CTSH cathepsin H [Homo sapiens (human)] - Gene

Summary

Official Symbol: CTSHprovided by HGNC
Official Full Name: cathepsin Hprovided by HGNC
Primary source: HGNC:HGNC:2535
See related: Ensembl:ENSG00000103811 MIM:116820; AllianceGenome:HGNC:2535
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: ACC4; ACC5; CPSB; ACC-4; ACC-5
Summary: The protein encoded by this gene is a lysosomal cysteine proteinase important in the overall degradation of lysosomal proteins. It is composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. The encoded protein, which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. Increased expression of this gene has been correlated with malignant progression of prostate tumors. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
Expression: Broad expression in lung (RPKM 144.1), kidney (RPKM 97.7) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q25.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (78921058..78945046, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (76784722..76808716, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (79213400..79237388, complement)

Chromosome 15 - NC_000015.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.
Title: Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.
Cathepsin H: Molecular characteristics and clues to function and mechanism.
Title: Cathepsin H: Molecular characteristics and clues to function and mechanism.
Genetic and environmental factors regulate the type 1 diabetes gene CTSH via differential DNA methylation.
Title: Genetic and environmental factors regulate the type 1 diabetes gene CTSH via differential DNA methylation.
The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells.
Title: The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells.
Study presents the crystal structures of human procathepsin H at 2.00 A and 1.66 A resolution. These structures allow us to explore in detail the molecular basis for the inhibition of the mature domain by the prodomain. Comparison with cathepsin H structure reveals how mini-chain reorients upon activation. Results demonstrate that procathepsin H is not auto-activated but can be trans-activated by cathepsin L.
Title: Crystal structures of human procathepsin H.
the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts).
Title: Cathepsin H-Mediated Degradation of HDAC4 for Matrix Metalloproteinase Expression in Hepatic Stellate Cells: Implications of Epigenetic Suppression of Matrix Metalloproteinases in Fibrosis through Stabilization of Class IIa Histone Deacetylases.
Especially, rs3825932 in CTSH has integrative functional evidence supporting the association with type 1 diabetes mellitus.
Title: Functional relevance for type 1 diabetes mellitus-associated genetic variants by using integrative analyses.
p41 fragment is also shown to reduce the secretion of interleukin-12 (IL-12/p70) during the subsequent maturation of treated dendritic cells.
Title: Exogenous Thyropin from p41 Invariant Chain Diminishes Cysteine Protease Activity and Affects IL-12 Secretion during Maturation of Human Dendritic Cells.
In conclusion, CTSH/rs3825932 and ERBB3/rs2292239 SNPs were associated with reduced risk of progression to proliferative diabetic retinopathy and two-step progression of diabetic retinopathy on the ETDRS scale accordingly.
Title: Polymorphisms in the CTSH gene may influence the progression of diabetic retinopathy: a candidate-gene study in the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).
mutation in LRPAP1 is associated with high myopia. Further studies are expected to evaluate the pathogenicity of the variants in CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2.
Title: Detection of mutations in LRPAP1, CTSH, LEPREL1, ZNF644, SLC39A5, and SCO2 in 298 families with early-onset high myopia by exome sequencing.

Submit: New GeneRIF Correction See all GeneRIFs (30)

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 and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study on bipolar disorder in the Bulgarian population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. 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
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of cathepsin H (CTSH) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed

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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

G54095 (e-PCR)
- UniSTS:109332

RH103543 (e-PCR)
- UniSTS:97868

STS-X16832 (e-PCR)
- UniSTS:53095

D2S2841 (e-PCR)
- UniSTS:3710

D15S1349 (e-PCR)
- UniSTS:79001

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables HLA-A specific activating MHC class I receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables aminopeptidase activity	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 activator activity involved in apoptotic process	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	PubMed
enables cysteine-type peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables thyroid hormone binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in T cell mediated cytotoxicity	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 apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in bradykinin catabolic process	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 dichotomous subdivision of terminal units involved in lung branching	ISS Inferred from Sequence or Structural Similarity more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response-regulating signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in metanephros development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuropeptide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of epithelial cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in proteolysis involved in protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to retinoic acid	ISS Inferred from Sequence or Structural Similarity more info
involved_in surfactant homeostasis	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 alveolar lamellar body	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in cytoplasmic ribonucleoprotein granule	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA 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
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 lumen	TAS Traceable Author Statement more info
located_in secretory granule lumen	TAS Traceable Author Statement more info
located_in tertiary granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: pro-cathepsin H

Names: N-benzoylarginine-beta-naphthylamide hydrolase; aleurain; cathepsin B3; cathepsin BA

NP_001306066.1

EC 3.4.22.16

NP_001398024.1

EC 3.4.22.16

NP_004381.2

EC 3.4.22.16

XP_016877440.1

EC 3.4.22.16

XP_054233346.1

EC 3.4.22.16

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

NG_009614.2 RefSeqGene

Range

5000..28988

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001319137.2 → NP_001306066.1 pro-cathepsin H isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at an alternate start codon, compared to variant 1. It encodes isoform c which is shorter and has a distinct N-terminus, compared to isoform a.

Source sequence(s)

AC011944

Conserved Domains (1) summary

pfam00112
Location:32 → 198

Peptidase_C1; Papain family cysteine protease
NM_001411095.1 → NP_001398024.1 pro-cathepsin H isoform d

Status: REVIEWED

Source sequence(s)

AC011944

Consensus CDS

CCDS92047.1

UniProtKB/TrEMBL

E9PKT6, Q6IBC3

Related

ENSP00000504051.1, ENST00000677316.1
NM_004390.5 → NP_004381.2 pro-cathepsin H isoform a preproprotein

See identical proteins and their annotated locations for NP_004381.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the longer isoform (a).

Source sequence(s)

AC011944

Consensus CDS

CCDS10308.1

UniProtKB/Swiss-Prot

B2RBK0, P09668, Q96NY6, Q9BUM7

UniProtKB/TrEMBL

Q6IBC3

Related

ENSP00000220166.6, ENST00000220166.10

Conserved Domains (2) summary

pfam00112
Location:117 → 332

Peptidase_C1; Papain family cysteine protease

pfam08246
Location:35 → 90

Inhibitor_I29; Cathepsin propeptide inhibitor domain (I29)

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

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

78921058..78945046 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017021951.2 → XP_016877440.1 pro-cathepsin H isoform X1

UniProtKB/TrEMBL

Q6IBC3

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

76784722..76808716 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054377371.1 → XP_054233346.1 pro-cathepsin H isoform X1

UniProtKB/TrEMBL

Q6IBC3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_148979.2: Suppressed sequence

Description

NM_148979.2: This RefSeq was permanently suppressed because it represents a poorly supported variant with non-consensus splice sites.