The protein encoded by this gene is an antagonist of angiopoietin 1 (Ang-1), and both (Ang-1 and Ang-2) are ligands for the endothelial tyrosine kinase receptor (Tie2). These two ligands affect angiogenesis during embryogenesis and tumorigenesis. The encoded protein disrupts the vascular remodeling ability of Ang-1 and may induce endothelial cell apoptosis. Three transcript var... See more...

Aliases for ANGPT2 Gene

Aliases for ANGPT2 Gene

  • Angiopoietin 2 2 3 5
  • Angiopoietin-2 3 4
  • ANG-2 3 4
  • Angiopoietin-2B 3
  • Angiopoietin-2a 3
  • Tie2-Ligand 3
  • ANGPT2 5
  • AGPT2 3
  • ANG2 3
  • Ang2 2

External Ids for ANGPT2 Gene

Previous GeneCards Identifiers for ANGPT2 Gene

  • GC08M006424
  • GC08M006614
  • GC08M006347
  • GC08M006139

Summaries for ANGPT2 Gene

Entrez Gene Summary for ANGPT2 Gene

  • The protein encoded by this gene is an antagonist of angiopoietin 1 (Ang-1), and both (Ang-1 and Ang-2) are ligands for the endothelial tyrosine kinase receptor (Tie2). These two ligands affect angiogenesis during embryogenesis and tumorigenesis. The encoded protein disrupts the vascular remodeling ability of Ang-1 and may induce endothelial cell apoptosis. Three transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Nov 2019]

GeneCards Summary for ANGPT2 Gene

ANGPT2 (Angiopoietin 2) is a Protein Coding gene. Diseases associated with ANGPT2 include Placental Insufficiency and Microvascular Complications Of Diabetes 1. Among its related pathways are Immune response IL-23 signaling pathway and Cell surface interactions at the vascular wall. Gene Ontology (GO) annotations related to this gene include signaling receptor binding and receptor tyrosine kinase binding. An important paralog of this gene is ANGPT1.

UniProtKB/Swiss-Prot Summary for ANGPT2 Gene

  • Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.

Gene Wiki entry for ANGPT2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ANGPT2 Gene

Genomics for ANGPT2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ANGPT2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ANGPT2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ANGPT2

Top Transcription factor binding sites by QIAGEN in the ANGPT2 gene promoter:
  • AhR
  • AML1a
  • Arnt
  • FOXO1
  • FOXO1a
  • GATA-6
  • STAT5A
  • YY1

Genomic Locations for ANGPT2 Gene

Genomic Locations for ANGPT2 Gene
chr8:6,499,632-6,563,420
(GRCh38/hg38)
Size:
63,789 bases
Orientation:
Minus strand
chr8:6,357,172-6,420,930
(GRCh37/hg19)
Size:
63,759 bases
Orientation:
Minus strand

Genomic View for ANGPT2 Gene

Genes around ANGPT2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ANGPT2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ANGPT2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ANGPT2 Gene

Proteins for ANGPT2 Gene

  • Protein details for ANGPT2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15123-ANGP2_HUMAN
    Recommended name:
    Angiopoietin-2
    Protein Accession:
    O15123
    Secondary Accessions:
    • A0AV38
    • A8K205
    • B7ZLM7
    • Q9NRR7
    • Q9P2Y7

    Protein attributes for ANGPT2 Gene

    Size:
    496 amino acids
    Molecular mass:
    56919 Da
    Quaternary structure:
    • Interacts with TEK/TIE2, competing for the same binding site as ANGPT1.

    Three dimensional structures from OCA and Proteopedia for ANGPT2 Gene

    Alternative splice isoforms for ANGPT2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ANGPT2 Gene

Post-translational modifications for ANGPT2 Gene

  • Glycosylation at Asn89, Asn151, Asn119, Asn133, Asn240, and Asn304
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • ANGP2_HUMAN (664)

Other Protein References for ANGPT2 Gene

Antibody Products

No data available for DME Specific Peptides for ANGPT2 Gene

Domains & Families for ANGPT2 Gene

Gene Families for ANGPT2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for ANGPT2 Gene

InterPro:
Blocks:
  • Fibrinogen, beta/gamma chain, C-terminal globular
ProtoNet:

Suggested Antigen Peptide Sequences for ANGPT2 Gene

GenScript: Design optimal peptide antigens:
  • Angiopoietin-2 (ANGP2_HUMAN)
  • Angiopoietin-2a (Q9H4C0_HUMAN)
  • Angiopoietin-2B (Q9H4C1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O15123

UniProtKB/Swiss-Prot:

ANGP2_HUMAN :
  • The Fibrinogen C-terminal domain mediates interaction with the TEK/TIE2 receptor.
Domain:
  • The Fibrinogen C-terminal domain mediates interaction with the TEK/TIE2 receptor.
genes like me logo Genes that share domains with ANGPT2: view

Function for ANGPT2 Gene

Molecular function for ANGPT2 Gene

UniProtKB/Swiss-Prot Function:
Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.
GENATLAS Biochemistry:
angiopoietin 1,75kDa,secreted ligand,for the vascular endothelial restricted receptor tyrosine kinase TEK,including phosphorylation of TEK,expressed only at sites of vascular remodeling in adult,antagonizing ANGPT1 by blocking its ability to activate its ligand

LifeMap Function Summary for ANGPT2 Gene

During embryonic development, ANGPT2 as signaling molecule is secreted from the following cells
It affects the following cells:

Phenotypes From GWAS Catalog for ANGPT2 Gene

Gene Ontology (GO) - Molecular Function for ANGPT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005102 signaling receptor binding TAS,IBA 21873635
GO:0005515 protein binding IPI 20708158
GO:0030971 receptor tyrosine kinase binding IEA,IPI 19922791
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with ANGPT2: view
genes like me logo Genes that share phenotypes with ANGPT2: view

Animal Models for ANGPT2 Gene

MGI Knock Outs for ANGPT2:

CRISPR Products

miRNA for ANGPT2 Gene

miRTarBase miRNAs that target ANGPT2

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ANGPT2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ANGPT2 Gene

Localization for ANGPT2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ANGPT2 Gene

Secreted.

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 ANGPT2 gene
Compartment Confidence
extracellular 5
plasma membrane 3
nucleus 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for ANGPT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space TAS,IDA 9660821
GO:0005634 nucleus IEA --
GO:0005886 plasma membrane IEA --
GO:0042995 cell projection IEA --
genes like me logo Genes that share ontologies with ANGPT2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ANGPT2 Gene

Pathways & Interactions for ANGPT2 Gene

PathCards logo

SuperPathways for ANGPT2 Gene

SuperPathway Contained pathways
1 PEDF Induced Signaling
.94
.94
.73
.71
.62
.61
.57
.51
.47
.46
.43
2 TGF-Beta Pathway
.60
.60
.57
.51
.43
.41
3 Immune response IL-23 signaling pathway
.38
.36
4 Akt Signaling
.60
.60
.55
5 ERK Signaling
.61
.61
.51
genes like me logo Genes that share pathways with ANGPT2: view

Pathways by source for ANGPT2 Gene

1 GeneGo (Thomson Reuters) pathway for ANGPT2 Gene
  • Development Angiopoietin - Tie2 signaling
26 Qiagen pathways for ANGPT2 Gene
  • Akt Signaling
  • all-trans-Retinoic Acid Signaling in Brain
  • Angiopoietin-TIE2 Signaling
  • Antioxidant Action of Vitamin-C
  • Endothelin-1 Signaling Pathway
2 Cell Signaling Technology pathways for ANGPT2 Gene

SIGNOR curated interactions for ANGPT2 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for ANGPT2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA,IBA 21873635
GO:0001666 response to hypoxia IEA --
GO:0007165 signal transduction TAS 10766762
GO:0007275 multicellular organism development IEA --
GO:0007281 germ cell development IEA --
genes like me logo Genes that share ontologies with ANGPT2: view

Drugs & Compounds for ANGPT2 Gene

(26) Drugs for ANGPT2 Gene - From: DGIdb and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Trebananib Investigational Pharma inhibitor 33
AMG 386 Pharma inhibitor 0
CVX-060 Pharma antibody Others 0
MED13617 Pharma antagonist Angiopoietin 2 antagonist 0
MEDI3617 Pharma antibody 0

(14) Additional Compounds for ANGPT2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ANGPT2: view

Transcripts for ANGPT2 Gene

mRNA/cDNA for ANGPT2 Gene

3 REFSEQ mRNAs :
16 NCBI additional mRNA sequence :
4 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 ANGPT2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ANGPT2 Gene

No ASD Table

Relevant External Links for ANGPT2 Gene

GeneLoc Exon Structure for
ANGPT2

Expression for ANGPT2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ANGPT2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ANGPT2 Gene

This gene is overexpressed in Artery - Tibial (x4.9).

Protein differential expression in normal tissues from HIPED for ANGPT2 Gene

This gene is overexpressed in Urinary Bladder (64.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ANGPT2 Gene



Protein tissue co-expression partners for ANGPT2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ANGPT2

SOURCE GeneReport for Unigene cluster for ANGPT2 Gene:

Hs.583870

Evidence on tissue expression from TISSUES for ANGPT2 Gene

  • Nervous system(4.7)
  • Heart(4.7)
  • Lung(4.5)
  • Intestine(4.5)
  • Muscle(3)
  • Blood(2.8)
  • Kidney(2.6)
  • Spleen(2.5)
  • Liver(2.5)
  • Eye(2.5)
  • Lymph node(2.5)
  • Bone marrow(2.3)
  • Skin(2.2)
genes like me logo Genes that share expression patterns with ANGPT2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for ANGPT2 Gene

Orthologs for ANGPT2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ANGPT2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ANGPT2 30 31
  • 99.53 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ANGPT2 31
  • 90 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia ANGPT2 31
  • 90 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia ANGPT2 30 31
  • 88.6 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia ANGPT2 30 31
  • 87.47 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Angpt2 30 17 31
  • 81.01 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Angpt2 30
  • 80.94 (n)
Chicken
(Gallus gallus)
Aves ANGIOPOIETIN-2 31
  • 85 (a)
OneToOne
ANGPT2 30
  • 81.59 (n)
Lizard
(Anolis carolinensis)
Reptilia ANGPT2 31
  • 81 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia LOC100485272 30
  • 62.12 (n)
Zebrafish
(Danio rerio)
Actinopterygii angpt2a 30 31
  • 64.28 (n)
OneToOne
Species where no ortholog for ANGPT2 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)
  • 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)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • 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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ANGPT2 Gene

ENSEMBL:
Gene Tree for ANGPT2 (if available)
TreeFam:
Gene Tree for ANGPT2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ANGPT2: view image

Paralogs for ANGPT2 Gene

(13) SIMAP similar genes for ANGPT2 Gene using alignment to 2 proteins:

  • ANGP2_HUMAN
  • E7EVQ3_HUMAN
genes like me logo Genes that share paralogs with ANGPT2: view

Variants for ANGPT2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ANGPT2 Gene

SNP ID Clinical significance and condition Chr 08 pos Variation AA Info Type
715614 Benign: not provided 6,521,199(-) T/A MISSENSE_VARIANT,INTRON_VARIANT
723096 Benign: not provided 6,509,053(-) A/G SYNONYMOUS_VARIANT,INTRON_VARIANT
723421 Likely Benign: not provided 6,499,917(-) C/A MISSENSE_VARIANT,THREE_PRIME_UTR_VARIANT,INTRON_VARIANT
723650 Benign: not provided 6,521,273(-) A/G MISSENSE_VARIANT,INTRON_VARIANT
725884 Benign: not provided 6,519,986(-) C/G MISSENSE_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for ANGPT2 Gene

Structural Variations from Database of Genomic Variants (DGV) for ANGPT2 Gene

Variant ID Type Subtype PubMed ID
dgv2029e212 CNV loss 25503493
esv2422383 CNV duplication 17116639
esv2736532 CNV deletion 23290073
esv3616093 CNV loss 21293372
esv3616094 CNV gain 21293372
esv3891314 CNV gain 25118596
nsv1021684 CNV loss 25217958
nsv1022895 CNV loss 25217958
nsv1025860 CNV loss 25217958
nsv397733 CNV deletion 16902084
nsv522043 CNV loss 19592680
nsv610004 CNV gain 21841781
nsv958484 CNV deletion 24416366

Variation tolerance for ANGPT2 Gene

Residual Variation Intolerance Score: 19.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.17; 39.34% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ANGPT2 Gene

Human Gene Mutation Database (HGMD)
ANGPT2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ANGPT2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ANGPT2 Gene

Disorders for ANGPT2 Gene

MalaCards: The human disease database

(51) MalaCards diseases for ANGPT2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
placental insufficiency
  • uteroplacental vascular insufficiency
microvascular complications of diabetes 1
  • pdr
pyogenic granuloma
  • lobular capillary hemangioma
macular holes
  • macular hole
plasmodium vivax malaria
  • malaria by plasmodium vivax
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for ANGPT2

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 ANGPT2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ANGPT2 Gene

Publications for ANGPT2 Gene

  1. Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium. (PMID: 19223473) Yuan HT … Parikh SM (Molecular and cellular biology 2009) 3 4 23
  2. Biological characterization of angiopoietin-3 and angiopoietin-4. (PMID: 15284220) Lee HJ … Koh GY (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2004) 3 4 23
  3. Characterization and expression of a novel alternatively spliced human angiopoietin-2. (PMID: 10766762) Kim I … Koh GY (The Journal of biological chemistry 2000) 3 4 23
  4. Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface. (PMID: 19922791) Hansen TM … Brindle NP (Cellular signalling 2010) 3 23
  5. Angiopoietin-2 promotes disease progression of neuroendocrine tumors. (PMID: 20068079) Detjen KM … Scholz A (Clinical cancer research : an official journal of the American Association for Cancer Research 2010) 3 23

Products for ANGPT2 Gene

Sources for ANGPT2 Gene