Papain-like cysteine endopeptidase (IPR039417)

Short name: Peptidase_C1A_papain-like

Overlapping homologous superfamilies

Domain relationships


This entry represents homologues of papain, from peptidase family C1 subfamily A, including the mammalian CPs (cathepsins F, H, L, K, O, S, V, X and W) [PMID: 11517925]. Cathepsins B and C, which differ in their activation peptides, are not included here [PMID: 11440158]. Papain is an endopeptidase with specific substrate preferences, primarily for bulky hydrophobic or aromatic residues at the S2 subsite, a hydrophobic pocket in papain that accommodates the P2 sidechain of the substrate (the second residue away from the scissile bond). Most members of the papain subfamily are endopeptidases. Some exceptions to this rule can be explained by specific details of the catalytic domains like the occluding loop in cathepsin B which confers an additional peptidyl-dipeptidase activity and the mini-chain of cathepsin H resulting in an N-terminal exopeptidase activity [PMID: 10350606].

Papain-like CPs have different functions in various organisms. Plant CPs are used to mobilize storage proteins in seeds. Parasitic CPs act extracellularly to help invade tissues and cells, to hatch or to evade the host immune system [PMID: 11322895]. Mammalian CPs are primarily lysosomal enzymes with the exception of cathepsin W, which is retained in the endoplasmic reticulum [PMID: 12554931]. They are responsible for protein degradation in the lysosome. Papain-like CPs are synthesized as inactive proenzymes with N-terminal propeptide regions, which are removed upon activation. In addition to its inhibitory role, the propeptide is required for proper folding of the newly synthesized enzyme and its stabilization in denaturing pH conditions. Residues within the propeptide region also play a role in the transport of the proenzyme to lysosomes or acidified vesicles [PMID: 14515150]. Also included in this entry are proteins classified as non-peptidase homologues, which lack peptidase activity because active site residues are missing.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.