MCA3_TRYBB
ID MCA3_TRYBB Reviewed; 357 AA.
AC Q8T8E6;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=Metacaspase-3 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000269|PubMed:21949125};
DE AltName: Full=TbMCA3 {ECO:0000303|PubMed:12062425};
DE Contains:
DE RecName: Full=Large subunit p20 {ECO:0000305};
DE Contains:
DE RecName: Full=Small subunit p10 {ECO:0000305};
DE Flags: Precursor;
GN Name=MCA3 {ECO:0000303|PubMed:12062425};
OS Trypanosoma brucei brucei.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX NCBI_TaxID=5702;
RN [1] {ECO:0000312|EMBL:CAD24804.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12062425; DOI=10.1016/s0014-5793(02)02608-x;
RA Szallies A., Kubata B.K., Duszenko M.;
RT "A metacaspase of Trypanosoma brucei causes loss of respiration competence
RT and clonal death in the yeast Saccharomyces cerevisiae.";
RL FEBS Lett. 517:144-150(2002).
RN [2] {ECO:0000305}
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=EATRO 795 {ECO:0000269|PubMed:16507595};
RX PubMed=16507595; DOI=10.1242/jcs.02809;
RA Helms M.J., Ambit A., Appleton P., Tetley L., Coombs G.H., Mottram J.C.;
RT "Bloodstream form Trypanosoma brucei depend upon multiple metacaspases
RT associated with RAB11-positive endosomes.";
RL J. Cell Sci. 119:1105-1117(2006).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=21949125; DOI=10.1074/jbc.m111.292334;
RA Proto W.R., Castanys-Munoz E., Black A., Tetley L., Moss C.X., Juliano L.,
RA Coombs G.H., Mottram J.C.;
RT "Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence
RT factor.";
RL J. Biol. Chem. 286:39914-39925(2011).
CC -!- FUNCTION: Cysteine protease that cleaves specifically after arginine or
CC lysine residues (PubMed:21949125). In the bloodstream form, may cleave
CC inactive metacaspase-4 MCA4 prior to MCA4 secretion (PubMed:21949125).
CC {ECO:0000269|PubMed:21949125}.
CC -!- ACTIVITY REGULATION: Activated by Ca(2+).
CC {ECO:0000305|PubMed:21949125}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome {ECO:0000305|PubMed:16507595}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed in the mammalian blood
CC stage form (at protein level). {ECO:0000269|PubMed:16507595}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes no defect in the
CC growth of the bloodstream stage form (PubMed:16507595). Simultaneous
CC RNAi-mediated knockdown of MCA2, MCA3 and MCA5 in the bloodstream stage
CC form causes a growth arrest resulting from a block prior to
CC cytokinesis; DNA replication and mitosis are normal (PubMed:16507595).
CC Has no effect on VSG protein recycling (PubMed:16507595). Triple
CC knockout of MCA2, MCA3 and MCA5 in the bloodstream form causes an
CC initial slower growth rate in vitro which reaches wild-type levels
CC after several weeks of culture (PubMed:16507595). Triple knockouts have
CC a normal growth rate and virulence in infected mice (PubMed:16507595).
CC {ECO:0000269|PubMed:16507595}.
CC -!- SIMILARITY: Belongs to the peptidase C14B family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ437303; CAD24804.1; -; mRNA.
DR AlphaFoldDB; Q8T8E6; -.
DR SMR; Q8T8E6; -.
DR ChEMBL; CHEMBL1075156; -.
DR MEROPS; C14.044; -.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
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.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR SUPFAM; SSF52129; SSF52129; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Calcium; Endosome; Hydrolase; Metal-binding;
KW Protease; Thiol protease; Zymogen.
FT CHAIN 1..357
FT /note="Metacaspase-3"
FT /id="PRO_0000451282"
FT PROPEP 1..?
FT /evidence="ECO:0000305"
FT /id="PRO_0000451281"
FT CHAIN ?..278
FT /note="Large subunit p20"
FT /evidence="ECO:0000250|UniProtKB:Q8T8E7"
FT /id="PRO_0000451283"
FT CHAIN 279..357
FT /note="Small subunit p10"
FT /evidence="ECO:0000250|UniProtKB:Q8T8E7"
FT /id="PRO_0000451284"
FT ACT_SITE 168
FT /evidence="ECO:0000250|UniProtKB:Q08601"
FT ACT_SITE 223
FT /evidence="ECO:0000250|UniProtKB:Q8T8E7"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT SITE 22..23
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:21949125"
SQ SEQUENCE 357 AA; 38724 MW; C4C74A94F5A3E595 CRC64;
MAVDPRCLLS LCSTISKASS AKGTNDFVKI GMELWQTAQP YLVQALGLQP PPPKVDVDAA
VANAGDAHGE QPWVATPLPG QTVRALFIGI NYYGTSAALS GCCNDVKQML ATLQKKGLPI
NEAVILVDED NFPGRTDQPT RDNIVRYMAW LVKDAKPGDV LFFHYSGHGT QCKSRGDSDE
KYDQCIAPVD FQKSGCIVDD DIHKLLFSRL PEKVRLTAVF DCCHSGSIMD LPFTYVCSGG
EQASGTPHMK RIREGNDVLG DVMMISGCAD EQTSADVKNT ATFGTGSTGA GGAATQCITC
MLMNNQSLSY GKLLIETRDM LKRKRFKQVP QLSASKAIDL DQTFSLTEMF SVDRSVQ
