CTSL (cathepsin L1)

Written2009-01Brigitte Goulet, Alain Nepveu
Cancer research Laboratory Program, London Regional Cancer Program at London Health Science Centre, the University of Western Ontario, London, Canada (BG); Department of Biochemistry, Goodman Cancer Centre, McGill University, Montreal, Canada (AN)

(Note : for Links provided by Atlas : click)

1. Identity

General Information
cathepsin L1
Alias_symbol (synonym)FLJ31037
Other aliasCATL
LocusID (NCBI) 1514
Atlas_Id 40208
Location 9q21.33  [Link to chromosome band 9q21]
Location_base_pair Starts at 87726059 and ends at 87731469 bp from pter ( according to hg19-Feb_2009)  [Mapping CTSL.png]
Local_order DAPK1 CTSL1 CTSL3
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BCAR3 (1p22.1) / CTSL (9q21.33)CTSL (9q21.33) / CTSL (9q21.33)CTSL (9q21.33) / EIF4A1 (17p13.1)
CTSL (9q21.33) / FHL1 (Xq26.3)PGM5 (9q21.11) / CTSL (9q21.33)


  Shown are the eight exons and seven intron of the human Cathepsin L1 gene. The black boxes correspond to protein coding.
Description The human Cathepsin L1 gene comprises eight exons and seven introns, and span 5411 bases. The first AUG translation initiation site is located within exon 2. Three spliced variants of hCATL-A have been identified; hCATL-AI, hCATL-AII, hCATL-AIII (Rescheleit et al., 1996; Bakhshi et al., 2001; Aurora et al., 2002; Jean et al., 2002). These spliced forms lack 27 nucleotide (nt), 90 nt and 144 nt from the 3' end of exon 1 respectively and lead to mRNA species that differ in the 5' untranslated regions. However, they are translated into identical proteins. The shorter 5'UTR lack secondary loops and are translated more effectively than hCATL-A (Aurora et al., 2002).
Transcription One major transcription initiation site is situated at -290 from the starting AUG on the human cDNA sequence (Joseph et al., 1988; Chatham et al., 1993; Bakhshi et al., 2001; Aurora et al., 2002; Jean et al., 2002). This mRNA of 1.7 Kb corresponds to hCATL-A. Another mRNA, hCATL-B, is transcribed from another TATA-less promoter localized within the first intron of hCATL-A and encodes the same cathepsin L protein (Joseph et al., 1988; Bakhshi et al., 2001; Seth, gene 2003). The hCATL-B therefore differs from hCATL-A in the 5' untranslated region (Bakhshi et al., 2001; Jean et al., 2002). The transcription factors NF-Y, SP1 and SP3 have been shown to be responsible for more than 85% of Cathepsin L expression in melanoma cells (Jean et al., 2002). In melanoma and in lymphoma cells, Cathepsin L expression is also regulated by CpG methylation, and gene amplification has been observed in one melanoma cell line (Jean et al., 2006). In tissue culture models, phorbol esters, certain oncogenes such as ras, v-src, SV-40 Large T and raf, cytokines such as IL-1, IL-6 and TNF-alpha, and hypoxia have all been shown to induce cathepsin L expression (Troen et al., 1991; Lemaire et al., 1994; Kakegawa et al., 1995; Lemaire et al., 1997; Heinrich et al., 2000; Gerber et al., 2001; Jean et al., 2008).
Pseudogene Using the program TBLASTN three pseudogenes, closely related to cathepsin L were identified on chromosome 10 (Rossi et al., 2004).

3. Protein

  Shown is a schematic representation of the various human cathepsin L isoforms. The full-length protein is composed of a signal peptide (pre), a pro-domain and the mature polypeptide. PF stands for proform, SC for single chain, HC for heavy chain and S correspond to the various short isoforms that are devoid of signal peptide and whose translation is initiated from internal, in-frame, AUGs located within the prodomain coding sequence.
Description CSTL1 codes for a protein of 333 amino-acids. Like all lysosomal enzymes, cathepsin L is translated as an inactive pre-pro-enzyme. The pre-region, located at the amino terminus of the protein, is a 17 amino-acid signal peptide (or signal sequence). Human cathepsin L is N-glycosylated at Asn 204. This glycosylation event is not required for proper folding of the protein or for its enzymatic activity or stability, but is important for lysosomal targeting (Smith et al., 1989; Kane, 1993). In certain cases, especially in transformed cells, secretion of procathepsin L (MEP) is observed (Gottesman, 1978). The crystal structure of procathepsin L has been resolved (Coulombe et al., 1996). Structurally, like most enzymes from the papain family, the mature cathepsin L consists of two globular regions, the R-domain (right) and L- domain (left) (Turk et al., 1997). These two domains are organized to form an open V-shaped active site cleft. The propiece of cathepsin L can also be separated into two regions. The amino-terminal part, which consists of the first 60 amino acids, is important for proper folding and glycosylation of procathepsin L (Chapman et al., 1997). Expression of the carboxy-terminal part of the prodomain is responsible for the inhibitory role of the propiece, by preventing the entry of the substrate into the active cleft. In order to do so, when the amino-terminus binds to the prodomain binding loop, the carboxy-terminus of the proregion bends over the groove of the active site in the opposite direction that the substrate would have been (Coulombe et al., 1996). The removal of the propiece occurs via an intra and/or inter molecular mechanism as the zymogen reaches the acidic environment of late endosomes or lysosomes (Nishimura et al., 1989; Salminen et al., 1990; Nomura et al., 1997; Ishidoh, et al., 2002). In order for the enzyme to become active, the proregion must be removed (Mason et al., 1992; Ishidoh et al., 1995). Studies have shown that other lysosomal enzymes, such as cathepsin D can also process procathepsin L and be involved in the initial steps of activation (Nishimura et al., 1989). In some cell types, the mature single chain form of cathepsin L is further processed into a two chains, heavy and light, by cleavage of the carboxy-terminus (Mason et al., 1985; Gal et al., 1986; Erickson, 1989). The optimal activity of mature cathepsin L requires a slightly acidic pH and a reducing environment which permits the active cysteine to be oxidized. The maximal activity of cathepsin L, using small synthetic peptides as substrates is at pH 5.5. The enzyme is most stable between pH 4.5 and 5.5. Like all cysteine proteases, the active site of cathepsin L is composed of a reactive cysteine (Cys 25), and a histidine (His 159). In the active form, both residues are charged, forming a thiolate-imidazolium ion pair (McGrath, 1999). Cathepsin L prefers a hydrophobic residue (mainly L/I) in the P2 position (cleavage occurs between residues P1 and P1') (Chapman et al., 1997). In addition, a shorter isoform of Cathepsin L has been detected. Translation at downstream, in-frame, AUGs is responsible for generating a protein that is devoid of a signal peptide which cannot be routed to the endoplasmic reticulum (Goulet et al., 2004; Goulet et al., 2007).
Localisation Cathepsin L is ubiquitously expressed. It is generally localized to the endosomes/lysosomes or secreted. Recently, various groups have reported the presence of Cathepsin L in the nucleus and the cytoplasm in various cell types (Goulet et al., 2004; Bulynko et al., 2006; Varanou et al., 2006; Sever et al., 2007; Duncan et al., 2008). Moreover, in neuroendocrine chromaffin cell types, Cathepsin L is detected in regulatory secretory vesicules (Yasothornsrikul et al., 2003).
Function Cathepsin L is a lysosomal enzyme originally thought to be involved in terminal protein degradation only. However, knockout mice showed that terminal protein degradation was not the work of a single cathepsin, as none of these mice had defects in protein degradation. The various phenotypes of these mice rather suggested that this protease has other specific biological roles. One knockout was generated, and two mice with natural mutations within the cathepsin L gene were also identified, Furless and Nackt. The furless mice possess a G-to-A mutation, which substitute an arginine for a glycine at position 149 of the cathepsin L protein sequence, resulting in an inactive enzyme (Roth et al., 2000). The nackt mice display a deletion in the cathepsin L gene, preventing the generation of any functional protein (Benavides et al., 2002). These three animal phenotypes have revealed that Cathepsin L plays a role in various physiological events in different tissues.
For example, Cathepsin L is important for epidermal homeostasis, regulation of the hair cycle, control of keratinocyte proliferation, MHC class-II mediated antigen presentation and selection of CD4+ T cells in cortical epithelial cells of the thymus (Nakagawa et al., 1998; Roth et al., 2000; Benavides et al., 2002; Reinheckel et al., 2005). Cathepsin L expression in thymocytes has been shown to be essential for natural killer cell development (Honey et al., 2002). Knockout mice models have demonstrated that Cathepsin L directly participates in atherosclerosis and in neovascularisation induced by endothelial progenitor cells (Maehr et al., 2005; Urbich et al., 2005; Kitamoto et al., 2007). These knockout mice have been observed to develop heart disease similar to human dilated cardiomyopathy (Stypmann et al., 2002). In general, pups lacking cathepsin L also have a slightly higher mortality upon weaning than their littermates (Reinheckel et al., 2001). Cathepsin L is responsible for the processing of viral proteins (Chandran et al., 2005; Pager et al., 2005; Kaletsky et al., 2007; Bosch et al., 2008) and the generation of neuropeptides and thyroid hormone (Funkelstein et al., 2008; Funkelstein et al., 2008). Cathepsin L activity is responsible for adipogenesis and glucose tolerance by degrading matrix fibronectin and processing the insulin receptor and IGF-1R beta (Yang et al., 2007). It is involved in intestinal epithelial cell polarization and differentiation (Boudreau et al., 2007) and in proteinuric kidney disease (Sever et al., 2007). Nuclear Cathepsin L was shown to proteolytically process a transcription factor during the G1/S progression of the cell cycle (Goulet et al., 2004) and histone H3 during mouse embryonic stem cell differentiation (Duncan et al., 2008). The landscape modifications of the histone on the Y chromosome and pericentromeric heterochromatine are stabilized by Cathepsin L (Bulynko et al., 2006). The role of Cathepsin L in cancer has been studied extensively. Secreted Cathepsin L degrades basal membrane and extracellular matrix therefore could increase the development of metastases. Intracellular cathepsin L activity can lead to activation of oncogenes or inactivation of tumor suppressors (Goulet et al., 2007). A recent paper also indicate that Cathepsin L plays a role in drug resistance (Zheng et al., 2008).
Homology Human Cathepsin L1 belongs to the papain superfamily. Cathepsin L2 (formerly called Cathepsin V) originated from ancestral Cathepsin L as they share 77% amino-acids identity. Moreover, both are similar to mouse cathepsin L (72% and 75% respectively) and other mammals (Itoh et al., 1999).

4. Mutations

Note Not determined.

5. Implicated in

Entity Various cancers
Oncogenesis Cathepsin L was initially identified as the major excreted protein (MEP) secreted from transformed fibroblastic cells (Gottesman, 1978; Troen et al., 1987; Troen et al., 1988). Oncogenic signals such as Ras, Raf, v-Src, fos, SV40 Large T as well as tumor promoters like phorbol ester can induce MEP expression and secretion (Joseph et al., 1987; Taniguchi et al., 1990; Troen et al., 1991; Lemaire et al., 1994; Heinrich et al., 2000). Moreover, cathepsin L secretion correlated with the metastatic potential of transformed cell lines (Denhardt et al., 1987; Chambers et al., 1992). Increased cathepsin L activity and secretion has been observed in many human cancers (Watanabe et al., 1987; Sheahan et al., 1989; Chauhan et al., 1991; Heidtmann et al., 1993; Nishida et al., 1995; Plebani et al., 1995; Park et al., 1996; Shuja et al., 1996; Sivaparvathi et al., 1996; Leto et al., 1997; Kim et al., 1998; Dohchin et al., 2000). Various reports also suggested that cathepsin L levels could be used as a potential indicator of tumor aggressiveness and metastasis (Thomssen et al., 1995; Park et al., 1996). Increased nuclear Cathepsin L expression and activity was recently found in various cancer cells, suggesting a different mechanism of cellular transformation (Goulet et al., 2007).
Therefore, although the association of cathepsin L and cancer is well established, its specific roles have not yet been fully elucidated.
Entity Breast cancer
Prognosis In breast cancer, numerous studies have indicated that secreted cathepsin L could be a strong and independent prognostic factor, with a strength similar to lymph node status and grading (Castiglioni et al., 1994; Thomssen et al., 1995; Duffy, 1996; Foekens et al., 1998; Thomssen et al., 1998; Harbeck et al., 2000; Harbeck et al., 2001; Levicar et al., 2002). Cathepsin L expression could also predict response to adjuvant chemotherapy (Jagodic et al., 2005).
Entity Gastric carcinoma
Prognosis Cathepsin L expression correlates with an early event in gastric carcinogenesis and with depth of invasion in early stage of gastric carcinoma. Higher expression is associated with worst prognosis (Plebani et al., 1995; Farinati et al., 1996; Dohchin et al., 2000).
Entity Skin cancer
Prognosis Higher concentration of Cathepsin L in early primary melanomas correlates with poor prognosis and indicate possible early metastasis spread (Stabuc et al., 2006). In malignant cells of squamous cell carcinoma, Cathepsin L is mainly overexpressed at the periphery of the tumor. Cathepsin L is also overexpressed in various inflammatory skin diseases such as psoriasis and atopic eczema (Bylaite et al., 2006).
Entity Ovarian cancer
Prognosis Cathepsin L expression is increased in ovarian cancer sample as well as in the serum of patients with ovarian cancer. Serum levels of Cathepsin L could be used in early detection of ovarian cancers (Nishida et al., 1995).
Entity Bladder cancer
Prognosis Urinary Cathepsin L is an independent predictor of bladder urothelial cell cancer and invasiveness (Svatek et al., 2008).
Entity Brain cancer (neuroblastoma)
Prognosis Cathepsin L has no prognostic value in glioma, but its expression is increased in tumor cells (Strojnik et al., 2005). In invasive benign meningioma and pituitary adenomas, Cathepesin L levels are also higher (Strojnik et al., 2001; Strojnik et al., 2005).
Entity Pancreatic adenocarcinoma
Prognosis Cathepsin L is a strong independent prognostic marker in resectable cancers (Niedergethmann et al., 2004).

6. Bibliography

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PMID 1482371
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PMID 15367886
Increased cathepsin L levels in serum in some patients with ovarian cancer: comparison with CA125 and CA72-4.
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PMID 2658811
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PMID 9020032
Cathepsin L is involved in proteolytic processing of the Hendra virus fusion protein.
Pager CT, Dutch RE.
J Virol. 2005 Oct;79(20):12714-20.
PMID 16188974
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PMID 8835762
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PMID 8625115
The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling.
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PMID 16079282
Sequence analysis and distribution of two new human cathepsin L splice variants.
Rescheleit DK, Rommerskirch WJ, Wiederanders B.
FEBS Lett. 1996 Oct 7;394(3):345-8.
PMID 8830671
Comprehensive search for cysteine cathepsins in the human genome.
Rossi A, Deveraux Q, Turk B, Sali A.
Biol Chem. 2004 May;385(5):363-72.
PMID 15195995
Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling.
Roth W, Deussing J, Botchkarev VA, Pauly-Evers M, Saftig P, Hafner A, Schmidt P, Schmahl W, Scherer J, Anton-Lamprecht I, Von Figura K, Paus R, Peters C.
FASEB J. 2000 Oct;14(13):2075-86.
PMID 11023992
Inhibitor studies indicate that active cathepsin L is probably essential to its own processing in cultured fibroblasts.
Salminen A, Gottesman MM.
Biochem J. 1990 Nov 15;272(1):39-44.
PMID 2264836
Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease.
Sever S, Altintas MM, Nankoe SR, Moller CC, Ko D, Wei C, Henderson J, del Re EC, Hsing L, Erickson A, Cohen CD, Kretzler M, Kerjaschki D, Rudensky A, Nikolic B, Reiser J.
J Clin Invest. 2007 Aug;117(8):2095-104.
PMID 17671649
Cysteine protease activities and tumor development in human colorectal carcinoma.
Sheahan K, Shuja S, Murnane MJ.
Cancer Res. 1989 Jul 15;49(14):3809-14.
PMID 2544258
Marked increases in cathepsin B and L activities distinguish papillary carcinoma of the thyroid from normal thyroid or thyroid with non-neoplastic disease.
Shuja S, Murnane MJ.
Int J Cancer. 1996 May 16;66(4):420-6.
PMID 8635854
Expression and immunohistochemical localization of cathepsin L during the progression of human gliomas.
Sivaparvathi M, Yamamoto M, Nicolson GL, Gokaslan ZL, Fuller GN, Liotta LA, Sawaya R, Rao JS.
Clin Exp Metastasis. 1996 Jan;14(1):27-34.
PMID 8521613
Glycosylation of procathepsin L does not account for species molecular-mass differences and is not required for proteolytic activity.
Smith SM, Kane SE, Gal S, Mason RW, Gottesman MM.
Biochem J. 1989 Sep 15;262(3):931-8.
PMID 2480110
Expression and prognostic significance of Cathepsin L in early cutaneous malignant melanoma.
Stabuc B, Mrevlje Z, Markovic J, Stabuc-Silih M.
Neoplasma. 2006;53(3):259-62.
PMID 16652198
Immunohistochemical staining of cathepsins B, L and stefin A in human hypophysis and pituitary adenomas.
Strojnik T, Lah TT, Zidanik B.
Anticancer Res. 2005 Jan-Feb;25(1B):587-94.
PMID 15816632
Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L.
Stypmann J, Glaser K, Roth W, Tobin DJ, Petermann I, Matthias R, Monnig G, Haverkamp W, Breithardt G, Schmahl W, Peters C, Reinheckel T.
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6234-9. Epub 2002 Apr 23.
PMID 11972068
Role of urinary cathepsin B and L in the detection of bladder urothelial cell carcinoma.
Svatek RS, Karam J, Karakiewicz PI, Gallina A, Casella R, Roehrborn CG, Shariat SF.
J Urol. 2008 Feb;179(2):478-84; discussion 484.
PMID 18076936
Augmented excretion of procathepsin L of a fos-transferred highly metastatic rat cell line.
Taniguchi S, Nishimura Y, Takahashi T, Baba T, Kato K.
Biochem Biophys Res Commun. 1990 Apr 30;168(2):520-6.
PMID 2185753
Identification of low-risk node-negative breast cancer patients by tumor biological factors PAI-1 and cathepsin L.
Thomssen C, Oppelt P, Janicke F, Ulm K, Harbeck N, Hofler H, Kuhn W, Graeff H, Schmitt M.
Anticancer Res. 1998 May-Jun;18(3C):2173-80.
PMID 9703780
Cloning and expression of the gene for the major excreted protein of transformed mouse fibroblasts. A secreted lysosomal protease regulated by transformation.
Troen BR, Ascherman D, Atlas D, Gottesman MM.
J Biol Chem. 1988 Jan 5;263(1):254-61.
PMID 2826441
Downstream sequences mediate induction of the mouse cathepsin L promoter by phorbol esters.
Troen BR, Chauhan SS, Ray D, Gottesman MM.
Cell Growth Differ. 1991 Jan;2(1):23-31.
PMID 1848774
Sequence and expression of the cDNA for MEP (major excreted protein), a transformation-regulated secreted cathepsin.
Troen BR, Gal S, Gottesman MM.
Biochem J. 1987 Sep 15;246(3):731-5.
PMID 3689328
Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors.
Turk B, Turk V, Turk D.
Biol Chem. 1997 Mar-Apr;378(3-4):141-50.
PMID 9165064
Cathepsin L is required for endothelial progenitor cell-induced neovascularization.
Urbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi MR, Vajkoczy P, Hofmann WK, Peters C, Pennacchio LA, Abolmaali ND, Chavakis E, Reinheckel T, Zeiher AM, Dimmeler S.
Nat Med. 2005 Feb;11(2):206-13. Epub 2005 Jan 23.
PMID 15665831
The importance of cysteine cathepsin proteases for placental development.
Varanou A, Withington SL, Lakasing L, Williamson C, Burton GJ, Hemberger M.
J Mol Med. 2006 Apr;84(4):305-17. Epub 2006 Jan 27.
PMID 16440214
Elevation of tissue cathepsin B and L activities in gastric cancer.
Watanabe M, Higashi T, Hashimoto M, Tomoda I, Tominaga S, Hashimoto N, Morimoto S, Yamauchi Y, Nakatsukasa H, Kobayashi M, et al.
Hepatogastroenterology. 1987 Jun;34(3):120-2.
PMID 3610018
Cathepsin L activity controls adipogenesis and glucose tolerance.
Yang M, Zhang Y, Pan J, Sun J, Liu J, Libby P, Sukhova GK, Doria A, Katunuma N, Peroni OD, Guerre-Millo M, Kahn BB, Clement K, Shi GP.
Nat Cell Biol. 2007 Aug;9(8):970-7. Epub 2007 Jul 22.
PMID 17643114
Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter.
Yasothornsrikul S, Greenbaum D, Medzihradszky KF, Toneff T, Bundey R, Miller R, Schilling B, Petermann I, Dehnert J, Logvinova A, Goldsmith P, Neveu JM, Lane WS, Gibson B, Reinheckel T, Peters C, Bogyo M, Hook V.
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9590-5. Epub 2003 Jul 17.
PMID 12869695
Cathepsin L Inhibition Suppresses Drug Resistance in Vitro and in Vivo: a Putative Mechanism.
Zheng X, Chu F, Chou PM, Gallati C, Dier U, Mirkin BL, Mousa SA, Rebbaa A.
Am J Physiol Cell Physiol. 2009 Jan;296(1):C65-74. Epub 2008 Oct 29.
PMID 18971393

7. Citation

This paper should be referenced as such :
Goulet, B ; Nepveu, A
CTSL1 (cathepsin L1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(12):918-924.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/CTSL1ID40208ch9q21.html

8. External links

HGNC (Hugo)CTSL   2537
Entrez_Gene (NCBI)CTSL  1514  cathepsin L
GeneCards (Weizmann)CTSL
Ensembl hg19 (Hinxton)ENSG00000135047 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000135047 [Gene_View] &nbspENSG00000135047 [Sequence]  chr9:87726059-87731469 [Contig_View]  CTSL [Vega]
ICGC DataPortalENSG00000135047
Genatlas (Paris)CTSL
SOURCE (Princeton)CTSL
Genetics Home Reference (NIH)CTSL
Genomic and cartography
GoldenPath hg38 (UCSC)CTSL  -     chr9:87726059-87731469 +  9q21.33   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CTSL  -     9q21.33   [Description]    (hg19-Feb_2009)
EnsemblCTSL - 9q21.33 [CytoView hg19]  CTSL - 9q21.33 [CytoView hg38]
Mapping of homologs : NCBICTSL [Mapview hg19]  CTSL [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF217997 AF304301 AF467444 AK055599 AK075100
RefSeq transcript (Entrez)NM_001257971 NM_001257972 NM_001257973 NM_001912 NM_145918
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CTSL
Cluster EST : UnigeneHs.731507 [ NCBI ]
CGAP (NCI)Hs.731507
Alternative Splicing GalleryENSG00000135047
Gene ExpressionCTSL [ NCBI-GEO ]   CTSL [ EBI - ARRAY_EXPRESS ]   CTSL [ SEEK ]   CTSL [ MEM ]
Gene Expression Viewer (FireBrowse)CTSL [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)1514
GTEX Portal (Tissue expression)CTSL
Human Protein AtlasENSG00000135047-CTSL [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP07711   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP07711  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP07711
Splice isoforms : SwissVarP07711
Catalytic activity : Enzyme3.4.22.15 [ Enzyme-Expasy ] [ IntEnz-EBI ] [ BRENDA ] [ KEGG ]   
Domaine pattern : Prosite (Expaxy)THIOL_PROTEASE_ASN (PS00640)    THIOL_PROTEASE_CYS (PS00139)    THIOL_PROTEASE_HIS (PS00639)   
Domains : Interpro (EBI)Pept_asp_AS    Pept_cys_AS    Pept_his_AS    Peptidase_C1A    Peptidase_C1A_C    Prot_inhib_I29   
Domain families : Pfam (Sanger)Inhibitor_I29 (PF08246)    Peptidase_C1 (PF00112)   
Domain families : Pfam (NCBI)pfam08246    pfam00112   
Domain families : Smart (EMBL)Inhibitor_I29 (SM00848)  Pept_C1 (SM00645)  
Conserved Domain (NCBI)CTSL
DMDM Disease mutations1514
Blocks (Seattle)CTSL
PDB (RSDB)1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
PDB Europe1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
PDB (PDBSum)1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
PDB (IMB)1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
Structural Biology KnowledgeBase1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
SCOP (Structural Classification of Proteins)1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
CATH (Classification of proteins structures)1CJL    1CS8    1ICF    1MHW    2NQD    2VHS    2XU1    2XU3    2XU4    2XU5    2YJ2    2YJ8    2YJ9    2YJB    2YJC    3BC3    3H89    3H8B    3H8C    3HHA    3HWN    3IV2    3K24    3KSE    3OF8    3OF9    4AXL    4AXM    5F02    5I4H    5MAE    5MAJ    5MQY   
Human Protein Atlas [tissue]ENSG00000135047-CTSL [tissue]
Peptide AtlasP07711
IPIIPI00012887   IPI00640540   
Protein Interaction databases
IntAct (EBI)P07711
Ontologies - Pathways
Ontology : AmiGOfibronectin binding  adaptive immune response  cysteine-type endopeptidase activity  cysteine-type endopeptidase activity  cysteine-type endopeptidase activity  serine-type endopeptidase activity  protein binding  collagen binding  extracellular region  extracellular region  extracellular space  extracellular space  nucleus  lysosome  lysosome  proteolysis  cysteine-type peptidase activity  antigen processing and presentation  antigen processing and presentation of exogenous peptide antigen via MHC class II  extracellular matrix disassembly  collagen catabolic process  collagen catabolic process  endolysosome lumen  histone binding  lysosomal lumen  proteoglycan binding  regulation of keratinocyte differentiation  proteolysis involved in cellular protein catabolic process  proteolysis involved in cellular protein catabolic process  extracellular exosome  macrophage apoptotic process  cellular response to thyroid hormone stimulus  serpin family protein binding  
Ontology : EGO-EBIfibronectin binding  adaptive immune response  cysteine-type endopeptidase activity  cysteine-type endopeptidase activity  cysteine-type endopeptidase activity  serine-type endopeptidase activity  protein binding  collagen binding  extracellular region  extracellular region  extracellular space  extracellular space  nucleus  lysosome  lysosome  proteolysis  cysteine-type peptidase activity  antigen processing and presentation  antigen processing and presentation of exogenous peptide antigen via MHC class II  extracellular matrix disassembly  collagen catabolic process  collagen catabolic process  endolysosome lumen  histone binding  lysosomal lumen  proteoglycan binding  regulation of keratinocyte differentiation  proteolysis involved in cellular protein catabolic process  proteolysis involved in cellular protein catabolic process  extracellular exosome  macrophage apoptotic process  cellular response to thyroid hormone stimulus  serpin family protein binding  
Pathways : KEGGLysosome    Phagosome    Antigen processing and presentation    Proteoglycans in cancer    Rheumatoid arthritis   
REACTOMEP07711 [protein]
REACTOME PathwaysR-HSA-8939242 [pathway]   
NDEx NetworkCTSL
Atlas of Cancer Signalling NetworkCTSL
Wikipedia pathwaysCTSL
Orthology - Evolution
GeneTree (enSembl)ENSG00000135047
Phylogenetic Trees/Animal Genes : TreeFamCTSL
Homologs : HomoloGeneCTSL
Homology/Alignments : Family Browser (UCSC)CTSL
Gene fusions - Rearrangements
Fusion : QuiverCTSL
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCTSL [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CTSL
Exome Variant ServerCTSL
ExAC (Exome Aggregation Consortium)ENSG00000135047
GNOMAD BrowserENSG00000135047
Varsome BrowserCTSL
Genetic variants : HAPMAP1514
Genomic Variants (DGV)CTSL [DGVbeta]
DECIPHERCTSL [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCTSL 
ICGC Data PortalCTSL 
TCGA Data PortalCTSL 
Broad Tumor PortalCTSL
OASIS PortalCTSL [ Somatic mutations - Copy number]
Mutations and Diseases : HGMDCTSL
BioMutasearch CTSL
DgiDB (Drug Gene Interaction Database)CTSL
DoCM (Curated mutations)CTSL (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CTSL (select a term)
NCG5 (London)CTSL
Cancer3DCTSL(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry CTSL
NextProtP07711 [Medical]
Target ValidationCTSL
Huge Navigator CTSL [HugePedia]
snp3D : Map Gene to Disease1514
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1514
Chemical/Pharm GKB GenePA162382890
Clinical trialCTSL
canSAR (ICR)CTSL (select the gene name)
DataMed IndexCTSL
PubMed226 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Jan 17 18:52:27 CET 2019

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