ID   CYSP_TRYBB              Reviewed;         450 AA.
AC   P14658;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   03-AUG-2022, entry version 104.
DE   RecName: Full=Cysteine proteinase;
DE            EC=3.4.22.-;
DE   Flags: Precursor;
OS   Trypanosoma brucei brucei.
OC   Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC   Trypanosomatida; Trypanosomatidae; Trypanosoma.
OX   NCBI_TaxID=5702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=I STAR Serodeme;
RX   PubMed=2599086; DOI=10.1016/0014-5793(89)81655-2;
RA   Mottram J.C., North M.J., Barry J.D., Coombs G.H.;
RT   "A cysteine proteinase cDNA from Trypanosoma brucei predicts an enzyme with
RT   an unusual C-terminal extension.";
RL   FEBS Lett. 258:211-215(1989).
RN   [2]
RP   PARTIAL PROTEIN SEQUENCE.
RX   PubMed=2651912; DOI=10.1016/0166-6851(89)90039-x;
RA   Cazzulo J.J., Couso R., Raimondi A., Wernstedt C., Hellman U.;
RT   "Further characterization and partial amino acid sequence of a cysteine
RT   proteinase from Trypanosoma cruzi.";
RL   Mol. Biochem. Parasitol. 33:33-42(1989).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Rhodesiense WRATAT 1.1;
RX   PubMed=2235508; DOI=10.1093/nar/18.20.6141;
RA   Pamer E.G., Davis C.E., Eakin A., So M.;
RT   "Cloning and sequencing of the cysteine protease cDNA from Trypanosoma
RT   brucei rhodesiense.";
RL   Nucleic Acids Res. 18:6141-6141(1990).
CC   -!- FUNCTION: The cysteine proteinases have a potential role in host-
CC       parasite interaction and virulence.
CC   -!- SUBCELLULAR LOCATION: Lysosome.
CC   -!- DEVELOPMENTAL STAGE: Predominantly expressed by stumpy forms, which are
CC       preadapted for differentiation into procyclic trypanosomes in the tse-
CC       tse midgut.
CC   -!- MISCELLANEOUS: The 108-residue extension appears likely to be processed
CC       in part to produce the mature enzyme, and may be involved in targeting
CC       the protein within the cell.
CC   -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC       ECO:0000255|PROSITE-ProRule:PRU10090}.
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DR   EMBL; X16465; CAA34485.1; -; mRNA.
DR   EMBL; X54353; CAA38238.1; -; mRNA.
DR   PIR; S07051; S07051.
DR   PIR; S12099; S12099.
DR   AlphaFoldDB; P14658; -.
DR   SMR; P14658; -.
DR   MEROPS; C01.072; -.
DR   SwissPalm; P14658; -.
DR   PRIDE; P14658; -.
DR   GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd02248; Peptidase_C1A; 1.
DR   InterPro; IPR021981; DUF3586.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR025661; Pept_asp_AS.
DR   InterPro; IPR000169; Pept_cys_AS.
DR   InterPro; IPR025660; Pept_his_AS.
DR   InterPro; IPR000668; Peptidase_C1A_C.
DR   InterPro; IPR039417; Peptidase_C1A_papain-like.
DR   InterPro; IPR013201; Prot_inhib_I29.
DR   Pfam; PF12131; DUF3586; 1.
DR   Pfam; PF08246; Inhibitor_I29; 1.
DR   Pfam; PF00112; Peptidase_C1; 1.
DR   PRINTS; PR00705; PAPAIN.
DR   SMART; SM00848; Inhibitor_I29; 1.
DR   SMART; SM00645; Pept_C1; 1.
DR   SUPFAM; SSF54001; SSF54001; 1.
DR   PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR   PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR   PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW   Lysosome; Protease; Signal; Thiol protease; Virulence; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000305"
FT   PROPEP          21..125
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000026370"
FT   CHAIN           126..450
FT                   /note="Cysteine proteinase"
FT                   /id="PRO_0000026371"
FT   REGION          343..450
FT                   /note="108-residue extension"
FT   ACT_SITE        150
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        287
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        307
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        120
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        147..188
FT                   /evidence="ECO:0000250"
FT   VARIANT         115
FT                   /note="L -> V (in strain: Rhodesiense WRATAT 1.1)"
FT   VARIANT         143
FT                   /note="V -> D (in strain: Rhodesiense WRATAT 1.1)"
FT   VARIANT         186
FT                   /note="S -> F (in strain: Rhodesiense WRATAT 1.1)"
FT   VARIANT         189
FT                   /note="N -> G (in strain: Rhodesiense WRATAT 1.1)"
FT   VARIANT         267
FT                   /note="E -> T (in strain: Rhodesiense WRATAT 1.1)"
FT   VARIANT         283
FT                   /note="K -> E (in strain: Rhodesiense WRATAT 1.1)"
SQ   SEQUENCE   450 AA;  48451 MW;  BB81B00693F20F90 CRC64;
     MPRTEMVRFV RLPVVLLAMA ACLASVALGS LHVEESLEMR FAAFKKKYGK VYKDAKEEAF
     RFRAFEENME QAKIQAAANP YATFGVTPFS DMTREEFRAR YRNGASYFAA AQKRLRKTVN
     VTTGRAPAAV DWREKGAVTP VKVQGQCGSC WAFSTIGNIE GQWQVAGNPL VSLSEQMLVS
     CDTIDSGCNG GLMDNAFNWI VNSNGGNVFT EASYPYVSGN GEQPQCQMNG HEIGAAITDH
     VDLPQDEDAI AAYLAENGPL AIAVDAESFM DYNGGILTSC TSKQLDHGVL LVGYNDNSNP
     PYWIIKNSWS NMWGEDGYIR IEKGTNQCLM NQAVSSAVVG GPTPPPPPPP PPSATFTQDF
     CEGKGCTKGC SHATFPTGEC VQTTGVGSVI ATCGASNLTQ IIYPLSRSCS GPSVPITVPL
     DKCIPILIGS VEYHCSTNPP TKAARLVPHQ