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PR01872

Identifier
CLAUDIN12  [View Relations]  [View Alignment]  
Accession
PR01872
No. of Motifs
4
Creation Date
09-JUN-2003
Title
Claudin-12 signature
Database References
PRINTS; PR01077 CLAUDIN
Literature References
1. TSUKITA, S. AND FURUSE, M.
Occludin and claudins in tight-junction strands: leading or supporting
players?
TRENDS CELL BIOL. 9 268-273 (1999).
 
2. KOLLMAR, R., NAKAMURA, S.K., KAPPLER, J.A. AND HUDSPETH, A.J.
Expression and phylogeny of claudins in vertebrate primordia.
PROC.NATL.ACAD.SCI.U.S.A. 98 10196-10201 (2001).
 
3. 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).
 
4. 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).
 
5. 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).
 
6. HEISKALA, M., PETERSON, P.A. AND YANG, Y.
The roles of the claudin superfamily proteins in paracellular transport.
TRAFFIC 2 92-98 (2001).

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], which are members of the tetraspanin superfamily
[2]. Immunofluorescence studies have shown that claudins are targeted to
and incorporated into tight junctions [3]. 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
[4].
 
The claudin protein family is encoded by at least 18 human genes, with
many homologues cloned from other species. Tissue distribution patterns for
the claudin family members are distinct [5]. Claudin 11, for example, is
found predominantly in the CNS; and claudin 16 mRNA is expressed in the
kidney. Defects in claudin genes, therefore, give rise to diseases in a
tissue-specific manner, e.g. alterations in claudin 11 have been implicated 
in multiple sclerosis, and mutations in the claudin 16 gene affect the
re-uptake of magnesium ions in the kidney, leading to renal failure [6].
 
The claudins are believed to share a common topology, comprising four
membrane-spanning helices (TM1 to 4) with the N- and C-termini located in
the cytoplasm. The first extracellular loop is longer and more hydrophobic
than the second, and is believed to bridge the extracellular space. Among
claudins, the greatest level of sequence conservation is observed in TM1
and 4, as well as the extracellular loops. The sequences of TM2, TM3 and,
in particular, the C-terminus display the greatest level of diversity in
primary structure. Many claudin family members feature a -Y-V motif at the
C-teminus; this sequence interacts with the PDZ domain, a module of 80-90
residues found in other tight junction-associated membrane proteins, such
as ZO-1.
 
Orthologues of the claudin 12 subtype have been identifed in humans and
zebrafish. Whilst these proteins clearly belong to the tetraspanin
superfamily, they represent the most divergent claudin subtype in terms of
primary structure [2]. Claudin 12 mRNA has been detected in the brain,
prostate, colon and uterus [6].
 
CLAUDIN12 is a 4-element fingerprint that provides a signature for the
claudin-12 subtype. The fingerprint was derived from an initial alignment
of 3 sequences: the motifs were drawn from conserved regions that 
characterise claudin-12 proteins but distinguish them from related claudin 
paralogues - motifs 1 and 2 lie in the first extracellular loop; motif 3 
resides in the first cytoplasmic loop; and motif 4 is located between the 
third putative TM domain and the second extracellular loop. A single 
iteration on SPTR40_22f was required to reach convergence, no further 
sequences being identified beyond the starting set.
Summary Information
3 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
CLDC_HUMAN    Q90XR1        Q90XR3        
Sequence Titles
CLDC_HUMAN  Claudin-12 - Homo sapiens (Human).            
Q90XR1 Claudin 12 isoform fc43a12 - Brachydanio rerio (Zebrafish) (Danio rerio).
Q90XR3 Claudin 12 isoform fc27c11 - Brachydanio rerio (Zebrafish) (Danio rerio).
Scan History
SPTR40_22f 1  100  NSINGLE    
Initial Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LLTFNRNAKNVTVYDG Q90XR1 38 38 -
LLTFNRNAKNVTVYDG Q90XR3 38 38 -
LITFNRNEKNLTVYTG CLDC_HUMAN 38 38 -

Motif 2 width=17
Element Seqn Id St Int Rpt
SGCYYFDSDWYAKVDQL Q90XR1 65 11 -
SGCYYFDSDWYAKVDQL Q90XR3 65 11 -
SDCLMYDTTWYSSVDQL CLDC_HUMAN 65 11 -

Motif 3 width=13
Element Seqn Id St Int Rpt
SRCLVNSSGCHLV Q90XR1 124 42 -
SRCLVNSSGCHLV Q90XR3 124 42 -
AKCLVNSAGCHLV CLDC_HUMAN 123 41 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PSVWFLFHTRHL Q90XR1 151 14 -
PSVWFLFHTRHL Q90XR3 151 14 -
PSIWVIFYNIHL CLDC_HUMAN 150 14 -
Final Motifs
Motif 1  width=16
Element Seqn Id St Int Rpt
LLTFNRNAKNVTVYDG Q90XR1 38 38 -
LLTFNRNAKNVTVYDG Q90XR3 38 38 -
LITFNRNEKNLTVYTG CLDC_HUMAN 38 38 -

Motif 2 width=17
Element Seqn Id St Int Rpt
SGCYYFDSDWYAKVDQL Q90XR1 65 11 -
SGCYYFDSDWYAKVDQL Q90XR3 65 11 -
SDCLMYDTTWYSSVDQL CLDC_HUMAN 65 11 -

Motif 3 width=13
Element Seqn Id St Int Rpt
SRCLVNSSGCHLV Q90XR1 124 42 -
SRCLVNSSGCHLV Q90XR3 124 42 -
AKCLVNSAGCHLV CLDC_HUMAN 123 41 -

Motif 4 width=12
Element Seqn Id St Int Rpt
PSVWFLFHTRHL Q90XR1 151 14 -
PSVWFLFHTRHL Q90XR3 151 14 -
PSIWVIFYNIHL CLDC_HUMAN 150 14 -