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 24-JUL-2024, entry version 241. 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; 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; 232. DR IntAct; P07711; 25. 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; 742 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 Reference proteome; Secreted; Signal; 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 //