Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Volume-regulated anion channel subunit LRRC8A

Gene

LRRC8A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (PubMed:24725410, PubMed:24790029, PubMed:26530471, PubMed:26824658). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). 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). 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).By similarity5 Publications

GO - Molecular functioni

  • volume-sensitive anion channel activity Source: UniProtKB

GO - Biological processi

  • anion transport Source: UniProtKB
  • cell volume homeostasis Source: UniProtKB
  • pre-B cell differentiation Source: UniProtKB
  • response to osmotic stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Differentiation, Ion transport, Transport

Protein family/group databases

TCDBi1.A.25.3.1. the gap junction-forming innexin (innexin) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Volume-regulated anion channel subunit LRRC8A
Alternative name(s):
Leucine-rich repeat-containing protein 8A
Swelling protein 1
Gene namesi
Name:LRRC8A
Synonyms:KIAA1437, LRRC8, SWELL1
ORF Names:UNQ221/PRO247
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:19027. LRRC8A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 25CytoplasmicSequence analysisAdd BLAST25
Transmembranei26 – 45HelicalSequence analysisAdd BLAST20
Topological domaini46 – 123ExtracellularSequence analysisAdd BLAST78
Transmembranei124 – 146HelicalSequence analysisAdd BLAST23
Topological domaini147 – 262CytoplasmicSequence analysisAdd BLAST116
Transmembranei263 – 285HelicalSequence analysisAdd BLAST23
Topological domaini286 – 319ExtracellularSequence analysisAdd BLAST34
Transmembranei320 – 342HelicalSequence analysisAdd BLAST23
Topological domaini343 – 810Cytoplasmic1 PublicationAdd BLAST468

GO - Cellular componenti

  • cell surface Source: MGI
  • ion channel complex Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Agammaglobulinemia 5, autosomal dominant (AGM5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving LRRC8 has been found in a patient with congenital agammaglobulinemia. Translocation t(9;20)(q33.2;q12). The translocation truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of the seventh LRR domains.
Disease descriptionA primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life.
See also OMIM:613506

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44T → A or C: Altered anion selectivity. 1 Publication1
Mutagenesisi66N → A: Abolishes N-glycosylation; when associated with A-83. 1 Publication1
Mutagenesisi83N → A: Abolishes N-glycosylation; when associated with A-66. 1 Publication1

Organism-specific databases

DisGeNETi56262.
MalaCardsiLRRC8A.
MIMi613506. phenotype.
OpenTargetsiENSG00000136802.
Orphaneti33110. Autosomal agammaglobulinemia.
PharmGKBiPA134909315.

Polymorphism and mutation databases

BioMutaiLRRC8A.
DMDMi37537912.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000844991 – 810Volume-regulated anion channel subunit LRRC8AAdd BLAST810

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Glycosylationi66N-linked (GlcNAc...)Sequence analysis1
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Modified residuei200PhosphothreonineBy similarity1
Modified residuei202PhosphoserineBy similarity1
Modified residuei215PhosphothreonineCombined sources1
Modified residuei217PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8IWT6.
MaxQBiQ8IWT6.
PaxDbiQ8IWT6.
PeptideAtlasiQ8IWT6.
PRIDEiQ8IWT6.

PTM databases

iPTMnetiQ8IWT6.
PhosphoSitePlusiQ8IWT6.

Expressioni

Tissue specificityi

Expressed in brain, kidney, ovary, lung, liver, heart, and fetal brain and liver. Found at high levels in bone marrow; lower levels are detected in peripheral blood cells. Expressed on T-cells as well as on B-lineage cells.2 Publications

Gene expression databases

BgeeiENSG00000136802.
CleanExiHS_LRRC8A.
ExpressionAtlasiQ8IWT6. baseline and differential.
GenevisibleiQ8IWT6. HS.

Organism-specific databases

HPAiHPA016811.

Interactioni

Subunit structurei

Heterooligomer; heterooligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E), possibly to form a heterohexamer (PubMed:24782309, PubMed:24790029, PubMed:26824658). 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).Curated3 Publications

Protein-protein interaction databases

BioGridi121126. 23 interactors.
DIPiDIP-61360N.
IntActiQ8IWT6. 4 interactors.
STRINGi9606.ENSP00000259324.

Structurei

3D structure databases

ProteinModelPortaliQ8IWT6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati373 – 401LRR 1Add BLAST29
Repeati402 – 424LRR 2Add BLAST23
Repeati425 – 447LRR 3Add BLAST23
Repeati448 – 470LRR 4Add BLAST23
Repeati471 – 494LRR 5Add BLAST24
Repeati495 – 518LRR 6Add BLAST24
Repeati519 – 545LRR 7Add BLAST27
Repeati546 – 568LRR 8Add BLAST23
Repeati569 – 592LRR 9Add BLAST24
Repeati593 – 615LRR 10Add BLAST23
Repeati616 – 640LRR 11Add BLAST25
Repeati641 – 663LRR 12Add BLAST23
Repeati664 – 686LRR 13Add BLAST23
Repeati687 – 706LRR 14Add BLAST20
Repeati707 – 732LRR 15Add BLAST26
Repeati733 – 755LRR 16Add BLAST23
Repeati756 – 777LRR 17Add BLAST22

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

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ8IWT6.
OMAiHIAYIPM.
OrthoDBiEOG091G01ER.
PhylomeDBiQ8IWT6.
TreeFamiTF331443.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13855. LRR_8. 3 hits.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8IWT6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD
60 70 80 90 100
KMICLPCKWV TKDSCNDSFR GWAAPGPEPT YPNSTILPTP DTGPTGIKYD
110 120 130 140 150
LDRHQYNYVD AVCYENRLHW FAKYFPYLVL LHTLIFLACS NFWFKFPRTS
160 170 180 190 200
SKLEHFVSIL LKCFDSPWTT RALSETVVEE SDPKPAFSKM NGSMDKKSST
210 220 230 240 250
VSEDVEATVP MLQRTKSRIE QGIVDRSETG VLDKKEGEQA KALFEKVKKF
260 270 280 290 300
RTHVEEGDIV YRLYMRQTII KVIKFILIIC YTVYYVHNIK FDVDCTVDIE
310 320 330 340 350
SLTGYRTYRC AHPLATLFKI LASFYISLVI FYGLICMYTL WWMLRRSLKK
360 370 380 390 400
YSFESIREES SYSDIPDVKN DFAFMLHLID QYDPLYSKRF AVFLSEVSEN
410 420 430 440 450
KLRQLNLNNE WTLDKLRQRL TKNAQDKLEL HLFMLSGIPD TVFDLVELEV
460 470 480 490 500
LKLELIPDVT IPPSIAQLTG LKELWLYHTA AKIEAPALAF LRENLRALHI
510 520 530 540 550
KFTDIKEIPL WIYSLKTLEE LHLTGNLSAE NNRYIVIDGL RELKRLKVLR
560 570 580 590 600
LKSNLSKLPQ VVTDVGVHLQ KLSINNEGTK LIVLNSLKKM ANLTELELIR
610 620 630 640 650
CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH
660 670 680 690 700
IAYIPIQIGN LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTFL
710 720 730 740 750
PADIGLLQNL QNLAITANRI ETLPPELFQC RKLRALHLGN NVLQSLPSRV
760 770 780 790 800
GELTNLTQIE LRGNRLECLP VELGECPLLK RSGLVVEEDL FNTLPPEVKE
810
RLWRADKEQA
Length:810
Mass (Da):94,199
Last modified:March 1, 2003 - v1
Checksum:iE0C5E6EBEE8275E8
GO

Sequence cautioni

The sequence AAQ88653 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA92675 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC11161 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti323S → P in BAC11161 (PubMed:14702039).Curated1
Sequence conflicti744Q → R in BAC11161 (PubMed:14702039).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY143166 mRNA. Translation: AAN18279.1.
AB037858 mRNA. Translation: BAA92675.1. Different initiation.
AL672142 Genomic DNA. Translation: CAI10839.1.
BC051322 mRNA. Translation: AAH51322.1.
AY358286 mRNA. Translation: AAQ88653.1. Different initiation.
AK074723 mRNA. Translation: BAC11161.1. Different initiation.
CCDSiCCDS35155.1.
RefSeqiNP_001120716.1. NM_001127244.1.
NP_001120717.1. NM_001127245.1.
NP_062540.2. NM_019594.3.
XP_005252152.1. XM_005252095.2.
XP_005252153.1. XM_005252096.3.
XP_006717249.1. XM_006717186.2.
XP_011517165.1. XM_011518863.1.
XP_011517166.1. XM_011518864.2.
XP_011517167.1. XM_011518865.2.
UniGeneiHs.643600.

Genome annotation databases

EnsembliENST00000259324; ENSP00000259324; ENSG00000136802.
ENST00000372599; ENSP00000361680; ENSG00000136802.
ENST00000372600; ENSP00000361682; ENSG00000136802.
GeneIDi56262.
KEGGihsa:56262.
UCSCiuc004bwl.5. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Cross-referencesi

Web resourcesi

LRRC8Abase

LRRC8A mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY143166 mRNA. Translation: AAN18279.1.
AB037858 mRNA. Translation: BAA92675.1. Different initiation.
AL672142 Genomic DNA. Translation: CAI10839.1.
BC051322 mRNA. Translation: AAH51322.1.
AY358286 mRNA. Translation: AAQ88653.1. Different initiation.
AK074723 mRNA. Translation: BAC11161.1. Different initiation.
CCDSiCCDS35155.1.
RefSeqiNP_001120716.1. NM_001127244.1.
NP_001120717.1. NM_001127245.1.
NP_062540.2. NM_019594.3.
XP_005252152.1. XM_005252095.2.
XP_005252153.1. XM_005252096.3.
XP_006717249.1. XM_006717186.2.
XP_011517165.1. XM_011518863.1.
XP_011517166.1. XM_011518864.2.
XP_011517167.1. XM_011518865.2.
UniGeneiHs.643600.

3D structure databases

ProteinModelPortaliQ8IWT6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121126. 23 interactors.
DIPiDIP-61360N.
IntActiQ8IWT6. 4 interactors.
STRINGi9606.ENSP00000259324.

Protein family/group databases

TCDBi1.A.25.3.1. the gap junction-forming innexin (innexin) family.

PTM databases

iPTMnetiQ8IWT6.
PhosphoSitePlusiQ8IWT6.

Polymorphism and mutation databases

BioMutaiLRRC8A.
DMDMi37537912.

Proteomic databases

EPDiQ8IWT6.
MaxQBiQ8IWT6.
PaxDbiQ8IWT6.
PeptideAtlasiQ8IWT6.
PRIDEiQ8IWT6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000259324; ENSP00000259324; ENSG00000136802.
ENST00000372599; ENSP00000361680; ENSG00000136802.
ENST00000372600; ENSP00000361682; ENSG00000136802.
GeneIDi56262.
KEGGihsa:56262.
UCSCiuc004bwl.5. human.

Organism-specific databases

CTDi56262.
DisGeNETi56262.
GeneCardsiLRRC8A.
HGNCiHGNC:19027. LRRC8A.
HPAiHPA016811.
MalaCardsiLRRC8A.
MIMi608360. gene.
613506. phenotype.
neXtProtiNX_Q8IWT6.
OpenTargetsiENSG00000136802.
Orphaneti33110. Autosomal agammaglobulinemia.
PharmGKBiPA134909315.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ8IWT6.
OMAiHIAYIPM.
OrthoDBiEOG091G01ER.
PhylomeDBiQ8IWT6.
TreeFamiTF331443.

Miscellaneous databases

ChiTaRSiLRRC8A. human.
GeneWikiiLRRC8A.
GenomeRNAii56262.
PROiQ8IWT6.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136802.
CleanExiHS_LRRC8A.
ExpressionAtlasiQ8IWT6. baseline and differential.
GenevisibleiQ8IWT6. HS.

Family and domain databases

Gene3Di3.80.10.10. 2 hits.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13855. LRR_8. 3 hits.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRC8A_HUMAN
AccessioniPrimary (citable) accession number: Q8IWT6
Secondary accession number(s): Q6UXM2, Q8NCI0, Q9P2B1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2003
Last sequence update: March 1, 2003
Last modified: November 30, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.