O14493 · CLD4_HUMAN
- ProteinClaudin-4
- GeneCLDN4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids209 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Can associate with other claudins to regulate tight junction structural and functional strand dynamics (PubMed:35773259, PubMed:36008380).
May coassemble with CLDN8 into tight junction strands containing anion-selective channels that convey paracellular chloride permeability in renal collecting ducts (By similarity) (PubMed:36008380).
May integrate into CLDN3 strands to modulate localized tight junction barrier properties (PubMed:35773259, PubMed:36008380).
May disrupt strand assembly of channel-forming CLDN2 and CLDN15 and inhibit cation conductance (PubMed:35773259, PubMed:36008380).
Cannot form tight junction strands on its own (PubMed:35773259, PubMed:36008380).
May coassemble with CLDN8 into tight junction strands containing anion-selective channels that convey paracellular chloride permeability in renal collecting ducts (By similarity) (PubMed:36008380).
May integrate into CLDN3 strands to modulate localized tight junction barrier properties (PubMed:35773259, PubMed:36008380).
May disrupt strand assembly of channel-forming CLDN2 and CLDN15 and inhibit cation conductance (PubMed:35773259, PubMed:36008380).
Cannot form tight junction strands on its own (PubMed:35773259, PubMed:36008380).
Catalytic activity
- chloride(in) = chloride(out)
- bromide(in) = bromide(out)
- iodide(out) = iodide(in)
- fluoride(in) = fluoride(out)
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameClaudin-4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO14493
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-7 | Cytoplasmic | ||||
Sequence: MASMGLQ | ||||||
Transmembrane | 8-28 | Helical | ||||
Sequence: VMGIALAVLGWLAVMLCCALP | ||||||
Topological domain | 29-81 | Extracellular | ||||
Sequence: MWRVTAFIGSNIVTSQTIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAAR | ||||||
Transmembrane | 82-102 | Helical | ||||
Sequence: ALVIISIIVAALGVLLSVVGG | ||||||
Topological domain | 103-117 | Cytoplasmic | ||||
Sequence: KCTNCLEDESAKAKT | ||||||
Transmembrane | 118-138 | Helical | ||||
Sequence: MIVAGVVFLLAGLMVIVPVSW | ||||||
Topological domain | 139-160 | Extracellular | ||||
Sequence: TAHNIIQDFYNPLVASGQKREM | ||||||
Transmembrane | 161-181 | Helical | ||||
Sequence: GASLYVGWAASGLLLLGGGLL | ||||||
Topological domain | 182-209 | Cytoplasmic | ||||
Sequence: CCNCPPRTDKPYSAKYSAARSAAASNYV |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 35 | Decreases interaction with Clostridium perfringens CPE. | ||||
Sequence: F → A | ||||||
Mutagenesis | 35 | Abolishes interaction with Clostridium perfringens CPE. | ||||
Sequence: F → D | ||||||
Mutagenesis | 40 | No effect on interaction with Clostridium perfringens CPE. | ||||
Sequence: I → A | ||||||
Mutagenesis | 40 | Strongly decreases interaction with Clostridium perfringens CPE. | ||||
Sequence: I → D | ||||||
Mutagenesis | 53 | Decreases interaction with Clostridium perfringens CPE. | ||||
Sequence: N → A or D | ||||||
Mutagenesis | 208 | Loss of phosphorylation by EPHA2. | ||||
Sequence: Y → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 258 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000144743 | 1-209 | Claudin-4 | |||
Sequence: MASMGLQVMGIALAVLGWLAVMLCCALPMWRVTAFIGSNIVTSQTIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALVIISIIVAALGVLLSVVGGKCTNCLEDESAKAKTMIVAGVVFLLAGLMVIVPVSWTAHNIIQDFYNPLVASGQKREMGASLYVGWAASGLLLLGGGLLCCNCPPRTDKPYSAKYSAARSAAASNYV | ||||||
Disulfide bond | 54↔64 | |||||
Sequence: CVVQSTGQMQC | ||||||
Modified residue | 208 | Phosphotyrosine; by EPHA2 | ||||
Sequence: Y |
Post-translational modification
Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Developmental stage
Expressed in the lungs from 23 weeks of gestation till birth.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Can form heteropolymeric strands with other claudins (PubMed:36008380).
Interacts with CLDN8 (By similarity).
Interacts with CLDN1 (PubMed:20375010).
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 CLDN8 (By similarity).
Interacts with CLDN1 (PubMed:20375010).
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).
(Microbial infection) Interacts (via both extracellular domains) with Clostridium perfringens enterotoxin CPE; the interaction may disrupt claudin assembly in tight junctions.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O14493 | AQP6 Q13520 | 3 | EBI-9316372, EBI-13059134 | |
BINARY | O14493 | ARL13B Q3SXY8 | 3 | EBI-9316372, EBI-11343438 | |
BINARY | O14493 | CLEC14A Q86T13 | 3 | EBI-9316372, EBI-17710733 | |
BINARY | O14493 | FAM209A Q5JX71 | 3 | EBI-9316372, EBI-18304435 | |
BINARY | O14493 | FFAR2 O15552 | 3 | EBI-9316372, EBI-2833872 | |
BINARY | O14493 | GJA8 P48165 | 3 | EBI-9316372, EBI-17458373 | |
BINARY | O14493 | GOLM1 Q8NBJ4 | 3 | EBI-9316372, EBI-712073 | |
BINARY | O14493 | HSD17B13 Q7Z5P4 | 3 | EBI-9316372, EBI-18053395 | |
BINARY | O14493 | ICAM3 P32942 | 3 | EBI-9316372, EBI-725421 | |
BINARY | O14493 | MFSD14B Q5SR56 | 3 | EBI-9316372, EBI-373355 | |
BINARY | O14493 | SYT2 Q8N9I0 | 3 | EBI-9316372, EBI-8032987 | |
BINARY | O14493 | TMEM237 Q96Q45-2 | 3 | EBI-9316372, EBI-10982110 | |
BINARY | O14493 | TMEM52B Q4KMG9 | 3 | EBI-9316372, EBI-18178701 | |
BINARY | O14493 | TRIM59 Q8IWR1 | 3 | EBI-9316372, EBI-10262539 | |
BINARY | O14493 | TSPO2 Q5TGU0 | 3 | EBI-9316372, EBI-12195249 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-103 | Interaction with EPHA2 | ||||
Sequence: MASMGLQVMGIALAVLGWLAVMLCCALPMWRVTAFIGSNIVTSQTIWEGLWMNCVVQSTGQMQCKVYDSLLALPQDLQAARALVIISIIVAALGVLLSVVGGK | ||||||
Region | 208-209 | Interactions with TJP1, TJP2 and TJP3 | ||||
Sequence: YV |
Sequence similarities
Belongs to the claudin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length209
- Mass (Da)22,077
- Last updated1998-01-01 v1
- Checksum0659A93AA5F0E4C5
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB000712 EMBL· GenBank· DDBJ | BAA22984.1 EMBL· GenBank· DDBJ | mRNA | ||
BT006989 EMBL· GenBank· DDBJ | AAP35635.1 EMBL· GenBank· DDBJ | mRNA | ||
BC000671 EMBL· GenBank· DDBJ | AAH00671.1 EMBL· GenBank· DDBJ | mRNA |