Caspase-14 (CASP14)
The protein contains 242 amino acids for an estimated molecular weight of 27680 Da.
Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum (PubMed:15556625). Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin (By similarity). In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF (PubMed:16854378, PubMed:19960512). Involved in processing of prosaposin in the epidermis (By similarity). May be involved in retinal pigment epithelium cell barrier function (PubMed:25121097). Involved in DNA degradation in differentiated keratinocytes probably by cleaving DFFA/ICAD leading to liberation of DFFB/CAD (PubMed:24743736). (updated: Nov. 22, 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
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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Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic process
Apoptotic process
Cornification
Epidermis development
Execution phase of apoptosis
Extrinsic apoptotic signaling pathway in absence of ligand
Intrinsic apoptotic signaling pathway in response to DNA damage
Keratinization
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Extracellular matrix
Keratin filament
Mitochondrion
Nucleoplasm
Nucleus
Molecular Function
Cysteine-type endopeptidase activity
Cysteine-type endopeptidase activity involved in apoptotic process
Cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cysteine-type endopeptidase activity involved in execution phase of apoptosis
Endopeptidase activity
The reference OMIM entry for this protein is 605848
Caspase 14, apoptosis-related cysteine protease; casp14
DESCRIPTION
CASP14 belongs to the evolutionarily conserved caspase family. Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis (Van de Craen et al., 1998). See CASP1 (147678) for additional background information on caspases.CLONING
Using database searches for caspase sequences, Van de Craen et al. (1998) identified CASP14 in human genomic sequence data and cloned both human and mouse CASP14 cDNAs. By Northern blot and RT-PCR analyses, Van de Craen et al. (1998) detected Casp14 expression in mouse skin and developing mouse embryos (embryonic day 7, 15, 16, and 17). Expression generally increased during maturation of the mouse embryo but dropped temporarily to an undetectable level around embryonic day 11 to 12. The authors suggested that Casp14 may play a role in ontogenesis and skin physiology. Eckhart et al. (2000) cloned a full-length CASP14 cDNA encoding a 242-amino acid protein with potential AP1 (165160) and KLF4 (602253) interaction sites. They identified 2 CASP14 transcripts, designated CASP14a and CASP14b, that differ in the C terminus due to a shifted open reading frame. Use of an alternative splice acceptor site within intron 5 results in a 74-nucleotide insertion in CASP14b. CASP14b lacks homology with the caspase consensus sequence and does not have a counterpart in mouse. In situ hybridization analysis detected CASP14 within the epidermis, in hair follicles, and in the cells of the sebaceous glands, with highest expression in the keratogenous zone and the inner root sheeth of the hair follicle and in the peripheral cells of the sebaceous glands. Using immunohistochemical analysis, Denecker et al. (2007) confirmed that mouse Casp14 was expressed only in cornifying epithelia, such as the epidermis and Hassall bodies, and in forestomach, which is cornified like epidermis.GENE FUNCTION
Using Northern blot and semiquantitative RT-PCR analyses, Eckhart et al. (2000) showed that CASP14 was transcriptionally upregulated during maintenance of confluent cultures of human epidermal keratinocytes. The transcriptional upregulation was suppressed in the presence of a high extracellular calcium concentration.GENE STRUCTURE
Eckhart et al. (2000) determined that the CASP14 gene contains 7 exons.MAPPING
Van de Craen et al. (1998) identified CASP14 sequences in a cosmid clone assigned to chromosome 19p13.1 (GenBank GENBANK AF097874).ANIMAL MODEL
Denecker et al. (2007) found that Casp14 -/- mice were born at the expected mendelian ratio, were fertile and healthy, and showed long-term survival indistinguishable from that of wildtype mice. However, the skin of Casp14 -/- mice was shiny and lichenified. Casp14 -/- epidermis contained significantly more alveolar keratohyalin F-granules, the profilaggrin (135940) stores, and showed altered profilaggrin processing. Casp14 -/- epidermis was characterized by reduced skin-hydration levels and increased water loss, which could be explained by aberrant filaggrin processing. The skin of Casp14 -/- mice was highly sensitive to formation of cyclobutane pyrimidine dimers after ultraviolet B (UVB) irradiation, leading to increased UVB-induced apoptosis. Wildtype mice stripped of the stratum corneum were at least as sensitive as nonstripped Casp14 -/- mice to UVB irradiation, indicating that Casp14 controls the UBV scavenging capacity of stratum corneum. ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 605848 was added.