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1.H.1.1.5
Claudin-19 (Cldn19) (interacts with Cldn3 and Cldn16 to form divalent cation (Mg2+ and Ca2+)-selective tight junctions; mutations in both proteins can give rise to hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an inherited disorder (Hou et al., 2008). Claudins 16 and 19 belong to the PMP22-Claudin subfamily.  The structure of Claudin 19 with Clostridium perfringens enterotoxin bound (3.7Å resolution) revelaed interactions with the two extracellular loops of the claudin giving rise to helix displacement as the mechanism of tight junction disruption (Saitoh et al. 2015).  Claudin-16 and -19 form a stable dimer through cis-association of transmembrane domains 3 and 4, and mutations disrupting the claudin-16/19 cis-interaction increase tight junction ultrastructural complexity but reduce its permeability (Gong et al. 2015).

Accession Number:Q8N6F1
Protein Name:Cldn19
Length:224
Molecular Weight:23229.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:5
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate Mg2+, Ca2+

Cross database links:

Genevestigator: Q8N6F1
HEGENOM: HBG716859
RefSeq: NP_001116867.1    NP_683763.2   
Entrez Gene ID: 149461   
Pfam: PF00822   
OMIM: 248190  phenotype
610036  gene
KEGG: hsa:149461   

Gene Ontology

GO:0016323 C:basolateral plasma membrane
GO:0016021 C:integral to membrane
GO:0005923 C:tight junction
GO:0042802 F:identical protein binding
GO:0016338 P:calcium-independent cell-cell adhesion
GO:0050896 P:response to stimulus
GO:0007601 P:visual perception

References (3)

[1] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement.”  Konrad M.et.al.   17033971

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MANSGLQLLG YFLALGGWVG IIASTALPQW KQSSYAGDAI ITAVGLYEGL WMSCASQSTG 
61:	QVQCKLYDSL LALDGHIQSA RALMVVAVLL GFVAMVLSVV GMKCTRVGDS NPIAKGRVAI 
121:	AGGALFILAG LCTLTAVSWY ATLVTQEFFN PSTPVNARYE FGPALFVGWA SAGLAVLGGS 
181:	FLCCTCPEPE RPNSSPQPYR PGPSAAAREP VVKLPASAKG PLGV