General Information

  • ID:  hor005464
  • Uniprot ID:  P0DMC2
  • Protein name:  Apelin receptor early endogenous ligand
  • Gene name:  apela
  • Organism:  Danio rerio (Zebrafish) (Brachydanio rerio)
  • Family:  Elabela/Toddler family
  • Source:  animal
  • Expression:  Expressed from the mid-blastula transition (MBT) to 3 days post-fertilization (dpf) . |Expressed ubiquitously during late blastula and gastrula stages and becomes restricted to the lateral mesoderm, endoderm, and anterior and posterior notochord after gas
  • Disease:  NA
  • Comments:  NA
  • Taxonomy:  Danio (genus), Danioninae (subfamily), Danionidae (family), Cyprinoidei (suborder), Cypriniformes (order), Cypriniphysae (superorder), Otophysi, Ostariophysi (subcohort), Otomorpha (cohort), Clupeocephala, Osteoglossocephalai, Teleostei (infraclass), Neopterygii (subclass), Actinopteri (class), Actinopterygii (superclass), Euteleostomi, Teleostomi, Gnathostomata, Vertebrata, Craniata (subphylum), Chordata (phylum), Deuterostomia, Bilateria, Eumetazoa, Metazoa (kingdom), Opisthokonta, Eukaryota (superkingdom), cellular organisms
  • GO MF:  GO:0005179 hormone activity; GO:0031704 apelin receptor binding; GO:0048018 receptor ligand activity
  • GO BP:  GO:0001525 angiogenesis; GO:0001570 vasculogenesis; GO:0002040 sprouting angiogenesis; GO:0007368 determination of left/right symmetry; GO:0007369 gastrulation; GO:0007492 endoderm development; GO:0007507 heart development; GO:0007509 mesoderm migration involved in gastrulation; GO:0007512 adult heart development; GO:0030154 cell differentiation; GO:0035050 embryonic heart tube development; GO:0035479 angioblast cell migration from lateral mesoderm to midline; GO:0035987 endodermal cell differentiation; GO:0042074 cell migration involved in gastrulation; GO:0043009 chordate embryonic development; GO:0045766 positive regulation of angiogenesis; GO:0045823 positive regulation of heart contraction; GO:0060183 apelin receptor signaling pathway; GO:0060976 coronary vasculature development; GO:0061371 determination of heart left/right asymmetry; GO:0070121 Kupffer's vesicle development; GO:0070374 positive regulation of ERK1 and ERK2 cascade; GO:0071910 determination of liver left/right asymmetry; GO:0090133 mesendoderm migration; GO:0090134 cell migration involved in mesendoderm migration; GO:1901165 positive regulation of trophoblast cell migration; GO:1903589 positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis
  • GO CC:  GO:0005576 extracellular region; GO:0005615 extracellular space

Sequence Information

  • Sequence:  DKHGTKHDFLNLRRKYRRHNCPKKRCLPLHSRVPFP
  • Length:  36
  • Propeptide:  MRFFHPLYLLLLLLTVLVLISADKHGTKHDFLNLRRKYRRHNCPKKRCLPLHSRVPFP
  • Signal peptide:  MRFFHPLYLLLLLLTVLVLISA
  • Modification:  NA
  • Glycosylation:  NA
  • Mutagenesis:  NA

Activity

  • Function:  Hormone required for mesendodermal differentiation, blood vessels formation and heart morphogenesis during early development and for adult cardiovascular homeostasis. Acts as a motogen by promoting mesendodermal cell migration during gastrulation by binding and activating the apelin receptor. Acts as an early embryonic regulator of cellular movement with a role in migration and development of cardiac progenitor cells. May act as a chemoattractant for the activation of angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis. Positively regulates sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel sprouting. Involved in cardioprotective functions during heart failure. Mediates myocardial contractility in an ERK1/2-dependent manner
  • Mechanism:  Was named Toddler based on the phenotype.
  • Cross BBB:  NA
  • Target:  NA
  • Target Unid:  NA
  • IC50: NA
  • EC50: NA
  • ED50: NA
  • kd: NA
  • Half life: NA

Structure

  • Disulfide bond:  NA
  • Structure ID:  AF-P0DMC2-F1(AlphaFold_DB_ID)

  • Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)
    •    hor005464_AF2.pdbhor005464_ESM.pdb

Physical Information

Mass: 507669 Formula: C197H317N69O46S2
Absent amino acids: AEIMQW Common amino acids: R
pI: 11.62 Basic residues: 15
Polar residues: 8 Hydrophobic residues: 7
Hydrophobicity: -146.94 Boman Index: -13956
Half-Life: 1.1 hour Half-Life Yeast: 3 min
Half-Life E.Coli: >10 hour Aliphatic Index 51.39
Instability Index: 9013.89 Extinction Coefficient cystines: 1615
Absorbance 280nm: 46.14

Literature

  • PubMed ID:  24316148
  • Title:  ELABELA: a hormone essential for heart development signals via the apelin receptor.
  • PubMed ID:  24407481
  • Title:   Toddler: an embryonic signal that promotes cell movement via apelin receptors.
  • PubMed ID:  26017639
  • Title:  The hormonal peptide Elabela guides angioblasts to the midline during vasculogenesis.
  • PubMed ID:  29117894
  • Title:   Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling.