CTSL cathepsin L [Homo sapiens (human)] - Gene

Summary

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: mouse all
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Genomic context

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_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC171390P2 (e-PCR)
- UniSTS:271634

GDB:594510 (e-PCR)
- UniSTS:157990

D9S1706 (e-PCR)
- UniSTS:70460

GDB:451830 (e-PCR)
- UniSTS:157379

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 more info	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 more info	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

EC 3.4.22.15

NP_001244901.1

EC 3.4.22.15

NP_001244902.1

EC 3.4.22.15

NP_001369686.1

EC 3.4.22.15

NP_001369687.1

EC 3.4.22.15

NP_001369695.1

EC 3.4.22.15

NP_001369696.1

EC 3.4.22.15

NP_001369697.1

EC 3.4.22.15

NP_001903.1

EC 3.4.22.15

NP_666023.1

EC 3.4.22.15

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)

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
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
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
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
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)
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
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
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
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
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