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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003674 molecular_function | ND GO_REF:0000015 | REMOVE | 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. Reason: The placeholder is superseded by an informative molecular function (extracellular matrix structural constituent, refined here to extracellular matrix constituent conferring elasticity),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. Supporting Evidence: PMID:16982180 All tropoelastins shared a predominant and characteristic alternating domain arrangement, as well as the fundamental crosslinking sequence motifs. PMID:37408270 the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin |
| GO:0005201 extracellular matrix structural constituent | IEA GO_REF:0000002 | MODIFY | 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. 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 replacements: extracellular matrix constituent conferring elasticity Supporting Evidence: PMID:16982180 All tropoelastins shared a predominant and characteristic alternating domain arrangement, as well as the fundamental crosslinking sequence motifs. PMID:35216218 Alignments of protein sequences with EMBOSS-Needle (EMBL-EBI) revealed that Elna was closer to human tropoelastin (ELN) than Elnb. PMID:17112714 In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined |
| GO:0008150 biological_process | ND GO_REF:0000015 | REMOVE | 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. Reason: Superseded by the proposed GO:0048251 elastic fiber assembly annotation, which is supported by the germline elna mutant. Supporting Evidence: PMID:37408270 the valves of elnasa12235/+ and elnasa12235/sa12235 mutants were found to have a markedly diminished quantity of elastin |
| GO:0031012 extracellular matrix | IEA GO_REF:0000002 | ACCEPT | 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. Reason: Extracellular matrix is the correct general location for a tropoelastin. A more specific location, elastic fiber, is proposed as a NEW annotation. Supporting Evidence: PMID:17112714 In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined |
| GO:0071953 elastic fiber | IDA PMID:17112714 Differential expression of two tropoelastin genes in zebrafi... | NEW | 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. 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. Supporting Evidence: PMID:17112714 In general, both genes were expressed and their gene products deposited in most of the elastic tissues examined PMID:37408270 elastin a seems to be the prevalent isoform expressed in this specific structure file:DANRE/elna/elna-deep-research-falcon.md Tropoelastin is the soluble precursor; mature elastin is an insoluble, covalently cross-linked elastic-fiber component. |
| GO:0048251 elastic fiber assembly | IMP PMID:37408270 Characterization of the Zebrafish Elastin a (elna(sa12235)) ... | NEW | 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. 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. Supporting Evidence: PMID:37408270 This change leads to the loss of a tyrosine (Tyr88) for a stop codon at the very beginning of the protein sequence. PMID:37408270 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 |
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Download this section (compressed HTML)Q: Is elnb transcriptionally upregulated in elna sa12235 (PTC) mutants, and does this explain why valve disease appears only in adults?
Q: Does the elna swim bladder phenotype reported for morphants reproduce in germline elna mutants?
Experiment: Compare elna sa12235 (PTC) mutants with a promoter-deletion (RNA-less) elna allele and measure elnb expression, to separate genetic compensation from true redundancy.
Type: genetic loss-of-function comparison
Experiment: Paralog-specific antibodies or tagged knock-in alleles to measure the contribution of Elna versus Elnb to elastin in each tissue.
Type: immunohistochemistry
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