LRC8C_RAT
ID LRC8C_RAT Reviewed; 803 AA.
AC Q498T9;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-SEP-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8C {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8C {ECO:0000303|PubMed:28833202};
GN Name=Lrrc8c {ECO:0000303|PubMed:28833202, ECO:0000312|RGD:1306585};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212 AND SER-215, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=28833202; DOI=10.1113/jp275053;
RA Schober A.L., Wilson C.S., Mongin A.A.;
RT "Molecular composition and heterogeneity of the LRRC8-containing swelling-
RT activated osmolyte channels in primary rat astrocytes.";
RL J. Physiol. (Lond.) 595:6939-6951(2017).
CC -!- FUNCTION: Non-essential component of the volume-regulated anion channel
CC (VRAC, also named VSOAC channel), an anion channel required to maintain
CC a constant cell volume in response to extracellular or intracellular
CC osmotic changes (PubMed:28833202). The VRAC channel conducts iodide
CC better than chloride and can also conduct organic osmolytes like
CC taurine (By similarity). Plays a redundant role in the efflux of amino
CC acids, such as aspartate and glutamate, in response to osmotic stress
CC (By similarity). The VRAC channel also mediates transport of
CC immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune
CC messenger produced in response to DNA virus in the cytosol (By
CC similarity). Channel activity requires LRRC8A plus at least one other
CC family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel
CC characteristics depend on the precise subunit composition
CC (PubMed:28833202). {ECO:0000250|UniProtKB:Q8TDW0,
CC ECO:0000269|PubMed:28833202}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2',3'-cGAMP(out) = 2',3'-cGAMP(in); Xref=Rhea:RHEA:66320,
CC ChEBI:CHEBI:143093; Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66321;
CC Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:66322;
CC Evidence={ECO:0000250|UniProtKB:Q8TDW0};
CC -!- SUBUNIT: Heterohexamer (By similarity). Oligomerizes with other LRRC8
CC proteins (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E) to form a heterohexamer
CC (Probable). Detected in a channel complex that contains LRRC8A, LRRC8C
CC and LRRC8E (By similarity). In vivo, the subunit composition may depend
CC primarily on expression levels, and heterooligomeric channels
CC containing various proportions of the different LRRC8 proteins may
CC coexist (Probable). {ECO:0000250|UniProtKB:Q8R502,
CC ECO:0000250|UniProtKB:Q8TDW0, ECO:0000305|PubMed:28833202}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28833202};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q8TDW0}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q8TDW0}. Note=In the absence
CC of LRRC8A, resides primarily in a cytoplasmic compartment, probably the
CC endoplasmic reticulum. Requires LRRC8A for expression at the cell
CC membrane. {ECO:0000250|UniProtKB:Q8TDW0}.
CC -!- DOMAIN: The volume-regulated anion channel (VRAC) channel forms a
CC trimer of dimers, with symmetry mismatch between the pore-forming
CC domain and the cytosolic LRR repeats, a topology similar to gap
CC junction proteins. {ECO:0000250|UniProtKB:Q8IWT6}.
CC -!- DOMAIN: The cytoplasmic N-terminus preceding the first transmembrane
CC (residues 1-22) regulates volume-regulated anion channel (VRAC)
CC conductance, ion permeability and inactivation gating.
CC {ECO:0000250|UniProtKB:Q8TDW0}.
CC -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
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DR EMBL; BC100076; AAI00077.1; -; mRNA.
DR RefSeq; NP_001032256.1; NM_001037179.1.
DR RefSeq; XP_006250604.1; XM_006250542.3.
DR AlphaFoldDB; Q498T9; -.
DR SMR; Q498T9; -.
DR STRING; 10116.ENSRNOP00000002896; -.
DR GlyGen; Q498T9; 2 sites.
DR iPTMnet; Q498T9; -.
DR PhosphoSitePlus; Q498T9; -.
DR jPOST; Q498T9; -.
DR PaxDb; Q498T9; -.
DR PRIDE; Q498T9; -.
DR Ensembl; ENSRNOT00000104559; ENSRNOP00000082962; ENSRNOG00000065000.
DR GeneID; 289443; -.
DR KEGG; rno:289443; -.
DR CTD; 84230; -.
DR RGD; 1306585; Lrrc8c.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159250; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q498T9; -.
DR OMA; LYIMYVR; -.
DR OrthoDB; 167523at2759; -.
DR PhylomeDB; Q498T9; -.
DR TreeFam; TF331443; -.
DR Reactome; R-RNO-5223345; Miscellaneous transport and binding events.
DR PRO; PR:Q498T9; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000002122; Expressed in ovary and 18 other tissues.
DR Genevisible; Q498T9; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0034702; C:ion channel complex; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005225; F:volume-sensitive anion channel activity; ISS:UniProtKB.
DR GO; GO:0098656; P:anion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0015810; P:aspartate transmembrane transport; IMP:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IMP:UniProtKB.
DR GO; GO:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0015734; P:taurine transport; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR021040; LRRC8_Pannexin-like.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 9.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Ion channel; Ion transport; Leucine-rich repeat; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..803
FT /note="Volume-regulated anion channel subunit LRRC8C"
FT /id="PRO_0000076249"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..125
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 126..146
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 147..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..320
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 342..803
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 397..420
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 421..443
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 446..466
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 467..488
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 490..513
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 515..537
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 541..563
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 565..587
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 588..611
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 613..635
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 637..659
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 660..682
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 684..705
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 706..728
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 730..751
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 752..774
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 776..799
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REGION 177..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..308
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
FT DISULFID 115..293
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
SQ SEQUENCE 803 AA; 92463 MW; A9D0342A73FCE140 CRC64;
MIPVTEFRQF SEQQPAFRVL KPWWDVFTDY LSVAMLMIGV FGCTLQVMQD KIICLPKRVQ
PAQNHSSLSN VSQTVINTTP LPPPKPSPTN PATVEMKGLK TDLDLQQYSF INQMCYERAL
HWYAKYFPYL VLIHTLVFML CSNFWFKFPG SSSKIEHFIS ILGKCFDSPW TTRALSEVSG
EDSEEKDNRK NNMNRSNTIQ SGPEGSLVKS QSLKSIPEKF VVDKSTAGAL DKKEGEQAKA
LFEKVKKFRL HVEEGDILYA MYVRQTVLKV IKFLIIIAYN SALVSKVQFT VDCNVDIQDM
TGYKNFSCNH TMAHLFSKLS FCYLCFVSIY GLTCLYTLYW LFYRSLREYS FEYVRQETGI
DDIPDVKNDF AFMLHMIDQY DPLYSKRFAV FLSEVSENKL KQLNLNNEWT PDKLRQKLQT
NAHNRLELPL IMLSGLPDTV FEITELQSLK LEIIKNVMIP ATIAQLDNLQ ELSLHQCSVK
IHSAALSFLK ENLKVLSVKF DDMRELPPWM YGLRNLEELY LVGSLSHDIS KNVTLESLRD
LKSLKILSIK SNVSKIPQAV VDVSSHLQKM CIHNDGTKLV MLNNLKKMTN LTELELVHCD
LERIPHAVFS LLSLQELDLK ENNLKSIEEI VSFQHLRKLT VLKLWYNSIA YIPEHIKKLT
SLERLFFSHN KVEVLPSHLF LCNKIRYLDL SYNDIRFIPP EIGVLQSLQY FSITCNKVES
LPDELYFCKK LKTLKIGKNS LSVLSPKIGN LLFLSYLDIK GNHFEVLPPE LGDCRALKRA
GLVVEDALFE TLPSDVREQM KAD
