CTSS cathepsin S [Homo sapiens (human)] - Gene

Summary

Official Symbol: CTSSprovided by HGNC
Official Full Name: cathepsin Sprovided by HGNC
Primary source: HGNC:HGNC:2545
See related: Ensembl:ENSG00000163131 MIM:116845; AllianceGenome:HGNC:2545
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
Summary: The preproprotein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. The mature protein cleaves the invariant chain of MHC class II molecules in endolysosomal compartments and enables the formation of antigen-MHC class II complexes and the proper display of extracellular antigenic peptides by MHC-II. The mature protein also functions as an elastase over a broad pH range. When secreted from cells, this protein can remodel components of the extracellular matrix such as elastin, collagen, and fibronectin. This gene is implicated in the pathology of many inflammatory and autoimmune diseases and, given its elastase activity, plays a significant role in some pulmonary diseases. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Broad expression in spleen (RPKM 89.0), appendix (RPKM 75.4) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (150730188..150765778, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (149853594..149889583, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (150702664..150738254, complement)

Chromosome 1 - NC_000001.11 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 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?

Potential role of CTSS in AMDImmune modulatory and anti-angiogenic effects of cathepsin S knockdown in ARPE-19 cells.
Title: Potential role of CTSS in AMDImmune modulatory and anti-angiogenic effects of cathepsin S knockdown in ARPE-19 cells.
Elevated Cathepsin S Serum Levels in New-Onset Type 1 Diabetes and Autoantibody-Positive Siblings.
Title: Elevated Cathepsin S Serum Levels in New-Onset Type 1 Diabetes and Autoantibody-Positive Siblings.
Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.
Title: Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis.
Granulomatous rosacea in Chinese patients: Clinical-histopathological analysis and pathogenesis exploration.
Title: Granulomatous rosacea in Chinese patients: Clinical-histopathological analysis and pathogenesis exploration.
Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-kappaB Signaling.
Title: Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling.
Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: bioinformatics and in vivo and vitro experiments.
Title: Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: bioinformatics and in vivo and vitro experiments.
Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential.
Title: Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential.
Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients.
Title: Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients.
Knockdown of CD44 inhibits proliferation, migration and invasion of osteosarcoma cells accompanied by downregulation of cathepsin S.
Title: Knockdown of CD44 inhibits proliferation, migration and invasion of osteosarcoma cells accompanied by downregulation of cathepsin S.
Association of Circulating Cathepsin S and Cardiovascular Disease Among Patients With Type 2 Diabetes: A Cross-Sectional Community-Based Study.
Title: Association of Circulating Cathepsin S and Cardiovascular Disease Among Patients With Type 2 Diabetes: A Cross-Sectional Community-Based Study.

Submit: New GeneRIF Correction See all GeneRIFs (135)

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

EBI GWAS Catalog

Description
Genome-wide association study identifies genetic risk underlying primary rhegmatogenous retinal detachment. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association data identifies novel susceptibility loci for obesity. EBI GWAS Catalog EBI GWAS CatalogPubMed

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 S cleaves HIV-1 gp120 at positions Q208-A209 and S261-T262 (C2 domain), T322-T323 (V3 domain), and Y435-A436 (C4 domain), which is important for antigen processing and presentation	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of cathepsin S (CTSS) in primary human brain microvascular endothelial cells	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

RH68555 (e-PCR)
- UniSTS:83234

RH119963 (e-PCR)
- UniSTS:133165

AL034054 (e-PCR)
- UniSTS:93816

RH80467 (e-PCR)
- UniSTS:84094

RH44919 (e-PCR)
- UniSTS:4239

WI-18164 (e-PCR)
- UniSTS:17808

CTSS_573 (e-PCR)
- UniSTS:277137

SHGC-35262 (e-PCR)
- UniSTS:60387

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables collagen binding	IDA Inferred from Direct Assay more info	PubMed
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	TAS Traceable Author Statement more info
enables fibronectin binding	IPI Inferred from Physical Interaction more info	PubMed
enables laminin binding	IDA Inferred from Direct Assay more info	PubMed
enables proteoglycan binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
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	IDA Inferred from Direct Assay 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	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in basement membrane disassembly	IDA Inferred from Direct Assay more info	PubMed
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 extracellular matrix disassembly	TAS Traceable Author Statement more info
involved_in positive regulation of cation channel activity	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	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 response to acidic pH	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in endolysosome lumen	TAS Traceable Author Statement more info
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
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 ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
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 phagocytic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: cathepsin S

NP_001186668.1

EC 3.4.22.27

NP_004070.3

EC 3.4.22.27

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_001199739.2 → NP_001186668.1 cathepsin S isoform 2 preproprotein

See identical proteins and their annotated locations for NP_001186668.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the CDS, so encodes a shorter isoform (2), as compared to variant 1.

Source sequence(s)

AK301472, AL356292

Consensus CDS

CCDS55634.1

UniProtKB/TrEMBL

A0A7P0T904

Related

ENSP00000506001.1, ENST00000680288.1

Conserved Domains (2) summary

smart00848
Location:28 → 83

Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)

pfam00112
Location:82 → 279

Peptidase_C1; Papain family cysteine protease
NM_004079.5 → NP_004070.3 cathepsin S isoform 1 preproprotein

See identical proteins and their annotated locations for NP_004070.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes a longer isoform (1).

Source sequence(s)

AL356292, BC002642, M90696

Consensus CDS

CCDS968.1

UniProtKB/Swiss-Prot

B4DWC9, D3DV05, P25774, Q5T5I0, Q6FHS5, Q9BUG3

UniProtKB/TrEMBL

A0A7P0T844

Related

ENSP00000357981.3, ENST00000368985.8

Conserved Domains (3) summary

PTZ00203
Location:5 → 326

PTZ00203; cathepsin L protease; Provisional

smart00848
Location:28 → 87

Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)

pfam00112
Location:115 → 329

Peptidase_C1; Papain family cysteine protease