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FLASH GENE
Symbol APLN contributors: mct/npt - updated : 16-04-2016
HGNC name apelin
HGNC id 16665
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • secretory signal sequence
  • HOMOLOGY
    Homologene
    FAMILY
  • apelin family
  • CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    intracellular,nuclear envelope
    basic FUNCTION
  • neuropeptide expressed in the supraoptic and paraventricular nuclei acting on specific receptors located on vasopressinergic neurons
  • stimulates myosin light chain phosphorylation in vascular smooth muscle cells
  • endogenous ligands for the G protein-coupled receptor APJ (APLNR) (Medhurst 2003)
  • potent stimulators of cardiac contractility contributing to the pathophysiology of cardiac heart failure
  • stomach peptide with a potential physiological role in the gastrointestinal tract
  • angiogenic factor in retinal endothelial cells
  • acting as a novel adipocyte endocrine secretion and having a potential link with obesity-associated variations of insulin sensitivity status
  • promote tumor angiogenesis
  • produces direct cardioprotective actions involving the reperfusion injury salvage kinase pathway and the mitochondrial permeability transition pore (Simpkin 2007)
  • mitogenic for endothelial cells, and potent activator of tumour neoangiogenesis (Sorli 2007)
  • plays an important role in heart physiology and pathophysiology, inflammation, and angiogenesis (Principe 2008)
  • is a novel growth factor for embryonic stem cells-derived hematopoietic and endothelial cells
  • modulated the proliferation, migration, spreading, survival of Müller cells and the expressions of GFAP and VEGFA
  • beneficial adipokine with anti-insulin resistance properties
  • released from endothelial cells, regulates vascular tone and myocardial contractility in VSMC and cardiomyocytes
  • APLN/APLNR system functions as a critical mediator of cardiovascular homeostasis and is involved in the pathophysiology of cardiovascular diseases.
  • is a positive regulator of ACE2 in failing hearts
  • may play a profibrotic role in the development of proliferative diabetic retinopathy (PDR)
  • antioxidant properties of apelin in adipocytes
  • plays a prominent role in body fluid and cardiovascular homeostasis
  • APLN/APLNR axis is involved in hypoxia-induced proliferation of Endothelial progenitor cells (EPCs)
  • APLN and APLNR may play a role in human follicular development and the pathogenesis of polycystic ovary syndrome (PCOS)
  • is a novel myokine and may play a key role in regulating energy metabolism
  • spinal apelin&
  • 8209;APLNR system may drive neuropathic pain
    CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • APLN forms a heterodimer with OPRK1 and leads to increased PKC and decreased protein kinase A activity leading to a significant increase in cell proliferation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • AGTRL1 receptor ligand
  • ACE2 hydrolyzes APLN with similar potency to AGT and, therefore, is responsible for the degradation of both peptides
  • its expression is strongly downregulated by BMP in an endothelial cell line as well as in lung endothelial microvascular cells
  • APLN, APLNR signaling is a potent regulator of endothelial MEF2C function in the developing cardiovascular system
  • induced the proliferation and migration of VSMCs as well as the upregulation of SPP1 via the upregulation of EGR1
  • endogenous ligand for the G-protein-coupled APLNR and plays an important role in regulating the cardiovascular system
  • is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide
  • is down-regulated by ATF4 via the pro-apoptotic MAPK14 pathway under endoplasmic reticulum (ER) stress
  • is a key regulator of cardiovascular function and is activated by two different endogenous peptide ligands, APLN and APELA, each with different isoforms diversified by length and amino acid sequence
  • orphan receptor GPR25 possesses two potential ligands APLN and APELA and its activation decreases intracellular cAMP levels in non-mammalian vertebrates, but also facilitates to unravel the physiological roles of GPR25 signaling in vertebrates
  • cell & other
    REGULATION
    repressed by regulated in a tissue-dependent manner and according to the severity of insulin resistance (Dray 2010)
    Other regulated by insulin in adipocytes
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in cardiac heart failure and coronary heart disease
    constitutional     --over  
    during adipocyte differentiation stage
    constitutional     --over  
    in hepatic cirrhosis (Principe 2008)
    constitutional     --other  
    might be involved in the mechanism of establishment of overt diabetes mellitus as well as associated atherosclerotic complications (Erdem 2008)
    constitutional     --over  
    in aortic valve stenosis, of the apelin-APLNR signaling pathway (Peltonen 2009)
    constitutional     --low  
    in women with polycystic ovary syndrome
    constitutional     --over  
    of APLN or APLNR promoted the hypoxia-induced proliferation of the Endothelial progenitor cells (EPCs)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders
    obesity  
    autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders
    obesity  
    blocking apelin signaling with anti-apelin antibodies will lead not only to inhibition of angiogenesis in adipose tissue but also to decreased adiposity
    cardiovascularaquired 
    apelin-APLNR signaling pathway, is a possible novel target for drug discovery in calcified aortic valve disease by suppressing chemotaxis, angiogenesis and osteoblast activity, all of which are well-documented phenomena in the disease process
    digestiveliver 
    hepatic apelin system is a novel therapeutic target in liver disease
    ANIMAL & CELL MODELS