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PR01445

Identifier
CLAUDIN6  [View Relations]  [View Alignment]  
Accession
PR01445
No. of Motifs
4
Creation Date
15-NOV-2000
Title
Claudin-6 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-6 was identified through searching expressed sequence tag (EST)
databases for sequences similar to claudin-1 and -2 [4]. It was 
subsequently cloned and expressed in cells, where it was shown to
concentrate at tight junctions [4]. Human and mouse isoforms have been 
identified. Claudin-6 shares ~25-70% overall similarity with other claudin
family members at the amino acid level, displaying highest similarity to
claudin-9.
 
CLAUDIN6 is a 4-element fingerprint that provides a signature for claudin-6
proteins. The fingerprint was derived from an initial alignment of 2 
sequences: the motifs were drawn from conserved regions within the
C-terminal half of the alignment, focusing on those sections that 
characterise claudin-6 and distinguish it from other family members - motif
1 lies in the intracellular loop; motif 2 resides within TM domain 3; and
motifs 3 and 4 lie within the cytoplasmic C-terminal 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  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
42222
30000
20000
1234
True Positives
CLD6_HUMAN    CLD6_MOUSE    
Sequence Titles
CLD6_HUMAN  Claudin-6 - Homo sapiens (Human).             
CLD6_MOUSE Claudin-6 - Mus musculus (Mouse).
Scan History
SPTR39_14f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=7
Element Seqn Id St Int Rpt
EEKDSKA CLD6_HUMAN 109 109 -
EDRNSKS CLD6_MOUSE 109 109 -

Motif 2 width=7
Element Seqn Id St Int Rpt
ISGVLTL CLD6_HUMAN 127 11 -
ISGVLTL CLD6_MOUSE 127 11 -

Motif 3 width=12
Element Seqn Id St Int Rpt
SGGSQGPSHYMA CLD6_HUMAN 187 53 -
SGGTQGPRHYMA CLD6_MOUSE 187 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
SRGPSEYPTKNY CLD6_HUMAN 208 9 -
SRGPSEYPTKNY CLD6_MOUSE 207 8 -
Final Motifs
Motif 1  width=7
Element Seqn Id St Int Rpt
EEKDSKA CLD6_HUMAN 109 109 -
EDRNSKS CLD6_MOUSE 109 109 -

Motif 2 width=7
Element Seqn Id St Int Rpt
ISGVLTL CLD6_HUMAN 127 11 -
ISGVLTL CLD6_MOUSE 127 11 -

Motif 3 width=12
Element Seqn Id St Int Rpt
SGGSQGPSHYMA CLD6_HUMAN 187 53 -
SGGTQGPRHYMA CLD6_MOUSE 187 53 -

Motif 4 width=12
Element Seqn Id St Int Rpt
SRGPSEYPTKNY CLD6_HUMAN 208 9 -
SRGPSEYPTKNY CLD6_MOUSE 207 8 -