CED4_CAEBR
ID CED4_CAEBR Reviewed; 569 AA.
AC Q60Z52; A8XSP2;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 13-OCT-2009, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Cell death protein 4;
GN Name=ced-4 {ECO:0000250|UniProtKB:P30429}; ORFNames=CBG17963;
OS Caenorhabditis briggsae.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6238;
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AF16 {ECO:0000269|PubMed:14624247};
RX PubMed=14624247; DOI=10.1371/journal.pbio.0000045;
RA Stein L.D., Bao Z., Blasiar D., Blumenthal T., Brent M.R., Chen N.,
RA Chinwalla A., Clarke L., Clee C., Coghlan A., Coulson A., D'Eustachio P.,
RA Fitch D.H.A., Fulton L.A., Fulton R.E., Griffiths-Jones S., Harris T.W.,
RA Hillier L.W., Kamath R., Kuwabara P.E., Mardis E.R., Marra M.A.,
RA Miner T.L., Minx P., Mullikin J.C., Plumb R.W., Rogers J., Schein J.E.,
RA Sohrmann M., Spieth J., Stajich J.E., Wei C., Willey D., Wilson R.K.,
RA Durbin R.M., Waterston R.H.;
RT "The genome sequence of Caenorhabditis briggsae: a platform for comparative
RT genomics.";
RL PLoS Biol. 1:166-192(2003).
CC -!- FUNCTION: Plays a major role in programmed cell death (PCD, apoptosis).
CC egl-1 binds to and directly inhibits the activity of ced-9, releasing
CC the cell death activator ced-4 from a ced-9/ced-4 containing protein
CC complex and allowing ced-4 to induce caspase ced-3 autoproteolytic
CC cleavage and activation. Also forms an holoenzyme with processed ced-3
CC enhancing ced-3 activity. Component of the egl-1, ced-9, ced-4 and ced-
CC 3 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 upstream of ced-3 but independently of egl-1.
CC May regulate germline apoptosis in response to DNA damage, probably
CC downstream of let-60/ras and mpk-1 pathway. Regulates CEP neuron
CC apoptosis in response to high Al(3+) levels. During male tail
CC morphogenesis, promotes apoptosis of the tail-spike cell. During larval
CC development, required for the elimination of transient presynaptic
CC components downstream of egl-1 and ced-9 and upstream of ced-3
CC apoptotic pathway. Together with ain-1, a component of the miRNA-
CC induced-silencing complex (miRISC), and probably upstream of ced-3,
CC regulates temporal cell fate patterning during larval development. May
CC play a role in resistance to S.typhimurium-mediated infection.
CC {ECO:0000250|UniProtKB:P30429}.
CC -!- SUBUNIT: Associates as an asymmetric homodimer with ced-9. Upon release
CC from ced-9, forms an octamer, known as the apoptosome, and interacts
CC with ced-3; the interaction results in ced-3 autoproteolytic cleavage
CC and activation. The octamer (a tetramer of an asymmetric dimer) also
CC interacts with two processed ced-3 to form a stable holoenzyme.
CC Interacts with sex-determining protein fem-1. May form a complex
CC composed of ced-3, ced-4 and mac-1 or of ced-9, ced-4 and mac-1. Within
CC the complex, interacts with ced-4. {ECO:0000250|UniProtKB:P30429}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P30429}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P30429}. Note=In
CC non cell death induced cells, ced-9 is required for mitochondrial
CC localization. Perinuclear in cell death induced cells.
CC {ECO:0000250|UniProtKB:P30429}.
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DR EMBL; HE600963; CAP35494.3; -; Genomic_DNA.
DR AlphaFoldDB; Q60Z52; -.
DR SMR; Q60Z52; -.
DR STRING; 6238.CBG17963; -.
DR EnsemblMetazoa; CBG17963a.1; CBG17963a.1; WBGene00037464.
DR WormBase; CBG17963a; CBP37567; WBGene00037464; Cbr-ced-4.
DR eggNOG; KOG4658; Eukaryota.
DR HOGENOM; CLU_496380_0_0_1; -.
DR InParanoid; Q60Z52; -.
DR OMA; YYEHVIW; -.
DR OrthoDB; 1576724at2759; -.
DR Proteomes; UP000008549; Chromosome III.
DR GO; GO:0008303; C:caspase complex; IEA:EnsemblMetazoa.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:EnsemblMetazoa.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043531; F:ADP binding; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051432; F:BH1 domain binding; IEA:EnsemblMetazoa.
DR GO; GO:0051434; F:BH3 domain binding; IEA:EnsemblMetazoa.
DR GO; GO:0089720; F:caspase binding; IEA:EnsemblMetazoa.
DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IEA:EnsemblMetazoa.
DR GO; GO:0061133; F:endopeptidase activator activity; IEA:EnsemblMetazoa.
DR GO; GO:0042802; F:identical protein binding; IEA:EnsemblMetazoa.
DR GO; GO:0000287; F:magnesium ion 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:0006915; P:apoptotic process; ISS:UniProtKB.
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:0048598; P:embryonic morphogenesis; IEA:EnsemblMetazoa.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IEA:EnsemblMetazoa.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IEA:EnsemblMetazoa.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; 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:0030155; P:regulation of cell adhesion; IEA:EnsemblMetazoa.
DR GO; GO:0008361; P:regulation of cell size; IEA:EnsemblMetazoa.
DR GO; GO:0040034; P:regulation of development, heterochronic; IEA:EnsemblMetazoa.
DR GO; GO:0031647; P:regulation of protein stability; IEA:EnsemblMetazoa.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR016854; Apop_reg_Ced-4.
DR InterPro; IPR001315; CARD.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR002182; NB-ARC.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00619; CARD; 1.
DR Pfam; PF00931; NB-ARC; 1.
DR PIRSF; PIRSF027202; Apop_reg_Ced-4; 1.
DR SMART; SM00114; CARD; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
PE 3: Inferred from homology;
KW Apoptosis; ATP-binding; Cytoplasm; Magnesium; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Reference proteome.
FT CHAIN 1..569
FT /note="Cell death protein 4"
FT /id="PRO_0000089469"
FT DOMAIN 1..91
FT /note="CARD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046"
FT DOMAIN 116..442
FT /note="NB-ARC"
FT /evidence="ECO:0000255"
FT BINDING 131
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30429"
FT BINDING 162..167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30429"
FT BINDING 166
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P30429"
FT BINDING 171
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P30429"
SQ SEQUENCE 569 AA; 65244 MW; 861130FB564AFD36 CRC64;
MLCEIECRAL NAAHTMLIQD FEPRDALTYL EGEKIFTEDH SDLISNMPTR LERIANFLRA
YRRQASELAP LIDFFEYNNQ NHLKDFLDEY LWFATHQPDK LRPVVLVPKF SRQMLDRKLL
LGNVPKQMNC FSREFHVDRV IEKLDEMCDL ESFFLFLHGR SGSGKSVIAS QALSKSDQLI
GINYDSVVWL KDSGTTPKAT FDLFTDLLLM LKRARVVSDT DDSHNMPDFI NRVLSRSEDD
LLNFPSVEHV TSVVLKRMIA NALIDRPNTL FVLDDVVQED TIRWAQELRL RCLITTRDVE
ISNAASPECE FIEVTPLESY ECFELLESYG MPVPAIERDE DILHKTIDLT SGNPAALMMI
FKSCEPKTFE KMAQLNSKLE TRGLSAIECI TPYCYKSLSS SLQRCVEVLS DEDRSALAFA
VIMPPGIDIP VKIWSCVIPV DICSNEEDQL DDEVADRLKR LSKRGALLSG KRSPVLTYKI
DHVIHLFLKH VVDVQTIANG ISILEQRLHE LGNNNTPTPE RHMPSKFRRT SAGDMFPKVE
DSVIRPEDYS KFMQIHRTFY DSLKKFTSQ
