ID CED4_CAEEL Reviewed; 571 AA. AC P30429; Q5BHI5; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 29-MAR-2005, sequence version 2. DT 27-MAR-2024, entry version 181. DE RecName: Full=Cell death protein 4; GN Name=ced-4; ORFNames=C35D10.9; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; OC Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A), FUNCTION, DEVELOPMENTAL RP STAGE, AND DISRUPTION PHENOTYPE. RX PubMed=1286611; DOI=10.1242/dev.116.2.309; RA Yuan J., Horvitz H.R.; RT "The Caenorhabditis elegans cell death gene ced-4 encodes a novel protein RT and is expressed during the period of extensive programmed cell death."; RL Development 116:309-320(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for investigating RT biology."; RL Science 282:2012-2018(1998). RN [3] RP FUNCTION. RX PubMed=3955651; DOI=10.1016/0092-8674(86)90004-8; RA Ellis H.M., Horvitz H.R.; RT "Genetic control of programmed cell death in the nematode C. elegans."; RL Cell 44:817-829(1986). RN [4] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=8706125; DOI=10.1016/s0092-8674(00)80092-6; RA Shaham S., Horvitz H.R.; RT "An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death RT inhibitor."; RL Cell 86:201-208(1996). RN [5] RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND INTERACTION WITH CED-9. RX PubMed=9027313; DOI=10.1126/science.275.5303.1126; RA Wu D., Wallen H.D., Nunez G.; RT "Interaction and regulation of subcellular localization of CED-4 by RT CED-9."; RL Science 275:1126-1129(1997). RN [6] RP FUNCTION. RX PubMed=9927601; DOI=10.1242/dev.126.5.1011; RA Gumienny T.L., Lambie E., Hartwieg E., Horvitz H.R., Hengartner M.O.; RT "Genetic control of programmed cell death in the Caenorhabditis elegans RT hermaphrodite germline."; RL Development 126:1011-1022(1999). RN [7] RP INTERACTION WITH MAC-1, AND MUTAGENESIS OF ILE-280. RX PubMed=10101135; DOI=10.1242/dev.126.9.2021; RA Wu D., Chen P.J., Chen S., Hu Y., Nunez G., Ellis R.E.; RT "C. elegans MAC-1, an essential member of the AAA family of ATPases, can RT bind CED-4 and prevent cell death."; RL Development 126:2021-2031(1999). RN [8] RP FUNCTION, AND INTERACTION WITH FEM-1. RX PubMed=10764728; DOI=10.1074/jbc.c000146200; RA Chan S.L., Yee K.S., Tan K.M., Yu V.C.; RT "The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 RT substrate that associates with CED-4 and mediates apoptosis in mammalian RT cells."; RL J. Biol. Chem. 275:17925-17928(2000). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=10688797; DOI=10.1126/science.287.5457.1485; RA Chen F., Hersh B.M., Conradt B., Zhou Z., Riemer D., Gruenbaum Y., RA Horvitz H.R.; RT "Translocation of C. elegans CED-4 to nuclear membranes during programmed RT cell death."; RL Science 287:1485-1489(2000). RN [10] RP FUNCTION. RX PubMed=11226309; DOI=10.1073/pnas.041613098; RA Aballay A., Ausubel F.M.; RT "Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis RT elegans from Salmonella typhimurium-mediated killing."; RL Proc. Natl. Acad. Sci. U.S.A. 98:2735-2739(2001). RN [11] RP MUTAGENESIS OF 80-GLN--CYS-571. RX PubMed=12944970; DOI=10.1038/nature01920; RA Bloss T.A., Witze E.S., Rothman J.H.; RT "Suppression of CED-3-independent apoptosis by mitochondrial betaNAC in RT Caenorhabditis elegans."; RL Nature 424:1066-1071(2003). RN [12] RP FUNCTION, AND INTERACTION WITH CED-9. RX PubMed=15383288; DOI=10.1016/j.molcel.2004.08.022; RA Yan N., Gu L., Kokel D., Chai J., Li W., Han A., Chen L., Xue D., Shi Y.; RT "Structural, biochemical, and functional analyses of CED-9 recognition by RT the proapoptotic proteins EGL-1 and CED-4."; RL Mol. Cell 15:999-1006(2004). RN [13] RP FUNCTION. RX PubMed=17329362; DOI=10.1242/dev.02818; RA Maurer C.W., Chiorazzi M., Shaham S.; RT "Timing of the onset of a developmental cell death is controlled by RT transcriptional induction of the C. elegans ced-3 caspase-encoding gene."; RL Development 134:1357-1368(2007). RN [14] RP FUNCTION. RX PubMed=21901106; DOI=10.1371/journal.pgen.1002238; RA Rutkowski R., Dickinson R., Stewart G., Craig A., Schimpl M., Keyse S.M., RA Gartner A.; RT "Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell RT apoptosis by Ras/MAPK signaling."; RL PLoS Genet. 7:E1002238-E1002238(2011). RN [15] RP FUNCTION. RX PubMed=22629231; DOI=10.1371/journal.pbio.1001331; RA Pinan-Lucarre B., Gabel C.V., Reina C.P., Hulme S.E., Shevkoplyas S.S., RA Slone R.D., Xue J., Qiao Y., Weisberg S., Roodhouse K., Sun L., RA Whitesides G.M., Samuel A., Driscoll M.; RT "The core apoptotic executioner proteins CED-3 and CED-4 promote initiation RT of neuronal regeneration in Caenorhabditis elegans."; RL PLoS Biol. 10:E1001331-E1001331(2012). RN [16] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=23106139; DOI=10.1111/jnc.12072; RA VanDuyn N., Settivari R., LeVora J., Zhou S., Unrine J., Nass R.; RT "The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine RT neuron degeneration."; RL J. Neurochem. 124:147-157(2013). RN [17] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=25432023; DOI=10.7554/elife.04265; RA Weaver B.P., Zabinsky R., Weaver Y.M., Lee E.S., Xue D., Han M.; RT "CED-3 caspase acts with miRNAs to regulate non-apoptotic gene expression RT dynamics for robust development in C. elegans."; RL Elife 3:E04265-E04265(2014). RN [18] RP FUNCTION. RX PubMed=26074078; DOI=10.1016/j.celrep.2015.05.031; RA Meng L., Mulcahy B., Cook S.J., Neubauer M., Wan A., Jin Y., Yan D.; RT "The cell death pathway regulates synapse elimination through cleavage of RT gelsolin in Caenorhabditis elegans neurons."; RL Cell Rep. 11:1737-1748(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF ISOFORM A IN COMPLEX WITH ATP; RP MAGNESIUM AND CED-9, FUNCTION, AND MUTAGENESIS OF VAL-252; ARG-255; MET-256 RP AND 272-ASP-ASP-273. RX PubMed=16208361; DOI=10.1038/nature04002; RA Yan N., Chai J., Lee E.S., Gu L., Liu Q., He J., Wu J.W., Kokel D., Li H., RA Hao Q., Xue D., Shi Y.; RT "Structure of the CED-4-CED-9 complex provides insights into programmed RT cell death in Caenorhabditis elegans."; RL Nature 437:831-837(2005). RN [20] RP X-RAY CRYSTALLOGRAPHY (3.53 ANGSTROMS) IN COMPLEX WITH CED-3; MAGNESIUM AND RP ATP, AND FUNCTION. RX PubMed=20434985; DOI=10.1016/j.cell.2010.03.017; RA Qi S., Pang Y., Hu Q., Liu Q., Li H., Zhou Y., He T., Liang Q., Liu Y., RA Yuan X., Luo G., Li H., Wang J., Yan N., Shi Y.; RT "Crystal structure of the Caenorhabditis elegans apoptosome reveals an RT octameric assembly of CED-4."; RL Cell 141:446-457(2010). RN [21] RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) IN COMPLEX WITH CED-3 AND ATP RP (ISOFORM A), FUNCTION, AND MUTAGENESIS OF ALA-416. RX PubMed=24065769; DOI=10.1101/gad.224428.113; RA Huang W., Jiang T., Choi W., Qi S., Pang Y., Hu Q., Xu Y., Gong X., RA Jeffrey P.D., Wang J., Shi Y.; RT "Mechanistic insights into CED-4-mediated activation of CED-3."; RL Genes Dev. 27:2039-2048(2013). CC -!- FUNCTION: Component of the egl-1, ced-9, ced-4 and ced-3 apoptotic CC signaling cascade required for the initiation of programmed cell death CC in cells fated to die during embryonic and postembryonic development CC (PubMed:3955651). During oogenesis, required for germline apoptosis CC downstream of ced-9 and upstream of ced-3 but independently of egl-1 CC (PubMed:9927601). May regulate germline apoptosis in response to DNA CC damage, probably downstream of let-60/ras and mpk-1 pathway CC (PubMed:21901106). Regulates CEP neuron apoptosis in response to high CC Al(3+) levels (PubMed:23106139). During male tail morphogenesis, CC promotes apoptosis of the tail-spike cell upstream of ced-3 but CC independently of egl-1 and ced-9 (PubMed:17329362). May play a role in CC sex-specific cell apoptosis, probably by promoting ced-3-mediated CC cleavage of sex-determining protein fem-1 (PubMed:10764728). During CC larval development, required for the elimination of transient CC presynaptic components downstream of egl-1 and ced-9 and upstream of CC ced-3 apoptotic pathway (PubMed:26074078). Downstream of calreticulin CC crt-1 and upstream of ced-3 and independently of egl-1 and ced-9, plays CC a role in the initial steps of axonal regrowth following axotomy CC (PubMed:22629231). 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 CC (PubMed:25432023). May play a role in resistance to S.typhimurium- CC mediated infection (PubMed:11226309). {ECO:0000269|PubMed:10764728, CC ECO:0000269|PubMed:11226309, ECO:0000269|PubMed:17329362, CC ECO:0000269|PubMed:21901106, ECO:0000269|PubMed:22629231, CC ECO:0000269|PubMed:23106139, ECO:0000269|PubMed:25432023, CC ECO:0000269|PubMed:26074078, ECO:0000269|PubMed:3955651, CC ECO:0000269|PubMed:9927601}. CC -!- FUNCTION: [Isoform a]: Plays a major role in programmed cell death CC (PubMed:1286611, PubMed:8706125). egl-1 binds to and directly inhibits CC the activity of ced-9, releasing the cell death activator ced-4 from a CC ced-9/ced-4 containing protein complex and allowing ced-4 to induce CC caspase ced-3 autoproteolytic cleavage and activation (PubMed:15383288, CC PubMed:16208361, PubMed:20434985, PubMed:24065769). Also forms a CC holoenzyme with processed ced-3 enhancing ced-3 activity CC (PubMed:20434985). {ECO:0000269|PubMed:10688797, CC ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:15383288, CC ECO:0000269|PubMed:16208361, ECO:0000269|PubMed:20434985, CC ECO:0000269|PubMed:24065769, ECO:0000269|PubMed:8706125}. CC -!- FUNCTION: [Isoform b]: Prevents programmed cell death. CC {ECO:0000269|PubMed:8706125}. CC -!- SUBUNIT: Associates as an asymmetric homodimer with ced-9 CC (PubMed:16208361, PubMed:9027313, PubMed:15383288). Upon release from CC ced-9, forms an octamer, known as the apoptosome, and interacts with CC ced-3; the interaction results in ced-3 autoproteolytic cleavage and CC activation (PubMed:20434985, PubMed:24065769). The octamer (a tetramer CC of an asymmetric dimer) also interacts with two processed ced-3 to form CC a stable holoenzyme (PubMed:20434985). Interacts with sex-determining CC protein fem-1 (PubMed:10764728). May form a complex composed of ced-3, CC ced-4 and mac-1 or of ced-9, ced-4 and mac-1 (PubMed:10101135). Within CC the complex, interacts with ced-4 (PubMed:10101135). CC {ECO:0000269|PubMed:10101135, ECO:0000269|PubMed:10764728, CC ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361, CC ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, CC ECO:0000269|PubMed:9027313}. CC -!- INTERACTION: CC P30429; P42573: ced-3; NbExp=10; IntAct=EBI-494118, EBI-494247; CC P30429; P41958: ced-9; NbExp=17; IntAct=EBI-494118, EBI-494110; CC P30429; Q20924: sun-1; NbExp=3; IntAct=EBI-494118, EBI-15599048; CC P30429-2; P42573: ced-3; NbExp=13; IntAct=EBI-536271, EBI-494247; CC P30429-2; P41958: ced-9; NbExp=5; IntAct=EBI-536271, EBI-494110; CC P30429-2; Q9NAG4: mac-1; NbExp=8; IntAct=EBI-536271, EBI-2005767; CC P30429-2; Q07817-1: BCL2L1; Xeno; NbExp=2; IntAct=EBI-536271, EBI-287195; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:10688797, CC ECO:0000269|PubMed:9027313}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Note=In non CC cell death induced cells, ced-9 is required for mitochondrial CC localization. Perinuclear in cell death induced cells. CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=b {ECO:0000312|WormBase:C35D10.9b}; Synonyms=Long CC {ECO:0000303|PubMed:8706125}; CC IsoId=P30429-1; Sequence=Displayed; CC Name=a {ECO:0000312|WormBase:C35D10.9a}; Synonyms=Short CC {ECO:0000303|PubMed:8706125}; CC IsoId=P30429-2; Sequence=VSP_013199; CC -!- DEVELOPMENTAL STAGE: Abundantly expressed during embryogenesis and to a CC lesser extent in larvae and adults (PubMed:1286611). Expression starts CC at the 100-cell stage and persists through embryogenesis (at protein CC level) (PubMed:9027313). Not expressed in larvae and adults (at protein CC level) (PubMed:9027313). {ECO:0000269|PubMed:1286611, CC ECO:0000269|PubMed:9027313}. CC -!- DISRUPTION PHENOTYPE: Mutants exhibit a block in almost all programmed CC cell deaths that normally occur during development (PubMed:1286611). CC RNAi-mediated knockdown causes a defect in egg laying in a small CC proportion of animals (PubMed:25432023). Also causes a moderate CC increase in CEP neuron survival in response to high Al(3+) levels CC (PubMed:23106139). In an ain-1 mutant background, enhances the CC proportion of animals arrested at the larval stage, with egg-laying CC defects and with a ruptured vulva (PubMed:25432023). CC {ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:23106139, CC ECO:0000269|PubMed:25432023}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X69016; CAA48781.1; -; Genomic_DNA. DR EMBL; BX284603; CCD66781.1; -; Genomic_DNA. DR EMBL; BX284603; CCD66782.1; -; Genomic_DNA. DR PIR; S72566; S72566. DR RefSeq; NP_001021202.1; NM_001026031.2. [P30429-2] DR RefSeq; NP_001021203.1; NM_001026032.1. [P30429-1] DR PDB; 2A5Y; X-ray; 2.60 A; B/C=1-571. DR PDB; 3LQQ; X-ray; 3.53 A; A/B=1-571. DR PDB; 3LQR; X-ray; 3.90 A; A/B=1-571. DR PDB; 4M9S; X-ray; 3.21 A; A/B/C/D=1-571. DR PDB; 4M9X; X-ray; 3.34 A; A/B=1-571. DR PDB; 4M9Y; X-ray; 4.20 A; A/B=1-571. DR PDB; 4M9Z; X-ray; 3.40 A; A/B/C/D=1-571. DR PDB; 8JNS; EM; 4.20 A; A/B/C/D/E/F/G/H/I=1-571. DR PDB; 8JO0; EM; 3.60 A; A/B/C/D/E/F/G=1-571, H/I/J/K/L/M=1-110. DR PDB; 8JOL; EM; 3.00 A; A/B=1-571. DR PDBsum; 2A5Y; -. DR PDBsum; 3LQQ; -. DR PDBsum; 3LQR; -. DR PDBsum; 4M9S; -. DR PDBsum; 4M9X; -. DR PDBsum; 4M9Y; -. DR PDBsum; 4M9Z; -. DR PDBsum; 8JNS; -. DR PDBsum; 8JO0; -. DR PDBsum; 8JOL; -. DR AlphaFoldDB; P30429; -. DR EMDB; EMD-36450; -. DR EMDB; EMD-36451; -. DR EMDB; EMD-36459; -. DR SMR; P30429; -. DR BioGRID; 40877; 17. DR ComplexPortal; CPX-1358; ced-3-ced-4-mac-1 complex. DR ComplexPortal; CPX-1359; ced-4-ced-9-mac-1 complex. DR ComplexPortal; CPX-1360; ced-3-ced-4 caspase complex. DR ComplexPortal; CPX-399; ced-9-ced-4 complex. DR DIP; DIP-1016N; -. DR IntAct; P30429; 7. DR STRING; 6239.C35D10.9b.2; -. DR EPD; P30429; -. DR PaxDb; 6239-C35D10-9b; -. DR PeptideAtlas; P30429; -. DR EnsemblMetazoa; C35D10.9a.1; C35D10.9a.1; WBGene00000418. [P30429-2] DR EnsemblMetazoa; C35D10.9b.1; C35D10.9b.1; WBGene00000418. [P30429-1] DR GeneID; 175643; -. DR KEGG; cel:CELE_C35D10.9; -. DR UCSC; C35D10.9b; c. elegans. [P30429-1] DR AGR; WB:WBGene00000418; -. DR WormBase; C35D10.9a; CE01203; WBGene00000418; ced-4. [P30429-2] DR WormBase; C35D10.9b; CE38154; WBGene00000418; ced-4. [P30429-1] DR eggNOG; KOG4658; Eukaryota. DR HOGENOM; CLU_496380_0_0_1; -. DR InParanoid; P30429; -. DR OMA; YYEHVIW; -. DR OrthoDB; 2891563at2759; -. DR PhylomeDB; P30429; -. DR SignaLink; P30429; -. DR EvolutionaryTrace; P30429; -. DR PRO; PR:P30429; -. DR Proteomes; UP000001940; Chromosome III. DR Bgee; WBGene00000418; Expressed in germ line (C elegans) and 4 other cell types or tissues. DR GO; GO:0008303; C:caspase complex; IDA:ComplexPortal. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:WormBase. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0043531; F:ADP binding; IEA:InterPro. DR GO; GO:0005524; F:ATP binding; IDA:WormBase. DR GO; GO:0051432; F:BH1 domain binding; IPI:WormBase. DR GO; GO:0051434; F:BH3 domain binding; IPI:WormBase. DR GO; GO:0089720; F:caspase binding; IPI:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0061133; F:endopeptidase activator activity; IDA:WormBase. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB. DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; IDA:WormBase. DR GO; GO:0030042; P:actin filament depolymerization; IMP:UniProtKB. DR GO; GO:0097202; P:activation of cysteine-type endopeptidase activity; IMP:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB. DR GO; GO:1902742; P:apoptotic process involved in development; IMP:UniProtKB. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB. DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:WormBase. DR GO; GO:0048598; P:embryonic morphogenesis; IGI:WormBase. DR GO; GO:0046716; P:muscle cell cellular homeostasis; IGI:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IMP:ComplexPortal. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:WormBase. DR GO; GO:1904747; P:positive regulation of apoptotic process involved in development; IMP:UniProtKB. DR GO; GO:0010954; P:positive regulation of protein processing; IDA:UniProtKB. DR GO; GO:1905808; P:positive regulation of synapse pruning; IMP:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:0008361; P:regulation of cell size; IGI:WormBase. DR GO; GO:0040034; P:regulation of development, heterochronic; IGI:UniProtKB. DR GO; GO:0031647; P:regulation of protein stability; IGI:UniProtKB. DR DisProt; DP03045; -. [P30429-2] DR Gene3D; 1.10.8.490; Ced-4 linker helical domain-like; 1. DR Gene3D; 1.10.533.10; Death Domain, Fas; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.10.10.10; Winged helix-like DNA-binding domain superfamily/Winged helix DNA-binding domain; 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; SSF47986; DEATH domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF46785; Winged helix' DNA-binding domain; 1. DR PROSITE; PS50209; CARD; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cytoplasm; KW Magnesium; Metal-binding; Mitochondrion; Nucleotide-binding; KW Reference proteome. FT CHAIN 1..571 FT /note="Cell death protein 4" FT /id="PRO_0000089470" FT DOMAIN 1..91 FT /note="CARD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00046" FT DOMAIN 133..439 FT /note="NB-ARC" FT /evidence="ECO:0000255" FT BINDING 131 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, FT ECO:0007744|PDB:2A5Y, ECO:0007744|PDB:3LQQ, FT ECO:0007744|PDB:3LQR, ECO:0007744|PDB:4M9S, FT ECO:0007744|PDB:4M9X, ECO:0007744|PDB:4M9Y, FT ECO:0007744|PDB:4M9Z" FT BINDING 162..167 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, FT ECO:0007744|PDB:2A5Y, ECO:0007744|PDB:3LQQ, FT ECO:0007744|PDB:3LQR, ECO:0007744|PDB:4M9S, FT ECO:0007744|PDB:4M9X, ECO:0007744|PDB:4M9Y, FT ECO:0007744|PDB:4M9Z" FT BINDING 166 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:16208361, FT ECO:0000269|PubMed:20434985" FT BINDING 171 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:24065769, FT ECO:0007744|PDB:4M9S" FT VAR_SEQ 212..234 FT /note="ARVVSDTDDSHSITDFINRVLSR -> K (in isoform a)" FT /evidence="ECO:0000305" FT /id="VSP_013199" FT MUTAGEN 80..571 FT /note="Missing: In n1162; reduces the number of apoptotic FT corpses and restores the number of male tail rays in an FT icd-1 RNAi background." FT /evidence="ECO:0000269|PubMed:12944970" FT MUTAGEN 252 FT /note="V->D: Loss of dimerization without affecting FT interaction with ced-9, loss of ced-3 activation and severe FT reduction in the number of cell corpses in embryos in a FT ced-1 mutant background; when associated with E-255 and FT E-256." FT /evidence="ECO:0000269|PubMed:16208361" FT MUTAGEN 255 FT /note="R->E: Severe reduction in the number of cell corpses FT in embryos in a ced-1 mutant background. Loss of FT dimerization without affecting interaction with ced-9, loss FT of ced-3 activation and severe reduction in the number of FT cell corpses in embryos in a ced-1 mutant background; when FT associated with E-252 and E-256." FT /evidence="ECO:0000269|PubMed:16208361" FT MUTAGEN 256 FT /note="M->E: Loss of dimerization without affecting FT interaction with ced-9, loss of ced-3 activation and severe FT reduction in the number of cell corpses in embryos in a FT ced-1 mutant background; when associated with E-252 and FT E-255." FT /evidence="ECO:0000269|PubMed:16208361" FT MUTAGEN 272..273 FT /note="DD->AA: Severe reduction in the number of cell FT corpses in embryos in a ced-1 mutant background." FT /evidence="ECO:0000269|PubMed:16208361" FT MUTAGEN 280 FT /note="I->N: In n1948; no effect on the interaction with FT mac-1." FT /evidence="ECO:0000269|PubMed:10101135" FT MUTAGEN 416 FT /note="A->W: Reduced interaction with ced-3." FT /evidence="ECO:0000269|PubMed:24065769" FT HELIX 4..20 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 23..26 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 27..32 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 38..45 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 50..64 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 69..77 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 81..96 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 101..104 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 105..108 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 112..121 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 134..147 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 150..158 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 165..175 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 181..183 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 184..191 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:8JOL" FT HELIX 199..211 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 234..236 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 239..241 FT /evidence="ECO:0007829|PDB:4M9S" FT HELIX 250..261 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 267..274 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 277..285 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 289..296 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 297..302 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 307..311 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 317..326 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 336..348 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 352..359 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 364..366 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 367..380 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:8JOL" FT STRAND 389..395 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 396..405 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 409..414 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 417..419 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 429..435 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 450..458 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 459..461 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 466..469 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 471..473 FT /evidence="ECO:0007829|PDB:2A5Y" FT STRAND 475..477 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 480..487 FT /evidence="ECO:0007829|PDB:2A5Y" FT HELIX 493..499 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 503..505 FT /evidence="ECO:0007829|PDB:2A5Y" FT TURN 510..512 FT /evidence="ECO:0007829|PDB:4M9Z" FT HELIX 555..558 FT /evidence="ECO:0007829|PDB:4M9S" FT HELIX 559..562 FT /evidence="ECO:0007829|PDB:2A5Y" SQ SEQUENCE 571 AA; 65336 MW; 6BE9893946B79E6C CRC64; MLCEIECRAL STAHTRLIHD FEPRDALTYL EGKNIFTEDH SELISKMSTR LERIANFLRI YRRQASELGP LIDFFNYNNQ SHLADFLEDY IDFAINEPDL LRPVVIAPQF SRQMLDRKLL LGNVPKQMTC YIREYHVDRV IKKLDEMCDL DSFFLFLHGR AGSGKSVIAS QALSKSDQLI GINYDSIVWL KDSGTAPKST FDLFTDILLM LARVVSDTDD SHSITDFINR VLSRSEDDLL NFPSVEHVTS VVLKRMICNA LIDRPNTLFV FDDVVQEETI RWAQELRLRC LVTTRDVEIS NAASQTCEFI EVTSLEIDEC YDFLEAYGMP MPVGEKEEDV LNKTIELSSG NPATLMMFFK SCEPKTFEKM AQLNNKLESR GLVGVECITP YSYKSLAMAL QRCVEVLSDE DRSALAFAVV MPPGVDIPVK LWSCVIPVDI CSNEEEQLDD EVADRLKRLS KRGALLSGKR MPVLTFKIDH IIHMFLKHVV DAQTIANGIS ILEQRLLEIG NNNVSVPERH IPSHFQKFRR SSASEMYPKT TEETVIRPED FPKFMQLHQK FYDSLKNFAC C //