Lrrc8a
entrez
311846
canonical
uniprot
Q4V8I7
canonical
ensembl
ENSRNOG00000025296
resolver
ensembl
ENSRNOG00055007041
resolver
ensembl
ENSRNOG00060031166
resolver
ensembl
ENSRNOG00065020426
resolver
ensp
ENSRNOP00000031726
resolver
ensp
ENSRNOP00055009158
resolver
ensp
ENSRNOP00060044869
resolver
ensp
ENSRNOP00065027680
resolver
enst
ENSRNOT00000033934
resolver
enst
ENSRNOT00055011626
resolver
enst
ENSRNOT00060054089
resolver
enst
ENSRNOT00065034533
resolver
genesymbol
Lrrc8a
resolver
genesymbol_syn
Lrrc8
resolver
genesymbol_syn
SWELL1
resolver
uniprot_entry
LRC8A_RAT
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by (4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid), which plugs the channel like a cork in a bottle by binding in the extracellular selectivity filter and sterically occluding ion conduction (By similarity). Lipids may block conduction in closed heterohexameric channels (By similarity). {ECO:0000250|UniProtKB:Q80WG5}.
uniprot
proteins
amino_acid_sequence
MIPVTELRYFADTQPAYRILKPWWDVFTDYISIVMLMIAVFGGTLQVTQDKMICLPCKWVTKDSCNDSFRGWGASSPEPTYPNSTVLPTPDTGPTGIKYDLDRHQYNYVDAVCYENRLHWFAKYFPYLVLLHTLIFLACSNFWFKFPRTSSKLEHFVSILLKCFDSPWTTRALSETVVEESDPKPAFSKMNGSMDKKSSTVSEDVEATVPMLQRTKSRIEQGIVDRSETGVLDKKEGEQAKALFEKVKKFRTHVEEGDIVYRLYMRQTIIKVIKFFLIICYTVYYVHNIKFDVDCTVDIESLTGYRTYRCAHPLATLFKILASFYISLVIFYGLICMYTLWWMLRRSLKKYSFESIREESSYSDIPDVKNDFAFMLHLIDQYDPLYSKRFAVFLSEVSENKLRQLNLNNEWTLDKLRQRLTKNAQDKLELHLFMLSGIPDTVFDLLELEVLKLELIPDVTIPPSIAQLTGLKELWLYHTAAKIEAPALAFLRENLRALHIKFTDIKEIPLWIYSLKTLEELHLTGNLSAENNRYIVIDGLRELKRLKVLRLKSNLSKLPQVVTDVGVHLQKLSINNEGTKLIVLNSLKKMVNLTELELIRCDLERIPHSIFSLHNLQEIDLKDNNLKTIEEIISFQHLHRLTCLKLWYNHIAYIPIQIGNLTNLERLYLNRNKIEKIPTQLFYCRKLRYLDLSHNNLTLLPADIGLLQNLQNLAVTANRIEALPPELFQCRKLRALHLGNNVLQSLPSRVGELTNLTQIELRGNRLECLPVELGECPLLKRSGLVVEEDLFSTLPPEVKERLWRADKEQA
uniprot
proteins
function
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 (PubMed:28833202). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:28833202). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). In complex with LRRC8C or LRRC8E, acts as a transporter of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol: mediates both import and export of 2'-3'-cGAMP, thereby promoting transfer of 2'-3'-cGAMP to bystander cells (By similarity). In contrast, complexes containing LRRC8D inhibit transport of 2'-3'-cGAMP (By similarity). Required for in vivo channel activity, together with at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:28833202). 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 (By similarity). Also required for T-cell development (By similarity). Required for myoblast differentiation: VRAC activity promotes membrane hyperpolarization and regulates insulin-stimulated glucose metabolism and oxygen consumption (By similarity). 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). Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (By similarity). Acts as a key factor in NLRP3 inflammasome activation by modulating itaconate efflux and mitochondria function (By similarity). {ECO:0000250|UniProtKB:Q80WG5, ECO:0000250|UniProtKB:Q8IWT6, ECO:0000269|PubMed:28833202}.
uniprot
proteins
mass_dalton
94162
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8IWT6}.
uniprot
proteins
protein_family
LRRC8 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
28833202
uniprot
proteins
sequence_length
810
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:28833202}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IWT6}. Lysosome membrane {ECO:0000250|UniProtKB:Q8IWT6}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8IWT6}. Note=Mainly localizes to the cell membrane, with some intracellular localization to lysosomes. {ECO:0000250|UniProtKB:Q8IWT6}.
uniprot
proteins
transmembrane_region
TRANSMEM 23..47; /note="Helical; Name=1"; /evidence="ECO:0000250|UniProtKB:Q80WG5"; TRANSMEM 124..142; /note="Helical; Name=2"; /evidence="ECO:0000250|UniProtKB:Q80WG5"; TRANSMEM 265..286; /note="Helical; Name=3"; /evidence="ECO:0000250|UniProtKB:Q80WG5"; TRANSMEM 317..341; /note="Helical; Name=4"; /evidence="ECO:0000250|UniProtKB:Q80WG5
uniprot
proteins