UniProtKB - Q7L1W4 (LRC8D_HUMAN)
Protein
Volume-regulated anion channel subunit LRRC8D
Gene
LRRC8D
Organism
Homo sapiens (Human)
Status
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
- anion transmembrane transport Source: UniProtKB
- aspartate transmembrane transport Source: UniProtKB
- cellular response to osmotic stress Source: UniProtKB
- taurine transport Source: UniProtKB
- transmembrane transport Source: Reactome
Keywordsi
Molecular function | Ion channel |
Biological process | Ion transport, Transport |
Enzyme and pathway databases
PathwayCommonsi | Q7L1W4 |
Reactomei | R-HSA-5223345, Miscellaneous transport and binding events |
Protein family/group databases
TCDBi | 1.A.25.3.1, the gap junction-forming innexin (innexin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Volume-regulated anion channel subunit LRRC8DAlternative name(s): Leucine-rich repeat-containing protein 5 Leucine-rich repeat-containing protein 8D |
Gene namesi | Name:LRRC8D Synonyms:LRRC5 ORF Names:UNQ213/PRO239 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000171492.14 |
HGNCi | HGNC:16992, LRRC8D |
MIMi | 612890, gene |
neXtProti | NX_Q7L1W4 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication1 Publication
Plasma membrane
- Cell membrane 3 Publications; Multi-pass membrane protein Curated
Note: In the absence of LRRC8A, resides primarily in a cytoplasmic compartment, probably the endoplasmic reticulum (PubMed:24782309, PubMed:24790029). Requires LRRC8A for expression at the cell membrane (PubMed:24790029).2 Publications
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Plasma Membrane
- integral component of plasma membrane Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- ion channel complex Source: UniProtKB
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 22 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 23 – 43 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 44 – 163 | ExtracellularSequence analysisAdd BLAST | 120 | |
Transmembranei | 164 – 184 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 185 – 318 | CytoplasmicSequence analysisAdd BLAST | 134 | |
Transmembranei | 319 – 339 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 340 – 364 | ExtracellularSequence analysisAdd BLAST | 25 | |
Transmembranei | 365 – 385 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 386 – 858 | CytoplasmicSequence analysisAdd BLAST | 473 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 44 | T → C: Alters channel anion selectivity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 55144 |
OpenTargetsi | ENSG00000171492 |
PharmGKBi | PA30464 |
Miscellaneous databases
Pharosi | Q7L1W4, Tdark |
Polymorphism and mutation databases
BioMutai | LRRC8D |
DMDMi | 51701663 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000084493 | 1 – 858 | Volume-regulated anion channel subunit LRRC8DAdd BLAST | 858 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 54 ↔ 354 | By similarity | ||
Modified residuei | 241 | PhosphoserineCombined sources | 1 | |
Modified residuei | 242 | PhosphoserineCombined sources | 1 | |
Modified residuei | 246 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Disulfide bond, PhosphoproteinProteomic databases
EPDi | Q7L1W4 |
jPOSTi | Q7L1W4 |
MassIVEi | Q7L1W4 |
MaxQBi | Q7L1W4 |
PaxDbi | Q7L1W4 |
PeptideAtlasi | Q7L1W4 |
PRIDEi | Q7L1W4 |
ProteomicsDBi | 68752 |
TopDownProteomicsi | Q7L1W4 |
PTM databases
GlyGeni | Q7L1W4, 2 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q7L1W4 |
PhosphoSitePlusi | Q7L1W4 |
Expressioni
Gene expression databases
Bgeei | ENSG00000171492, Expressed in corpus callosum and 246 other tissues |
ExpressionAtlasi | Q7L1W4, baseline and differential |
Genevisiblei | Q7L1W4, HS |
Organism-specific databases
HPAi | ENSG00000171492, Tissue enhanced (brain) |
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 PublicationsBinary interactionsi
Q7L1W4
With | #Exp. | IntAct |
---|---|---|
LRRC8A [Q8IWT6] | 2 | EBI-861997,EBI-10970086 |
Protein-protein interaction databases
BioGRIDi | 120447, 14 interactors |
CORUMi | Q7L1W4 |
DIPi | DIP-31280N |
IntActi | Q7L1W4, 9 interactors |
STRINGi | 9606.ENSP00000338887 |
Miscellaneous databases
RNActi | Q7L1W4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 514 – 534 | LRR 1Add BLAST | 21 | |
Repeati | 538 – 559 | LRR 2Add BLAST | 22 | |
Repeati | 561 – 582 | LRR 3Add BLAST | 22 | |
Repeati | 589 – 609 | LRR 4Add BLAST | 21 | |
Repeati | 612 – 632 | LRR 5Add BLAST | 21 | |
Repeati | 636 – 657 | LRR 6Add BLAST | 22 | |
Repeati | 659 – 680 | LRR 7Add BLAST | 22 | |
Repeati | 684 – 705 | LRR 8Add BLAST | 22 | |
Repeati | 707 – 728 | LRR 9Add BLAST | 22 | |
Repeati | 730 – 751 | LRR 10Add BLAST | 22 | |
Repeati | 753 – 774 | LRR 11Add BLAST | 22 | |
Repeati | 776 – 797 | LRR 12Add BLAST | 22 | |
Repeati | 799 – 820 | LRR 13Add BLAST | 22 |
Sequence similaritiesi
Belongs to the LRRC8 family.Curated
Keywords - Domaini
Leucine-rich repeat, Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0619, Eukaryota |
GeneTreei | ENSGT00940000154043 |
HOGENOMi | CLU_019019_0_0_1 |
InParanoidi | Q7L1W4 |
OMAi | QLFKCVK |
OrthoDBi | 187778at2759 |
PhylomeDBi | Q7L1W4 |
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 IPR021040, LRRC8_Pannexin-like |
Pfami | View protein in Pfam PF13855, LRR_8, 2 hits PF12534, Pannexin_like, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 7 hits |
PROSITEi | View protein in PROSITE PS51450, LRR, 9 hits |
(1+)i Sequence
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
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
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PMF9 | E9PMF9_HUMAN | Volume-regulated anion channel subu... | LRRC8D | 274 | Annotation score: | ||
E9PJS7 | E9PJS7_HUMAN | Volume-regulated anion channel subu... | LRRC8D | 121 | Annotation score: | ||
Q5VWA0 | Q5VWA0_HUMAN | Volume-regulated anion channel subu... | LRRC8D | 116 | Annotation score: | ||
E9PL08 | E9PL08_HUMAN | Volume-regulated anion channel subu... | LRRC8D | 186 | Annotation score: | ||
E9PJ89 | E9PJ89_HUMAN | Volume-regulated anion channel subu... | LRRC8D | 30 | Annotation 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051132 | 371 | S → 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. |
CCDSi | CCDS726.1 |
RefSeqi | NP_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 |
Genome annotation databases
Ensembli | ENST00000337338; ENSP00000338887; ENSG00000171492 ENST00000394593; ENSP00000378093; ENSG00000171492 |
GeneIDi | 55144 |
KEGGi | hsa:55144 |
UCSCi | uc001dnm.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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. |
CCDSi | CCDS726.1 |
RefSeqi | NP_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 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6M04 | electron microscopy | 4.36 | A/B/C/D/E/F | 1-858 | [»] | |
SMRi | Q7L1W4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 120447, 14 interactors |
CORUMi | Q7L1W4 |
DIPi | DIP-31280N |
IntActi | Q7L1W4, 9 interactors |
STRINGi | 9606.ENSP00000338887 |
Protein family/group databases
TCDBi | 1.A.25.3.1, the gap junction-forming innexin (innexin) family |
PTM databases
GlyGeni | Q7L1W4, 2 sites, 1 O-linked glycan (2 sites) |
iPTMneti | Q7L1W4 |
PhosphoSitePlusi | Q7L1W4 |
Polymorphism and mutation databases
BioMutai | LRRC8D |
DMDMi | 51701663 |
Proteomic databases
EPDi | Q7L1W4 |
jPOSTi | Q7L1W4 |
MassIVEi | Q7L1W4 |
MaxQBi | Q7L1W4 |
PaxDbi | Q7L1W4 |
PeptideAtlasi | Q7L1W4 |
PRIDEi | Q7L1W4 |
ProteomicsDBi | 68752 |
TopDownProteomicsi | Q7L1W4 |
Protocols and materials databases
Antibodypediai | 2631, 48 antibodies |
DNASUi | 55144 |
Genome annotation databases
Ensembli | ENST00000337338; ENSP00000338887; ENSG00000171492 ENST00000394593; ENSP00000378093; ENSG00000171492 |
GeneIDi | 55144 |
KEGGi | hsa:55144 |
UCSCi | uc001dnm.4, human |
Organism-specific databases
CTDi | 55144 |
DisGeNETi | 55144 |
EuPathDBi | HostDB:ENSG00000171492.14 |
GeneCardsi | LRRC8D |
HGNCi | HGNC:16992, LRRC8D |
HPAi | ENSG00000171492, Tissue enhanced (brain) |
MIMi | 612890, gene |
neXtProti | NX_Q7L1W4 |
OpenTargetsi | ENSG00000171492 |
PharmGKBi | PA30464 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0619, Eukaryota |
GeneTreei | ENSGT00940000154043 |
HOGENOMi | CLU_019019_0_0_1 |
InParanoidi | Q7L1W4 |
OMAi | QLFKCVK |
OrthoDBi | 187778at2759 |
PhylomeDBi | Q7L1W4 |
TreeFami | TF331443 |
Enzyme and pathway databases
PathwayCommonsi | Q7L1W4 |
Reactomei | R-HSA-5223345, Miscellaneous transport and binding events |
Miscellaneous databases
BioGRID-ORCSi | 55144, 7 hits in 843 CRISPR screens |
ChiTaRSi | LRRC8D, human |
GeneWikii | LRRC8D |
GenomeRNAii | 55144 |
Pharosi | Q7L1W4, Tdark |
PROi | PR:Q7L1W4 |
RNActi | Q7L1W4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000171492, Expressed in corpus callosum and 246 other tissues |
ExpressionAtlasi | Q7L1W4, baseline and differential |
Genevisiblei | Q7L1W4, HS |
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 IPR021040, LRRC8_Pannexin-like |
Pfami | View protein in Pfam PF13855, LRR_8, 2 hits PF12534, Pannexin_like, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 7 hits |
PROSITEi | View protein in PROSITE PS51450, LRR, 9 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | LRC8D_HUMAN | |
Accessioni | Q7L1W4Primary (citable) accession number: Q7L1W4 Secondary accession number(s): D3DT29, Q6UWB2, Q9NVW3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 31, 2004 |
Last sequence update: | July 5, 2004 | |
Last modified: | December 2, 2020 | |
This is version 155 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
3D-structure, Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations