Cathepsin D (CTSD)
The protein contains 412 amino acids for an estimated molecular weight of 44552 Da.
Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. (updated: Dec. 20, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| Associated with increased risk for AD | |
| CLN10 | |
| dbSNP:rs147278302 | |
| CLN10 |
Biological Process
Antigen processing and presentation of exogenous peptide antigen via MHC class II
Autophagy
Collagen catabolic process
Extracellular matrix disassembly
Extracellular matrix organization
Lipoprotein catabolic process
Neutrophil degranulation
Positive regulation of apoptotic process
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
Protein catabolic process
Proteolysis
Regulation of establishment of protein localization
The reference OMIM entry for this protein is 116840
Cathepsin d; ctsd
DESCRIPTION
Cathepsin D (EC 3.4.23.5) is one of the lysosomal proteinases. It is ubiquitously expressed and is involved in proteolytic degradation, cell invasion, and apoptosis (Steinfeld et al., 2006).CLONING
Faust et al. (1985) cloned human cathepsin D from a kidney cDNA library. The cDNA encodes a 412-amino acid protein with 20 and 44 amino acids in a pre- and prosegment, respectively.MAPPING
By study of somatic cell hybrids, Hasilik et al. (1982) assigned the structural gene for cathepsin D to chromosome 11 and specifically to the region 11pter-11q12. By somatic cell hybrid deletion mapping and in situ hybridization, Qin et al. (1987) mapped CTSD to 11p15. Henry et al. (1989) likewise mapped CTSD to 11p15 using somatic cell hybrids with specific deletions. CTSD mapped distal to a breakpoint at 11p15.4.MOLECULAR GENETICS
In mice and sheep, cathepsin D deficiency causes a fatal neurodegenerative disease. Steinfeld et al. (2006) reported a novel disorder in a child with early blindness and progressive psychomotor disability (CLN10; 610127) who was compound heterozygous for missense mutations in the CTSD gene (F229I, 116840.0001 and W383C, 116840.0002). The mutations caused markedly reduced proteolytic activity and a diminished amount of cathepsin D in the patient's fibroblasts. Expression of cathepsin D mutants in fibroblasts of Ctsd -/- mice revealed disturbed posttranslational processing and intracellular targeting for W383C and diminished maximal enzyme velocity for F229I. Computer modeling suggested larger structural alterations for W383C than for F229I. In a Pakistani infant with severe congenital CLN10, Siintola et al. (2006) identified a homozygous null mutation (116840.0003) in the CTSD gene.ANIMAL MODEL
Tyynela et al. (2000) identified a mutation in ovine cathepsin D that accounts for congenital ovine neuronal ceroid lipofuscinosis (CONCL). In this disorder, which is transmitted as an autosomal recessive, newborn lambs are weak, trembling, and unable to rise and support their bodies. However, they are able to vocalize, support their heads, and to suckle if bottle-fed. At autopsy, the brains of affected lambs are strikingly small. The deep layers of the cerebral cortex show pronounced neuronal loss, reactive astrocytosis, and infiltration of macrophages. There is severe degeneration of hippocampal pyramidal neurons. The cerebellum is less affected. The basal ganglia, thalamus, and brainstem are relatively spared. Visceral tissues are unaffected. These animals have normal palmitoyl protein thioesterase activity, indicating that the molecular bases of human infantile neuronal ceroid lipofuscinosis (see 256730) and CONCL are distinct. As the pathology of CONCL suggested a lysosomal storage disease, Tyynela et al. (2000) measured a range of lysosomal enzyme activities and found strikingly deficient cathepsin D activity, which was about 40% of normal in heterozygous lambs. A G-to-A transition at nucleotide 934 was found in homozygosity in all affected animals. This mutation results in a substitution of an asparagine for aspartate at the codon corresponding to human asp295 of cathepsin D and asp215 of pepsin (see 169700). This residue is conserved among all aspartyl proteinases and represents 1 of the 2 aspartate residues that are essential for catalytic function of these proteins. ... More on the omim web site
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 116840 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed