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    CTSC cathepsin C [ Homo sapiens (human) ]

    Gene ID: 1075, updated on 28-Oct-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
    mouse all
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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. Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients. Hart PS, et al. J Med Genet, 2000 Dec. PMID 11106356, Free PMC Article
    2. Novel cathepsin C mutation in a Brazilian family with Papillon-Lefèvre syndrome: case report and mutation update. Pallos D, et al. J Dent Child (Chic), 2010 Jan-Apr. PMID 20359428, Free PMC Article
    3. 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
    4. Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. Turk D, et al. EMBO J, 2001 Dec 3. PMID 11726493, Free PMC Article
    5. Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation. Allende LM, et al. Hum Mutat, 2001 Feb. PMID 11180601

    See all (135) 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
    		not available
    Papillon-Lefevre syndrome
    MedGen: C0030360 OMIM: 245000 GeneReviews: Not available
    		not available
    Periodontitis, aggressive 1
    MedGen: C4551681 OMIM: 170650 GeneReviews: Not available
    		not available

    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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    NEW Try the new Transcript table

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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