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PR00932

Identifier
AMINO1PTASE  [View Relations]  [View Alignment]  
Accession
PR00932
No. of Motifs
6
Creation Date
11-SEP-1998  (UPDATE 06-JUN-1999)
Title
Aminopeptidase I zinc metalloprotease (M18) signature
Database References

PROSITE; PS00142 ZINC_PROTEASE
BLOCKS; BL00142
INTERPRO; IPR001948
Literature References
1. RAWLINGS, N.D. AND BARRETT, A.J.
Evolutionary families of metallopeptidases.
METHODS ENZYMOL. 248 183-228 (1995).
 
2. RAWLINGS, N.D. AND BARRETT, A.J.
MEROPS - Peptidase Database
http://www.bi.bbsrc.ac.uk/merops/merops.htm
 
3. RAWLINGS, N.D. AND BARRETT, A.J.
Family M18 - Clan MH - Aminopeptidase I
http://www.bi.bbsrc.ac.uk/merops/famcards/m18.htm
 
4. CHANG, Y.H. AND SMITH, J.A.
Molecular cloning and sequencing of genomic DNA encoding aminopeptidase I
from Saccharomyces cerevisiae. 
J.BIOL.CHEM. 264 6979-6983 (1989). 

Documentation
Metalloproteases are the most diverse of the four main types of protease,
with more than 30 families identified to date [1]. Of these, around
half contain the HEXXH motif, which has been shown in crystallographic
studies to form part of the metal-binding site [1]. The HEXXH motif is 
relatively common, but can be more stringently defined for metallo-
proteases as abXHEbbHbc, where a is most often valine or threonine and 
forms part of the S1' subsite in thermolysin and neprilysin, b is an
uncharged residue, and c a hydrophobic residue. Proline is never found
in this site, possibly because it would break the helical structure 
adopted by this motif in metalloproteases [1].
 
Metalloproteases can be split into five groups on the basis of their metal-
binding residues: the first three contain the HEXXH motif, the other two
do not [1]. In the first group, a glutamic acid completes the active site -
these are termed HEXXH+E: all families in this group show some sequence
relationship and have been assigned to clan MA [1]. The second group, which
have a third histidine as the extra metal-binding residue, are termed
HEXXH+H and are grouped into clan MB on the basis of their inter-relation-
ship[1]. In the third group, the additional metal-binding residues are
unidentified. The fourth group is diverse - the metal-binding residues are
known but do not form the HEXXH motif. And the fifth group comprises the
remaining families where the metal-binding residues are as yet unknown [1,2].
 
Aminopeptidase I is a metallopeptidase that belongs to the M18 protease
family, which is part of the MH clan [1,3]. Proteins of this clan have two
catalytic zinc ions at the active site, bound by His/Asp, Asp, Glu, Asp/Glu
and His. The catalysed reaction involves the release of an N-terminal amino-
acid, usually neutral or hydrophobic, from a polypeptide. 
 
The yeast sequence has been deduced, and the mature protein shown to consist
of 469 amino acids [4]. A 45-residue presequence contains both positively-
and negatively-charged and hydrophobic residues, which could be arranged 
in an N-terminal amphiphilic alpha-helix [4]. The presequence differs from
signal sequences that direct proteins across bacterial plasma membranes and
endoplasmic reticulum or into mitochondria. It is unclear how this unique
presequence targets aminopeptidase I to yeast vacuoles, and how this
sorting utilises classical protein secretory pathways [4]. 
 
AMINO1PTASE is a 6-element fingerprint that provides a signature for the 
aminopeptidase I family of zinc metalloproteases (M18). The fingerprint was 
derived from an initial alignment of 8 sequences: the motifs were drawn 
from conserved regions spanning virtually the full length of the mature
protein. Two iterations on OWL30.2 were required to reach convergence, at
which point a true set comprising 10 sequences was identified.
 
An update on SPTR37_9f identified a true set of 9 sequences.
Summary Information
9 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
6999999
5000000
4000000
3000000
2000000
123456
True Positives
AMPL_YEAST    O06634        O36014        O51572        
O86957 Q19087 Q45055 Q50022
YHR3_YEAST
Sequence Titles
AMPL_YEAST  VACUOLAR AMINOPEPTIDASE I PRECURSOR (EC 3.4.11.22) (POLYPEPTIDASE) (LEUCINE AMINOPEPTIDASE IV) (LAPIV) (AMINOPEPTIDASE III) (AMINOPEPTIDASE YSCI) - SACCHAROMYCES CEREVISIAE (BAKER'S YEAST). 
O06634 HYPOTHETICAL 46.0 KD PROTEIN - MYCOBACTERIUM TUBERCULOSIS.
O36014 PROBABLE VACUOLAR AMINOPEPTIDASE I PRECURSOR (EC 3.4.11.22) (POLYPEP-TIDASE) (LEUCINE AMINOPEPTIDASE IV) (LAPIV) (AMINOPEPTIDASE III) (AMINOPEPTIDASE YSCI) - SCHIZOSACCHAROMYCES POMBE (FISSION YEAST).
O51572 VACUOLAR X-PROLYL DIPEPTIDYL AMINOPEPTIDASE I (PEPX) - BORRELIA BURGDORFERI (LYME DISEASE SPIROCHETE).
O86957 AMINOPEPTIDASE - THERMOTOGA NEAPOLITANA.
Q19087 SIMILAR TO S. CEREVISIAE VACUOLAR AMINOPEPTIDASE - CAENORHABDITIS ELEGANS.
Q45055 AMINOPEPTIDASEI-LIKE - BORRELIA BURGDORFERI (LYME DISEASE SPIROCHETE).
Q50022 PEPX - MYCOBACTERIUM LEPRAE.
YHR3_YEAST HYPOTHETICAL 54.2 KD PROTEIN IN ERP5-ORC6 INTERGENIC REGION - SACCHAROMYCES CEREVISIAE (BAKER'S YEAST).
Scan History
OWL30_2    2  25   NSINGLE    
SPTR37_9f 2 10 NSINGLE
Initial Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FRIVGAHTDSPNLRVKQ MLCB526 90 90 -
FRIVGAHTDSPNLRVKQ MTCY7H7A8 73 73 -
FSIVVGHTDSPCLRVKP CELF01F14 86 86 -
FSIIATHTDSPTLRLKP D89276 6 6 -
FSIIATHTDSPTLRLKP SPAC4F101 81 81 -
FLIAAAHTDSPGLKLKI B70178 78 78 -
IAITGAHTDSPALRIKP YHR3_YEAST 91 91 -
VGVIGSHVDALTVKLKP AMPL_YEAST 126 126 -

Motif 2 width=21
Element Seqn Id St Int Rpt
YGGGIWHTWFDRDLSLAGRVM D89276 39 16 -
YGGGIWHTWFDRDLSLAGRVM SPAC4F101 114 16 -
YGSPIISTWIDRDLSLAGIVY B70178 111 16 -
YGGGIWRTWFDRDLSVAGLVI CELF01F14 119 16 -
YGGVWLHSWLDRDLGISGRLS MTCY7H7A8 106 16 -
YGGAWLNSWLDRDLGVSGRLS MLCB526 123 16 -
YGGTLNELWLDRDLGIGGRLL AMPL_YEAST 160 17 -
YGGAIWHSWFDKDLGVAGRVF YHR3_YEAST 124 16 -

Motif 3 width=18
Element Seqn Id St Int Rpt
PLPVCRIPSLAPHFGKPA AMPL_YEAST 198 17 -
NRPLLKIPTLAIHLDRDV YHR3_YEAST 161 16 -
IENIGIIPNLAIHLNRQI B70178 145 13 -
DRPLLRIPTLAIHLDPSA SPAC4F101 150 15 -
DRPLLRIPTLAIHLDPSA D89276 75 15 -
KKPVLFIPNLAIHLETDR CELF01F14 154 14 -
DDPILRVPQLAIHLAEDR MTCY7H7A8 141 14 -
DDPILRVPQLAIHLAEDR MLCB526 161 17 -

Motif 4 width=19
Element Seqn Id St Int Rpt
FDHEEVGSTSDRGARSNLL MLCB526 273 94 -
FDHEEVGSASGHGAQSDLL MTCY7H7A8 261 102 -
FDNEEVGSDSAMGASSSFT CELF01F14 296 124 -
FDHEEIGSVSTQGAESTFL D89276 214 121 -
FDHEEIGSVSAQGAESTFL SPAC4F101 289 121 -
FDNEEVGSLTSRGADSNFL B70178 254 91 -
YDNEEIGSLTRQGAKGGLL AMPL_YEAST 336 120 -
FDHEEIGSSSAQGADSNFL YHR3_YEAST 305 126 -

Motif 5 width=17
Element Seqn Id St Int Rpt
SFNISIDSVHGIHPGYT B70178 297 24 -
SFLVSADMAHAMHPNYS SPAC4F101 331 23 -
SFLVSADMAHAMHPNYS D89276 256 23 -
SMLISADQAHATHPNYS CELF01F14 337 22 -
SMLASADMAHATHPNYP MTCY7H7A8 304 24 -
SLLVSADMAHATHPNYP MLCB526 316 24 -
SFFLSSDVAHAVHPNYA YHR3_YEAST 356 32 -
SIILSADVNHLYNPNFP AMPL_YEAST 379 24 -

Motif 6 width=16
Element Seqn Id St Int Rpt
TVDVGCPQLAMHSIRE CELF01F14 426 72 -
TLDLGNPMLSMHSCRE D89276 345 72 -
TLDLGNPMLSMHSCRE SPAC4F101 420 72 -
TIDIGTPMWAMHSLRE B70178 386 72 -
TLDLGNPVLSMHSIRE YHR3_YEAST 445 72 -
TIDLGIAQLSMHSIRA AMPL_YEAST 468 72 -
TVDVGAAQLAMHSARE MLCB526 405 72 -
TVDVGAAQLAMHSARE MTCY7H7A8 393 72 -
Final Motifs
Motif 1  width=17
Element Seqn Id St Int Rpt
FRIVGAHTDSPNLRVKQ Q50022 90 90 -
FSIIATHTDSPTLRLKP O36014 81 81 -
FRIVGAHTDSPNLRVKQ O06634 73 73 -
IAITGAHTDSPALRIKP YHR3_YEAST 91 91 -
FSIVVGHTDSPCLRVKP Q19087 86 86 -
FLIAAAHTDSPGLKLKI O51572 78 78 -
MNFIVSHTDSPRLDAKP Q45055 89 89 -
VGVIGSHVDALTVKLKP AMPL_YEAST 126 126 -
LNLVVAHIDSPRLDFKP O86957 87 87 -

Motif 2 width=21
Element Seqn Id St Int Rpt
YGGAWLNSWLDRDLGVSGRLS Q50022 123 16 -
YGGGIWHTWFDRDLSLAGRVM O36014 114 16 -
YGGVWLHSWLDRDLGISGRLS O06634 106 16 -
YGGAIWHSWFDKDLGVAGRVF YHR3_YEAST 124 16 -
YGGGIWRTWFDRDLSVAGLVI Q19087 119 16 -
YGSPIISTWIDRDLSLAGIVY O51572 111 16 -
YGGIKKYQWLSTPLSIRGVVF Q45055 122 16 -
YGGTLNELWLDRDLGIGGRLL AMPL_YEAST 160 17 -
YGGIKKYHWFNIPLEIHGVLF O86957 120 16 -

Motif 3 width=18
Element Seqn Id St Int Rpt
DDPILRVPQLAIHLAEDR Q50022 161 17 -
DRPLLRIPTLAIHLDPSA O36014 150 15 -
DDPILRVPQLAIHLAEDR O06634 141 14 -
NRPLLKIPTLAIHLDRDV YHR3_YEAST 161 16 -
KKPVLFIPNLAIHLETDR Q19087 154 14 -
IENIGIIPNLAIHLNRQI O51572 145 13 -
NDPVFVIPDILPHLDRKI Q45055 158 15 -
PLPVCRIPSLAPHFGKPA AMPL_YEAST 198 17 -
EDPVFTIPDLLPHLDKED O86957 156 15 -

Motif 4 width=19
Element Seqn Id St Int Rpt
FDHEEVGSTSDRGARSNLL Q50022 273 94 -
FDHEEIGSVSAQGAESTFL O36014 289 121 -
FDHEEVGSASGHGAQSDLL O06634 261 102 -
FDHEEIGSSSAQGADSNFL YHR3_YEAST 305 126 -
FDNEEVGSDSAMGASSSFT Q19087 296 124 -
FDNEEVGSLTSRGADSNFL O51572 254 91 -
VDKEEIGSTGSTGLDSRYL Q45055 283 107 -
YDNEEIGSLTRQGAKGGLL AMPL_YEAST 336 120 -
LDKEEIGSDGNTGAKARFY O86957 276 102 -

Motif 5 width=17
Element Seqn Id St Int Rpt
SLLVSADMAHATHPNYP Q50022 316 24 -
SFLVSADMAHAMHPNYS O36014 331 23 -
SMLASADMAHATHPNYP O06634 304 24 -
SFFLSSDVAHAVHPNYA YHR3_YEAST 356 32 -
SMLISADQAHATHPNYS Q19087 337 22 -
SFNISIDSVHGIHPGYT O51572 297 24 -
SKSISADVCAAINPLFS Q45055 329 27 -
SIILSADVNHLYNPNFP AMPL_YEAST 379 24 -
SAVISGDVCAAVNPPYK O86957 322 27 -

Motif 6 width=16
Element Seqn Id St Int Rpt
TVDVGAAQLAMHSARE Q50022 405 72 -
TLDLGNPMLSMHSCRE O36014 420 72 -
TVDVGAAQLAMHSARE O06634 393 72 -
TLDLGNPVLSMHSIRE YHR3_YEAST 445 72 -
TVDVGCPQLAMHSIRE Q19087 426 72 -
TIDIGTPMWAMHSLRE O51572 386 72 -
TIDMGPAVISMHSPME Q45055 423 77 -
TIDLGIAQLSMHSIRA AMPL_YEAST 468 72 -
VYDMGPALLGMHSPFE O86957 416 77 -