ID   MCA3_TRYCC              Reviewed;         358 AA.
AC   Q2VLK6;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   10-JAN-2006, sequence version 1.
DT   25-MAY-2022, entry version 37.
DE   RecName: Full=Metacaspase-3 {ECO:0000303|PubMed:16213036};
DE            EC=3.4.22.- {ECO:0000269|PubMed:22402587};
DE   AltName: Full=TcMCA3 {ECO:0000303|PubMed:16213036};
GN   Name=MCA3 {ECO:0000303|PubMed:16213036};
OS   Trypanosoma cruzi (strain CL Brener).
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX   NCBI_TaxID=353153;
RN   [1] {ECO:0000312|EMBL:AAY84581.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], DEVELOPMENTAL STAGE, AND SUBCELLULAR
RP   LOCATION.
RC   STRAIN=CL Brener {ECO:0000312|EMBL:AAY84581.1};
RX   PubMed=16213036; DOI=10.1016/j.molbiopara.2005.09.001;
RA   Kosec G., Alvarez V.E., Aguero F., Sanchez D., Dolinar M., Turk B.,
RA   Turk V., Cazzulo J.J.;
RT   "Metacaspases of Trypanosoma cruzi: possible candidates for programmed cell
RT   death mediators.";
RL   Mol. Biochem. Parasitol. 145:18-28(2006).
RN   [2] {ECO:0000305}
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP   DEVELOPMENTAL STAGE, LACK OF PROTEOLYTIC CLEAVAGE, ACTIVE SITE, AND
RP   MUTAGENESIS OF HIS-168 AND CYS-223.
RX   PubMed=22402587; DOI=10.1038/cdd.2012.12;
RA   Laverriere M., Cazzulo J.J., Alvarez V.E.;
RT   "Antagonic activities of Trypanosoma cruzi metacaspases affect the balance
RT   between cell proliferation, death and differentiation.";
RL   Cell Death Differ. 19:1358-1369(2012).
CC   -!- FUNCTION: Cysteine protease that cleaves specifically after arginine or
CC       lysine residues (PubMed:22402587). In epimastigotes, may play a role in
CC       cell cycle G1/S transition (PubMed:22402587).
CC       {ECO:0000269|PubMed:22402587}.
CC   -!- ACTIVITY REGULATION: Activated by Ca(2+).
CC       {ECO:0000269|PubMed:22402587}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16213036,
CC       ECO:0000269|PubMed:22402587}. Nucleus {ECO:0000269|PubMed:16213036}.
CC       Note=Localizes to cytoplasm in epimastigotes (PubMed:16213036).
CC       Translocates to the nucleus following apoptosis induced by human serum
CC       (PubMed:16213036). {ECO:0000269|PubMed:16213036}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in epimastigotes, amastigotes and cell
CC       derived trypomastigotes and in metacyclic trypomastigotes (at protein
CC       level). {ECO:0000269|PubMed:16213036, ECO:0000269|PubMed:22402587}.
CC   -!- PTM: In epimastigotes, the unprocessed enzyme appears to be the main
CC       form (PubMed:22402587). Auto-processing is dispensable for catalytic
CC       activity towards small oligopeptide substrates (PubMed:22402587).
CC       {ECO:0000269|PubMed:22402587}.
CC   -!- SIMILARITY: Belongs to the peptidase C14B family. {ECO:0000305}.
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DR   EMBL; DQ015870; AAY84581.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q2VLK6; -.
DR   SMR; Q2VLK6; -.
DR   MEROPS; C14.044; -.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
PE   1: Evidence at protein level;
KW   Calcium; Cytoplasm; Hydrolase; Metal-binding; Nucleus; Protease;
KW   Thiol protease.
FT   CHAIN           1..358
FT                   /note="Metacaspase-3"
FT                   /id="PRO_0000451285"
FT   REGION          1..84
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000269|PubMed:22402587"
FT   ACT_SITE        168
FT                   /evidence="ECO:0000305|PubMed:22402587"
FT   ACT_SITE        223
FT                   /evidence="ECO:0000305|PubMed:22402587"
FT   MUTAGEN         168
FT                   /note="H->A: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:22402587"
FT   MUTAGEN         223
FT                   /note="C->A: Loss of catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:22402587"
SQ   SEQUENCE   358 AA;  39032 MW;  945DE42C68E63B0B CRC64;
     MGFDFGCLLK LCSTVLKPGG APGPINYMEI GLNLIKIAAP YIVQYLGIME RPPRVDVEEF
     FQQAEVTEGF KPWEAPTHVS GTFRALFIGI NYYCTSAELS GCCNDVKQII ATLQRKRIPI
     DEMSILVDER GFPGANGLPT RDNIVRYMAW LFGGAKPGDV LFMHYSGHGT HTRATSDTEE
     KFDQCLAPVD FSTKGCILDN DIFRILLSGL LQGVRLTVVF DCCHSGSMLD LPYTFVGSRS
     LRRSVAGHMQ RIRKGNDCAG DVLMISGCAD EQTSADVSNA ATFGTGASGA GGAATQCLAY
     TILKVSNLSY QDMLIATRDM LRRKGFTQVP QLSASKPINL QQKFSLMTTF EVDPAVAT