CATLL_FASHE
ID CATLL_FASHE Reviewed; 326 AA.
AC Q24940; P91727;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 79.
DE RecName: Full=Cathepsin L-like proteinase;
DE EC=3.4.22.-;
DE Flags: Precursor;
GN Name=Cat-1 {ECO:0000303|PubMed:8192668};
OS Fasciola hepatica (Liver fluke).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Platyhelminthes; Trematoda;
OC Digenea; Plagiorchiida; Echinostomata; Echinostomatoidea; Fasciolidae;
OC Fasciola.
OX NCBI_TaxID=6192;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAA29136.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 107-122; 188-206 AND
RP 277-291, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, AND
RP HYDROXYLATION AT PRO-109 AND PRO-196.
RC STRAIN=Crompton {ECO:0000312|EMBL:AAA29136.1};
RX PubMed=8192668; DOI=10.1042/bj2990781;
RA Wijffels G.L., Panaccio M., Salvatore L., Wilson L., Walker I.D.,
RA Spithill T.W.;
RT "The secreted cathepsin L-like proteinases of the trematode Fasciola
RT hepatica, contain 3-hydroxyproline residues.";
RL Biochem. J. 299:781-790(1994).
CC -!- FUNCTION: Thiol protease. Probably involved in interaction with host
CC tissues. Displays a similar activity to that of papain. Has high
CC activity on Z-Phe-Arg-NHMec, but no activity on Z-Arg-NHMec.
CC {ECO:0000269|PubMed:8192668, ECO:0000303|PubMed:8192668}.
CC -!- ACTIVITY REGULATION: Strongly inhibited by Antipain, E64 and Leupeptin,
CC and weakly inhibited by iodoacetic acid (IAA) and phenylmethylsulfonyl
CC fluoride (PMSF). Requires the presence of dithiothreitol (DTT) for
CC activity. {ECO:0000269|PubMed:8192668}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=46 uM for Z-Phe-Arg-NHMec (at pH 7.45)
CC {ECO:0000269|PubMed:8192668};
CC pH dependence:
CC Optimum pH is 7-9 in a mixed-buffer system. In a Tris buffer high
CC levels of activity were detected at very alkaline pHs.
CC {ECO:0000269|PubMed:8192668};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:8192668}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8192668}.
CC -!- PTM: Contains cysteine residues involved in intramolecular disulfide
CC bonding. {ECO:0000269|PubMed:8192668}.
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}.
CC -!- CAUTION: It is not clear whether the mature peptide starts at Ala-107
CC or at Val-108. {ECO:0000305}.
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DR EMBL; L33771; AAA29136.1; -; mRNA.
DR PIR; S43991; S43991.
DR PDB; 2O6X; X-ray; 1.40 A; A=17-326.
DR PDBsum; 2O6X; -.
DR AlphaFoldDB; Q24940; -.
DR SMR; Q24940; -.
DR DrugBank; DB12245; Triclabendazole.
DR MEROPS; C01.033; -.
DR BRENDA; 3.4.22.B49; 2230.
DR BRENDA; 3.4.22.B60; 2230.
DR EvolutionaryTrace; Q24940; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 1.
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; 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 3D-structure; Direct protein sequencing; Disulfide bond; Hydrolase;
KW Hydroxylation; Protease; Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..106
FT /note="Activation peptide"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:8192668"
FT /id="PRO_0000042858"
FT CHAIN 107..326
FT /note="Cathepsin L-like proteinase"
FT /evidence="ECO:0000269|PubMed:8192668"
FT /id="PRO_0000042859"
FT ACT_SITE 132
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 269
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 289
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT MOD_RES 109
FT /note="3-hydroxyproline; partial"
FT /evidence="ECO:0000269|PubMed:8192668"
FT MOD_RES 196
FT /note="3-hydroxyproline; partial"
FT /evidence="ECO:0000269|PubMed:8192668"
FT DISULFID 129..172
FT /evidence="ECO:0000250|UniProtKB:P25774"
FT DISULFID 163..204
FT /evidence="ECO:0000250|UniProtKB:P25774"
FT DISULFID 262..311
FT /evidence="ECO:0000250|UniProtKB:P25774"
FT HELIX 18..28
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 34..59
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 62..67
FT /evidence="ECO:0007829|PDB:2O6X"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 77..84
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 132..149
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 157..163
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 177..184
FT /evidence="ECO:0007829|PDB:2O6X"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 213..221
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 226..236
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 239..243
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 247..250
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 269..279
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 300..304
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:2O6X"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:2O6X"
FT TURN 313..315
FT /evidence="ECO:0007829|PDB:2O6X"
FT STRAND 316..324
FT /evidence="ECO:0007829|PDB:2O6X"
SQ SEQUENCE 326 AA; 36896 MW; 7FDDB3094D3134A6 CRC64;
MRLFILAVLT VGVLGSNDDL WHQWKRMYNK EYNGADDQHR RNIWEKNVKH IQEHNLRHDL
GLVTYTLGLN QFTDMTFEEF KAKYLTEMSR ASDILSHGVP YEANNRAVPD KIDWRESGYV
TEVKDQGNCG SCWAFSTTGT MEGQYMKNER TSISFSEQQL VDCSGPWGNN GCSGGLMENA
YQYLKQFGLE TESSYPYTAV EGQCRYNKQL GVAKVTGYYT VHSGSEVELK NLVGARRPAA
VAVDVESDFM MYRSGIYQSQ TCSPLRVNHA VLAVGYGTQG GTDYWIVKNS WGTYWGERGY
IRMARNRGNM CGIASLASLP MVARFP
