cytoplasmic polyadenylation element-binding protein - RNA binding protein - forms amyloid-like oligomers enriched in the synaptic membrane - critical for the persistence of long-term memory
Gene model reviewed during 5.46
Low-frequency RNA-Seq exon junction(s) not annotated.
Genes with CDS overlap: isoforms of orb2 and CG43783 share two different promoters, 5' UTR exons, and N-terminal coding sequences (162 residues); overlapping structure not conserved outside of Drosophila.
Double stop-codon suppression (UAA, UAG) postulated; FBrf0234051 and FlyBase analysis.
Gene model reviewed during 6.25
Monomer (PubMed:22284910, PubMed:23083740). Upon neuronal stimulation, forms stable amyloid-like oligomers composed of isoform A and isoform B which are required for formation of persistent long-term memory (PubMed:22284910, PubMed:23083740). Isoform A is critical for oligomer formation (PubMed:22284910, PubMed:23083740). Phe-5 of isoform A is required for amyloid-like oligomerization (PubMed:22284910, PubMed:26812143). Rapidly forms amyloids and toxic intermediates are extremely transient (PubMed:26812143). Interacts with the translational regulator bol (PubMed:23209437). Interacts with Tob; the interaction is enhanced by neuronal stimulation, stabilizes isoform A and induces oligomerization (PubMed:24523662).
Phosphorylation regulates interaction with Tob and oligomerization. Protein phosphatase 2A keeps both Orb2 and Tob in an unphosphorylated form. Following synaptic activation, unphosphorylated Orb2 is bound and stabilized by unphosphorylated Tob. Tob recruits activated LimK which phosphorylates both Orb2 and Tob and enhances Orb2 oligomerization.
Isoform A: The N-terminal Gln/His-rich domain is necessary and sufficient for long-term memory and is required for formation of amyloid-like oligomers with isoform B (PubMed:17965711, PubMed:23083740). Isoform B: The N-terminal Gln/His-rich domain is both dispensable and insufficient for long-term memory and for formation of amyloid-like oligomers with isoform A (PubMed:23083740).
Isoform A: The RNA-binding region is not essential for long-term memory. Isoform B: The RNA-binding region is essential for long-term memory.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\orb2 using the Feature Mapper tool.
The transcript isoforms RB, RC and RD of orb2 are detected in embryos and in the head and gonads of adult flies. The isoform RA is only detected in the testis. In embryos, orb2 transcript is enriched in the central nervous system in the extended germ band stage. In the ovary, orb2 is weakly expressed in the cytoplasm of all germline cells in previtellogenic stage chambers. From oogenesis stages S8 to S10, orb2 transcript is expressed more strongly and excluded from the oocyte, unlike the orb2 protein.
As interconnected spermatocytes begin to grow, there is a substatial upregulation of orb2 mRNA and protein. orb2 expression peaks as the mature spermatocytes go through meiosis and high levels of orb2 are found in 32 and 64 cell spermatid cysts. In elongating spermatids, orb2 is distributed along the entire axoneme bundle. The highest concentrations are found in a prominent band close to the distal tip of the growing flagellar axonemes. In the region behind the band, orb2 is organized into a series of striated lines that extend towards the sperm nuclei at the proximal (basal) tip of the spermatid and presumably correspond to individual flagellar
axonemes in the spermatid bundle. orb2 disappears once elongation and nuclear condensation are completed.
orb2 protein is deposited maternally and expressed throughout embryogenesis with a decrease in expression between 4-8h AEL. Expression of orb2 protein is detected in the cell bodies of neurons in the CNS and PNS, being excluded from longitudinal and commissural axon tracts. orb2 protein labels the lineage of the Even-skipped positive neuroblast NB4-2. It also labels the cytoplasm of mesodermal cells, in which it co-localises with Scer\GAL4twi.PU. Western blot analysis indicates that in adults, the isoform orb2-PA is restricted to the testis, while the other isoforms orb2-PB,PC and PD are detected in ovaries and testis. orb2 protein is detected in the cell bodies of a subset of neurons in the larval brain and ventral nerve cord. In the adult, orb2 protein is expressed in the ellipsoid body, in two unindentified and symmetrical structures dorsal to the ellipsoid body, in an unpaired structure on the left hemisphere, lateral to the ellipsoid body and in the fan-shaped body. In adult neurons, orb2 protein seems to be localised to the synaptic terminals. In the ovaries, in previtellogenic stage chambers, orb2 protein is detected in all of the cells but enriched in a cap posterior to the oocyte. At oogenesis stages S8 to S10, orb2 protein is enriched in the cortex of the oocyte, similarly to orb protein. orb2 protein is expressed around the nucleus of the nurse cells, unlike the orb2 transcript. It is also detected in a gradient in the cytoplasm of the nurse cells, with expression being strongest in the most posterior cells (closest to the oocyte). orb2 protein is released from these cells into the oocyte via ring canals.
GBrowse - Visual display of RNA-Seq signalsView Dmel\orb2 in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: orb2 CG5735
Annotation CG43113 split into CG43782 (corresponds to orb2) and CG43783 in release 5.45 of the genome annotation. CG43782 is a reinstatement of the CG5735 annotation and CG43783 is a reinstatement of the CG5741 annotation (CG5735 and CG5741 were merged in release 5.32 to produce CG43113).
Annotations CG43782 and CG43783 share some exons at the 5' end, including some coding sequence.
Annotations CG5735 and CG5741 merged as CG43113 in release 5.32 of the genome annotation.
Source for merge of orb2 anon-WO0140519.222 was sequence comparison ( date:051113 ).