[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.
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. Read more...
Mouse over the ending of each transcript gives tissues from which the supporting cDNAs were extracted. Details on tissue of origin for each intron and exon is available from the intron and exons table.
Click on any transcript to open the specific mRNA page, to see the exact cDNA clone support and eventual SNPs and to get details on tissues, sequences, mRNA and protein annotations. Proteins supported by a single continuous cDNA sequence lead to underlining the name/ending of the variant. Names not underlined result from cDNA concatenation in the coding region and should be experimentally checked.
Introns are depicted by broken lines; the height of the top of each intron reflects the relative number of clones supporting this intron. ]^[ A pink broken line denotes an intron with standard boundaries (gt-ag or gc-ag) that is exactly supported (i.e. a cDNA sequence exactly matches the genome over 16 bp, 8 on both sides of the intron). ] ^ ] A blue broken line denotes non-standard introns, exactly supported, but with non-standard at-ac or any other boundaries. ]-[ Pink and ] - ] blue straight lines represent 'fuzzy' introns of the standard and non-standard types respectively, those introns do not follow the 16 bp rule. Black straight lines ]-[denote gaps in the alignments.
Exons: Wide filled pink areas represent putative protein coding regions, narrow empty pink boxes represent the 5'UTR (on the left) and 3' UTR (on the right). Flags identify validated endings: cap site on the 5' side, polyadenylation site on the 3' side. Filled flags correspond to frequent events while empty flags have lesser supporting cDNAs (yet all are validated); at the 3' side, black flags are associated to the main AATAAA signal, blue flags to any single letter variant of the main . More explanations are given in the gene help file
The mRNAs diagrams with the aligned cDNA sequence accessions and their mismatches are available in the mRNA pages accessible from the tab at the top of the page, or here:
In Flash: .a, .b, .c, .d, .e.
or in GIF: .a, .b, .c, .d, .e
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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