MCA5_TRYCC
ID MCA5_TRYCC Reviewed; 442 AA.
AC Q2VLK8; Q4DS77;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 32.
DE RecName: Full=Metacaspase-5 {ECO:0000303|PubMed:16213036};
DE EC=3.4.22.- {ECO:0000269|PubMed:22402587};
DE AltName: Full=TcMCA5 {ECO:0000303|PubMed:16213036};
DE Flags: Precursor;
GN Name=MCA5 {ECO:0000303|PubMed:16213036};
GN ORFNames=Tc00.1047053510759.160 {ECO:0000312|EMBL:EAN95387.1};
OS Trypanosoma cruzi (strain CL Brener).
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Trypanosoma; Schizotrypanum.
OX NCBI_TaxID=353153 {ECO:0000312|Proteomes:UP000002296};
RN [1] {ECO:0000312|EMBL:AAY84579.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=CL Brener {ECO:0000312|EMBL:AAY84579.1};
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:0000312|Proteomes:UP000002296}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CL Brener {ECO:0000312|Proteomes:UP000002296};
RX PubMed=16020725; DOI=10.1126/science.1112631;
RA El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G.,
RA Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G.,
RA Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B.,
RA Anupama A., Arner E., Aslund L., Attipoe P., Bontempi E., Bringaud F.,
RA Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H.,
RA da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G.,
RA Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y.,
RA Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J.,
RA Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y.,
RA Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M.,
RA Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L.,
RA Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J.,
RA Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C.,
RA Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D.,
RA Andersson B.;
RT "The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas
RT disease.";
RL Science 309:409-415(2005).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, LACK OF PROTEOLYTIC
RP CLEAVAGE, ACTIVE SITE, AND MUTAGENESIS OF HIS-146 AND CYS-201.
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). May play a role in apoptosis
CC (PubMed:22402587). {ECO:0000269|PubMed:22402587}.
CC -!- ACTIVITY REGULATION: Activated by Ca(2+).
CC {ECO:0000269|PubMed:22402587}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome
CC {ECO:0000250|UniProtKB:Q8IEW1}. Note=Localizes to RAB11-positive
CC recycling endosomes. {ECO:0000250|UniProtKB:Q8IEW1}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed in epimastigotes (at
CC protein level). {ECO:0000269|PubMed:16213036}.
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}.
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; DQ015868; AAY84579.1; -; Genomic_DNA.
DR EMBL; AAHK01000216; EAN95387.1; -; Genomic_DNA.
DR RefSeq; XP_817238.1; XM_812145.1.
DR AlphaFoldDB; Q2VLK8; -.
DR SMR; Q2VLK8; -.
DR STRING; 5693.XP_817238.1; -.
DR MEROPS; C14.043; -.
DR EnsemblProtists; EAN95387; EAN95387; Tc00.1047053510759.160.
DR GeneID; 3549235; -.
DR KEGG; tcr:510759.160; -.
DR eggNOG; KOG1546; Eukaryota.
DR OMA; CLIPLDH; -.
DR OrthoDB; 821819at2759; -.
DR Proteomes; UP000002296; Unassembled WGS sequence.
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 Calcium; Endosome; Glycoprotein; Hydrolase; Metal-binding; Protease;
KW Reference proteome; Signal; Thiol protease.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..442
FT /note="Metacaspase-5"
FT /evidence="ECO:0000255"
FT /id="PRO_0000451287"
FT REGION 19..62
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000269|PubMed:22402587"
FT REGION 336..442
FT /note="Negatively regulates catalytic activity"
FT /evidence="ECO:0000269|PubMed:22402587"
FT REGION 348..442
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 348..373
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..434
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 146
FT /evidence="ECO:0000305|PubMed:22402587"
FT ACT_SITE 201
FT /evidence="ECO:0000305|PubMed:22402587"
FT BINDING 161
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 177
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 331
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 146
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22402587"
FT MUTAGEN 201
FT /note="C->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:22402587"
SQ SEQUENCE 442 AA; 48698 MW; 490B5569BFC0C89C CRC64;
MDLLLGVLSS GILQNALPFV AGVGRVKRPK RVKLEEAFRE AHLCRPVIPY RAPTPYTGGR
VKALFVGINY TGTRNKLSGC VNDVRQMLGT LQRIQFPISE CCILVDDMRF PNFTALPTRE
NIIKHMAWLV HDVRPGDVLF FHYSGHGTET KAERDSEELY DQCLVPLDYQ VQGAILDDDL
FELLVKGLPA GVRMTAVFDC CHSASLLDLP FAFVGNNNFY SGGRHEMRKV RANNFSMGDV
VVFSGCDDSG TSADVSNVSS FGSGLVASGG AATQALTWAL VNTSQLSYAD IFIRTREILR
QKGYKQVPQL SSSKPVDLYK PFSLFGPITV NTSLIHYVPQ QYLQPWGPPQ PYYPPPQPQQ
PYYPPPQPQQ PYYPSSQLPT QYNNLAPTAG IPLMTSSSEV PPGQYPQALS GDQNGGVPPQ
YPSDQSTYYS SAQYLSGVGK PL
