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PR01448

Identifier
CLAUDIN18  [View Relations]  [View Alignment]  
Accession
PR01448
No. of Motifs
5
Creation Date
15-NOV-2000
Title
Claudin-18 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.
 
Human and mouse isoforms of claudin-18 have been cloned. Claudin-18 shares
~22-40% overall similarity with other claudin family members at the amino
acid level, displaying highest similarity to claudin-1.
 
CLAUDIN18 is a 5-element fingerprint that provides a signature for
claudin-18 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-18 and distinguish it from other family members - 
motif 1 lies in TM domain 1; motif 2 resides within the first extracellular
loop; motif 3 spans part of TM domain 2 and part of the intracellular loop;
motif 4 lies partially in TM domain 4 and partially in the intracellular
C-terminal region; and motif 5 lies within the C-terminal cytoplasmic 
region. A single iteration on SPTR39_14f was required to reach convergence,
no further sequences being identified beyond the starting set.
Summary Information
2 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
522222
400000
300000
200000
12345
True Positives
CLDI_HUMAN    CLDI_MOUSE    
Sequence Titles
CLDI_HUMAN  Claudin-18 - Homo sapiens (Human).            
CLDI_MOUSE Claudin-18 - Mus musculus (Mouse).
Scan History
SPTR39_14f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
ILGLAGCIAATGMD CLDI_HUMAN 15 15 -
LLGLAGCIAATGMD CLDI_MOUSE 15 15 -

Motif 2 width=14
Element Seqn Id St Int Rpt
TQDLYDNPVTSVFQ CLDI_HUMAN 32 3 -
TQDLYDNPVTAVFQ CLDI_MOUSE 32 3 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SIFALKCIRIGSME CLDI_HUMAN 97 51 -
SIFALKCIRIGSMD CLDI_MOUSE 97 51 -

Motif 4 width=16
Element Seqn Id St Int Rpt
MCIACRGLAPEETNYK CLDI_HUMAN 192 81 -
MCIACRGLTPDDSNFK CLDI_MOUSE 195 84 -

Motif 5 width=20
Element Seqn Id St Int Rpt
HSVAYKPGGFKASTGFGSNT CLDI_HUMAN 216 8 -
QNVAYRPGGFKASTGFGSNT CLDI_MOUSE 219 8 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
ILGLAGCIAATGMD CLDI_HUMAN 15 15 -
LLGLAGCIAATGMD CLDI_MOUSE 15 15 -

Motif 2 width=14
Element Seqn Id St Int Rpt
TQDLYDNPVTSVFQ CLDI_HUMAN 32 3 -
TQDLYDNPVTAVFQ CLDI_MOUSE 32 3 -

Motif 3 width=14
Element Seqn Id St Int Rpt
SIFALKCIRIGSME CLDI_HUMAN 97 51 -
SIFALKCIRIGSMD CLDI_MOUSE 97 51 -

Motif 4 width=16
Element Seqn Id St Int Rpt
MCIACRGLAPEETNYK CLDI_HUMAN 192 81 -
MCIACRGLTPDDSNFK CLDI_MOUSE 195 84 -

Motif 5 width=20
Element Seqn Id St Int Rpt
HSVAYKPGGFKASTGFGSNT CLDI_HUMAN 216 8 -
QNVAYRPGGFKASTGFGSNT CLDI_MOUSE 219 8 -