CATL1_BOVIN
ID CATL1_BOVIN Reviewed; 334 AA.
AC P25975; O77502; Q3T0P2;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Procathepsin L {ECO:0000305};
DE EC=3.4.22.15 {ECO:0000250|UniProtKB:P07711};
DE AltName: Full=Cathepsin L1;
DE Contains:
DE RecName: Full=Cathepsin L;
DE Contains:
DE RecName: Full=Cathepsin L heavy chain;
DE Contains:
DE RecName: Full=Cathepsin L light chain;
DE Flags: Precursor;
GN Name=CTSL; Synonyms=CTSL1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retinal pigment epithelium;
RA Voelkel H., Schultz J.E., Kurz U.;
RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-301.
RA Miyashita N.;
RT "Bos taurus cathepsin L gene.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 114-132 AND 293-311.
RX PubMed=2044774; DOI=10.1016/0014-5793(91)80620-i;
RA Ritonja A., Colic A., Dolenc I., Ogrinc T., Podobnik M., Turk V.;
RT "The complete amino acid sequence of bovine cathepsin S and a partial
RT sequence of bovine cathepsin L.";
RL FEBS Lett. 283:329-331(1991).
RN [5]
RP PROTEIN SEQUENCE OF 114-132 AND 293-311.
RC TISSUE=Kidney;
RX PubMed=1515067; DOI=10.1515/bchm3.1992.373.2.407;
RA Dolenc I., Ritonja A., Colic A., Podobnik M., Ogrinc T., Turk V.;
RT "Bovine cathepsins S and L: isolation and amino acid sequences.";
RL Biol. Chem. Hoppe-Seyler 373:407-412(1992).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12869695; DOI=10.1073/pnas.1531542100;
RA Yasothornsrikul S., Greenbaum D., Medzihradszky K.F., Toneff T., Bundey R.,
RA Miller R., Schilling B., Petermann I., Dehnert J., Logvinova A.,
RA Goldsmith P., Neveu J.M., Lane W.S., Gibson B., Reinheckel T., Peters C.,
RA Bogyo M., Hook V.;
RT "Cathepsin L in secretory vesicles functions as a prohormone-processing
RT enzyme for production of the enkephalin peptide neurotransmitter.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9590-9595(2003).
CC -!- FUNCTION: Thiol protease important for the overall degradation of
CC proteins in lysosomes (By similarity). Plays a critical for normal
CC cellular functions such as general protein turnover, antigen processing
CC and bone remodeling. Involved in the solubilization of cross-linked
CC TG/thyroglobulin and in the subsequent release of thyroid hormone
CC thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the
CC thyroid follicle lumen (By similarity). In neuroendocrine chromaffin
CC cells secretory vesicles, catalyzes the prohormone proenkephalin
CC processing to the active enkephalin peptide neurotransmitter
CC (PubMed:12869695). In thymus, regulates CD4(+) T cell positive
CC selection by generating the major histocompatibility complex class II
CC (MHCII) bound peptide ligands presented by cortical thymic epithelial
CC cells. Also mediates invariant chain processing in cortical thymic
CC epithelial cells. Major elastin-degrading enzyme at neutral pH.
CC Accumulates as a mature and active enzyme in the extracellular space of
CC antigen presenting cells (APCs) to regulate degradation of the
CC extracellular matrix in the course of inflammation (By similarity).
CC Secreted form generates endostatin from COL18A1 (By similarity).
CC Critical for cardiac morphology and function. Plays an important role
CC in hair follicle morphogenesis and cycling, as well as epidermal
CC differentiation (By similarity). Required for maximal stimulation of
CC steroidogenesis by TIMP1 (By similarity).
CC {ECO:0000250|UniProtKB:P06797, ECO:0000250|UniProtKB:P07154,
CC ECO:0000250|UniProtKB:P07711, ECO:0000269|PubMed:12869695}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specificity close to that of papain. As compared to cathepsin
CC B, cathepsin L exhibits higher activity toward protein substrates,
CC but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-
CC dipeptidase activity.; EC=3.4.22.15;
CC -!- ACTIVITY REGULATION: Inhibited by the propeptide produced by
CC autocleavage (By similarity). Long isoform of CD74/Ii chain stabilizes
CC the conformation of mature CTSL by binding to its active site and
CC serving as a chaperone to help maintain a pool of mature enzyme in
CC endocytic compartments and extracellular space of APCs. IFNG enhances
CC the conversion into the CTSL mature and active form (By similarity).
CC Inhibited by CST6. Inhibited by the glycopeptide antibiotic
CC teicoplanin. Inhibited by amantadine (By similarity).
CC {ECO:0000250|UniProtKB:P06797, ECO:0000250|UniProtKB:P07711}.
CC -!- SUBUNIT: Dimer of a heavy and a light chain linked by disulfide bonds.
CC Interacts with Long isoform of CD74/Ii chain; the interaction
CC stabilizes the conformation of mature CTSL.
CC {ECO:0000250|UniProtKB:P06797}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P06797}. Apical
CC cell membrane {ECO:0000250|UniProtKB:P06797}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P06797}; Extracellular side
CC {ECO:0000250|UniProtKB:P06797}. Cytoplasmic vesicle, secretory vesicle,
CC chromaffin granule {ECO:0000269|PubMed:12869695}. Secreted,
CC extracellular space {ECO:0000250|UniProtKB:P06797}. Secreted
CC {ECO:0000250|UniProtKB:P06797}. Note=Localizes to the apical membrane
CC of thyroid epithelial cells. Released at extracellular space by
CC activated dendritic cells and macrophages.
CC {ECO:0000250|UniProtKB:P06797}.
CC -!- TISSUE SPECIFICITY: Expresseed by neuroendocrine chromaffin cells.
CC {ECO:0000269|PubMed:12869695}.
CC -!- PTM: During export along the endocytic pathway, pro-CTSL undergoes
CC several proteolytic cleavages to generate the CTSL single-chain and
CC two-chain mature forms, composed of a heavy chain linked to a light
CC chain by disulfide bonds (By similarity). Autocleavage; produces the
CC single-chain CTSL after cleavage of the propeptide. The cleavage can be
CC intermolecular (By similarity). {ECO:0000250|UniProtKB:P06797,
CC ECO:0000250|UniProtKB:P07711}.
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; X91755; CAA62870.1; -; mRNA.
DR EMBL; BC102312; AAI02313.1; -; mRNA.
DR EMBL; AB017648; BAA33398.1; -; Genomic_DNA.
DR PIR; S15845; S15845.
DR RefSeq; NP_776457.1; NM_174032.2.
DR AlphaFoldDB; P25975; -.
DR SMR; P25975; -.
DR STRING; 9913.ENSBTAP00000022710; -.
DR BindingDB; P25975; -.
DR ChEMBL; CHEMBL2113; -.
DR MEROPS; C01.032; -.
DR PaxDb; P25975; -.
DR PeptideAtlas; P25975; -.
DR Ensembl; ENSBTAT00000022710; ENSBTAP00000022710; ENSBTAG00000017077.
DR GeneID; 281108; -.
DR KEGG; bta:281108; -.
DR CTD; 1515; -.
DR VEuPathDB; HostDB:ENSBTAG00000017077; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000154367; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; P25975; -.
DR OMA; DNHWNLW; -.
DR OrthoDB; 1275401at2759; -.
DR TreeFam; TF313739; -.
DR Reactome; R-BTA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-BTA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-BTA-2132295; MHC class II antigen presentation.
DR Reactome; R-BTA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR PRO; PR:P25975; -.
DR Proteomes; UP000009136; Chromosome 8.
DR Bgee; ENSBTAG00000017077; Expressed in metanephros cortex and 102 other tissues.
DR ExpressionAtlas; P25975; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042583; C:chromaffin granule; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0048002; P:antigen processing and presentation of peptide antigen; ISS:UniProtKB.
DR GO; GO:0043373; P:CD4-positive, alpha-beta T cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0060309; P:elastin catabolic process; ISS:UniProtKB.
DR GO; GO:0034230; P:enkephalin processing; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR GO; GO:0031638; P:zymogen activation; ISS: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 Cell membrane; Cytoplasmic vesicle; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Membrane; Protease;
KW Reference proteome; Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:P07154"
FT PROPEP 18..117
FT /note="Activation peptide"
FT /id="PRO_0000026236"
FT CHAIN 118..334
FT /note="Cathepsin L"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT /id="PRO_0000450784"
FT CHAIN 118..289
FT /note="Cathepsin L heavy chain"
FT /id="PRO_0000026237"
FT PROPEP 290..291
FT /id="PRO_0000026238"
FT CHAIN 292..334
FT /note="Cathepsin L light chain"
FT /id="PRO_0000026239"
FT ACT_SITE 138
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 277
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 301
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 106..107
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 107..108
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 112..113
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT SITE 113..114
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 135..178
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 169..212
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 270..323
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT CONFLICT 72
FT /note="G -> A (in Ref. 1; CAA62870)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="K -> W (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="S -> C (in Ref. 1; CAA62870)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="P -> G (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="N -> G (in Ref. 4; AA sequence and 5; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 334 AA; 37347 MW; ECA5D7415DDECFC9 CRC64;
MNPSFFLTVL CLGVASAAPK LDPNLDAHWH QWKATHRRLY GMNEEEWRRA VWEKNKKIID
LHNQEYSEGK HGFRMAMNAF GDMTNEEFRQ VMNGFQNQKH KKGKLFHEPL LVDVPKSVDW
TKKGYVTPVK NQGQCGSCWA FSATGALEGQ MFRKTGKLVS LSEQNLVDCS RAQGNQGCNG
GLMDNAFQYI KDNGGLDSEE SYPYLATDTN SCNYKPECSA ANDTGFVDIP QREKALMKAV
ATVGPISVAI DAGHTSFQFY KSGIYYDPDC SSKDLDHGVL VVGYGFEGTD SNNNKFWIVK
NSWGPEWGWN GYVKMAKDQN NHCGIATAAS YPTV
