APLN apelin [Homo sapiens (human)] - Gene

Summary

Official Symbol: APLNprovided by HGNC
Official Full Name: apelinprovided by HGNC
Primary source: HGNC:HGNC:16665
See related: Ensembl:ENSG00000171388 MIM:300297
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APEL; XNPEP2
Summary: This gene encodes a peptide that functions as an endogenous ligand for the G-protein coupled apelin receptor. The encoded preproprotein is proteolytically processed into biologically active C-terminal peptide fragments. These peptide fragments activate different tissue specific signaling pathways that regulate diverse biological functions including fluid homeostasis, cardiovascular function and insulin secretion. This protein also functions as a coreceptor for the human immunodeficiency virus 1. [provided by RefSeq, Feb 2016]
Expression: Biased expression in placenta (RPKM 42.1), lung (RPKM 12.5) and 5 other tissues See more
Orthologs: mouse all

Genomic context

Location:: Xq26.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	X	NC_000023.11 (129645259..129654956, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (128779236..128788933, complement)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Given the role of apelin/APJ and Elabela/APJ in cardiovascular and other diseases, we believe that the combination of these agonists and antagonists with apelin and Elabela will play a corresponding role in various pathophysiological effects with further development of research.
Title: Targeting drugs to APJ receptor: From signaling to pathophysiological effects.
Studied blood levels of apelin in hypertensive and type 2 diabetic (T2D) patients in association with cardiac remodeling; found patients with hypertension and T2D have significant lower apelin blood levels compared to healthy controls.
Title: Relations of Apelin with Cardiac Remodeling in Patients with Hypertension and Type 2 Diabetes.
Apelin may participate in lymphangiogenesis and the progression of ESCC [esophageal squamous cell carcinoma].
Title: Assessment of apelin, apelin receptor, resistin, and adiponectin levels in the primary tumor and serum of patients with esophageal squamous cell carcinoma.
Study provides the biophysical characterization of the two longest isoforms, apelin-55 and -36, in the presence of membrane-mimetic surfactant micelles. Apelin secondary structuring as a function of environment was characterized by far-UV circular dichroism spectropolarimetry alongside NMR spectroscopy.
Title: Apelin conformational and binding equilibria upon micelle interaction primarily depend on membrane-mimetic headgroup.
This meta-analysis revealed that there was no correlation between apelin polymorphisms, rs3761581 and rs56204867, and the prevalence of hypertension.
Title: The association between apelin polymorphisms and hypertension in China: A meta-analysis.
These findings revealed positive regulatory feedback between physical activity, apelin and muscle function.
Title: The exerkine apelin reverses age-associated sarcopenia.
we discuss the role of apelin/APJ system in vascular diseases, such as atherosclerosis, hypertension, and chronic kidney disease (CKD) from the point of VSMC. Above all, apelin/APJ system is a promising target for managing vascular disease.
Title: Apelin/APJ system: A critical regulator of vascular smooth muscle cell.
This meta-analysis presents evidence that apelin circulatory levels are higher in type 2 diabetic subjects than normal controls. [meta-analysis; review]
Title: Elevated blood apelin levels in type 2 diabetes mellitus: A systematic review and meta-analysis.
this study revealed that Apelin/APJ axis may play a key role in atrial thrombogenesis in Valve Heart Disease patients with Atrial Fibrillation.
Title: Involvement of Apelin/APJ Axis in Thrombogenesis in Valve Heart Disease Patients with Atrial Fibrillation.
Binary logistic regression analyses showed that the plasma apelin-12 level was substantially higher in moyamoya patients than inpatients with intracranial atherosclerotic disease.
Title: Prospective evaluation of the diagnostic value of plasma apelin 12 levels for differentiating patients with moyamoya and intracranial atherosclerotic diseases.

Submit: New GeneRIF Correction See all GeneRIFs (207)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	APJ, a seven transmembrane domain G-protein-coupled receptor, functions as a coreceptor for gp120 from some HIV-1 strains; a natural peptide ligand for APJ, apelin-13, efficiently blocks APJ coreceptor activity	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Go to the top of the page Help

Apelin signaling pathway, organism-specific biosystem (from KEGG)
Apelin signaling pathway, organism-specific biosystemApelin is an endogenous peptide capable of binding the apelin receptor (APJ), which was originally described as an orphan G-protein-coupled receptor. Apelin and APJ are widely expressed in various ti...
Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH91453 (e-PCR)
- UniSTS:92224

RH18197 (e-PCR)
- UniSTS:23741

APLN_3269 (e-PCR)
- UniSTS:462030

Homology

Homologs of the APLN gene: The APLN gene is conserved in dog, cow, mouse, and rat.
Orthologs from Annotation Pipeline: 213 organisms have orthologs with human gene APLN
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
apelin receptor binding	IDA Inferred from Direct Assay more info	PubMed
hormone activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein homodimerization activity	IEA Inferred from Electronic Annotation more info
signaling receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
angiogenesis	IEA Inferred from Electronic Annotation more info
apelin receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
apelin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
coronary vasculature development	ISS Inferred from Sequence or Structural Similarity more info
drinking behavior	ISS Inferred from Sequence or Structural Similarity more info
gastrulation	IEA Inferred from Electronic Annotation more info
immune response	TAS Traceable Author Statement more info	PubMed
lactation	TAS Traceable Author Statement more info	PubMed
negative regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of fibroblast growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of vascular smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
positive regulation of G protein-coupled receptor internalization	IDA Inferred from Direct Assay more info	PubMed
positive regulation of corticotropin secretion	IEA Inferred from Electronic Annotation more info
positive regulation of corticotropin-releasing hormone secretion	IEA Inferred from Electronic Annotation more info
positive regulation of heart contraction	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of heat generation	IEA Inferred from Electronic Annotation more info
positive regulation of phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of pri-miRNA transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of vascular endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
regulation of respiratory gaseous exchange	IEA Inferred from Electronic Annotation more info
regulation of the force of heart contraction	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
extracellular region	IDA Inferred from Direct Assay more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: apelin

Names: AGTRL1 ligand; APJ endogenous ligand

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.