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Protein

Claudin-4

Gene

CLDN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney. Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Ion channel
Biological processIon transport, Transport
LigandChloride

Enzyme and pathway databases

ReactomeiR-HSA-420029 Tight junction interactions

Protein family/group databases

TCDBi1.H.1.1.6 the claudin tight junction (claudin1) family

Names & Taxonomyi

Protein namesi
Recommended name:
Claudin-4
Alternative name(s):
Clostridium perfringens enterotoxin receptor1 Publication
Short name:
CPE-R1 Publication
Short name:
CPE-receptor1 Publication
Williams-Beuren syndrome chromosomal region 8 protein
Gene namesi
Name:CLDN4
Synonyms:CPER1 Publication, CPETR11 Publication, WBSCR8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000189143.9
HGNCiHGNC:2046 CLDN4
MIMi602909 gene
neXtProtiNX_O14493

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7CytoplasmicSequence analysis7
Transmembranei8 – 28HelicalSequence analysisAdd BLAST21
Topological domaini29 – 81ExtracellularSequence analysisAdd BLAST53
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Topological domaini103 – 117CytoplasmicSequence analysisAdd BLAST15
Transmembranei118 – 138HelicalSequence analysisAdd BLAST21
Topological domaini139 – 160ExtracellularSequence analysisAdd BLAST22
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Topological domaini182 – 209CytoplasmicSequence analysisAdd BLAST28

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35F → A: Decreases interaction with Clostridium perfringens CPE. 1 Publication1
Mutagenesisi35F → D: Abolishes interaction with Clostridium perfringens CPE. 1 Publication1
Mutagenesisi40I → A: No effect on interaction with Clostridium perfringens CPE. 1 Publication1
Mutagenesisi40I → D: Strongly decreases interaction with Clostridium perfringens CPE. 1 Publication1
Mutagenesisi53N → A or D: Decreases interaction with Clostridium perfringens CPE. 1 Publication1
Mutagenesisi208Y → F: Loss of phosphorylation by EPHA2. 1 Publication1

Keywords - Diseasei

Williams-Beuren syndrome

Organism-specific databases

DisGeNETi1364
OpenTargetsiENSG00000189143
PharmGKBiPA26572

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001447431 – 209Claudin-4Add BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi54 ↔ 64Combined sources1 Publication
Modified residuei208Phosphotyrosine; by EPHA21 Publication1

Post-translational modificationi

Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

EPDiO14493
PaxDbiO14493
PeptideAtlasiO14493
PRIDEiO14493
ProteomicsDBi48036

PTM databases

iPTMnetiO14493
PhosphoSitePlusiO14493
SwissPalmiO14493

Expressioni

Gene expression databases

BgeeiENSG00000189143 Expressed in 152 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_CLDN4
ExpressionAtlasiO14493 baseline and differential
GenevisibleiO14493 HS

Organism-specific databases

HPAiCAB002610

Interactioni

Subunit structurei

Directly interacts with TJP1/ZO-1 (PubMed:16236711). Interacts with TJP2/ZO-2 and TJP3/ZO-3 (By similarity). Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (PubMed:16236711). Interacts with CLDN1 (PubMed:20375010). Interacts with CLDN8 (By similarity).By similarity2 Publications
(Microbial infection) Interacts (via both extracellular domains) with Clostridium perfringens enterotoxin CPE; the interaction may disrupt claudin assembly in tight junctions.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107756, 2 interactors
IntActiO14493, 15 interactors
STRINGi9606.ENSP00000342445

Structurei

Secondary structure

1209
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO14493
SMRiO14493
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 103Interaction with EPHA21 PublicationAdd BLAST103
Regioni208 – 209Interactions with TJP1, TJP2 and TJP3By similarity2

Sequence similaritiesi

Belongs to the claudin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIJR Eukaryota
ENOG410YA61 LUCA
GeneTreeiENSGT00760000118928
HOGENOMiHOG000220937
HOVERGENiHBG000643
InParanoidiO14493
KOiK06087
OMAiTAHNVIR
OrthoDBiEOG091G0MMR
PhylomeDBiO14493
TreeFamiTF331936

Family and domain databases

InterProiView protein in InterPro
IPR006187 Claudin
IPR003550 Claudin4
IPR017974 Claudin_CS
IPR004031 PMP22/EMP/MP20/Claudin
PANTHERiPTHR12002 PTHR12002, 1 hit
PfamiView protein in Pfam
PF00822 PMP22_Claudin, 1 hit
PRINTSiPR01379 CLAUDIN4
PROSITEiView protein in PROSITE
PS01346 CLAUDIN, 1 hit

Sequencei

Sequence statusi: Complete.

O14493-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL
60 70 80 90 100
WMNCVVQSTG QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV
110 120 130 140 150
GGKCTNCLED ESAKAKTMIV AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP
160 170 180 190 200
LVASGQKREM GASLYVGWAA SGLLLLGGGL LCCNCPPRTD KPYSAKYSAA

RSAAASNYV
Length:209
Mass (Da):22,077
Last modified:January 1, 1998 - v1
Checksum:i0659A93AA5F0E4C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA Translation: BAA22984.1
BT006989 mRNA Translation: AAP35635.1
BC000671 mRNA Translation: AAH00671.1
CCDSiCCDS5560.1
RefSeqiNP_001296.1, NM_001305.4
UniGeneiHs.647036
Hs.729359

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143
ENST00000431918; ENSP00000388639; ENSG00000189143
ENST00000435050; ENSP00000409544; ENSG00000189143
GeneIDi1364
KEGGihsa:1364

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA Translation: BAA22984.1
BT006989 mRNA Translation: AAP35635.1
BC000671 mRNA Translation: AAH00671.1
CCDSiCCDS5560.1
RefSeqiNP_001296.1, NM_001305.4
UniGeneiHs.647036
Hs.729359

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5B2GX-ray3.50A/C/E/G1-183[»]
ProteinModelPortaliO14493
SMRiO14493
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107756, 2 interactors
IntActiO14493, 15 interactors
STRINGi9606.ENSP00000342445

Protein family/group databases

TCDBi1.H.1.1.6 the claudin tight junction (claudin1) family

PTM databases

iPTMnetiO14493
PhosphoSitePlusiO14493
SwissPalmiO14493

Proteomic databases

EPDiO14493
PaxDbiO14493
PeptideAtlasiO14493
PRIDEiO14493
ProteomicsDBi48036

Protocols and materials databases

DNASUi1364
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143
ENST00000431918; ENSP00000388639; ENSG00000189143
ENST00000435050; ENSP00000409544; ENSG00000189143
GeneIDi1364
KEGGihsa:1364

Organism-specific databases

CTDi1364
DisGeNETi1364
EuPathDBiHostDB:ENSG00000189143.9
GeneCardsiCLDN4
HGNCiHGNC:2046 CLDN4
HPAiCAB002610
MIMi602909 gene
neXtProtiNX_O14493
OpenTargetsiENSG00000189143
PharmGKBiPA26572
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIJR Eukaryota
ENOG410YA61 LUCA
GeneTreeiENSGT00760000118928
HOGENOMiHOG000220937
HOVERGENiHBG000643
InParanoidiO14493
KOiK06087
OMAiTAHNVIR
OrthoDBiEOG091G0MMR
PhylomeDBiO14493
TreeFamiTF331936

Enzyme and pathway databases

ReactomeiR-HSA-420029 Tight junction interactions

Miscellaneous databases

ChiTaRSiCLDN4 human
GeneWikiiCLDN4
GenomeRNAii1364
PROiPR:O14493
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000189143 Expressed in 152 organ(s), highest expression level in mucosa of transverse colon
CleanExiHS_CLDN4
ExpressionAtlasiO14493 baseline and differential
GenevisibleiO14493 HS

Family and domain databases

InterProiView protein in InterPro
IPR006187 Claudin
IPR003550 Claudin4
IPR017974 Claudin_CS
IPR004031 PMP22/EMP/MP20/Claudin
PANTHERiPTHR12002 PTHR12002, 1 hit
PfamiView protein in Pfam
PF00822 PMP22_Claudin, 1 hit
PRINTSiPR01379 CLAUDIN4
PROSITEiView protein in PROSITE
PS01346 CLAUDIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCLD4_HUMAN
AccessioniPrimary (citable) accession number: O14493
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 155 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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