CED9_CAEEL
ID CED9_CAEEL Reviewed; 280 AA.
AC P41958;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Apoptosis regulator ced-9;
DE AltName: Full=Cell death protein 9;
GN Name=ced-9; ORFNames=T07C4.8;
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], FUNCTION, AND DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2;
RX PubMed=7907274; DOI=10.1016/0092-8674(94)90506-1;
RA Hengartner M.O., Horvitz H.R.;
RT "C. elegans cell survival gene ced-9 encodes a functional homolog of the
RT mammalian proto-oncogene bcl-2.";
RL Cell 76:665-676(1994).
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, INTERACTION WITH CED-4, AND MUTAGENESIS OF TYR-149 AND GLY-169.
RC STRAIN=Bristol N2;
RX PubMed=9024666; DOI=10.1038/385653a0;
RA Spector M.S., Desnoyers S., Hoeppner D.J., Hengartner M.O.;
RT "Interaction between the C. elegans cell-death regulators CED-9 and CED-
RT 4.";
RL Nature 385:653-656(1997).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CED-4.
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 CED-
RT 9.";
RL Science 275:1126-1129(1997).
RN [5]
RP FUNCTION, AND INTERACTION WITH EGL-1.
RX PubMed=9604928; DOI=10.1016/s0092-8674(00)81182-4;
RA Conradt B., Horvitz H.R.;
RT "The C. elegans protein EGL-1 is required for programmed cell death and
RT interacts with the Bcl-2-like protein CED-9.";
RL Cell 93:519-529(1998).
RN [6]
RP IDENTIFICATION IN A CED-3; CED-4 AND MAC-1 COMPLEX.
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 [7]
RP INTERACTION WITH DCT-1.
RX PubMed=11114722; DOI=10.1038/sj.onc.1203929;
RA Cizeau J., Ray R., Chen G., Gietz R.D., Greenberg A.H.;
RT "The C. elegans orthologue ceBNIP3 interacts with CED-9 and CED-3 but kills
RT through a BH3- and caspase-independent mechanism.";
RL Oncogene 19:5453-5463(2000).
RN [8]
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 [9]
RP INTERACTION WITH DRE-1.
RX PubMed=23431138; DOI=10.1073/pnas.1217271110;
RA Chiorazzi M., Rui L., Yang Y., Ceribelli M., Tishbi N., Maurer C.W.,
RA Ranuncolo S.M., Zhao H., Xu W., Chan W.C., Jaffe E.S., Gascoyne R.D.,
RA Campo E., Rosenwald A., Ott G., Delabie J., Rimsza L.M., Shaham S.,
RA Staudt L.M.;
RT "Related F-box proteins control cell death in Caenorhabditis elegans and
RT human lymphoma.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:3943-3948(2013).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-149 AND GLY-169.
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 68-242 IN COMPLEX WITH EGL-1, AND
RP FUNCTION.
RX PubMed=12894216; DOI=10.1038/sj.cdd.4401303;
RA Woo J.-S., Jung J.-S., Ha N.-C., Shin J., Kin K.-H., Lee W., Oh B.-H.;
RT "Unique structural features of a BCL-2 family protein CED-9 and biophysical
RT characterization of CED-9/EGL-1 interactions.";
RL Cell Death Differ. 10:1310-1319(2003).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 68-237 IN COMPLEX WITH EGL-1,
RP FUNCTION, AND INTERACTION WITH CED-4.
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 X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 48-251 IN COMPLEX WITH CED-4, AND
RP FUNCTION.
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 [14]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=17021039; DOI=10.1242/dev.02614;
RA Park D., Jia H., Rajakumar V., Chamberlin H.M.;
RT "Pax2/5/8 proteins promote cell survival in C. elegans.";
RL Development 133:4193-4202(2006).
CC -!- FUNCTION: Plays a major role in programmed cell death (PCD, apoptosis)
CC (PubMed:7907274, PubMed:10688797). 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 activate
CC the cell-killing caspase ced-3 (PubMed:9024666, PubMed:9027313,
CC PubMed:9604928, PubMed:12894216, PubMed:15383288, PubMed:16208361).
CC During larval development, required for the elimination of transient
CC presynaptic components downstream of egl-1 and upstream of ced-4 and
CC ced-3 apoptotic pathway (PubMed:26074078).
CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:15383288,
CC ECO:0000269|PubMed:26074078, ECO:0000269|PubMed:7907274,
CC ECO:0000269|PubMed:9024666, ECO:0000269|PubMed:9027313,
CC ECO:0000269|PubMed:9604928}.
CC -!- SUBUNIT: Interacts with asymmetric homodimer ced-4; the interaction
CC sequesters ced-4 (PubMed:9024666, PubMed:9027313, PubMed:15383288,
CC PubMed:16208361). Interacts with egl-1; the interaction results in ced-
CC 4 release (PubMed:9604928, PubMed:12894216, PubMed:15383288). Interacts
CC with dre-1; the interaction inhibits ced-9 activity, either directly or
CC indirectly (PubMed:23431138). Interacts with dct-1 (PubMed:11114722).
CC May form a complex composed of ced-9, ced-4 and mac-1
CC (PubMed:10101135). {ECO:0000269|PubMed:10101135,
CC ECO:0000269|PubMed:11114722, ECO:0000269|PubMed:12894216,
CC ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361,
CC ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:9024666,
CC ECO:0000269|PubMed:9027313, ECO:0000269|PubMed:9604928}.
CC -!- INTERACTION:
CC P41958; P42573: ced-3; NbExp=4; IntAct=EBI-494110, EBI-494247;
CC P41958; P30429: ced-4; NbExp=17; IntAct=EBI-494110, EBI-494118;
CC P41958; P30429-2: ced-4; NbExp=5; IntAct=EBI-494110, EBI-536271;
CC P41958; O61667: egl-1; NbExp=7; IntAct=EBI-494110, EBI-495949;
CC -!- SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:26074078}. Synapse
CC {ECO:0000269|PubMed:26074078}. Endomembrane system
CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}; Peripheral
CC membrane protein. Mitochondrion membrane {ECO:0000269|PubMed:10688797,
CC ECO:0000269|PubMed:9027313}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Cytoplasm
CC {ECO:0000269|PubMed:17021039}. Note=Intracellular membranes,
CC mitochondrial, and perinuclear region (PubMed:9027313,
CC PubMed:10688797). Localizes to synapses of DD motor neurons
CC (PubMed:26074078). Synaptic localization is dependent on axonal
CC mitochondria (PubMed:26074078). {ECO:0000269|PubMed:26074078}.
CC -!- DEVELOPMENTAL STAGE: Abundant expression is seen in embryos and adults
CC (PubMed:7907274). Expressed in embryos prior to elongation, at comma
CC stage, at 1.5-fold stage and in adult gonad (PubMed:17021039).
CC {ECO:0000269|PubMed:17021039, ECO:0000269|PubMed:7907274}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
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DR EMBL; L26545; AAA20080.1; -; Genomic_DNA.
DR EMBL; Z29443; CAA82573.2; -; Genomic_DNA.
DR PIR; A53189; A53189.
DR PIR; H88578; H88578.
DR RefSeq; NP_499284.1; NM_066883.5.
DR PDB; 1OHU; X-ray; 2.03 A; A/B=68-242.
DR PDB; 1TY4; X-ray; 2.20 A; A/B=68-237.
DR PDB; 2A5Y; X-ray; 2.60 A; A=48-251.
DR PDBsum; 1OHU; -.
DR PDBsum; 1TY4; -.
DR PDBsum; 2A5Y; -.
DR AlphaFoldDB; P41958; -.
DR SMR; P41958; -.
DR BioGRID; 533094; 14.
DR ComplexPortal; CPX-1359; ced-4-ced-9-mac-1 complex.
DR ComplexPortal; CPX-398; ced-9-egl-1 complex.
DR ComplexPortal; CPX-399; ced-9-ced-4 complex.
DR DIP; DIP-250N; -.
DR ELM; P41958; -.
DR IntAct; P41958; 4.
DR STRING; 6239.T07C4.8; -.
DR TCDB; 1.A.21.1.12; the bcl-2 (bcl-2) family.
DR iPTMnet; P41958; -.
DR EPD; P41958; -.
DR PaxDb; P41958; -.
DR PeptideAtlas; P41958; -.
DR EnsemblMetazoa; T07C4.8.1; T07C4.8.1; WBGene00000423.
DR GeneID; 3565776; -.
DR KEGG; cel:CELE_T07C4.8; -.
DR UCSC; T07C4.8.1; c. elegans.
DR CTD; 3565776; -.
DR WormBase; T07C4.8; CE25104; WBGene00000423; ced-9.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244872; -.
DR HOGENOM; CLU_1046733_0_0_1; -.
DR InParanoid; P41958; -.
DR OMA; KEHNRSW; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; P41958; -.
DR Reactome; R-CEL-9648002; RAS processing.
DR EvolutionaryTrace; P41958; -.
DR PRO; PR:P41958; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000423; Expressed in embryo and 5 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:WormBase.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:WormBase.
DR GO; GO:0005739; C:mitochondrion; IDA:WormBase.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0031090; C:organelle membrane; IDA:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:WormBase.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IDA:WormBase.
DR GO; GO:0046982; F:protein heterodimerization activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0140311; F:protein sequestering activity; IDA:UniProtKB.
DR GO; GO:0030042; P:actin filament depolymerization; IMP: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:0000422; P:autophagy of mitochondrion; IMP:WormBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IBA:GO_Central.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:WormBase.
DR GO; GO:1900118; P:negative regulation of execution phase of apoptosis; IMP:ComplexPortal.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0043069; P:negative regulation of programmed cell death; IMP:WormBase.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; EXP:ComplexPortal.
DR GO; GO:0090727; P:positive regulation of brood size; IMP:UniProtKB.
DR GO; GO:0040019; P:positive regulation of embryonic development; IMP:UniProtKB.
DR GO; GO:1905516; P:positive regulation of fertilization; IGI:UniProtKB.
DR GO; GO:0010636; P:positive regulation of mitochondrial fusion; IMP:WormBase.
DR GO; GO:1901046; P:positive regulation of oviposition; IMP:UniProtKB.
DR GO; GO:1905808; P:positive regulation of synapse pruning; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0050807; P:regulation of synapse organization; IGI:UniProtKB.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR SMART; SM00337; BCL; 1.
DR SMART; SM00265; BH4; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; Membrane; Mitochondrion;
KW Reference proteome; Synapse.
FT CHAIN 1..280
FT /note="Apoptosis regulator ced-9"
FT /id="PRO_0000143097"
FT REGION 33..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 80..99
FT /note="BH4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00025"
FT MOTIF 160..179
FT /note="BH1"
FT /evidence="ECO:0000255"
FT MOTIF 213..229
FT /note="BH2"
FT /evidence="ECO:0000305"
FT COMPBIAS 39..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 149
FT /note="Y->N: In n1653; no effect on the interaction with
FT ced-4. Normal elimination of presynaptic components in RME
FT neurons in adults."
FT /evidence="ECO:0000269|PubMed:26074078,
FT ECO:0000269|PubMed:9024666"
FT MUTAGEN 169
FT /note="G->E: In n1950; gain of function mutant. No effect
FT on the interaction with ced-4. Impaired elimination of
FT presynaptic components in RME neurons in adults. Abnormal
FT accumulation of F-actin at the non-eliminated transient
FT synapses in DD neuron dorsal cord in L4 larvae."
FT /evidence="ECO:0000269|PubMed:26074078,
FT ECO:0000269|PubMed:9024666"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:2A5Y"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 80..94
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 111..138
FT /evidence="ECO:0007829|PDB:1OHU"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 146..153
FT /evidence="ECO:0007829|PDB:1OHU"
FT TURN 154..157
FT /evidence="ECO:0007829|PDB:2A5Y"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 168..185
FT /evidence="ECO:0007829|PDB:1OHU"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 195..211
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:1OHU"
FT HELIX 221..239
FT /evidence="ECO:0007829|PDB:1OHU"
SQ SEQUENCE 280 AA; 31824 MW; 7603675E490DD3EB CRC64;
MTRCTADNSL TNPAYRRRTM ATGEMKEFLG IKGTEPTDFG INSDAQDLPS PSRQASTRRM
SIGESIDGKI NDWEEPRLDI EGFVVDYFTH RIRQNGMEWF GAPGLPCGVQ PEHEMMRVMG
TIFEKKHAEN FETFCEQLLA VPRISFSLYQ DVVRTVGNAQ TDQCPMSYGR LIGLISFGGF
VAAKMMESVE LQGQVRNLFV YTSLFIKTRI RNNWKEHNRS WDDFMTLGKQ MKEDYERAEA
EKVGRRKQNR RWSMIGAGVT AGAIGIVGVV VCGRMMFSLK
