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PR01704

Identifier
FUNRIBOTOXIN  [View Relations]  [View Alignment]  
Accession
PR01704
No. of Motifs
5
Creation Date
21-NOV-2001
Title
Fungal allergen ribonucleotoxin signature
Database References

PFAM; PF02804 RNase_U2
INTERPRO; IPR004025
PDB; 1AQZ
SCOP; 1AQZ
CATH; 1AQZ
Literature References
1. LAMY, B., MOUTAOUAKIL, M., LATGE, J.-P. AND DAVIES, J.
Secretion of a potential virulence factor, a fungal ribonucleotoxin, during
human aspergillosis infections.
MOL.MICROBIOL. 5 1811-1815 (1991).
 
2. KAO, R. AND DAVIES, J.
Molecular dissection of Mitogillin reveals that the fungal ribotoxins are a 
family of natural genetically engineered ribonucleases.
J.BIOL.CHEM. 274 12576-12582 (1999).
 
3. KAO, R. AND DAVIES, J.
Single amino acid substitutions affecting the specificity of the fungal 
ribotoxin mitogillin.
FEBS LETT. 21 87-90 (2000).

Documentation
Fungi are ubiquitous in nature, and numerous fungal diseases in humans, 
cattle, poultry, etc., have been described. The major pathogenic species
of Aspergillus for humans is Aspergillus fumigatus [1], which is responsible
for a variety of allergic and invasive diseases; the most severe form is
invasive aspergillosis, which is an increasingly important cause of
mortality in severely immunocompromised patients, especially those with
acute leukaemia. During human fungal infections, a variety of complex 
circulating antigens are found in the urine and serum of patients. Of these,
the major antigen is a 18kDa protein, whose amino acid composition is
similar to that of mitogillin and restrictocin [1].
 
The fungal ribotoxins are a family of highly specific ribonucleases that 
inactivate the ribosome by cleavage of the 23-28S RNA of the large ribosomal 
subunit at a single phosphodiester bond. Cleavage abolishes the capacity of
ribosomes to carry out protein synthesis by inhibiting elongation factor 1-
dependent binding of aminoacyl-tRNA and GTP-dependent binding of elongation
factor 2 to ribosomes. Mitogillin-like ribotoxins are among the most potent
inhibitors of translation so far identified, and they have been investigated
as potential anti-tumour agents, or components of immunotoxins [2].
 
Mitogillin and the related Aspergillus fungal ribotoxins, restrictocin (from 
which mitogillin differs by only one amino acid) and a-sarcin (with which it 
has 86% amino acid sequence identity), are small basic proteins of ~17kDa, 
consisting of a single polypeptide chain. These proteins share amino acid
sequence similarity with T1/U2-like ribonucleases, but their ability to
interact specifically with the ribosome and cause a single ribonucleolytic
cleavage in the large subunit rRNA is unique. Similarities and differences
in the amino acid sequences of ribotoxins and other guanyl/purine 
ribonucleases may represent domains or residues key to ribonucleolytic
activity and specificity [2,3]. The presence of such domains (some of 
which are similar to sequences in ribosome-associated proteins) in fungal 
ribotoxins, led to the hypothesis that fungal ribotoxins are a family of 
naturally engineered toxins with ribosomal targeting elements inserted 
into non-essential regions of T1-like ribonucleases. 
FUNRIBOTOXIN is a 5-element fingerprint that provides a signature for the 
major allergen fungal ribotoxins. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning the full alignment length - motif 1 includes beta-strand 1,
which bears the first active site His residue; motif 2 includes strand 2,
which houses the active site Asp; motif 3 encodes the N-terminus of strand
3, which bears the active site Arg; motif 4 spans the C-terminus of strand 3
and the N-terminal portion of strand 4; and motif 5 includes strand 5, which
houses the second active site His. Two iterations on SPTR39_17f were 
required to reach convergence, at which point a true set comprising 11
sequences was identified.
Summary Information
11 codes involving  5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
51111111111
400000
300000
200000
12345
True Positives
O13322        O13323        O13324        O13325        
O14446 P78572 P87063 Q9P4F0
RNAS_ASPGI RNCL_ASPCL RNMG_ASPRE
Sequence Titles
O13322      A-SARCIN PRECURSOR - Penicillium resedanum.   
O13323 A-SARCIN PRECURSOR - Penicillium spinulosum.
O13324 A-SARCIN PRECURSOR - Penicillium digitatum.
O13325 A-SARCIN PRECURSOR - Penicillium chermesinum.
O14446 A-SARCIN PRECURSOR - Penicillium aculeatum, and Penicillium daleae.
P78572 C-SARCIN PRECURSOR - Aspergillus clavatus.
P87063 GIGANTIN PRECURSOR - Aspergillus giganteus.
Q9P4F0 MAJOR ALLERGEN I 18KDA ANTIGEN - Aspergillus fumigatus (Sartorya fumigata).
RNAS_ASPGI RIBONUCLEASE ALPHA-SARCIN PRECURSOR (EC 3.1.27.10) - Aspergillus giganteus.
RNCL_ASPCL RIBONUCLEASE CLAVIN PRECURSOR (EC 3.1.27.-) - Aspergillus clavatus.
RNMG_ASPRE RIBONUCLEASE MITOGILLIN PRECURSOR (EC 3.1.27.-) (RESTRICTOCIN) (MAJOR ALLERGEN ASP F 1) (ASP F I) (ALLERGEN I/A) (IGE-BINDING RIBOTOXIN) - Aspergillus restrictus, and Aspergillus fumigatus (Sartorya fumigata).
Scan History
SPTR39_17f 2  100  NSINGLE    
Initial Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
PLSDGKTGSSYPHWFTNGYDG P87063 65 65 -
PLSDGKTGSSYPHWFTNGYDG RNAS_ASPGI 65 65 -
PLSDGKTGSSYPHWFTNGYDG O13323 65 65 -
PLSDGKTGSSYPHWFTNGYDG O13325 65 65 -
PLSDGKTGSSYPHWFTNGYDG RNMG_ASPRE 64 64 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DHYLLEFPTFPDGH P87063 118 32 -
DHYLLEFPTFPDGH RNAS_ASPGI 118 32 -
DHYLLEFPTFPDGH O13323 118 32 -
DHYLLEFPTFPDGH O13325 118 32 -
DHYLLEFPTFPDGH RNMG_ASPRE 117 32 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FDSKKPKEDPGPAR P87063 135 3 -
FDSKKPKENPGPAR RNAS_ASPGI 135 3 -
FDSKKPKEDPGPAR O13323 135 3 -
FDSKKPKEDPGPAR O13325 135 3 -
FDSKKPKEDPGPAR RNMG_ASPRE 134 3 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RVIYTYPNKVFCG P87063 148 -1 -
RVIYTYPNKVFCG RNAS_ASPGI 148 -1 -
RVIYTYPNKAFCG O13323 148 -1 -
RVIYTYPNKVFCG O13325 148 -1 -
RVIYTYPNKVFCG RNMG_ASPRE 147 -1 -

Motif 5 width=14
Element Seqn Id St Int Rpt
HTRENQGELKLCSH P87063 164 3 -
HTKENQGELKLCSH RNAS_ASPGI 164 3 -
HTKENQGDLKLCSH O13323 164 3 -
HTKENQRALKLCSH O13325 164 3 -
HQRGNQGDLRLCSH RNMG_ASPRE 163 3 -
Final Motifs
Motif 1  width=21
Element Seqn Id St Int Rpt
PLSDGKTGSSYPHWFTNGYDG O13322 65 65 -
PLSDGKTGSSYPHWFTNGYDG O14446 65 65 -
PLSDGKTGSSYPHWFTNGYDG O13324 65 65 -
PLSDGKTGSSYPHWFTNGYDG P78572 65 65 -
PLSDGKTGSSYPHWFTNGYDG RNCL_ASPCL 65 65 -
PLSDGKTGSSYPHWFTNGYDG P87063 65 65 -
PLSDGKTGSSYPHWFTNGYDG RNAS_ASPGI 65 65 -
PLSDGKTGSSYPHWFTNGYDG O13323 65 65 -
PLSDGKTGSSYPHWFTNGYDG O13325 65 65 -
PLSDGKTGSSYPHWFTNGYDG RNMG_ASPRE 64 64 -
PLSDGKTGSSYAHWFTNGYDG Q9P4F0 37 37 -

Motif 2 width=14
Element Seqn Id St Int Rpt
DHYLLEFPTFPDGH O13322 118 32 -
DHYLLEFPTFPDGH O14446 118 32 -
DHYLLEFPTFPDGH O13324 118 32 -
DHYLLEFPTFPDGH P78572 118 32 -
DHYLLEFPTFPDGH RNCL_ASPCL 118 32 -
DHYLLEFPTFPDGH P87063 118 32 -
DHYLLEFPTFPDGH RNAS_ASPGI 118 32 -
DHYLLEFPTFPDGH O13323 118 32 -
DHYLLEFPTFPDGH O13325 118 32 -
DHYLLEFPTFPDGH RNMG_ASPRE 117 32 -
DHYLLEFPTFPDGH Q9P4F0 90 32 -

Motif 3 width=14
Element Seqn Id St Int Rpt
FDSKKPKEDPGPAR O13322 135 3 -
FDSKKPKEDPGPAR O14446 135 3 -
FDSKKPKEDPGPAR O13324 135 3 -
FDSKKPKEDPGPAR P78572 135 3 -
FDSKKPKEDPGPAR RNCL_ASPCL 135 3 -
FDSKKPKEDPGPAR P87063 135 3 -
FDSKKPKENPGPAR RNAS_ASPGI 135 3 -
FDSKKPKEDPGPAR O13323 135 3 -
FDSKKPKEDPGPAR O13325 135 3 -
FDSKKPKEDPGPAR RNMG_ASPRE 134 3 -
DSKNKPKEDPGPAR Q9P4F0 108 4 -

Motif 4 width=13
Element Seqn Id St Int Rpt
RVIYTYPNKVFCG O13322 148 -1 -
RVIYTYPNKVFCG O14446 148 -1 -
RVIYTYPNKVFCG O13324 148 -1 -
RVIYTYPNKVFCG P78572 148 -1 -
RVIYTYPNKVFCG RNCL_ASPCL 148 -1 -
RVIYTYPNKVFCG P87063 148 -1 -
RVIYTYPNKVFCG RNAS_ASPGI 148 -1 -
RVIYTYPNKAFCG O13323 148 -1 -
RVIYTYPNKVFCG O13325 148 -1 -
RVIYTYPNKVFCG RNMG_ASPRE 147 -1 -
RVIYTYPNKVFCG Q9P4F0 121 -1 -

Motif 5 width=14
Element Seqn Id St Int Rpt
HTKENQGDLKLCSH O13322 164 3 -
HTKENQGDLKLCSH O14446 164 3 -
HTKENQGDLKLCSH O13324 164 3 -
HTRENQGDLKLCSH P78572 164 3 -
HTRENQGDLKLCSH RNCL_ASPCL 164 3 -
HTRENQGELKLCSH P87063 164 3 -
HTKENQGELKLCSH RNAS_ASPGI 164 3 -
HTKENQGDLKLCSH O13323 164 3 -
HTKENQRALKLCSH O13325 164 3 -
HQRGNQGDLRLCSH RNMG_ASPRE 163 3 -
HQRGNEGDLRLCSH Q9P4F0 137 3 -