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PR01553

Identifier
TYPE4SSCAGA  [View Relations]  [View Alignment]  
Accession
PR01553
No. of Motifs
11
Creation Date
24-APR-2001
Title
Type IV secretion system CagA exotoxin signature 
Database References
Literature References
1. CENSINI, S., LANGE, C., XIANG, Z., CRABTREE, J.E., GHIARA, P., 
BORODOVSKY, M., RAPPUOLI, R. AND COVACCI, A.
Cag, a pathogenicity island of Helicobacter pylori, encodes type-1-specific
and disease-associated virulence factors.
PROC.NATL.ACAD.SCI.U.S.A. 93 14648-14653 (1996).
 
2. CHRISTIE, P.J. AND VOGEL, J.P.
Bacterial type IV secretion: conjugation systems adapted to deliver effector
molecules to host cells.
TRENDS MICROBIOL. 8 354-367 (2000).
 
3. ASAHI, M., AZUMA, T., ITO, S., ITO, Y., SUTO, H., NAGAI, Y., TSUBOKAWA, 
M., MAEDA, S., OMATA, M., SUZUKI, T. AND SASAKAWA, C.
Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric
epithelial cells.
J.EXP.MED. 191 593-602 (2000).
 
4. COVACCI, A. AND RAPPUOLI, R.
Tyrosine-phosphorylated bacterial proteins: trojan horses for the host cell.
J.EXP.MED. 191 587-592 (2000). 

Documentation
Helicobacter pylori is a Gram-negative flagellated pathogen that causes   
gastric and peptic ulcers. In its chronic state, it can also contribute to 
gastric cancer development, through elicitation of a huge host inflammatory 
response [1]. It has been suggested that activated leukocytes may be 
responsible for tissue damage, and that phagocytes contribute to 
carcinogenesis. The Helicobacter genome contains several virulence factors;
clinical strains may be divided roughly into two types, depending on 
whether they contain the functional cag pathogenicity island. Type I strains 
can cause malignant disease, as they possess the active cag island and 
its associated exotoxin, CagA.
 
The bacterium makes use of a type IV secretion system similar in mechanism 
to the conjugation machine of Agrobacterium tumefaciens [2]. These machines
secrete three different types of substrate: DNA conjugation intermediates,
as in A.tumefaciens; multimeric proteins, such as the pertussis toxin of
Bordetella pertussis; and the CagA protein of H.pylori [3]. CagA has been
linked to the more severe forms of gastric ulcers and duodenal cancers [3].
Both CagA and the secretion system apparatus are encoded in the large
pathogenicity island, termed cag [3], possessed by the malignant disease-
causing type I bacterial strains.
 
The CagA exotoxin is encoded in the last portion of the island, and
mutants lacking the gene fail to induce IL-8 secretion, and to activate 
NF-kappa-B in vivo [4]. CagA is believed to have a similar function to 
EPEC type III secreted effectors; both are tyrosine-phosphorylated once 
translocated into the target cell [4], and allow engulfment by the host via
rearrangement of the actin cytoskeleton.
 
TYPE4SSCAGA is an 11-element fingerprint that provides a signature for the
type IV secretion system CagA exotoxin family. The fingerprint was derived
from an initial alignment of 8 sequences: the motifs were drawn from
conserved regions spanning virtually the full alignment length (~1266 
amino acids). A single iteration on SPTR39_14f was required to reach 
convergence, no further sequences being identified beyond the starting set.
Summary Information
8 codes involving 11 elements
0 codes involving 10 elements
0 codes involving 9 elements
0 codes involving 8 elements
0 codes involving 7 elements
0 codes involving 6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
1188888888888
1000000000000
900000000000
800000000000
700000000000
600000000000
500000000000
400000000000
300000000000
200000000000
1234567891011
True Positives
CGA0_HELPY    CGA1_HELPY    CGA2_HELPY    O07910        
O86064 Q9RF15 Q9RF16 Q9ZLT1
Sequence Titles
CGA0_HELPY  CYTOTOXICITY ASSOCIATED IMMUNODOMINANT ANTIGEN (120 KDA PROTEIN) (CAG PATHOGENICITY ISLAND PROTEIN 26) - Helicobacter pylori (Campylobacter pylori). 
CGA1_HELPY CYTOTOXICITY ASSOCIATED IMMUNODOMINANT ANTIGEN (120 KDA PROTEIN) - Helicobacter pylori (Campylobacter pylori).
CGA2_HELPY CYTOTOXICITY ASSOCIATED IMMUNODOMINANT ANTIGEN (120 KDA PROTEIN) - Helicobacter pylori (Campylobacter pylori).
O07910 CAGA (CYTOTOXIN ASSOCIATED PROTEIN A) - Helicobacter pylori (Campylobacter pylori).
O86064 CYTOTOXIN ASSOCIATED PROTEIN III - Helicobacter pylori (Campylobacter pylori).
Q9RF15 CAGA - Helicobacter pylori (Campylobacter pylori).
Q9RF16 CAGA - Helicobacter pylori (Campylobacter pylori).
Q9ZLT1 CAG ISLAND PROTEIN, CYTOTOXICITY ASSOCIATED IMMUNODOMINANT ANTIGEN - Helicobacter pylori J99 (Campylobacter pylori J99).
Scan History
SPTR39_14f 1  50   NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
FINNLQVAFLKVDNAVASYD O07910 21 21 -
FINNLQVAFLKVDNAVASYD Q9RF15 21 21 -
FINNLQVAFLKVDNAVASYD CGA1_HELPY 21 21 -
FINNLQVAFIKVDNVVASFD CGA0_HELPY 26 26 -
FINNLQVAFLKVDNAVASYD O86064 21 21 -
FINNLQVAFLKVDNAVASYD CGA2_HELPY 21 21 -
FINNLQVAFIKVDNAVASFD Q9RF16 22 22 -
FINNLQVAFIKVDNVVASFD Q9ZLT1 21 21 -

Motif 2 width=21
Element Seqn Id St Int Rpt
DKNDRDNRQAFDGISQLREEY O07910 48 7 -
DKNDRDNRQAFDGISQLREEY Q9RF15 48 7 -
DKNDRDNRQAFEGISQLREEY CGA1_HELPY 48 7 -
DKNDRDNRQAFDGISQLREEY CGA0_HELPY 53 7 -
DKNDRDNRQAFDGISQLREEY O86064 48 7 -
DKNDRDNRQAFEGISQLREEY CGA2_HELPY 48 7 -
DKNDKDNRQAYEKISQLREEY Q9RF16 49 7 -
DKNDRDNRQAFEKISQLREEF Q9ZLT1 48 7 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KKNQYFSDFINKSNDLINKD O07910 78 9 -
KKNQYFSDFINKSNDLINKD Q9RF15 78 9 -
KKNQYFSDFINKSNDLINKD CGA1_HELPY 78 9 -
KKNQYFSDFIDKSNDLINKD CGA0_HELPY 83 9 -
KKNQYFLDFINKSNGLINKD O86064 78 9 -
KKNQYFSDFINKSNDLINKD CGA2_HELPY 78 9 -
KKNQYFSDFINKSNDLINKD Q9RF16 79 9 -
KKNQYFSSFISKSNDLIDKD Q9ZLT1 78 9 -

Motif 4 width=15
Element Seqn Id St Int Rpt
TTTTHIQGLPPESRD O07910 242 144 -
TTTTHIQGLPPESRD Q9RF15 242 144 -
TTTTDIQGLPPEARD CGA1_HELPY 242 144 -
TTTTDIQGLPPEARD CGA0_HELPY 247 144 -
TTTTDIQGLPPESRD O86064 242 144 -
TSTTHIQGLPPESRD CGA2_HELPY 242 144 -
TTTTDIQGLPPEARD Q9RF16 243 144 -
TTTTDIQSLPPEARD Q9ZLT1 246 148 -

Motif 5 width=20
Element Seqn Id St Int Rpt
NGGFGAKHDWNATVGYKNQQ O07910 322 65 -
NGGFGAKHDWNATVGYKNQQ Q9RF15 322 65 -
NGGPGARHDWNATVGYKDQQ CGA1_HELPY 322 65 -
NGGFGDKHDWNATVGYKDQQ CGA0_HELPY 327 65 -
NGGFGAKHDWNATVGYKDQQ O86064 323 66 -
NGGFGAKHDWNATVGYKDQQ CGA2_HELPY 322 65 -
NGGPEARHDWNATVGYKNQQ Q9RF16 323 65 -
NGGPEARHDWNATVGYKNQR Q9ZLT1 326 65 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KGINNPSFYLYKEDQLTG O07910 366 24 -
KGINNPSFYLYKEDQLTG Q9RF15 366 24 -
KGINNPSFYLYKEDQLTG CGA1_HELPY 366 24 -
KGINNPSFYLYKEDQLTG CGA0_HELPY 371 24 -
KGINNPSFYLYKEDQLTG O86064 367 24 -
KGINNPSFYLYKEDQLTG CGA2_HELPY 366 24 -
DGIKNPSFYLYKEDQLTG Q9RF16 367 24 -
KGINNPSFYLYKEDQLTG Q9ZLT1 370 24 -

Motif 7 width=20
Element Seqn Id St Int Rpt
KEKEKFQNEIEDFQKDSKAY O07910 416 32 -
KEKEKFQNEIEDFQKDSKAY Q9RF15 416 32 -
KEKEKFRTEIKDFQKDSKAY CGA1_HELPY 416 32 -
KEKEKFQNEIEDFQKDSKAY CGA0_HELPY 421 32 -
KEKEKFRNEIKDFQKDSKPY O86064 417 32 -
KEKEKFRNEIKDFQKDSKPY CGA2_HELPY 416 32 -
KEKEKFQTEIENFQKDRKAY Q9RF16 417 32 -
KEKEKFQNEIEDFQKDSKAY Q9ZLT1 420 32 -

Motif 8 width=18
Element Seqn Id St Int Rpt
YDEVKKAQKDLEKSLRKR O07910 604 168 -
YDEVKKAQKDLEKSLRKR Q9RF15 604 168 -
YDEVKKAQKDLEKSLRKR CGA1_HELPY 604 168 -
YDEVKKAQKDLEKSLRKR CGA0_HELPY 609 168 -
YDEVKKAQKDLEKSLRKR O86064 605 168 -
YDEVKRAQKDLEKSLKKR CGA2_HELPY 604 168 -
YDEVKKAQKDLEKSLRKR Q9RF16 605 168 -
YDEVKQAQKDLEKSLKKR Q9ZLT1 608 168 -

Motif 9 width=18
Element Seqn Id St Int Rpt
NEFKNGKNKDFSKVTQAK O07910 747 125 -
NEFKNGKNKDFSKVTQAK Q9RF15 747 125 -
NEFKNGKNKDFSKVTQAK CGA1_HELPY 747 125 -
NEFKNGKNKDFSKVTQAK CGA0_HELPY 752 125 -
NEFKNGKNKDFSKVTQAK O86064 748 125 -
NEFKNGKNKDFSKVTQAK CGA2_HELPY 748 126 -
NDFKNGKNKDFSKVTQAK Q9RF16 748 125 -
NEFKNGKNKDFSKVTQAK Q9ZLT1 751 125 -

Motif 10 width=16
Element Seqn Id St Int Rpt
GFNQKNMKDYSDSFKF O07910 1181 416 -
GFNQKNMKDYSDSFKF Q9RF15 1181 416 -
GFNQKNMKDYSDSFKF CGA1_HELPY 1080 315 -
GFNQKNMKDYSDSFKF CGA0_HELPY 1120 350 -
GFNQKNMKDYSDSFKF O86064 1117 351 -
GFSQKNMKDYSDSFKF CGA2_HELPY 1116 350 -
GFNQKNMKDYSDSFKF Q9RF16 1107 341 -
GFNQKNMKDYSDSFKF Q9ZLT1 1101 332 -

Motif 11 width=15
Element Seqn Id St Int Rpt
EHGIKNVNTKGGFQK O07910 1232 35 -
EHGIKNVNTKGGFQK Q9RF15 1232 35 -
EHGIKNVNTKGGFQK CGA1_HELPY 1132 36 -
EHGIKNVNTKGGFQK CGA0_HELPY 1171 35 -
EHGIKNVNTKGGFQK O86064 1168 35 -
EHGIKNANTKGGFQK CGA2_HELPY 1167 35 -
EHGVKNTNTKGGFQK Q9RF16 1158 35 -
EHGVKNTNTKGGFQK Q9ZLT1 1152 35 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
FINNLQVAFLKVDNAVASYD O07910 21 21 -
FINNLQVAFLKVDNAVASYD Q9RF15 21 21 -
FINNLQVAFLKVDNAVASYD CGA1_HELPY 21 21 -
FINNLQVAFIKVDNVVASFD CGA0_HELPY 26 26 -
FINNLQVAFLKVDNAVASYD O86064 21 21 -
FINNLQVAFLKVDNAVASYD CGA2_HELPY 21 21 -
FINNLQVAFIKVDNAVASFD Q9RF16 22 22 -
FINNLQVAFIKVDNVVASFD Q9ZLT1 21 21 -

Motif 2 width=21
Element Seqn Id St Int Rpt
DKNDRDNRQAFDGISQLREEY O07910 48 7 -
DKNDRDNRQAFDGISQLREEY Q9RF15 48 7 -
DKNDRDNRQAFEGISQLREEY CGA1_HELPY 48 7 -
DKNDRDNRQAFDGISQLREEY CGA0_HELPY 53 7 -
DKNDRDNRQAFDGISQLREEY O86064 48 7 -
DKNDRDNRQAFEGISQLREEY CGA2_HELPY 48 7 -
DKNDKDNRQAYEKISQLREEY Q9RF16 49 7 -
DKNDRDNRQAFEKISQLREEF Q9ZLT1 48 7 -

Motif 3 width=20
Element Seqn Id St Int Rpt
KKNQYFSDFINKSNDLINKD O07910 78 9 -
KKNQYFSDFINKSNDLINKD Q9RF15 78 9 -
KKNQYFSDFINKSNDLINKD CGA1_HELPY 78 9 -
KKNQYFSDFIDKSNDLINKD CGA0_HELPY 83 9 -
KKNQYFLDFINKSNGLINKD O86064 78 9 -
KKNQYFSDFINKSNDLINKD CGA2_HELPY 78 9 -
KKNQYFSDFINKSNDLINKD Q9RF16 79 9 -
KKNQYFSSFISKSNDLIDKD Q9ZLT1 78 9 -

Motif 4 width=15
Element Seqn Id St Int Rpt
TTTTHIQGLPPESRD O07910 242 144 -
TTTTHIQGLPPESRD Q9RF15 242 144 -
TTTTDIQGLPPEARD CGA1_HELPY 242 144 -
TTTTDIQGLPPEARD CGA0_HELPY 247 144 -
TTTTDIQGLPPESRD O86064 242 144 -
TSTTHIQGLPPESRD CGA2_HELPY 242 144 -
TTTTDIQGLPPEARD Q9RF16 243 144 -
TTTTDIQSLPPEARD Q9ZLT1 246 148 -

Motif 5 width=20
Element Seqn Id St Int Rpt
NGGFGAKHDWNATVGYKNQQ O07910 322 65 -
NGGFGAKHDWNATVGYKNQQ Q9RF15 322 65 -
NGGPGARHDWNATVGYKDQQ CGA1_HELPY 322 65 -
NGGFGDKHDWNATVGYKDQQ CGA0_HELPY 327 65 -
NGGFGAKHDWNATVGYKDQQ O86064 323 66 -
NGGFGAKHDWNATVGYKDQQ CGA2_HELPY 322 65 -
NGGPEARHDWNATVGYKNQQ Q9RF16 323 65 -
NGGPEARHDWNATVGYKNQR Q9ZLT1 326 65 -

Motif 6 width=18
Element Seqn Id St Int Rpt
KGINNPSFYLYKEDQLTG O07910 366 24 -
KGINNPSFYLYKEDQLTG Q9RF15 366 24 -
KGINNPSFYLYKEDQLTG CGA1_HELPY 366 24 -
KGINNPSFYLYKEDQLTG CGA0_HELPY 371 24 -
KGINNPSFYLYKEDQLTG O86064 367 24 -
KGINNPSFYLYKEDQLTG CGA2_HELPY 366 24 -
DGIKNPSFYLYKEDQLTG Q9RF16 367 24 -
KGINNPSFYLYKEDQLTG Q9ZLT1 370 24 -

Motif 7 width=20
Element Seqn Id St Int Rpt
KEKEKFQNEIEDFQKDSKAY O07910 416 32 -
KEKEKFQNEIEDFQKDSKAY Q9RF15 416 32 -
KEKEKFRTEIKDFQKDSKAY CGA1_HELPY 416 32 -
KEKEKFQNEIEDFQKDSKAY CGA0_HELPY 421 32 -
KEKEKFRNEIKDFQKDSKPY O86064 417 32 -
KEKEKFRNEIKDFQKDSKPY CGA2_HELPY 416 32 -
KEKEKFQTEIENFQKDRKAY Q9RF16 417 32 -
KEKEKFQNEIEDFQKDSKAY Q9ZLT1 420 32 -

Motif 8 width=18
Element Seqn Id St Int Rpt
YDEVKKAQKDLEKSLRKR O07910 604 168 -
YDEVKKAQKDLEKSLRKR Q9RF15 604 168 -
YDEVKKAQKDLEKSLRKR CGA1_HELPY 604 168 -
YDEVKKAQKDLEKSLRKR CGA0_HELPY 609 168 -
YDEVKKAQKDLEKSLRKR O86064 605 168 -
YDEVKRAQKDLEKSLKKR CGA2_HELPY 604 168 -
YDEVKKAQKDLEKSLRKR Q9RF16 605 168 -
YDEVKQAQKDLEKSLKKR Q9ZLT1 608 168 -

Motif 9 width=18
Element Seqn Id St Int Rpt
NEFKNGKNKDFSKVTQAK O07910 747 125 -
NEFKNGKNKDFSKVTQAK Q9RF15 747 125 -
NEFKNGKNKDFSKVTQAK CGA1_HELPY 747 125 -
NEFKNGKNKDFSKVTQAK CGA0_HELPY 752 125 -
NEFKNGKNKDFSKVTQAK O86064 748 125 -
NEFKNGKNKDFSKVTQAK CGA2_HELPY 748 126 -
NDFKNGKNKDFSKVTQAK Q9RF16 748 125 -
NEFKNGKNKDFSKVTQAK Q9ZLT1 751 125 -

Motif 10 width=16
Element Seqn Id St Int Rpt
GFNQKNMKDYSDSFKF O07910 1181 416 -
GFNQKNMKDYSDSFKF Q9RF15 1181 416 -
GFNQKNMKDYSDSFKF CGA1_HELPY 1080 315 -
GFNQKNMKDYSDSFKF CGA0_HELPY 1120 350 -
GFNQKNMKDYSDSFKF O86064 1117 351 -
GFSQKNMKDYSDSFKF CGA2_HELPY 1116 350 -
GFNQKNMKDYSDSFKF Q9RF16 1107 341 -
GFNQKNMKDYSDSFKF Q9ZLT1 1101 332 -

Motif 11 width=15
Element Seqn Id St Int Rpt
EHGIKNVNTKGGFQK O07910 1232 35 -
EHGIKNVNTKGGFQK Q9RF15 1232 35 -
EHGIKNVNTKGGFQK CGA1_HELPY 1132 36 -
EHGIKNVNTKGGFQK CGA0_HELPY 1171 35 -
EHGIKNVNTKGGFQK O86064 1168 35 -
EHGIKNANTKGGFQK CGA2_HELPY 1167 35 -
EHGVKNTNTKGGFQK Q9RF16 1158 35 -
EHGVKNTNTKGGFQK Q9ZLT1 1152 35 -