id: A0A8M2B7W1 gene_symbol: eef1db product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: eef1db (eukaryotic translation elongation factor 1 delta b) is one of two zebrafish co-orthologs of vertebrate EEF1D, retained from the teleost-specific genome duplication; its paralog is eef1da. It encodes the delta subunit of the eEF1B complex, the guanine-nucleotide exchange factor that regenerates GTP-bound eEF1A during translation elongation. The protein has a leucine zipper for complex assembly, an acidic region and a C-terminal GEF domain that is 81% identical to human EEF1D and 89% identical to eef1da. The gene makes short isoforms (274-298 aa) and predicted long isoforms (554-578 aa; the reviewed entry is a 578-aa model) whose N-terminal extension shows weak similarity to the mammalian eEF1BdeltaL extension, a nuclear heat-shock-responsive isoform. eef1db mRNA is broadly expressed in the same tissues as eef1da. No gene-specific functional study exists in zebrafish. existing_annotations: - term: id: GO:0003746 label: translation elongation factor activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR001326 - InterPro:IPR014038 - InterPro:IPR049720 review: summary: InterPro2GO mapping from the EF1B beta/delta GEF and conserved-site signatures. action: ACCEPT reason: The eef1db product keeps the conserved EF-1-delta core, including a complete GEF region 78-81% identical to human EEF1D and 89% identical between the two zebrafish paralogs (DANRE/eef1da/eef1da-bioinformatics/RESULTS.md). eEF1Bdelta is an elongation factor acting as the nucleotide-exchange subunit for eEF1A. No zebrafish biochemical data exist; the annotation rests on strong sequence conservation. supported_by: - reference_id: file:DANRE/eef1da/eef1da-bioinformatics/RESULTS.md supporting_text: No copy has lost any part of the GEF region - reference_id: PMID:36576126 supporting_text: the eEF1B complex acts as a guanine exchange factor (GEF) of GTP for GDP indirectly catalyzing the release of eEF1A from the ribosome. - term: id: GO:0005085 label: guanyl-nucleotide exchange factor activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - PANTHER:PTN000174394 - SGD:S000000003 review: summary: PAINT inference at the EF1B beta/delta node (seeded by yeast EFB1) that the family has guanyl-nucleotide exchange activity toward eEF1A. action: ACCEPT reason: Core molecular function of the EF-1beta/delta family, which is placed deep in the eukaryotic tree. The catalytic GEF region is complete and highly conserved in both zebrafish paralogs; there is no sign of loss or divergence of the catalytic domain in either copy. supported_by: - reference_id: PMID:36576126 supporting_text: the eEF1B complex acts as a guanine exchange factor (GEF) of GTP for GDP indirectly catalyzing the release of eEF1A from the ribosome. - reference_id: file:DANRE/eef1da/eef1da-bioinformatics/RESULTS.md supporting_text: No copy has lost any part of the GEF region - term: id: GO:0005829 label: cytosol evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - AGI_LocusCode:AT1G30230 - PANTHER:PTN000174394 review: summary: PAINT inference that the family is active in the cytosol. action: ACCEPT reason: eEF1B acts on cytosolic eEF1A during translation elongation; in mammals the short EEF1D isoforms also anchor the complex to the ER surface, which is still cytosolic-facing. supported_by: - reference_id: PMID:30787422 supporting_text: EEF1D encodes a ubiquitously expressed translational elongation factor functioning in the cytoplasm. - term: id: GO:0005853 label: eukaryotic translation elongation factor 1 complex evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of supporting_entities: - InterPro:IPR049720 review: summary: InterPro2GO mapping placing the protein in the eukaryotic translation elongation factor 1 complex. action: ACCEPT reason: EF-1delta is a subunit of the eEF1B(alpha-beta-gamma-delta) complex; the leucine zipper that mediates assembly is present in both zebrafish copies. supported_by: - reference_id: PMID:36576126 supporting_text: The gene EEF1D encodes the eEF1Bδ subunit of the eEF1B complex. - term: id: GO:0006414 label: translational elongation evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - CGD:CAL0000176377 - PANTHER:PTN000174394 - SGD:S000000003 review: summary: PAINT inference at the EF1B beta/delta node. action: ACCEPT reason: 'Core process: recycling eEF1A-GDP to eEF1A-GTP for each elongation cycle. The zebrafish protein keeps the conserved core.' supported_by: - reference_id: PMID:25686034 supporting_text: canonical eEF1Bδ, is highly conserved from worm to human, especially the leucine-zipper motif and GEF domain. - term: id: GO:0006414 label: translational elongation evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in supporting_entities: - InterPro:IPR001326 - InterPro:IPR014038 review: summary: InterPro2GO mapping from the EF1B beta/delta signatures. action: ACCEPT reason: Same process as the IBA row; correct. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: PMID:36576126 title: 'Expanding the spectrum of EEF1D neurodevelopmental disorders: Biallelic variants in the guanine exchange domain.' findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; human EEF1D; defines eEF1B GEF role and the long/short isoforms. - id: PMID:30787422 title: Biallelic loss of EEF1D function links heat shock response pathway to autosomal recessive intellectual disability. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only; human; ubiquitous cytoplasmic elongation factor, long-isoform-specific disease variants. - id: PMID:21597468 title: Transformation of eEF1Bδ into heat-shock response transcription factor by alternative splicing. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Abstract only; mammalian eEF1BdeltaL is nuclear and cooperates with HSF1. Not tested in fish. - id: PMID:25686034 title: Regulation of translation factor EEF1D gene function by alternative splicing. findings: [] reference_review: relevance: MEDIUM correctness: DISPUTED review_notes: Review. Its statement that eEF1BdeltaL orthologs are absent below reptiles conflicts with current gar and zebrafish long-isoform gene models (eef1da-bioinformatics/RESULTS.md); those models are computational. - id: PMID:42230146 title: The ER anchoring and abundance of the EEF1B complex is affected by tissue-specific alternative EEF1D splicing. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Full text; mouse/human short-isoform exon 5 anchors eEF1B to the ER. Exon correspondence in zebrafish not examined. - id: PMID:10375624 title: The elongation factor-1delta (EF-1delta) originates from gene duplication of an EF-1beta ancestor and fusion with a protein-binding domain. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only; family evolution (EF-1beta and EF-1delta share the C-terminal GEF domain). - id: PMID:8647113 title: The guanine-nucleotide-exchange complex (EF-1 beta gamma delta) of elongation factor-1 contains two similar leucine-zipper proteins EF-1 delta, p34 encoded by EF-1 delta 1 and p36 encoded by EF-1 delta 2. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only; Xenopus laevis (allotetraploid) keeps two EF-1 delta proteins in the same complex; a comparator for duplicated EF-1delta. - id: file:DANRE/eef1da/eef1da-bioinformatics/RESULTS.md title: eef1da/eef1db/human EEF1D/gar EEF1D isoform, domain and expression comparison reference_review: relevance: HIGH correctness: VERIFIED review_notes: Manual audit verified this sidecar supports both zebrafish copies retaining the EEF1Bdelta GEF core, with divergent predicted long-isoform extensions and an expression difference rather than a demonstrated biochemical partition. findings: - statement: The GEF region is complete in every zebrafish isoform and 89% identical between the paralogs; long-isoform extensions have diverged. supporting_text: No copy has lost any part of the GEF region core_functions: - description: 'Delta subunit of the eEF1B complex: guanine-nucleotide exchange on eEF1A during translation elongation. Molecular function inferred from the conserved GEF domain; shared with eef1da.' molecular_function: id: GO:0005085 label: guanyl-nucleotide exchange factor activity directly_involved_in: - id: GO:0006414 label: translational elongation locations: - id: GO:0005829 label: cytosol in_complex: id: GO:0005853 label: eukaryotic translation elongation factor 1 complex supported_by: - reference_id: PMID:36576126 supporting_text: the eEF1B complex acts as a guanine exchange factor (GEF) of GTP for GDP indirectly catalyzing the release of eEF1A from the ribosome. - reference_id: file:DANRE/eef1da/eef1da-bioinformatics/RESULTS.md supporting_text: No copy has lost any part of the GEF region suggested_questions: - question: Are eef1db long isoforms (N-terminal extension) actually translated in zebrafish, and do they enter the nucleus like mammalian eEF1BdeltaL? - question: Do eef1da and eef1db proteins both assemble into eEF1B, in what ratio, and does the ratio change between oocyte/early embryo (eef1da-biased) and later tissues? - question: Is eef1db dispensable, and is eef1da upregulated in eef1db mutants? suggested_experiments: - hypothesis: The paralogs are dosage-redundant eEF1B subunits. description: Generate eef1db and eef1da single and double mutants (including RNA-less alleles) and measure viability, growth and global translation (puromycin incorporation, polysome profiles). experiment_type: genetic interaction analysis - hypothesis: Both paralog proteins are incorporated into eEF1B. description: Paralog-specific peptide quantification (targeted proteomics) of eEF1B immunoprecipitates from embryos and adult tissues. experiment_type: proteomics