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CASP14 Gene(Protein Coding)

Caspase 14

GCID:
GC19P015049
GIFtS:
62
Genes Participants
UDN Logo

Aliases for CASP14 Gene

Aliases for CASP14 Gene

  • Caspase 14 2 3 5
  • Caspase 14, Apoptosis-Related Cysteine Peptidase 2 3
  • Caspase 14, Apoptosis-Related Cysteine Protease 2 3
  • Apoptosis-Related Cysteine Protease 2 3
  • CASP-14 3 4
  • EC 3.4.22.- 4
  • Caspase-14 3
  • ARCI12 3

External Ids for CASP14 Gene

Previous GeneCards Identifiers for CASP14 Gene

  • GC19P015542
  • GC19P015008
  • GC19P015024
  • GC19P015160
  • GC19P014730

Summaries for CASP14 Gene

Entrez Gene Summary for CASP14 Gene

  • This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier. [provided by RefSeq, Jul 2008]

GeneCards Summary for CASP14 Gene

CASP14 (Caspase 14) is a Protein Coding gene. Diseases associated with CASP14 include Diabetes Mellitus, Insulin-Dependent, 17 and Childhood Leukemia. Among its related pathways are Development ERBB-family signaling and Apoptosis and Autophagy. GO annotations related to this gene include cysteine-type endopeptidase activity and cysteine-type endopeptidase activity involved in apoptotic signaling pathway. An important paralog of this gene is CASP3.

UniProtKB/Swiss-Prot for CASP14 Gene

  • 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).

Tocris Summary for CASP14 Gene

  • Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into initiators and effectors. The initiator isoforms are activated by, and interact with, upstream adaptor molecules.

Gene Wiki entry for CASP14 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CASP14 Gene

Genomics for CASP14 Gene

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  1. Regulatory Element

Regulatory Elements for CASP14 Gene

Enhancers for CASP14 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19G015072 0.8 ENCODE 4.9 +24.2 24238 3.1 ELF3 MLX SIN3A RAD21 ZBTB7B ZNF207 RCOR1 ZHX2 CEBPB ZNF592 CASP14 AKAP8 SLC1A6 GC19P015064 GC19P015085
GH19G015050 0.5 FANTOM5 4.8 +1.0 984 0.3 ZNF692 YBX1 CASP14 GC19M015059
GH19G015044 0.3 FANTOM5 0.7 -4.9 -4915 0.3 ZNF333 CASP14 SLC1A6
GH19G015038 0.5 ENCODE 0.4 -10.9 -10880 0.2 ZNF217 GATA3 NFIB FOXP2 ZIC2 OR7C1 CASP14 SLC1A6
GH19G015037 0.2 ENCODE 0.4 -11.6 -11620 0.2 OR7C1 SLC1A6 CASP14
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around CASP14 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the CASP14 gene promoter:

Genomic Location for CASP14 Gene

Chromosome:
19
Start:
15,049,384 bp from pter
End:
15,058,293 bp from pter
Size:
8,910 bases
Orientation:
Plus strand

Genomic View for CASP14 Gene

Genes around CASP14 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CASP14 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CASP14 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for CASP14 Gene

Proteins for CASP14 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for CASP14 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P31944-CASPE_HUMAN
    Recommended name:
    Caspase-14
    Protein Accession:
    P31944
    Secondary Accessions:
    • O95823
    • Q3SYC9

    Protein attributes for CASP14 Gene

    Size:
    242 amino acids
    Molecular mass:
    27680 Da
    Quaternary structure:
    • Heterodimer of a large and a small subunit, both processed from the precursor; the mature active form is a p17/p10 dimer and the intermediate form a p20/p8 dimer.
    Miscellaneous:
    • Expressed in bacteria requires high concentrations of kosmotropic salts to be activated (PubMed:15301553). The mature and the intermediate form differ in activity towards synthetic caspase substrates: the p17/p10 mature form but not the p20/p8 intermediate form is active on WEHD-MCA; p20/p8 is active on a number of other caspase substrates without any marked preference (VEID-AFC, DEVD-AFC, LEVD-AFC and LEHD-AFC) (PubMed:22825846).

neXtProt entry for CASP14 Gene

Protein Expression for CASP14 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for CASP14 Gene

  • Maturation by proteolytic processing appears to be a two-step process. The precursor is processed by KLK7 to yield the p20/p8 intermediate form which acts on the precursor to yield the p17/p10 mature form (PubMed:22825846). Initially, cleavage between Ile-152 and Lys-153 has been proposed to yield the large and small subunits of the active enzyme (PubMed:12200134).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CASP14 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for CASP14 (CASP14)
  • Cloud-Clone Corp. Antibodies for CASP14

No data available for DME Specific Peptides for CASP14 Gene

Domains & Families for CASP14 Gene

Gene Families for CASP14 Gene

HGNC:
IUPHAR :

Protein Domains for CASP14 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for CASP14 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P31944

UniProtKB/Swiss-Prot:

CASPE_HUMAN :
  • Belongs to the peptidase C14A family.
Family:
  • Belongs to the peptidase C14A family.
genes like me logo Genes that share domains with CASP14: view

Function for CASP14 Gene

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  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for CASP14 Gene

GENATLAS Biochemistry:
caspase 14,cysteine containing aspartate-specific protease,stored in the mitochondrial intermembrane space and released into cytosol after appropriate apoptotic stimuli,promoting apoptosis,homolog to murine CASP14 expressed in embryo and in adult skin
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by caspase-1 inhibitor YVAD-FMK and the pan-caspase inhibitor VAD-FMK.
UniProtKB/Swiss-Prot Function:
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).
UniProtKB/Swiss-Prot Induction:
In undifferentiated keratinocytes under postconfluency growth conditions (in vitro) (PubMed:11175259). By high glucose in retinal pigment epithelia cells (PubMed:25121097).

Enzyme Numbers (IUBMB) for CASP14 Gene

Gene Ontology (GO) - Molecular Function for CASP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004175 endopeptidase activity TAS --
GO:0004197 cysteine-type endopeptidase activity TAS --
GO:0005515 protein binding IPI 24872419
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with CASP14: view
genes like me logo Genes that share phenotypes with CASP14: view

Animal Models for CASP14 Gene

MGI Knock Outs for CASP14:

Animal Model Products

  • Taconic Biosciences Mouse Models for CASP14

miRNA for CASP14 Gene

miRTarBase miRNAs that target CASP14

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for CASP14 Gene

Localization for CASP14 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CASP14 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CASP14 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
cytoskeleton 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for CASP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA 23377137
GO:0005737 cytoplasm IDA 23377137
GO:0005829 cytosol TAS --
GO:0031012 extracellular matrix IDA 23979707
GO:0045095 keratin filament IEA --
genes like me logo Genes that share ontologies with CASP14: view

Pathways & Interactions for CASP14 Gene

genes like me logo Genes that share pathways with CASP14: view

Pathways by source for CASP14 Gene

3 Sino Biological pathways for CASP14 Gene
1 GeneTex pathway for CASP14 Gene
1 Cell Signaling Technology pathway for CASP14 Gene

Gene Ontology (GO) - Biological Process for CASP14 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0008544 epidermis development TAS 10203698
GO:0030154 cell differentiation IEA --
GO:0031424 keratinization TAS 18309324
GO:0070268 cornification TAS 18309324
genes like me logo Genes that share ontologies with CASP14: view

No data available for SIGNOR curated interactions for CASP14 Gene

Drugs & Compounds for CASP14 Gene

Products:

  1. Drug

(7) Drugs for CASP14 Gene - From: ApexBio, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Apoptosis Activator 2 Pharma Indoledione caspase activator, cell-permeable 0
Boc-D-FMK Pharma Pan-caspase inhibitor 0
PAC-1 Pharma Procaspase-3 activator, Activator of procaspase-3; pro-apoptotic 0
MDL 28170 Pharma Calpain and cathepsin B inhibitor, selective, Potent, selective calpain and cathepsin B inhibitor 0
PD 150606 Pharma Non-peptide calpain inhibitor, Cell permeable calpain inhibitor 0

(5) Additional Compounds for CASP14 Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
MG 101
110044-82-1

(3) Tocris Compounds for CASP14 Gene

Compound Action Cas Number
MDL 28170 Potent, selective calpain and cathepsin B inhibitor 88191-84-8
MG 101 Calpain inhibitor; activates p53-dependent apoptosis 110044-82-1
PD 150606 Cell permeable calpain inhibitor 179528-45-1

(3) ApexBio Compounds for CASP14 Gene

Compound Action Cas Number
Apoptosis Activator 2 Indoledione caspase activator, cell-permeable 79183-19-0
Boc-D-FMK Pan-caspase inhibitor 187389-53-3, 634911-80-1
PAC-1 Procaspase-3 activator 315183-21-2
genes like me logo Genes that share compounds with CASP14: view

Transcripts for CASP14 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for CASP14 Gene

(2) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(16) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CASP14 Gene

Caspase 14, apoptosis-related cysteine peptidase:
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CASP14 Gene

No ASD Table

Relevant External Links for CASP14 Gene

GeneLoc Exon Structure for
CASP14
ECgene alternative splicing isoforms for
CASP14

Expression for CASP14 Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CASP14 Gene

mRNA expression in normal human tissues for CASP14 Gene
mRNA expression by GTEx for CASP14 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CASP14 Gene

This gene is overexpressed in Skin - Sun Exposed (Lower leg) (x28.0) and Skin - Not Sun Exposed (Suprapubic) (x23.3).

Protein differential expression in normal tissues from HIPED for CASP14 Gene

This gene is overexpressed in Skin (19.0), Hair follicle (14.3), and Oral epithelium (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CASP14 Gene



NURSA nuclear receptor signaling pathways regulating expression of CASP14 Gene:

CASP14

SOURCE GeneReport for Unigene cluster for CASP14 Gene:

Hs.466057

mRNA Expression by UniProt/SwissProt for CASP14 Gene:

P31944-CASPE_HUMAN
Tissue specificity: Expressed in keratinocytes of adult skin suprabasal layers (from spinous layers to the stratum granulosum and stratum corneum) (at protein level). Expressed in keratinocytes of hair shaft and sebaceous glands (at protein level). In psoriatic skin only expressed at very low levels (PubMed:11175259). The p17/10 mature form is expressed in epidermis stratum corneum, the p20/p8 intermediate form in epidermis upper granular cells of the stratum granulosum (PubMed:22825846).

Evidence on tissue expression from TISSUES for CASP14 Gene

  • Skin(4.8)
  • Nervous system(4)
genes like me logo Genes that share expression patterns with CASP14: view

Primer Products

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for CASP14 Gene

Orthologs for CASP14 Gene

This gene was present in the common ancestor of animals.

Orthologs for CASP14 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia CASP14 34 35
  • 98.76 (n)
dog
(Canis familiaris)
 Mammalia CASP14 34 35
  • 83.47 (n)
cow
(Bos Taurus)
 Mammalia CASP14 34 35
  • 82.23 (n)
mouse
(Mus musculus)
 Mammalia Casp14 34 16 35
  • 78.84 (n)
rat
(Rattus norvegicus)
 Mammalia Casp14 34
  • 76.94 (n)
oppossum
(Monodelphis domestica)
 Mammalia CASP14 35
  • 62 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 35
  • 35 (a)
 ManyToMany
chicken
(Gallus gallus)
 Aves CASP17 35
  • 17 (a)
 ManyToMany
lizard
(Anolis carolinensis)
 Reptilia -- 35
  • 33 (a)
 OneToMany
zebrafish
(Danio rerio)
 Actinopterygii caspa 35
  • 18 (a)
 ManyToMany
fruit fly
(Drosophila melanogaster)
 Insecta Nc 35
  • 11 (a)
 ManyToMany
Dredd 35
  • 10 (a)
 ManyToMany
worm
(Caenorhabditis elegans)
 Secernentea csp-3 35
  • 17 (a)
 ManyToMany
Species where no ortholog for CASP14 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for CASP14 Gene

ENSEMBL:
Gene Tree for CASP14 (if available)
TreeFam:
Gene Tree for CASP14 (if available)

Paralogs for CASP14 Gene

Paralogs for CASP14 Gene

(3) SIMAP similar genes for CASP14 Gene using alignment to 3 proteins:

Pseudogenes.org Pseudogenes for CASP14 Gene

genes like me logo Genes that share paralogs with CASP14: view

Variants for CASP14 Gene

Sequence variations from dbSNP and Humsavar for CASP14 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
rs1057519339 Pathogenic 15,055,216(+) AAAGA(-/CA)GCCCA reference, frameshift-variant
rs1000254363 -- 15,054,240(+) CCATG(C/T)CCAAC intron-variant
rs1000446748 -- 15,053,050(+) GAAAT(G/T)TAAGT intron-variant
rs1000640009 -- 15,055,366(+) ACGCC(C/T)TTCCA intron-variant, reference, synonymous-codon
rs1000987619 -- 15,055,601(+) CTGAG(-/CCT)CCTCC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CASP14 Gene

Variant ID Type Subtype PubMed ID
dgv654e214 CNV gain 21293372
esv2758746 CNV gain 17122850
esv3643762 CNV gain 21293372

Variation tolerance for CASP14 Gene

Residual Variation Intolerance Score: 89% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.35; 26.73% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for CASP14 Gene

Human Gene Mutation Database (HGMD)
CASP14
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CASP14

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CASP14 Gene

Disorders for CASP14 Gene

MalaCards: The human disease database

(3) MalaCards diseases for CASP14 Gene - From: DISEASES and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

CASPE_HUMAN
  • Ichthyosis, congenital, autosomal recessive 12 (ARCI12) [MIM:617320]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269 PubMed:27494380}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for CASP14

Genetic Association Database (GAD)
CASP14
Human Genome Epidemiology (HuGE) Navigator
CASP14
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
CASP14
genes like me logo Genes that share disorders with CASP14: view

No data available for Genatlas for CASP14 Gene

Publications for CASP14 Gene

  1. Activation and substrate specificity of caspase-14. (PMID: 15301553) Mikolajczyk J. … Salvesen G.S. (Biochemistry 2004) 2 3 4 22 64
  2. Purification and characterization of active caspase-14 from human epidermis and development of the cleavage site-directed antibody. (PMID: 19960512) Hibino T. … Momoi T. (J. Cell. Biochem. 2010) 3 4 22 64
  3. Mutational analysis of caspase-14 gene in common carcinomas. (PMID: 17558860) Yoo N.J. … Lee S.H. (Pathology 2007) 3 22 46 64
  4. Expression and characterization of constitutively active human caspase-14. (PMID: 16854378) Park K. … Presland R.B. (Biochem. Biophys. Res. Commun. 2006) 3 4 22 64
  5. Expression and transcriptional regulation of caspase-14 in simple and complex epithelia. (PMID: 12181750) Pistritto G. … Alnemri E.S. (Cell Death Differ. 2002) 3 4 22 64

Products for CASP14 Gene

Sources for CASP14 Gene

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