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PR01371

Identifier
BACYPHPHTASE  [View Relations]  [View Alignment]  
Accession
PR01371
No. of Motifs
5
Creation Date
11-JUL-2000
Title
Salmonella/Yersinia modular tyrosine phosphatase signature
Database References
PRINTS; PR00700 PRTYPHPHTASE
PROSITE; PS00383 TYR_PHOSPHATASE_1; PS50056 TYR_PHOSPHATASE_2; PS50055 TYR_PHOSPHATASE_PTP

PFAM; PF00102 Y_phosphatase
INTERPRO; IPR000242; IPR000387
PDB; 1YTN; 1YTW; 1YTS; 1YPT
SCOP; 1YTN; 1YTW; 1YTS; 1YPT
CATH; 1YTN; 1YTW; 1YTS; 1YPT
Literature References
1. KANIGA, K., URALIL, J., BLISKA, J.B. AND GALAN, J.E.
A secreted protein tyrosine phosphatase with modular effector domains in 
the bacterial pathogen Salmonella typhimurium.
MOL.MICROBIOL. 21 633-641 (1996).
 
2. GUAN, K.L. AND DIXON, J.E.
Bacterial and viral tyrosine phosphatases.
SEMIN.CELL BIOL. 4 389-396 (1993).
 
3. HUECK, C.J.
Type III protein secretion systems in bacterial pathogens of animals and 
plants.
MICROBIOL.MOL.BIOL.REV. 379-433 (1998).
 
4. FU, Y. AND GALAN, J.E.
A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell 
recovery after bacterial invasion.
NATURE 401 293-297 (1999).
 
5. FAUMAN, E.B., YUVANIYAMA, C., SCHUBERT, H.L., STUCKEY, J.A. AND
SAPER, M.A.
The X-ray crystal structures of Yersinia tyrosine phosphatase with bound
tungstate and nitrate. Mechanistic implications.
J.BIOL.CHEM. 271 18780-18788 (1996). 

Documentation
Secretion of virulence factors in Gram-negative bacteria involves 
transportation of the protein across two membranes to reach the cell 
exterior [3]. There have been four secretion systems described in 
animal enteropathogens, such as Salmonella and Yersinia, with further 
sequence similarities in plant pathogens like Ralstonia and Erwinia [3].
 
The type III secretion system is of great interest, as it is used to 
transport virulence factors from the pathogen directly into the host cell 
[3] and is only triggered when the bacterium comes into close contact with
the host. The protein subunits of the system are very similar to those of 
bacterial flagellar biosynthesis [3]. However, while the latter forms a
ring structure to allow secretion of flagellin and is an integral part of
the flagellum itself [3], type III subunits in the outer membrane
translocate secreted proteins through a channel-like structure.
 
Exotoxins secreted by the type III system do not possess a secretion signal,
and are considered unique for this reason [3]. Salmonella/Yersinia spp.  
secrete a protein, SptP, with tyrosine phosphatase activity [1,2]. SptP 
exerts its function by acting as a GTPase-activating protein [4], and 
counteracts the effects of SopE [4]. This is similar to the Yersinia 
exotoxin YopH, which degrades host cell signal transduction [3].
 
X-ray crystal structures of the Yersinia tyrosine phosphatase (PTPase) in 
complex with tungstate and nitrate have been solved to 2.4A resolution [5].
The fold belongs to the alpha-beta class. The crystal structure reveals
that the nucleophilic cysteine (Cys 403) is positioned at the centre of a
distinctive phosphate-binding loop [5]. This loop is at the hub of
several hydrogen-bond arrays that not only stabilise a bound oxyanion, but
may activate Cys 403 as a reactive thiolate [5]. Binding of tungstate
triggers a conformational change that traps the oxyanion and swings Asp 356,
an important catalytic residue that resides in a flexible loop, by ~6A into
the active site [5]. 
 
BACYPHPHTASE is a 5-element fingerprint that provides a signature for
Salmonella/Yersinia type III secreted modular tyrosine phosphatases. The
fingerprint was derived from an initial alignment of 2 sequences: the motifs
were drawn from conserved regions spanning the full alignment length - 
motif 2 spans beta-strand 2 and part of alpha-helix 3; motif 3 spans strand
4 and the N-terminus of strand 5; motif 4 spans strand 7 and part of the
flexible loop that contains the putative general acid; and motif 5 spans
strand 8 and the phosphate-binding loop. Two iterations on SPTR37_10f were
required to reach convergence, at which point a true set comprising 5 
sequences was identified.
Summary Information
5 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
555555
400000
300000
200000
12345
True Positives
O68720        P74851        P74873        YOPH_YEREN    
YOPH_YERPS
Sequence Titles
O68720      YOPH (EC 3.1.3.48) - YERSINIA PESTIS.         
P74851 SIPA, SIPF, AND STPA GENES - SALMONELLA TYPHI.
P74873 PROTEIN TYROSINE PHOSPHATASE SPTP - SALMONELLA TYPHIMURIUM.
YOPH_YEREN PROTEIN-TYROSINE PHOSPHATASE YOPH (EC 3.1.3.48) (VIRULENCE PROTEIN) - YERSINIA ENTEROCOLITICA.
YOPH_YERPS PROTEIN-TYROSINE PHOSPHATASE YOPH (EC 3.1.3.48) (VIRULENCE PROTEIN) - YERSINIA PSEUDOTUBERCULOSIS.
Scan History
SPTR37_10f 2  25   NSINGLE    
Initial Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
RSDQMTLQDAKVLLEAALR YOPH_YERPS 104 104 -
KNNDVGAESKQPLLDIALK P74873 159 159 -

Motif 2 width=14
Element Seqn Id St Int Rpt
GNTRTIACQYPLQS YOPH_YERPS 252 129 -
GKPVALAGSYPKNT P74873 340 162 -

Motif 3 width=17
Element Seqn Id St Int Rpt
PDYFRQSGTYGSITVES YOPH_YERPS 299 33 -
PPYFRGSYTFGEVHTNS P74873 387 33 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KTISVPVVHVGNWPD YOPH_YERPS 342 26 -
KRYTIPVLHVKNWPD P74873 427 23 -

Motif 5 width=12
Element Seqn Id St Int Rpt
PVIHCRAGVGRT YOPH_YERPS 399 42 -
PMIHCLGGVGRT P74873 477 35 -
Final Motifs
Motif 1  width=19
Element Seqn Id St Int Rpt
RSDQMTLQDAKVLLEAALR O68720 104 104 -
RSDQMTLQDAKVLLEAALR YOPH_YERPS 104 104 -
RSDQMTLQDAKVLLEAALR YOPH_YEREN 104 104 -
KNNDVGAESKQPLLDIALK P74873 159 159 -
QNNDVGAESKQPLLDIALK P74851 159 159 -

Motif 2 width=14
Element Seqn Id St Int Rpt
GNTRTIACQYPLQS O68720 252 129 -
GNTRTIACQYPLQS YOPH_YERPS 252 129 -
GNTRTIACQYPLQS YOPH_YEREN 252 129 -
GKPVALAGSYPKNT P74873 340 162 -
GKPVALAGSCPKNT P74851 340 162 -

Motif 3 width=17
Element Seqn Id St Int Rpt
PDYFRQSGTYGSITVES O68720 299 33 -
PDYFRQSGTYGSITVES YOPH_YERPS 299 33 -
PDYFRQSGTYGSITVES YOPH_YEREN 299 33 -
PPYFRGSYTFGEVHTNS P74873 387 33 -
PAYFRGSYTFGEVHTNS P74851 387 33 -

Motif 4 width=15
Element Seqn Id St Int Rpt
KTISVPVVHVGNWPD O68720 342 26 -
KTISVPVVHVGNWPD YOPH_YERPS 342 26 -
KTISVPVVHVGNWPD YOPH_YEREN 342 26 -
KRYTIPVLHVKNWPD P74873 427 23 -
KRYTIPVLHVKNWPD P74851 427 23 -

Motif 5 width=12
Element Seqn Id St Int Rpt
PVIHCRAGVGRT O68720 399 42 -
PVIHCRAGVGRT YOPH_YERPS 399 42 -
PVIHCRAGVGRT YOPH_YEREN 399 42 -
PMIHCLGGVGRT P74873 477 35 -
PMIHCLGGVGRT P74851 477 35 -