ID CATL1_HUMAN Reviewed; 333 AA.
AC P07711; Q6IAV1; Q96QJ0;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 02-OCT-2024, entry version 242.
DE RecName: Full=Procathepsin L {ECO:0000305};
DE EC=3.4.22.15 {ECO:0000269|PubMed:9468501};
DE AltName: Full=Cathepsin L1 {ECO:0000305};
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|HGNC:HGNC:2537}; Synonyms=CTSL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3421948; DOI=10.1042/bj2530303;
RA Gal S., Gottesman M.M.;
RT "Isolation and sequence of a cDNA for human pro-(cathepsin L).";
RL Biochem. J. 253:303-306(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2835398; DOI=10.1172/jci113497;
RA Joseph L.J., Chang L.C., Stamenkovich D., Sukhatme V.P.;
RT "Complete nucleotide and deduced amino acid sequences of human and murine
RT preprocathepsin L. An abundant transcript induced by transformation of
RT fibroblasts.";
RL J. Clin. Invest. 81:1621-1629(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [7]
RP PROTEIN SEQUENCE OF 114-288 AND 292-333.
RX PubMed=3342889; DOI=10.1016/0014-5793(88)80028-0;
RA Ritonja A., Popovic T., Kotnik M., Machleidt W., Turk V.;
RT "Amino acid sequences of the human kidney cathepsins H and L.";
RL FEBS Lett. 228:341-345(1988).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-154.
RX PubMed=3550705; DOI=10.1093/nar/15.7.3186;
RA Joseph L.J., Lapid S., Sukhatme V.P.;
RT "The major ras induced protein in NIH3T3 cells is cathepsin L.";
RL Nucleic Acids Res. 15:3186-3186(1987).
RN [9]
RP PROTEIN SEQUENCE OF 114-154 AND 292-333.
RX PubMed=3545185; DOI=10.1042/bj2400373;
RA Mason R.W., Walker J.E., Northrop F.D.;
RT "The N-terminal amino acid sequences of the heavy and light chains of human
RT cathepsin L. Relationship to a cDNA clone for a major cysteine proteinase
RT from a mouse macrophage cell line.";
RL Biochem. J. 240:373-377(1986).
RN [10]
RP FUNCTION, PROTEOLYTICAL CLEAVAGE, MUTAGENESIS OF CYS-138, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND ACTIVE
RP SITE.
RX PubMed=9468501; DOI=10.1074/jbc.273.8.4478;
RA Menard R., Carmona E., Takebe S., Dufour E., Plouffe C., Mason P.,
RA Mort J.S.;
RT "Autocatalytic processing of recombinant human procathepsin L. Contribution
RT of both intermolecular and unimolecular events in the processing of
RT procathepsin L in vitro.";
RL J. Biol. Chem. 273:4478-4484(1998).
RN [11]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10716919; DOI=10.1093/emboj/19.6.1187;
RA Felbor U., Dreier L., Bryant R.A., Ploegh H.L., Olsen B.R., Mothes W.;
RT "Secreted cathepsin L generates endostatin from collagen XVIII.";
RL EMBO J. 19:1187-1194(2000).
RN [12]
RP GLYCOSYLATION AT ASN-221.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15099520; DOI=10.1016/s1097-2765(04)00209-6;
RA Goulet B., Baruch A., Moon N.S., Poirier M., Sansregret L.L., Erickson A.,
RA Bogyo M., Nepveu A.;
RT "A cathepsin L isoform that is devoid of a signal peptide localizes to the
RT nucleus in S phase and processes the CDP/Cux transcription factor.";
RL Mol. Cell 14:207-219(2004).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [15]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=16081529; DOI=10.1073/pnas.0505577102;
RA Simmons G., Gosalia D.N., Rennekamp A.J., Reeves J.D., Diamond S.L.,
RA Bates P.;
RT "Inhibitors of cathepsin L prevent severe acute respiratory syndrome
RT coronavirus entry.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:11876-11881(2005).
RN [16]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=16339146; DOI=10.1074/jbc.m508381200;
RA Huang I.C., Bosch B.J., Li F., Li W., Lee K.H., Ghiran S., Vasilieva N.,
RA Dermody T.S., Harrison S.C., Dormitzer P.R., Farzan M., Rottier P.J.,
RA Choe H.;
RT "SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to
RT infect ACE2-expressing cells.";
RL J. Biol. Chem. 281:3198-3203(2006).
RN [17]
RP FUNCTION (MICROBIAL INFECTION), AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18562523; DOI=10.1128/jvi.00415-08;
RA Bosch B.J., Bartelink W., Rottier P.J.;
RT "Cathepsin L functionally cleaves the severe acute respiratory syndrome
RT coronavirus class I fusion protein upstream of rather than adjacent to the
RT fusion peptide.";
RL J. Virol. 82:8887-8890(2008).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22905912; DOI=10.1021/pr300539b;
RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P.,
RA Mariman E.C., Renes J.;
RT "Resveratrol-induced changes of the human adipocyte secretion profile.";
RL J. Proteome Res. 11:4733-4743(2012).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP FUNCTION (MICROBIAL INFECTION), AND ACTIVITY REGULATION.
RX PubMed=26953343; DOI=10.1074/jbc.m116.716100;
RA Zhou N., Pan T., Zhang J., Li Q., Zhang X., Bai C., Huang F., Peng T.,
RA Zhang J., Liu C., Tao L., Zhang H.;
RT "Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late
RT Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East
RT Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory
RT Syndrome Coronavirus (SARS-CoV).";
RL J. Biol. Chem. 291:9218-9232(2016).
RN [23]
RP ACTIVITY REGULATION.
RX PubMed=30425301; DOI=10.1038/s41436-018-0355-3;
RA van den Bogaard E.H.J., van Geel M., van Vlijmen-Willems I.M.J.J.,
RA Jansen P.A.M., Peppelman M., van Erp P.E.J., Atalay S., Venselaar H.,
RA Simon M.E.H., Joosten M., Schalkwijk J., Zeeuwen P.L.J.M.;
RT "Deficiency of the human cysteine protease inhibitor cystatin M/E causes
RT hypotrichosis and dry skin.";
RL Genet. Med. 21:1559-1567(2019).
RN [24]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32142651; DOI=10.1016/j.cell.2020.02.052;
RA Hoffmann M., Kleine-Weber H., Schroeder S., Krueger N., Herrler T.,
RA Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A.,
RA Mueller M.A., Drosten C., Poehlmann S.;
RT "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a
RT clinically proven protease inhibitor.";
RL Cell 181:1-10(2020).
RN [25]
RP ACTIVITY REGULATION.
RX PubMed=32361028; DOI=10.1016/j.ijantimicag.2020.106004;
RA Smieszek S.P., Przychodzen B.P., Polymeropoulos M.H.;
RT "Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19
RT treatment.";
RL Int. J. Antimicrob. Agents 55:106004-106004(2020).
RN [26]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32221306; DOI=10.1038/s41467-020-15562-9;
RA Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T.,
RA Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z.;
RT "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and
RT its immune cross-reactivity with SARS-CoV.";
RL Nat. Commun. 11:1620-1620(2020).
RN [27]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=32855215; DOI=10.1126/science.abb3753;
RA Bruchez A., Sha K., Johnson J., Chen L., Stefani C., McConnell H.,
RA Gaucherand L., Prins R., Matreyek K.A., Hume A.J., Muehlberger E.,
RA Schmidt E.V., Olinger G.G., Stuart L.M., Lacy-Hulbert A.;
RT "MHC class II transactivator CIITA induces cell resistance to Ebola virus
RT and SARS-like coronaviruses.";
RL Science 370:241-247(2020).
RN [28]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=34159616; DOI=10.15252/embj.2021107821;
RA Koch J., Uckeley Z.M., Doldan P., Stanifer M., Boulant S., Lozach P.Y.;
RT "TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect
RT host cells.";
RL EMBO J. 40:1-20(2021).
RN [29] {ECO:0007744|PDB:1CJL, ECO:0007744|PDB:1CS8}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 18-333.
RX PubMed=8896443; DOI=10.1002/j.1460-2075.1996.tb00934.x;
RA Coulombe R., Grochulski P., Sivaraman J., Menard R., Mort J.S., Cygler M.;
RT "Structure of human procathepsin L reveals the molecular basis of
RT inhibition by the prosegment.";
RL EMBO J. 15:5492-5503(1996).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-333.
RX PubMed=9141479; DOI=10.1016/s0014-5793(97)00216-0;
RA Fujishima A., Imai Y., Nomura T., Fujisawa Y., Yamamoto Y., Sugarawa T.;
RT "The crystal structure of human cathepsin L complexed with E-64.";
RL FEBS Lett. 407:47-50(1997).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 18-333.
RA Cygler M., Coulombe R.;
RL Submitted (AUG-1999) to the PDB data bank.
CC -!- FUNCTION: Thiol protease important for the overall degradation of
CC proteins in lysosomes (Probable). Plays a critical for normal cellular
CC functions such as general protein turnover, antigen processing and bone
CC 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 cells
CC (By similarity). 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 (PubMed:10716919).
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:P25975, ECO:0000269|PubMed:10716919,
CC ECO:0000305}.
CC -!- FUNCTION: (Microbial infection) In cells lacking TMPRSS2 expression,
CC facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via
CC a slow acid-activated route with the proteolysis of coronavirus spike
CC (S) glycoproteins in lysosome for entry into host cell
CC (PubMed:16339146, PubMed:18562523, PubMed:32142651, PubMed:32221306).
CC Proteolysis within lysosomes is sufficient to activate membrane fusion
CC by coronaviruses SARS-CoV and EMC (HCoV-EMC) S as well as Zaire
CC ebolavirus glycoproteins (PubMed:16081529, PubMed:18562523,
CC PubMed:26953343). {ECO:0000269|PubMed:16081529,
CC ECO:0000269|PubMed:16339146, ECO:0000269|PubMed:18562523,
CC ECO:0000269|PubMed:26953343, ECO:0000269|PubMed:32142651,
CC ECO:0000269|PubMed:32221306, ECO:0000269|PubMed:32855215}.
CC -!- FUNCTION: [Isoform 2]: Functions in the regulation of cell cycle
CC progression through proteolytic processing of the CUX1 transcription
CC factor (PubMed:15099520). Translation initiation at downstream start
CC sites allows the synthesis of isoforms that are devoid of a signal
CC peptide and localize to the nucleus where they cleave the CUX1
CC transcription factor and modify its DNA binding properties
CC (PubMed:15099520). {ECO:0000269|PubMed:15099520}.
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:0000269|PubMed:9468501};
CC -!- ACTIVITY REGULATION: Inhibited by the propeptide produced by
CC autocleavage (PubMed:9468501). 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 teicoplanin
CC (PubMed:26953343). Inhibited by amantadine (PubMed:32361028).
CC {ECO:0000250|UniProtKB:P06797, ECO:0000269|PubMed:26953343,
CC ECO:0000269|PubMed:30425301, ECO:0000269|PubMed:32361028,
CC ECO:0000269|PubMed:9468501}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.5, also active at pH 7.0 with CUX1 as substrate.
CC {ECO:0000269|PubMed:10716919, ECO:0000269|PubMed:15099520,
CC ECO:0000269|PubMed:18562523, ECO:0000269|PubMed:9468501};
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 -!- INTERACTION:
CC P07711; O60911: CTSV; NbExp=3; IntAct=EBI-1220160, EBI-1549974;
CC P07711; O43765: SGTA; NbExp=3; IntAct=EBI-1220160, EBI-347996;
CC P07711; P0DTC2: S; Xeno; NbExp=3; IntAct=EBI-1220160, EBI-25474821;
CC P07711; P59594: S; Xeno; NbExp=2; IntAct=EBI-1220160, EBI-15582614;
CC P07711; G5EFH4: srp-6; Xeno; NbExp=2; IntAct=EBI-1220160, EBI-1549936;
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:0000250|UniProtKB:P25975}. 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 -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:15099520}. Note=Translation initiation at
CC downstream start sites allows the synthesis of isoforms that are devoid
CC of a signal peptide and do not transit through the endoplasmic
CC reticulum to localize to the nucleus (PubMed:15099520). Nuclear
CC location varies during the cell cycle, with higher levels during S
CC phase (PubMed:15099520). {ECO:0000269|PubMed:15099520}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=P07711-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P07711-3; Sequence=VSP_060720;
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 (PubMed:9468501). {ECO:0000250|UniProtKB:P06797,
CC ECO:0000269|PubMed:9468501}.
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 -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40208/CTSL1";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X12451; CAA30981.1; -; mRNA.
DR EMBL; M20496; AAA66974.1; -; mRNA.
DR EMBL; CR457053; CAG33334.1; -; mRNA.
DR EMBL; BX537395; CAD97637.1; -; mRNA.
DR EMBL; AL160279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012612; AAH12612.1; -; mRNA.
DR EMBL; X05256; CAA28877.1; -; mRNA.
DR CCDS; CCDS6675.1; -. [P07711-1]
DR CCDS; CCDS94433.1; -. [P07711-3]
DR PIR; S01002; KHHUL.
DR RefSeq; NP_001244900.1; NM_001257971.1. [P07711-1]
DR RefSeq; NP_001244901.1; NM_001257972.1. [P07711-1]
DR RefSeq; NP_001903.1; NM_001912.4. [P07711-1]
DR RefSeq; NP_666023.1; NM_145918.2. [P07711-1]
DR RefSeq; XP_005251773.1; XM_005251716.3.
DR PDB; 1CJL; X-ray; 2.20 A; A=22-333.
DR PDB; 1CS8; X-ray; 1.80 A; A=19-333.
DR PDB; 1ICF; X-ray; 2.00 A; A/C=114-288, B/D=292-333.
DR PDB; 1MHW; X-ray; 1.90 A; A/B=114-288, C/D=292-333.
DR PDB; 2NQD; X-ray; 1.75 A; B=113-333.
DR PDB; 2VHS; X-ray; 1.50 A; A/B/C/D=114-333.
DR PDB; 2XU1; X-ray; 1.45 A; A/B/C/D=114-333.
DR PDB; 2XU3; X-ray; 0.90 A; A=114-333.
DR PDB; 2XU4; X-ray; 1.12 A; A=114-333.
DR PDB; 2XU5; X-ray; 1.60 A; A=114-333.
DR PDB; 2YJ2; X-ray; 1.15 A; A=114-333.
DR PDB; 2YJ8; X-ray; 1.30 A; A=114-333.
DR PDB; 2YJ9; X-ray; 1.35 A; A=114-333.
DR PDB; 2YJB; X-ray; 1.40 A; A=114-333.
DR PDB; 2YJC; X-ray; 1.14 A; A=114-333.
DR PDB; 3BC3; X-ray; 2.20 A; A/B=114-333.
DR PDB; 3H89; X-ray; 2.50 A; A/B/C/D/E/F=114-333.
DR PDB; 3H8B; X-ray; 1.80 A; A/B/C/D/E/F=114-333.
DR PDB; 3H8C; X-ray; 2.50 A; A/B=114-333.
DR PDB; 3HHA; X-ray; 1.27 A; A/B/C/D=114-333.
DR PDB; 3HWN; X-ray; 2.33 A; A/B/C/D=76-333.
DR PDB; 3IV2; X-ray; 2.20 A; A/B=114-333.
DR PDB; 3K24; X-ray; 2.50 A; A/B=114-333.
DR PDB; 3KSE; X-ray; 1.71 A; A/B/C=114-333.
DR PDB; 3OF8; X-ray; 2.20 A; A=113-333.
DR PDB; 3OF9; X-ray; 1.76 A; A=113-333.
DR PDB; 4AXL; X-ray; 1.92 A; A=114-333.
DR PDB; 4AXM; X-ray; 2.80 A; A/B/F/I/L/O=114-333.
DR PDB; 5F02; X-ray; 1.43 A; A=114-333.
DR PDB; 5I4H; X-ray; 1.42 A; A=113-218, B=222-333.
DR PDB; 5MAE; X-ray; 1.00 A; A=114-333.
DR PDB; 5MAJ; X-ray; 1.00 A; A=114-333.
DR PDB; 5MQY; X-ray; 1.13 A; A=114-333.
DR PDB; 6EZP; X-ray; 1.37 A; A=114-333.
DR PDB; 6EZX; X-ray; 2.34 A; A/B=114-333.
DR PDB; 6F06; X-ray; 2.02 A; A/B=114-333.
DR PDB; 6JD0; X-ray; 1.80 A; A=18-333.
DR PDB; 6JD8; X-ray; 1.46 A; A=18-333.
DR PDB; 7QKB; X-ray; 1.80 A; A/B/C/D=114-333.
DR PDB; 7QKC; X-ray; 1.69 A; A/B/C/D=114-333.
DR PDB; 7QKD; X-ray; 1.50 A; A/B/C/D=114-333.
DR PDB; 7W33; X-ray; 2.39 A; A=1-333.
DR PDB; 7W34; X-ray; 2.89 A; A=1-333.
DR PDB; 7Z3T; X-ray; 1.60 A; A/B/C/D=114-333.
DR PDB; 7Z58; X-ray; 1.35 A; A/B/C/D=114-333.
DR PDB; 7ZS7; X-ray; 1.60 A; A/B/C/D=114-333.
DR PDB; 7ZVF; X-ray; 1.60 A; A/B/C/D=114-333.
DR PDB; 7ZXA; X-ray; 1.60 A; A/B/C/D=114-333.
DR PDB; 8A4U; X-ray; 1.90 A; A/B/C/D=114-333.
DR PDB; 8A4V; X-ray; 1.65 A; A/B/C/D=114-333.
DR PDB; 8A4W; X-ray; 1.40 A; A/B/C/D=114-333.
DR PDB; 8A4X; X-ray; 1.80 A; A/B/C/D=114-333.
DR PDB; 8A5B; X-ray; 1.80 A; A/B/C/D=114-333.
DR PDB; 8AHV; X-ray; 1.70 A; A/B/C/D=114-333.
DR PDB; 8B4F; X-ray; 1.90 A; A/B/C/D=114-333.
DR PDB; 8C77; X-ray; 1.70 A; A/B/C/D=114-333.
DR PDB; 8GX2; X-ray; 2.00 A; A/B=1-333.
DR PDB; 8HET; X-ray; 2.00 A; A=114-333.
DR PDB; 8HFV; X-ray; 2.10 A; A/B/C/D=114-333.
DR PDB; 8OFA; X-ray; 1.90 A; A/B/C/D=114-333.
DR PDB; 8OZA; X-ray; 1.80 A; A/B/C/D=114-333.
DR PDB; 8PRX; X-ray; 1.80 A; A/B/C/D=114-333.
DR PDB; 8QKB; X-ray; 1.60 A; A/B/C/D=114-333.
DR PDB; 8UAC; X-ray; 1.40 A; A/B=114-333.
DR PDBsum; 1CJL; -.
DR PDBsum; 1CS8; -.
DR PDBsum; 1ICF; -.
DR PDBsum; 1MHW; -.
DR PDBsum; 2NQD; -.
DR PDBsum; 2VHS; -.
DR PDBsum; 2XU1; -.
DR PDBsum; 2XU3; -.
DR PDBsum; 2XU4; -.
DR PDBsum; 2XU5; -.
DR PDBsum; 2YJ2; -.
DR PDBsum; 2YJ8; -.
DR PDBsum; 2YJ9; -.
DR PDBsum; 2YJB; -.
DR PDBsum; 2YJC; -.
DR PDBsum; 3BC3; -.
DR PDBsum; 3H89; -.
DR PDBsum; 3H8B; -.
DR PDBsum; 3H8C; -.
DR PDBsum; 3HHA; -.
DR PDBsum; 3HWN; -.
DR PDBsum; 3IV2; -.
DR PDBsum; 3K24; -.
DR PDBsum; 3KSE; -.
DR PDBsum; 3OF8; -.
DR PDBsum; 3OF9; -.
DR PDBsum; 4AXL; -.
DR PDBsum; 4AXM; -.
DR PDBsum; 5F02; -.
DR PDBsum; 5I4H; -.
DR PDBsum; 5MAE; -.
DR PDBsum; 5MAJ; -.
DR PDBsum; 5MQY; -.
DR PDBsum; 6EZP; -.
DR PDBsum; 6EZX; -.
DR PDBsum; 6F06; -.
DR PDBsum; 6JD0; -.
DR PDBsum; 6JD8; -.
DR PDBsum; 7QKB; -.
DR PDBsum; 7QKC; -.
DR PDBsum; 7QKD; -.
DR PDBsum; 7W33; -.
DR PDBsum; 7W34; -.
DR PDBsum; 7Z3T; -.
DR PDBsum; 7Z58; -.
DR PDBsum; 7ZS7; -.
DR PDBsum; 7ZVF; -.
DR PDBsum; 7ZXA; -.
DR PDBsum; 8A4U; -.
DR PDBsum; 8A4V; -.
DR PDBsum; 8A4W; -.
DR PDBsum; 8A4X; -.
DR PDBsum; 8A5B; -.
DR PDBsum; 8AHV; -.
DR PDBsum; 8B4F; -.
DR PDBsum; 8C77; -.
DR PDBsum; 8GX2; -.
DR PDBsum; 8HET; -.
DR PDBsum; 8HFV; -.
DR PDBsum; 8OFA; -.
DR PDBsum; 8OZA; -.
DR PDBsum; 8PRX; -.
DR PDBsum; 8QKB; -.
DR PDBsum; 8UAC; -.
DR AlphaFoldDB; P07711; -.
DR SMR; P07711; -.
DR BioGRID; 107894; 233.
DR IntAct; P07711; 33.
DR MINT; P07711; -.
DR STRING; 9606.ENSP00000345344; -.
DR BindingDB; P07711; -.
DR ChEMBL; CHEMBL3837; -.
DR DrugBank; DB07477; Felbinac.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB03661; L-cysteic acid.
DR DrugBank; DB14962; Trastuzumab deruxtecan.
DR DrugCentral; P07711; -.
DR GuidetoPHARMACOLOGY; 2351; -.
DR MEROPS; C01.032; -.
DR MEROPS; I29.001; -.
DR GlyConnect; 1081; 12 N-Linked glycans (1 site).
DR GlyCosmos; P07711; 2 sites, 14 glycans.
DR GlyGen; P07711; 3 sites, 13 N-linked glycans (1 site), 1 O-linked glycan (2 sites).
DR iPTMnet; P07711; -.
DR PhosphoSitePlus; P07711; -.
DR BioMuta; CTSL; -.
DR DMDM; 115741; -.
DR jPOST; P07711; -.
DR MassIVE; P07711; -.
DR PaxDb; 9606-ENSP00000345344; -.
DR PeptideAtlas; P07711; -.
DR ProteomicsDB; 52023; -.
DR Pumba; P07711; -.
DR ABCD; P07711; 1 sequenced antibody.
DR Antibodypedia; 4374; 748 antibodies from 39 providers.
DR DNASU; 1514; -.
DR Ensembl; ENST00000340342.11; ENSP00000365061.5; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000343150.10; ENSP00000345344.5; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000676480.1; ENSP00000504279.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000676531.1; ENSP00000503439.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000676769.1; ENSP00000504405.1; ENSG00000135047.16. [P07711-3]
DR Ensembl; ENST00000676881.1; ENSP00000502901.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000676946.1; ENSP00000503470.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000677019.1; ENSP00000504473.1; ENSG00000135047.16. [P07711-3]
DR Ensembl; ENST00000677262.1; ENSP00000503851.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000677761.1; ENSP00000503938.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000677821.1; ENSP00000503298.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000677864.1; ENSP00000503881.1; ENSG00000135047.16. [P07711-3]
DR Ensembl; ENST00000678442.1; ENSP00000503897.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000679149.1; ENSP00000504313.1; ENSG00000135047.16. [P07711-1]
DR Ensembl; ENST00000679157.1; ENSP00000502968.1; ENSG00000135047.16. [P07711-1]
DR GeneID; 1514; -.
DR KEGG; hsa:1514; -.
DR MANE-Select; ENST00000343150.10; ENSP00000345344.5; NM_001912.5; NP_001903.1.
DR UCSC; uc004aph.4; human. [P07711-1]
DR AGR; HGNC:2537; -.
DR CTD; 1514; -.
DR DisGeNET; 1514; -.
DR GeneCards; CTSL; -.
DR HGNC; HGNC:2537; CTSL.
DR HPA; ENSG00000135047; Tissue enhanced (placenta).
DR MIM; 116880; gene.
DR neXtProt; NX_P07711; -.
DR OpenTargets; ENSG00000135047; -.
DR PharmGKB; PA162382890; -.
DR VEuPathDB; HostDB:ENSG00000135047; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000154367; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; P07711; -.
DR OMA; VYYDEEC; -.
DR OrthoDB; 5472948at2759; -.
DR PhylomeDB; P07711; -.
DR TreeFam; TF313739; -.
DR BRENDA; 3.4.22.15; 2681.
DR BRENDA; 3.4.22.43; 2681.
DR BRENDA; 3.4.22.B49; 2681.
DR PathwayCommons; P07711; -.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR Reactome; R-HSA-9678110; Attachment and Entry.
DR Reactome; R-HSA-9694614; Attachment and Entry.
DR SignaLink; P07711; -.
DR SIGNOR; P07711; -.
DR BioGRID-ORCS; 1514; 28 hits in 1168 CRISPR screens.
DR ChiTaRS; CTSL; human.
DR EvolutionaryTrace; P07711; -.
DR GeneWiki; Cathepsin_L1; -.
DR GenomeRNAi; 1514; -.
DR Pharos; P07711; Tclin.
DR PRO; PR:P07711; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P07711; protein.
DR Bgee; ENSG00000135047; Expressed in stromal cell of endometrium and 214 other cell types or tissues.
DR ExpressionAtlas; P07711; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042583; C:chromaffin granule; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0071682; C:endocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0036021; C:endolysosome lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005771; C:multivesicular body; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; TAS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0005518; F:collagen binding; IDA:BHF-UCL.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:UniProtKB.
DR GO; GO:0001968; F:fibronectin binding; IPI:BHF-UCL.
DR GO; GO:0042393; F:histone binding; IDA:BHF-UCL.
DR GO; GO:0043394; F:proteoglycan binding; IPI:BHF-UCL.
DR GO; GO:0097655; F:serpin family protein binding; IPI:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEP:UniProtKB.
DR GO; GO:0019882; P:antigen processing and presentation; TAS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
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:0097067; P:cellular response to thyroid hormone stimulus; IEP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0071888; P:macrophage apoptotic process; NAS:BHF-UCL.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0019065; P:receptor-mediated endocytosis of virus by host cell; IDA:UniProtKB.
DR GO; GO:0046718; P:symbiont entry into host cell; IDA:UniProtKB.
DR GO; GO:0031638; P:zymogen activation; IDA:UniProtKB.
DR CDD; cd02248; Peptidase_C1A; 1.
DR Gene3D; 3.90.70.10; Cysteine proteinases; 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; IPR013128; Peptidase_C1A.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR PANTHER; PTHR12411; CYSTEINE PROTEASE FAMILY C1-RELATED; 1.
DR PANTHER; PTHR12411:SF902; PROCATHEPSIN L; 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; Cysteine proteinases; 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; Alternative initiation; Cell membrane; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Hydrolase; Lysosome; Membrane; Nucleus; Protease;
KW Proteomics identification; Reference proteome; Secreted; Signal;
KW Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:P07154"
FT PROPEP 18..113
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:9468501"
FT /id="PRO_0000026244"
FT CHAIN 114..333
FT /note="Cathepsin L"
FT /evidence="ECO:0000269|PubMed:9468501"
FT /id="PRO_0000450791"
FT CHAIN 114..288
FT /note="Cathepsin L heavy chain"
FT /id="PRO_0000026245"
FT PROPEP 289..291
FT /id="PRO_0000026246"
FT CHAIN 292..333
FT /note="Cathepsin L light chain"
FT /evidence="ECO:0000269|PubMed:3545185"
FT /id="PRO_0000026247"
FT ACT_SITE 138
FT /evidence="ECO:0000305|PubMed:9468501"
FT ACT_SITE 276
FT ACT_SITE 300
FT SITE 106..107
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:9468501"
FT SITE 107..108
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:9468501"
FT SITE 112..113
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:9468501"
FT SITE 113..114
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:9468501"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT DISULFID 135..178
FT /evidence="ECO:0000269|PubMed:8896443,
FT ECO:0007744|PDB:1CJL, ECO:0007744|PDB:1CS8"
FT DISULFID 169..211
FT /evidence="ECO:0000269|PubMed:8896443,
FT ECO:0007744|PDB:1CJL, ECO:0007744|PDB:1CS8"
FT DISULFID 269..322
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000269|PubMed:8896443,
FT ECO:0007744|PDB:1CJL, ECO:0007744|PDB:1CS8"
FT VAR_SEQ 1..55
FT /note="Missing (in isoform 2)"
FT /id="VSP_060720"
FT MUTAGEN 138
FT /note="C->S: Catalytically inactive. Unable to autocleave
FT procathepsin L."
FT /evidence="ECO:0000269|PubMed:9468501"
FT CONFLICT 56
FT /note="M -> V (in Ref. 6; AAH12612)"
FT /evidence="ECO:0000305"
FT CONFLICT 268
FT /note="D -> N (in Ref. 7; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:6JD8"
FT HELIX 26..35
FT /evidence="ECO:0007829|PDB:6JD8"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:6JD8"
FT HELIX 45..67
FT /evidence="ECO:0007829|PDB:6JD8"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:6JD8"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:6JD8"
FT HELIX 85..91
FT /evidence="ECO:0007829|PDB:6JD8"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:6JD8"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:6EZX"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 138..155
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 163..169
FT /evidence="ECO:0007829|PDB:2XU3"
FT TURN 171..174
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:2XU4"
FT HELIX 183..193
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:2XU3"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 232..241
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:4AXL"
FT STRAND 276..285
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:6EZP"
FT TURN 307..309
FT /evidence="ECO:0007829|PDB:7W34"
FT STRAND 311..315
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:2XU3"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:2XU3"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:2XU3"
FT STRAND 329..332
FT /evidence="ECO:0007829|PDB:2XU3"
SQ SEQUENCE 333 AA; 37564 MW; 8CD17D00EF859D85 CRC64;
MNPTLILAAF CLGIASATLT FDHSLEAQWT KWKAMHNRLY GMNEEGWRRA VWEKNMKMIE
LHNQEYREGK HSFTMAMNAF GDMTSEEFRQ VMNGFQNRKP RKGKVFQEPL FYEAPRSVDW
REKGYVTPVK NQGQCGSCWA FSATGALEGQ MFRKTGRLIS LSEQNLVDCS GPQGNEGCNG
GLMDYAFQYV QDNGGLDSEE SYPYEATEES CKYNPKYSVA NDTGFVDIPK QEKALMKAVA
TVGPISVAID AGHESFLFYK EGIYFEPDCS SEDMDHGVLV VGYGFESTES DNNKYWLVKN
SWGEEWGMGG YVKMAKDRRN HCGIASAASY PTV
//