Summary for peptidase A01.053: necepsin-1

Summary Alignment Tree Sequences Sequence features Distribution Literature Substrates

 

Names
MEROPS Namenecepsin-1
Other namesasp-1 g.p. (Caenorhabditis elegans), Mername-AA046 peptidase, Na-APR-2 g.p. (Necator americanus), nemepsin-3, Sc-ASP110 (Steinernema carpocapsae), Sc-ASP155 (Steinernema carpocapsae)
Name and HistoryThe name 'necepsin' was first applied to the gene sequences of ncp1 and ncp2 from Necator americanus deposited in the EMBL database in 1999. The name "nemepsin" was used by Williamson et al., 2003. Neither name has been used in subsequent literature.
Domain architecture
MEROPS Classification
Classification Clan AA >> Subclan (none) >> Family A1 >> Subfamily A >> A01.053
Holotypenecepsin-1 (Caenorhabditis elegans) (peptidase unit: 54-391), MERNUM MER0004851
History Identifier created: MEROPS 5.3 (4 December 2000)
Activity
Catalytic typeAspartic
NC-IUBMBNot yet included in IUBMB recommendations.
Proteolytic eventsCutDB database (78 cleavages)
PreparationRecombinant necepsin-1 has been expressed in Spodoptera frugiperda Sf9 cells (Williamson et al., 2003).
SpecificityNecepsin-1 has a preference for cleaving within stretches of aliphatic, hydrophobic amino acids, except for Ile and Met, which are not accepted in most of the P4-P4' positions.
pH optimum5.0 (Williamson et al., 2003).
StructureThe pre-pro-peptide has a mass of 42.7 kDa and the mature protein of approximately 40 kDa. Being a lysosomal protein, it would be expected that necepsin-1 is glycosylated, and there is a potential N-linked glycosylation site at Asn71 (Tcherepanova et al., 2000).
LocationLysosomal (Tcherepanova et al., 2000).
PhysiologyIn Caenorhabditis elegans, the asp-1 gene is exclusively transcribed in the intestinal cells, with the highest levels of expression observed at late embryonic and early larval stages of development. Transcription is not observed in the adult nematodes or mature larvae (Tcherepanova et al., 2000).
Biological aspectsIn Caenorhabditis elegans, Asp-1 is synthesized as a 396-residue, 42.7 kDa precursor, which is processed to a 40 kDa lysosomal protein. Its gene is exclusively transcribed in intestinal cells, with the highest levels of expression observed at late embryonic and early larval stages. It is not transcribed in the adult nematodes or mature larvae (Tcherepanova et al., 2000). However, in the hookworm Necator Americanus it is only transcribed in last, fourth stage larva and adults (Williamson et al., 2003).
KnockoutIn Caenorhabditis elegans, knockout of the asp-1 gene reduces neurodegeneration (Syntichaki et al., 2002).
Pharmaceutical relevanceNecepsin-1 has been proposed for use in the development of an anti-hookworm vaccine (Williamson et al., 2003).
Distinguishing featuresNecepsin-3 is distinguished from cathepsin D (A01.009) by the differences in cleavage of hemoglobin chains (Williamson et al., 2003).
Contributing authorsMatthew Jenner, former summer student with MEROPS (current address: Centre of Mass Spectrometry, School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK)
Cleavage site specificity Explanations of how to interpret the following cleavage site sequence logo and specificity matrix can be found here.
Cleavage pattern-/-/-/-Scissile bond-/-/-/- (based on 133 cleavages)
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Specificity matrix
 
Amino acid P4 P3 P2 P1 P1' P2' P3' P4'
Gly 10 8 9 14 6 13 8 13
Pro 8 6 12 1 5 5 4 6
Ala 13 14 15 17 16 19 10 10
Val 15 10 13 14 12 12 15 16
Leu 19 15 12 22 13 15 23 20
Ile 0 0 1 0 1 1 1 0
Met 1 1 1 0 0 1 3 0
Phe 10 3 9 15 7 5 8 6
Tyr 2 3 1 2 4 2 4 2
Trp 0 0 1 3 3 1 1 1
Ser 8 12 7 5 10 12 8 12
Thr 7 10 6 5 11 5 7 6
Cys 2 1 1 1 2 2 0 2
Asn 5 5 8 5 6 2 2 6
Gln 2 5 3 3 1 5 4 4
Asp 6 7 8 8 10 9 4 4
Glu 7 9 6 4 4 6 2 4
Lys 11 11 8 6 14 11 16 12
Arg 1 3 4 2 4 3 3 2
His 5 9 7 6 4 4 9 6