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CTSC cathepsin C [ Homo sapiens (human) ]

Gene ID: 1075, updated on 3-Nov-2024

Summary

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Official Symbol
CTSCprovided by HGNC
Official Full Name
cathepsin Cprovided by HGNC
Primary source
HGNC:HGNC:2528
See related
Ensembl:ENSG00000109861 MIM:602365; AllianceGenome:HGNC:2528
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
JP; HMS; JPD; PLS; CPPI; DPP1; DPPI; PALS; DPP-I; PDON1
Summary
This gene encodes a member of the peptidase C1 family and lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in cells of the immune system. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate heavy and light chains that form a disulfide-linked dimer. A portion of the propeptide acts as an intramolecular chaperone for the folding and stabilization of the mature enzyme. This enzyme requires chloride ions for activity and can degrade glucagon. Defects in the encoded protein have been shown to be a cause of Papillon-Lefevre syndrome, an autosomal recessive disorder characterized by palmoplantar keratosis and periodontitis. [provided by RefSeq, Nov 2015]
Expression
Broad expression in placenta (RPKM 28.5), lung (RPKM 26.8) and 24 other tissues See more
Orthologs
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Genomic context

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See CTSC in Genome Data Viewer
Location:
11q14.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (88293592..88337736, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (88212614..88256755, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (88026760..88070904, complement)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984361 Neighboring gene NANOG hESC enhancer GRCh37_chr11:87550635-87551136 Neighboring gene MT-CYB pseudogene 41 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:87636982-87638181 Neighboring gene RAB38, member RAS oncogene family Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:87678230-87678751 Neighboring gene NANOG hESC enhancer GRCh37_chr11:87681659-87682160 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5376 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5377 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5378 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:87957258-87957458 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:87979456-87980655 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5379 Neighboring gene microRNA 3166 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:88030550-88031243 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr11:88040649-88041604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5380 Neighboring gene MPRA-validated peak1386 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5381 Neighboring gene Sharpr-MPRA regulatory region 1780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5382 Neighboring gene uncharacterized LOC101929174 Neighboring gene CRISPRi-validated cis-regulatory element chr11.4755 Neighboring gene CRISPRi-validated cis-regulatory element chr11.4758 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5383 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5385 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5386 Neighboring gene glyceraldehyde 3 phosphate dehydrogenase pseudogene 70 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3833 Neighboring gene GRM5 antisense RNA 1 Neighboring gene glutamate metabotropic receptor 5

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 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. Haim Munk syndrome: report of two siblings of northern India treated with acitretin. Mohan RS, et al. Indian J Dermatol Venereol Leprol, 2011 Mar-Apr. PMID 21393975
  2. The crystal structure of human dipeptidyl peptidase I (cathepsin C) in complex with the inhibitor Gly-Phe-CHN2. Mølgaard A, et al. Biochem J, 2007 Feb 1. PMID 17020538, Free PMC Article
  3. Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. Méthot N, et al. J Biol Chem, 2007 Jul 20. PMID 17535802
  4. Novel mutations of cathepsin C gene in two Chinese patients with Papillon-Lefèvre syndrome. Yang Y, et al. J Dent Res, 2007 Aug. PMID 17652201
  5. Detection of an intragenic deletion expands the spectrum of CTSC mutations in Papillon-Lefèvre syndrome. Jouary T, et al. J Invest Dermatol, 2008 Feb. PMID 17943190

See all (136) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. [Single-cell transcriptomic sequencing coupled with Mendelian randomization analysis elucidates the pivotal role of CTSC in chronic rhinosinusitis].
    Title: [Single-cell transcriptomic sequencing coupled with Mendelian randomization analysis elucidates the pivotal role of CTSC in chronic rhinosinusitis].
  2. Possible relation of cathepsin C activity and seasonal fluctuation of skin lesions in Papillon-Lefevre syndrome.
    Title: Possible relation of cathepsin C activity and seasonal fluctuation of skin lesions in Papillon-Lefèvre syndrome.
  3. Papillon-Lefevre syndrome in twelve Egyptian patients: Five novel CTSC variants and functional characterization of a missense variant and its effect on splicing.
    Title: Papillon-Lefevre syndrome in twelve Egyptian patients: Five novel CTSC variants and functional characterization of a missense variant and its effect on splicing.
  4. Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders.
    Title: Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders.
  5. Expression and significance of cathepsin C and cathepsin D during pregnancy and Preeclampsia.
    Title: Expression and significance of cathepsin C and cathepsin D during pregnancy and Preeclampsia.
  6. Cathepsin C promotes colorectal cancer metastasis by regulating immune escape through upregulating CSF1.
    Title: Cathepsin C promotes colorectal cancer metastasis by regulating immune escape through upregulating CSF1.
  7. Evolutionary Analysis of Dipeptidyl Peptidase I.
    Title: Evolutionary Analysis of Dipeptidyl Peptidase I.
  8. Downregulation of cathepsin C alleviates endothelial cell dysfunction by suppressing p38 MAPK/NF-kappaB pathway in preeclampsia.
    Title: Downregulation of cathepsin C alleviates endothelial cell dysfunction by suppressing p38 MAPK/NF-κB pathway in preeclampsia.
  9. Cathepsin C Regulates Cytokine-Induced Apoptosis in beta-Cell Model Systems.
    Title: Cathepsin C Regulates Cytokine-Induced Apoptosis in β-Cell Model Systems.
  10. A novel mutation in the cathepsin C (CTSC) gene in Iranian family with Papillon-Lefevre syndrome.
    Title: A novel mutation in the cathepsin C (CTSC) gene in Iranian family with Papillon-Lefevre syndrome.
Submit: New GeneRIF Correction See all GeneRIFs (60)

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

Associated conditions

Description Tests
Haim-Munk syndrome
MedGen: C1855627 OMIM: 245010 GeneReviews: Not available
Compare labs
Papillon-Lefevre syndrome
MedGen: C0030360 OMIM: 245000 GeneReviews: Not available
Compare labs
Periodontitis, aggressive 1
MedGen: C4551681 OMIM: 170650 GeneReviews: Not available
Compare labs

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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Replication interactions

Interaction Pubs
Knockdown of cathepsin C (CTSC) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with CTSC; predicted interaction to be within the endoplasmic reticulum PubMed
Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of cathepsin C (CTSC) 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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables chloride ion binding IEA
Inferred from Electronic Annotation
more info
  
enables cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables dipeptidyl-peptidase activity IEA
Inferred from Electronic Annotation
more info
  
enables identical protein binding IEA
Inferred from Electronic Annotation
more info
  
enables peptidase activator activity involved in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
enables phosphatase binding ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-folding chaperone binding ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
enables serine-type endopeptidase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in T cell mediated cytotoxicity IEA
Inferred from Electronic Annotation
more info
  
involved_in apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in immune response TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of myelination IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of apoptotic signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of microglial cell activation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of proteolysis involved in protein catabolic process ISS
Inferred from Sequence or Structural Similarity
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
  
Component Evidence Code Pubs
located_in COPII-coated ER to Golgi transport vesicle TAS
Traceable Author Statement
more info
  
located_in azurophil granule lumen TAS
Traceable Author Statement
more info
  
located_in centrosome IDA
Inferred from Direct Assay
more info
  
located_in collagen-containing extracellular matrix HDA PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum-Golgi intermediate compartment membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space HDA PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
is_active_in lysosome IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in lysosome ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
located_in lysosome TAS
Traceable Author Statement
more info
 PubMed 
located_in membrane HDA PubMed 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
dipeptidyl peptidase 1
Names
cathepsin J
dipeptidyl transferase
dipeptidyl-peptidase I
NP_001107645.1
NP_001805.4
NP_680475.1

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.

Genomic

  1. NG_007952.1 RefSeqGene

    Range
    5001..49182
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_50

mRNA and Protein(s)

  1. NM_001114173.3 → NP_001107645.1  dipeptidyl peptidase 1 isoform c precursor

    See identical proteins and their annotated locations for NP_001107645.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the coding sequence and 3' UTR compared to variant 1. This results in an isoform (c) that is much shorter and contains a different C-terminus than isoform a.
    Source sequence(s)
    AC011088, BC113850, BX537913, CN368896
    Consensus CDS
    CCDS44693.1
    UniProtKB/TrEMBL
    A0A7I2V3A2
    Related
    ENSP00000433539.1, ENST00000529974.2
    Conserved Domains (1) summary
    pfam08773
    Location:26 → 106
    CathepsinC_exc; Cathepsin C exclusion domain

  2. NM_001814.6 → NP_001805.4  dipeptidyl peptidase 1 isoform a preproprotein

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shortest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AC011088
    Consensus CDS
    CCDS8282.1
    UniProtKB/Swiss-Prot
    A8K7V2, B5MDD5, P53634, Q2HIY8, Q53G93, Q71E75, Q71E76, Q7M4N9, Q7Z3G7, Q7Z5U7, Q8WY99, Q8WYA7, Q8WYA8
    UniProtKB/TrEMBL
    A0A7I2V2Q8
    Related
    ENSP00000227266.4, ENST00000227266.10
    Conserved Domains (2) summary
    cd02621
    Location:231 → 460
    Peptidase_C1A_CathepsinC; Cathepsin C; also known as Dipeptidyl Peptidase I (DPPI), an atypical papain-like cysteine peptidase with chloride dependency and dipeptidyl aminopeptidase activity, resulting from its tetrameric structure which limits substrate access. Each subunit of ...
    pfam08773
    Location:26 → 138
    CathepsinC_exc; Cathepsin C exclusion domain

  3. NM_148170.5 → NP_680475.1  dipeptidyl peptidase 1 isoform b precursor

    See identical proteins and their annotated locations for NP_680475.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the coding sequence and 3' UTR compared to variant 1. This results in an isoform (b) that is much shorter and contains a different C-terminus than isoform a. Isoform b may act as a negative regulator of a stable mature enzyme.
    Source sequence(s)
    AC011088, BX537913
    Consensus CDS
    CCDS31654.1
    UniProtKB/TrEMBL
    A0A7I2V3A2
    Related
    ENSP00000432541.1, ENST00000524463.6
    Conserved Domains (1) summary
    pfam08773
    Location:26 → 106
    CathepsinC_exc; Cathepsin C exclusion domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

    Range
    88293592..88337736 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060935.1 Alternate T2T-CHM13v2.0

    Range
    88212614..88256755 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P53634.2 GenPept UniProtKB/Swiss-Prot:P53634

Gene LinkOut

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