Volume-regulated anion channel subunit LRRC8A (Leucine-rich repeat-containing protein 8A) (HsLRRC8A) (Swelling protein 1)
1_MIPVT 6_ ELRYF 11_ ADTQP 16_ AYRIL 21_ KPWWD 26_ VFTDY 31_ ISIVM 36_ LMIAV 41_ FGGTL 46_ QVTQD 51_ KMICL 56_ PCKWV 61_ TKDSC 66_ NDSFR 71_ GWAAP 76_ GPEPT 81_ YPNST 86_ ILPTP 91_ DTGPT 96_ GIKYD 101_ LDRHQ 106_ YNYVD 111_ AVCYE 116_ NRLHW 121_ FAKYF 126_ PYLVL 131_ LHTLI 136_ FLACS 141_ NFWFK 146_ FPRTS 151_ SKLEH 156_ FVSIL 161_ LKCFD 166_ SPWTT 171_ RALSE 176_ TVVEE 181_ SDPKP 186_ AFSKM 191_ NGSMD 196_ KKSST 201_ VSEDV 206_ EATVP 211_ MLQRT 216_ KSRIE 221_ QGIVD 226_ RSETG 231_ VLDKK 236_ EGEQA 241_ KALFE 246_ KVKKF 251_ RTHVE 256_ EGDIV 261_ YRLYM 266_ RQTII 271_ KVIKF 276_ ILIIC 281_ YTVYY 286_ VHNIK 291_ FDVDC 296_ TVDIE 301_ SLTGY 306_ RTYRC 311_ AHPLA 316_ TLFKI 321_ LASFY 326_ ISLVI 331_ FYGLI 336_ CMYTL 341_ WWMLR 346_ RSLKK 351_ YSFES 356_ IREES 361_ SYSDI 366_ PDVKN 371_ DFAFM 376_ LHLID 381_ QYDPL 386_ YSKRF 391_ AVFLS 396_ EVSEN 401_ KLRQL 406_ NLNNE 411_ WTLDK 416_ LRQRL 421_ TKNAQ 426_ DKLEL 431_ HLFML 436_ SGIPD 441_ TVFDL 446_ VELEV 451_ LKLEL 456_ IPDVT 461_ IPPSI 466_ AQLTG 471_ LKELW 476_ LYHTA 481_ AKIEA 486_ PALAF 491_ LRENL 496_ RALHI 501_ KFTDI 506_ KEIPL 511_ WIYSL 516_ KTLEE 521_ LHLTG 526_ NLSAE 531_ NNRYI 536_ VIDGL 541_ RELKR 546_ LKVLR 551_ LKSNL 556_ SKLPQ 561_ VVTDV 566_ GVHLQ 571_ KLSIN 576_ NEGTK 581_ LIVLN 586_ SLKKM 591_ ANLTE 596_ LELIR 601_ CDLER 606_ IPHSI 611_ FSLHN 616_ LQEID 621_ LKDNN 626_ LKTIE 631_ EIISF 636_ QHLHR 641_ LTCLK 646_ LWYNH 651_ IAYIP 656_ IQIGN 661_ LTNLE 666_ RLYLN 671_ RNKIE 676_ KIPTQ 681_ LFYCR 686_ KLRYL 691_ DLSHN 696_ NLTFL 701_ PADIG 706_ LLQNL 711_ QNLAI 716_ TANRI 721_ ETLPP 726_ ELFQC 731_ RKLRA 736_ LHLGN 741_ NVLQS 746_ LPSRV 751_ GELTN 756_ LTQIE 761_ LRGNR 766_ LECLP 771_ VELGE 776_ CPLLK 781_ RSGLV 786_ VEEDL 791_ FNTLP 796_ PEVKE 801_RLWRA
1: 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:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658, PubMed:28193731, PubMed:30095067). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (PubMed:28193731). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). 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 (PubMed:33171122). In contrast, complexes containing LRRC8D inhibit transport of 2'-3'-cGAMP (PubMed:33171122). 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:24790029, PubMed:26824658, PubMed:28193731). Can form functional channels by itself (in vitro) (PubMed:26824658). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746). 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 (PubMed:29371604). 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 (PubMed:31270356, PubMed:33139539). Acts as a key factor in NLRP3 inflammasome activation by modulating itaconate efflux and mitochondria function (PubMed:39909992)