MCA4_TRYBB
ID MCA4_TRYBB Reviewed; 353 AA.
AC Q8T8E5;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 25-MAY-2022, entry version 52.
DE RecName: Full=Inactive metacaspase-4 {ECO:0000305};
DE AltName: Full=TbMCA4 {ECO:0000303|PubMed:12062425};
GN Name=MCA4 {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:CAD24805.1}
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 FUNCTION, LACK OF CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, PROTEOLYTIC CLEAVAGE, PALMITOYLATION, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF GLY-2 AND SER-219.
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: Inactive metacaspase which plays a role in parasite
CC bloodstream form growth and in parasite virulence within the mammalian
CC host. {ECO:0000269|PubMed:21949125}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC {ECO:0000269|PubMed:21949125}; Lipid-anchor
CC {ECO:0000269|PubMed:21949125}; Cytoplasmic side
CC {ECO:0000269|PubMed:21949125}. Secreted {ECO:0000269|PubMed:21949125}.
CC Note=Secreted by the parasite bloodstream form (PubMed:21949125).
CC Membrane localization is required for MCA4 processing but is
CC dispensable for MCA4 secretion, and parasite growth and virulence in
CC the mammalian host (PubMed:21949125). {ECO:0000269|PubMed:21949125}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed in the bloodstream form (at
CC protein level). {ECO:0000269|PubMed:21949125}.
CC -!- PTM: Palmitoylated. {ECO:0000269|PubMed:21949125}.
CC -!- PTM: Proteolytic cleavage by MCA3 occurs prior or during secretion and
CC requires MCA4 membrane localization (PubMed:21949125). Cleavage is
CC dispensable for secretion and parasite growth and virulence in the
CC mammalian host (PubMed:21949125). In vitro, can be cleaved by MCA2 but
CC specifically cleaved by MCA3 in vivo (PubMed:21949125).
CC {ECO:0000269|PubMed:21949125}.
CC -!- DISRUPTION PHENOTYPE: Knockouts in the bloodstream form have an initial
CC slower growth rate in vitro which reaches wild-type levels after
CC several weeks of culture (PubMed:21949125). Knockouts in the
CC bloodstream form have a reduced growth rate and virulence in infected
CC mice (PubMed:21949125). RNAi-mediated knockdown at the bloodstream
CC stage results in a more severe phenotype characterized by a growth
CC arrest due to a failure to undergo cytokinesis (PubMed:21949125).
CC {ECO:0000269|PubMed:21949125}.
CC -!- SIMILARITY: Belongs to the peptidase C14B family. {ECO:0000305}.
CC -!- CAUTION: In contrast to other metacaspases (MCA) of the peptidase C14B
CC family, contains a serine residue at the position of the canonical
CC catalytic cysteine and has been shown to lack protease activity.
CC {ECO:0000269|PubMed:21949125}.
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DR EMBL; AJ437304; CAD24805.1; -; mRNA.
DR AlphaFoldDB; Q8T8E5; -.
DR SMR; Q8T8E5; -.
DR MEROPS; C14.044; -.
DR GO; GO:0060170; C:ciliary membrane; IDA:GeneDB.
DR GO; GO:0005737; C:cytoplasm; IDA:GeneDB.
DR GO; GO:1903561; C:extracellular vesicle; IDA:GeneDB.
DR GO; GO:0031514; C:motile cilium; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:GeneDB.
DR GO; GO:0008233; F:peptidase activity; IGI:GeneDB.
DR GO; GO:0006508; P:proteolysis; ISM:GeneDB.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR SUPFAM; SSF52129; SSF52129; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cilium; Flagellum; Lipoprotein; Membrane;
KW Myristate; Palmitate; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..353
FT /note="Inactive metacaspase-4"
FT /id="PRO_0000451286"
FT SITE 64..65
FT /note="Cleavage; by MCA3"
FT /evidence="ECO:0000269|PubMed:21949125"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000255"
FT MUTAGEN 2
FT /note="G->A: Loss of flagellum membrane localization. No
FT defect in MCA4 secretion, however processing of the
FT secreted form is impaired. No defect in growth rate and
FT virulence in infected mice."
FT /evidence="ECO:0000269|PubMed:21949125"
FT MUTAGEN 219
FT /note="S->C: Restores calcium-dependent auto-processing
FT activity and catalytic activity towards substrates."
FT /evidence="ECO:0000269|PubMed:21949125"
SQ SEQUENCE 353 AA; 38993 MW; 1ADB0FCA1EA996BC CRC64;
MGGCVSTALK VGAETVAEGH IDLISFAINY FKNAVPYIVK YLGRQQRPKE VDMEATLTEA
KESKGFQPWK ISCQPKGAVR GLFIGVNYGN TEAQLSGCCH DIMMMIGALQ KRNFPLTEVV
ILADEEDVPG RTGEPTRANI LRYLAWLAQD AQPNDVLFFH YSGHGTRANA RDDDCEEYDQ
CIVPMDYVEN GCIVDNEIHE ILVSQLPKGV RLTAVFDCSH SGSMLDLPYA YVCDSSKDGS
GSCGMKRVRE DNDVQADVLM ISACADDEAA LGVDNTQDFY ESGKDSGGAA TFCLTAMMMR
EEPLTFLDLL VHTREMLKSR GFTQVPHLSA SKPINLMQRF SLEGLFPQER TLL
