ID   CLD4_CHLAE              Reviewed;         209 AA.
AC   O19005;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=Claudin-4;
DE   AltName: Full=Clostridium perfringens enterotoxin receptor;
DE            Short=CPE-R;
DE            Short=CPE-receptor;
GN   Name=CLDN4; Synonyms=CPER, CPETR1;
OS   Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC   Cercopithecidae; Cercopithecinae; Chlorocebus.
OX   NCBI_TaxID=9534;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9087440; DOI=10.1083/jcb.136.6.1239;
RA   Katahira J., Inoue N., Horiguchi Y., Matsuda M., Sugimoto N.;
RT   "Molecular cloning and functional characterization of the receptor for
RT   Clostridium perfringens enterotoxin.";
RL   J. Cell Biol. 136:1239-1247(1997).
CC   -!- FUNCTION: Channel-forming tight junction protein that mediates
CC       paracellular chloride transport in the kidney. Plays a critical role in
CC       the paracellular reabsorption of filtered chloride in the kidney
CC       collecting ducts. Claudins play a major role in tight junction-specific
CC       obliteration of the intercellular space, through calcium-independent
CC       cell-adhesion activity. {ECO:0000250|UniProtKB:O35054}.
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 (By similarity). Interacts with CLDN1 (By
CC       similarity). Interacts with CLDN8 (By similarity).
CC       {ECO:0000250|UniProtKB:O14493, ECO:0000250|UniProtKB:O35054}.
CC   -!- SUBCELLULAR LOCATION: Cell junction, tight junction
CC       {ECO:0000250|UniProtKB:O35054}. Cell membrane
CC       {ECO:0000250|UniProtKB:O35054}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=CLDN4 is required for tight junction localization
CC       in the kidney. {ECO:0000250|UniProtKB:O35054}.
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; D88492; BAA22781.1; -; mRNA.
DR   AlphaFoldDB; O19005; -.
DR   SMR; O19005; -.
DR   GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005254; F:chloride channel activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0005198; F:structural molecule activity; IEA:InterPro.
DR   GO; GO:0016338; P:calcium-independent cell-cell adhesion via plasma membrane cell-adhesion molecules; ISS:UniProtKB.
DR   GO; GO:0070293; P:renal absorption; ISS:UniProtKB.
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   2: Evidence at transcript level;
KW   Cell junction; Cell membrane; Chloride; Chloride channel; Disulfide bond;
KW   Ion channel; Ion transport; Membrane; Phosphoprotein; Tight junction;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..209
FT                   /note="Claudin-4"
FT                   /id="PRO_0000144742"
FT   TOPO_DOM        1..9
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        10..30
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        31..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..160
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        161..181
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        182..209
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..103
FT                   /note="Interaction with EPHA2"
FT                   /evidence="ECO:0000250|UniProtKB:O14493"
FT   REGION          208..209
FT                   /note="Interactions with TJP1, TJP2 and TJP3"
FT                   /evidence="ECO:0000250|UniProtKB:O35054"
FT   MOD_RES         208
FT                   /note="Phosphotyrosine; by EPHA2"
FT                   /evidence="ECO:0000250|UniProtKB:O14493"
FT   DISULFID        54..64
FT                   /evidence="ECO:0000250|UniProtKB:O14493"
SQ   SEQUENCE   209 AA;  22029 MW;  474DB3099F95289E CRC64;
     MASMGLQVTG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL WMNCVVQSTG
     QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV GGKCTNCLED ESAKAKTMIV
     AGVVFLLAGL LVIVPVSWTA HNIIQDFYNP LVASGQKREM GASLYVGWAA SGLLLLGGGL
     LCCNCPPRTD KPYSAKYSAA RSAAASNYV