Protein detail

CLD4

Claudin-4 (Clostridium perfringens enterotoxin receptor) (CPE-R) (CPE-receptor) (Williams-Beuren syndrome chromosomal region 8 protein)

Entry name CLD4	UniProt ID O14493	EVMP confidence score 0.72
Supporting publications (n) 18	Transmembrane count 4	Protein classification Cancer-related genesDisease related genesHuman disease related genesPotential drug targetsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Claudin-4 (Clostridium perfringens enterotoxin receptor) (CPE-R) (CPE-receptor) (Williams-Beuren syndrome chromosomal region 8 protein)

Protein Class (6)

Cancer-related genesDisease related genesHuman disease related genesPotential drug targetsPredicted membrane proteinsTransporters

Protein Function (5)

Human disease related genes:Other congenital disorders:Chromosomal abnormalities
Potential drug targets
Cancer-related genes:Candidate cancer biomarkers
Transporters:Transporter channels and pores
Disease related genes

Transmembrane

8..28; Helical; 82..102; Helical; 118..138; Helical; 161..181; Helical

Transmembrane Count

Ensembl

ENSG00000189143

Entrez Gene Symbol

CLDN4

Gene Synonym (5)

CPE-RCPETRCPETR1hCPE-RWBSCR8

Gene Description

Claudin 4

Chromosome

Position

73799542-73832690

Supporting publications (n)

EVMP confidence score

0.72

Fluorescence & Localization3

Tissue SpecificgallbladderCell SpecificEpicardial cellsSingle-Nuclei Brain Specificmammillary body

Function & Pathway8

Protein Function (5)

Human disease related genes:Other congenital disorders:Chromosomal abnormalities
Potential drug targets
Cancer-related genes:Candidate cancer biomarkers
Transporters:Transporter channels and pores
Disease related genes

Cellular Component (9)

Molecular Function (5)

Biological Process (3)

KEGG (7)

Reactome (3)

Canonical Pathways (2)

M257 Pid ephrinb rev pathway
M62 Pid ephb fwd pathway

Mediation Categories (3)

Adhesion and uptake mediationFusion and delivery mediationReceptor-signaling mediation

Relations & Evidence35

Enzyme-Mediated Modification (4)

4 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
CLDN4	EPHA2	P29317	Y	208	phosphorylation	phosphoELM_MIMPPhosphoSite_MIMPMIMPProtMapperKEAphosphoELMPhosphoSitePhosphoSite_ProtMapper	phosphoELM:16236711 KEA:16236711
CLDN4	PRKCA	P17252	S	194	phosphorylation	PhosphoSite_MIMPMIMPProtMapperPhosphoSitePhosphoSite_ProtMapper
CLDN4	PRKCE	Q02156	S	194	phosphorylation	Sparser_ProtMapperProtMapper	ProtMapper:17678893 ProtMapper:18786529
CLDN4	PRKCE	Q02156	T	189	phosphorylation	Sparser_ProtMapperProtMapper	ProtMapper:17678893 ProtMapper:18786529

Ligand-Receptor Signaling (28)

28 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
intracellular	intracellular	ComPPI	No	No	No	No	No
intracellular	intracellular	OmniPath	No	No	No	No	No
cell_adhesion	cell_adhesion	Cellinker	Yes	Yes	No	No	No
adhesion	adhesion	OmniPath	Yes	Yes	No	No	No
cell_adhesion	cell_adhesion	OmniPath	Yes	Yes	No	No	No
ion_channel	ion_channel	DGIdb	No	Yes	No	No	No
transporter	transporter	OmniPath	No	Yes	No	No	No
ion_channel	ion_channel	OmniPath	No	Yes	No	No	No
tight_junction	tight_junction	GO_Intercell	Yes	Yes	No	No	No
tight_junction	tight_junction	Zhong2015	Yes	Yes	No	No	No

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Regulatory Interaction Network (2)

2 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
EPHA2	P29317	CLD4	O14493	Yes	No	Yes	phosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointSIGNORProtMapperHPRDPhosphoSite_KEAKEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperREACH_ProtMapperPhosphoSitePhosphoSite_ProtMapper	HPRD:16236711 SIGNOR:16236711 ProtMapper:16236711 PhosphoSite:16236711 ProtMapper:18036336 phosphoELM:16236711 KEA:16236711
KPCA	P17252	CLD4	O14493	Yes	No	No	PhosphoSite_MIMPMIMPiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:18786529

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion Chromatography	Mass spectrometryWestern blotting	1	38716512

Sequence, Structure & Domains9

Sequences

Length

209

Mass

22,077

Sequence

MASMGLQVMGIALAVLGWLAVMLCCALPMWRVTAFIGSNIVTSQTIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALVIISIIVAALGVLLSVVGGKCTNCLEDESAKAKTMIVAGVVFLLAGLMVIVPVSWTAHNIIQDFYNPLVASGQKREMGASLYVGWAASGLLLLGGGLLCCNCPPRTDKPYSAKYSAARSAAASNYV

3D Structural Models

Helix

7..26; 75..100; 113..148; 162..182

Beta Strand

1..3; 30..35; 44..48; 50..56; 58..60; 63..66; 70..73; 101..105; 158..160

3D Structure

Electron microscopy (6); X-ray crystallography (2)

Domain & Motif Annotations

Region

1..103; Interaction with EPHA2; 208..209; Interactions with TJP1, TJP2 and TJP3

Protein Families

Claudin family

Sequence Similarities

Belongs to the claudin family.

Clinical Relevance2

Disease Involvement (2)

Cancer-related genesWilliams-Beuren syndrome

Antibody

CAB002610

Supporting Publications17

PMID	Title	Abstract
19837982	Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature.	A conspicuous finding of this comparative analysis was the presence of host cell-specific (LIM1215 exosome) proteins such as A33, cadherin-17, carcinoembryonic antigen, epithelial cell surface antigen (EpCAM), proliferating cell nuclear antigen, epidermal growth factor receptor, mucin 13, misshapen-like kinase 1, keratin 18, mitogen-activated protein kinase 4, claudins (1, 3, and 7), centrosomal protein 55 kDa, and ephrin-B1 and -B2. Here, we describe an immunoaffinity capture method using the colon epithelial cell-specific A33 antibody to purify colorectal cancer cell (LIM1215)-derived exosomes.
21630462	Proteomic analysis of microvesicles derived from human colorectal cancer ascites.	No abstract available
27894104	Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers.	No abstract available
28986585	Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics.	No abstract available
29045505	Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients.	Proteomic analysis of the exosome 'surfaceome' revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers.
32284825	Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine.	No abstract available
34817906	Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform.	No abstract available
34980157	Proteomic analysis of extracellular vesicles secreted by primary human epithelial endometrial cells reveals key proteins related to embryo implantation.	No abstract available
36398564	Differential ultracentrifugation enables deep plasma proteomics through enrichment of extracellular vesicles.	No abstract available
37205098	Proteomic profiling of extracellular vesicles in synovial fluid and plasma from Oligoarticular Juvenile Idiopathic Arthritis patients reveals novel immunopathogenic biomarkers.	No abstract available

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