CYSP_TRYCR
ID CYSP_TRYCR Reviewed; 467 AA.
AC P25779;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Cruzipain;
DE EC=3.4.22.51;
DE AltName: Full=Cruzaine;
DE AltName: Full=Major cysteine proteinase;
DE Flags: Precursor;
OS Trypanosoma cruzi.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=5693;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=Tulahuen;
RX PubMed=1559982; DOI=10.1016/s0021-9258(18)42533-1;
RA Eakin A.E., Mills A.A., Harth G., McKerrow J.H., Craik C.S.;
RT "The sequence, organization, and expression of the major cysteine protease
RT (cruzain) from Trypanosoma cruzi.";
RL J. Biol. Chem. 267:7411-7420(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CLONES 1800-2 AND 1800-4).
RC STRAIN=Tulahuen 2;
RX PubMed=1311053; DOI=10.1016/0166-6851(92)90219-a;
RA Campetella O., Henriksson J., Aaslund L., Frasch A.C.C., Pettersson U.,
RA Cazzulo J.J.;
RT "The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is
RT encoded by multiple polymorphic tandemly organized genes located on
RT different chromosomes.";
RL Mol. Biochem. Parasitol. 50:225-234(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 141-306.
RC STRAIN=RA;
RX PubMed=2406590; DOI=10.1016/0166-6851(90)90002-4;
RA Eakin A.E., Bouvier J., Sakanari J.A., Craik C.S., McKerrow J.H.;
RT "Amplification and sequencing of genomic DNA fragments encoding cysteine
RT proteases from protozoan parasites.";
RL Mol. Biochem. Parasitol. 39:1-8(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 295-467.
RC STRAIN=Tulahuen 2;
RX PubMed=2038364; DOI=10.1016/0166-6851(91)90103-d;
RA Aaslund L., Henriksson J., Campetella O., Frasch A.C.C., Pettersson U.,
RA Cazzulo J.J.;
RT "The C-terminal extension of the major cysteine proteinase (cruzipain) from
RT Trypanosoma cruzi.";
RL Mol. Biochem. Parasitol. 45:345-348(1991).
RN [5]
RP AUTOCATALYSIS OF C-TERMINAL.
RC STRAIN=Tulahuen 2;
RX PubMed=2011151; DOI=10.1016/0166-6851(91)90216-s;
RA Hellman U., Wernstedt C., Cazzulo J.J.;
RT "Self-proteolysis of the cysteine proteinase, cruzipain, from Trypanosoma
RT cruzi gives a major fragment corresponding to its carboxy-terminal
RT domain.";
RL Mol. Biochem. Parasitol. 44:15-21(1991).
RN [6]
RP SPECIFICITY.
RC STRAIN=Tulahuen 2;
RX PubMed=2407295; DOI=10.1016/0167-4838(90)90166-d;
RA Cazzulo J.J., Cazzulo-Franke M.C., Martinez J., Franke de Cazzulo B.M.;
RT "Some kinetic properties of a cysteine proteinase (cruzipain) from
RT Trypanosoma cruzi.";
RL Biochim. Biophys. Acta 1037:186-191(1990).
RN [7]
RP PROTEIN SEQUENCE OF 123-146 AND 304-317.
RX PubMed=2651912; DOI=10.1016/0166-6851(89)90039-x;
RA Cazzulo J.J., Couso R., Raimondi A., Wernstedt C., Hellman U.;
RT "Further characterization and partial amino acid sequence of a cysteine
RT proteinase from Trypanosoma cruzi.";
RL Mol. Biochem. Parasitol. 33:33-42(1989).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 123-337.
RX PubMed=9260273; DOI=10.1002/pro.5560060801;
RA Gillmor S.A., Craik C.S., Fletterick R.J.;
RT "Structural determinants of specificity in the cysteine protease cruzain.";
RL Protein Sci. 6:1603-1611(1997).
CC -!- FUNCTION: Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys;
CC requires at least one more amino acid, preferably Arg, Phe, Val or Leu,
CC between the terminal Arg or Lys and the amino-blocking group.
CC -!- FUNCTION: The cysteine protease may play an important role in the
CC development and differentiation of the parasites at several stages of
CC their life cycle.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity similar to that of cathepsin
CC L.; EC=3.4.22.51;
CC -!- ACTIVITY REGULATION: Strongly inhibited by E-64 (L-trans-
CC epoxysuccinylleucylamido(4-guanidino)butane), Leupeptin, and N-alpha-p-
CC tosyl-L-lysine chloromethyl ketone.
CC -!- DEVELOPMENTAL STAGE: Present in all developmental stages.
CC -!- MISCELLANEOUS: Purified cruzipain is able to degrade itself, yielding a
CC complex mixture of small peptides, and a major 25 kDa fragment.
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; M84342; AAA30181.1; -; Genomic_DNA.
DR EMBL; M69121; AAA30269.1; -; Genomic_DNA.
DR EMBL; M69121; AAA30270.1; -; Genomic_DNA.
DR EMBL; X54414; CAA38278.1; -; mRNA.
DR EMBL; M27305; AAA30180.1; -; Genomic_DNA.
DR PIR; A60667; A60667.
DR PIR; S16162; S16162.
DR PDB; 1AIM; X-ray; 2.00 A; A=123-337.
DR PDB; 1EWL; X-ray; 2.00 A; A=123-337.
DR PDB; 1EWM; X-ray; 2.00 A; A=123-337.
DR PDB; 1EWO; X-ray; 2.10 A; A=123-337.
DR PDB; 1EWP; X-ray; 1.75 A; A=123-337.
DR PDB; 1F29; X-ray; 2.15 A; A/B/C=123-337.
DR PDB; 1F2A; X-ray; 1.60 A; A=123-337.
DR PDB; 1F2B; X-ray; 1.80 A; A=123-337.
DR PDB; 1F2C; X-ray; 2.00 A; A=123-337.
DR PDB; 1ME3; X-ray; 1.20 A; A=123-337.
DR PDB; 1ME4; X-ray; 1.20 A; A=123-337.
DR PDB; 1U9Q; X-ray; 2.30 A; X=123-337.
DR PDB; 2AIM; X-ray; 2.20 A; A=123-337.
DR PDB; 2OZ2; X-ray; 1.95 A; A/C=123-337.
DR PDB; 3HD3; X-ray; 1.75 A; A/B=123-337.
DR PDB; 3I06; X-ray; 1.10 A; A=123-337.
DR PDB; 3IUT; X-ray; 1.20 A; A=123-337.
DR PDB; 3KKU; X-ray; 1.28 A; A=123-337.
DR PDB; 3LXS; X-ray; 1.50 A; A/C=123-337.
DR PDB; 4KLB; X-ray; 2.62 A; A/B/C/D/E=123-337.
DR PDB; 4PI3; X-ray; 1.27 A; A/B=122-337.
DR PDB; 4QH6; X-ray; 3.13 A; A/B/C/D/E=123-337.
DR PDB; 4W5B; X-ray; 2.70 A; A/B/C=123-337.
DR PDB; 4W5C; X-ray; 3.27 A; A/B/C/D/E=122-337.
DR PDB; 4XUI; X-ray; 2.51 A; A/B/C=122-337.
DR PDB; 6N3S; X-ray; 1.19 A; A/B=123-337.
DR PDB; 6O2X; X-ray; 1.19 A; A/B=123-337.
DR PDB; 6UX6; X-ray; 1.94 A; A=123-337.
DR PDB; 7JUJ; X-ray; 2.20 A; A/B/C/D/E/F=123-337.
DR PDB; 7S18; X-ray; 2.14 A; A=123-337.
DR PDB; 7S19; X-ray; 2.08 A; A=123-337.
DR PDBsum; 1AIM; -.
DR PDBsum; 1EWL; -.
DR PDBsum; 1EWM; -.
DR PDBsum; 1EWO; -.
DR PDBsum; 1EWP; -.
DR PDBsum; 1F29; -.
DR PDBsum; 1F2A; -.
DR PDBsum; 1F2B; -.
DR PDBsum; 1F2C; -.
DR PDBsum; 1ME3; -.
DR PDBsum; 1ME4; -.
DR PDBsum; 1U9Q; -.
DR PDBsum; 2AIM; -.
DR PDBsum; 2OZ2; -.
DR PDBsum; 3HD3; -.
DR PDBsum; 3I06; -.
DR PDBsum; 3IUT; -.
DR PDBsum; 3KKU; -.
DR PDBsum; 3LXS; -.
DR PDBsum; 4KLB; -.
DR PDBsum; 4PI3; -.
DR PDBsum; 4QH6; -.
DR PDBsum; 4W5B; -.
DR PDBsum; 4W5C; -.
DR PDBsum; 4XUI; -.
DR PDBsum; 6N3S; -.
DR PDBsum; 6O2X; -.
DR PDBsum; 6UX6; -.
DR PDBsum; 7JUJ; -.
DR PDBsum; 7S18; -.
DR PDBsum; 7S19; -.
DR AlphaFoldDB; P25779; -.
DR BMRB; P25779; -.
DR SMR; P25779; -.
DR BindingDB; P25779; -.
DR ChEMBL; CHEMBL3563; -.
DR DrugBank; DB02200; 3-[N-[benzyloxycarbonyl]-phenylalaninyl-amino]-5-phenyl-pentane-1-sulfonylmethylbenzene.
DR DrugBank; DB04427; 4-Methyl-N-[(2S)-1-oxo-3-phenyl-1-[[(3S)-1-phenyl-5-(phenylmethoxysulfamoyl)pentan-3-yl]amino]propan-2-yl]piperazine-1-carboxamide.
DR DrugBank; DB02051; 4-Nitrophenyl (3S)-3-({N-[(benzyloxy)carbonyl]-L-phenylalanyl}amino)-5-phenyl-1-pentanesulfonate.
DR DrugBank; DB01871; [1-(1-Benzyl-3-Hydroxy-2-Oxo-Propylcarbamoyl)-2-Phenyl-Ethyl]-Carbamic Acid Benzyl Ester.
DR DrugBank; DB01810; [1-(1-Methyl-4,5-Dioxo-Pent-2-Enylcarbamoyl)-2-Phenyl-Ethyl]-Carbamic Acid Benzyl Ester.
DR DrugBank; DB02128; [1-(3-hydroxy-2-oxo-1-phenethyl-propylcarbamoyl)2-phenyl-ethyl]-carbamic acid pyridin-4-ylmethyl ester.
DR DrugBank; DB03536; Benzyl N-[(2S)-5-(diaminomethylamino)-1-[[(2S)-4-fluoro-3-oxobutan-2-yl]amino]-1-oxopentan-2-yl]carbamate.
DR DrugBank; DB03691; WRR-112.
DR DrugBank; DB04502; WRR-204.
DR DrugBank; DB03573; WRR-99.
DR DrugCentral; P25779; -.
DR MEROPS; C01.075; -.
DR VEuPathDB; TriTrypDB:BCY84_22436; -.
DR VEuPathDB; TriTrypDB:C3747_50g3; -.
DR VEuPathDB; TriTrypDB:C3747_50g6; -.
DR VEuPathDB; TriTrypDB:C3747_50g7; -.
DR VEuPathDB; TriTrypDB:C4B63_89g68; -.
DR VEuPathDB; TriTrypDB:Tc_MARK_8050; -.
DR VEuPathDB; TriTrypDB:Tc_MARK_8695; -.
DR VEuPathDB; TriTrypDB:TcBrA4_0068180; -.
DR VEuPathDB; TriTrypDB:TcCL_NonESM02572; -.
DR VEuPathDB; TriTrypDB:TcCLB.507603.260; -.
DR VEuPathDB; TriTrypDB:TcCLB.509429.320; -.
DR VEuPathDB; TriTrypDB:TCDM_05847; -.
DR VEuPathDB; TriTrypDB:TcG_06121; -.
DR VEuPathDB; TriTrypDB:TCSYLVIO_008967; -.
DR VEuPathDB; TriTrypDB:TcYC6_0061420; -.
DR VEuPathDB; TriTrypDB:TcYC6_0061430; -.
DR VEuPathDB; TriTrypDB:TcYC6_0061460; -.
DR VEuPathDB; TriTrypDB:TcYC6_0061470; -.
DR BRENDA; 3.4.22.51; 6524.
DR SABIO-RK; P25779; -.
DR EvolutionaryTrace; P25779; -.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR021981; DUF3586.
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; PF12131; DUF3586; 1.
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 3D-structure; Autocatalytic cleavage; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Protease; Signal; Thiol protease;
KW Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000305"
FT PROPEP 19..122
FT /note="Activation peptide"
FT /evidence="ECO:0000305|PubMed:2651912"
FT /id="PRO_0000026372"
FT CHAIN 123..467
FT /note="Cruzipain"
FT /id="PRO_0000026373"
FT REGION 333..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 147
FT ACT_SITE 284
FT ACT_SITE 304
FT SITE 337..338
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:1559982"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 377
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 144..185
FT DISULFID 178..223
FT DISULFID 277..325
FT VARIANT 9
FT /note="L -> S (in clone 1800-2)"
FT VARIANT 35
FT /note="T -> A (in clone 1800-2)"
FT VARIANT 39
FT /note="A -> V (in clone 1800-2)"
FT VARIANT 51
FT /note="S -> N (in clone 1800-4)"
FT VARIANT 56
FT /note="A -> R (in clone 1800-2)"
FT VARIANT 76
FT /note="N -> G (in clone 1800-4)"
FT VARIANT 109
FT /note="Q -> G (in clone 1800-4)"
FT VARIANT 117
FT /note="K -> N (in clone 1800-2)"
FT VARIANT 146
FT /note="S -> G"
FT VARIANT 157..158
FT /note="EC -> SG (in strain: RA)"
FT VARIANT 186
FT /note="S -> G (in clones 1800-2 and 1800-4)"
FT VARIANT 204
FT /note="A -> G (in strain: RA)"
FT VARIANT 250..251
FT /note="WL -> CV (in clones 1800-2 and 1800-4)"
FT VARIANT 261..262
FT /note="VD -> H (in strain: RA)"
FT VARIANT 286
FT /note="V -> F (in clone 1800-4)"
FT VARIANT 286
FT /note="V -> L (in strain: RA)"
FT VARIANT 308
FT /note="T -> A (in clone 1800-2)"
FT VARIANT 313
FT /note="E -> D"
FT VARIANT 409
FT /note="L -> F (in clone 1800-2)"
FT VARIANT 427
FT /note="K -> Q (in clone 1800-2)"
FT VARIANT 430
FT /note="R -> W (in clone 1800-2)"
FT VARIANT 457
FT /note="H -> Y (in clone 1800-2)"
FT VARIANT 461
FT /note="H -> Q (in clone 1800-2)"
FT CONFLICT 357
FT /note="S -> C (in Ref. 4)"
FT /evidence="ECO:0000305"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 129..132
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:6UX6"
FT HELIX 147..162
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 172..178
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 190..200
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 204..207
FT /evidence="ECO:0007829|PDB:3I06"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:2AIM"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:1F2A"
FT STRAND 230..239
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 244..254
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:4QH6"
FT HELIX 266..268
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 271..274
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 284..297
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:3I06"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:7JUJ"
FT STRAND 315..322
FT /evidence="ECO:0007829|PDB:3I06"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:3I06"
FT STRAND 329..336
FT /evidence="ECO:0007829|PDB:3I06"
SQ SEQUENCE 467 AA; 49836 MW; B93EBA49B511363D CRC64;
MSGWARALLL AAVLVVMACL VPAATASLHA EETLTSQFAE FKQKHGRVYE SAAEEAFRLS
VFRENLFLAR LHAAANPHAT FGVTPFSDLT REEFRSRYHN GAAHFAAAQE RARVPVKVEV
VGAPAAVDWR ARGAVTAVKD QGQCGSCWAF SAIGNVECQW FLAGHPLTNL SEQMLVSCDK
TDSGCSGGLM NNAFEWIVQE NNGAVYTEDS YPYASGEGIS PPCTTSGHTV GATITGHVEL
PQDEAQIAAW LAVNGPVAVA VDASSWMTYT GGVMTSCVSE QLDHGVLLVG YNDSAAVPYW
IIKNSWTTQW GEEGYIRIAK GSNQCLVKEE ASSAVVGGPG PTPEPTTTTT TSAPGPSPSY
FVQMSCTDAA CIVGCENVTL PTGQCLLTTS GVSAIVTCGA ETLTEEVFLT STHCSGPSVR
SSVPLNKCNR LLRGSVEFFC GSSSSGRLAD VDRQRRHQPY HSRHRRL
