[Wormbase] The fem-1 gene encodes an ankyrin repeat-containing protein orthologous to human FEM1A and is required for masculinization of germline and somatic tissues; FEM-1 is widely expressed and functions as a second messenger in the sex determination pathway, connecting the membrane protein TRA-2A to the transcription factor TRA-1A which it negatively regulates; FEM-1 may also play a role in apoptosis, as it is a substrate for the CED-3 protease and can induce apoptosis when overexpressed in mammalian cells.
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 3 spliced variants.
AceView synopsis, each blue text links to tables and details Expression: According to AceView, this gene is expressed at high level, 3.2 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 14%, L1 or L2 larvae 14%, L3 to adult (including dauer) 72%. See the in situ hybridization pattern in Kohara NextDB. The sequence of this gene is defined by 15 cDNA clones and 27 elements defined by RNA-seq, some from mixed (seen 7 times), embryo (3), l2 (2). We annotate structural defects or features in 2 cDNA clones. Alternative mRNA variants and regulation: The gene contains 11 distinct gt-ag introns. Transcription produces 4 different mRNAs, 3 alternatively spliced variants and 1 unspliced form. Variant d is transpliced to SL1. There are 3 probable alternative promotors, 2 non overlapping alternative last exons and 2 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, splicing versus retention of 2 introns.
Efficacy of translation may be reduced by the presence of a shorter translated product (uORF) initiating at an AUG upstream of the main open reading frame (in variant c). Function: There are 19 articles specifically referring to this gene in PubMed. In addition we point below to 80 abstracts. This essential gene is associated to a phenotype (FEMinization of XX and XO animals, STerile Progeny). Proteins are expected to localize in cytoplasm. These proteins appear to interact with other proteins (CED-3, CED-4). The gene interacts with 7 other genes (FEM-3, FOG-3, GLD-1, SEL-10, TRA-1, TRA-2, TRA-3). Protein coding potential: 3 spliced mRNAs putatively encode good proteins, altogether 3 different isoforms (2 complete, 1 partial), some containing ankyrin domain [Pfam], a second peroximal domain [Psort2]. The remaining mRNA variant (unspliced) appears not to encode a good protein.
Isoform fem-1.c is annotated using as Met a Kozak-compatible a..TTGg start, thereby gaining 94 amino acids N-terminal to the first AUG.
Please quote: AceView: a comprehensive cDNA-supported gene and transcripts annotation, Genome Biology 2006, 7(Suppl 1):S12. Map on chromosome IV, links to other databases and other names Map: This essential gene fem-1 maps on chomosome IV at position +2.34 (interpolated). In AceView, it covers 4.84 kb, from 5537962 to 5533120 (WS190), on the reverse strand. Links to:WormBase, NextDB, RNAiDB.
as Other names: The gene is also known isx-1, in Wormgenes/AceView by its positional name 4G298, in Wormbase by its cosmid.number name F35D6.1, in NextDB, the Nematode expression pattern database, as CEYK198. Closest AceView homologs in other species ? The closest human gene, according to BlastP, is the AceView gene FEM1C (e=10-07). The closest mouse gene, according to BlastP, is the AceView gene Fem1c (e=8 10-08). The closest A.thaliana genes, according to BlastP, are the AceView genes AT3G04710 (e=3 10-16), AT2G31820 (e=3 10-14), AKT1 (e=7 10-14), AT1G07710 (e=2 10-13), AT2G03430 (e=2 10-13)
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.
or in GIF: .a, .b, .c, .d
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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