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Protein

Caspase-14

Gene

CASP14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 substate [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).By similarity1 Publication6 Publications

Enzyme regulationi

Inhibited by caspase-1 inhibitor YVAD-FMK and the pan-caspase inhibitor VAD-FMK.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei89 – 891By similarity
Active sitei132 – 1321By similarity

GO - Molecular functioni

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
  • cornification Source: UniProtKB
  • epidermis development Source: ProtInc
  • extrinsic apoptotic signaling pathway in absence of ligand Source: GO_Central
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: GO_Central
  • keratinization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Differentiation

Protein family/group databases

MEROPSiC14.018.

Names & Taxonomyi

Protein namesi
Gene namesi
Name:CASP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1502. CASP14.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: CACAO
  • extracellular exosome Source: UniProtKB
  • keratin filament Source: Ensembl
  • nucleus Source: CACAO
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26085.

Polymorphism and mutation databases

BioMutaiCASP14.
DMDMi12231007.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 178178Caspase-14 subunit p20, intermediate formPRO_0000432793Add
BLAST
Propeptidei1 – 551 PublicationPRO_0000004652
Chaini6 – 146141Caspase-14 subunit p17, mature formPRO_0000432794Add
BLAST
Propeptidei147 – 15261 PublicationPRO_0000432795
Chaini153 – 24290Caspase-14 subunit p10, mature formPRO_0000004654Add
BLAST
Chaini179 – 24264Caspase-14 subunit p8, intermediate formPRO_0000432796Add
BLAST

Post-translational modificationi

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).1 Publication2 Publications

Keywords - PTMi

Zymogen

Proteomic databases

MaxQBiP31944.
PaxDbiP31944.
PeptideAtlasiP31944.
PRIDEiP31944.

Miscellaneous databases

PMAP-CutDBP31944.

Expressioni

Tissue specificityi

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).3 Publications

Inductioni

In undifferentiated keratinocytes under postconfluency growth conditions (in vitro) (PubMed:11175259). By high glucose in retinal pigment epithelia cells (PubMed:25121097).2 Publications

Gene expression databases

BgeeiP31944.
CleanExiHS_CASP14.
ExpressionAtlasiP31944. baseline and differential.
GenevestigatoriP31944.

Organism-specific databases

HPAiCAB010059.
HPA027062.

Interactioni

Subunit structurei

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MEOX2A4D1273EBI-2510738,EBI-10172134
PSAPP076023EBI-2510738,EBI-716699

Protein-protein interaction databases

BioGridi117116. 19 interactions.
IntActiP31944. 7 interactions.
STRINGi9606.ENSP00000221740.

Structurei

3D structure databases

ProteinModelPortaliP31944.
SMRiP31944. Positions 28-241.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiNOG327631.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050804.
InParanoidiP31944.
KOiK04401.
OMAiCVTKARE.
OrthoDBiEOG7VQJDT.
PhylomeDBiP31944.
TreeFamiTF102023.

Family and domain databases

Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P31944-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSNPRSLEEE KYDMSGARLA LILCVTKARE GSEEDLDALE HMFRQLRFES
60 70 80 90 100
TMKRDPTAEQ FQEELEKFQQ AIDSREDPVS CAFVVLMAHG REGFLKGEDG
110 120 130 140 150
EMVKLENLFE ALNNKNCQAL RAKPKVYIIQ ACRGEQRDPG ETVGGDEIVM
160 170 180 190 200
VIKDSPQTIP TYTDALHVYS TVEGYIAYRH DQKGSCFIQT LVDVFTKRKG
210 220 230 240
HILELLTEVT RRMAEAELVQ EGKARKTNPE IQSTLRKRLY LQ
Length:242
Mass (Da):27,680
Last modified:January 11, 2001 - v2
Checksum:iE539FB7E8DD808A2
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097874 mRNA. Translation: AAD16173.1.
BC069541 mRNA. Translation: AAH69541.1.
BC103868 mRNA. Translation: AAI03869.1.
BC103869 mRNA. Translation: AAI03870.1.
CCDSiCCDS12323.1.
PIRiJC7517.
RefSeqiNP_036246.1. NM_012114.2.
UniGeneiHs.466057.

Genome annotation databases

EnsembliENST00000427043; ENSP00000393417; ENSG00000105141.
GeneIDi23581.
KEGGihsa:23581.
UCSCiuc010dzv.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF097874 mRNA. Translation: AAD16173.1.
BC069541 mRNA. Translation: AAH69541.1.
BC103868 mRNA. Translation: AAI03869.1.
BC103869 mRNA. Translation: AAI03870.1.
CCDSiCCDS12323.1.
PIRiJC7517.
RefSeqiNP_036246.1. NM_012114.2.
UniGeneiHs.466057.

3D structure databases

ProteinModelPortaliP31944.
SMRiP31944. Positions 28-241.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117116. 19 interactions.
IntActiP31944. 7 interactions.
STRINGi9606.ENSP00000221740.

Chemistry

BindingDBiP31944.
ChEMBLiCHEMBL5991.

Protein family/group databases

MEROPSiC14.018.

Polymorphism and mutation databases

BioMutaiCASP14.
DMDMi12231007.

Proteomic databases

MaxQBiP31944.
PaxDbiP31944.
PeptideAtlasiP31944.
PRIDEiP31944.

Protocols and materials databases

DNASUi23581.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000427043; ENSP00000393417; ENSG00000105141.
GeneIDi23581.
KEGGihsa:23581.
UCSCiuc010dzv.2. human.

Organism-specific databases

CTDi23581.
GeneCardsiGC19P015160.
HGNCiHGNC:1502. CASP14.
HPAiCAB010059.
HPA027062.
MIMi605848. gene.
neXtProtiNX_P31944.
PharmGKBiPA26085.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG327631.
GeneTreeiENSGT00760000118912.
HOGENOMiHOG000231878.
HOVERGENiHBG050804.
InParanoidiP31944.
KOiK04401.
OMAiCVTKARE.
OrthoDBiEOG7VQJDT.
PhylomeDBiP31944.
TreeFamiTF102023.

Miscellaneous databases

ChiTaRSiCASP14. human.
GeneWikiiCaspase_14.
GenomeRNAii23581.
NextBioi46186.
PMAP-CutDBP31944.
PROiP31944.
SOURCEiSearch...

Gene expression databases

BgeeiP31944.
CleanExiHS_CASP14.
ExpressionAtlasiP31944. baseline and differential.
GenevestigatoriP31944.

Family and domain databases

Gene3Di3.40.50.1460. 1 hit.
InterProiIPR029030. Caspase-like_dom.
IPR011600. Pept_C14_caspase.
IPR001309. Pept_C14_ICE_p20.
IPR016129. Pept_C14_ICE_p20_AS.
IPR002138. Pept_C14_p10.
IPR015917. Pept_C14A_p45_core.
[Graphical view]
PfamiPF00656. Peptidase_C14. 1 hit.
[Graphical view]
PRINTSiPR00376. IL1BCENZYME.
SMARTiSM00115. CASc. 1 hit.
[Graphical view]
PROSITEiPS01122. CASPASE_CYS. 1 hit.
PS50207. CASPASE_P10. 1 hit.
PS50208. CASPASE_P20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Caspase-14: analysis of gene structure and mRNA expression during keratinocyte differentiation."
    Eckhart L., Ban J., Fischer H., Tschachler E.
    Biochem. Biophys. Res. Commun. 277:655-659(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Expression and transcriptional regulation of caspase-14 in simple and complex epithelia."
    Pistritto G., Jost M., Srinivasula S.M., Baffa R., Poyet J.-L., Kari C., Lazebnik Y., Rodeck U., Alnemri E.S.
    Cell Death Differ. 9:995-1006(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes."
    Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E., Vandekerckhove J.
    Electrophoresis 13:960-969(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 68-74; 137-147 AND 154-162.
    Tissue: Keratinocyte.
  5. "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.
    Cell Death Differ. 7:1218-1224(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
  6. "Processing of native caspase-14 occurs at an atypical cleavage site in normal epidermal differentiation."
    Chien A.J., Presland R.B., Kuechle M.K.
    Biochem. Biophys. Res. Commun. 296:911-917(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 153-163, PROTEOLYTIC PROCESSING, SUBUNIT, SUBCELLULAR LOCATION.
  7. Cited for: FUNCTION.
  8. Cited for: FUNCTION, TISSUE SPECIFICITY.
  9. "Expression and characterization of constitutively active human caspase-14."
    Park K., Kuechle M.K., Choe Y., Craik C.S., Lawrence O.T., Presland R.B.
    Biochem. Biophys. Res. Commun. 347:941-948(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Purification and characterization of active caspase-14 from human epidermis and development of the cleavage site-directed antibody."
    Hibino T., Fujita E., Tsuji Y., Nakanishi J., Iwaki H., Katagiri C., Momoi T.
    J. Cell. Biochem. 109:487-497(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, SUBUNIT, ENZYME REGULATION, FUNCTION.
  11. "Kallikrein-related peptidase-7 regulates caspase-14 maturation during keratinocyte terminal differentiation by generating an intermediate form."
    Yamamoto M., Miyai M., Matsumoto Y., Tsuboi R., Hibino T.
    J. Biol. Chem. 287:32825-32834(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT, FUNCTION.
  12. "Caspase-14 expression impairs retinal pigment epithelium barrier function: potential role in diabetic macular edema."
    Beasley S., El-Sherbiny M., Megyerdi S., El-Shafey S., Choksi K., Kaddour-Djebbar I., Sheibani N., Hsu S., Al-Shabrawey M.
    Biomed. Res. Int. 2014:417986-417986(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION, FUNCTION.
  13. "Multiple pathways are involved in DNA degradation during keratinocyte terminal differentiation."
    Yamamoto-Tanaka M., Makino T., Motoyama A., Miyai M., Tsuboi R., Hibino T.
    Cell Death Dis. 5:E1181-E1181(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiCASPE_HUMAN
AccessioniPrimary (citable) accession number: P31944
Secondary accession number(s): O95823, Q3SYC9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 11, 2001
Last modified: May 27, 2015
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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).2 Publications

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.