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PR01600

Identifier
ZONOCCLUDNS3  [View Relations]  [View Alignment]  
Accession
PR01600
No. of Motifs
5
Creation Date
07-AUG-2001
Title
Zona occludens protein ZO-3 signature
Database References
PRINTS; PR01597 ZONOCCLUDNS
PRODOM; PD068424; PD072431
Literature References
1. TSUKITA, S. AND FURUSE, M.
Overcoming barriers in the study of tight junction functions: from occludin
to claudin.
GENES CELLS 3 569-573 (1998).
 
2. TSUKITA, S. AND FURUSE, M.
Occludins and claudins in tight-junction strands: leading or supporting
players?
TRENDS CELL BIOL. 9 268-273 (1999).
 
3. ITOH, M., NAHAFUCHI, A., MOROI, S. AND TSUKITA, S.
Involvement of ZO-1 in cadherin-based cell adhesion through its direct 
binding to alpha catenin and actin filaments.
J.CELL BIOL. 138 181-192 (1997).
 
4. ITOH, M., FURUSE, M., MORITA, K., KUBOTA, K., SAITOU, M. AND TSUKITA S.
Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and 
ZO-3, with the COOH termini of claudins.
J.CELL BIOL. 147 1351-1363 (1999).
 
5. FANNING, A., JAMESON, B., JESAITIS, L. AND ANDERSON, J.
The tight junction protein ZO-1 establishes a link between the transmembrane
protein occludin and the actin cytoskeleton.
J.BIOL.CHEM. 273 29745-29753 (1998).
 
6. BALDA, M., GONZALEZ-MARISCAL, L., MATTER, K., CEREIJIDO, M. AND 
ANDERSON, J. 
Assembly of the tight junction: the role of diacylglycerol.
J.CELL.BIOL. 123, 293-302 (1993).
 
7. HASKINS, J., GU, L., WITTCHEN, E., HIBBARD, J. AND STEVENSON, B.
ZO-3, a novel member of the MAGUK protein family found at the tight 
junction, interacts with ZO-1 and occludin.
J.CELL.BIOL. 141 199-288 (1998).

Documentation
Zona occludens (ZO), or tight junctions (TJ), are specialised membrane 
domains found at the most apical region of polarised epithelial and endo-
thelial cells that create a primary barrier, preventing paracellular 
transport of solutes, and restricting the lateral diffusion of membrane 
lipids and proteins, thus maintaining cellular polarity [1]. Under freeze-
fracture electron microscopy, TJs appear as a network of continuous 
anastomosing intramembranous strands. These strands consist mainly of 
claudins and occludin, which are transmembrane proteins that polymerise 
within plasma membranes to form fibrils [2].
 
The zona occuldens proteins (ZO-1, ZO-2 and ZO-3) are a family of TJ- 
associated proteins that function as cross-linkers, anchoring the TJ strand 
proteins to the actin-based cytoskeleton [3,4]. Each protein contains three 
PDZ (postsynaptic density, disc-large, ZO-1) domains, a single SH3 (Src 
Homology-3) domain and a GK (guanylate kinase) domain, the presence of which
identifies them as members of the membrane-associated guanylate kinase 
(MAGUK) protein family. They also share an acidic domain at the C-terminal 
region of the molecules not found in other MAGUK proteins. It has been 
demonstrated that the first PDZ domain is involved in binding the C-terminal
-Y-V motif of claudins [4]. By contrast, the occludin-binding domain of
ZO-1 has been shown to lie in the GK and acidic domains [5]. Although the
precise location of the actin-binding motif has not been elucidated, it 
appears to be within the C-terminal half of the molecules, since 
transfection of this region into fibroblasts induces co-localisation 
of ZO-1 and ZO-2 with actin fibres [5].
 
ZO-3 was first identified as a 130kDa protein that co-immunoprecipitates
with ZO-1 [6]. It shares ~65% overall similarity with ZO-1 and ZO-2 
proteins, with highest levels of similarity in the MAGUK and acid domains.
In vitro binding studies indicate that ZO-3 may interact directly with ZO-1
through its second PDZ domain, although it does not appear to bind directly
to ZO-2 [7].
 
ZONOCCLUDNS3 is a 5-element fingerprint that provides a signature for the 
zona occludens protein ZO-3. The fingerprint was derived from an initial 
alignment of 3 sequences: the motifs were drawn from conserved regions 
spanning virtually the full alignment length, focusing on those sections 
that characterise ZO-3 but distinguish it from other family members - motif
1 lies between the first and second PDZ domain; motifs 2 and 3 reside 
between the SH3 and GK domains; motif 4 encodes part of the GK domain; and
motif 5 lies beyond the GK domain in the C-terminal portion of the
alignment. A single iteration on SPTR39.22_17.3f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
3 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
533333
400000
300000
200000
12345
True Positives
ZO3_CANFA     ZO3_HUMAN     ZO3_MOUSE     
Sequence Titles
ZO3_CANFA   TIGHT JUNCTION PROTEIN ZO-3 (ZONULA OCCLUDENS 3 PROTEIN) (ZONA OCCLUDENS 3 PROTEIN) (TIGHT JUNCTION PROTEIN 3) - Canis familiaris (Dog). 
ZO3_HUMAN TIGHT JUNCTION PROTEIN ZO-3 (ZONULA OCCLUDENS 3 PROTEIN) (ZONA OCCLUDENS 3 PROTEIN) (TIGHT JUNCTION PROTEIN 3) - Homo sapiens (Human).
ZO3_MOUSE TIGHT JUNCTION PROTEIN ZO-3 (ZONULA OCCLUDENS 3 PROTEIN) (ZONA OCCLUDENS 3 PROTEIN) (TIGHT JUNCTION PROTEIN 3) - Mus musculus (Mouse).
Scan History
SPTR39.22_17.3f 1  300  NSINGLE    
Initial Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
RSRRPRPGRRGRAG ZO3_HUMAN 145 145 -
RSRRARTGRRNQAG ZO3_CANFA 137 137 -
RSRRSRAGRRGRVG ZO3_MOUSE 137 137 -

Motif 2 width=16
Element Seqn Id St Int Rpt
QRAVGVGPGSSAGSNA ZO3_HUMAN 569 410 -
QRAVGAGPGASVGSSA ZO3_CANFA 544 393 -
QRAAGVGPGASVGSNP ZO3_MOUSE 547 396 -

Motif 3 width=10
Element Seqn Id St Int Rpt
LSALTRQGRY ZO3_HUMAN 609 24 -
LSALTRQGHY ZO3_CANFA 584 24 -
LSALTRQGHY ZO3_MOUSE 588 25 -

Motif 4 width=14
Element Seqn Id St Int Rpt
KIIKLDTVRVIAEK ZO3_HUMAN 671 52 -
KIIKLDTVRVIAEK ZO3_CANFA 646 52 -
KIIKLDTVRVIAER ZO3_MOUSE 650 52 -

Motif 5 width=17
Element Seqn Id St Int Rpt
YQELKAIIREQQTRPIW ZO3_HUMAN 767 82 -
YQELKAVVREQQTRPIW ZO3_CANFA 742 82 -
YQEVKAVIQQQQARPIW ZO3_MOUSE 746 82 -
Final Motifs
Motif 1  width=14
Element Seqn Id St Int Rpt
RSRRPRPGRRGRAG ZO3_HUMAN 145 145 -
RSRRARTGRRNQAG ZO3_CANFA 137 137 -
RSRRSRAGRRGRVG ZO3_MOUSE 137 137 -

Motif 2 width=16
Element Seqn Id St Int Rpt
QRAVGVGPGSSAGSNA ZO3_HUMAN 569 410 -
QRAVGAGPGASVGSSA ZO3_CANFA 544 393 -
QRAAGVGPGASVGSNP ZO3_MOUSE 547 396 -

Motif 3 width=10
Element Seqn Id St Int Rpt
LSALTRQGRY ZO3_HUMAN 609 24 -
LSALTRQGHY ZO3_CANFA 584 24 -
LSALTRQGHY ZO3_MOUSE 588 25 -

Motif 4 width=14
Element Seqn Id St Int Rpt
KIIKLDTVRVIAEK ZO3_HUMAN 671 52 -
KIIKLDTVRVIAEK ZO3_CANFA 646 52 -
KIIKLDTVRVIAER ZO3_MOUSE 650 52 -

Motif 5 width=17
Element Seqn Id St Int Rpt
YQELKAIIREQQTRPIW ZO3_HUMAN 767 82 -
YQELKAVVREQQTRPIW ZO3_CANFA 742 82 -
YQEVKAVIQQQQARPIW ZO3_MOUSE 746 82 -