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, cardiovasc... See more...

Aliases for APLN Gene

Aliases for APLN Gene

  • Apelin 2 2 3 4 5
  • APJ Endogenous Ligand 3 4
  • XNPEP2 2 3
  • APEL 3 4
  • Apelin, AGTRL1 Ligand 2
  • AGTRL1 Ligand 3
  • APLN 5

External Ids for APLN Gene

Previous GeneCards Identifiers for APLN Gene

  • GC0XM126724
  • GC0XM127485
  • GC0XM128504
  • GC0XM128607
  • GC0XM128779
  • GC0XM118183

Summaries for APLN Gene

Entrez Gene Summary for APLN Gene

  • 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]

GeneCards Summary for APLN Gene

APLN (Apelin) is a Protein Coding gene. Diseases associated with APLN include Severe Pre-Eclampsia and Heart Disease. Among its related pathways are Signaling by GPCR and Apelin signaling pathway. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and G protein-coupled receptor binding.

UniProtKB/Swiss-Prot Summary for APLN Gene

  • Endogenous ligand for the apelin receptor (APLNR) (PubMed:10525157). Drives internalization of the apelin receptor (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity).
  • (Microbial infection) Endogenous ligand for the apelin receptor (APLNR), an alternative coreceptor with CD4 for HIV-1 infection (PubMed:11090199). Inhibits HIV-1 entry in cells coexpressing CD4 and APLNR (PubMed:11090199). Apelin-36 has a greater inhibitory activity on HIV infection than other synthetic apelin derivatives (PubMed:11090199).

Tocris Summary for APLN Gene

  • Apelin-36, apelin-13 and [Pyr1]-apelin-13 are the predominant endogenous ligands for the apelin receptor (APJ) receptor. The APJ receptor and apelin peptides act as mediators of cardiovascular function, fluid homeostasis and adipocyte endocrine secretion.

Gene Wiki entry for APLN Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for APLN Gene

Genomics for APLN Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for APLN Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ129654 Promoter 1.6 EPDnew Ensembl CraniofacialAtlas 600.7 +0.5 455 1.8 ZNF692 ZIC2 PATZ1 ZNF501 ZNF341 ZNF37A SCRT2 SOX13 HES1 KLF9 APLN lnc-OCRL-3 OCRL
GH0XJ129731 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 12.8 -80.8 -80773 9.9 GATAD2A REST ZNF512 IKZF1 JUND ZSCAN4 SP1 SOX13 NR2C2 ESRRA XPNPEP2 APLN piR-31199-402
GH0XJ129677 Promoter/Enhancer 1.1 ENCODE CraniofacialAtlas 13.3 -23.3 -23273 1.9 HNRNPL CTCF FOXA1 ZSCAN4 RXRB PATZ1 SP1 GATAD2B ZNF316 FOXA2 ENSG00000287024 LOC105373334 APLN ZDHHC9 RF00017-8704 XPNPEP2
GH0XJ129754 Promoter/Enhancer 1 Ensembl ENCODE dbSUPER 12.5 -99.7 -99711 0.5 CTCF REST ZNF740 CTBP1 SMC3 RAD21 ZNF143 GATA2 CC2D1A APLN ZDHHC9 XPNPEP2 SASH3
GH0XJ129755 Promoter/Enhancer 1 Ensembl ENCODE dbSUPER 12.5 -101.3 -101250 1.4 RAD21 RUNX3 USF1 SMC3 CTCF RXRA RAD51 USF2 APLN ZDHHC9 XPNPEP2 SASH3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around APLN on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for APLN

Top Transcription factor binding sites by QIAGEN in the APLN gene promoter:
  • AP-1
  • ATF-2
  • c-Fos
  • c-Jun
  • GR
  • GR-alpha
  • oct-B2
  • oct-B3

Genomic Locations for APLN Gene

Genomic Locations for APLN Gene
chrX:129,645,259-129,654,956
(GRCh38/hg38)
Size:
9,698 bases
Orientation:
Minus strand
chrX:128,779,236-128,788,933
(GRCh37/hg19)
Size:
9,698 bases
Orientation:
Minus strand

Genomic View for APLN Gene

Genes around APLN on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
APLN Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for APLN Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for APLN Gene

Proteins for APLN Gene

  • Protein details for APLN Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9ULZ1-APEL_HUMAN
    Recommended name:
    Apelin
    Protein Accession:
    Q9ULZ1
    Secondary Accessions:
    • Q4VY08
    • Q8WU89

    Protein attributes for APLN Gene

    Size:
    77 amino acids
    Molecular mass:
    8569 Da
    Quaternary structure:
    No Data Available

neXtProt entry for APLN Gene

Post-translational modifications for APLN Gene

  • Several active peptides may be produced by proteolytic processing of the peptide precursor.

Other Protein References for APLN Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for APLN

No data available for DME Specific Peptides for APLN Gene

Domains & Families for APLN Gene

Gene Families for APLN Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted secreted proteins

Protein Domains for APLN Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for APLN Gene

GenScript: Design optimal peptide antigens:
  • APJ endogenous ligand (APEL_HUMAN)
  • cDNA, FLJ92342, Homo sapiens apelin (APLN), mRNA (B2R550_HUMAN)
  • Apelin, AGTRL1 ligand, isoform CRA_a (D3DTF8_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9ULZ1

UniProtKB/Swiss-Prot:

APEL_HUMAN :
  • Belongs to the apelin family.
Family:
  • Belongs to the apelin family.
genes like me logo Genes that share domains with APLN: view

Function for APLN Gene

Molecular function for APLN Gene

UniProtKB/Swiss-Prot Function:
Endogenous ligand for the apelin receptor (APLNR) (PubMed:10525157). Drives internalization of the apelin receptor (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity).
UniProtKB/Swiss-Prot Function:
(Microbial infection) Endogenous ligand for the apelin receptor (APLNR), an alternative coreceptor with CD4 for HIV-1 infection (PubMed:11090199). Inhibits HIV-1 entry in cells coexpressing CD4 and APLNR (PubMed:11090199). Apelin-36 has a greater inhibitory activity on HIV infection than other synthetic apelin derivatives (PubMed:11090199).

LifeMap Function Summary for APLN Gene

APLN as growth factor is involved in stem cell differentiation protocols towards the derivation of the following cells:

Phenotypes From GWAS Catalog for APLN Gene

Gene Ontology (GO) - Molecular Function for APLN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS 9792798
GO:0005179 hormone activity IMP 28137936
GO:0031704 apelin receptor binding IDA 28137936
GO:0042802 identical protein binding IEA --
genes like me logo Genes that share ontologies with APLN: view
genes like me logo Genes that share phenotypes with APLN: view

Animal Models for APLN Gene

MGI Knock Outs for APLN:

Animal Model Products

  • Taconic Biosciences Mouse Models for APLN

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APLN

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for APLN Gene

Localization for APLN Gene

Subcellular locations from UniProtKB/Swiss-Prot for APLN Gene

Secreted. Secreted, extracellular space. Note=Abundantly secreted in the colostrum. Lower level in milk. Decreases rapidly within several days after parturition in milk, but is still detectable even in commercial milk. {ECO:0000250 UniProtKB:Q9TUI9}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for APLN gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
nucleus 2
endoplasmic reticulum 2
cytosol 2
peroxisome 1
endosome 1
lysosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for APLN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IBA 21873635
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with APLN: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for APLN Gene

Pathways & Interactions for APLN Gene

genes like me logo Genes that share pathways with APLN: view

SIGNOR curated interactions for APLN Gene

Is activated by:

Gene Ontology (GO) - Biological Process for APLN Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0002026 regulation of the force of heart contraction IEA --
GO:0006955 immune response TAS --
GO:0007165 signal transduction TAS 9792798
GO:0007186 G protein-coupled receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with APLN: view

Drugs & Compounds for APLN Gene

(9) Drugs for APLN Gene - From: ApexBio, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Apelin-36 (rat, mouse) Pharma Endogenous APJ receptor agonist 0
[Pyr1]-Apelin-13 Pharma Potent peptide agonist for APJ receptor 0
Apelin-17 (human, bovine) Pharma Endogenous APJ receptor agonist 0
Apelin-36 (human) Pharma Endogenous APJ receptor agonist 0

(4) Additional Compounds for APLN Gene - From: Novoseek and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ML 233

(5) Tocris Compounds for APLN Gene

Compound Action Cas Number
[Pyr1]-Apelin-13 Potent peptide agonist for APJ receptor 217082-60-5
Apelin-17 (human, bovine) Endogenous APJ receptor agonist 217082-57-0
Apelin-36 (human) Endogenous APJ receptor agonist 252642-12-9
Apelin-36 (rat, mouse) Endogenous APJ receptor agonist 230299-95-3
ML 233 Non-peptide apelin receptor agonist

(1) ApexBio Compounds for APLN Gene

Compound Action Cas Number
Apelin-36 (rat, mouse) 230299-95-3
genes like me logo Genes that share compounds with APLN: view

Drug Products

Transcripts for APLN Gene

mRNA/cDNA for APLN Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for APLN

Alternative Splicing Database (ASD) splice patterns (SP) for APLN Gene

No ASD Table

Relevant External Links for APLN Gene

GeneLoc Exon Structure for
APLN

Expression for APLN Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for APLN Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for APLN Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x5.9) and Brain - Substantia nigra (x4.2).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for APLN

SOURCE GeneReport for Unigene cluster for APLN Gene:

Hs.303084

mRNA Expression by UniProt/SwissProt for APLN Gene:

Q9ULZ1-APEL_HUMAN
Tissue specificity: Expressed in the brain with highest levels in the frontal cortex, thalamus, hypothalamus and midbrain (PubMed:10617103). Secreted by the mammary gland into the colostrum and the milk.

Evidence on tissue expression from TISSUES for APLN Gene

  • Nervous system(4.5)
  • Kidney(4.4)
  • Heart(2.6)
  • Blood(2.5)
  • Muscle(2.5)
genes like me logo Genes that share expression patterns with APLN: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for APLN Gene

Orthologs for APLN Gene

This gene was present in the common ancestor of mammals.

Orthologs for APLN Gene

Organism Taxonomy Gene Similarity Type Details
Dog
(Canis familiaris)
Mammalia APLN 30
  • 87.01 (n)
Rat
(Rattus norvegicus)
Mammalia Apln 30
  • 85.71 (n)
Cow
(Bos Taurus)
Mammalia APLN 30 31
  • 84.85 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Apln 30 17 31
  • 82.25 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia APLN 31
  • 28 (a)
OneToOne
Species where no ortholog for APLN was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chimpanzee (Pan troglodytes)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for APLN Gene

ENSEMBL:
Gene Tree for APLN (if available)
TreeFam:
Gene Tree for APLN (if available)
Aminode:
Evolutionary constrained regions (ECRs) for APLN: view image

Paralogs for APLN Gene

No data available for Paralogs for APLN Gene

Variants for APLN Gene

Additional dbSNP identifiers (rs#s) for APLN Gene

Structural Variations from Database of Genomic Variants (DGV) for APLN Gene

Variant ID Type Subtype PubMed ID
esv2758893 CNV gain+loss 17122850
nsv508800 CNV insertion 20534489
nsv528290 CNV gain 19592680

Variation tolerance for APLN Gene

Gene Damage Index Score: 5.93; 74.47% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for APLN Gene

Human Gene Mutation Database (HGMD)
APLN
SNPedia medical, phenotypic, and genealogical associations of SNPs for
APLN

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for APLN Gene

Disorders for APLN Gene

MalaCards: The human disease database

(10) MalaCards diseases for APLN Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
severe pre-eclampsia
  • antepartum severe pre-eclampsia
heart disease
  • congenital heart disease
placental insufficiency
  • uteroplacental vascular insufficiency
body mass index quantitative trait locus 11
  • bmiq11
cardiovascular system disease
  • disease of subdivision of hemolymphoid system
- elite association - COSMIC cancer census association via MalaCards
Search APLN in MalaCards View complete list of genes associated with diseases

Additional Disease Information for APLN

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with APLN: view

No data available for UniProtKB/Swiss-Prot and Genatlas for APLN Gene

Publications for APLN Gene

  1. Association of apelin genetic variants with type 2 diabetes and related clinical features in Chinese Hans. (PMID: 19567136) Zhang R … Jia WP (Chinese medical journal 2009) 3 23 41
  2. Family-based analysis of apelin and AGTRL1 gene polymorphisms with hypertension in Han Chinese. (PMID: 19307984) Li WW … Zhu DL (Journal of hypertension 2009) 3 23 41
  3. Characterization of apelin, the ligand for the APJ receptor. (PMID: 10617103) Lee DK … O'Dowd BF (Journal of neurochemistry 2000) 3 4 23
  4. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. (PMID: 11090199) Cayabyab M … Sodroski J (Journal of virology 2000) 3 4 23
  5. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. (PMID: 9792798) Tatemoto K … Fujino M (Biochemical and biophysical research communications 1998) 2 3 4

Products for APLN Gene

Sources for APLN Gene