029).
Requires LRRC8A for expression at the cell membrane (PubMed:24790029).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-22Cytoplasmic
Transmembrane23-48Helical
Topological domain49-163Extracellular
Transmembrane164-182Helical
Topological domain183-308Cytoplasmic
Transmembrane309-328Helical
Topological domain329-360Extracellular
Transmembrane361-386Helical
Topological domain387-858Cytoplasmic

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis44Alters channel anion selectivity.
Mutagenesis143Affects ion selectivity of the channel. Reduced permeability to negatively charged glutamate and gluconate.
Natural variantVAR_051132371in dbSNP:rs11552246

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 760 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, disulfide bond, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00000844931-858UniProtVolume-regulated anion channel subunit LRRC8D
Disulfide bond54↔354UniProt
Modified residue (large scale data)221PRIDEPhosphoserine
Modified residue (large scale data)233PRIDEPhosphothreonine
Modified residue (large scale data)239PRIDEPhosphoserine
Modified residue241UniProtPhosphoserine
Modified residue242UniProtPhosphoserine
Modified residue246UniProtPhosphoserine
Modified residue (large scale data)246PRIDEPhosphoserine
Modified residue (large scale data)248PRIDEPhosphoserine
Modified residue (large scale data)251PRIDEPhosphothreonine
Modified residue (large scale data)604PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Heterohexamer (PubMed:32415200).
Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:26530471, PubMed:26824658, PubMed:28193731).
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)

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q7L1W4LRRC8A Q8IWT62EBI-861997, EBI-10970086

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, repeat.

TypeIDPosition(s)Description
Region221-251Disordered
Compositional bias227-251Polar residues
Repeat514-534LRR 1
Repeat538-559LRR 2
Repeat561-582LRR 3
Repeat589-609LRR 4
Repeat612-632LRR 5
Repeat636-657LRR 6
Repeat659-680LRR 7
Repeat684-705LRR 8
Repeat707-728LRR 9
Repeat730-751LRR 10
Repeat753-774LRR 11
Repeat776-797LRR 12
Repeat799-820LRR 13

Domain

The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.

Sequence similarities

Belongs to the LRRC8 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    858
  • Mass (Da)
    98,201
  • Last updated
    2004-07-05 v1
  • Checksum
    52A8B6EEF6F0FE2B
MFTLAEVASLNDIQPTYRILKPWWDVFMDYLAVVMLMVAIFAGTMQLTKDQVVCLPVLPSPVNSKAHTPPGNAEVTTNIPKMEAATNQDQDGRTTNDISFGTSAVTPDIPLRATYPRTDFALPNQEAKKEKKDPTGRKTNLDFQQYVFINQMCYHLALPWYSKYFPYLALIHTIILMVSSNFWFKYPKTCSKVEHFVSILGKCFESPWTTKALSETACEDSEENKQRITGAQTLPKHVSTSSDEGSPSASTPMINKTGFKFSAEKPVIEVPSMTILDKKDGEQAKALFEKVRKFRAHVEDSDLIYKLYVVQTVIKTAKFIFILCYTANFVNAISFEHVCKPKVEHLIGYEVFECTHNMAYMLKKLLISYISIICVYGFICLYTLFWLFRIPLKEYSFEKVREESSFSDIPDVKNDFAFLLHMVDQYDQLYSKRFGVFLSEVSENKLREISLNHEWTFEKLRQHISRNAQDKQELHLFMLSGVPDAVFDLTDLDVLKLELIPEAKIPAKISQMTNLQELHLCHCPAKVEQTAFSFLRDHLRCLHVKFTDVAEIPAWVYLLKNLRELYLIGNLNSENNKMIGLESLRELRHLKILHVKSNLTKVPSNITDVAPHLTKLVIHNDGTKLLVLNSLKKMMNVAELELQNCELERIPHAIFSLSNLQELDLKSNNIRTIEEIISFQHLKRLTCLKLWHNKIVTIPPSITHVKNLESLYFSNNKLESLPVAVFSLQKLRCLDVSYNNISMIPIEIGLLQNLQHLHITGNKVDILPKQLFKCIKLRTLNLGQNCITSLPEKVGQLSQLTQLELKGNCLDRLPAQLGQCRMLKKSGLVVEDHLFDTLPLEVKEALNQDINIPFANGI

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
Q5VWA0Q5VWA0_HUMANLRRC8D116
E9PMF9E9PMF9_HUMANLRRC8D274
E9PJ89E9PJ89_HUMANLRRC8D30
E9PJS7E9PJS7_HUMANLRRC8D121
E9PL08E9PL08_HUMANLRRC8D186

Sequence caution

The sequence AAQ89233.1 differs from that shown. Reason: Erroneous initiation
The sequence BAA91631.1 differs from that shown. Reason: Erroneous initiation

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias227-251Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AL391497
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH471097
EMBL· GenBank· DDBJ
EAW73130.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471097
EMBL· GenBank· DDBJ
EAW73131.1
EMBL· GenBank· DDBJ
Genomic DNA
CH471097
EMBL· GenBank· DDBJ
EAW73132.1
EMBL· GenBank· DDBJ
Genomic DNA
BC024159
EMBL· GenBank· DDBJ
AAH24159.2
EMBL· GenBank· DDBJ
mRNA
AK001332
EMBL· GenBank· DDBJ
BAA91631.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AY358874
EMBL· GenBank· DDBJ
AAQ89233.1
EMBL· GenBank· DDBJ
mRNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

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