Lrrc8a

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 (PubMed:28833202). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (PubMed:28833202). 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). 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).By similarity1 Publication

GO - Molecular functionⁱ

identical protein binding Source: Ensembl
volume-sensitive anion channel activity
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28833202

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

anion transmembrane transport Source: UniProtKB
anion transport Source: UniProtKB
aspartate transmembrane transport
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28833202
cell volume homeostasis Source: UniProtKB
pre-B cell differentiation Source: UniProtKB
protein hexamerization Source: UniProtKB
response to osmotic stress
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28833202
signal transduction Source: GO_Central
taurine transport
Source: UniProtKB
Inferred from mutant phenotypeⁱ
- 28833202

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Ion channel
Biological process	Differentiation, Ion transport, Transport

Enzyme and pathway databases

Reactomeⁱ	R-RNO-5223345 Miscellaneous transport and binding events

Reactomeⁱ

R-RNO-5223345 Miscellaneous transport and binding events

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Volume-regulated anion channel subunit LRRC8A Alternative name(s): Leucine-rich repeat-containing protein 8A
Gene namesⁱ	Name:Lrrc8a Synonyms:Lrrc8
Organismⁱ	Rattus norvegicus (Rat)
Taxonomic identifierⁱ	10116 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus
Proteomesⁱ	UP000002494 Componentⁱ: Chromosome 3

Organism-specific databases

Rat genome database More...RGDⁱ	1311690 Lrrc8a

RGDⁱ

1311690 Lrrc8a

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 22	CytoplasmicSequence analysisAdd BLAST	22
Transmembraneⁱ	23 – 43	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	44 – 123	ExtracellularSequence analysisAdd BLAST	80
Transmembraneⁱ	124 – 144	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	145 – 268	CytoplasmicSequence analysisAdd BLAST	124
Transmembraneⁱ	269 – 289	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	290 – 323	ExtracellularSequence analysisAdd BLAST	34
Transmembraneⁱ	324 – 344	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	345 – 810	CytoplasmicSequence analysisAdd BLAST	466

Keywords - Cellular componentⁱ

Cell membrane, Membrane

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000084501	1 – 810	Volume-regulated anion channel subunit LRRC8AAdd BLAST		810

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	1	N-acetylmethionineBy similarity	1
Disulfide bondⁱ	54 ↔ 310	By similarity
Disulfide bondⁱ	57 ↔ 65	By similarity
Glycosylationⁱ	66	N-linked (GlcNAc...) asparagineSequence analysis	1
Glycosylationⁱ	83	N-linked (GlcNAc...) asparagineSequence analysis	1
Disulfide bondⁱ	113 ↔ 295	By similarity
Modified residueⁱ	200	PhosphothreonineBy similarity	1
Modified residueⁱ	202	PhosphoserineCombined sources	1
Modified residueⁱ	215	PhosphothreonineBy similarity	1
Modified residueⁱ	217	PhosphoserineCombined sources	1

Post-translational modificationⁱ

N-glycosylated.By similarity

Keywords - PTMⁱ

Acetylation, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbⁱ	Q4V8I7
PRIDEⁱ	Q4V8I7

PTM databases

iPTMnetⁱ	Q4V8I7
PhosphoSitePlusⁱ	Q4V8I7

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSRNOG00000025296 Expressed in 10 organ(s), highest expression level in brain
Genevisibleⁱ	Q4V8I7 RN

Interactionⁱ

Subunit structureⁱ

Hexamer. Heterohexamer; oligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer. Can form homohexamers in vitro, but these have lower conductance than heterohexamers (By similarity). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity). 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).By similarity1 Publication

GO - Molecular functionⁱ

identical protein binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

STRINGⁱ	10116.ENSRNOP00000031726

STRINGⁱ

10116.ENSRNOP00000031726

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q4V8I7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Repeatⁱ	399 – 422	LRR 1Sequence analysisAdd BLAST	24
Repeatⁱ	423 – 445	LRR 2Sequence analysisAdd BLAST	23
Repeatⁱ	447 – 468	LRR 3Sequence analysisAdd BLAST	22
Repeatⁱ	469 – 492	LRR 4Sequence analysisAdd BLAST	24
Repeatⁱ	493 – 515	LRR 5Sequence analysisAdd BLAST	23
Repeatⁱ	518 – 542	LRR 6Sequence analysisAdd BLAST	25
Repeatⁱ	543 – 565	LRR 7Sequence analysisAdd BLAST	23
Repeatⁱ	567 – 589	LRR 8Sequence analysisAdd BLAST	23
Repeatⁱ	590 – 613	LRR 9Sequence analysisAdd BLAST	24
Repeatⁱ	614 – 637	LRR 10Sequence analysisAdd BLAST	24
Repeatⁱ	639 – 661	LRR 11Sequence analysisAdd BLAST	23
Repeatⁱ	662 – 684	LRR 12Sequence analysisAdd BLAST	23
Repeatⁱ	686 – 707	LRR 13Sequence analysisAdd BLAST	22
Repeatⁱ	708 – 730	LRR 14Sequence analysisAdd BLAST	23
Repeatⁱ	732 – 753	LRR 15Sequence analysisAdd BLAST	22
Repeatⁱ	754 – 776	LRR 16Sequence analysisAdd BLAST	23
Repeatⁱ	778 – 801	LRR 17Sequence analysisAdd BLAST	24

Sequence similaritiesⁱ

Belongs to the LRRC8 family.Curated

Keywords - Domainⁱ

Leucine-rich repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG0619 Eukaryota COG4886 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00920000148937
HOGENOMⁱ	HOG000231806
HOVERGENⁱ	HBG052360
InParanoidⁱ	Q4V8I7
KEGG Orthology (KO) More...KOⁱ	K22038
OMAⁱ	VDTQPAY
PhylomeDBⁱ	Q4V8I7
TreeFamⁱ	TF331443

Family and domain databases

Gene3Dⁱ	3.80.10.10, 2 hits
InterProⁱ	View protein in InterPro IPR001611 Leu-rich_rpt IPR003591 Leu-rich_rpt_typical-subtyp IPR032675 LRR_dom_sf IPR038960 LRRC8 IPR021040 LRRC8_Pannexin-like
PANTHERⁱ	PTHR43945 PTHR43945, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF13855 LRR_8, 3 hits PF12534 Pannexin_like, 1 hit
SMARTⁱ	View protein in SMART SM00369 LRR_TYP, 8 hits
PROSITEⁱ	View protein in PROSITE PS51450 LRR, 11 hits

Sequenceⁱ

Sequence statusⁱ: Complete.

Q4V8I7-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MIPVTELRYF ADTQPAYRIL KPWWDVFTDY ISIVMLMIAV FGGTLQVTQD 
        60         70         80         90        100
KMICLPCKWV TKDSCNDSFR GWGASSPEPT YPNSTVLPTP 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 KVIKFFLIIC 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 TVFDLLELEV 
       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 VNLTELELIR 
       610        620        630        640        650
CDLERIPHSI FSLHNLQEID LKDNNLKTIE EIISFQHLHR LTCLKLWYNH 
       660        670        680        690        700
IAYIPIQIGN LTNLERLYLN RNKIEKIPTQ LFYCRKLRYL DLSHNNLTLL 
       710        720        730        740        750
PADIGLLQNL QNLAVTANRI EALPPELFQC RKLRALHLGN NVLQSLPSRV 
       760        770        780        790        800
GELTNLTQIE LRGNRLECLP VELGECPLLK RSGLVVEEDL FSTLPPEVKE 
       810
RLWRADKEQA

Length:810

Mass (Da):94,162

Last modified:July 5, 2005 - v1

Checksum:ⁱA05EE234C10615C0

GO

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	BC097371 mRNA Translation: AAH97371.1
NCBI Reference Sequences More...RefSeqⁱ	NP_001019953.1, NM_001024782.1 XP_017447329.1, XM_017591840.1 XP_017447330.1, XM_017591841.1 XP_017447331.1, XM_017591842.1 XP_017447332.1, XM_017591843.1
UniGeneⁱ	Rn.33512

Genome annotation databases

Ensemblⁱ	ENSRNOT00000033934; ENSRNOP00000031726; ENSRNOG00000025296 ENSRNOT00000078932; ENSRNOP00000071543; ENSRNOG00000025296
GeneIDⁱ	311846
KEGGⁱ	rno:311846
UCSC genome browser More...UCSCⁱ	RGD:1311690 rat

Similar proteinsⁱ

90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q4V8I7	Volume-regulated anion channel subunit LRRC8A	)	HUMAN		810	UniRef90_Q8IWT6
Volume-regulated anion channel subunit LRRC8A	)	MOUSE		810
Leucine rich repeat containing 8 VRAC subunit A		MACMU		810
LRRC8A isoform 1		PANTR		810
Leucine rich repeat containing 8 family, member A (Predicted)		PAPAN		810
+207

Protein	Similar proteins		Species	Score	Length	Source
Q4V8I7	Volume-regulated anion channel subunit LRRC8A	)	HUMAN		810	UniRef50_Q8IWT6
Volume-regulated anion channel subunit LRRC8A	)	MOUSE		810
Leucine rich repeat containing 8 VRAC subunit A		MACMU		810
LRRC8A isoform 1		PANTR		810
Leucine rich repeat containing 8 family, member A (Predicted)		PAPAN		810
+383

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	BC097371 mRNA Translation: AAH97371.1
RefSeqⁱ	NP_001019953.1, NM_001024782.1 XP_017447329.1, XM_017591840.1 XP_017447330.1, XM_017591841.1 XP_017447331.1, XM_017591842.1 XP_017447332.1, XM_017591843.1
UniGeneⁱ	Rn.33512

3D structure databases

ProteinModelPortalⁱ	Q4V8I7
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

STRINGⁱ	10116.ENSRNOP00000031726

STRINGⁱ

10116.ENSRNOP00000031726

PTM databases

iPTMnetⁱ	Q4V8I7
PhosphoSitePlusⁱ	Q4V8I7

Proteomic databases

PaxDbⁱ	Q4V8I7
PRIDEⁱ	Q4V8I7

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSRNOT00000033934; ENSRNOP00000031726; ENSRNOG00000025296 ENSRNOT00000078932; ENSRNOP00000071543; ENSRNOG00000025296
GeneIDⁱ	311846
KEGGⁱ	rno:311846
UCSCⁱ	RGD:1311690 rat

Organism-specific databases

CTDⁱ	56262
RGDⁱ	1311690 Lrrc8a

Phylogenomic databases

eggNOGⁱ	KOG0619 Eukaryota COG4886 LUCA
GeneTreeⁱ	ENSGT00920000148937
HOGENOMⁱ	HOG000231806
HOVERGENⁱ	HBG052360
InParanoidⁱ	Q4V8I7
KOⁱ	K22038
OMAⁱ	VDTQPAY
PhylomeDBⁱ	Q4V8I7
TreeFamⁱ	TF331443

Enzyme and pathway databases

Reactomeⁱ	R-RNO-5223345 Miscellaneous transport and binding events

Reactomeⁱ

R-RNO-5223345 Miscellaneous transport and binding events

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q4V8I7

PROⁱ

PR:Q4V8I7

Gene expression databases

Bgeeⁱ	ENSRNOG00000025296 Expressed in 10 organ(s), highest expression level in brain
Genevisibleⁱ	Q4V8I7 RN

Family and domain databases

Gene3Dⁱ	3.80.10.10, 2 hits
InterProⁱ	View protein in InterPro IPR001611 Leu-rich_rpt IPR003591 Leu-rich_rpt_typical-subtyp IPR032675 LRR_dom_sf IPR038960 LRRC8 IPR021040 LRRC8_Pannexin-like
PANTHERⁱ	PTHR43945 PTHR43945, 1 hit
Pfamⁱ	View protein in Pfam PF13855 LRR_8, 3 hits PF12534 Pannexin_like, 1 hit
SMARTⁱ	View protein in SMART SM00369 LRR_TYP, 8 hits
PROSITEⁱ	View protein in PROSITE PS51450 LRR, 11 hits
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	LRC8A_RAT
Accessionⁱ	Q4V8I7Primary (citable) accession number: Q4V8I7
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	February 7, 2006
	Last sequence update:	July 5, 2005
	Last modified:	September 12, 2018
	This is version 106 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

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UniProtKB - Q4V8I7 (LRC8A_RAT)

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Volume-regulated anion channel subunit LRRC8A

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Plasma membrane

Plasma Membrane

Other locations

Topology

Keywords - Cellular componenti

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ