CASPE_HUMAN
ID CASPE_HUMAN Reviewed; 242 AA.
AC P31944; O95823; Q3SYC9;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2001, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Caspase-14;
DE Short=CASP-14;
DE EC=3.4.22.-;
DE Contains:
DE RecName: Full=Caspase-14 subunit p17, mature form;
DE Contains:
DE RecName: Full=Caspase-14 subunit p10, mature form;
DE Contains:
DE RecName: Full=Caspase-14 subunit p20, intermediate form;
DE Contains:
DE RecName: Full=Caspase-14 subunit p8, intermediate form;
DE Flags: Precursor;
GN Name=CASP14;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11062009; DOI=10.1006/bbrc.2000.3698;
RA Eckhart L., Ban J., Fischer H., Tschachler E.;
RT "Caspase-14: analysis of gene structure and mRNA expression during
RT keratinocyte differentiation.";
RL Biochem. Biophys. Res. Commun. 277:655-659(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=12181750; DOI=10.1038/sj.cdd.4401061;
RA Pistritto G., Jost M., Srinivasula S.M., Baffa R., Poyet J.-L., Kari C.,
RA Lazebnik Y., Rodeck U., Alnemri E.S.;
RT "Expression and transcriptional regulation of caspase-14 in simple and
RT complex epithelia.";
RL Cell Death Differ. 9:995-1006(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 68-74; 137-147 AND 154-162.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11175259; DOI=10.1038/sj.cdd.4400785;
RA Lippens S., Kockx M., Knaapen M., Mortier L., Polakowska R., Verheyen A.,
RA Garmyn M., Zwijsen A., Formstecher P., Huylebroeck D., Vandenabeele P.,
RA Declercq W.;
RT "Epidermal differentiation does not involve the pro-apoptotic executioner
RT caspases, but is associated with caspase-14 induction and processing.";
RL Cell Death Differ. 7:1218-1224(2000).
RN [6]
RP PROTEIN SEQUENCE OF 153-163, PROTEOLYTIC PROCESSING, SUBUNIT, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12200134; DOI=10.1016/s0006-291x(02)02015-6;
RA Chien A.J., Presland R.B., Kuechle M.K.;
RT "Processing of native caspase-14 occurs at an atypical cleavage site in
RT normal epidermal differentiation.";
RL Biochem. Biophys. Res. Commun. 296:911-917(2002).
RN [7]
RP FUNCTION.
RX PubMed=15301553; DOI=10.1021/bi0498048;
RA Mikolajczyk J., Scott F.L., Krajewski S., Sutherlin D.P., Salvesen G.S.;
RT "Activation and substrate specificity of caspase-14.";
RL Biochemistry 43:10560-10569(2004).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15556625; DOI=10.1016/j.febslet.2004.10.046;
RA Fischer H., Stichenwirth M., Dockal M., Ghannadan M., Buchberger M.,
RA Bach J., Kapetanopoulos A., Declercq W., Tschachler E., Eckhart L.;
RT "Stratum corneum-derived caspase-14 is catalytically active.";
RL FEBS Lett. 577:446-450(2004).
RN [9]
RP FUNCTION.
RX PubMed=16854378; DOI=10.1016/j.bbrc.2006.06.156;
RA Park K., Kuechle M.K., Choe Y., Craik C.S., Lawrence O.T., Presland R.B.;
RT "Expression and characterization of constitutively active human caspase-
RT 14.";
RL Biochem. Biophys. Res. Commun. 347:941-948(2006).
RN [10]
RP PROTEOLYTIC PROCESSING, SUBUNIT, ACTIVITY REGULATION, AND FUNCTION.
RX PubMed=19960512; DOI=10.1002/jcb.22425;
RA Hibino T., Fujita E., Tsuji Y., Nakanishi J., Iwaki H., Katagiri C.,
RA Momoi T.;
RT "Purification and characterization of active caspase-14 from human
RT epidermis and development of the cleavage site-directed antibody.";
RL J. Cell. Biochem. 109:487-497(2010).
RN [11]
RP PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT,
RP AND FUNCTION.
RX PubMed=22825846; DOI=10.1074/jbc.m112.357467;
RA Yamamoto M., Miyai M., Matsumoto Y., Tsuboi R., Hibino T.;
RT "Kallikrein-related peptidase-7 regulates caspase-14 maturation during
RT keratinocyte terminal differentiation by generating an intermediate form.";
RL J. Biol. Chem. 287:32825-32834(2012).
RN [12]
RP INDUCTION, AND FUNCTION.
RX PubMed=25121097; DOI=10.1155/2014/417986;
RA Beasley S., El-Sherbiny M., Megyerdi S., El-Shafey S., Choksi K.,
RA Kaddour-Djebbar I., Sheibani N., Hsu S., Al-Shabrawey M.;
RT "Caspase-14 expression impairs retinal pigment epithelium barrier function:
RT potential role in diabetic macular edema.";
RL Biomed. Res. Int. 2014:417986-417986(2014).
RN [13]
RP FUNCTION.
RX PubMed=24743736; DOI=10.1038/cddis.2014.145;
RA Yamamoto-Tanaka M., Makino T., Motoyama A., Miyai M., Tsuboi R., Hibino T.;
RT "Multiple pathways are involved in DNA degradation during keratinocyte
RT terminal differentiation.";
RL Cell Death Dis. 5:E1181-E1181(2014).
RN [14]
RP INVOLVEMENT IN ARCI12.
RX PubMed=27494380; DOI=10.2340/00015555-2510;
RA Kirchmeier P., Zimmer A., Bouadjar B., Roesler B., Fischer J.;
RT "Whole-Exome-Sequencing reveals small deletions in CASP14 in patients with
RT autosomal recessive inherited ichthyosis.";
RL Acta Derm. Venereol. 96:102-104(2017).
CC -!- FUNCTION: Non-apoptotic caspase involved in epidermal differentiation.
CC Is the predominant caspase in epidermal stratum corneum
CC (PubMed:15556625). Seems to play a role in keratinocyte differentiation
CC and is required for cornification. Regulates maturation of the
CC epidermis by proteolytically processing filaggrin (By similarity). In
CC vitro has a preference for the substrate [WY]-X-X-D motif and is active
CC on the synthetic caspase substrate WEHD-ACF (PubMed:16854378,
CC PubMed:19960512). Involved in processing of prosaposin in the epidermis
CC (By similarity). May be involved in retinal pigment epithelium cell
CC barrier function (PubMed:25121097). Involved in DNA degradation in
CC differentiated keratinocytes probably by cleaving DFFA/ICAD leading to
CC liberation of DFFB/CAD (PubMed:24743736).
CC {ECO:0000250|UniProtKB:O89094, ECO:0000269|PubMed:15301553,
CC ECO:0000269|PubMed:15556625, ECO:0000269|PubMed:16854378,
CC ECO:0000269|PubMed:19960512, ECO:0000269|PubMed:22825846,
CC ECO:0000269|PubMed:24743736, ECO:0000305|PubMed:25121097}.
CC -!- ACTIVITY REGULATION: Inhibited by caspase-1 inhibitor YVAD-FMK and the
CC pan-caspase inhibitor VAD-FMK. {ECO:0000269|PubMed:19960512}.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit, both processed
CC from the precursor; the mature active form is a p17/p10 dimer and the
CC intermediate form a p20/p8 dimer. {ECO:0000269|PubMed:12200134,
CC ECO:0000269|PubMed:19960512, ECO:0000269|PubMed:22825846}.
CC -!- INTERACTION:
CC P31944; P50222: MEOX2; NbExp=3; IntAct=EBI-2510738, EBI-748397;
CC P31944; P07602: PSAP; NbExp=3; IntAct=EBI-2510738, EBI-716699;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11175259,
CC ECO:0000269|PubMed:12200134, ECO:0000269|PubMed:22825846}. Nucleus
CC {ECO:0000269|PubMed:11175259}.
CC -!- TISSUE SPECIFICITY: Expressed in keratinocytes of adult skin suprabasal
CC layers (from spinous layers to the stratum granulosum and stratum
CC corneum) (at protein level). Expressed in keratinocytes of hair shaft
CC and sebaceous glands (at protein level). In psoriatic skin only
CC expressed at very low levels (PubMed:11175259). The p17/10 mature form
CC is expressed in epidermis stratum corneum, the p20/p8 intermediate form
CC in epidermis upper granular cells of the stratum granulosum
CC (PubMed:22825846). {ECO:0000269|PubMed:11175259,
CC ECO:0000269|PubMed:15556625, ECO:0000269|PubMed:22825846}.
CC -!- INDUCTION: In undifferentiated keratinocytes under postconfluency
CC growth conditions (in vitro) (PubMed:11175259). By high glucose in
CC retinal pigment epithelia cells (PubMed:25121097).
CC {ECO:0000269|PubMed:11175259, ECO:0000269|PubMed:25121097}.
CC -!- PTM: Maturation by proteolytic processing appears to be a two-step
CC process. The precursor is processed by KLK7 to yield the p20/p8
CC intermediate form which acts on the precursor to yield the p17/p10
CC mature form (PubMed:22825846). Initially, cleavage between Ile-152 and
CC Lys-153 has been proposed to yield the large and small subunits of the
CC active enzyme (PubMed:12200134). {ECO:0000269|PubMed:19960512,
CC ECO:0000269|PubMed:22825846, ECO:0000305|PubMed:12200134}.
CC -!- DISEASE: Ichthyosis, congenital, autosomal recessive 12 (ARCI12)
CC [MIM:617320]: A form of autosomal recessive congenital ichthyosis, a
CC disorder of keratinization with abnormal differentiation and
CC desquamation of the epidermis, resulting in abnormal skin scaling over
CC the whole body. The main skin phenotypes are lamellar ichthyosis (LI)
CC and non-bullous congenital ichthyosiform erythroderma (NCIE), although
CC phenotypic overlap within the same patient or among patients from the
CC same family can occur. Lamellar ichthyosis is a condition often
CC associated with an embedment in a collodion-like membrane at birth;
CC skin scales later develop, covering the entire body surface. Non-
CC bullous congenital ichthyosiform erythroderma characterized by fine
CC whitish scaling on an erythrodermal background; larger brownish scales
CC are present on the buttocks, neck and legs.
CC {ECO:0000269|PubMed:27494380}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Expressed in bacteria requires high concentrations of
CC kosmotropic salts to be activated (PubMed:15301553). The mature and the
CC intermediate form differ in activity towards synthetic caspase
CC substrates: the p17/p10 mature form but not the p20/p8 intermediate
CC form is active on WEHD-MCA; p20/p8 is active on a number of other
CC caspase substrates without any marked preference (VEID-AFC, DEVD-AFC,
CC LEVD-AFC and LEHD-AFC) (PubMed:22825846). {ECO:0000269|PubMed:15301553,
CC ECO:0000269|PubMed:22825846}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; AF097874; AAD16173.1; -; mRNA.
DR EMBL; BC069541; AAH69541.1; -; mRNA.
DR EMBL; BC103868; AAI03869.1; -; mRNA.
DR EMBL; BC103869; AAI03870.1; -; mRNA.
DR CCDS; CCDS12323.1; -.
DR PIR; JC7517; JC7517.
DR RefSeq; NP_036246.1; NM_012114.2.
DR AlphaFoldDB; P31944; -.
DR SMR; P31944; -.
DR BioGRID; 117116; 180.
DR IntAct; P31944; 33.
DR MINT; P31944; -.
DR STRING; 9606.ENSP00000393417; -.
DR BindingDB; P31944; -.
DR ChEMBL; CHEMBL5991; -.
DR GuidetoPHARMACOLOGY; 1627; -.
DR MEROPS; C14.018; -.
DR GlyGen; P31944; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P31944; -.
DR PhosphoSitePlus; P31944; -.
DR BioMuta; CASP14; -.
DR DMDM; 12231007; -.
DR EPD; P31944; -.
DR jPOST; P31944; -.
DR MassIVE; P31944; -.
DR MaxQB; P31944; -.
DR PaxDb; P31944; -.
DR PeptideAtlas; P31944; -.
DR PRIDE; P31944; -.
DR ProteomicsDB; 54815; -.
DR TopDownProteomics; P31944; -.
DR Antibodypedia; 4107; 496 antibodies from 45 providers.
DR DNASU; 23581; -.
DR Ensembl; ENST00000427043.4; ENSP00000393417.2; ENSG00000105141.6.
DR GeneID; 23581; -.
DR KEGG; hsa:23581; -.
DR MANE-Select; ENST00000427043.4; ENSP00000393417.2; NM_012114.3; NP_036246.1.
DR UCSC; uc010dzv.3; human.
DR CTD; 23581; -.
DR DisGeNET; 23581; -.
DR GeneCards; CASP14; -.
DR GeneReviews; CASP14; -.
DR HGNC; HGNC:1502; CASP14.
DR HPA; ENSG00000105141; Tissue enriched (skin).
DR MalaCards; CASP14; -.
DR MIM; 605848; gene.
DR MIM; 617320; phenotype.
DR neXtProt; NX_P31944; -.
DR OpenTargets; ENSG00000105141; -.
DR PharmGKB; PA26085; -.
DR VEuPathDB; HostDB:ENSG00000105141; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00940000162117; -.
DR HOGENOM; CLU_036904_2_2_1; -.
DR InParanoid; P31944; -.
DR OMA; EETYDMS; -.
DR OrthoDB; 1092723at2759; -.
DR PhylomeDB; P31944; -.
DR TreeFam; TF102023; -.
DR PathwayCommons; P31944; -.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P31944; -.
DR BioGRID-ORCS; 23581; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; CASP14; human.
DR GeneWiki; Caspase_14; -.
DR GenomeRNAi; 23581; -.
DR Pharos; P31944; Tchem.
DR PRO; PR:P31944; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P31944; protein.
DR Bgee; ENSG00000105141; Expressed in skin of abdomen and 76 other tissues.
DR ExpressionAtlas; P31944; baseline and differential.
DR Genevisible; P31944; HS.
DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045095; C:keratin filament; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IBA:GO_Central.
DR GO; GO:0070268; P:cornification; TAS:UniProtKB.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0031424; P:keratinization; TAS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00032; CASc; 1.
DR InterPro; IPR033174; Caspase-14.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR002398; Pept_C14.
DR InterPro; IPR002138; Pept_C14_p10.
DR InterPro; IPR001309; Pept_C14_p20.
DR InterPro; IPR015917; Pept_C14A.
DR PANTHER; PTHR10454; PTHR10454; 1.
DR PANTHER; PTHR10454:SF131; PTHR10454:SF131; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Differentiation; Direct protein sequencing; Hydrolase;
KW Ichthyosis; Nucleus; Protease; Reference proteome; Thiol protease; Zymogen.
FT CHAIN 1..178
FT /note="Caspase-14 subunit p20, intermediate form"
FT /id="PRO_0000432793"
FT PROPEP 1..5
FT /evidence="ECO:0000269|PubMed:19960512"
FT /id="PRO_0000004652"
FT CHAIN 6..146
FT /note="Caspase-14 subunit p17, mature form"
FT /id="PRO_0000432794"
FT PROPEP 147..152
FT /evidence="ECO:0000269|PubMed:19960512"
FT /id="PRO_0000432795"
FT CHAIN 153..242
FT /note="Caspase-14 subunit p10, mature form"
FT /id="PRO_0000004654"
FT CHAIN 179..242
FT /note="Caspase-14 subunit p8, intermediate form"
FT /id="PRO_0000432796"
FT ACT_SITE 89
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 132
FT /evidence="ECO:0000250|UniProtKB:P29466"
SQ SEQUENCE 242 AA; 27680 MW; E539FB7E8DD808A2 CRC64;
MSNPRSLEEE KYDMSGARLA LILCVTKARE GSEEDLDALE HMFRQLRFES TMKRDPTAEQ
FQEELEKFQQ AIDSREDPVS CAFVVLMAHG REGFLKGEDG EMVKLENLFE ALNNKNCQAL
RAKPKVYIIQ ACRGEQRDPG ETVGGDEIVM VIKDSPQTIP TYTDALHVYS TVEGYIAYRH
DQKGSCFIQT LVDVFTKRKG HILELLTEVT RRMAEAELVQ EGKARKTNPE IQSTLRKRLY
LQ
