CLD4_MOUSE
ID CLD4_MOUSE Reviewed; 210 AA.
AC O35054;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Claudin-4 {ECO:0000303|PubMed:20921420};
DE AltName: Full=Clostridium perfringens enterotoxin receptor {ECO:0000303|PubMed:9334247};
DE Short=CPE-R {ECO:0000303|PubMed:9334247};
DE Short=CPE-receptor {ECO:0000303|PubMed:9334247};
GN Name=Cldn4 {ECO:0000312|MGI:MGI:1313314};
GN Synonyms=Cper {ECO:0000303|PubMed:9334247},
GN Cpetr1 {ECO:0000303|PubMed:9334247};
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].
RX PubMed=9334247; DOI=10.1074/jbc.272.42.26652;
RA Katahira J., Sugiyama H., Inoue N., Horiguchi Y., Matsuda M., Sugimoto N.;
RT "Clostridium perfringens enterotoxin utilizes two structurally related
RT membrane proteins as functional receptors in vivo.";
RL J. Biol. Chem. 272:26652-26658(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Kidney;
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 [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 INTERACTION WITH TJP1.
RX PubMed=16236711; DOI=10.1074/jbc.m503786200;
RA Tanaka M., Kamata R., Sakai R.;
RT "EphA2 phosphorylates the cytoplasmic tail of Claudin-4 and mediates
RT paracellular permeability.";
RL J. Biol. Chem. 280:42375-42382(2005).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH CLDN8,
RP AND MUTAGENESIS OF ARG-31; GLU-48; LYS-65; ASP-68 AND ASP-76.
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 SUBCELLULAR LOCATION.
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: Channel-forming tight junction protein that mediates
CC paracellular chloride transport in the kidney (PubMed:20921420). Plays
CC a critical role in the paracellular reabsorption of filtered chloride
CC in the kidney collecting ducts (PubMed:20921420). Claudins play a major
CC role in tight junction-specific obliteration of the intercellular
CC space, through calcium-independent cell-adhesion activity.
CC {ECO:0000269|PubMed:20921420}.
CC -!- SUBUNIT: Interacts with EPHA2; phosphorylates CLDN4 and may regulate
CC tight junctions (By similarity). Directly interacts with TJP1/ZO-1,
CC TJP2/ZO-2 and TJP3/ZO-3 (PubMed:10601346, PubMed:16236711). Interacts
CC with CLDN1 (By similarity). Interacts with CLDN8 (PubMed:20921420).
CC {ECO:0000250|UniProtKB:O14493, ECO:0000269|PubMed:10601346,
CC ECO:0000269|PubMed:16236711, ECO:0000269|PubMed:20921420}.
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}. Note=CLDN4 is required for tight
CC junction localization in the kidney (PubMed:20921420, PubMed:25831548).
CC {ECO:0000269|PubMed:20921420, ECO:0000269|PubMed:25831548}.
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: Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1
CC and alters interaction with TJP1 (By similarity).
CC {ECO:0000250|UniProtKB:O14493}.
CC -!- SIMILARITY: Belongs to the claudin family. {ECO:0000305}.
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DR EMBL; AB000713; BAA22985.1; -; mRNA.
DR EMBL; AF087822; AAD09757.1; -; mRNA.
DR CCDS; CCDS19728.1; -.
DR RefSeq; NP_034033.1; NM_009903.2.
DR AlphaFoldDB; O35054; -.
DR SMR; O35054; -.
DR BioGRID; 198746; 1.
DR DIP; DIP-40781N; -.
DR IntAct; O35054; 1.
DR MINT; O35054; -.
DR STRING; 10090.ENSMUSP00000053420; -.
DR iPTMnet; O35054; -.
DR PhosphoSitePlus; O35054; -.
DR PaxDb; O35054; -.
DR PRIDE; O35054; -.
DR ProteomicsDB; 283378; -.
DR Antibodypedia; 3618; 577 antibodies from 38 providers.
DR DNASU; 12740; -.
DR Ensembl; ENSMUST00000051401; ENSMUSP00000053420; ENSMUSG00000047501.
DR GeneID; 12740; -.
DR KEGG; mmu:12740; -.
DR UCSC; uc008zxd.3; mouse.
DR CTD; 1364; -.
DR MGI; MGI:1313314; Cldn4.
DR VEuPathDB; HostDB:ENSMUSG00000047501; -.
DR eggNOG; ENOG502QSCN; Eukaryota.
DR GeneTree; ENSGT00940000154762; -.
DR HOGENOM; CLU_076370_0_0_1; -.
DR InParanoid; O35054; -.
DR OMA; RSNDKPY; -.
DR OrthoDB; 1231389at2759; -.
DR PhylomeDB; O35054; -.
DR TreeFam; TF331936; -.
DR BioGRID-ORCS; 12740; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Cldn4; mouse.
DR PRO; PR:O35054; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O35054; protein.
DR Bgee; ENSMUSG00000047501; Expressed in endoderm of midgut and 116 other tissues.
DR ExpressionAtlas; O35054; baseline and differential.
DR Genevisible; O35054; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016327; C:apicolateral plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0070160; C:tight junction; IDA:ARUK-UCL.
DR GO; GO:0005254; F:chloride channel activity; IMP:UniProtKB.
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 GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0061436; P:establishment of skin barrier; ISO:MGI.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI.
DR GO; GO:1905050; P:positive regulation of metallopeptidase activity; ISO:MGI.
DR GO; GO:0090303; P:positive regulation of wound healing; ISO:MGI.
DR GO; GO:0022604; P:regulation of cell morphogenesis; ISO:MGI.
DR GO; GO:0070293; P:renal absorption; IMP:UniProtKB.
DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl.
DR InterPro; IPR006187; Claudin.
DR InterPro; IPR003550; Claudin4.
DR InterPro; IPR017974; Claudin_CS.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR PANTHER; PTHR12002; PTHR12002; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01379; CLAUDIN4.
DR PROSITE; PS01346; CLAUDIN; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Chloride; Chloride channel; Disulfide bond;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Tight junction; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..210
FT /note="Claudin-4"
FT /id="PRO_0000144744"
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..116
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 138..160
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 161..181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 182..210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..103
FT /note="Interaction with EPHA2"
FT /evidence="ECO:0000250|UniProtKB:O14493"
FT REGION 209..210
FT /note="Interactions with TJP1, TJP2 and TJP3"
FT /evidence="ECO:0000269|PubMed:10601346"
FT MOD_RES 209
FT /note="Phosphotyrosine; by EPHA2"
FT /evidence="ECO:0000250|UniProtKB:O14493"
FT DISULFID 54..64
FT /evidence="ECO:0000250|UniProtKB:O14493"
FT MUTAGEN 31
FT /note="R->T: No effect."
FT /evidence="ECO:0000269|PubMed:20921420"
FT MUTAGEN 48
FT /note="E->Q: No effect."
FT /evidence="ECO:0000269|PubMed:20921420"
FT MUTAGEN 65
FT /note="K->T: Abolishes ability to form paracellular
FT chloride channel."
FT /evidence="ECO:0000269|PubMed:20921420"
FT MUTAGEN 68
FT /note="D->N: No effect."
FT /evidence="ECO:0000269|PubMed:20921420"
FT MUTAGEN 76
FT /note="D->N: No effect."
FT /evidence="ECO:0000269|PubMed:20921420"
SQ SEQUENCE 210 AA; 22339 MW; 3B6D571EC71D6564 CRC64;
MASMGLQVLG ISLAVLGWLG IILSCALPMW RVTAFIGSNI VTAQTSWEGL WMNCVVQSTG
QMQCKMYDSM LALPQDLQAA RALMVISIIV GALGMLLSVV GGKCTNCMED ETVKAKIMIT
AGAVFIVASM LIMVPVSWTA HNVIRDFYNP MVASGQKREM GASLYVGWAA SGLLLLGGGL
LCCSCPPRSN DKPYSAKYSA ARSVPASNYV
