CLD8_MOUSE
ID CLD8_MOUSE Reviewed; 225 AA.
AC Q9Z260;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Claudin-8 {ECO:0000303|PubMed:20921420, ECO:0000303|PubMed:25831548};
GN Name=Cldn8 {ECO:0000312|MGI:MGI:1859286};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9892664; DOI=10.1073/pnas.96.2.511;
RA Morita K., Furuse M., Fujimoto K., Tsukita S.;
RT "Claudin multigene family encoding four-transmembrane domain protein
RT components of tight junction strands.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:511-516(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
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 [3]
RP INTERACTION WITH TJP1; TJP2 AND TJP3.
RX PubMed=10601346; DOI=10.1083/jcb.147.6.1351;
RA Itoh M., Furuse M., Morita K., Kubota K., Saitou M., Tsukita S.;
RT "Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and
RT ZO-3, with the COOH termini of claudins.";
RL J. Cell Biol. 147:1351-1363(1999).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CLDN4, AND TISSUE
RP SPECIFICITY.
RX PubMed=20921420; DOI=10.1073/pnas.1009399107;
RA Hou J., Renigunta A., Yang J., Waldegger S.;
RT "Claudin-4 forms paracellular chloride channel in the kidney and requires
RT claudin-8 for tight junction localization.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18010-18015(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, INTERACTION WITH
RP KLHL3, UBIQUITINATION AT LYS-213, AND MUTAGENESIS OF LYS-213.
RX PubMed=25831548; DOI=10.1073/pnas.1421441112;
RA Gong Y., Wang J., Yang J., Gonzales E., Perez R., Hou J.;
RT "KLHL3 regulates paracellular chloride transport in the kidney by
RT ubiquitination of claudin-8.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:4340-4345(2015).
CC -!- FUNCTION: Tight-junction protein required for paracellular chloride
CC transport in the kidney (PubMed:20921420, PubMed:25831548). Mediates
CC recruitment of CLDN4 to tight junction in the kidney (PubMed:20921420,
CC PubMed:25831548). Claudins play a major role in tight junction-specific
CC obliteration of the intercellular space, through calcium-independent
CC cell-adhesion activity. {ECO:0000269|PubMed:20921420,
CC ECO:0000269|PubMed:25831548}.
CC -!- SUBUNIT: Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3
CC (PubMed:10601346). Interacts with CLDN4 (PubMed:20921420). Interacts
CC with KLHL3 (PubMed:25831548). {ECO:0000269|PubMed:10601346,
CC ECO:0000269|PubMed:20921420, ECO:0000269|PubMed:25831548}.
CC -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC {ECO:0000269|PubMed:20921420, ECO:0000269|PubMed:25831548,
CC ECO:0000269|PubMed:9892664}. Cell membrane
CC {ECO:0000269|PubMed:20921420, ECO:0000269|PubMed:9892664}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed primarily in lung and kidney
CC (PubMed:9892664). Present in both cortical and medullar collecting
CC ducts (at protein level) (PubMed:20921420).
CC {ECO:0000269|PubMed:20921420, ECO:0000269|PubMed:9892664}.
CC -!- PTM: Ubiquitinated by the BCR(KLHL3) E3 ubiquitin ligase complex in the
CC kidney, leading to its degradation. {ECO:0000269|PubMed:25831548}.
CC -!- DISRUPTION PHENOTYPE: Conditional knockout mice lacking Cldn8 in the
CC collecting duct of kidney show hypotension, hypokalemia, and metabolic
CC alkalosis (PubMed:25831548). {ECO:0000269|PubMed:25831548}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR EMBL; AF087826; AAD09761.1; -; mRNA.
DR EMBL; BC003868; AAH03868.1; -; mRNA.
DR CCDS; CCDS28296.1; -.
DR RefSeq; NP_061248.1; NM_018778.3.
DR AlphaFoldDB; Q9Z260; -.
DR SMR; Q9Z260; -.
DR MINT; Q9Z260; -.
DR STRING; 10090.ENSMUSP00000051887; -.
DR iPTMnet; Q9Z260; -.
DR PhosphoSitePlus; Q9Z260; -.
DR PaxDb; Q9Z260; -.
DR PRIDE; Q9Z260; -.
DR ProteomicsDB; 285491; -.
DR Antibodypedia; 6589; 252 antibodies from 28 providers.
DR DNASU; 54420; -.
DR Ensembl; ENSMUST00000049697; ENSMUSP00000051887; ENSMUSG00000050520.
DR GeneID; 54420; -.
DR KEGG; mmu:54420; -.
DR UCSC; uc007zuz.2; mouse.
DR CTD; 9073; -.
DR MGI; MGI:1859286; Cldn8.
DR VEuPathDB; HostDB:ENSMUSG00000050520; -.
DR eggNOG; ENOG502RTNJ; Eukaryota.
DR GeneTree; ENSGT00940000159077; -.
DR HOGENOM; CLU_076370_1_2_1; -.
DR InParanoid; Q9Z260; -.
DR OMA; YQDSVYE; -.
DR OrthoDB; 1314055at2759; -.
DR PhylomeDB; Q9Z260; -.
DR TreeFam; TF331936; -.
DR BioGRID-ORCS; 54420; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Cldn8; mouse.
DR PRO; PR:Q9Z260; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q9Z260; protein.
DR Bgee; ENSMUSG00000050520; Expressed in seminal vesicle and 131 other tissues.
DR ExpressionAtlas; Q9Z260; baseline and differential.
DR Genevisible; Q9Z260; MM.
DR GO; GO:0016327; C:apicolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:MGI.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR GO; GO:0070830; P:bicellular tight junction assembly; IBA:GO_Central.
DR GO; GO:0016338; P:calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR InterPro; IPR006187; Claudin.
DR InterPro; IPR003926; Claudin8.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR PANTHER; PTHR12002:SF24; PTHR12002:SF24; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Isopeptide bond; Membrane;
KW Reference proteome; Tight junction; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..225
FT /note="Claudin-8"
FT /id="PRO_0000144754"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..81
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 82..102
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 103..117
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 139..166
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 224..225
FT /note="Interactions with TJP1, TJP2 and TJP3"
FT /evidence="ECO:0000269|PubMed:10601346"
FT CROSSLNK 213
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:25831548"
FT MUTAGEN 213
FT /note="K->R: Resistant to KLHL3-dependent protein
FT degradation."
FT /evidence="ECO:0000269|PubMed:25831548"
SQ SEQUENCE 225 AA; 24947 MW; 12BB3C460F23D876 CRC64;
MATYALQMAA LVLGGVGMVG TVAVTIMPQW RVSAFIESNI VVFENRWEGL WMNCMRHANI
RMQCKVYDSL LALSPDLQAS RGLMCAASVL AFLAFMTAIL GMKCTRCTGD DENVKSRILL
TAGIIFFITG LVVLIPVSWV ANSIIRDFYN PLVDVALKRE LGEALYIGWT TALVLIAGGA
LFCCVFCCTE RSNSYRYSVP SHRTTQRSFH AEKRSPSIYS KSQYV
