CATL1_RAT
ID CATL1_RAT Reviewed; 334 AA.
AC P07154; Q9QV07;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Procathepsin L;
DE EC=3.4.22.15;
DE AltName: Full=Cathepsin L1;
DE AltName: Full=Cyclic protein 2;
DE Short=CP-2;
DE AltName: Full=Major excreted protein;
DE Short=MEP;
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 {ECO:0000312|RGD:2448}; Synonyms=Ctsl1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Kidney;
RX PubMed=3666143; DOI=10.1016/0014-5793(87)80511-2;
RA Ishidoh K., Towatari T., Imajoh S., Kawasaki H., Kominami E., Katunuma N.,
RA Suzuki K.;
RT "Molecular cloning and sequencing of cDNA for rat cathepsin L.";
RL FEBS Lett. 223:69-73(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2599113; DOI=10.1016/0014-5793(89)81497-8;
RA Ishidoh K., Kominami E., Suzuki K., Katunuma N.;
RT "Gene structure and 5'-upstream sequence of rat cathepsin L.";
RL FEBS Lett. 259:71-74(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-42, TISSUE SPECIFICITY, AND
RP INDUCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=11356678; DOI=10.1210/endo.142.6.8106;
RA Zabludoff S.D., Charron M., DeCerbo J.N., Simukova N., Wright W.W.;
RT "Male germ cells regulate transcription of the cathepsin L gene by rat
RT Sertoli cells.";
RL Endocrinology 142:2318-2327(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 88-334.
RC TISSUE=Sertoli cell;
RX PubMed=1791830; DOI=10.1210/mend-5-12-1789;
RA Erickson-Lawrence M., Zabludoff S.D., Wright W.W.;
RT "Cyclic protein-2, a secretory product of rat Sertoli cells, is the
RT proenzyme form of cathepsin L.";
RL Mol. Endocrinol. 5:1789-1798(1991).
RN [6]
RP PROTEIN SEQUENCE OF 18-37, FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Sertoli cell;
RX PubMed=7777858; DOI=10.1126/science.7777858;
RA Boujrad N., Ogwuegbu S.O., Garnier M., Lee C.-H., Martin B.M.,
RA Papadopoulos V.;
RT "Identification of a stimulator of steroid hormone synthesis isolated from
RT testis.";
RL Science 268:1609-1612(1995).
RN [7]
RP PROTEIN SEQUENCE OF 18-28, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Epidermis;
RX PubMed=10699763; DOI=10.1016/s0923-1811(99)00063-8;
RA Kawada A., Hara K., Kominami E., Tezuka T., Takahashi M., Takahara H.;
RT "Precursor of rat epidermal cathepsin L: purification and
RT immunohistochemical localization.";
RL J. Dermatol. Sci. 23:36-45(2000).
RN [8]
RP PROTEIN SEQUENCE OF 114-288 AND 291-334.
RC TISSUE=Liver;
RX PubMed=3402618; DOI=10.1016/0014-5793(88)80285-0;
RA Towatari T., Katunuma N.;
RT "Amino acid sequence of rat liver cathepsin L.";
RL FEBS Lett. 236:57-61(1988).
RN [9]
RP CLEAVAGE OF SIGNAL PEPTIDE AFTER ALA-17, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=26479776; DOI=10.1021/acs.jproteome.5b00820;
RA Tsuchiya T., Osaki T., Minamino N., Sasaki K.;
RT "Peptidomics for studying limited proteolysis.";
RL J. Proteome Res. 14:4921-4931(2015).
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 (By
CC similarity). In thymus, regulates CD4(+) T cell positive selection by
CC generating the major histocompatibility complex class II (MHCII) bound
CC peptide ligands presented by cortical thymic epithelial cells. Also
CC mediates invariant chain processing in cortical thymic epithelial
CC cells. Major elastin-degrading enzyme at neutral pH. Accumulates as a
CC mature and active enzyme in the extracellular space of antigen
CC presenting cells (APCs) to regulate degradation of the extracellular
CC matrix in the course of inflammation (By similarity). Secreted form
CC generates endostatin from COL18A1 (By similarity). Critical for cardiac
CC morphology and function. Plays an important role in hair follicle
CC morphogenesis and cycling, as well as epidermal differentiation (By
CC similarity). Required for maximal stimulation of steroidogenesis by
CC TIMP1 (PubMed:7777858). {ECO:0000250|UniProtKB:P06797,
CC ECO:0000250|UniProtKB:P07711, ECO:0000250|UniProtKB:P25975,
CC ECO:0000269|PubMed:7777858}.
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 Evidence={ECO:0000250|UniProtKB:P07711};
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:0000269|PubMed:7777858}. 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:0000250|UniProtKB:P25975}. Secreted,
CC extracellular space {ECO:0000250|UniProtKB:P06797}. Secreted
CC {ECO:0000269|PubMed:7777858}. Note=Localizes to the apical membrane of
CC thyroid epithelial cells. Released at extracellular space by activated
CC dendritic cells and macrophages. {ECO:0000250|UniProtKB:P06797}.
CC -!- TISSUE SPECIFICITY: Both mature cathepsin L1 and procathepsin L are
CC found in the upper epidermis. The lower epidermis predominantly
CC contains procathepsin L. In seminiferous tubules expression is greater
CC at stages VI-VII than at stages IX-XII. {ECO:0000269|PubMed:10699763,
CC ECO:0000269|PubMed:11356678}.
CC -!- INDUCTION: Expression in Sertoli cells is repressed by germ cells.
CC {ECO:0000269|PubMed:11356678}.
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; Y00697; CAA68691.1; -; mRNA.
DR EMBL; AF025476; AAB81616.1; -; Genomic_DNA.
DR EMBL; BC063175; AAH63175.1; -; mRNA.
DR EMBL; S85184; AAB21516.1; -; mRNA.
DR PIR; S07098; KHRTL.
DR RefSeq; NP_037288.1; NM_013156.2.
DR AlphaFoldDB; P07154; -.
DR SMR; P07154; -.
DR BioGRID; 247726; 1.
DR IntAct; P07154; 1.
DR STRING; 10116.ENSRNOP00000025462; -.
DR BindingDB; P07154; -.
DR ChEMBL; CHEMBL2305; -.
DR MEROPS; C01.032; -.
DR PhosphoSitePlus; P07154; -.
DR jPOST; P07154; -.
DR PaxDb; P07154; -.
DR PRIDE; P07154; -.
DR GeneID; 25697; -.
DR KEGG; rno:25697; -.
DR UCSC; RGD:2448; rat.
DR CTD; 1514; -.
DR RGD; 2448; Ctsl.
DR VEuPathDB; HostDB:ENSRNOG00000018566; -.
DR eggNOG; KOG1543; Eukaryota.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; P07154; -.
DR OMA; CSHPQGN; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; P07154; -.
DR TreeFam; TF313739; -.
DR BRENDA; 3.4.22.15; 5301.
DR Reactome; R-RNO-1442490; Collagen degradation.
DR Reactome; R-RNO-1474228; Degradation of the extracellular matrix.
DR Reactome; R-RNO-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-RNO-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-RNO-2132295; MHC class II antigen presentation.
DR Reactome; R-RNO-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR SABIO-RK; P07154; -.
DR PRO; PR:P07154; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000018566; Expressed in kidney and 20 other tissues.
DR ExpressionAtlas; P07154; baseline and differential.
DR Genevisible; P07154; RN.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042583; C:chromaffin granule; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:RGD.
DR GO; GO:0005902; C:microvillus; IDA:RGD.
DR GO; GO:0005771; C:multivesicular body; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005730; C:nucleolus; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0043204; C:perikaryon; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0005773; C:vacuole; IDA:RGD.
DR GO; GO:0004177; F:aminopeptidase activity; IDA:RGD.
DR GO; GO:0005518; F:collagen binding; ISO:RGD.
DR GO; GO:0016807; F:cysteine-type carboxypeptidase activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:CAFA.
DR GO; GO:0008234; F:cysteine-type peptidase activity; ISO:RGD.
DR GO; GO:0004175; F:endopeptidase activity; ISO:RGD.
DR GO; GO:0001968; F:fibronectin binding; ISO:RGD.
DR GO; GO:0042393; F:histone binding; ISO:RGD.
DR GO; GO:0030984; F:kininogen binding; IPI:RGD.
DR GO; GO:0042277; F:peptide binding; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0043394; F:proteoglycan binding; ISO:RGD.
DR GO; GO:0097655; F:serpin family protein binding; ISO:RGD.
DR GO; GO:0002250; P:adaptive immune response; ISO:RGD.
DR GO; GO:0048002; P:antigen processing and presentation of peptide antigen; ISS:UniProtKB.
DR GO; GO:0048102; P:autophagic cell death; IEP:RGD.
DR GO; GO:0043373; P:CD4-positive, alpha-beta T cell lineage commitment; ISS:UniProtKB.
DR GO; GO:0007154; P:cell communication; IDA:RGD.
DR GO; GO:0009267; P:cellular response to starvation; IEP:RGD.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; ISO:RGD.
DR GO; GO:0030574; P:collagen catabolic process; ISS:UniProtKB.
DR GO; GO:0046697; P:decidualization; IEP:RGD.
DR GO; GO:0060309; P:elastin catabolic process; ISS:UniProtKB.
DR GO; GO:0034230; P:enkephalin processing; ISS:UniProtKB.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; ISO:RGD.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; ISO:RGD.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; ISO:RGD.
DR GO; GO:0021675; P:nerve development; IEP:RGD.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0030163; P:protein catabolic process; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; IDA:CAFA.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; ISO:RGD.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; ISO:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0034698; P:response to gonadotropin; IEP:RGD.
DR GO; GO:1990834; P:response to odorant; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0060008; P:Sertoli cell differentiation; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0006590; P:thyroid hormone generation; ISO:RGD.
DR GO; GO:0046718; P:viral entry into host cell; ISO:RGD.
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; Hydrolase; Lysosome; Membrane; Protease;
KW Reference proteome; Secreted; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:10699763,
FT ECO:0000269|PubMed:26479776, ECO:0000269|PubMed:7777858"
FT PROPEP 18..113
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:3402618"
FT /id="PRO_0000026256"
FT CHAIN 114..334
FT /note="Cathepsin L"
FT /id="PRO_0000304796"
FT CHAIN 114..288
FT /note="Cathepsin L heavy chain"
FT /id="PRO_0000026257"
FT PROPEP 289..290
FT /evidence="ECO:0000269|PubMed:3402618"
FT /id="PRO_0000026258"
FT CHAIN 291..334
FT /note="Cathepsin L light chain"
FT /id="PRO_0000026259"
FT ACT_SITE 138
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 276
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT ACT_SITE 300
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 DISULFID 135..178
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 169..211
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT DISULFID 269..322
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000250|UniProtKB:P07711"
FT CONFLICT 238
FT /note="A -> P (in Ref. 1; CAA68691)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 334 AA; 37660 MW; AFFA997582E34AF6 CRC64;
MTPLLLLAVL CLGTALATPK FDQTFNAQWH QWKSTHRRLY GTNEEEWRRA VWEKNMRMIQ
LHNGEYSNGK HGFTMEMNAF GDMTNEEFRQ IVNGYRHQKH KKGRLFQEPL MLQIPKTVDW
REKGCVTPVK NQGQCGSCWA FSASGCLEGQ MFLKTGKLIS LSEQNLVDCS HDQGNQGCNG
GLMDFAFQYI KENGGLDSEE SYPYEAKDGS CKYRAEYAVA NDTGFVDIPQ QEKALMKAVA
TVGPISVAMD ASHPSLQFYS SGIYYEPNCS SKDLDHGVLV VGYGYEGTDS NKDKYWLVKN
SWGKEWGMDG YIKIAKDRNN HCGLATAASY PIVN
