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PR01346

Identifier
HELNAPAPROT  [View Relations]  [View Alignment]  
Accession
PR01346
No. of Motifs
3
Creation Date
24-MAY-2000
Title
Helicobacter neutrophil-activating protein A family signature 
Database References

PROSITE; PS00818 DPS_1; PS00819 DPS_2
BLOCKS; BL00818
Literature References
1. EVANS JR., D.J., EVANS, D.G., TAKEMURA, T., NAKANO, H., LAMPERT, H.C.,
GRAHAM, D.Y., GRANGER, D.N. AND KVIETYS, P.R.
Characterization of a Helicobacter pylori neutrophil-activating protein
INFECT.IMMUN. 63(6) 2213-2220 (1995).
 
2. TONELLO, F., DUNDON, W.D., SATIN, B., MOLINARI, M., TOGNON, G.,
GRANDI, G., DEL GIUDICE, G., RAPPUOLI, R. AND MONTECUCCO, C.
The Helicobacter pylori neutrophil-activating protein is an iron-binding 
protein with dodecameric structure.
MOL.MICROBIOL. 34 238-246 (1999).
 
3. GRANT, R.A., FILMAN, D.J., FINKEL, S.E., KOLTER, R. AND HOGLE, J.M.
The crystal structure of Dps, a ferritin homolog that binds and protects
DNA.
NAT.STRUCT.BIOL. 5 294-303 (1998).
 
4. SATIN, B., DEL GIUDICE, G., DELLA BIANCA, V., DUSI, S., LAUDANNA, C., 
TONELLO, F., KELLEHER, D., RAPPUOLI, R. AND MONTECUCCO, C.
The neutrophil-activating protein (HP-NAP) of Helicobacter pylori is a 
protective antigen and a major virulence factor
J.EXP.MED. 191 1467-1476 (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. 
 
One of the bacterium's many virulence factors is neutrophil-activating 
protein A (NAPA), a 15kDa peptide that forms dodecameric complexes upon 
secretion from the pathogen [2]. It belongs to the iron-binding ferritin 
family, and is structurally similar to E.coli DNA-binding Dps protein [3]. 
The complex is able to bind up to 500 atoms of iron, but does not have
DNA-binding properties. Each monomer has four alpha-helices arranged as a 
bundle. 
 
Recent work has demonstrated that NAPA protein, used as an oral vaccine, 
confers protection on mice against H.pylori infection [4]. It has also shown
the amino acid sequence to be similar to other bacteroferritin/DNA-binding 
proteins, such as B.subtilis MRGA, TYF1 antigen from Treponema spp., and 
hypothetical iron binding proteins from Rickettsia and Streptomyces [4].
 
HELNAPAPROT is an 3-element fingerprint that provides a signature for 
the Helicobacter pylori neutrophil-activating protein A family. The
fingerprint was derived from an initial alignment of 4 sequences: the
motifs were drawn from conserved regions spanning the full alignment length 
(~180 amino acids) - motif 1 overlaps the N-terminus of helix 2, and motif
2 the C-terminus; while motif 3 spans the N-terminus of helix 4. Two 
iterations on SPTR37_10f were required to reach convergence, at which point
a true set comprising 16 sequences was identified. A single partial match
was also found, a NAPA protein from Borrelia burgdorferi that fails to
make a significant match with motif 2.
Summary Information
  16 codes involving  3 elements
1 codes involving 2 elements
Composite Feature Index
3161616
2101
123
True Positives
DPS_ECOLI     FRI_LISIN     FTPA_HAEDU    G20U_BACSU    
MRGA_BACSU NAPA_HELPY O30701 O85254
O86816 Q9ZCF0 Q9ZMJ1 TPF1_TREPA
TYF1_TREPE YD49_HAEIN YI94_SYNY3 YLT2_ANAVA
True Positive Partials
Codes involving 2 elements
O51633
Sequence Titles
DPS_ECOLI   DNA PROTECTION DURING STARVATION PROTEIN - ESCHERICHIA COLI. 
FRI_LISIN NON-HEME IRON-CONTAINING FERRITIN - LISTERIA INNOCUA.
FTPA_HAEDU FINE TANGLED PILI MAJOR SUBUNIT (24 KD SURFACE PROTEIN) - HAEMOPHILUS DUCREYI.
G20U_BACSU GENERAL STRESS PROTEIN 20U (GSP20U) (DPS PROTEIN HOMOLOG) - BACILLUS SUBTILIS.
MRGA_BACSU METALLOREGULATION DNA-BINDING STRESS PROTEIN - BACILLUS SUBTILIS.
NAPA_HELPY NEUTROPHIL-ACTIVATING PROTEIN A (NAP A) (BACTERIOFERRITIN) - HELICOBACTER PYLORI (CAMPYLOBACTER PYLORI).
O30701 SURFACE LOCATED PROTEIN - LACTOBACILLUS RHAMNOSUS.
O85254 HYPOTHETICAL 19.3 KD PROTEIN - STREPTOCOCCUS PNEUMONIAE.
O86816 HYPOTHETICAL 16.6 KD PROTEIN - STREPTOMYCES COELICOLOR.
Q9ZCF0 HYPOTHETICAL 16.5 KD PROTEIN - RICKETTSIA PROWAZEKII.
Q9ZMJ1 NEUTROPHIL-ACTIVATING PROTEIN A - HELICOBACTER PYLORI J99.
TPF1_TREPA ANTIGEN TPF1 (ANTIGEN C1-5) (ANTIGEN 4D) - TREPONEMA PALLIDUM.
TYF1_TREPE ANTIGEN TYF1 - TREPONEMA PALLIDUM (SUBSP. PERTENUE) (YAWS TREPONEME).
YD49_HAEIN HYPOTHETICAL PROTEIN HI1349 - HAEMOPHILUS INFLUENZAE.
YI94_SYNY3 HYPOTHETICAL 17.8 KD PROTEIN SLR1894 - SYNECHOCYSTIS SP. (STRAIN PCC 6803).
YLT2_ANAVA HYPOTHETICAL 20.2 KD LOW TEMPERATURE-INDUCED PROTEIN (ORF2) - ANABAENA VARIABILIS.

O51633 NEUTROPHIL ACTIVATING PROTEIN (NAPA) - BORRELIA BURGDORFERI (LYME DISEASE SPIROCHETE).
Scan History
SPTR37_10f 2  25   NSINGLE    
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HWYVKGPHFFTLHEKFE MRGA_BACSU 35 35 -
HWNVKGTDFFNVHKATE NAPA_HELPY 25 25 -
HWNMRGANFIAVHEMLD DPS_ECOLI 50 50 -
HWNVVGPQFIAVHEMLD FTPA_HAEDU 65 65 -

Motif 2 width=17
Element Seqn Id St Int Rpt
ETVDTIAERLLAIGGQP MRGA_BACSU 59 7 -
DMFDDLAERIVQLGHHP NAPA_HELPY 49 7 -
DHLDTMAERAVQLGGVA DPS_ECOLI 74 7 -
DFIDEIAERMATLGVAP FTPA_HAEDU 89 7 -

Motif 3 width=19
Element Seqn Id St Int Rpt
TADLFVGLIEEVEKQVWML MRGA_BACSU 130 54 -
TVTYADDQLAKLQKSIWML NAPA_HELPY 121 55 -
TADILTAASRDLDKFLWFI DPS_ECOLI 143 52 -
SEDLLVAQTRSLEKLQWFI FTPA_HAEDU 160 54 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
HWYVKGPHFFTLHEKFE MRGA_BACSU 35 35 -
HWHIYGIEFKQVHELLE TPF1_TREPA 56 56 -
HWHIYGIEFKQVHELLE TYF1_TREPE 56 56 -
HWYMRGRGFMVWHPKMD O85254 48 48 -
HWNVKGTDFFNVHKATE NAPA_HELPY 25 25 -
HWNVKGTDFFNVHKATE Q9ZMJ1 25 25 -
HWYMRGHNFFTLHEKMD FRI_LISIN 31 31 -
HWNVEGAEFRSLHLLFE Q9ZCF0 25 25 -
HWNVVGPRFRSVHLQLD O86816 38 38 -
HWNMRGANFIAVHEMLD DPS_ECOLI 50 50 -
HWDVVGPQFRSLHQLWE YLT2_ANAVA 38 38 -
HWYMRGPNFLKLHPLMD O30701 28 28 -
HWNVVGPQFIAVHEMLD FTPA_HAEDU 65 65 -
HWNIKGVNFFALHAKFE YD49_HAEIN 38 38 -
HWYVKGKDFFTLHEKFE G20U_BACSU 26 26 -
HWNVTGPQFRDLHLMFE YI94_SYNY3 38 38 -

Motif 2 width=17
Element Seqn Id St Int Rpt
ETVDTIAERLLAIGGQP MRGA_BACSU 59 7 -
EAFDTIAERLLQLGAQA TPF1_TREPA 80 7 -
EAFDTIAERLLQLGAQA TYF1_TREPE 80 7 -
GHLDEISERLITLGGSP O85254 72 7 -
DMFDDLAERIVQLGHHP NAPA_HELPY 49 7 -
DMFDDLAERIVQLGHHP Q9ZMJ1 49 7 -
EQMDEVAERLLAIGGSP FRI_LISIN 55 7 -
ESLDEIAERIRSLGTKV Q9ZCF0 49 7 -
THSDTVAERASALGVSP O86816 62 7 -
DHLDTMAERAVQLGGVA DPS_ECOLI 74 7 -
ENIDAIAERVRTLGGYP YLT2_ANAVA 62 7 -
SQLDVISERLIALDGSP O30701 52 7 -
DFIDEIAERMATLGVAP FTPA_HAEDU 89 7 -
ARVDEVAERILTLGYTP YD49_HAEIN 62 7 -
TYIDDLAERLLALNGKP G20U_BACSU 50 7 -
LAVDDIAERIRSLDVFA YI94_SYNY3 62 7 -

Motif 3 width=19
Element Seqn Id St Int Rpt
TADLFVGLIEEVEKQVWML MRGA_BACSU 130 54 -
TDGIITDILRTLGKAIWML TPF1_TREPA 152 55 -
TDGIITDILRTLGKAIWML TYF1_TREPE 152 55 -
TNDIFVGAKAELEKTVWML O85254 144 55 -
TVTYADDQLAKLQKSIWML NAPA_HELPY 121 55 -
TVTYADDQLAKLQKSIWML Q9ZMJ1 121 55 -
TNDMLIAFKASIDKHIWMF FRI_LISIN 128 56 -
TADMIIGRIKVHEKNRWML Q9ZCF0 119 53 -
SQDIFIQITADLEKQHWMF O86816 133 54 -
TADILTAASRDLDKFLWFI DPS_ECOLI 143 52 -
TADFLTGLMEEHEEIAWML YLT2_ANAVA 135 56 -
TQDIFIGLKTAIEKKIWMI O30701 125 56 -
SEDLLVAQTRSLEKLQWFI FTPA_HAEDU 160 54 -
TASQMSDYIKEQEKLVWMF YD49_HAEIN 133 54 -
TGDMLLAIHQNIEKHNWML G20U_BACSU 121 54 -
TIALASDRMRVHEKTAWML YI94_SYNY3 133 54 -