LRC8C_BOVIN
ID LRC8C_BOVIN Reviewed; 803 AA.
AC A5PK13;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8C {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 8C {ECO:0000250|UniProtKB:Q8TDW0};
GN Name=LRRC8C {ECO:0000250|UniProtKB:Q8TDW0};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Thymus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
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. The VRAC channel conducts iodide better than chloride
CC and can also conduct organic osmolytes like taurine. Plays a redundant
CC role in the efflux of amino acids, such as aspartate and glutamate, in
CC response to osmotic stress. 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. Channel
CC activity requires LRRC8A plus at least one other family member (LRRC8B,
CC LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the
CC precise subunit composition. {ECO:0000250|UniProtKB:Q8TDW0}.
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: Heterooligomer; heterooligomerizes with other LRRC8 proteins
CC (LRRC8A, LRRC8B, LRRC8D and/or LRRC8E), possibly to form a
CC heterohexamer. In vivo, the subunit composition may depend primarily on
CC expression levels, and heterooligomeric channels containing various
CC proportions of the different LRRC8 proteins may coexist.
CC {ECO:0000250|UniProtKB:Q8TDW0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8TDW0};
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC142315; AAI42316.1; -; mRNA.
DR RefSeq; NP_001092509.1; NM_001099039.2.
DR AlphaFoldDB; A5PK13; -.
DR SMR; A5PK13; -.
DR STRING; 9913.ENSBTAP00000001193; -.
DR PaxDb; A5PK13; -.
DR PRIDE; A5PK13; -.
DR Ensembl; ENSBTAT00000001193; ENSBTAP00000001193; ENSBTAG00000000900.
DR Ensembl; ENSBTAT00000085971; ENSBTAP00000072625; ENSBTAG00000000900.
DR GeneID; 527708; -.
DR KEGG; bta:527708; -.
DR CTD; 84230; -.
DR VEuPathDB; HostDB:ENSBTAG00000000900; -.
DR VGNC; VGNC:31031; LRRC8C.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000159250; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; A5PK13; -.
DR OMA; LYIMYVR; -.
DR OrthoDB; 167523at2759; -.
DR TreeFam; TF331443; -.
DR Reactome; R-BTA-5223345; Miscellaneous transport and binding events.
DR Proteomes; UP000009136; Chromosome 3.
DR Bgee; ENSBTAG00000000900; Expressed in oocyte and 105 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0034702; C:ion channel complex; ISS: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:0140361; P:cyclic-GMP-AMP transmembrane import across plasma membrane; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR026906; LRR_5.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR021040; LRRC8_Pannexin-like.
DR Pfam; PF13306; LRR_5; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF12534; Pannexin_like; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR PROSITE; PS51450; LRR; 7.
PE 2: Evidence at transcript level;
KW Cell membrane; Endoplasmic reticulum; Glycoprotein; Ion channel;
KW 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_0000367049"
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..419
FT /note="LRR 1"
FT REPEAT 420..443
FT /note="LRR 2"
FT REPEAT 446..465
FT /note="LRR 3"
FT REPEAT 468..490
FT /note="LRR 4"
FT REPEAT 492..513
FT /note="LRR 5"
FT REPEAT 515..536
FT /note="LRR 6"
FT REPEAT 543..563
FT /note="LRR 7"
FT REPEAT 566..586
FT /note="LRR 8"
FT REPEAT 590..611
FT /note="LRR 9"
FT REPEAT 613..634
FT /note="LRR 10"
FT REPEAT 638..659
FT /note="LRR 11"
FT REPEAT 661..682
FT /note="LRR 12"
FT REPEAT 684..705
FT /note="LRR 13"
FT REPEAT 707..728
FT /note="LRR 14"
FT REPEAT 730..751
FT /note="LRR 15"
FT REPEAT 753..774
FT /note="LRR 16"
FT REPEAT 776..799
FT /note="LRR 17"
FT REGION 177..209
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..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TDW0"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q498T9"
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"
SQ SEQUENCE 803 AA; 92319 MW; AC6E6C4CEDA332B5 CRC64;
MIPVTEFRQF SEQQPAFRVL KPWWDVFTDY LSVAMLMIGV FGCTLQVMQD KIICLPKRVQ
PSQNQSSVSN VSQAVASTTP LPPPKPSPSN PVTVEMKGLK TDLDLQQYSF INQMCYERAL
HWYAKYFPYL VLIHTLVFML CSNFWFKFPG SSSKIEHFIS ILGKCFDSPW TTRALSEVSG
EDSEEKDNRK NNMSRSNTTQ SGPEGSLVNS QSLKSIPEKF VVDKSTAGAL DKKEGEQAKA
LFEKVKKFRL HVEEGDILYA MYVRQTVLKV IKFLIIIAYN SALVSKVQFT VDCNVDIQDM
TGYKNFSCNH TMAHLFSKLS FCYLCFVSIY GLTCLYTLYW LFYRSLKEYS FEYVRQETGI
DDIPDVKNDF AFMLHMIDQY DPLYSKRFAV FLSEVSENKL KQLNLNNEWT PDKLRQKLQT
NAHNRLELPL IMLSGLPDTV FEITELQSLK LEIIKNVMIP ATIAQLDNLQ ELSLHQCSVK
IHSAALSFLK ENLKVLSVKF DDMRELPPWM YGLRNLEELY LVGSLSHDIS RNVTLESLRD
LKSLKILSIK SNVSKIPQAV VDVSSHLQKM CIHNDGTKLV MLNNLKKMTN LTELELVHCD
LERIPHAVFS LLSLQELDLK ENNLKSIEEI VSFQHLRKLT VLKLWHNSIT YIPEHIKKLT
SLERLSFSHN KIEVLPSHLF LCNKIRYLDL SYNDIRFIPP EIGVLQSLQY FSITCNKVES
LPDELYFCKK LKTLKIGKNS LSVLSPKIGN LLFLSYLDVK GNHFEILPPE LGDCRALKRA
GLVVEDALFE TLPSDVREQM KTE
