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; Vega:OTTHUMG00000022371
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	current	GRCh38.p12 (GCF_000001405.38)	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

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

The aims of this study were to evaluate and correlate circulating chemerin, apelin, vaspin, and omentin-1 levels in obese type 2 diabetic Egyptian patients with coronary artery stenosis (CAS), and to assess their usefulness as noninvasive diagnostic biomarkers.
Title: Serum levels of chemerin, apelin, vaspin, and omentin-1 in obese type 2 diabetic Egyptian patients with coronary artery stenosis.
increase in VEGF and Apelin, and decrease in Annexin A5 supports roles of hemo-dynamic alterations in fetoplacental circulation and structural alterations in uteroplacental bed occurring in preeclampsia.
Title: Investigation of role of vascular endothelial growth factor, Annexin A5 and Apelin by immunohistochemistry method in placenta of preeclampsia patients.
these observations suggest apelin-APJ signaling in hepatocytes functions to protect against lipid accumulation in liver through two signaling pathways, that is, via AMPK activation and PPARalpha induction.
Title: Apelin protects against liver X receptor-mediated steatosis through AMPK and PPARα in human and mouse hepatocytes.
Studies suggest that apelin/APJ system may be applied to the treatment of cancers by regulating apoptosis, which may play a vital role in anticancer therapy [review].
Title: Novel pathogenesis: regulation of apoptosis by Apelin/APJ system.
miR-497 contributes to oxLDL-induced lipid deposition in macrophages largely via targeting of apelin.
Title: miR-497 accelerates oxidized low-density lipoprotein-induced lipid accumulation in macrophages by repressing the expression of apelin.
we have identified APLN as putative predictive bvz biomarker in CRC patients. High APLN levels predict a poor response to bvz therapy in CRC.
Title: Apelin: A putative novel predictive biomarker for bevacizumab response in colorectal cancer.
serum level not associated with increased odds of severe hypertension
Title: Associations of Apelin, Visfatin, and Urinary 8-Isoprostane With Severe Hypertension in African Americans: The MH-GRID Study.
Apelin-12 influences troponin I levels in the acute phase of STEMI, whereas during the non-acute phase, low apelin levels were associated with a high rate of MACE.
Title: Influence of apelin-12 on troponin levels and the rate of MACE in STEMI patients.
Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with rheumatoid arthritis. These relations are partially dependent on population origin and systemic inflammatory status.
Title: Apelin concentrations are associated with altered atherosclerotic plaque stability mediator levels and atherosclerosis in rheumatoid arthritis.
APLN and APLNR are present in human ovarian cells and APLN increases IGF1-induced steroidogenesis in granulosa cells through an increase in HSD3B protein expression and activation of the MAPK3/1 and Akt pathways. Therefore, APLN and APLNR may play a role in human follicular development and the pathogenesis of PCOS.
Title: Apelin (APLN) and Apelin Receptor (APLNR) in Human Ovary: Expression, Signaling, and Regulation of Steroidogenesis in Primary Human Luteinized Granulosa Cells.

Submit: New GeneRIF Correction See all GeneRIFs (193)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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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

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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: 164 organisms have orthologs with human gene APLN
The Hierarchical Catalog of 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 signaling receptor activity	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

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Preferred Names: apelin

Names: AGTRL1 ligand; APJ endogenous ligand

NCBI Reference Sequences (RefSeq)

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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.