UniProt functional annotation for P30429



	UniProt functional annotation for P30429

UniProt code: P30429.

Organism: Caenorhabditis elegans.

Taxonomy: Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.

Function: Component of the egl-1, ced-9, ced-4 and ced-3 apoptotic signaling cascade required for the initiation of programmed cell death in cells fated to die during embryonic and postembryonic development (PubMed:3955651). During oogenesis, required for germline apoptosis downstream of ced-9 and upstream of ced-3 but independently of egl-1 (PubMed:9927601). May regulate germline apoptosis in response to DNA damage, probably downstream of let-60/ras and mpk-1 pathway (PubMed:21901106). Regulates CEP neuron apoptosis in response to high Al(3+) levels (PubMed:23106139). During male tail morphogenesis, promotes apoptosis of the tail-spike cell upstream of ced-3 but independently of egl-1 and ced-9 (PubMed:17329362). May play a role in sex-specific cell apoptosis, probably by promoting ced-3-mediated cleavage of sex-determining protein fem-1 (PubMed:10764728). During larval development, required for the elimination of transient presynaptic components downstream of egl-1 and ced-9 and upstream of ced-3 apoptotic pathway (PubMed:26074078). Downstream of calreticulin crt-1 and upstream of ced-3 and independently of egl-1 and ced-9, plays a role in the initial steps of axonal regrowth following axotomy (PubMed:22629231). Together with ain-1, a component of the miRNA- induced-silencing complex (miRISC), and probably upstream of ced-3, regulates temporal cell fate patterning during larval development (PubMed:25432023). May play a role in resistance to S.typhimurium- mediated infection (PubMed:11226309). {ECO:0000269|PubMed:10764728, ECO:0000269|PubMed:11226309, ECO:0000269|PubMed:17329362, ECO:0000269|PubMed:21901106, ECO:0000269|PubMed:22629231, ECO:0000269|PubMed:23106139, ECO:0000269|PubMed:25432023, ECO:0000269|PubMed:26074078, ECO:0000269|PubMed:3955651, ECO:0000269|PubMed:9927601}.

Function: [Isoform a]: Plays a major role in programmed cell death (PubMed:1286611, PubMed:8706125). egl-1 binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to induce caspase ced-3 autoproteolytic cleavage and activation (PubMed:15383288, PubMed:16208361, PubMed:20434985, PubMed:24065769). Also forms a holoenzyme with processed ced-3 enhancing ced-3 activity (PubMed:20434985). {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361, ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, ECO:0000269|PubMed:8706125}.

Function: [Isoform b]: Prevents programmed cell death. {ECO:0000269|PubMed:8706125}.

Subunit: Associates as an asymmetric homodimer with ced-9 (PubMed:16208361, PubMed:9027313, PubMed:15383288). Upon release from ced-9, forms an octamer, known as the apoptosome, and interacts with ced-3; the interaction results in ced-3 autoproteolytic cleavage and activation (PubMed:20434985, PubMed:24065769). The octamer (a tetramer of an asymmetric dimer) also interacts with two processed ced-3 to form a stable holoenzyme (PubMed:20434985). Interacts with sex-determining protein fem-1 (PubMed:10764728). May form a complex composed of ced-3, ced-4 and mac-1 or of ced-9, ced-4 and mac-1 (PubMed:10101135). Within the complex, interacts with ced-4 (PubMed:10101135). {ECO:0000269|PubMed:10101135, ECO:0000269|PubMed:10764728, ECO:0000269|PubMed:15383288, ECO:0000269|PubMed:16208361, ECO:0000269|PubMed:20434985, ECO:0000269|PubMed:24065769, ECO:0000269|PubMed:9027313}.

Subcellular location: Mitochondrion {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}. Note=In non cell death induced cells, ced-9 is required for mitochondrial localization. Perinuclear in cell death induced cells. {ECO:0000269|PubMed:10688797, ECO:0000269|PubMed:9027313}.

Developmental stage: Abundantly expressed during embryogenesis and to a lesser extent in larvae and adults (PubMed:1286611). Expression starts at the 100-cell stage and persists through embryogenesis (at protein level) (PubMed:9027313). Not expressed in larvae and adults (at protein level) (PubMed:9027313). {ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:9027313}.

Disruption phenotype: Mutants exhibit a block in almost all programmed cell deaths that normally occur during development (PubMed:1286611). RNAi-mediated knockdown causes a defect in egg laying in a small proportion of animals (PubMed:25432023). Also causes a moderate increase in CEP neuron survival in response to high Al(3+) levels (PubMed:23106139). In an ain-1 mutant background, enhances the proportion of animals arrested at the larval stage, with egg-laying defects and with a ruptured vulva (PubMed:25432023). {ECO:0000269|PubMed:1286611, ECO:0000269|PubMed:23106139, ECO:0000269|PubMed:25432023}.

Annotations taken from UniProtKB at the EBI.


Organism:		Caenorhabditis elegans.
Taxonomy:		Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida; Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.



Function:		Component of the egl-1, ced-9, ced-4 and ced-3 apoptotic signaling cascade required for the initiation of programmed cell death in cells fated to die during embryonic and postembryonic development (PubMed:3955651). During oogenesis, required for germline apoptosis downstream of ced-9 and upstream of ced-3 but independently of egl-1 (PubMed:9927601). May regulate germline apoptosis in response to DNA damage, probably downstream of let-60/ras and mpk-1 pathway (PubMed:21901106). Regulates CEP neuron apoptosis in response to high Al(3+) levels (PubMed:23106139). During male tail morphogenesis, promotes apoptosis of the tail-spike cell upstream of ced-3 but independently of egl-1 and ced-9 (PubMed:17329362). May play a role in sex-specific cell apoptosis, probably by promoting ced-3-mediated cleavage of sex-determining protein fem-1 (PubMed:10764728). During larval development, required for the elimination of transient presynaptic components downstream of egl-1 and ced-9 and upstream of ced-3 apoptotic pathway (PubMed:26074078). Downstream of calreticulin crt-1 and upstream of ced-3 and independently of egl-1 and ced-9, plays a role in the initial steps of axonal regrowth following axotomy (PubMed:22629231). Together with ain-1, a component of the miRNA- induced-silencing complex (miRISC), and probably upstream of ced-3, regulates temporal cell fate patterning during larval development (PubMed:25432023). May play a role in resistance to S.typhimurium- mediated infection (PubMed:11226309). {ECO:0000269\|PubMed:10764728, ECO:0000269\|PubMed:11226309, ECO:0000269\|PubMed:17329362, ECO:0000269\|PubMed:21901106, ECO:0000269\|PubMed:22629231, ECO:0000269\|PubMed:23106139, ECO:0000269\|PubMed:25432023, ECO:0000269\|PubMed:26074078, ECO:0000269\|PubMed:3955651, ECO:0000269\|PubMed:9927601}.



Function:		[Isoform a]: Plays a major role in programmed cell death (PubMed:1286611, PubMed:8706125). egl-1 binds to and directly inhibits the activity of ced-9, releasing the cell death activator ced-4 from a ced-9/ced-4 containing protein complex and allowing ced-4 to induce caspase ced-3 autoproteolytic cleavage and activation (PubMed:15383288, PubMed:16208361, PubMed:20434985, PubMed:24065769). Also forms a holoenzyme with processed ced-3 enhancing ced-3 activity (PubMed:20434985). {ECO:0000269\|PubMed:10688797, ECO:0000269\|PubMed:1286611, ECO:0000269\|PubMed:15383288, ECO:0000269\|PubMed:16208361, ECO:0000269\|PubMed:20434985, ECO:0000269\|PubMed:24065769, ECO:0000269\|PubMed:8706125}.



Function:		[Isoform b]: Prevents programmed cell death. {ECO:0000269\|PubMed:8706125}.


Subunit:		Associates as an asymmetric homodimer with ced-9 (PubMed:16208361, PubMed:9027313, PubMed:15383288). Upon release from ced-9, forms an octamer, known as the apoptosome, and interacts with ced-3; the interaction results in ced-3 autoproteolytic cleavage and activation (PubMed:20434985, PubMed:24065769). The octamer (a tetramer of an asymmetric dimer) also interacts with two processed ced-3 to form a stable holoenzyme (PubMed:20434985). Interacts with sex-determining protein fem-1 (PubMed:10764728). May form a complex composed of ced-3, ced-4 and mac-1 or of ced-9, ced-4 and mac-1 (PubMed:10101135). Within the complex, interacts with ced-4 (PubMed:10101135). {ECO:0000269\|PubMed:10101135, ECO:0000269\|PubMed:10764728, ECO:0000269\|PubMed:15383288, ECO:0000269\|PubMed:16208361, ECO:0000269\|PubMed:20434985, ECO:0000269\|PubMed:24065769, ECO:0000269\|PubMed:9027313}.
Subcellular location:		Mitochondrion {ECO:0000269\|PubMed:10688797, ECO:0000269\|PubMed:9027313}. Cytoplasm, perinuclear region {ECO:0000269\|PubMed:10688797, ECO:0000269\|PubMed:9027313}. Note=In non cell death induced cells, ced-9 is required for mitochondrial localization. Perinuclear in cell death induced cells. {ECO:0000269\|PubMed:10688797, ECO:0000269\|PubMed:9027313}.
Developmental stage:		Abundantly expressed during embryogenesis and to a lesser extent in larvae and adults (PubMed:1286611). Expression starts at the 100-cell stage and persists through embryogenesis (at protein level) (PubMed:9027313). Not expressed in larvae and adults (at protein level) (PubMed:9027313). {ECO:0000269\|PubMed:1286611, ECO:0000269\|PubMed:9027313}.
Disruption phenotype:		Mutants exhibit a block in almost all programmed cell deaths that normally occur during development (PubMed:1286611). RNAi-mediated knockdown causes a defect in egg laying in a small proportion of animals (PubMed:25432023). Also causes a moderate increase in CEP neuron survival in response to high Al(3+) levels (PubMed:23106139). In an ain-1 mutant background, enhances the proportion of animals arrested at the larval stage, with egg-laying defects and with a ruptured vulva (PubMed:25432023). {ECO:0000269\|PubMed:1286611, ECO:0000269\|PubMed:23106139, ECO:0000269\|PubMed:25432023}.