id: A0A8N1TQS2 gene_symbol: elna product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:7955 label: Danio rerio description: >- elna (elastin a, formerly eln1) is one of two zebrafish tropoelastin genes, co-orthologous with the single tetrapod ELN gene, that arose in the teleost-specific whole-genome duplication together with its paralog elnb. It encodes a secreted, non-enzymatic tropoelastin precursor (about 101 kDa, 57 exons) with the alternating hydrophobic and lysine-containing crosslinking domain arrangement characteristic of all tropoelastins; it is the zebrafish copy closest in sequence to human ELN. Elna is expressed broadly in elastic tissues, including head skeletal cartilage, the cardiac outflow tract (bulbus arteriosus and ventral aorta), heart valves and the swim bladder wall, a breadth that resembles the single elastin gene of the non-teleost Polypterus. Its product is deposited as elastin in the extracellular matrix, where it is the predominant elastin of the atrioventricular and ventriculo-bulbar valves. A germline nonsense allele (sa12235) is viable through embryogenesis but reduces valve elastin and causes adult valve disorganization, cardiac enlargement and shortened lifespan; morphants show a swim bladder defect and a mild reduction in bulbus arteriosus deformation, without the bulbus hypoplasia or cell-fate change seen for elnb. existing_annotations: - term: id: GO:0003674 label: molecular_function evidence_type: ND original_reference_id: GO_REF:0000015 qualifier: enables review: summary: >- Root-term ND placeholder recording that no molecular function had been curated for elna. That is no longer the state of knowledge: Elna is a tropoelastin with the conserved elastin domain architecture, and an elna nonsense mutant loses elastin from the heart valves. action: REMOVE reason: >- The placeholder is superseded by an informative molecular function (extracellular matrix structural constituent, refined here to extracellular matrix constituent conferring elasticity), supported by sequence architecture and by loss-of-function evidence that elna supplies valve elastin. supported_by: - reference_id: PMID:16982180 supporting_text: All tropoelastins shared a predominant and characteristic alternating domain arrangement, as well as the fundamental crosslinking sequence motifs. - reference_id: PMID:37408270 supporting_text: the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin nd_case: STALE - term: id: GO:0005201 label: extracellular matrix structural constituent evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR003979 review: summary: >- InterPro2GO mapping from the tropoelastin signature (IPR003979). Correct: Elna is a tropoelastin whose product is deposited into elastic tissues, and it is the zebrafish copy closest to human ELN. The term is accurate but general; the specific activity of elastin is captured by GO:0030023 extracellular matrix constituent conferring elasticity, the term used for mammalian elastin. action: MODIFY reason: >- The annotation is sound but under-specific. Elastin proteins are the defining members of GO:0030023 (a child of GO:0005201), and Elna retains the elastin domain arrangement and crosslinking motifs and supplies elastin to zebrafish valves. The same refinement is proposed for elnb so the paralog pair is annotated consistently at the molecular-function level. proposed_replacement_terms: - id: GO:0030023 label: extracellular matrix constituent conferring elasticity supported_by: - reference_id: PMID:16982180 supporting_text: All tropoelastins shared a predominant and characteristic alternating domain arrangement, as well as the fundamental crosslinking sequence motifs. - reference_id: PMID:35216218 supporting_text: Alignments of protein sequences with EMBOSS-Needle (EMBL-EBI) revealed that Elna was closer to human tropoelastin (ELN) than Elnb. - reference_id: PMID:17112714 supporting_text: In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined - term: id: GO:0008150 label: biological_process evidence_type: ND original_reference_id: GO_REF:0000015 qualifier: involved_in review: summary: >- Root-term ND placeholder. Loss-of-function data now exist: the elna sa12235 nonsense mutant has reduced valve elastin, and a process annotation for elastic fiber assembly is proposed below. action: REMOVE reason: >- Superseded by the proposed GO:0048251 elastic fiber assembly annotation, which is supported by the germline elna mutant. supported_by: - reference_id: PMID:37408270 supporting_text: the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin nd_case: STALE - term: id: GO:0031012 label: extracellular matrix evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: located_in supporting_entities: - InterPro:IPR003979 review: summary: >- InterPro2GO location from the tropoelastin signature. Correct: Elna is a secreted tropoelastin (signal peptide in UniProt) whose product is deposited in the extracellular matrix of elastic tissues. action: ACCEPT reason: >- Extracellular matrix is the correct general location for a tropoelastin. A more specific location, elastic fiber, is proposed as a NEW annotation. supported_by: - reference_id: PMID:17112714 supporting_text: In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined - term: id: GO:0071953 label: elastic fiber evidence_type: IDA original_reference_id: PMID:17112714 review: summary: >- Proposed location. Miao et al. detected the eln1 (elna) gene product deposited in most elastic tissues of zebrafish, and loss of elna removes elastin from the heart valves, where Elna is the predominant elastin. Human and mouse elastin carry this term by direct assay. action: NEW reason: >- Elastin forms the core of elastic fibers; this is the specific location of the mature Elna product and is more informative than the extracellular matrix IEA. The same term is proposed for elnb because both gene products are deposited as elastin. supported_by: - reference_id: PMID:17112714 supporting_text: In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined - reference_id: PMID:37408270 supporting_text: elastin a seems to be the prevalent isoform expressed in this specific structure - reference_id: file:DANRE/elna/elna-deep-research-falcon.md supporting_text: Tropoelastin is the soluble precursor; mature elastin is an insoluble, covalently cross-linked elastic-fiber component. - term: id: GO:0048251 label: elastic fiber assembly evidence_type: IMP original_reference_id: PMID:37408270 review: summary: >- Proposed process. The elna sa12235 allele introduces a stop codon at Tyr88, and heterozygous and homozygous mutants have markedly less elastin in the heart valves, with disorganized, honeycomb-like valve matrix. action: NEW reason: >- Participation test: tropoelastin is not a substrate of elastic fiber assembly but the structural monomer that self-associates and is crosslinked to form the fiber core, so Elna does part of the work of the process (the structure case). Comparator check: mammalian elastin is annotated to the parent GO:0085029 extracellular matrix assembly (mouse Eln, IMP), and the elastic fiber structural proteins FBN1, FBLN5, EMILIN1 and MFAP4 carry GO:0048251 itself. Evidence is loss of valve elastin in a germline nonsense mutant; the same term is proposed for elnb, whose loss reduces bulbus arteriosus elastin. supported_by: - reference_id: PMID:37408270 supporting_text: This change leads to the loss of a tyrosine (Tyr88) for a stop codon at the very beginning of the protein sequence. - reference_id: PMID:37408270 supporting_text: the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin, according to both the orcein staining and the anti-elastin immunohistochemistry assay core_functions: - description: >- Elna is a secreted tropoelastin that is deposited and crosslinked into elastic fibers of the extracellular matrix, where it provides elasticity to a broad set of tissues (head cartilage, outflow tract, ventral aorta, swim bladder). It is the predominant elastin of the adult heart valves, and its loss causes progressive valve disorganization and reduced survival. This broad role resembles that of the single ancestral elastin gene. molecular_function: id: GO:0030023 label: extracellular matrix constituent conferring elasticity directly_involved_in: - id: GO:0048251 label: elastic fiber assembly locations: - id: GO:0071953 label: elastic fiber supported_by: - reference_id: PMID:37408270 supporting_text: the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin - reference_id: PMID:26783159 supporting_text: In contrast, elna was expressed not only in the BA but also other tissues, such as the cranial skeleton and swim bladder references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000015 title: Use of the ND evidence code for Gene Ontology (GO) terms findings: [] - id: PMID:16982180 title: 'Sequences and domain structures of mammalian, avian, amphibian and teleost tropoelastins: Clues to the evolutionary history of elastins.' findings: - statement: Zebrafish expresses two tropoelastin genes that share the characteristic tropoelastin domain arrangement and crosslinking motifs. supporting_text: Unlike other species, two tropoelastin genes were expressed in zebrafish. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract only; original description of the two zebrafish tropoelastins. PMID matches UniProt RN [1]. - id: PMID:17112714 title: Differential expression of two tropoelastin genes in zebrafish. findings: - statement: Both tropoelastins are expressed in most elastic tissues; eln2 (elnb) predominates in the bulbus arteriosus. supporting_text: with the notable exception of the bulbus arteriosus in which eln2 expression and its gene product was predominant reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract only. eln1 = elna, eln2 = elnb (UniProt synonyms). - id: PMID:17628459 title: 'Comparative genomics of elastin: Sequence analysis of a highly repetitive protein.' findings: - statement: Both zebrafish elastins show a block of putative exon duplications. supporting_text: exons 20-31 in both zebrafish elastins reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only; sequence-evolution background, no functional data for elna specifically. - id: PMID:26783159 title: Evolution of the fish heart by sub/neofunctionalization of an elastin gene. findings: - statement: elna and elnb arose by duplication after the split from gar, with limk1a/limk1b neighbours supporting duplication of the locus in the TGD. supporting_text: Taken together, these results indicate that genomic locus including eln and limk1 genes was duplicated in the 3R WGD. - statement: elna is broadly expressed, like the single Polypterus eln. supporting_text: As expected, Polypterus had one elastin gene, and its expression was observed in various tissues including OFT, which is similar to that of zebrafish elna - statement: elna morphants have a swim bladder defect but no bulbus arteriosus morphology defect. supporting_text: elna morphants exhibited a swim bladder defect, where elna expression level is relatively high - statement: elna mRNA cannot rescue the elnb morphant bulbus phenotype. supporting_text: injection of elnb MO and elna full-length mRNA did not rescue the elnb morphant phenotype reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text. elna data are morpholino (and F0 CRISPR) only. - id: PMID:35216218 title: Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies. findings: - statement: Elna is closer to human ELN (about 37% identity) than Elnb is (about 18%). supporting_text: They share approximately 37% identity and 41% similarity, whereas for Elnb, around 18% identity and 21% similarity were calculated. reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Review; used for sequence comparison and synteny summary. - id: PMID:37408270 title: 'Characterization of the Zebrafish Elastin a (elna(sa12235)) Mutant: A New Model of Elastinopathy Leading to Heart Valve Defects.' findings: - statement: elna nonsense mutants have reduced valve elastin and shortened lifespan, but normal embryonic survival. supporting_text: Heterozygous (elnasa12235/+) and homozygous (elnasa12235/sa12235) mutants were found to have a significantly decreased life expectancy compared with their wild-type siblings. reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; germline ENU nonsense allele (PTC, Tyr88*). Transcriptional adaptation of elnb was not tested. - id: PMID:41465165 title: Duplication, Divergence and Cardiac Expression of Tropoelastin in Jawed Fishes, Including Tetraploid Rainbow Trout (Oncorhynchus mykiss). findings: - statement: Non-teleost fishes have a single eln gene; teleosts have elna and elnb in a conserved eln-septin4/5-limk1 syntenic block. supporting_text: All non-teleost genomes contain a single eln gene, whereas duplicated elna and elnb genes were found in teleosts reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Full text; genome survey of 51 jawed fishes plus trout qPCR. - id: file:DANRE/elna/elna-deep-research-falcon.md title: Deep research report for elna (Falcon) findings: [] reference_review: relevance: MEDIUM correctness: UNVERIFIED review_notes: Used as a literature pointer only; all claims here are anchored to cached primary papers. suggested_questions: - question: >- Is elnb transcriptionally upregulated in elna sa12235 (PTC) mutants, and does this explain why valve disease appears only in adults? - question: >- Does the elna swim bladder phenotype reported for morphants reproduce in germline elna mutants? suggested_experiments: - description: >- Compare elna sa12235 (PTC) mutants with a promoter-deletion (RNA-less) elna allele and measure elnb expression, to separate genetic compensation from true redundancy. experiment_type: genetic loss-of-function comparison - description: >- Paralog-specific antibodies or tagged knock-in alleles to measure the contribution of Elna versus Elnb to elastin in each tissue. experiment_type: immunohistochemistry