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Protein

Volume-regulated anion channel subunit LRRC8D

Gene

LRRC8D

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

Functioni

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). 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). 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). LRRC8A and LRRC8D are required for the uptake of the drug cisplatin (PubMed:26530471). Mediates the import of the antibiotic blasticidin-S into the cell (PubMed:24782309).5 Publications

GO - Molecular functioni

  • volume-sensitive anion channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIon channel
Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-5223345 Miscellaneous transport and binding events

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 LRRC8D
Alternative name(s):
Leucine-rich repeat-containing protein 5
Leucine-rich repeat-containing protein 8D
Gene namesi
Name:LRRC8D
Synonyms:LRRC5
ORF Names:UNQ213/PRO239
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000171492.14
HGNCiHGNC:16992 LRRC8D
MIMi612890 gene
neXtProtiNX_Q7L1W4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22CytoplasmicSequence analysisAdd BLAST22
Transmembranei23 – 43HelicalSequence analysisAdd BLAST21
Topological domaini44 – 163ExtracellularSequence analysisAdd BLAST120
Transmembranei164 – 184HelicalSequence analysisAdd BLAST21
Topological domaini185 – 318CytoplasmicSequence analysisAdd BLAST134
Transmembranei319 – 339HelicalSequence analysisAdd BLAST21
Topological domaini340 – 364ExtracellularSequence analysisAdd BLAST25
Transmembranei365 – 385HelicalSequence analysisAdd BLAST21
Topological domaini386 – 858CytoplasmicSequence analysisAdd BLAST473

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44T → C: Alters channel anion selectivity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000171492
PharmGKBiPA30464

Polymorphism and mutation databases

BioMutaiLRRC8D
DMDMi51701663

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000844931 – 858Volume-regulated anion channel subunit LRRC8DAdd BLAST858

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 354By similarity
Modified residuei241PhosphoserineCombined sources1
Modified residuei242PhosphoserineCombined sources1
Modified residuei246PhosphoserineCombined sources1

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiQ7L1W4
MaxQBiQ7L1W4
PaxDbiQ7L1W4
PeptideAtlasiQ7L1W4
PRIDEiQ7L1W4
ProteomicsDBi68752
TopDownProteomicsiQ7L1W4

PTM databases

iPTMnetiQ7L1W4
PhosphoSitePlusiQ7L1W4

Expressioni

Gene expression databases

BgeeiENSG00000171492 Expressed in 235 organ(s), highest expression level in corpus callosum
CleanExiHS_LRRC8D
ExpressionAtlasiQ7L1W4 baseline and differential
GenevisibleiQ7L1W4 HS

Organism-specific databases

HPAiHPA014745

Interactioni

Subunit structurei

Heterohexamer (Probable). Oligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:26530471, PubMed:28193731, 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).Curated5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
LRRC8AQ8IWT62EBI-861997,EBI-10970086

Protein-protein interaction databases

BioGridi120447, 9 interactors
CORUMiQ7L1W4
DIPiDIP-31280N
IntActiQ7L1W4, 2 interactors
STRINGi9606.ENSP00000338887

Structurei

3D structure databases

ProteinModelPortaliQ7L1W4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati514 – 534LRR 1Add BLAST21
Repeati538 – 559LRR 2Add BLAST22
Repeati561 – 582LRR 3Add BLAST22
Repeati589 – 609LRR 4Add BLAST21
Repeati612 – 632LRR 5Add BLAST21
Repeati636 – 657LRR 6Add BLAST22
Repeati659 – 680LRR 7Add BLAST22
Repeati684 – 705LRR 8Add BLAST22
Repeati707 – 728LRR 9Add BLAST22
Repeati730 – 751LRR 10Add BLAST22
Repeati753 – 774LRR 11Add BLAST22
Repeati776 – 797LRR 12Add BLAST22
Repeati799 – 820LRR 13Add BLAST22

Sequence similaritiesi

Belongs to the LRRC8 family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00930000150868
HOGENOMiHOG000231806
HOVERGENiHBG052360
InParanoidiQ7L1W4
KOiK22038
OMAiQLFKCVK
OrthoDBiEOG091G01ER
PhylomeDBiQ7L1W4
TreeFamiTF331443

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR038960 LRRC8
IPR021040 LRRC8_Pannexin-like
PANTHERiPTHR43945 PTHR43945, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF12534 Pannexin_like, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
PROSITEiView protein in PROSITE
PS51450 LRR, 9 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

Q7L1W4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MFTLAEVASL NDIQPTYRIL KPWWDVFMDY LAVVMLMVAI FAGTMQLTKD
60 70 80 90 100
QVVCLPVLPS PVNSKAHTPP GNAEVTTNIP KMEAATNQDQ DGRTTNDISF
110 120 130 140 150
GTSAVTPDIP LRATYPRTDF ALPNQEAKKE KKDPTGRKTN LDFQQYVFIN
160 170 180 190 200
QMCYHLALPW YSKYFPYLAL IHTIILMVSS NFWFKYPKTC SKVEHFVSIL
210 220 230 240 250
GKCFESPWTT KALSETACED SEENKQRITG AQTLPKHVST SSDEGSPSAS
260 270 280 290 300
TPMINKTGFK FSAEKPVIEV PSMTILDKKD GEQAKALFEK VRKFRAHVED
310 320 330 340 350
SDLIYKLYVV QTVIKTAKFI FILCYTANFV NAISFEHVCK PKVEHLIGYE
360 370 380 390 400
VFECTHNMAY MLKKLLISYI SIICVYGFIC LYTLFWLFRI PLKEYSFEKV
410 420 430 440 450
REESSFSDIP DVKNDFAFLL HMVDQYDQLY SKRFGVFLSE VSENKLREIS
460 470 480 490 500
LNHEWTFEKL RQHISRNAQD KQELHLFMLS GVPDAVFDLT DLDVLKLELI
510 520 530 540 550
PEAKIPAKIS QMTNLQELHL CHCPAKVEQT AFSFLRDHLR CLHVKFTDVA
560 570 580 590 600
EIPAWVYLLK NLRELYLIGN LNSENNKMIG LESLRELRHL KILHVKSNLT
610 620 630 640 650
KVPSNITDVA PHLTKLVIHN DGTKLLVLNS LKKMMNVAEL ELQNCELERI
660 670 680 690 700
PHAIFSLSNL QELDLKSNNI RTIEEIISFQ HLKRLTCLKL WHNKIVTIPP
710 720 730 740 750
SITHVKNLES LYFSNNKLES LPVAVFSLQK LRCLDVSYNN ISMIPIEIGL
760 770 780 790 800
LQNLQHLHIT GNKVDILPKQ LFKCIKLRTL NLGQNCITSL PEKVGQLSQL
810 820 830 840 850
TQLELKGNCL DRLPAQLGQC RMLKKSGLVV EDHLFDTLPL EVKEALNQDI

NIPFANGI
Length:858
Mass (Da):98,201
Last modified:July 5, 2004 - v1
Checksum:i52A8B6EEF6F0FE2B
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PMF9E9PMF9_HUMAN
Volume-regulated anion channel subu...
LRRC8D
274Annotation score:
E9PL08E9PL08_HUMAN
Volume-regulated anion channel subu...
LRRC8D
186Annotation score:
E9PJS7E9PJS7_HUMAN
Volume-regulated anion channel subu...
LRRC8D
121Annotation score:
Q5VWA0Q5VWA0_HUMAN
Volume-regulated anion channel subu...
LRRC8D
116Annotation score:
E9PJ89E9PJ89_HUMAN
Volume-regulated anion channel subu...
LRRC8D
30Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051132371S → Y. Corresponds to variant dbSNP:rs11552246Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL391497 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW73130.1
CH471097 Genomic DNA Translation: EAW73131.1
CH471097 Genomic DNA Translation: EAW73132.1
BC024159 mRNA Translation: AAH24159.2
AK001332 mRNA Translation: BAA91631.1 Different initiation.
AY358874 mRNA Translation: AAQ89233.1 Different initiation.
CCDSiCCDS726.1
RefSeqiNP_001127951.1, NM_001134479.1
NP_060573.2, NM_018103.4
XP_011539991.1, XM_011541689.1
XP_016857088.1, XM_017001599.1
XP_016857089.1, XM_017001600.1
XP_016857090.1, XM_017001601.1
XP_016857091.1, XM_017001602.1
UniGeneiHs.482087

Genome annotation databases

EnsembliENST00000337338; ENSP00000338887; ENSG00000171492
ENST00000394593; ENSP00000378093; ENSG00000171492
GeneIDi55144
KEGGihsa:55144
UCSCiuc001dnm.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL391497 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW73130.1
CH471097 Genomic DNA Translation: EAW73131.1
CH471097 Genomic DNA Translation: EAW73132.1
BC024159 mRNA Translation: AAH24159.2
AK001332 mRNA Translation: BAA91631.1 Different initiation.
AY358874 mRNA Translation: AAQ89233.1 Different initiation.
CCDSiCCDS726.1
RefSeqiNP_001127951.1, NM_001134479.1
NP_060573.2, NM_018103.4
XP_011539991.1, XM_011541689.1
XP_016857088.1, XM_017001599.1
XP_016857089.1, XM_017001600.1
XP_016857090.1, XM_017001601.1
XP_016857091.1, XM_017001602.1
UniGeneiHs.482087

3D structure databases

ProteinModelPortaliQ7L1W4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120447, 9 interactors
CORUMiQ7L1W4
DIPiDIP-31280N
IntActiQ7L1W4, 2 interactors
STRINGi9606.ENSP00000338887

Protein family/group databases

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

PTM databases

iPTMnetiQ7L1W4
PhosphoSitePlusiQ7L1W4

Polymorphism and mutation databases

BioMutaiLRRC8D
DMDMi51701663

Proteomic databases

EPDiQ7L1W4
MaxQBiQ7L1W4
PaxDbiQ7L1W4
PeptideAtlasiQ7L1W4
PRIDEiQ7L1W4
ProteomicsDBi68752
TopDownProteomicsiQ7L1W4

Protocols and materials databases

DNASUi55144
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000337338; ENSP00000338887; ENSG00000171492
ENST00000394593; ENSP00000378093; ENSG00000171492
GeneIDi55144
KEGGihsa:55144
UCSCiuc001dnm.4 human

Organism-specific databases

CTDi55144
EuPathDBiHostDB:ENSG00000171492.14
GeneCardsiLRRC8D
HGNCiHGNC:16992 LRRC8D
HPAiHPA014745
MIMi612890 gene
neXtProtiNX_Q7L1W4
OpenTargetsiENSG00000171492
PharmGKBiPA30464
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00930000150868
HOGENOMiHOG000231806
HOVERGENiHBG052360
InParanoidiQ7L1W4
KOiK22038
OMAiQLFKCVK
OrthoDBiEOG091G01ER
PhylomeDBiQ7L1W4
TreeFamiTF331443

Enzyme and pathway databases

ReactomeiR-HSA-5223345 Miscellaneous transport and binding events

Miscellaneous databases

ChiTaRSiLRRC8D human
GeneWikiiLRRC8D
GenomeRNAii55144
PROiPR:Q7L1W4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171492 Expressed in 235 organ(s), highest expression level in corpus callosum
CleanExiHS_LRRC8D
ExpressionAtlasiQ7L1W4 baseline and differential
GenevisibleiQ7L1W4 HS

Family and domain databases

Gene3Di3.80.10.10, 2 hits
InterProiView protein in InterPro
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR038960 LRRC8
IPR021040 LRRC8_Pannexin-like
PANTHERiPTHR43945 PTHR43945, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF12534 Pannexin_like, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 7 hits
PROSITEiView protein in PROSITE
PS51450 LRR, 9 hits
ProtoNetiSearch...

Entry informationi

Entry nameiLRC8D_HUMAN
AccessioniPrimary (citable) accession number: Q7L1W4
Secondary accession number(s): D3DT29, Q6UWB2, Q9NVW3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 5, 2004
Last modified: November 7, 2018
This is version 141 of the entry and version 1 of the sequence. See 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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