MCA5_TRYBB
ID MCA5_TRYBB Reviewed; 500 AA.
AC Q8IEW1; Q8T8E4;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Metacaspase-5 {ECO:0000305};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q2VLK8};
DE AltName: Full=TbMCA5 {ECO:0000303|PubMed:12062425};
DE Flags: Precursor;
GN Name=MCA5 {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:CAD55946.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=EATRO 795 {ECO:0000312|EMBL:CAD55946.1};
RA Mottram J.C., Helms M.J., Coombs G.H., Sajid M.;
RT "Clan CD cysteine peptidases of parasitic protoza.";
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000312|EMBL:CAD24806.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-340.
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 [3] {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).
CC -!- FUNCTION: Cysteine protease that cleaves specifically after arginine or
CC lysine residues. {ECO:0000250|UniProtKB:Q2VLK8}.
CC -!- SUBCELLULAR LOCATION: Recycling endosome {ECO:0000269|PubMed:16507595}.
CC Note=Localizes to RAB11-positive recycling endosomes.
CC {ECO:0000269|PubMed:16507595}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the mammalian blood stage form and
CC insect procyclic form (at protein level).
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). Knockout has no
CC defect in the growth of the procyclic form (PubMed:16507595).
CC Simultaneous RNAi-mediated knockdown of MCA2, MCA3 and MCA5 in the
CC bloodstream stage form causes a growth arrest resulting from a block
CC prior to cytokinesis; DNA replication and mitosis are normal
CC (PubMed:16507595). Has no effect on VSG protein recycling
CC (PubMed:16507595). Triple knockout of MCA2, MCA3 and MCA5 in the
CC bloodstream form causes an initial slower growth rate in vitro which
CC reaches wild-type levels after several weeks of culture
CC (PubMed:16507595). Triple knockouts have a normal growth rate and
CC virulence in infected mice (PubMed:16507595).
CC {ECO:0000269|PubMed:16507595}.
CC -!- SIMILARITY: Belongs to the peptidase C14B family. {ECO:0000305}.
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DR EMBL; AJ514941; CAD55946.1; -; Genomic_DNA.
DR EMBL; AJ437305; CAD24806.1; -; mRNA.
DR AlphaFoldDB; Q8IEW1; -.
DR SMR; Q8IEW1; -.
DR MEROPS; C14.043; -.
DR EnsemblProtists; EAN77286; EAN77286; Tb09.211.4760.
DR HOGENOM; CLU_545783_0_0_1; -.
DR OMA; CLIPLDH; -.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
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 Calcium; Endosome; Glycoprotein; Hydrolase; Metal-binding; Protease;
KW Signal; Thiol protease.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..500
FT /note="Metacaspase-5"
FT /evidence="ECO:0000255"
FT /id="PRO_5004308349"
FT REGION 19..63
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:Q2VLK8"
FT REGION 358..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 444..500
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..390
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 463..479
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 147
FT /evidence="ECO:0000250|UniProtKB:Q2VLK8"
FT ACT_SITE 202
FT /evidence="ECO:0000250|UniProtKB:Q2VLK8"
FT BINDING 162
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 179
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:Q585F3"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 219
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 264
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CONFLICT 90
FT /note="Q -> K (in Ref. 2; CAD24806)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="H -> D (in Ref. 2; CAD24806)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 55443 MW; 5C614B6DE8B62EA4 CRC64;
MDAALALLFG QVATAVLPYV VNSIGRVPRP KRVDVKKAMG EAHQCRPVVP YRAPRPYTEG
RVKALFIGIN YTGSSAQLGG CVNDVMHMLQ TLQRIEFPIS ECCILVDDRR FPNFTAMPTR
ENIIKYMAWL VYDVRPGDVL FFHFSGHGAE TKGGRDSNEK MDQCLVPLDY DKAGAILDDD
LFELMIKGLP AGVRMTAVFD CCHSASLLDL PFAFVAGRNV SSNQRHEMRM VRKDNYSRGD
VVMFSGCEDS GTSADVTNTS SFGNGTVAAG GAATQAFTWA LLNTTGYSYI DIFMKTREVL
RQKGYKQVPQ LSSSKPVDLY KQFSLFGPLT MNASLVQHLP QEYVQPWAPH PAYQQPHEAT
LPASVSQPHS QPVMGIPVAS TSNGKSNPGV SDGGRASGEV YPPTQYPSSH PAPQQQAYYQ
PPQQAYYQPP QQAYYQPPQQ AYYQPPQQAY YQPPQQAYYQ PEPHHQPAPP PPPKKENKPA
RPGYPMSYCM KFSQGKPGRK
