LRC8D_RAT
ID LRC8D_RAT Reviewed; 858 AA.
AC Q5U308;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8D {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 5 {ECO:0000312|RGD:1309601};
DE AltName: Full=Leucine-rich repeat-containing protein 8D {ECO:0000303|PubMed:28833202};
GN Name=Lrrc8d {ECO:0000303|PubMed:28833202, ECO:0000312|RGD:1309601};
GN Synonyms=Lrrc5 {ECO:0000312|RGD:1309601};
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=Kidney;
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 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, in response to osmotic stress (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). Also acts as a regulator of glucose-sensing in
CC pancreatic beta cells: VRAC currents, generated in response to
CC hypotonicity- or glucose-induced beta cell swelling, depolarize cells,
CC thereby causing electrical excitation, leading to increase glucose
CC sensitivity and insulin secretion (By similarity). VRAC channels
CC containing LRRC8D inhibit transport of immunoreactive cyclic
CC dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in
CC response to DNA virus in the cytosol (By similarity).
CC {ECO:0000250|UniProtKB:Q7L1W4, ECO:0000250|UniProtKB:Q8BGR2,
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:Q7L1W4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000250|UniProtKB:Q7L1W4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000250|UniProtKB:Q7L1W4};
CC -!- SUBUNIT: Heterohexamer. Oligomerizes with other LRRC8 proteins (LRRC8A,
CC LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer. In vivo, the
CC subunit composition may depend primarily on expression levels, and
CC heterooligomeric channels containing various proportions of the
CC different LRRC8 proteins may coexist. {ECO:0000305|PubMed:28833202}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28833202};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q7L1W4}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q7L1W4}; Multi-pass membrane
CC protein {ECO:0000250|UniProtKB:Q7L1W4}. Note=In the absence of LRRC8A,
CC resides primarily in a cytoplasmic compartment, probably the
CC endoplasmic reticulum. Requires LRRC8A for expression at the cell
CC membrane. {ECO:0000250|UniProtKB:Q7L1W4}.
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:Q7L1W4}.
CC -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
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DR EMBL; BC085783; AAH85783.1; -; mRNA.
DR RefSeq; NP_001008339.2; NM_001008338.1.
DR RefSeq; XP_006250618.1; XM_006250556.3.
DR RefSeq; XP_017454645.1; XM_017599156.1.
DR RefSeq; XP_017454646.1; XM_017599157.1.
DR RefSeq; XP_017454647.1; XM_017599158.1.
DR RefSeq; XP_017454648.1; XM_017599159.1.
DR RefSeq; XP_017454649.1; XM_017599160.1.
DR AlphaFoldDB; Q5U308; -.
DR SMR; Q5U308; -.
DR STRING; 10116.ENSRNOP00000002888; -.
DR iPTMnet; Q5U308; -.
DR PhosphoSitePlus; Q5U308; -.
DR PaxDb; Q5U308; -.
DR PRIDE; Q5U308; -.
DR Ensembl; ENSRNOT00000094660; ENSRNOP00000096115; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000105738; ENSRNOP00000091428; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000106093; ENSRNOP00000081098; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000109682; ENSRNOP00000090251; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000112887; ENSRNOP00000087579; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000117756; ENSRNOP00000092059; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000118999; ENSRNOP00000096292; ENSRNOG00000002121.
DR Ensembl; ENSRNOT00000119904; ENSRNOP00000078114; ENSRNOG00000002121.
DR GeneID; 305131; -.
DR KEGG; rno:305131; -.
DR CTD; 55144; -.
DR RGD; 1309601; Lrrc8d.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000154043; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q5U308; -.
DR OrthoDB; 187778at2759; -.
DR PhylomeDB; Q5U308; -.
DR TreeFam; TF331443; -.
DR Reactome; R-RNO-5223345; Miscellaneous transport and binding events.
DR PRO; PR:Q5U308; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Genevisible; Q5U308; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
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:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IMP:UniProtKB.
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; 2.
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; Ion channel;
KW Ion transport; Leucine-rich repeat; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..858
FT /note="Volume-regulated anion channel subunit LRRC8D"
FT /id="PRO_0000084495"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TRANSMEM 23..48
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TOPO_DOM 49..163
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TRANSMEM 164..182
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TOPO_DOM 183..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TRANSMEM 309..330
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TOPO_DOM 331..360
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TRANSMEM 361..386
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT TOPO_DOM 387..858
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT REPEAT 514..534
FT /note="LRR 1"
FT REPEAT 538..559
FT /note="LRR 2"
FT REPEAT 561..582
FT /note="LRR 3"
FT REPEAT 589..609
FT /note="LRR 4"
FT REPEAT 612..632
FT /note="LRR 5"
FT REPEAT 636..657
FT /note="LRR 6"
FT REPEAT 659..680
FT /note="LRR 7"
FT REPEAT 684..705
FT /note="LRR 8"
FT REPEAT 707..728
FT /note="LRR 9"
FT REPEAT 730..751
FT /note="LRR 10"
FT REPEAT 753..774
FT /note="LRR 11"
FT REPEAT 776..797
FT /note="LRR 12"
FT REPEAT 799..820
FT /note="LRR 13"
FT REGION 118..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 123..137
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 227..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q7L1W4"
FT DISULFID 54..354
FT /evidence="ECO:0000250|UniProtKB:Q80WG5"
SQ SEQUENCE 858 AA; 97940 MW; EF3A1ACDEE6E1EFF CRC64;
MFTLAEVASL NDIQPTYRIL KPWWDVFMDY LAVVMLMVAI FAGTMQLTKD QVVCLPVLPS
PANSKAHTPP GNADVTTEVP KMETATPQDQ NGQTTNDIAF GTSAVTPDIP LQATYSHAES
TFPSQETKKE KRDPTGRKTN LDFQQYVFIN QMCYHLALPW YSKYFPYLAL IHTIILMVSS
NFWFKYPKTC SKVEHFVSIL GKCFESPWTT KALSETACED SEENKQRITG AQTLPKHVST
SSDEGSPSAS TPMINKTGFK FSAEKPVIEV PSMTILDKKD GEQAKALFEK VRKFRAHVED
SDLIYKLYVV QTLIKTAKFI FILCYTANFV NAISFEHVCK PKVEHLTGYE VFECTHNMAY
MLKKLLISYI SIICVYGFIC LYTLFWLFRI PLKEYSFEKV REESSFSDIP DVKNDFAFLL
HMVDQYDQLY SKRFGVFLSE VSENKLREIS LNHEWTFEKL RQHVSRNAQD KQELHLFMLS
GVPDAVFDLT DLDVLKLELI PEAKIPAKIS QMTNLQELHL CHCPAKVEQT AFSFLRDHLR
CLHVKFTDVA EIPAWVYLLK NLRELYLIGN LNSENNKMIG LESLRELRHL KILHVKSNLT
KVPSNITDVA PHLTKLVIHN DGTKLLVLNS LKKMMNVAEL ELQNCELERI PHAIFSLSNL
QELDLKSNSI RTIEEIISFQ HLKRLTCLKL WHNKIVAIPP SITHVKNLES LYFSNNKLES
LPVAVFSLQK LRCLDVSYNN ISTIPIEIGL LQNLQHLHIT GNKVDVLPKQ LFKCVKLRTL
NLGQNCIASL PEKISQLSQL TQLELKGNCL DRLPAQLGQC RMLKKSGLVV EDQLFDTLPL
EVKEALNQDV NVPFANGI
