LRC8D_HUMAN
ID LRC8D_HUMAN Reviewed; 858 AA.
AC Q7L1W4; D3DT29; Q6UWB2; Q9NVW3;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Volume-regulated anion channel subunit LRRC8D {ECO:0000305};
DE AltName: Full=Leucine-rich repeat-containing protein 5 {ECO:0000312|HGNC:HGNC:16992};
DE AltName: Full=Leucine-rich repeat-containing protein 8D {ECO:0000303|PubMed:22532330};
DE Short=HsLRRC8D {ECO:0000303|PubMed:32415200};
GN Name=LRRC8D {ECO:0000303|PubMed:22532330, ECO:0000312|HGNC:HGNC:16992};
GN Synonyms=LRRC5 {ECO:0000312|HGNC:HGNC:16992};
GN ORFNames=UNQ213/PRO239 {ECO:0000303|PubMed:12975309};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-858.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 335-858.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP IDENTIFICATION.
RX PubMed=22532330; DOI=10.1002/bies.201100173;
RA Abascal F., Zardoya R.;
RT "LRRC8 proteins share a common ancestor with pannexins, and may form
RT hexameric channels involved in cell-cell communication.";
RL Bioessays 34:551-560(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241 AND SER-242, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH LRRC8A;
RP LRRC8B AND LRRC8C.
RX PubMed=24782309; DOI=10.1074/jbc.m114.571257;
RA Lee C.C., Freinkman E., Sabatini D.M., Ploegh H.L.;
RT "The protein synthesis inhibitor blasticidin S enters mammalian cells via
RT leucine-rich repeat-containing protein 8D.";
RL J. Biol. Chem. 289:17124-17131(2014).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH LRRC8A, AND SUBCELLULAR
RP LOCATION.
RX PubMed=24790029; DOI=10.1126/science.1252826;
RA Voss F.K., Ullrich F., Muench J., Lazarow K., Lutter D., Mah N.,
RA Andrade-Navarro M.A., von Kries J.P., Stauber T., Jentsch T.J.;
RT "Identification of LRRC8 heteromers as an essential component of the
RT volume-regulated anion channel VRAC.";
RL Science 344:634-638(2014).
RN [12]
RP FUNCTION.
RX PubMed=26530471; DOI=10.15252/embj.201592409;
RA Planells-Cases R., Lutter D., Guyader C., Gerhards N.M., Ullrich F.,
RA Elger D.A., Kucukosmanoglu A., Xu G., Voss F.K., Reincke S.M., Stauber T.,
RA Blomen V.A., Vis D.J., Wessels L.F., Brummelkamp T.R., Borst P.,
RA Rottenberg S., Jentsch T.J.;
RT "Subunit composition of VRAC channels determines substrate specificity and
RT cellular resistance to Pt-based anti-cancer drugs.";
RL EMBO J. 34:2993-3008(2015).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF THR-44.
RX PubMed=26824658; DOI=10.1016/j.cell.2015.12.031;
RA Syeda R., Qiu Z., Dubin A.E., Murthy S.E., Florendo M.N., Mason D.E.,
RA Mathur J., Cahalan S.M., Peters E.C., Montal M., Patapoutian A.;
RT "LRRC8 proteins form volume-regulated anion channels that sense ionic
RT strength.";
RL Cell 164:499-511(2016).
RN [14]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=28193731; DOI=10.1242/jcs.196253;
RA Lutter D., Ullrich F., Lueck J.C., Kempa S., Jentsch T.J.;
RT "Selective transport of neurotransmitters and modulators by distinct
RT volume-regulated LRRC8 anion channels.";
RL J. Cell Sci. 130:1122-1133(2017).
RN [15]
RP FUNCTION.
RX PubMed=33171122; DOI=10.1016/j.molcel.2020.10.021;
RA Lahey L.J., Mardjuki R.E., Wen X., Hess G.T., Ritchie C., Carozza J.A.,
RA Boehnert V., Maduke M., Bassik M.C., Li L.;
RT "LRRC8A:C/E heteromeric channels are ubiquitous transporters of cGAMP.";
RL Mol. Cell 0:0-0(2020).
RN [16] {ECO:0007744|PDB:6M04}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.36 ANGSTROMS), FUNCTION, SUBUNIT,
RP DISULFIDE BOND, DOMAIN, AND MUTAGENESIS OF PHE-143.
RX PubMed=32415200; DOI=10.1038/s42003-020-0951-z;
RA Nakamura R., Numata T., Kasuya G., Yokoyama T., Nishizawa T.,
RA Kusakizako T., Kato T., Hagino T., Dohmae N., Inoue M., Watanabe K.,
RA Ichijo H., Kikkawa M., Shirouzu M., Jentsch T.J., Ishitani R., Okada Y.,
RA Nureki O.;
RT "Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform
RT identifies features important for substrate permeation.";
RL Commun. Biol. 3:240-240(2020).
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:24790029, PubMed:26530471, PubMed:26824658,
CC PubMed:28193731, PubMed:32415200). The VRAC channel conducts iodide
CC better than chloride and can also conduct organic osmolytes like
CC taurine (PubMed:24790029, PubMed:26824658, PubMed:28193731). Plays a
CC redundant role in the efflux of amino acids, such as aspartate, in
CC response to osmotic stress (PubMed:28193731). LRRC8A and LRRC8D are
CC required for the uptake of the drug cisplatin (PubMed:26530471).
CC Channel activity requires LRRC8A plus at least one other family member
CC (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on
CC the precise subunit composition (PubMed:24782309, PubMed:24790029,
CC PubMed:26824658, PubMed:28193731). Also acts as a regulator of glucose-
CC sensing in pancreatic beta cells: VRAC currents, generated in response
CC to hypotonicity- or glucose-induced beta cell swelling, depolarize
CC cells, thereby causing electrical excitation, leading to increase
CC glucose sensitivity and insulin secretion (By similarity). VRAC
CC channels 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 (PubMed:33171122). Mediates the
CC import of the antibiotic blasticidin-S into the cell (PubMed:24782309).
CC {ECO:0000250|UniProtKB:Q8BGR2, ECO:0000269|PubMed:24782309,
CC ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:26530471,
CC ECO:0000269|PubMed:26824658, ECO:0000269|PubMed:28193731,
CC ECO:0000269|PubMed:32415200, ECO:0000269|PubMed:33171122}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC ChEBI:CHEBI:17996; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC ChEBI:CHEBI:16382; Evidence={ECO:0000305|PubMed:24790029};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=taurine(out) = taurine(in); Xref=Rhea:RHEA:66328,
CC ChEBI:CHEBI:507393; Evidence={ECO:0000305|PubMed:24790029};
CC -!- SUBUNIT: Heterohexamer (PubMed:32415200). Oligomerizes with other LRRC8
CC proteins (LRRC8A, LRRC8B, LRRC8C and/or LRRC8E) to form a heterohexamer
CC (PubMed:24782309, PubMed:26530471, PubMed:28193731, PubMed:26824658).
CC In vivo, the subunit composition may depend primarily on expression
CC levels, and heterooligomeric channels containing various proportions of
CC the different LRRC8 proteins may coexist (Probable).
CC {ECO:0000269|PubMed:24782309, ECO:0000269|PubMed:24790029,
CC ECO:0000269|PubMed:26530471, ECO:0000269|PubMed:26824658,
CC ECO:0000269|PubMed:28193731, ECO:0000269|PubMed:32415200}.
CC -!- INTERACTION:
CC Q7L1W4; Q8IWT6: LRRC8A; NbExp=2; IntAct=EBI-861997, EBI-10970086;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24782309,
CC ECO:0000269|PubMed:24790029, ECO:0000269|PubMed:28193731}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:32415200}. Endoplasmic reticulum
CC membrane {ECO:0000269|PubMed:24782309, ECO:0000305|PubMed:24790029};
CC Multi-pass membrane protein {ECO:0000269|PubMed:32415200}. Note=In the
CC absence of LRRC8A, resides primarily in a cytoplasmic compartment,
CC probably the endoplasmic reticulum (PubMed:24782309, PubMed:24790029).
CC Requires LRRC8A for expression at the cell membrane (PubMed:24790029).
CC {ECO:0000269|PubMed:24782309, ECO:0000269|PubMed:24790029}.
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:0000269|PubMed:32415200}.
CC -!- SIMILARITY: Belongs to the LRRC8 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ89233.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA91631.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL391497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73130.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73131.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73132.1; -; Genomic_DNA.
DR EMBL; BC024159; AAH24159.2; -; mRNA.
DR EMBL; AK001332; BAA91631.1; ALT_INIT; mRNA.
DR EMBL; AY358874; AAQ89233.1; ALT_INIT; mRNA.
DR CCDS; CCDS726.1; -.
DR RefSeq; NP_001127951.1; NM_001134479.1.
DR RefSeq; NP_060573.2; NM_018103.4.
DR RefSeq; XP_011539991.1; XM_011541689.1.
DR RefSeq; XP_016857088.1; XM_017001599.1.
DR RefSeq; XP_016857089.1; XM_017001600.1.
DR RefSeq; XP_016857090.1; XM_017001601.1.
DR RefSeq; XP_016857091.1; XM_017001602.1.
DR PDB; 6M04; EM; 4.36 A; A/B/C/D/E/F=1-858.
DR PDBsum; 6M04; -.
DR AlphaFoldDB; Q7L1W4; -.
DR SMR; Q7L1W4; -.
DR BioGRID; 120447; 35.
DR CORUM; Q7L1W4; -.
DR DIP; DIP-31280N; -.
DR IntAct; Q7L1W4; 9.
DR STRING; 9606.ENSP00000338887; -.
DR TCDB; 1.A.25.3.1; the gap junction-forming innexin (innexin) family.
DR GlyGen; Q7L1W4; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q7L1W4; -.
DR PhosphoSitePlus; Q7L1W4; -.
DR BioMuta; LRRC8D; -.
DR DMDM; 51701663; -.
DR EPD; Q7L1W4; -.
DR jPOST; Q7L1W4; -.
DR MassIVE; Q7L1W4; -.
DR MaxQB; Q7L1W4; -.
DR PaxDb; Q7L1W4; -.
DR PeptideAtlas; Q7L1W4; -.
DR PRIDE; Q7L1W4; -.
DR ProteomicsDB; 68752; -.
DR TopDownProteomics; Q7L1W4; -.
DR Antibodypedia; 2631; 51 antibodies from 18 providers.
DR DNASU; 55144; -.
DR Ensembl; ENST00000337338.9; ENSP00000338887.5; ENSG00000171492.14.
DR Ensembl; ENST00000394593.7; ENSP00000378093.3; ENSG00000171492.14.
DR GeneID; 55144; -.
DR KEGG; hsa:55144; -.
DR MANE-Select; ENST00000337338.9; ENSP00000338887.5; NM_001134479.2; NP_001127951.1.
DR UCSC; uc001dnm.4; human.
DR CTD; 55144; -.
DR DisGeNET; 55144; -.
DR GeneCards; LRRC8D; -.
DR HGNC; HGNC:16992; LRRC8D.
DR HPA; ENSG00000171492; Tissue enhanced (brain).
DR MIM; 612890; gene.
DR neXtProt; NX_Q7L1W4; -.
DR OpenTargets; ENSG00000171492; -.
DR PharmGKB; PA30464; -.
DR VEuPathDB; HostDB:ENSG00000171492; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000154043; -.
DR HOGENOM; CLU_019019_0_0_1; -.
DR InParanoid; Q7L1W4; -.
DR OMA; VKFIFIL; -.
DR OrthoDB; 187778at2759; -.
DR PhylomeDB; Q7L1W4; -.
DR TreeFam; TF331443; -.
DR PathwayCommons; Q7L1W4; -.
DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events.
DR SignaLink; Q7L1W4; -.
DR BioGRID-ORCS; 55144; 13 hits in 1076 CRISPR screens.
DR ChiTaRS; LRRC8D; human.
DR GeneWiki; LRRC8D; -.
DR GenomeRNAi; 55144; -.
DR Pharos; Q7L1W4; Tbio.
DR PRO; PR:Q7L1W4; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q7L1W4; protein.
DR Bgee; ENSG00000171492; Expressed in inferior vagus X ganglion and 204 other tissues.
DR ExpressionAtlas; Q7L1W4; baseline and differential.
DR Genevisible; Q7L1W4; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA: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:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005225; F:volume-sensitive anion channel activity; IDA:UniProtKB.
DR GO; GO:0098656; P:anion transmembrane transport; IDA: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; IDA:UniProtKB.
DR GO; GO:0015734; P:taurine transport; IMP:UniProtKB.
DR Gene3D; 3.80.10.10; -; 3.
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 3D-structure; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Ion channel; 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_0000084493"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 23..48
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32415200,
FT ECO:0007744|PDB:6M04"
FT TOPO_DOM 49..163
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 164..182
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32415200,
FT ECO:0007744|PDB:6M04"
FT TOPO_DOM 183..308
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 309..328
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32415200,
FT ECO:0007744|PDB:6M04"
FT TOPO_DOM 329..360
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 361..386
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32415200,
FT ECO:0007744|PDB:6M04"
FT TOPO_DOM 387..858
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
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 221..251
FT /note="Disordered"
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:0007744|PubMed:18669648"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT DISULFID 54..354
FT /evidence="ECO:0000269|PubMed:32415200,
FT ECO:0007744|PDB:6M04"
FT VARIANT 371
FT /note="S -> Y (in dbSNP:rs11552246)"
FT /id="VAR_051132"
FT MUTAGEN 44
FT /note="T->C: Alters channel anion selectivity."
FT /evidence="ECO:0000269|PubMed:26824658"
FT MUTAGEN 143
FT /note="F->R: Affects ion selectivity of the channel.
FT Reduced permeability to negatively charged glutamate and
FT gluconate."
FT /evidence="ECO:0000269|PubMed:32415200"
SQ SEQUENCE 858 AA; 98201 MW; 52A8B6EEF6F0FE2B CRC64;
MFTLAEVASL NDIQPTYRIL KPWWDVFMDY LAVVMLMVAI FAGTMQLTKD QVVCLPVLPS
PVNSKAHTPP GNAEVTTNIP KMEAATNQDQ DGRTTNDISF GTSAVTPDIP LRATYPRTDF
ALPNQEAKKE KKDPTGRKTN LDFQQYVFIN QMCYHLALPW YSKYFPYLAL IHTIILMVSS
NFWFKYPKTC SKVEHFVSIL GKCFESPWTT KALSETACED SEENKQRITG AQTLPKHVST
SSDEGSPSAS TPMINKTGFK FSAEKPVIEV PSMTILDKKD GEQAKALFEK VRKFRAHVED
SDLIYKLYVV QTVIKTAKFI FILCYTANFV NAISFEHVCK PKVEHLIGYE VFECTHNMAY
MLKKLLISYI SIICVYGFIC LYTLFWLFRI PLKEYSFEKV REESSFSDIP DVKNDFAFLL
HMVDQYDQLY SKRFGVFLSE VSENKLREIS LNHEWTFEKL RQHISRNAQD KQELHLFMLS
GVPDAVFDLT DLDVLKLELI PEAKIPAKIS QMTNLQELHL CHCPAKVEQT AFSFLRDHLR
CLHVKFTDVA EIPAWVYLLK NLRELYLIGN LNSENNKMIG LESLRELRHL KILHVKSNLT
KVPSNITDVA PHLTKLVIHN DGTKLLVLNS LKKMMNVAEL ELQNCELERI PHAIFSLSNL
QELDLKSNNI RTIEEIISFQ HLKRLTCLKL WHNKIVTIPP SITHVKNLES LYFSNNKLES
LPVAVFSLQK LRCLDVSYNN ISMIPIEIGL LQNLQHLHIT GNKVDILPKQ LFKCIKLRTL
NLGQNCITSL PEKVGQLSQL TQLELKGNCL DRLPAQLGQC RMLKKSGLVV EDHLFDTLPL
EVKEALNQDI NIPFANGI
