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PR01598

Identifier
ZONOCCLUDNS1  [View Relations]  [View Alignment]  
Accession
PR01598
No. of Motifs
4
Creation Date
03-AUG-2001
Title
Zona occludens protein ZO-1 signature
Database References
PRINTS; PR01597 ZONOCCLUDNS
PRODOM; PD029525; PD333446; PD340257; PD044063
MIM; 601009
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. STEVENSON, B., SILICIANO, J., MOOSEKER, M. AND GOODENOUGH, D.
Identification of ZO-1: a high molecular weight polypeptide associated with
the tight junction (zonula occludens) in a variety of epithelia.
J.CELL BIOL. 103 755-766 (1986).
 
7. GUMBINER, B., LOWENKOPF, T. AND APATIRA, D.
Identification of a 160-kDa polypeptide that binds to the tight junction
protein ZO-1.
PROC.NATL.ACAD.SCI.U.S.A. 88 3460-3464 (1991).
 
8. 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 occludens 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-1 was first identified as a 220kDa antigen for a monoclonal antibody
raised to junction-enriched cell fractions [6]. The protein shares ~65% 
overall similarity with ZO-2 and ZO-3 proteins, with highest levels of 
similarity in the MAGUK and acid domains. The structure of ZO-1 is distinct
from the other ZO protein family members in that it contains a ZU5 domain 
at the C-terminal end of the molecule, although the function of this domain
is unknown. Binding and tranfection studies indicate that ZO-1 is capable 
of associating with ZO-2 and ZO-3 through binding of the second PDZ domains
[7,8].
 
ZONOCCLUDNS1 is a 4-element fingerprint that provides a signature for zona
occludens protein ZO-1. 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-1 but distinguish it from other family members - motifs
1 and 2 lie between the second and third PDZ domains; and motifs 3 and 4 
reside between the GK domain and the ZU5 domain in the C-terminal part 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  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
43333
30000
20000
1234
True Positives
O97758        ZO1_HUMAN     ZO1_MOUSE     
Sequence Titles
O97758      ZO-1 MDCK - Canis familiaris (Dog).           
ZO1_HUMAN TIGHT JUNCTION PROTEIN ZO-1 (ZONULA OCCLUDENS 1 PROTEIN) (ZONA OCCLUDENS 1 PROTEIN) (TIGHT JUNCTION PROTEIN 1) - Homo sapiens (Human).
ZO1_MOUSE TIGHT JUNCTION PROTEIN ZO-1 (ZONULA OCCLUDENS 1 PROTEIN) (ZONA OCCLUDENS 1 PROTEIN) (TIGHT JUNCTION PROTEIN 1) - Mus musculus (Mouse).
Scan History
SPTR39.22_17.3f 1  200  NSINGLE    
Initial Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
ERISKPGAVSTPVKHADDHTPK ZO1_HUMAN 332 332 -
ERISKPGAVSTPVKHADDHTHK O97758 343 343 -
ERMSKPGAISTPVKHVDDHPPK ZO1_MOUSE 344 344 -

Motif 2 width=26
Element Seqn Id St Int Rpt
VEEVTVERNEKQTPSLPEPKPVYAQV ZO1_HUMAN 355 1 -
VEEVVVERNEKQAPSLPEPKPVYAQV O97758 366 1 -
VEEVTVEKNEKQTPTLPEPKPVYAQV ZO1_MOUSE 367 1 -

Motif 3 width=23
Element Seqn Id St Int Rpt
YRYESSSYTDQFSRNYEHRLRYE ZO1_HUMAN 1047 666 -
YRYDSSSYTDQFSRNYDHRLRYE O97758 1058 666 -
YRYEVSSYTDQFSRNYDHRLRFE ZO1_MOUSE 1059 666 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EQTQKTVTPAYNRFTPKPYTSS ZO1_HUMAN 1502 432 -
EQTQKTVTPAYNRFTPKPYTSS O97758 1515 434 -
EQTQKTITPVYNRFTPKPYTSS ZO1_MOUSE 1511 429 -
Final Motifs
Motif 1  width=22
Element Seqn Id St Int Rpt
ERISKPGAVSTPVKHADDHTPK ZO1_HUMAN 332 332 -
ERISKPGAVSTPVKHADDHTHK O97758 343 343 -
ERMSKPGAISTPVKHVDDHPPK ZO1_MOUSE 344 344 -

Motif 2 width=26
Element Seqn Id St Int Rpt
VEEVTVERNEKQTPSLPEPKPVYAQV ZO1_HUMAN 355 1 -
VEEVVVERNEKQAPSLPEPKPVYAQV O97758 366 1 -
VEEVTVEKNEKQTPTLPEPKPVYAQV ZO1_MOUSE 367 1 -

Motif 3 width=23
Element Seqn Id St Int Rpt
YRYESSSYTDQFSRNYEHRLRYE ZO1_HUMAN 1047 666 -
YRYDSSSYTDQFSRNYDHRLRYE O97758 1058 666 -
YRYEVSSYTDQFSRNYDHRLRFE ZO1_MOUSE 1059 666 -

Motif 4 width=22
Element Seqn Id St Int Rpt
EQTQKTVTPAYNRFTPKPYTSS ZO1_HUMAN 1502 432 -
EQTQKTVTPAYNRFTPKPYTSS O97758 1515 434 -
EQTQKTITPVYNRFTPKPYTSS ZO1_MOUSE 1511 429 -