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PR00791

Identifier
PEPDIPTASEA  [View Relations]  [View Alignment]  
Accession
PR00791
No. of Motifs
8
Creation Date
01-JUL-1997  (UPDATE 22-JUN-1999)
Title
Peptidyl-dipeptidase A (M2) metalloprotease family signature
Database References

PROSITE; PS00142 ZINC_PROTEASE
BLOCKS; BL00142
INTERPRO; IPR001548
Literature References
1. RAWLINGS, N.D. AND BARRETT, A.J.
Evolutionary families of metallopeptidases.
METHODS ENZYMOL. 248 183-228 (1995).
 
2. WEI, L., ALHENC-GELAS, F., CORVOL, P. AND CLAUSER, E.
The two homologous domains of human angiotensin I-converting enzyme are
both catalytically active.
J.BIOL.CHEM. 266(14) 9002-9008 (1991).

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].
 
Pepetidyl-dipeptidase A (angiotensin-converting enzyme) is a mammalian 
enzyme responsible for cleavage of dipeptides from the C-termini of
proteins, notably converting angiotensin I to angiotensin II [1]. The enzyme
exists in two differentially transcribed forms, the most common of which
is from lung endothelium; this contains two homologous domains that have
arisen by gene duplication [1]. The testis-specific form contains only the 
C-terminal domain, arising from a duplicated promoter region present in
intron 12 of the gene [1]. 
 
Both enzymatic forms are membrane proteins that are anchored by means of a
C-terminal transmembrane domain. Both domains of the endothelial enzyme are
active, but have differing kinetic constants [1]. The catalytic residues and
zinc ligands have been identified, showing that the enzyme belongs to the 
HEXXH+E sub-group of metalloproteases [1,2]. A number of insect enzymes have
been shown to be similar to peptidyl-dipeptidase A, these containing a
single catalytic domain.
 
PEPDIPTASEA is an 8-element fingerprint that provides a signature for the 
peptidyl-dipeptidase A (M2) family of metalloproteases. The fingerprint was 
derived from an initial alignment of 8 sequences: the motifs were drawn
from conserved regions within a single catalytic domain - motif 4 includes
the region encoded by PROSITE pattern ZINC_PROTEASE (PS00142), which
contains the HEXXH motif; and motif 5 contains the additional zinc-binding
glutamate residue. Two iterations on OWL29.3 were required to reach
convergence, at which point a true set comprising 15 sequences was
identified. Two partial matches were also found: RATKII is an angiotensin-
converting enzyme fragment that matches motifs 1 and 2; CELC42D82 is a
sequence from cosmid C42D8 of C.elegans that matches motifs 1-3 and 6-8,
but does not contain the HEXXH motif or the additional glutamate zinc
ligand present in active members of the family. Note that the fingerprint
matches both domains of the mammalian endothelial enzymes.
 
An update on SPTR37_9f identified a true set of 12 sequences, and 1
partial match.
Summary Information
  12 codes involving  8 elements
0 codes involving 7 elements
0 codes involving 6 elements
1 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
81212121212121212
700000000
600000000
511000111
400000000
300000000
200000000
12345678
True Positives
ACET_HUMAN    ACET_MOUSE    ACET_RABIT    ACE_DROME     
ACE_HAEIE ACE_HUMAN ACE_MOUSE ACE_RABIT
ACE_RAT Q15540 Q17248 Q24222
True Positive Partials
Codes involving 5 elements
Q18581
Sequence Titles
ACET_HUMAN  ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, TESTIS-SPECIFIC (EC 3.4.15.1) (ACE-T) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - HOMO SAPIENS (HUMAN). 
ACET_MOUSE ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, TESTIS-SPECIFIC (EC 3.4.15.1) (ACE-T) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - MUS MUSCULUS (MOUSE).
ACET_RABIT ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, TESTIS-SPECIFIC (EC 3.4.15.1) (ACE-T) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - ORYCTOLAGUS CUNICULUS (RABBIT).
ACE_DROME ANGIOTENSIN CONVERTING ENZYME PRECURSOR (EC 3.4.15.1) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - DROSOPHILA MELANOGASTER (FRUIT FLY).
ACE_HAEIE ANGIOTENSIN CONVERTING ENZYME PRECURSOR (EC 3.4.15.1) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - HAEMATOBIA IRRITANS EXIGUA (BUFFALO FLY).
ACE_HUMAN ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, SOMATIC (EC 3.4.15.1) (ACE) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) (CD143 ANTIGEN) - HOMO SAPIENS (HUMAN).
ACE_MOUSE ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, SOMATIC (EC 3.4.15.1) (ACE) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - MUS MUSCULUS (MOUSE).
ACE_RABIT ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, SOMATIC (EC 3.4.15.1) (ACE) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - ORYCTOLAGUS CUNICULUS (RABBIT).
ACE_RAT ANGIOTENSIN-CONVERTING ENZYME PRECURSOR, SOMATIC (EC 3.4.15.1) (ACE) (DIPEPTIDYL CARBOXYPEPTIDASE I) (KININASE II) - RATTUS NORVEGICUS (RAT).
Q15540 TESTICULAR ANGIOTENSIN CONVERTING ENZYME - HOMO SAPIENS (HUMAN).
Q17248 ANGIOTENSIN-CONVERTING ENZYME-LIKE PROTEIN PRECURSOR - BOOPHILUS MICROPLUS (CATTLE TICK).
Q24222 METALLOPEPTIDASE - DROSOPHILA MELANOGASTER (FRUIT FLY).

Q18581 SIMILAR TO PEPTIDASE FAMILY M2 - CAENORHABDITIS ELEGANS.
Scan History
OWL29_3    2  100  NSINGLE    
SPTR37_9f 1 100 NSINGLE
Initial Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
LEKLYQELQPLYLNLHAYVRRSLHRHYG ACE_RAT 844 844 -
LERLFQELQPLYLNLHAYVGRALHRHYG ACET_RABIT 269 269 -
LERLFQELQPLYLNLHAYVRRALHRHYG ACE_HUMAN 838 838 -
LERLFQELQPLYLNLHAYVRRALHRHYG ACET_HUMAN 264 264 -
LERLFQELQPLYLNLHAYVRRALHRHYG HUMTACEB 226 226 -
LEHLYNQLEPLYLNLHAFVRRKLYDRYG ACE_CHICK 138 138 -
LDATFKQLLPLYRQLHGYVRFRLRQHYG DMACERMET 226 226 -
VDKLWEDLSPLYKKLHAYVRMKLREIYP BMU62809 241 241 -

Motif 2 width=22
Element Seqn Id St Int Rpt
GPIPAHLLGNMWAQTWSNIYDL ACE_RAT 879 7 -
GPIPAHLLGNMWAQTWSNIYDL ACET_RABIT 304 7 -
GPIPAHLLGNMWAQTWSNIYDL ACE_HUMAN 873 7 -
GPIPAHLLGNMWAQTWSNIYDL ACET_HUMAN 299 7 -
GPIPAHLLGNMWAQTWSNIYDL HUMTACEB 261 7 -
GPIPAHLLGNMWAQQWNNIYDL ACE_CHICK 173 7 -
GNIPISLLGNMWGQSWNELLDL DMACERMET 261 7 -
GTIPAHLLGNMWAQEWGTLYPH BMU62809 275 6 -

Motif 3 width=26
Element Seqn Id St Int Rpt
DGREVVCHASAWDFYNGKDFRIKQCT HUMTACEB 339 56 -
DGREVVCHASAWDFYNRKDFRIKQCT ACE_CHICK 251 56 -
DDRQVVCHASAWDFYQDSDVRIKMCT DMACERMET 338 55 -
EDREIQCHASAWNMYNGDDFRIKMCT BMU62809 350 53 -
DGREVVCHASAWDFYNGKDFRIKQCT ACET_HUMAN 377 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACE_HUMAN 951 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACET_RABIT 382 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACE_RAT 957 56 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LVVAHHEMGHIQYFMQY ACET_HUMAN 409 6 -
LVIAHHEMGHIQYFMQY ACE_RAT 989 6 -
LVVVHHEMGHIQYFMQY ACET_RABIT 414 6 -
LVVAHHEMGHIQYFMQY ACE_HUMAN 983 6 -
LRTVHHEMGHIEYYMQY BMU62809 382 6 -
FYVVHHELGHIQYYLQY DMACERMET 370 6 -
LFTVHHEMGHVQYYLQY ACE_CHICK 283 6 -
LVVAHHEMGHIQYFMQY HUMTACEB 371 6 -

Motif 5 width=21
Element Seqn Id St Int Rpt
NEGFHEAVGDLIALSVATKTH BMU62809 410 11 -
NPGFHEAIGDVLALSVSTPKH ACE_RAT 1017 11 -
NPGFHEAIGDVLALSVSTPKH ACET_RABIT 442 11 -
NPGFHEAIGDVLALSVSTPKH ACE_HUMAN 1011 11 -
NPGFHEAIGDVLALSVSTPKH ACET_HUMAN 437 11 -
NPGFHEAVGDVIALSVMSAKH DMACERMET 398 11 -
NPGFHEAIGDVMALSVSTPKH ACE_CHICK 909 609 -
NPGFHEAIGDVLALSVSTPKH HUMTACEB 399 11 -

Motif 6 width=26
Element Seqn Id St Int Rpt
LLMSALDKIAFLPFGYLLDKWRWTIF BMU62809 449 18 -
LMKMALDKIAFIPFSYLVDQWRWRVF ACET_HUMAN 478 20 -
LMKMALDKIAFIPFSYLVDQWRWRVF ACE_HUMAN 1052 20 -
LMKMALDKIAFIPFSYLVDEWRWRVF ACET_RABIT 483 20 -
LMKMALDKIAFIPFSYLIDQWRWRVF ACE_RAT 1058 20 -
LMKMALDKIAFIPFSYLVDQWRWRVF HUMTACEB 440 20 -
LMSIALDKIAFLPFGYLMDQWRWKVF ACE_CHICK 950 20 -
LFKQALSKIVFLPFGYAVDKYRYAVF DMACERMET 439 20 -

Motif 7 width=28
Element Seqn Id St Int Rpt
NQEWWSLRLKYQGLCPPVPRTQGDFDPG ACET_HUMAN 513 9 -
NEKFWEYRIKYQGVSPPVKRNESFFDGG BMU62809 484 9 -
NCGFWQMRSEFGGVEPPVFRTEKDFDPP DMACERMET 474 9 -
NQQWWNLRLKYQGLCPPVPRSEDDFDPG ACE_CHICK 985 9 -
NQEWWSLRLKYQGLCPPVPRTQGDFDPG ACE_HUMAN 1087 9 -
NQEWWSLRLKYQGLCPPAPRSQGDFDPG ACET_RABIT 518 9 -
NQEWWSLRLKYQGLCPPVPRSQGDFDPG ACE_RAT 1093 9 -
NQEWWSLRLKYQGLCPPVPRTQGDFDPG HUMTACEB 475 9 -

Motif 8 width=29
Element Seqn Id St Int Rpt
AKFHIPANVPYIRYFVSFVIQFQFHQALC ACE_CHICK 1013 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACE_HUMAN 1115 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACET_RABIT 546 0 -
SKFHVPANVPYIRYFISFIIQFQFHEALC ACE_RAT 1121 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACET_HUMAN 541 0 -
AKYHVALHVPYLRYFVAFILQFQFHEHLC BMU62809 512 0 -
AKYHIDADVEYLRYFAAHIFQFQFHKVLC DMACERMET 502 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC HUMTACEB 503 0 -
Final Motifs
Motif 1  width=28
Element Seqn Id St Int Rpt
LERLFQELQPLYLNLHAYVRRALHRHYG ACET_HUMAN 264 264 -
LERLFQELQPLYLNLHAYVRRALHRHYG ACE_HUMAN 838 838 -
LERLFQELQPLYLNLHAYVRRALHRHYG Q15540 226 226 -
LERLFQELQPLYLNLHAYVGRALHRHYG ACET_RABIT 269 269 -
LERLFQELQPLYLNLHAYVGRALHRHYG ACE_RABIT 842 842 -
LEKLYQELQPLYLNLHAYVRRSLHRHYG ACE_RAT 844 844 -
LEKLYQELQPLYLNLHAYVRRSLHRHYG ACE_MOUSE 843 843 -
LEKLYQELQPLYLNLHAYVRRSLHRHYG ACET_MOUSE 263 263 -
LEDIFADIRPLYQQIHGYVRFRLRKHYG ACE_DROME 217 217 -
LEAIFEDIKPLYDQVHGYVRYRLNKFYG ACE_HAEIE 217 217 -
VDKLWEDLSPLYKKLHAYVRMKLREIYP Q17248 241 241 -
LDATFKQLLPLYRQLHGYVRFRLRQHYG Q24222 226 226 -

Motif 2 width=22
Element Seqn Id St Int Rpt
GPIPAHLLGNMWAQTWSNIYDL ACET_HUMAN 299 7 -
GPIPAHLLGNMWAQTWSNIYDL ACE_HUMAN 873 7 -
GPIPAHLLGNMWAQTWSNIYDL Q15540 261 7 -
GPIPAHLLGNMWAQTWSNIYDL ACET_RABIT 304 7 -
GPIPAHLLGNMWAQTWSNIYDL ACE_RABIT 877 7 -
GPIPAHLLGNMWAQTWSNIYDL ACE_RAT 879 7 -
GPIPAHLLGNMWAQTWSNIYDL ACE_MOUSE 878 7 -
GPIPAHLLGNMWAQTWSNIYDL ACET_MOUSE 298 7 -
GPIPMHLLGNMWAQQWSEIADI ACE_DROME 252 7 -
GPLPMHLLGNMWAQQWSSIADI ACE_HAEIE 252 7 -
GTIPAHLLGNMWAQEWGTLYPH Q17248 275 6 -
GNIPISLLGNMWGQSWNELLDL Q24222 261 7 -

Motif 3 width=26
Element Seqn Id St Int Rpt
DGREVVCHASAWDFYNGKDFRIKQCT ACET_HUMAN 377 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACE_HUMAN 951 56 -
DGREVVCHASAWDFYNGKDFRIKQCT Q15540 339 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACET_RABIT 382 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACE_RABIT 955 56 -
DGREVVCHASAWDFYNGKDFRIKQCT ACE_RAT 957 56 -
DGREVVCHPSAWDFYNGKDFRIKQCT ACE_MOUSE 956 56 -
DGREVVCHPSAWDFYNGKDFRIKQCT ACET_MOUSE 376 56 -
DGRDLVCHASAWDFYLIDDVRIKQCT ACE_DROME 330 56 -
DGRDLVCHASAWDFYLTDDVRIKQCT ACE_HAEIE 330 56 -
EDREIQCHASAWNMYNGDDFRIKMCT Q17248 350 53 -
DDRQVVCHASAWDFYQDSDVRIKMCT Q24222 338 55 -

Motif 4 width=17
Element Seqn Id St Int Rpt
LVVAHHEMGHIQYFMQY ACET_HUMAN 409 6 -
LVVAHHEMGHIQYFMQY ACE_HUMAN 983 6 -
LVVAHHEMGHIQYFMQY Q15540 371 6 -
LVVVHHEMGHIQYFMQY ACET_RABIT 414 6 -
LVVVHHEMGHIQYFMQY ACE_RABIT 987 6 -
LVIAHHEMGHIQYFMQY ACE_RAT 989 6 -
LVIAHHEMGHIQYFMQY ACE_MOUSE 988 6 -
LVIAHHEMGHIQYFMQY ACET_MOUSE 408 6 -
LFTVHHELGHIQYFLQY ACE_DROME 362 6 -
FFTVHHEMGHIQYFLQY ACE_HAEIE 362 6 -
LRTVHHEMGHIEYYMQY Q17248 382 6 -
FYVVHHELGHIQYYLQY Q24222 370 6 -

Motif 5 width=21
Element Seqn Id St Int Rpt
NPGFHEAIGDVLALSVSTPKH ACET_HUMAN 437 11 -
NPGFHEAIGDVLALSVSTPKH ACE_HUMAN 1011 11 -
NPGFHEAIGDVLALSVSTPKH Q15540 399 11 -
NPGFHEAIGDVLALSVSTPKH ACET_RABIT 442 11 -
NPGFHEAIGDVLALSVSTPKH ACE_RABIT 1015 11 -
NPGFHEAIGDVLALSVSTPKH ACE_RAT 1017 11 -
NPGFHEAIGDIMALSVSTPKH ACE_MOUSE 1016 11 -
NPGFHEAIGDIMALSVSTPKH ACET_MOUSE 436 11 -
NPGFHEAVGDVLSLSVSTPKH ACE_DROME 390 11 -
NPGFHEAVGDVLSLSVSTPKH ACE_HAEIE 390 11 -
NEGFHEAVGDLIALSVATKTH Q17248 410 11 -
NPGFHEAVGDVIALSVMSAKH Q24222 398 11 -

Motif 6 width=26
Element Seqn Id St Int Rpt
LMKMALDKIAFIPFSYLVDQWRWRVF ACET_HUMAN 478 20 -
LMKMALDKIAFIPFSYLVDQWRWRVF ACE_HUMAN 1052 20 -
LMKMALDKIAFIPFSYLVDQWRWRVF Q15540 440 20 -
LMKMALDKIAFIPFSYLVDEWRWRVF ACET_RABIT 483 20 -
LMKMALDKIAFIPFSYLVDEWRWRVF ACE_RABIT 1056 20 -
LMKMALDKIAFIPFSYLIDQWRWRVF ACE_RAT 1058 20 -
LMKMALDKIAFIPFSYLIDQWRWRVF ACE_MOUSE 1057 20 -
LMKMALDKIAFIPFSYLIDQWRWRVF ACET_MOUSE 477 20 -
LFLTALDKIVFLPFAFTMDKYRWSLF ACE_DROME 431 20 -
LFLTALDKIVFLPFAFTMDKYRWALF ACE_HAEIE 431 20 -
LLMSALDKIAFLPFGYLLDKWRWTIF Q17248 449 18 -
LFKQALSKIVFLPFGYAVDKYRYAVF Q24222 439 20 -

Motif 7 width=28
Element Seqn Id St Int Rpt
NQEWWSLRLKYQGLCPPVPRTQGDFDPG ACET_HUMAN 513 9 -
NQEWWSLRLKYQGLCPPVPRTQGDFDPG ACE_HUMAN 1087 9 -
NQEWWSLRLKYQGLCPPVPRTQGDFDPG Q15540 475 9 -
NQEWWSLRLKYQGLCPPAPRSQGDFDPG ACET_RABIT 518 9 -
NQEWWSLRLKYQGLCPPAPRSQGDFDPG ACE_RABIT 1091 9 -
NQEWWSLRLKYQGLCPPVPRSQGDFDPG ACE_RAT 1093 9 -
NQEWWSLRLKYQGLCPPVPRSQGDFDPG ACE_MOUSE 1092 9 -
NQEWWSLRLKYQGLCPPVPRSQGDFDPG ACET_MOUSE 512 9 -
NCAFWKLRDEYSGIEPPVVRSEKDFDAP ACE_DROME 466 9 -
NCAFWKLREEYSGIEPPVVRTEKDFDAP ACE_HAEIE 466 9 -
NEKFWEYRIKYQGVSPPVKRNESFFDGG Q17248 484 9 -
NCGFWQMRSEFGGVEPPVFRTEKDFDPP Q24222 474 9 -

Motif 8 width=29
Element Seqn Id St Int Rpt
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACET_HUMAN 541 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACE_HUMAN 1115 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC Q15540 503 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACET_RABIT 546 0 -
AKFHIPSSVPYIRYFVSFIIQFQFHEALC ACE_RABIT 1119 0 -
SKFHVPANVPYIRYFISFIIQFQFHEALC ACE_RAT 1121 0 -
SKFHVPANVPYVRYFVSFIIQFQFHEALC ACE_MOUSE 1120 0 -
SKFHVPANVPYVRYFVSFIIQFQFHEALC ACET_MOUSE 540 0 -
AKYHISADVEYLRYLVSFIIQFQFYKSAC ACE_DROME 494 0 -
AKYHVSADVEYLRYLVSFIIQFQFYKSAC ACE_HAEIE 494 0 -
AKYHVALHVPYLRYFVAFILQFQFHEHLC Q17248 512 0 -
AKYHIDADVEYLRYFAAHIFQFQFHKVLC Q24222 502 0 -