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Protein

Caspase-14

Gene

CASP14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 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).By similarity1 Publication6 Publications

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

Activity regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei89By similarity1
Active sitei132By similarity1

GO - Molecular functioni

GO - Biological processi

  • cornification Source: UniProtKB
  • epidermis development Source: ProtInc
  • execution phase of apoptosis Source: GO_Central
  • keratinization Source: UniProtKB

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processDifferentiation

Enzyme and pathway databases

ReactomeiR-HSA-6809371 Formation of the cornified envelope

Protein family/group databases

MEROPSiC14.018

Names & Taxonomyi

Protein namesi
Gene namesi
Name:CASP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000105141.5
HGNCiHGNC:1502 CASP14
MIMi605848 gene
neXtProtiNX_P31944

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Ichthyosis, congenital, autosomal recessive 12 (ARCI12)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:617320

Keywords - Diseasei

Ichthyosis

Organism-specific databases

DisGeNETi23581
MalaCardsiCASP14
MIMi617320 phenotype
OpenTargetsiENSG00000105141
PharmGKBiPA26085

Chemistry databases

ChEMBLiCHEMBL5991
GuidetoPHARMACOLOGYi1627

Polymorphism and mutation databases

BioMutaiCASP14
DMDMi12231007

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004327931 – 178Caspase-14 subunit p20, intermediate formAdd BLAST178
PropeptideiPRO_00000046521 – 51 Publication5
ChainiPRO_00004327946 – 146Caspase-14 subunit p17, mature formAdd BLAST141
PropeptideiPRO_0000432795147 – 1521 Publication6
ChainiPRO_0000004654153 – 242Caspase-14 subunit p10, mature formAdd BLAST90
ChainiPRO_0000432796179 – 242Caspase-14 subunit p8, intermediate formAdd BLAST64

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

EPDiP31944
MaxQBiP31944
PaxDbiP31944
PeptideAtlasiP31944
PRIDEiP31944
ProteomicsDBi54815
TopDownProteomicsiP31944

PTM databases

iPTMnetiP31944
PhosphoSitePlusiP31944

Miscellaneous databases

PMAP-CutDBiP31944

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

BgeeiENSG00000105141 Expressed in 62 organ(s), highest expression level in skin of leg
CleanExiHS_CASP14
ExpressionAtlasiP31944 baseline and differential
GenevisibleiP31944 HS

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

Protein-protein interaction databases

BioGridi117116, 29 interactors
IntActiP31944, 11 interactors
STRINGi9606.ENSP00000221740

Chemistry databases

BindingDBiP31944

Structurei

3D structure databases

ProteinModelPortaliP31944
SMRiP31944
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase C14A family.Curated

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOGENOMiHOG000231878
HOVERGENiHBG050804
InParanoidiP31944
KOiK04401
OMAiSTMKRDP
OrthoDBiEOG091G0KY9
PhylomeDBiP31944
TreeFamiTF102023

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR033174 Caspase-14
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF131 PTHR10454:SF131, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit

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.3 human

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117116, 29 interactors
IntActiP31944, 11 interactors
STRINGi9606.ENSP00000221740

Chemistry databases

BindingDBiP31944
ChEMBLiCHEMBL5991
GuidetoPHARMACOLOGYi1627

Protein family/group databases

MEROPSiC14.018

PTM databases

iPTMnetiP31944
PhosphoSitePlusiP31944

Polymorphism and mutation databases

BioMutaiCASP14
DMDMi12231007

Proteomic databases

EPDiP31944
MaxQBiP31944
PaxDbiP31944
PeptideAtlasiP31944
PRIDEiP31944
ProteomicsDBi54815
TopDownProteomicsiP31944

Protocols and materials databases

DNASUi23581
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000427043; ENSP00000393417; ENSG00000105141
GeneIDi23581
KEGGihsa:23581
UCSCiuc010dzv.3 human

Organism-specific databases

CTDi23581
DisGeNETi23581
EuPathDBiHostDB:ENSG00000105141.5
GeneCardsiCASP14
HGNCiHGNC:1502 CASP14
HPAiCAB010059
HPA027062
MalaCardsiCASP14
MIMi605848 gene
617320 phenotype
neXtProtiNX_P31944
OpenTargetsiENSG00000105141
PharmGKBiPA26085
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3573 Eukaryota
ENOG410ZQIE LUCA
GeneTreeiENSGT00760000118912
HOGENOMiHOG000231878
HOVERGENiHBG050804
InParanoidiP31944
KOiK04401
OMAiSTMKRDP
OrthoDBiEOG091G0KY9
PhylomeDBiP31944
TreeFamiTF102023

Enzyme and pathway databases

ReactomeiR-HSA-6809371 Formation of the cornified envelope

Miscellaneous databases

ChiTaRSiCASP14 human
GeneWikiiCaspase_14
GenomeRNAii23581
PMAP-CutDBiP31944
PROiPR:P31944
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105141 Expressed in 62 organ(s), highest expression level in skin of leg
CleanExiHS_CASP14
ExpressionAtlasiP31944 baseline and differential
GenevisibleiP31944 HS

Family and domain databases

CDDicd00032 CASc, 1 hit
InterProiView protein in InterPro
IPR033174 Caspase-14
IPR029030 Caspase-like_dom_sf
IPR033139 Caspase_cys_AS
IPR002138 Pept_C14_p10
IPR001309 Pept_C14_p20
IPR015917 Pept_C14A
PANTHERiPTHR10454:SF131 PTHR10454:SF131, 1 hit
PRINTSiPR00376 IL1BCENZYME
SMARTiView protein in SMART
SM00115 CASc, 1 hit
SUPFAMiSSF52129 SSF52129, 1 hit
PROSITEiView protein in PROSITE
PS01122 CASPASE_CYS, 1 hit
PS50207 CASPASE_P10, 1 hit
PS50208 CASPASE_P20, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCASPE_HUMAN
AccessioniPrimary (citable) accession number: P31944
Secondary accession number(s): O95823, Q3SYC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: January 11, 2001
Last modified: September 12, 2018
This is version 169 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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