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PR01819

Identifier
DESMOGLEIN  [View Relations]  [View Alignment]  
Accession
PR01819
No. of Motifs
4
Creation Date
21-JAN-2003
Title
Desmoglein signature
Database References
PRINTS; PR01818 DESMOCADHERN
Literature References
1. LIAW, C.W., CANNON, C., POWER, M.D., KIBONEKA, P.K. AND RUBIN, L.L.
Identification and cloning of 2 species of cadherins in bovine endothelial
cells.
EMBO J. 9(9) 2701-2708 (1990).
 
2. GINSBERG, D., DESIMONE, D. AND GEIGER, B.
Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early
Xenopus embryos.
DEVELOPMENT 111(2) 315-325 (1991).
 
3. WALSH, F.S., BARTON, C.H., PUTT, W., MOORE, S.E., KELSELL, D., SPURR, N.
AND GOODFELLOW, P.N.
N-Cadherin gene maps to human chromosome 18 and is not linked to the
E-cadherin gene.
J.NEUROCHEM. 55(3) 805-812 (1990).
 
4. ISHII, K. AND GREEN, K.
Cadherin function: Breaking the barrier.
CURR.BIOL. 11 R569-R572 (2001).
 
5. GARROD, D., MERRITT, A. AND NIE, Z.
Desmosomal adhesion: structural basis, molecular mechanism and regulation. 
MOL.MEMBR.BIOL. 19 81-94 (2002).
 
6. ANGST, B., MARCOZZI, C. AND MAGEE, A. 
The cadherin superfamily: diversity in form and function.
J.CELL SCI. 114 629-641 (2001).
 
7. KING, I.A., ANGST, B.D., HUNT, D.M., KRUGER, M., ARNEMANN J. AND
BUXTON, R.S. 
Hierarchical expression of desmosomal cadherins during stratified epithelial
morphogenesis in the mouse.
DIFFERENTIATION 62 83-96 (1997).
 
8. MARCOZZI, C., BURDETT I.D., BUXTON, R.S. AND MAGEE, A.I.
Coexpression of both types of desmosomal cadherin and plakoglobin confers   
strong intercellular adhesion. 
J.CELL SCI. 111 495-509 (1998). 
 
9. AMAGAI, M.
Autoimmunity against desmosomal cadherins in pemphigus. 
J.DERMATOL.SCI. 20 92-102 (1999).
 
10. AMAGAI, M., MATSUYOSHI, N., WANG, Z.H., ANDL, C. AND STANLEY, J.R.
Toxin in bullous impetigo staphylococcal scalded-skin syndrome suggests 
targets desmoglein 1.
NATURE MED. 6 1275-1277 (2000).
 
11. RICKMAN, L., SIMRAK, D., STEVENS, H.P., HUNT, D.M., KING I.A.,
BRYANT, S.P., WADY, R.A., LEIGH, I.M., ARNEMANN, J., MAGEE, A.I., 
KELSELL, D.P. AND BUXTON, R.S.
N-terminal deletion in a desmosomal cadherin causes the autosomal domainat 
skin disease striate palmoplantar keratoderma
HUM.MOL.GENET. 8 971-976 (1999). 
 
12. HUNT, D.M., RICKMAN, L., WHITTOCK, N.V., EADY, R.A., SIMRAK, D., 
DOPPING-HEPENSTAL, P.J., STEVENS, H.P., ARMSTRONG, D.K., HENNIES, H.C., 
KUSTER, W., HUGHES, A.E., ARNEMANN, J., LEIGH, I.M., MCGRATH, J.A., 
KELSELL, D.P. AND BUXTON, R.S. 
Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1, 
causing the skin disease striate palmoplantar keratoderma.
EUR.J.HUM.GENET. 3 197-203 (2001).

Documentation
Cadherins, first discovered in mouse teratocarcinoma cells [1], are 
structurally and functionally similar molecules [2] that take part in 
selective calcium-dependent adhesion interactions between cell surfaces
[3]. There are a number of different isoforms distributed in a tissue-
specific manner in a wide variety of organisms. Cells containing different 
cadherins tend to segregate in vitro, while those that contain the same 
cadherins tend to preferentially aggregate together. This observation is 
linked to the finding that cadherin expression causes morphological changes
involving the positional segregation of cells into layers, suggesting they 
may play an important role in the sorting of different cell types during 
morphogenesis, histogenesis and regeneration. They may also be involved in 
the regulation of tight and gap junctions, and in the control of 
intercellular spacing.
 
Structurally, cadherins comprise a number of domains: these include a
signal sequence; a propeptide of ~130 residues; an extracellular domain of
~600 residues; a single transmembrane (TM) domain; and a well-conserved
C-terminal cytoplasmic domain of ~150 residues. The extracellular domain 
can be subdivided into 5 parts, 4 of which are repeats of ~110 residues, 
and the fifth contains 4 conserved cysteines. The calcium-binding region
of cadherins is thought to be located in the extracellular domain.
 
Desmosomes are localised junctions that hold cells tightly together, common 
in tissues subject to mechanical strain (e.g., epithelia). Desmosomal        
cadherins are TM protein components of desmosomes (for review, see [4-6]),
whose extracellular cadherin repeats are responsible for adhesion and whose
intracellular regions interact with intermediate filaments via desmosomal
plaque proteins plakoglobin, plakobilin and desmoplakin [7]. They are 
believed to play a wider role in regulation of epithelial differentiation
[5]. Two sub-families of desmosomal cadherin have been identified,
desmocollin (DSC) and desmoglein (DSG). 
 
For each subfamily, three subtypes have been identified, expressed in a
cell-type and differentiation-specific manner [7]. Studies in normally      
desmosome-free cells have shown that expression of at least one DSC and     
one DSG in combination with plakoglobin is required to promote adhesion [8].
Little is known about functional differences between the DSG or DSC sub-    
families. In sequence, however, DSG differs from DSC in having a longer
cytoplasmic region containing DSG repeats. 
 
Desmogleins have been implicated in autoimmune blistering skin lesion       
diseases. DSG1 has been shown to be a target antigen in pemphigus 
foliaceous, and DSG3 in pemphigus vulgaris [9]. DSG1 is also the target 
of the Staphylococcus aureus blister-causing toxin A [10]. Mutations in DSG1
resulting in reduced levels [11] or extracellularly truncated proteins [12] 
are the cause of hepatokeratotic bands on palms and soles, a dominant      
inherited disease termed palmoplantar keratoderma. 
 
DESMOGLEIN is a 4-element fingerprint that provides a signature for the
desmogleins. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from short conserved regions spanning
the full alignment length, focusing on those sections that characterise
desmogleins but distinguish them from other desmosomal cadherins - motif 1-4 
lie in the C-terminal intracellular domain. Two iterations on SPTR40_20f 
were required to reach convergence, at which point a true set comprising 5 
sequences was identified. 
Summary Information
5 codes involving  4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
45555
30000
20000
1234
True Positives
DSG1_BOVIN    DSG1_HUMAN    DSG2_HUMAN    DSG3_HUMAN    
Q9GKQ8
Sequence Titles
DSG1_BOVIN  Desmoglein 1 precursor (Desmosomal glycoprotein 1) (DG1) (DGI) (Pemphigus foliaceus antigen) - Bos taurus (Bovine). 
DSG1_HUMAN Desmoglein 1 precursor (Desmosomal glycoprotein 1) (DG1) (DGI) (Pemphigus foliaceus antigen) - Homo sapiens (Human).
DSG2_HUMAN Desmoglein 2 precursor (HDGC) - Homo sapiens (Human).
DSG3_HUMAN Desmoglein 3 precursor (130 kDa pemphigus vulgaris antigen) (PVA) - Homo sapiens (Human).
Q9GKQ8 DESMOGLEIN-1 PRECURSOR - Canis familiaris (Dog).
Scan History
SPTR40_20f 2  50   NSINGLE    
Initial Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
SMRECREGGLNMNFM DSG1_BOVIN 684 684 -
SMRECREGGLNMNFM DSG1_HUMAN 680 680 -
TNKDYADGAISMNFL DSG3_HUMAN 775 775 -
AGAQAAAVALNEEFL DSG2_HUMAN 757 757 -

Motif 2 width=15
Element Seqn Id St Int Rpt
ESYFCQKAYAYADED DSG1_BOVIN 699 0 -
ESYFCQKAYAYADED DSG1_HUMAN 695 0 -
DSYFSQKAFACAEED DSG3_HUMAN 790 0 -
RNYFTDKAASYTEED DSG2_HUMAN 772 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
EGRPSNDCLLIYDIEGA DSG1_BOVIN 714 0 -
EGRPSNDCLLIYDIEGV DSG1_HUMAN 710 0 -
DGQEANDCLLIYDNEGA DSG3_HUMAN 805 0 -
ENHTAKDCLLVYSQEET DSG2_HUMAN 787 0 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GSPAGSVGCCSFIGE DSG1_BOVIN 731 0 -
GSPAGSVGCCSFIGE DSG1_HUMAN 727 0 -
GSPVGSVGCCSFIAD DSG3_HUMAN 825 3 -
ESLNASIGCCSFIEG DSG2_HUMAN 804 0 -
Final Motifs
Motif 1  width=15
Element Seqn Id St Int Rpt
SMRECREGGLNMNFM DSG1_BOVIN 684 684 -
SMRECREGGLNMNFM Q9GKQ8 699 699 -
SMRECREGGLNMNFM DSG1_HUMAN 680 680 -
TNKDYADGAISMNFL DSG3_HUMAN 775 775 -
AGAQAAAVALNEEFL DSG2_HUMAN 757 757 -

Motif 2 width=15
Element Seqn Id St Int Rpt
ESYFCQKAYAYADED DSG1_BOVIN 699 0 -
ESYFCQKAYAYADED Q9GKQ8 714 0 -
ESYFCQKAYAYADED DSG1_HUMAN 695 0 -
DSYFSQKAFACAEED DSG3_HUMAN 790 0 -
RNYFTDKAASYTEED DSG2_HUMAN 772 0 -

Motif 3 width=17
Element Seqn Id St Int Rpt
EGRPSNDCLLIYDIEGA DSG1_BOVIN 714 0 -
EGRPSNDCLLIYDIEGV Q9GKQ8 729 0 -
EGRPSNDCLLIYDIEGV DSG1_HUMAN 710 0 -
DGQEANDCLLIYDNEGA DSG3_HUMAN 805 0 -
ENHTAKDCLLVYSQEET DSG2_HUMAN 787 0 -

Motif 4 width=15
Element Seqn Id St Int Rpt
GSPAGSVGCCSFIGE DSG1_BOVIN 731 0 -
GSPAGSVGCCSFIGE Q9GKQ8 746 0 -
GSPAGSVGCCSFIGE DSG1_HUMAN 727 0 -
GSPVGSVGCCSFIAD DSG3_HUMAN 825 3 -
ESLNASIGCCSFIEG DSG2_HUMAN 804 0 -