CASPASE-14 (Homo sapiens)
Description [+]
- Synonyms: CASPASE-14, CASP14, CASPASE 14, MICE, MGC119078, MGC119079
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Caspase-14 Precursor (CASP-14)(EC 3.4.22.-) [Source:UniProtKB/Swiss-Prot;Acc:P31944]
- Family: Caspase
- Process: cell death (other),
- Pathways: undefined,
- Criteria: manually curated
- Curator comment: Caspase-14 is associated with death of skin cells in a non-apoptotic manner
- Mouse ortholog(s): Caspase-14
- WIKI: CASPASE-14-H_sapiens
References [+]
- Identification of a new caspase homologue: caspase-14.
- Van de Craen M, Van Loo G, Pype S, Van Criekinge W, Van den brande I, Molemans F, Fiers W, Declercq W, Vandenabeele P
- Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis. Here, we report the identification of a new murine caspase homologue, viz. caspase-14. It is most related to human/murine caspase-2 and human caspase-9, possesses all the typical amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain. Murine caspase-14 shows 83% similarity to human caspase-14. Human caspase-14 is assigned to chromosome 19p13.1. Northern blot analysis revealed that mRNA expression of caspase-14 is undetectable in all mouse adult tissues examined except for skin, while it is abundantly expressed in mouse embryos. In contrast to many other caspase family members, murine caspase-14 is not cleaved by granzyme B, caspase-1, caspase-2, caspase-3, caspase-6, caspase-7 or caspase-11, but is weakly processed into p18 and p11 subunits by murine caspase-8. No aspartase activity of murine caspase-14 could be generated by bacterial or yeast expression. Transient overexpression of murine caspase-14 in mammalian cells did not elicit cell death and did not interfere with caspase-8-induced apoptosis. In conclusion, caspase-14 is a member of the caspase family but no proteolytic or biological activities have been identified so far. The high constitutive expression levels in embryos and specific expression in adult skin suggest a role in ontogenesis and skin physiology. Cell Death Differ. 1998 Oct;5(10):838-46.
- Epidermal differentiation does not involve the pro-apoptotic executioner caspases, but is associated with caspase-14 induction and processing.
- Lippens S,Kockx M,Knaapen M,Mortier L,Polakowska R,Verheyen A,Garmyn M,Zwijsen A,Formstecher P,Huylebroeck D,Vandenabeele P,Declercq W
- The epidermis is a stratified squamous epithelium in which keratinocytes progressively undergo terminal differentiation towards the skin surface leading to programmed cell death. In this respect we studied the role of caspases. Here, we show that caspase-14 synthesis in the skin is restricted to differentiating keratinocytes and that caspase-14 processing is associated with terminal epidermal differentiation. The pro-apoptotic executioner caspases-3, -6, and -7 are not activated during epidermal differentiation. Caspase-14 does not participate in apoptotic pathways elicited by treatment of differentiated keratinocytes with various death-inducing stimuli, in contrast to caspase-3. In addition, we show that non-cornifying oral keratinocyte epithelium does not express caspase-14 and that the parakeratotic regions of psoriatic skin lesions contain very low levels of caspase-14 as compared to normal stratum corneum. These observations strongly suggest that caspase-14 is involved in the keratinocyte terminal differentiation program leading to normal skin cornification, while the executioner caspases are not implicated. Cell Death and Differentiation (2000) 7, 1218 - 1224 Cell Death Differ. 2000 Dec;7(12):1218-24.
- References from Mouse ortholog(s):
- Identification of a new caspase homologue: caspase-14.
- Van de Craen M, Van Loo G, Pype S, Van Criekinge W, Van den brande I, Molemans F, Fiers W, Declercq W, Vandenabeele P
- Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis. Here, we report the identification of a new murine caspase homologue, viz. caspase-14. It is most related to human/murine caspase-2 and human caspase-9, possesses all the typical amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain. Murine caspase-14 shows 83% similarity to human caspase-14. Human caspase-14 is assigned to chromosome 19p13.1. Northern blot analysis revealed that mRNA expression of caspase-14 is undetectable in all mouse adult tissues examined except for skin, while it is abundantly expressed in mouse embryos. In contrast to many other caspase family members, murine caspase-14 is not cleaved by granzyme B, caspase-1, caspase-2, caspase-3, caspase-6, caspase-7 or caspase-11, but is weakly processed into p18 and p11 subunits by murine caspase-8. No aspartase activity of murine caspase-14 could be generated by bacterial or yeast expression. Transient overexpression of murine caspase-14 in mammalian cells did not elicit cell death and did not interfere with caspase-8-induced apoptosis. In conclusion, caspase-14 is a member of the caspase family but no proteolytic or biological activities have been identified so far. The high constitutive expression levels in embryos and specific expression in adult skin suggest a role in ontogenesis and skin physiology. Cell Death Differ. 1998 Oct;5(10):838-46.
- Caspase-14 protects against epidermal UVB photodamage and water loss.
- Denecker G, Hoste E, Gilbert B, Hochepied T, Ovaere P, Lippens S, Van den Broecke C, Van Damme P, D'Herde K, Hachem JP, Borgonie G, Presland RB, Schoonjans L, Libert C, Vandekerckhove J, Gevaert K, Vandenabeele P, Declercq W
- Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its expression is restricted almost exclusively to the suprabasal layers of the epidermis and the hair follicles. Moreover, the proteolytic activation of caspase-14 is associated with stratum corneum formation, implicating caspase-14 in terminal keratinocyte differentiation and cornification. Here, we show that the skin of caspase-14-deficient mice was shiny and lichenified, indicating an altered stratum-corneum composition. Caspase-14-deficient epidermis contained significantly more alveolar keratohyalin F-granules, the profilaggrin stores. Accordingly, caspase-14-deficient epidermis is characterized by an altered profilaggrin processing pattern and we show that recombinant caspase-14 can directly cleave profilaggrin in vitro. Caspase-14-deficient epidermis is characterized by reduced skin-hydration levels and increased water loss. In view of the important role of filaggrin in the structure and moisturization of the skin, the knockout phenotype could be explained by an aberrant processing of filaggrin. Importantly, the skin of caspase-14-deficient mice was highly sensitive to the formation of cyclobutane pyrimidine dimers after UVB irradiation, leading to increased levels of UVB-induced apoptosis. Removal of the stratum corneum indicate that caspase-14 controls the UVB scavenging capacity of the stratum corneum. Nat Cell Biol. 2007 Jun;9(6):666-74. Epub 2007 May 21.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
| Source | Domain Name | Start | End |
|---|---|---|---|
| PFAM A | Peptidase_C14 | 18 | 241 |
Protein sequence [+]
Caspase-14 | Homo sapiens | 9606 | length:242
MSNPRSLEEEKYDMSGARLALILCVTKAREGSEEDLDALEHMFRQLRFESTMKRDPTAEQ
FQEELEKFQQAIDSREDPVSCAFVVLMAHGREGFLKGEDGEMVKLENLFEALNNKNCQAL
RAKPKVYIIQACRGEQRDPGETVGGDEIVMVIKDSPQTIPTYTDALHVYSTVEGYIAYRH
DQKGSCFIQTLVDVFTKRKGHILELLTEVTRRMAEAELVQEGKARKTNPEIQSTLRKRLY
LQ
FQEELEKFQQAIDSREDPVSCAFVVLMAHGREGFLKGEDGEMVKLENLFEALNNKNCQAL
RAKPKVYIIQACRGEQRDPGETVGGDEIVMVIKDSPQTIPTYTDALHVYSTVEGYIAYRH
DQKGSCFIQTLVDVFTKRKGHILELLTEVTRRMAEAELVQEGKARKTNPEIQSTLRKRLY
LQ
Structure links:
Evolution [+]
View protein alignment and tree with Jalview:
Explore tree at phylomeDB: Click here.
Homologs list [+]
| Name | Relationship | Species |
|---|---|---|
| A_aegypti_AAEL011562-PA | orthology | Aedes |
| IPI00688117.2 | orthology | Cow |
| CASP14 | orthology | Dog |
| CASP14 | orthology | Gorilla |
| CASP14 | orthology | Horse |
| CASP14 | orthology | Macaca |
| CASP14 | orthology | Monodelphis |
| Caspase-14 | orthology | Mouse |
| CASP14 | orthology | Orangutan |
| CASP14 | orthology | Ornithorhynchus |
| CASP14 | orthology | Rabbit |
| Casp14_predicted | orthology | Rat |
| caspa | orthology | Zebrafish |
| A_aegypti_AAEL003444-PA | paralogy | Aedes |
| A_aegypti_AAEL014348-PA | paralogy | Aedes |
| CASPS1 | paralogy | Anopheles |
| CASPS14 | paralogy | Anopheles |
| CASPS7 | paralogy | Anopheles |
| CASPS2 | paralogy | Anopheles |
| CASPS8 | paralogy | Anopheles |
| CASPS6 | paralogy | Anopheles |
| CASPS3 | paralogy | Anopheles |
| CASPS4 | paralogy | Anopheles |
| CASPS5 | paralogy | Anopheles |
| NP_989923.1 | paralogy | Chicken |
| NP_001038154.1 | paralogy | Chicken |
| CASP2_CHICK | paralogy | Chicken |
| Q90WU0_CHICK | paralogy | Chicken |
| CASP7 | paralogy | Chicken |
| CASP10 | paralogy | Chicken |
| NP_990056.1 | paralogy | Chicken |
| CASP3_PANTR | paralogy | Chimpanzee |
| CASP7 | paralogy | Chimpanzee |
| CASP2 | paralogy | Chimpanzee |
| C_intestinalis_ENSCINP00000024485 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000007986 | paralogy | Ciona |
| C_intestinalis_ENSCINP00000003204 | paralogy | Ciona |
| NP_001039435.1 | paralogy | Cow |
| CASP3_BOVIN | paralogy | Cow |
| IPI00709460.3 | paralogy | Cow |
| IPI00704513.4 | paralogy | Cow |
| NP_001029681.1 | paralogy | Cow |
| IPI00689801.3 | paralogy | Cow |
| IPI00707783.1 | paralogy | Cow |
| Q38JA9_CANFA | paralogy | Dog |
| C_familiaris_ENSCAFP00000007585 | paralogy | Dog |
| CASP7 | paralogy | Dog |
| CASP3_CANFA | paralogy | Dog |
| C_familiaris_ENSCAFP00000032442 | paralogy | Dog |
| Q45T68_CANFA | paralogy | Dog |
| CASP2 | paralogy | Dog |
| CASP6 | paralogy | Dog |
| Dcp-1 | paralogy | Fly |
| Ice | paralogy | Fly |
| CASP9 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000024164 | paralogy | Fugu |
| CASP7 | paralogy | Fugu |
| NP_001027871.1 | paralogy | Fugu |
| T_rubripes_ENSTRUP00000044662 | paralogy | Fugu |
| CASP2 | paralogy | Fugu |
| CASP2 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000005791 | paralogy | Gasterosteus |
| CASP3 (1 of 4) | paralogy | Gasterosteus |
| CASP3 (4 of 4) | paralogy | Gasterosteus |
| CASP9 | paralogy | Gasterosteus |
| CASP3 (2 of 4) | paralogy | Gasterosteus |
| CASP3 (3 of 4) | paralogy | Gasterosteus |
| G_aculeatus_ENSGACP00000016983 | paralogy | Gasterosteus |
| CASP7 | paralogy | Gorilla |
| CASP9 | paralogy | Horse |
| Q3T2K7_HORSE | paralogy | Horse |
| CASP2 | paralogy | Horse |
| CASP8 | paralogy | Horse |
| E_caballus_ENSECAP00000006138 | paralogy | Horse |
| CASP7 | paralogy | Horse |
| CASP6 | paralogy | Horse |
| Q3S2Z5_HORSE | paralogy | Horse |
| CASP10 | paralogy | Human |
| CASP7 | paralogy | Human |
| CASP3 | paralogy | Human |
| CASP2 | paralogy | Human |
| CASP3 | paralogy | Lyzard |
| CASP14 | paralogy | Lyzard |
| CASP2 | paralogy | Lyzard |
| CASP7 | paralogy | Lyzard |
| CASP10 | paralogy | Lyzard |
| CASP8 | paralogy | Macaca |
| Q8SPP8_MACMU | paralogy | Macaca |
| Q8SPU2_MACMU | paralogy | Macaca |
| M_mulatta_ENSMMUP00000027593 | paralogy | Macaca |
| CASP7 | paralogy | Macaca |
| Q8JIS8_ORYLA | paralogy | Medaka |
| Q8JIS9_ORYLA | paralogy | Medaka |
| CASP9 | paralogy | Medaka |
| CASP2 | paralogy | Medaka |
| NP_001035238.1 | paralogy | Monodelphis |
| M_domestica_ENSMODP00000020556 | paralogy | Monodelphis |
| NP_001033059.1 | paralogy | Monodelphis |
| CASP8 | paralogy | Monodelphis |
| NP_001033061.1 | paralogy | Monodelphis |
| CASP2 | paralogy | Monodelphis |
| Casp6 | paralogy | Mouse |
| Casp7 | paralogy | Mouse |
| Casp9 | paralogy | Mouse |
| Casp3 | paralogy | Mouse |
| Casp2 | paralogy | Mouse |
| CASP3 | paralogy | Orangutan |
| Q5RB11_PONPY | paralogy | Orangutan |
| CASP7 | paralogy | Orangutan |
| CASP2 | paralogy | Orangutan |
| Q5RCR7_PONPY | paralogy | Orangutan |
| CASP8 | paralogy | Ornithorhynchus |
| CASP2 | paralogy | Ornithorhynchus |
| O_anatinus_ENSOANP00000019254 | paralogy | Ornithorhynchus |
| CASP3 | paralogy | Ornithorhynchus |
| CASP9 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Ornithorhynchus |
| CASP7 | paralogy | Rabbit |
| O_cuniculus_ENSOCUP00000000197 | paralogy | Rabbit |
| Casp3 | paralogy | Rat |
| Casp7 | paralogy | Rat |
| Casp2 | paralogy | Rat |
| Casp9 | paralogy | Rat |
| CASP7 | paralogy | Tetraodon |
| T_nigroviridis_ENSTNIP00000001216 | paralogy | Tetraodon |
| CASP3 | paralogy | Tetraodon |
| CASP9 | paralogy | Tetraodon |
| ced-3 | paralogy | Worm |
| CASP3 | paralogy | Xenopus |
| casp7 | paralogy | Xenopus |
| casp10 | paralogy | Xenopus |
| CASP2 | paralogy | Xenopus |
| CASP8 | paralogy | Zebra finch |
| CASP3 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000011206 | paralogy | Zebra finch |
| T_guttata_ENSTGUP00000013612 | paralogy | Zebra finch |
| CASP9 | paralogy | Zebra finch |
| LOC795066 | paralogy | Zebrafish |
| NP_001077331.1 | paralogy | Zebrafish |
| casp6l2 | paralogy | Zebrafish |
| D_rerio_ENSDARP00000047019 | paralogy | Zebrafish |
| casp2 | paralogy | Zebrafish |
| A2BGE2_DANRE | paralogy | Zebrafish |
| casp7 | paralogy | Zebrafish |
| casp3b | paralogy | Zebrafish |
| LOC100000522 | paralogy | Zebrafish |
| casp8l2 | paralogy | Zebrafish |
| casp3a | paralogy | Zebrafish |
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Gene Ontology [+]
| GO id | Name | Ontology type | Evidence |
|---|---|---|---|
| GO:0008544 | epidermis development | biological_proccess | TAS |
| GO:0030154 | cell differentiation | biological_proccess | IEA |
| GO:0006915 | apoptosis | biological_proccess | IEA |
| GO:0006508 | proteolysis | biological_proccess | IEA |
| GO:0006917 | induction of apoptosis | biological_proccess | IEA |
| GO:0004197 | cysteine-type endopeptidase activity | mollecular_function | TAS |
| GO:0008233 | peptidase activity | mollecular_function | IEA |
| GO:0008234 | cysteine-type peptidase activity | mollecular_function | IEA |
| GO:0005634 | nucleus | cell_component | IEA |
| GO:0005737 | cytoplasm | cell_component | IEA |
Check GO Evidence Codes here
Information from other databases [+]
- Gene info from HGNC [?] :1502
- Gene related info from GeneCards [?] : Caspase-14
- Ensembl genome browser [?] : ENSG00000105141
- Expression info from Arrayexpress [?] : ENSG00000105141
- Protein expression from Protein Atlas: [?] ENSG00000105141
- Community gene edition from Wikigenes: [?] 23581
- OMIM gene information: 605848
- OMIM disease information:
Click on [?] for more information.
