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CTSL cathepsin L [ Homo sapiens (human) ]

Gene ID: 1514, updated on 13-Mar-2024

Summary

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Official Symbol
CTSLprovided by HGNC
Official Full Name
cathepsin Lprovided by HGNC
Primary source
HGNC:HGNC:2537
See related
Ensembl:ENSG00000135047 MIM:116880; AllianceGenome:HGNC:2537
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MEP; CATL; CTSL1
Summary
The protein encoded by this gene is a lysosomal cysteine proteinase that plays a major role in intracellular protein catabolism. Its substrates include collagen and elastin, as well as alpha-1 protease inhibitor, a major controlling element of neutrophil elastase activity. The encoded protein has been implicated in several pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. This protein, which is a member of the peptidase C1 family, is a dimer composed of disulfide-linked heavy and light chains, both produced from a single protein precursor. Additionally, this protein cleaves the S1 subunit of the SARS-CoV-2 spike protein, which is necessary for entry of the virus into the cell. [provided by RefSeq, Aug 2020]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression
Broad expression in placenta (RPKM 162.6), kidney (RPKM 60.4) and 23 other tissues See more
Orthologs
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Genomic context

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Location:
9q21.33
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (87726119..87731469)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (99879735..99885089)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (90341034..90346384)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene death associated protein kinase 1 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr9:90145230-90146212 Neighboring gene ribosomal protein S29 pseudogene 18 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108388 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108397 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:90178705-90179204 Neighboring gene DAPK1 intronic transcript 1 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108408 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_108410 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:90186048-90186548 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:90207629-90208129 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:90215267-90215860 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28521 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28522 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:90234560-90235060 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:90249751-90250336 Neighboring gene ReSE screen-validated silencer GRCh37_chr9:90308876-90309094 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr9:90314444-90315643 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr9:90317453-90318652 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr9:90328302-90329501 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28523 Neighboring gene CTSL promoter region Neighboring gene CTSL 3' regulatory element Neighboring gene uncharacterized LOC124902198 Neighboring gene EIF3J pseudogene 3

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis. Mouawad JE, et al. Rheumatology (Oxford), 2023 Mar 1. PMID 35900152, Free PMC Article
  2. COVID-19 receptor and malignant cancers: Association of CTSL expression with susceptibility to SARS-CoV-2. Zhang L, et al. Int J Biol Sci, 2022. PMID 35414771, Free PMC Article
  3. Expressions and significances of CTSL, the target of COVID-19 on GBM. Dong Q, et al. J Cancer Res Clin Oncol, 2022 Mar. PMID 34807310, Free PMC Article
  4. Upregulation of cathepsin L gene under mild cold conditions in young Japanese male adults. Yasukochi Y, et al. J Physiol Anthropol, 2021 Oct 22. PMID 34686211, Free PMC Article
  5. The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis. Wang X, et al. J Exp Clin Cancer Res, 2021 May 1. PMID 33933142, Free PMC Article

See all (263) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.
    Title: Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.
  2. Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner.
    Title: Methyltransferase-like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6-methyladenosine-dependent manner.
  3. Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis.
    Title: Reduced Cathepsin L expression and secretion into the extracellular milieu contribute to lung fibrosis in systemic sclerosis.
  4. A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer.
    Title: A novel high-risk subpopulation identified by CTSL and ZBTB7B in gastric cancer.
  5. COVID-19 receptor and malignant cancers: Association of CTSL expression with susceptibility to SARS-CoV-2.
    Title: COVID-19 receptor and malignant cancers: Association of CTSL expression with susceptibility to SARS-CoV-2.
  6. Expressions and significances of CTSL, the target of COVID-19 on GBM.
    Title: Expressions and significances of CTSL, the target of COVID-19 on GBM.
  7. XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells.
    Title: XPA is susceptible to proteolytic cleavage by cathepsin L during lysis of quiescent cells.
  8. Mechanisms of L-Serine-Mediated Neuroprotection Include Selective Activation of Lysosomal Cathepsins B and L.
    Title: Mechanisms of L-Serine-Mediated Neuroprotection Include Selective Activation of Lysosomal Cathepsins B and L.
  9. The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis.
    Title: The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis.
  10. Upregulation of cathepsin L gene under mild cold conditions in young Japanese male adults.
    Title: Upregulation of cathepsin L gene under mild cold conditions in young Japanese male adults.
Submit: New GeneRIF Correction See all GeneRIFs (173)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Cathepsin L cleaves HIV-1 gp120 at positions A3-L4 (HSV-1gD domain), K327-G328 (V3 domain), and G431-K432 and Y435-A436 (C4 domain), which is important for antigen processing and presentation PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ31037

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables collagen binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type endopeptidase activator activity involved in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type endopeptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables cysteine-type endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables cysteine-type endopeptidase activity TAS
Traceable Author Statement
more info
  
enables cysteine-type peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables fibronectin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables histone binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables proteoglycan binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables serpin family protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in CD4-positive, alpha-beta T cell lineage commitment ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in adaptive immune response IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in antigen processing and presentation TAS
Traceable Author Statement
more info
 PubMed 
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II TAS
Traceable Author Statement
more info
  
involved_in antigen processing and presentation of peptide antigen ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in cellular response to thyroid hormone stimulus IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in collagen catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in elastin catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in enkephalin processing ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in fusion of virus membrane with host endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in fusion of virus membrane with host plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in immune response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in macrophage apoptotic process NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in positive regulation of apoptotic signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in positive regulation of peptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein autoprocessing IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in proteolysis involved in protein catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proteolysis involved in protein catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in receptor-mediated endocytosis of virus by host cell IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in symbiont entry into host cell IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in zymogen activation IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
  
located_in apical plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in chromaffin granule ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in collagen-containing extracellular matrix HDA PubMed 
located_in endocytic vesicle lumen TAS
Traceable Author Statement
more info
  
located_in endolysosome lumen TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in lysosomal lumen TAS
Traceable Author Statement
more info
  
is_active_in lysosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in multivesicular body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus TAS
Traceable Author Statement
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
procathepsin L
Names
cathepsin L1
major excreted protein
NP_001244900.1
NP_001244901.1
NP_001244902.1
NP_001369686.1
NP_001369687.1
NP_001369695.1
NP_001369696.1
NP_001369697.1
NP_001903.1
NP_666023.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001257971.2 → NP_001244900.1  procathepsin L isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001244900.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) has an alternate splice site in the 5' UTR, compared to variant 1. Variants 1-4 encode the same isoform (1).
    Source sequence(s)
    BM680778, BX647435, CB963086
    Consensus CDS
    CCDS6675.1
    UniProtKB/Swiss-Prot
    P07711, Q6IAV1, Q96QJ0
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000504313.1, ENST00000679149.1
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 332
    Peptidase_C1; Papain family cysteine protease

  2. NM_001257972.2 → NP_001244901.1  procathepsin L isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001244901.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) has an alternate splice site in the 5' UTR, compared to variant 1. Variants 1-4 encode the same isoform (1).
    Source sequence(s)
    BM680778, BX647102, CB963086
    Consensus CDS
    CCDS6675.1
    UniProtKB/Swiss-Prot
    P07711, Q6IAV1, Q96QJ0
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000503439.1, ENST00000676531.1
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 332
    Peptidase_C1; Papain family cysteine protease

  3. NM_001257973.2 → NP_001244902.1  procathepsin L isoform 2

    See identical proteins and their annotated locations for NP_001244902.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream AUG, compared to variant 1. The resulting isoform (2) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AF217997, BM680778, CB963086, DN993009
    UniProtKB/TrEMBL
    Q9HBQ7
    Conserved Domains (1) summary
    pfam00112
    Location:1 → 150
    Peptidase_C1; Papain family cysteine protease

  4. NM_001382757.1 → NP_001369686.1  procathepsin L isoform 1 preproprotein

    Status: REVIEWED

    Source sequence(s)
    AL160279
    Consensus CDS
    CCDS6675.1
    UniProtKB/Swiss-Prot
    P07711, Q6IAV1, Q96QJ0
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000503298.1, ENST00000677821.1
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 332
    Peptidase_C1; Papain family cysteine protease

  5. NM_001382758.1 → NP_001369687.1  procathepsin L isoform 3

    Status: REVIEWED

    Source sequence(s)
    AL160279
    Consensus CDS
    CCDS94433.1
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000504473.1, ENST00000677019.1
    Conserved Domains (2) summary
    pfam00112
    Location:59 → 277
    Peptidase_C1; Papain family cysteine protease
    pfam08246
    Location:1 → 33
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)

  6. NM_001382766.1 → NP_001369695.1  procathepsin L isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AL160279
    Consensus CDS
    CCDS94432.1
    UniProtKB/TrEMBL
    Q5T8F0
    Related
    ENSP00000340470.6, ENST00000342020.6
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 260
    Peptidase_C1; Papain family cysteine protease

  7. NM_001382767.1 → NP_001369696.1  procathepsin L isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AL160279
    Consensus CDS
    CCDS94432.1
    UniProtKB/TrEMBL
    Q5T8F0
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 260
    Peptidase_C1; Papain family cysteine protease

  8. NM_001382768.1 → NP_001369697.1  procathepsin L isoform 4 precursor

    Status: REVIEWED

    Source sequence(s)
    AL160279
    Consensus CDS
    CCDS94432.1
    UniProtKB/TrEMBL
    Q5T8F0
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 260
    Peptidase_C1; Papain family cysteine protease

  9. NM_001912.5 → NP_001903.1  procathepsin L isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_001903.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. Variants 1-4 encode the same isoform (1).
    Source sequence(s)
    AL160279, AL832167, BM680778, DN993009
    Consensus CDS
    CCDS6675.1
    UniProtKB/Swiss-Prot
    P07711, Q6IAV1, Q96QJ0
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000345344.5, ENST00000343150.10
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 332
    Peptidase_C1; Papain family cysteine protease

  10. NM_145918.3 → NP_666023.1  procathepsin L isoform 1 preproprotein

    See identical proteins and their annotated locations for NP_666023.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate splice site in the 5' UTR, compared to variant 1. Variants 1-4 encode the same isoform (1).
    Source sequence(s)
    AL832167, AW270438
    Consensus CDS
    CCDS6675.1
    UniProtKB/Swiss-Prot
    P07711, Q6IAV1, Q96QJ0
    UniProtKB/TrEMBL
    A5PLM9, B3KQK4
    Related
    ENSP00000502968.1, ENST00000679157.1
    Conserved Domains (2) summary
    smart00848
    Location:29 → 87
    Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)
    pfam00112
    Location:114 → 332
    Peptidase_C1; Papain family cysteine protease

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    87726119..87731469
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    99879735..99885089
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P07711.2 GenPept UniProtKB/Swiss-Prot:P07711

Gene LinkOut

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