MCA2_TRYBB
ID MCA2_TRYBB Reviewed; 347 AA.
AC Q8T8E7;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Metacaspase-2 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q585F3};
DE AltName: Full=TbMCA2 {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=MCA2 {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:CAD24803.1}
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, LACK OF PROTEOLYTIC CLEAVAGE,
RP 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).
CC -!- FUNCTION: Cysteine protease that cleaves specifically after arginine or
CC lysine residues. {ECO:0000250|UniProtKB:Q585F3}.
CC -!- ACTIVITY REGULATION: Activated by Ca(2+). In response to calcium
CC binding, the 280-loop, the 280-loop, a disordered loop consisting of
CC residues 269-275, undergoes a conformational change which stabilizes
CC substrates in the active site. The binding to the substrate triggers
CC the release of the N-terminal region resulting in the activation of the
CC enzyme. Proteolytic cleavage is required for catalytic activity towards
CC large protein substrates. {ECO:0000250|UniProtKB:Q585F3}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q585F3}.
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 -!- DOMAIN: There are 2 calcium binding sites with high and low affinity,
CC respectively. {ECO:0000250|UniProtKB:Q585F3}.
CC -!- PTM: Auto-proteolytic cleavage of the propeptide after Lys-55 and
CC between the large and small subunits after Lys-268 is required for
CC catalytic activity towards large protein substrates but is dispensable
CC towards small oligopeptide substrates. After processing, the propeptide
CC and the large and small subunits remain associated by non-covalent
CC bonds (By similarity). In vivo, the unprocessed enzyme appears to be
CC the predominant form (PubMed:16507595). {ECO:0000250|UniProtKB:Q585F3,
CC 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 -!- CAUTION: Unlike in strain 927/4 GUTat10.1, there is a Glu instead of a
CC Lys residue at position 55. Lys-55 is predicted to be conserved between
CC strains as the enzyme undergoes auto-processing at this site. It is not
CC clear if the presence of a Glu residue is due to a sequencing error.
CC {ECO:0000305}.
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DR EMBL; AJ437302; CAD24803.1; -; mRNA.
DR AlphaFoldDB; Q8T8E7; -.
DR SMR; Q8T8E7; -.
DR BindingDB; Q8T8E7; -.
DR ChEMBL; CHEMBL1075193; -.
DR MEROPS; C14.044; -.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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 PROPEP 1..?
FT /evidence="ECO:0000305"
FT /id="PRO_0000451277"
FT CHAIN ?..268
FT /note="Large subunit p20"
FT /evidence="ECO:0000305"
FT /id="PRO_0000451279"
FT CHAIN 269..347
FT /note="Small subunit p10"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT /id="PRO_0000451280"
FT CHAIN ?..347
FT /note="Metacaspase-2"
FT /id="PRO_0000451278"
FT REGION 1..70
FT /note="Regulates substrate access to the active site"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT ACT_SITE 158
FT /evidence="ECO:0000250|UniProtKB:Q08601"
FT ACT_SITE 213
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 189
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 190
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 220
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT SITE 95
FT /note="Important for Arg/Lys-specific substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT SITE 211
FT /note="Important for Arg/Lys-specific substrate
FT specificity"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT SITE 268
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
SQ SEQUENCE 347 AA; 37794 MW; E84004806DE914B0 CRC64;
MCSLITQLCD AGQLADYVGL GWLNAVSSQP YLVQALGLQP PPRRVDVDAA FRDAEGLHGH
QPWVATPLPG RTVRALFIGI NYYGTSAALS GCCNDVKQML ATLQKKGLPI NEAVILVDED
NFPGRTDQPT RDNIVRYMAW LVKDAKPGDV LFFHYSGHGT QCKSRGDSDE KYDQCIAPVD
FQKSGCIVDD DIHKLLFSRL PEKVRLTAVF DCCHSGSIMD LPFTYVCSGG EQASGTPHMK
RIREGNDVLG DVMMISGCAD EQTSADVKNT ATFGTGSTGA GGAATQCITC MLMNNQSLSY
GKLLIETRDM LKRKGFKQVP QLSASKAIDL DQTFSLTEMF SVDRSVQ
