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PR01589

Identifier
CLAUDIN2  [View Relations]  [View Alignment]  
Accession
PR01589
No. of Motifs
4
Creation Date
08-AUG-2001
Title
Claudin-2 signature
Database References
PRINTS; PR01077 CLAUDIN
Literature References
1. TSUKITA, S. AND FURUSE, M.
Occuldin and claudins in tight-junction strands: leading or supporting
players?
TRENDS CELL BIOL. 9 268-273 (1999).
 
2. FURUSE, M., FUJITA, K., HIIRAGI, T., FUJIMOTO, K. AND TSUKITA, S.
Claudin-1 and -2: novel integral membrane proteins localizing at tight 
junctions with no sequence similarity to occludin.
J.CELL BIOL. 141 1539-1550 (1998).
 
3.FURUSE, M., SASAKI, H., FUJIMOTO, K. AND TSUKITA, S.
A single gene product, claudin-1 or -2, reconstitutes tight junction 
strands and recruits occludin in fibroblasts.
J.CELL BIOL. 143 391-401 (1998).
 
4. MORITA, K., FURUSE, M., FUJIMOTO, K. AND TSUKITA, S.
Claudin multigene family encoding four-transmembrane domain protein
components of tight junction strands.
PROC.NATL.ACAD.SCI.U.S.A. 96 511-516 (1999).

Documentation
Tight junctions (TJs) are specialised membrane domains found at the most 
apical region of polarised epithelial and endothelial cells. They create a 
primary barrier, preventing paracellular transport of solutes and 
restricting lateral diffusion of membrane lipids and proteins. They also 
act as diffusion barriers within plasma membranes, creating and maintaining
apical and basolateral membrane domains.
 
Recently, the molecular architecture of tight junctions has begun to be
elucidated. One group of proteins thought to be major components of TJs 
is the claudin family [1]. Immunofluorescence studies have shown that 
claudins are targeted to and incorporated into tight junctions [2]. 
Furthermore, when claudins are introduced into cells that lack tight 
junctions, networks of strands and grooves form at cell-cell contact sites 
that closely resemble native TJs [3].
 
The claudin protein family is encoded by at least 17 human genes, with many
homologues cloned from other species. Tissue distribution patterns for the 
claudin family members are distinct. Claudin-1 and -2, for example, are 
expressed at high levels in the liver and kidney, whereas claudin-3 mRNA is
detected mainly in the lung and liver [2,4]. This suggests that multiple 
claudin family members may be involved in tight junction strand formation 
in a tissue-dependent manner.
 
Hydropathy analysis suggests that all claudins share a common transmembrane
(TM) topology. Each family member is predicted to possess 4 TM domains with
intracellular N- and C-termini. Although their C-terminal cytoplasmic domain
sequences vary, most claudin family members share a common motif of -Y-V in
this region. This has been postulated as a possible binding motif for PDZ 
domains of other tight junction-associated membrane proteins, such as ZO-1.
 
Claudin-2 was initially isolated as a peptide fragment from TJ-enriched 
junctional cell fractions. Following sequencing and similarity searching 
it was cloned and expressed in cells, where it was shown to concentrate at 
TJs [2]. Human and mouse isoforms have been identified. Claudin-2 shares 
~22-46% overall similarity with other claudin family members at the amino
acid level, displaying highest similarity to claudin-14.
 
CLAUDIN2 is a 4-element fingerprint that provides a signature for claudin-2
proteins. The fingerprint was derived from an initial alignment of 2
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise 
claudin-2 but distinguish it from other family members - motif 1 spans part
of the first extracellular loop and part of TM domain 2; motif 2 lies in 
the intracellular loop; and motifs 3 and 4 reside in the cytoplasmic C-
terminal region. A single iteration on SPTR39.22_17.3f was required to reach
convergence, no further sequences being identified beyond the starting set.
Summary Information
2 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
42222
30000
20000
1234
True Positives
CLD2_HUMAN    O88552        
Sequence Titles
CLD2_HUMAN  Claudin-2 - Homo sapiens (Human).             
O88552 CLAUDIN-2 - MUS MUSCULUS (MOUSE).
Scan History
SPTR39.22_17.3f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=26
Element Seqn Id St Int Rpt
LPADIQAAQAMMVTSSAISSLACIIS CLD2_HUMAN 73 73 -
LPADIQAAQAMMVTSSAMSSLACIIS O88552 73 73 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CTVFCQESRAKDRVA CLD2_HUMAN 104 5 -
CTVFCQDSRAKDRVA O88552 104 5 -

Motif 3 width=16
Element Seqn Id St Int Rpt
YDAYQAQPLATRSSPR CLD2_HUMAN 195 76 -
YDGYQAQPLATRSSPR O88552 195 76 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PKVKSEFNSYSL CLD2_HUMAN 215 4 -
PKAKSEFNSYSL O88552 215 4 -
Final Motifs
Motif 1  width=26
Element Seqn Id St Int Rpt
LPADIQAAQAMMVTSSAISSLACIIS CLD2_HUMAN 73 73 -
LPADIQAAQAMMVTSSAMSSLACIIS O88552 73 73 -

Motif 2 width=15
Element Seqn Id St Int Rpt
CTVFCQESRAKDRVA CLD2_HUMAN 104 5 -
CTVFCQDSRAKDRVA O88552 104 5 -

Motif 3 width=16
Element Seqn Id St Int Rpt
YDAYQAQPLATRSSPR CLD2_HUMAN 195 76 -
YDGYQAQPLATRSSPR O88552 195 76 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PKVKSEFNSYSL CLD2_HUMAN 215 4 -
PKAKSEFNSYSL O88552 215 4 -