CED3_CAERE
ID CED3_CAERE Reviewed; 508 AA.
AC P45436; E3M6B9;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2017, sequence version 2.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Cell death protein 3;
DE EC=3.4.22.60 {ECO:0000250|UniProtKB:P42573};
DE AltName: Full=Caspase ced-3 {ECO:0000305};
DE Contains:
DE RecName: Full=Cell death protein 3 subunit p17 {ECO:0000250|UniProtKB:P42573};
DE Contains:
DE RecName: Full=Cell death protein 3 subunit p15 {ECO:0000250|UniProtKB:P42573};
DE Contains:
DE RecName: Full=Cell death protein 3 subunit p13 {ECO:0000250|UniProtKB:P42573};
DE Flags: Precursor;
GN Name=ced-3 {ECO:0000312|EMBL:EFO93085.1};
GN ORFNames=CRE_10123 {ECO:0000312|EMBL:EFO93085.1};
OS Caenorhabditis remanei (Caenorhabditis vulgaris).
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=31234;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=PB4641;
RG Caenorhabditis remanei Sequencing Consortium;
RA Wilson R.K.;
RT "PCAP assembly of the Caenorhabditis remanei genome.";
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Acts as a cysteine protease in controlling programmed cell
CC death (apoptosis) by proteolytically activating or inactivating a wide
CC range of substrates. Component of the egl-1, ced-9, ced-4 and ced-3
CC apoptotic signaling cascade required for the initiation of programmed
CC cell death in cells fated to die during embryonic and postembryonic
CC development. During oogenesis, required for germline apoptosis
CC downstream of ced-9 and ced-4 but independently of egl-1. By cleaving
CC and activating ced-8, promotes phosphatidylserine exposure on the
CC surface of apoptotic cells; phosphatidylserine is a specific marker
CC only present at the surface of apoptotic cells and acts as a specific
CC signal for engulfment. By cleaving and converting dcr-1 into a
CC deoxyribonuclease (DNase), promotes apoptotic chromosomal DNA
CC fragmentation. By cleaving mitochondrial fission protein drp-1, may
CC regulate the removal of mitochondria during apoptosis. During germline
CC apoptosis, cleaves translation initiation factor ifg-1 (isoform p170)
CC promoting cap-independent translation. During male tail morphogenesis,
CC promotes apoptosis of the tail-spike cell downstream of ced-4 but
CC independently of egl-1 and ced-9. By cleaving cnt-1, prevents the
CC activation of the prosurvival akt-1/2 signaling pathway and thus
CC promotes apoptosis. Downstream of ced-4, may play a role in sex-
CC specific cell apoptosis by cleaving sex-determining protein fem-1. May
CC regulate germline apoptosis in response to DNA damage, probably
CC downstream of let-60/ras and mpk-1 pathway. Cleaves ced-9 in vitro.
CC Cleaves csp-2 isoform b resulting in the removal of the propeptide and
CC the generation of csp-2 subunit p31 in vitro. Independently of its
CC apoptotic role has additional functions. Probably by cleaving and
CC thereby activating actin-severing protein gsnl-1, required for the
CC elimination of transient presynaptic components during larval
CC development downstream of egl-1, ced-9 and ced-4 pathway. Together with
CC ain-1, a component of the miRNA-induced-silencing complex (miRISC),
CC regulates temporal cell fate patterning during larval development. Acts
CC in cell fate patterning by cleaving heterochronic protein lin-28,
CC likely promoting its degradation. Also cleaves heterochronic protein
CC lin-14 and exonuclease disl-2 in vitro. Downstream of calreticulin crt-
CC 1 and ced-4 and independently of egl-1 and ced-9, plays a role in the
CC initial steps of axonal regrowth following axotomy. Cleaves 14-3-3-like
CC protein ftt-2, tubulin tbb-2 and calreticulin crt-1 in vitro. Plays
CC also a role in resistance to S.typhimurium-mediated infection.
CC {ECO:0000250|UniProtKB:P42573}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Strict requirement for an Asp residue at position P1 and has a
CC preferred cleavage sequence of Asp-Glu-Val-Asp-|-.; EC=3.4.22.60;
CC Evidence={ECO:0000250|UniProtKB:P42573};
CC -!- ACTIVITY REGULATION: Octameric ced-4 activates zymogen autoprocessing
CC and enhances activity of processed ced-3. Zymogen autoactivation is
CC inhibited by csp-3. csp-3 has no effect on active ced-3. Zymogen
CC autoactivation is inhibited by csp-2. Inhibited by cysteine protease
CC inhibitor iodoacetic acid (CH3COOI). Inhibited by benzyloxycarbonyl-
CC DEVD-fluoro-methyl ketone (zDEVD-fmk). Inhibited by benzyloxycarbonyl-
CC VAD-fluoro-methyl ketone (zVAD-fmk). Not inhibited by N-[N-(L-3-
CC transcarboxirane-2-carbonyl)-leucyl]-agmatine (E-64) or by the serine
CC and cysteine protease inhibitor L-1-chloro-3-[4-to-osylamido]-7-amino-
CC 2-heptanone (TLCK). {ECO:0000250|UniProtKB:P42573}.
CC -!- SUBUNIT: The active form is probably a heterodimer of the p17 subunit
CC with either the p15 or p13 subunit which are all derived from the
CC precursor by autocatalysis. Interacts with octameric ced-4 (two ced-3
CC zymogens per one ced-4 octamer); the interaction causes the
CC autoproteolytic cleavage and activation of ced-3. Processed ced-3 also
CC interacts with ced-4 octamer to form a stable holoenzyme. Interacts
CC (via large subunit p17) with csp-3; the interaction prevents ced-3
CC autoactivation and delays ced-4-induced ced-3 processing. Interacts
CC (via large subunit p17 or small subunit p13 or p15) with csp-2; the
CC interaction inhibits ced-3 autoactivation. Interacts (via propeptide)
CC with nucleoporin npp-14; the interaction tethers ced-3 to the nuclear
CC membrane and prevents its autoprocessing in absence of ced-4. Interacts
CC with dct-1. May form a complex composed of ced-3, ced-4 and mac-1.
CC {ECO:0000250|UniProtKB:P42573}.
CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000250|UniProtKB:P42573}.
CC Perikaryon {ECO:0000250|UniProtKB:P42573}. Synapse
CC {ECO:0000250|UniProtKB:P42573}. Mitochondrion
CC {ECO:0000250|UniProtKB:P42573}. Cytoplasm
CC {ECO:0000250|UniProtKB:P42573}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P42573}. Note=Colocalizes with nucleoporin npp-
CC 14 to the perinuclear region in germ cells. Becomes diffused in the
CC cytoplasm in apoptotic germ cells. Localizes to axonal mitochondria and
CC synapses of DD motor neurons. Synaptic localization is dependent on
CC axonal mitochondria. {ECO:0000250|UniProtKB:P42573}.
CC -!- DOMAIN: The CARD domain is involved in ced-4 binding.
CC {ECO:0000250|UniProtKB:P42573}.
CC -!- PTM: Autocatalytic cleavage removes the propeptide and generates the
CC catalytic subunit p17 and two non-catalytic subunits p15 and p13;
CC autoproteolysis is induced by ced-4 oligomer. Cleaved by caspase csp-1
CC probably at Asp-146 and Asp-376. {ECO:0000250|UniProtKB:P42573}.
CC -!- SIMILARITY: Belongs to the peptidase C14A family. {ECO:0000305}.
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DR EMBL; DS268426; EFO93085.1; -; Genomic_DNA.
DR RefSeq; XP_003108285.1; XM_003108237.1.
DR AlphaFoldDB; P45436; -.
DR SMR; P45436; -.
DR STRING; 31234.CRE10123; -.
DR MEROPS; C14.002; -.
DR EnsemblMetazoa; CRE10123.1; CRE10123.1; WBGene00062743.
DR GeneID; 9828818; -.
DR CTD; 9828818; -.
DR eggNOG; KOG3573; Eukaryota.
DR HOGENOM; CLU_036904_5_2_1; -.
DR OMA; EHGELYG; -.
DR OrthoDB; 1092723at2759; -.
DR Proteomes; UP000008281; Unassembled WGS sequence.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0008303; C:caspase complex; IEA:EnsemblMetazoa.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:EnsemblMetazoa.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IEA:EnsemblMetazoa.
DR GO; GO:0097200; F:cysteine-type endopeptidase activity involved in execution phase of apoptosis; IEA:EnsemblMetazoa.
DR GO; GO:0042802; F:identical protein binding; IEA:EnsemblMetazoa.
DR GO; GO:0030042; P:actin filament depolymerization; IEA:EnsemblMetazoa.
DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IEA:EnsemblMetazoa.
DR GO; GO:1902742; P:apoptotic process involved in development; IEA:EnsemblMetazoa.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:EnsemblMetazoa.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEA:EnsemblMetazoa.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:EnsemblMetazoa.
DR GO; GO:1905803; P:negative regulation of cellular response to manganese ion; IEA:EnsemblMetazoa.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IEA:EnsemblMetazoa.
DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IEA:EnsemblMetazoa.
DR GO; GO:1905845; P:positive regulation of cellular response to gamma radiation; IEA:EnsemblMetazoa.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:EnsemblMetazoa.
DR GO; GO:1901046; P:positive regulation of oviposition; IEA:EnsemblMetazoa.
DR GO; GO:0010954; P:positive regulation of protein processing; IEA:EnsemblMetazoa.
DR GO; GO:1905808; P:positive regulation of synapse pruning; IEA:EnsemblMetazoa.
DR GO; GO:0016540; P:protein autoprocessing; IEA:EnsemblMetazoa.
DR GO; GO:0030163; P:protein catabolic process; IEA:EnsemblMetazoa.
DR GO; GO:0030155; P:regulation of cell adhesion; IEA:EnsemblMetazoa.
DR GO; GO:0042659; P:regulation of cell fate specification; IEA:EnsemblMetazoa.
DR GO; GO:0040034; P:regulation of development, heterochronic; IEA:EnsemblMetazoa.
DR GO; GO:0040012; P:regulation of locomotion; IEA:EnsemblMetazoa.
DR GO; GO:0031647; P:regulation of protein stability; IEA:EnsemblMetazoa.
DR GO; GO:0040028; P:regulation of vulval development; IEA:EnsemblMetazoa.
DR CDD; cd00032; CASc; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR029030; Caspase-like_dom_sf.
DR InterPro; IPR033139; Caspase_cys_AS.
DR InterPro; IPR016129; Caspase_his_AS.
DR InterPro; IPR011029; DEATH-like_dom_sf.
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 Pfam; PF00619; CARD; 1.
DR PRINTS; PR00376; IL1BCENZYME.
DR SMART; SM00114; CARD; 1.
DR SMART; SM00115; CASc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52129; SSF52129; 1.
DR PROSITE; PS50209; CARD; 1.
DR PROSITE; PS01122; CASPASE_CYS; 1.
DR PROSITE; PS01121; CASPASE_HIS; 1.
DR PROSITE; PS50207; CASPASE_P10; 1.
DR PROSITE; PS50208; CASPASE_P20; 1.
PE 3: Inferred from homology;
KW Apoptosis; Autocatalytic cleavage; Cytoplasm; Hydrolase; Membrane;
KW Mitochondrion; Nucleus; Protease; Reference proteome; Synapse;
KW Thiol protease; Zymogen.
FT PROPEP 1..223
FT /evidence="ECO:0000250|UniProtKB:P42573"
FT /id="PRO_0000441119"
FT CHAIN 224..376
FT /note="Cell death protein 3 subunit p17"
FT /evidence="ECO:0000305"
FT /id="PRO_0000004676"
FT CHAIN 377..508
FT /note="Cell death protein 3 subunit p15"
FT /evidence="ECO:0000305"
FT /id="PRO_0000004677"
FT CHAIN 392..508
FT /note="Cell death protein 3 subunit p13"
FT /evidence="ECO:0000305"
FT /id="PRO_0000441120"
FT DOMAIN 2..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT REGION 106..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..185
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 392..407
FT /note="Required for interaction with ced-4"
FT /evidence="ECO:0000250|UniProtKB:P42573"
FT COMPBIAS 114..130
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..185
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 317
FT /evidence="ECO:0000250|UniProtKB:P29466"
FT ACT_SITE 360
FT /evidence="ECO:0000250|UniProtKB:P42573"
FT SITE 223..224
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P42573"
FT SITE 376..377
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P42573"
FT SITE 391..392
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P42573"
SQ SEQUENCE 508 AA; 57415 MW; A635C0D101BD3EA8 CRC64;
MMRQDRRNLL ERNILVFSNK LQSEQILEVL IAKQILNADN GDVINSCRTE RDKRKEIVKA
VQRRGDVAFD AFYDALRDTG HHELAAVLEP LARTIDFITP RDLECPMSPA SHRRSRALSP
STFSSPTRVH RDSVSSVSSF TSTYQDVYTR ARSTSRSSRP LHASDRHNYV SPSNSFQSQP
SSANSSFTGC SSLGYSSSRT RSYSKASAHS QYIFHEEDMN YVDAPTIHRV FDEKTMYRNF
STPRGLCLII NNEHFEQMPT RNGTKADKDN ISNLFRCMGY IVHCKDNLTG RAMMLTIRDF
AKNETHGDSA ILVILSHGEE NVIIGVDDVS VNVHEIYDLL NAANAPRLAN KPKLVFVQAC
RGERRDNGFP VLDSVDGVPA LIRPRGWDKG DGPLFNFLGC VRPQAQQVWR KKPSQADILI
AYATTAQYVS WRNSARGSWF IQAVCEVFSL HAKDMDVVEL LTEVNKKVAC GFQTSQGANI
LKQMPELTSR LLKKFYFWPE DRNRSSAV
