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Protein

Volume-regulated anion channel subunit LRRC8C

Gene

LRRC8C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. The VRAC channel conducts iodide better than chloride and may also conduct organic osmolytes like taurine. Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition.2 Publications

GO - Molecular functioni

  • volume-sensitive anion channel activity Source: UniProtKB

GO - Biological processi

  • anion transmembrane transport Source: UniProtKB
  • fat cell differentiation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ion channel

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171488-MONOMER.

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 LRRC8C
Alternative name(s):
Factor for adipocyte differentiation 158
Leucine-rich repeat-containing protein 8C
Gene namesi
Name:LRRC8C
Synonyms:AD158, FAD158
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:25075. LRRC8C.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22CytoplasmicSequence analysisAdd BLAST22
Transmembranei23 – 43HelicalSequence analysisAdd BLAST21
Topological domaini44 – 125ExtracellularSequence analysisAdd BLAST82
Transmembranei126 – 146HelicalSequence analysisAdd BLAST21
Topological domaini147 – 266CytoplasmicSequence analysisAdd BLAST120
Transmembranei267 – 287HelicalSequence analysisAdd BLAST21
Topological domaini288 – 320ExtracellularSequence analysisAdd BLAST33
Transmembranei321 – 341HelicalSequence analysisAdd BLAST21
Topological domaini342 – 803CytoplasmicSequence analysisAdd BLAST462

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

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

DisGeNETi84230.
OpenTargetsiENSG00000171488.
PharmGKBiPA142671536.

Polymorphism and mutation databases

BioMutaiLRRC8C.
DMDMi317373383.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000762471 – 803Volume-regulated anion channel subunit LRRC8CAdd BLAST803

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Glycosylationi64N-linked (GlcNAc...)Sequence analysis1
Glycosylationi70N-linked (GlcNAc...)Sequence analysis1
Modified residuei198PhosphothreonineBy similarity1
Modified residuei212PhosphoserineCombined sources1
Modified residuei215PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ8TDW0.
MaxQBiQ8TDW0.
PaxDbiQ8TDW0.
PeptideAtlasiQ8TDW0.
PRIDEiQ8TDW0.

PTM databases

iPTMnetiQ8TDW0.
PhosphoSitePlusiQ8TDW0.

Expressioni

Tissue specificityi

Expressed at highest levels in skeletal muscle, and at moderate levels in heart, lung and peripheral blood leukocytes.1 Publication

Gene expression databases

BgeeiENSG00000171488.
CleanExiHS_LRRC8C.
ExpressionAtlasiQ8TDW0. baseline and differential.
GenevisibleiQ8TDW0. HS.

Organism-specific databases

HPAiHPA029347.

Interactioni

Subunit structurei

Heterooligomer; heterooligomerizes with other LRRC8 proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E), possibly to form a heterohexamer (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).Curated2 Publications

Protein-protein interaction databases

BioGridi123963. 7 interactors.
DIPiDIP-61362N.
MINTiMINT-4721599.
STRINGi9606.ENSP00000359483.

Structurei

3D structure databases

ProteinModelPortaliQ8TDW0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati397 – 419LRR 1Add BLAST23
Repeati420 – 443LRR 2Add BLAST24
Repeati446 – 465LRR 3Add BLAST20
Repeati468 – 490LRR 4Add BLAST23
Repeati492 – 513LRR 5Add BLAST22
Repeati515 – 536LRR 6Add BLAST22
Repeati543 – 563LRR 7Add BLAST21
Repeati566 – 586LRR 8Add BLAST21
Repeati590 – 611LRR 9Add BLAST22
Repeati613 – 634LRR 10Add BLAST22
Repeati638 – 659LRR 11Add BLAST22
Repeati661 – 682LRR 12Add BLAST22
Repeati684 – 705LRR 13Add BLAST22
Repeati707 – 728LRR 14Add BLAST22
Repeati730 – 751LRR 15Add BLAST22
Repeati753 – 774LRR 16Add BLAST22
Repeati776 – 799LRR 17Add BLAST24

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.
InParanoidiQ8TDW0.
OMAiNEWTADK.
OrthoDBiEOG091G01ER.
PhylomeDBiQ8TDW0.
TreeFamiTF331443.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR026906. LRR_5.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13306. LRR_5. 1 hit.
PF13855. LRR_8. 1 hit.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 7 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8TDW0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIPVTEFRQF SEQQPAFRVL KPWWDVFTDY LSVAMLMIGV FGCTLQVMQD
60 70 80 90 100
KIICLPKRVQ PAQNHSSLSN VSQAVASTTP LPPPKPSPAN PITVEMKGLK
110 120 130 140 150
TDLDLQQYSF INQMCYERAL HWYAKYFPYL VLIHTLVFML CSNFWFKFPG
160 170 180 190 200
SSSKIEHFIS ILGKCFDSPW TTRALSEVSG EDSEEKDNRK NNMNRSNTIQ
210 220 230 240 250
SGPEDSLVNS QSLKSIPEKF VVDKSTAGAL DKKEGEQAKA LFEKVKKFRL
260 270 280 290 300
HVEEGDILYA MYVRQTVLKV IKFLIIIAYN SALVSKVQFT VDCNVDIQDM
310 320 330 340 350
TGYKNFSCNH TMAHLFSKLS FCYLCFVSIY GLTCLYTLYW LFYRSLREYS
360 370 380 390 400
FEYVRQETGI DDIPDVKNDF AFMLHMIDQY DPLYSKRFAV FLSEVSENKL
410 420 430 440 450
KQLNLNNEWT PDKLRQKLQT NAHNRLELPL IMLSGLPDTV FEITELQSLK
460 470 480 490 500
LEIIKNVMIP ATIAQLDNLQ ELSLHQCSVK IHSAALSFLK ENLKVLSVKF
510 520 530 540 550
DDMRELPPWM YGLRNLEELY LVGSLSHDIS RNVTLESLRD LKSLKILSIK
560 570 580 590 600
SNVSKIPQAV VDVSSHLQKM CIHNDGTKLV MLNNLKKMTN LTELELVHCD
610 620 630 640 650
LERIPHAVFS LLSLQELDLK ENNLKSIEEI VSFQHLRKLT VLKLWHNSIT
660 670 680 690 700
YIPEHIKKLT SLERLSFSHN KIEVLPSHLF LCNKIRYLDL SYNDIRFIPP
710 720 730 740 750
EIGVLQSLQY FSITCNKVES LPDELYFCKK LKTLKIGKNS LSVLSPKIGN
760 770 780 790 800
LLFLSYLDVK GNHFEILPPE LGDCRALKRA GLVVEDALFE TLPSDVREQM

KTE
Length:803
Mass (Da):92,450
Last modified:January 11, 2011 - v2
Checksum:i95D179F028BF3F50
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti570M → T in BAG54591 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051129205D → G.Combined sources4 PublicationsCorresponds to variant rs474536dbSNPEnsembl.1
Natural variantiVAR_051130468N → S.Corresponds to variant rs12032393dbSNPEnsembl.1
Natural variantiVAR_051131800M → I.Corresponds to variant rs12036569dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081509 mRNA. Translation: BAB86303.1.
AK127881 mRNA. Translation: BAG54591.1.
AC093423 Genomic DNA. No translation available.
BC113973 mRNA. Translation: AAI13974.1.
AL136919 mRNA. Translation: CAB66853.2.
CCDSiCCDS725.1.
RefSeqiNP_115646.2. NM_032270.4.
XP_011540584.1. XM_011542282.2.
XP_016857992.1. XM_017002503.1.
UniGeneiHs.412836.

Genome annotation databases

EnsembliENST00000370454; ENSP00000359483; ENSG00000171488.
GeneIDi84230.
KEGGihsa:84230.
UCSCiuc001dnl.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB081509 mRNA. Translation: BAB86303.1.
AK127881 mRNA. Translation: BAG54591.1.
AC093423 Genomic DNA. No translation available.
BC113973 mRNA. Translation: AAI13974.1.
AL136919 mRNA. Translation: CAB66853.2.
CCDSiCCDS725.1.
RefSeqiNP_115646.2. NM_032270.4.
XP_011540584.1. XM_011542282.2.
XP_016857992.1. XM_017002503.1.
UniGeneiHs.412836.

3D structure databases

ProteinModelPortaliQ8TDW0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123963. 7 interactors.
DIPiDIP-61362N.
MINTiMINT-4721599.
STRINGi9606.ENSP00000359483.

Protein family/group databases

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

PTM databases

iPTMnetiQ8TDW0.
PhosphoSitePlusiQ8TDW0.

Polymorphism and mutation databases

BioMutaiLRRC8C.
DMDMi317373383.

Proteomic databases

EPDiQ8TDW0.
MaxQBiQ8TDW0.
PaxDbiQ8TDW0.
PeptideAtlasiQ8TDW0.
PRIDEiQ8TDW0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370454; ENSP00000359483; ENSG00000171488.
GeneIDi84230.
KEGGihsa:84230.
UCSCiuc001dnl.5. human.

Organism-specific databases

CTDi84230.
DisGeNETi84230.
GeneCardsiLRRC8C.
HGNCiHGNC:25075. LRRC8C.
HPAiHPA029347.
MIMi612889. gene.
neXtProtiNX_Q8TDW0.
OpenTargetsiENSG00000171488.
PharmGKBiPA142671536.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0619. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00840000129676.
HOGENOMiHOG000231806.
HOVERGENiHBG052360.
InParanoidiQ8TDW0.
OMAiNEWTADK.
OrthoDBiEOG091G01ER.
PhylomeDBiQ8TDW0.
TreeFamiTF331443.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000171488-MONOMER.

Miscellaneous databases

ChiTaRSiLRRC8C. human.
GenomeRNAii84230.
PROiQ8TDW0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171488.
CleanExiHS_LRRC8C.
ExpressionAtlasiQ8TDW0. baseline and differential.
GenevisibleiQ8TDW0. HS.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR026906. LRR_5.
IPR021040. LRRC8_Pannexin-like.
[Graphical view]
PfamiPF13306. LRR_5. 1 hit.
PF13855. LRR_8. 1 hit.
PF12534. Pannexin_like. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 7 hits.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 7 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRC8C_HUMAN
AccessioniPrimary (citable) accession number: Q8TDW0
Secondary accession number(s): B3KXS9, Q29RV6, Q9H075
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: January 11, 2011
Last modified: November 30, 2016
This is version 119 of the entry and version 2 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, Reference proteome

Documents

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