Caenorhabditis elegans gene ced-4, CEll Death abnormality, encoding death protein 4.
SUMMARY back to top
[Wormbase] ced-4 encodes a novel protein; along with CED-3, CED-4 is required for the initiation of programmed cell death; accordingly, genetic analyses indicate that ced-3 and ced-4 function upstream of ced-1, ced-2, and nuc-1 in the programmed cell death pathway; in yeast two-hybrid experiments, and upon coexpression in mammalian cells, CED-4 interacts with CED-9, an anti-apoptotic BCL-2 homolog; coexpression of CED-4 and CED-9 results in redistribution of CED-4 from the cytosol to organellar membranes, suggesting that CED-9 may negatively regulate CED-4 activity by sequestering CED-4 to intracellular membranes.
Wormbase predicts 2 models, but Caenorhabditis elegans cDNA sequences in GenBank, dbEST, Trace and SRA, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 4 spliced variants

AceView synopsis, each blue text links to tables and details
Expression: According to AceView, this gene is expressed at very high level, 4.3 times the average gene in this release, at all stages of development [Kohara cDNAs]. The expression profile for the gene, derived from the proportion of animals at each stage in each Kohara library is: embryos 9%, L1 or L2 larvae 63%, L3 to adult 27%. The sequence of this gene is defined by 17 cDNA clones and 39 elements defined by RNA-seq, some from l2 (seen 5 times), l1 (3), embryo (once), l4 (once).
Alternative mRNA variants and regulation: The gene contains 13 distinct gt-ag introns. Transcription produces at least 5 different mRNAs, 4 alternatively spliced variants and 1 unspliced form. ced-4.a is transpliced to SL2, SL4, SL1, SL3ced-4.d to SL2, SL3, SL4. There are 3 probable alternative promotors, 3 non overlapping alternative last exons and 4 validated alternative polyadenylation sites (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, overlapping exons with different boundaries.
Function: There are 97 articles specifically referring to this gene in PubMed. In addition we point below to 109 abstracts. This gene is associated to a phenotype (CEll Death abnormality). Functionally, the gene has been proposed to participate in processes (apoptosis, regulation of apoptosis). Proteins are expected to have molecular functions (ATP binding activity, protein binding activity) and to localize in various compartments (cytoplasm, endoplasmic reticulum membrane, intracellular). These proteins appear to interact with other proteins (CED-3, CED-4, CED-9, FEM-1, MAC-1). The gene interacts with 18 other genes (CDL-1, CED-1, CED-2, CED-7, CED-8, CED-13, CES-1, CES-2, CPS-6, CRN-1, CUP-5, EGL-1, GLD-1, ICD-1, MEV-1, SEL-10, SEL-12, WAH-1).
This gene appears to be the target of '26G' endo si-RNA[Han et al. 2009, see the top target genes]: 16 '26G' RNA sequences, from 8 distinct positions, are antisense to the mRNA. Expression profile: 0 tags were sequenced from embryos, 1 from oocytes, 11 from sperm and 4 from mixed stages N2; zero 26G was observed in glp-4(bn2) germ line defective mutant.
Protein coding potential: 3 spliced mRNAs putatively encode good proteins, altogether 3 different isoforms (2 complete, 1 partial), some containing domains Caspase Recruitment, NB-ARC [Pfam]. The remaining 2 mRNA variants (1 spliced, 1 unspliced; 1 partial) appear not to encode good proteins.

Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12.
Map on chromosome III, links to other databases and other names
Map: This gene ced-4 maps on chomosome III at position -2.32 (interpolated). In AceView, it covers 3.77 kb, from 4852288 to 4856059 (WS190), on the direct strand.
Links to: WormBase, RNAiDB.
Other names: The gene is also known in Wormgenes/AceView by its positional name 3F943, in Wormbase by its cosmid.number name C35D10.9.
Closest AceView homologs in other species ?
The closest human gene, according to BlastP, is the AceView gene APAF1 (e=0.001)
          Complete gene on genome diagram: back to top
Please choose between the zoomable GIF version., and the HTML5/SVG version.
This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones.
Compact gene diagram back to top
Gene ced-4 5' 3' encoded on plus strand of chromosome III from 4,852,288 to 4,855,172 a d c b e 1 2kb 0 451 bp exon 51 bp [gt-ag] intron 10 GenBank accessions 94 bp exon 45 bp [gt-ag] intron 11 GenBank accessions 90 bp exon 186 bp [gt-ag] intron 10 GenBank accessions 67 bp exon 50 bp [gt-ag] intron 10 GenBank accessions 338 bp exon 557 bp [gt-ag] intron 10 GenBank accessions 276 bp exon 48 bp [gt-ag] intron 12 GenBank accessions 106 bp exon 46 bp [gt-ag] intron 12 GenBank accessions 480 bp exon 44 accessions, some from l2 (seen 5 times) l1 (3), embryo (once) l4 (once) Transpliced 5' end, 9 accessions Validated 3' end, 55 accessions Validated 3' end, 1 accession 480 bp exon 132 bp exon 132 bp exon 132 bp exon 52 bp [gt-ag] intron 1 GenBank accession 2 accessions Transpliced 5' end, 1 accession 107 bp exon 88 bp exon 88 bp exon 114 bp [gt-ag] intron 1 GenBank accession 137 bp exon 1 accession 137 bp exon 204 bp exon 204 bp exon 66 bp uORF 204 bp exon 204 bp exon 95 bp [gt-ag] intron 2 GenBank accessions 139 bp exon 139 bp exon 45 bp [gt-ag] intron 3 GenBank accessions 114 bp exon 114 bp exon 49 bp [gt-ag] intron 3 GenBank accessions 150 bp exon 150 bp exon 47 bp [gt-ag] intron 3 GenBank accessions 117 bp exon 117 bp exon 6 accessions 117 bp exon 72 bp exon 72 bp exon 3 accessions Validated 3' end, 36 accessions 72 bp exon Alternative mRNAs are shown aligned from 5' to 3' on a virtual genome where introns have been shrunk to a minimal length. Exon size is proportional to length, intron height reflects the number of cDNAs supporting each intron, the small numbers show the support of the introns in deep sequencing (with details in mouse-over) . Introns of the same color are identical, of different colors are different. 'Good proteins' are pink, partial or not-good proteins are yellow, uORFs are green. 5' cap or3' poly A flags show completeness of the transcript.
Sequences: click on the numbers to get the DNA back to top
mRNA variant mRNA matching the genome Best predicted protein 5' UTR 3' UTR uORF Upstream sequence Transcription
Downstream sequence
a 1902 bp 549 aa 252 bp 2kb including Promoter 2885 bp 1kb
b 724 bp 166 aa 199 bp 24 bp 63 bp 2kb possibly including promoter 960 bp 1kb
c 225 bp 74 aa 2kb 339 bp 1kb
d 239 bp 33 aa 8 bp 129 bp 2kb including Promoter 291 bp 1kb
e 72 bp 9 aa 41 bp 2kb 72 bp 1kb

Gene neighbors and Navigator on chromosome III back to top
C fkh-5 C P 3F941 C P ced-4 D C I P 3F945 C R P 3F947 D C P 3F949 D C R P coq-8 C P 3F951 D C P 3F957 C 3F959 C 3F961 C I P C P C clec-156 D C P clec-157 C I P 3F936 C R 3F950 C P 3F958 C 3F962 D C P 3F966 5kb 0 3F917, 10 accessions acbp-7, 10 accessions 3 variants fkh-5, 5 accessions, 2 variants 3F941, 11 accessions, 2 variants ced-4, 56 accessions, 5 variants 3F945, 0 accession 3F947, 40 accessions, 3 variants 3F949, 55 accessions, 2 variants coq-8, 57 accessions, 5 variants 3F951, 0 accession 3F957, 63 accessions 3F959, 6 accessions, 3 variants 3F961, 31 accessions 3F956, 1 accession 3F910, 8 accessions nspd-9, 54 accessions clec-156, 0 accession clec-157, 40 accessions 3F936, 34 accessions, 2 variants 3F950, 31 accessions 3F958, 37 accessions 3F962, 8 accessions 3F966, 6 accessions ZOOM OUT                 D:disease, C:conserved, I:interactions, R:regulation, P:publications         Read more...
Annotated mRNA diagrams back to top
Bibliography back to top
Please see these 97 articles in PubMed.
In addition we found 109 papers for which we do not have a PubMed identifier
? Gene Summary Gene on genome mRNA:.a, .b, .c, .d, .e Alternative mRNAs features, proteins, introns, exons, sequences Expression Tissue Function, regulation, related genes DCI

To mine knowledge about the gene, please click the 'Gene Summary' or the 'Function, regulation, related genes ' tab at the top of the page. The 'Gene Summary' page includes all we learnt about the gene, functional annotations of neighboring genes, maps, links to other sites and the bibliography. The 'Function, regulation, related genes ' page includes Diseases (D), Pathways, GO annotations, conserved domains (C), interactions (I) reference into function, and pointers to all genes with the same functional annotation.
To compare alternative variants, their summarized annotations, predicted proteins, introns and exons, or to access any sequence, click the 'Alternative mRNAs features' tab. To see a specific mRNA variant diagram, sequence and annotation, click the variant name in the 'mRNA' tab. To examine expression data from all cDNAs clustered in this gene by AceView, click the 'Expression tissue'.

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