CPP2_ENTHI
ID CPP2_ENTHI Reviewed; 315 AA.
AC Q01958; C4M434;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Histolysain;
DE EC=3.4.22.35;
DE AltName: Full=Cysteine proteinase 2;
DE AltName: Full=Histolysin;
DE Flags: Precursor;
GN Name=CPP2; ORFNames=EHI_033710;
OS Entamoeba histolytica.
OC Eukaryota; Amoebozoa; Evosea; Archamoebae; Mastigamoebida; Entamoebidae;
OC Entamoeba.
OX NCBI_TaxID=5759;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=ATCC 30459 / HM-1:IMSS;
RX PubMed=1518524; DOI=10.1016/0166-6851(92)90101-o;
RA Tannich E., Nickel R., Buss H., Horstmann R.D.;
RT "Mapping and partial sequencing of the genes coding for two different
RT cysteine proteinases in pathogenic Entamoeba histolytica.";
RL Mol. Biochem. Parasitol. 54:109-111(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 30459 / HM-1:IMSS;
RX PubMed=15729342; DOI=10.1038/nature03291;
RA Loftus B.J., Anderson I., Davies R., Alsmark U.C., Samuelson J., Amedeo P.,
RA Roncaglia P., Berriman M., Hirt R.P., Mann B.J., Nozaki T., Suh B., Pop M.,
RA Duchene M., Ackers J., Tannich E., Leippe M., Hofer M., Bruchhaus I.,
RA Willhoeft U., Bhattacharya A., Chillingworth T., Churcher C.M., Hance Z.,
RA Harris B., Harris D., Jagels K., Moule S., Mungall K.L., Ormond D.,
RA Squares R., Whitehead S., Quail M.A., Rabbinowitsch E., Norbertczak H.,
RA Price C., Wang Z., Guillen N., Gilchrist C., Stroup S.E., Bhattacharya S.,
RA Lohia A., Foster P.G., Sicheritz-Ponten T., Weber C., Singh U.,
RA Mukherjee C., El-Sayed N.M.A., Petri W.A., Clark C.G., Embley T.M.,
RA Barrell B.G., Fraser C.M., Hall N.;
RT "The genome of the protist parasite Entamoeba histolytica.";
RL Nature 433:865-868(2005).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 30459 / HM-1:IMSS;
RA Lorenzi H., Amedeo P., Inman J., Schobel S., Caler E.;
RL Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 30459 / HM-1:IMSS;
RX PubMed=2898937; DOI=10.1042/bj2500903;
RA Luaces A.L., Barrett A.J.;
RT "Affinity purification and biochemical characterization of histolysin, the
RT major cysteine proteinase of Entamoeba histolytica.";
RL Biochem. J. 250:903-909(1988).
CC -!- FUNCTION: Involved in the destruction of human tissue by E.histolytica.
CC Can abolish adhesion and degrade matrix proteins such as collagen,
CC laminin and fibronectin. May play an important role in pathogenicity.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins, including basement membrane collagen
CC and azocasein. Preferential cleavage: Arg-Arg-|-Xaa in small molecule
CC substrates including Z-Arg-Arg-|-NHMec.; EC=3.4.22.35;
CC Evidence={ECO:0000269|PubMed:2898937};
CC -!- ACTIVITY REGULATION: Inhibited by leupeptin and such inhibitors of
CC cysteine proteinases as L-transepoxysuccinyl-L-leucylamido-(4-
CC guanidino)butane, peptidyldiazomethanes, iodoacetic acid and chicken
CC cystatin. {ECO:0000269|PubMed:2898937}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.5 uM for Z-Arg-Arg-NHMec {ECO:0000269|PubMed:2898937};
CC KM=31.8 uM for Z-Phe-Arg-NHMec {ECO:0000269|PubMed:2898937};
CC Note=kcat is 130 sec(-1) with Z-Arg-Arg-NHMec as substrate and 0.4
CC sec(-1) with Z-Phe-Arg-NHMec as substrate.;
CC pH dependence:
CC Optimum pH is 5.5 with azocasein as substrate, 7 with Z-Phe-Cit-
CC NHMec, and 9.5 with Z-Phe-Arg-NHMec and Z-Arg-Arg-NHMec as substrate.
CC {ECO:0000269|PubMed:2898937};
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC ECO:0000255|PROSITE-ProRule:PRU10090}.
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DR EMBL; M94163; AAA29091.1; -; Genomic_DNA.
DR EMBL; DS571252; EAL45256.1; -; Genomic_DNA.
DR RefSeq; XP_650642.1; XM_645550.2.
DR AlphaFoldDB; Q01958; -.
DR SMR; Q01958; -.
DR STRING; 5759.rna_EHI_033710-1; -.
DR MEROPS; C01.050; -.
DR EnsemblProtists; rna_EHI_033710-1; rna_EHI_033710-1; EHI_033710.
DR GeneID; 3404954; -.
DR KEGG; ehi:EHI_033710; -.
DR VEuPathDB; AmoebaDB:EHI5A_081530; -.
DR VEuPathDB; AmoebaDB:EHI7A_106950; -.
DR VEuPathDB; AmoebaDB:EHI8A_050360; -.
DR VEuPathDB; AmoebaDB:EHI_033710; -.
DR VEuPathDB; AmoebaDB:KM1_098010; -.
DR eggNOG; KOG1543; Eukaryota.
DR InParanoid; Q01958; -.
DR OMA; DGHCGTD; -.
DR BRENDA; 3.4.22.35; 2080.
DR Proteomes; UP000001926; Partially assembled WGS sequence.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR Pfam; PF08246; Inhibitor_I29; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00848; Inhibitor_I29; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Protease;
KW Reference proteome; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..13
FT /evidence="ECO:0000255"
FT PROPEP 14..93
FT /note="Activation peptide"
FT /id="PRO_0000026178"
FT CHAIN 94..315
FT /note="Histolysain"
FT /id="PRO_0000026179"
FT ACT_SITE 118
FT /evidence="ECO:0000250"
FT ACT_SITE 259
FT /evidence="ECO:0000250"
FT ACT_SITE 279
FT /evidence="ECO:0000250"
FT DISULFID 115..161
FT /evidence="ECO:0000250"
FT DISULFID 152..193
FT /evidence="ECO:0000250"
SQ SEQUENCE 315 AA; 34688 MW; E108F008DF6B822E CRC64;
MFAFICLLAI ASAIDFNTWA SKNNKHFTAI EKLRRRAIFN MNAKFVDSFN KIGSFKLSVD
GPFAAMTNEE YRTLLKSKRT TEENGQVKYL NIQAPESVDW RKEGKVTPIR DQAQCGSCYT
FGSLAALEGR LLIEKGGDAN TLDLSEEHMV QCTRDNGNNG CNGGLGSNVY DYIIEHGVAK
ESDYPYTGSD STCKTNVKSF AKITGYTKVP RNNEAELKAA LSQGLVDVSI DASSAKFQLY
KSGAYTDTKC KNNYFALNHE VCAVGYGVVD GKECWIVRNS WGTGWGDKGY INMVIEGNTC
GVATDPLYPT GVQYL
