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P25779 (CYSP_TRYCR) Reviewed, UniProtKB/Swiss-Prot

Last modified January 22, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cruzipain

EC=3.4.22.51
Alternative name(s):
Cruzaine
Major cysteine proteinase
OrganismTrypanosoma cruzi
Taxonomic identifier5693 [NCBI]
Taxonomic lineageEukaryotaEuglenozoaKinetoplastidaTrypanosomatidaeTrypanosomaSchizotrypanum

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group.

The cysteine protease may play an important role in the development and differentiation of the parasites at several stages of their life cycle.

Catalytic activity

Broad endopeptidase specificity similar to that of cathepsin L.

Enzyme regulation

Strongly inhibited by E-64 (L-trans-epoxysuccinylleucylamido(4-guanidino)butane), Leupeptin, and N-alpha-p-tosyl-L-lysine chloromethyl ketone.

Developmental stage

Present in all developmental stages.

Miscellaneous

Purified cruzipain is able to degrade itself, yielding a complex mixture of small peptides, and a major 25 kDa fragment.

Sequence similarities

Belongs to the peptidase C1 family.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Probable
Propeptide19 – 122104Activation peptide Probable
PRO_0000026372
Chain123 – 467345Cruzipain
PRO_0000026373

Sites

Active site1471
Active site2841
Active site3041
Site337 – 3382Cleavage; by autolysis Ref.1

Amino acid modifications

Glycosylation1691N-linked (GlcNAc...) Potential
Glycosylation2921N-linked (GlcNAc...) Potential
Glycosylation3771N-linked (GlcNAc...) Potential
Disulfide bond144 ↔ 185
Disulfide bond178 ↔ 223
Disulfide bond277 ↔ 325

Natural variations

Natural variant91L → S in clone 1800-2.
Natural variant351T → A in clone 1800-2.
Natural variant391A → V in clone 1800-2.
Natural variant511S → N in clone 1800-4.
Natural variant561A → R in clone 1800-2.
Natural variant761N → G in clone 1800-4.
Natural variant1091Q → G in clone 1800-4.
Natural variant1171K → N in clone 1800-2.
Natural variant1461S → G.
Natural variant157 – 1582EC → SG in strain: RA.
Natural variant1861S → G in clones 1800-2 and 1800-4.
Natural variant2041A → G in strain: RA.
Natural variant250 – 2512WL → CV in clones 1800-2 and 1800-4.
Natural variant261 – 2622VD → H in strain: RA.
Natural variant2861V → F in clone 1800-4.
Natural variant2861V → L in strain: RA.
Natural variant3081T → A in clone 1800-2.
Natural variant3131E → D.
Natural variant4091L → F in clone 1800-2.
Natural variant4271K → Q in clone 1800-2.
Natural variant4301R → W in clone 1800-2.
Natural variant4571H → Y in clone 1800-2.
Natural variant4611H → Q in clone 1800-2.

Experimental info

Sequence conflict3571S → C Ref.4

Secondary structure

............................................. 467
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P25779 [UniParc].

Last modified May 1, 1992. Version 1.
Checksum: B93EBA49B511363D

FASTA46749,836
        10         20         30         40         50         60 
MSGWARALLL AAVLVVMACL VPAATASLHA EETLTSQFAE FKQKHGRVYE SAAEEAFRLS 

        70         80         90        100        110        120 
VFRENLFLAR LHAAANPHAT FGVTPFSDLT REEFRSRYHN GAAHFAAAQE RARVPVKVEV 

       130        140        150        160        170        180 
VGAPAAVDWR ARGAVTAVKD QGQCGSCWAF SAIGNVECQW FLAGHPLTNL SEQMLVSCDK 

       190        200        210        220        230        240 
TDSGCSGGLM NNAFEWIVQE NNGAVYTEDS YPYASGEGIS PPCTTSGHTV GATITGHVEL 

       250        260        270        280        290        300 
PQDEAQIAAW LAVNGPVAVA VDASSWMTYT GGVMTSCVSE QLDHGVLLVG YNDSAAVPYW 

       310        320        330        340        350        360 
IIKNSWTTQW GEEGYIRIAK GSNQCLVKEE ASSAVVGGPG PTPEPTTTTT TSAPGPSPSY 

       370        380        390        400        410        420 
FVQMSCTDAA CIVGCENVTL PTGQCLLTTS GVSAIVTCGA ETLTEEVFLT STHCSGPSVR 

       430        440        450        460 
SSVPLNKCNR LLRGSVEFFC GSSSSGRLAD VDRQRRHQPY HSRHRRL 

« Hide

References

[1]"The sequence, organization, and expression of the major cysteine protease (cruzain) from Trypanosoma cruzi."
Eakin A.E., Mills A.A., Harth G., McKerrow J.H., Craik C.S.
J. Biol. Chem. 267:7411-7420(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE.
Strain: Tulahuen.
[2]"The major cysteine proteinase (cruzipain) from Trypanosoma cruzi is encoded by multiple polymorphic tandemly organized genes located on different chromosomes."
Campetella O., Henriksson J., Aaslund L., Frasch A.C.C., Pettersson U., Cazzulo J.J.
Mol. Biochem. Parasitol. 50:225-234(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (CLONES 1800-2 AND 1800-4).
Strain: Tulahuen 2.
[3]"Amplification and sequencing of genomic DNA fragments encoding cysteine proteases from protozoan parasites."
Eakin A.E., Bouvier J., Sakanari J.A., Craik C.S., McKerrow J.H.
Mol. Biochem. Parasitol. 39:1-8(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 141-306.
Strain: RA.
[4]"The C-terminal extension of the major cysteine proteinase (cruzipain) from Trypanosoma cruzi."
Aaslund L., Henriksson J., Campetella O., Frasch A.C.C., Pettersson U., Cazzulo J.J.
Mol. Biochem. Parasitol. 45:345-348(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 295-467.
Strain: Tulahuen 2.
[5]"Self-proteolysis of the cysteine proteinase, cruzipain, from Trypanosoma cruzi gives a major fragment corresponding to its carboxy-terminal domain."
Hellman U., Wernstedt C., Cazzulo J.J.
Mol. Biochem. Parasitol. 44:15-21(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOCATALYSIS OF C-TERMINAL.
Strain: Tulahuen 2.
[6]"Some kinetic properties of a cysteine proteinase (cruzipain) from Trypanosoma cruzi."
Cazzulo J.J., Cazzulo-Franke M.C., Martinez J., Franke de Cazzulo B.M.
Biochim. Biophys. Acta 1037:186-191(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: SPECIFICITY.
Strain: Tulahuen 2.
[7]"Further characterization and partial amino acid sequence of a cysteine proteinase from Trypanosoma cruzi."
Cazzulo J.J., Couso R., Raimondi A., Wernstedt C., Hellman U.
Mol. Biochem. Parasitol. 33:33-42(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 123-146 AND 304-317.
[8]"Structural determinants of specificity in the cysteine protease cruzain."
Gillmor S.A., Craik C.S., Fletterick R.J.
Protein Sci. 6:1603-1611(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 123-337.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M84342 Genomic DNA. Translation: AAA30181.1.
M69121 Genomic DNA. Translation: AAA30269.1.
M69121 Genomic DNA. Translation: AAA30270.1.
X54414 mRNA. Translation: CAA38278.1.
M27305 Genomic DNA. Translation: AAA30180.1.
PIRA60667.
S16162.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AIMX-ray2.00A123-337[»]
1EWLX-ray2.00A123-337[»]
1EWMX-ray2.00A123-337[»]
1EWOX-ray2.10A123-337[»]
1EWPX-ray1.75A123-337[»]
1F29X-ray2.15A/B/C123-337[»]
1F2AX-ray1.60A123-337[»]
1F2BX-ray1.80A123-337[»]
1F2CX-ray2.00A123-337[»]
1ME3X-ray1.20A123-337[»]
1ME4X-ray1.20A123-337[»]
1U9QX-ray2.30X123-337[»]
2AIMX-ray2.20A123-337[»]
2OZ2X-ray1.95A/C123-337[»]
3HD3X-ray1.75A/B123-337[»]
3I06X-ray1.10A123-337[»]
3IUTX-ray1.20A123-337[»]
3KKUX-ray1.28A123-337[»]
3LXSX-ray1.50A/C123-337[»]
4KLBX-ray2.62A/B/C/D/E123-337[»]
ProteinModelPortalP25779.
SMRP25779. Positions 123-337.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP25779.
ChEMBLCHEMBL3563.

Protein family/group databases

MEROPSC01.075.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

SABIO-RKP25779.

Family and domain databases

InterProIPR021981. DUF3586.
IPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR013201. Prot_inhib_I29.
[Graphical view]
PANTHERPTHR12411. PTHR12411. 1 hit.
PfamPF12131. DUF3586. 1 hit.
PF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]
PRINTSPR00705. PAPAIN.
SMARTSM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]
PROSITEPS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP25779.

Entry information

Entry nameCYSP_TRYCR
AccessionPrimary (citable) accession number: P25779
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: January 22, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references