Affinage

VPS51

Vacuolar protein sorting-associated protein 51 homolog · UniProt Q9UID3

Round 2 corrected
Length
782 aa
Mass
86.0 kDa
Annotated
2026-04-28
130 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VPS51 is a shared subunit of two heterotetrameric membrane-tethering complexes — GARP (with VPS52, VPS53, VPS54) at the trans-Golgi network and EARP (with VPS52, VPS53, syndetin) at recycling endosomes — that promote SNARE-dependent fusion of endosome-derived transport carriers (PMID:12446664, PMID:25799061). VPS51 assembles into these complexes via a conserved N-terminal coiled-coil that also engages TGN SNAREs (Syntaxin 6 in mammals; Tlg1 in yeast), thereby coordinating tethering with fusion-competent SNARE complex formation (PMID:16420526, PMID:20685960). Through GARP, VPS51 supports retrograde endosome-to-Golgi retrieval of cargo such as the cation-independent mannose 6-phosphate receptor, endosomal cholesterol trafficking, lysosomal enzyme sorting, and autophagy; through EARP, it facilitates recycling of endocytic receptors to the plasma membrane (PMID:20685960, PMID:25799061). Biallelic loss-of-function mutations in VPS51 cause a severe neurodevelopmental disorder with microcephaly, pontocerebellar abnormalities, epilepsy, and lysosomal dysfunction, linked to impaired GARP/EARP complex assembly and defective retrograde trafficking (PMID:30624672, PMID:31207318).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2002 High

    Identification of Vps51 as the fourth subunit of the yeast VFT/GARP tethering complex established that retrograde endosome-to-Golgi transport and autophagosome biogenesis require a dedicated tethering factor beyond Vps52–54.

    Evidence Genetic deletion, reciprocal co-IP, fluorescence microscopy, and prApe1 maturation assays in S. cerevisiae

    PMID:12446664

    Open questions at the time
    • No structural information on Vps51 or its contacts within the GARP complex
    • Mechanism by which Vps51 contributes to autophagosome size regulation unknown
  2. 2006 High

    A crystal structure of the Tlg1 N-terminal domain bound to a Vps51 peptide revealed the molecular basis for SNARE engagement but showed this interaction is dispensable for retrograde transport, raising the question of what other tethering contacts are essential.

    Evidence X-ray crystallography of Tlg1–Vps51 peptide complex; in vivo trafficking assays with Vps51 truncation mutants in yeast

    PMID:16420526

    Open questions at the time
    • Essential Vps51 domains for vesicle docking and fusion remain unidentified
    • No structure of full-length Vps51 or intact GARP complex
  3. 2010 High

    Demonstration that human Ang2/VPS51 is the missing fourth subunit of mammalian GARP extended the complex to metazoans and connected it to Syntaxin 6 engagement, lysosomal enzyme sorting, cholesterol trafficking, and autophagy.

    Evidence Yeast two-hybrid, co-IP, biochemical fractionation, siRNA knockdown with CI-MPR, filipin, and LC3 flux assays in human cells

    PMID:20685960

    Open questions at the time
    • Relative contributions of GARP versus other tethers to each trafficking pathway not delineated
    • Whether VPS51 has functions independent of the GARP complex was untested
  4. 2011 High

    Genetic analysis in C. elegans showed GARP (including Vps51) is conserved in metazoans and functionally overlaps with the COG complex, establishing redundancy among Golgi-resident tethers.

    Evidence Genetic deletion/RNAi, yeast two-hybrid SNARE binding, lysosome morphology, and synthetic lethality with COG mutants in C. elegans

    PMID:21613545

    Open questions at the time
    • Molecular basis of GARP–COG functional overlap not resolved
    • Tissue-specific requirements for Vps51 in multicellular organisms unexplored
  5. 2015 High

    Discovery of the EARP complex revealed that VPS51 is shared between two functionally distinct tethering complexes — GARP at the TGN and EARP at recycling endosomes — with the differential fourth subunit (VPS54 vs. syndetin) dictating localization and cargo specificity.

    Evidence AP-MS, reciprocal co-IP, confocal immunofluorescence, and transferrin recycling assays with siRNA knockdown in human cells

    PMID:25799061

    Open questions at the time
    • Mechanism by which VPS51 switches between GARP and EARP assembly is unknown
    • Structural basis for EARP-specific localization to recycling endosomes not determined
  6. 2019 High

    Identification of biallelic VPS51 mutations in patients with severe neurodevelopmental disease, supported by impaired GARP/EARP assembly and retrograde trafficking defects in patient cells, established VPS51 as a disease gene and demonstrated that both complexes are required for normal brain development.

    Evidence Exome sequencing, proteasome inhibitor rescue of mutant protein, co-IP for complex assembly, CI-MPR and lysosome morphology in patient fibroblasts; independent family with homozygous deletion confirmed by homozygosity mapping

    PMID:30624672 PMID:31207318

    Open questions at the time
    • Cell-type-specific contributions (neuronal vs. glial) of VPS51 loss to brain malformation not resolved
    • Whether residual EARP function partially compensates for GARP loss (or vice versa) in patient cells is unknown
    • No animal model recapitulating the full human phenotype has been reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of the intact GARP and EARP complexes, the mechanism governing VPS51 partitioning between GARP and EARP, and the neuron-specific pathways through which VPS51 deficiency leads to pontocerebellar hypoplasia.
  • No high-resolution structure of full-length VPS51 or assembled GARP/EARP complexes
  • Regulatory mechanisms controlling VPS51 allocation between GARP and EARP are unknown
  • Neuron-type-specific vulnerability to VPS51 loss not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3
Localization
GO:0005794 Golgi apparatus 3 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 2
Partners
STX6SYNDETINTLG1VPS52VPS53VPS54
Complex memberships
EARP (VPS51–VPS52–VPS53–syndetin)GARP (VPS51–VPS52–VPS53–VPS54)

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Yeast Vps51 (Ykr020w) is a subunit of the Vps fifty-three (VFT/GARP) tethering complex, composed of Vps52, Vps53, and Vps54. Vps51 is required for retrograde traffic from the early endosome back to the late Golgi and for Cvt vesicle formation. Loss of Vps51 blocks correct targeting of the prApe1-Cvt19-Cvt9 complex to the preautophagosomal structure and reduces autophagosome size. Genetic deletion, co-immunoprecipitation, fluorescence microscopy, maturation assays for prApe1 and Ape1 The Journal of biological chemistry High 12446664
2006 The N-terminal domain of yeast Tlg1 (a TGN SNARE) binds directly to a short N-terminal peptide (residues 18–30) of Vps51, forming a helix that docks into a conserved groove of Tlg1's three-helix bundle. Despite this physical interaction, deletion of the Tlg1-binding sequences from Vps51 does not block endosome-to-Golgi transport in vivo, indicating this interaction is not essential for vesicle docking or fusion. X-ray crystallography of Tlg1 N-terminal domain bound to Vps51 peptide; in vivo trafficking assays with truncation mutants Traffic (Copenhagen, Denmark) High 16420526
2010 Human Ang2 (the VPS51 ortholog, also called Fat-free) is the missing fourth subunit of the human GARP complex, interacting with human Vps52, Vps53, and Vps54 in an obligatory 1:1:1:1 stoichiometry. Human Ang2/VPS51 exhibits significant homology to yeast Vps51p in an N-terminal coiled-coil region that mediates assembly with other GARP subunits. The complex strongly interacts with the regulatory Habc domain of the TGN SNARE Syntaxin 6. Depletion of Ang2/VPS51 impairs protein retrieval to the TGN, lysosomal enzyme sorting, endosomal cholesterol trafficking, and autophagy. Yeast two-hybrid screen, co-immunoprecipitation, biochemical fractionation, siRNA knockdown with functional trafficking assays (CI-MPR distribution, filipin staining for cholesterol, LC3 flux) Molecular biology of the cell High 20685960
2011 The C. elegans GARP complex contains a conserved Vps51 subunit. GARP mutants are viable but display lysosomal morphology defects. C. elegans GARP subunits bind specific sets of Golgi SNAREs in yeast two-hybrid assays, consistent with a role in tethering and SNARE complex assembly at the Golgi. Loss of both GARP and COG tethering complexes produces a synthetic lethal phenotype, indicating overlapping functions in retrograde endosome-to-Golgi retrieval. Genetic deletion/RNAi, yeast two-hybrid, lysosome morphology assays, synthetic lethality screen Molecular biology of the cell High 21613545
2015 EARP (endosome-associated recycling protein) is a heterotetrameric tethering complex that shares three subunits with GARP — Ang2/VPS51, Vps52, and Vps53 — but contains syndetin instead of Vps54. The differential fourth subunit determines distinct localization: EARP localizes to recycling endosomes while GARP localizes to the TGN. EARP interacts with syntaxin 6 and promotes fusion of endocytic carriers with recycling endosomes; depletion of syndetin or syntaxin 6 delays transferrin recycling to the cell surface. Affinity purification–mass spectrometry, co-immunoprecipitation, confocal immunofluorescence, transferrin recycling assays with siRNA knockdown Nature cell biology High 25799061
2019 Compound heterozygous mutations in VPS51 cause a severe neurodevelopmental disorder in humans, characterized by global developmental delay, microcephaly, epilepsy, pontocerebellar abnormalities, and liver dysfunction. One allele produces a frameshift generating a longer but unstable protein degraded by the proteasome; the other produces a stable protein with a single amino acid substitution that assembles less efficiently with other GARP/EARP subunits. Patient fibroblasts have reduced levels of fully assembled GARP and EARP complexes, show altered distribution of the cation-independent mannose 6-phosphate receptor (CI-MPR), and exhibit lysosomal swelling in a fraction of cells. Exome sequencing, protein stability assays (proteasome inhibitor rescue), co-immunoprecipitation to measure complex assembly, CI-MPR immunofluorescence, lysosome morphology by microscopy Human molecular genetics High 30624672
2019 A homozygous intragenic deletion in VPS51 was identified in two siblings with postnatal microcephaly, severe intellectual disability, cerebellar atrophy, and hypoplastic corpus callosum, independently confirming VPS51 as a genetic locus for neurodevelopmental brain malformations and establishing that VPS51-dependent GARP/EARP function is required for normal brain development. Whole exome sequencing, homozygosity mapping European journal of medical genetics Medium 31207318

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer cell 517 21481792
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2011 A directed protein interaction network for investigating intracellular signal transduction. Science signaling 258 21900206
2016 Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages. Proceedings of the National Academy of Sciences of the United States of America 257 27044097
2016 Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment. Cancer cell 252 27960088
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
2013 Ang-2-VEGF-A CrossMab, a novel bispecific human IgG1 antibody blocking VEGF-A and Ang-2 functions simultaneously, mediates potent antitumor, antiangiogenic, and antimetastatic efficacy. Clinical cancer research : an official journal of the American Association for Cancer Research 154 24097868
2018 Discovery and Characterization of ZUFSP/ZUP1, a Distinct Deubiquitinase Class Important for Genome Stability. Molecular cell 150 29576527
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2019 The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2. Molecular cell 124 30639242
2010 A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in combination with VEGF inhibitors and chemotherapy agents in preclinical models. Molecular cancer therapeutics 123 20053776
1977 Sources of frequency following responses (FFR) in man. Electroencephalography and clinical neurophysiology 122 67025
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2003 Human cytotrophoblasts promote endothelial survival and vascular remodeling through secretion of Ang2, PlGF, and VEGF-C. Developmental biology 96 14568550
2015 EARP is a multisubunit tethering complex involved in endocytic recycling. Nature cell biology 95 25799061
2002 Vps51 is part of the yeast Vps fifty-three tethering complex essential for retrograde traffic from the early endosome and Cvt vesicle completion. The Journal of biological chemistry 94 12446664
2008 FOXC2 controls Ang-2 expression and modulates angiogenesis, vascular patterning, remodeling, and functions in adipose tissue. Proceedings of the National Academy of Sciences of the United States of America 92 18621714
2020 Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nature communications 90 32814769
2020 Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases. Molecular cell 88 32707033
2021 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Molecular systems biology 86 34709727
2022 Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression. The Journal of clinical investigation 71 35763346
2010 Ang2/fat-free is a conserved subunit of the Golgi-associated retrograde protein complex. Molecular biology of the cell 71 20685960
2015 A Phase I First-in-Human Study of Nesvacumab (REGN910), a Fully Human Anti-Angiopoietin-2 (Ang2) Monoclonal Antibody, in Patients with Advanced Solid Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 66 26490310
2000 Early effects of hypoxia/reoxygenation on VEGF, ang-1, ang-2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. Molecular and cellular biochemistry 66 11129953
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2015 Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation. Science signaling 61 25921289
2016 IL-35 Inhibits Angiogenesis through VEGF/Ang2/Tie2 Pathway in Rheumatoid Arthritis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 54 27960151
2019 A neurodevelopmental disorder caused by mutations in the VPS51 subunit of the GARP and EARP complexes. Human molecular genetics 51 30624672
2006 Structural analysis of the interaction between the SNARE Tlg1 and Vps51. Traffic (Copenhagen, Denmark) 46 16420526
2004 Hepatic expression of ANG2 RNA in metastatic colorectal cancer. Hepatology (Baltimore, Md.) 46 14768007
2020 Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma. Cancers 45 31991869
2009 Increased angiogenesis induced by chronic lymphocytic leukemia B cells is mediated by leukemia-derived Ang2 and VEGF. Leukemia research 45 19616847
2005 Purification and characterization of a furfural reductase (FFR) from Escherichia coli strain LYO1--an enzyme important in the detoxification of furfural during ethanol production. Journal of biotechnology 45 16111779
2019 A collagen IV-derived peptide disrupts α5β1 integrin and potentiates Ang2/Tie2 signaling. JCI insight 42 30668550
2010 Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute myeloid leukaemia and endothelial cells: studies of Tie-2 blocking antibodies, exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release. Expert opinion on investigational drugs 40 20050812
2007 Conditional activation of FGFR1 in the prostate epithelium induces angiogenesis with concomitant differential regulation of Ang-1 and Ang-2. Oncogene 40 17297442
2025 Durability and efficacy of solbinsiran, a GalNAc-conjugated siRNA targeting ANGPTL3, in adults with mixed dyslipidaemia (PROLONG-ANG3): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet (London, England) 39 40179932
2021 Ang2 inhibitors and Tie2 activators: potential therapeutics in perioperative treatment of early stage cancer. EMBO molecular medicine 38 34125494
2011 Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang-2. The Prostate 38 21809353
2002 Dual role of Ang2 in postnatal angiogenesis and lymphangiogenesis. Developmental cell 38 12361591
2021 Subcortical rather than cortical sources of the frequency-following response (FFR) relate to speech-in-noise perception in normal-hearing listeners. Neuroscience letters 34 33497718
2018 Ang-2 promotes lung cancer metastasis by increasing epithelial-mesenchymal transition. Oncotarget 33 29560103
2011 Expression of Ets-1, Ang-2 and maspin in ovarian cancer and their role in tumor angiogenesis. Journal of experimental & clinical cancer research : CR 32 21439064
2014 Arabidopsis UNHINGED encodes a VPS51 homolog and reveals a role for the GARP complex in leaf shape and vein patterning. Development (Cambridge, England) 31 24757006
2014 miRNA-dependent cross-talk between VEGF and Ang-2 in hypoxia-induced microvascular dysfunction. Biochemical and biophysical research communications 30 25172656
2011 Radiation attenuates physiological angiogenesis by differential expression of VEGF, Ang-1, tie-2 and Ang-2 in rat brain. Radiation research 30 21962003
2007 Angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2) and Tie-2 (a receptor tyrosine kinase) concentrations in peripheral blood of patients with thyroid cancers. Cytokine 30 17374490
2020 Timed Ang2-Targeted Therapy Identifies the Angiopoietin-Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis. Cancer discovery 28 33106316
2011 A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesis. Microcirculation (New York, N.Y. : 1994) 28 21851472
2024 Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 27 39708087
2020 Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis. Phytomedicine : international journal of phytotherapy and phytopharmacology 27 32823242
2014 Placental mRNA expression of angiopoietins (Ang)-1, Ang-2 and their receptor Tie-2 is altered in pregnancies complicated by preeclampsia. Placenta 27 25047691
2010 ChIP-on-chip analysis reveals angiopoietin 2 (Ang2, ANGPT2) as a novel target of steroidogenic factor-1 (SF-1, NR5A1) in the human adrenal gland. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 21163858
2009 A designed angiopoietin-2 variant, pentameric COMP-Ang2, strongly activates Tie2 receptor and stimulates angiogenesis. Biochimica et biophysica acta 27 19339208
2001 Pharmacokinetics and safety of FFR-rFVIIa after single doses in healthy subjects. Journal of clinical pharmacology 27 11504276
2006 Regulation of Ang2 release by PTEN/PI3-kinase/Akt in lung microvascular endothelial cells. Journal of cellular physiology 26 16447257
2010 Reduced plasma levels of Ang-2 and sEng as novel biomarkers in hereditary hemorrhagic telangiectasia (HHT). Clinica chimica acta; international journal of clinical chemistry 25 20067780
2015 Puerarin accelerate scardiac angiogenesis and improves cardiac function of myocardial infarction by upregulating VEGFA, Ang-1 and Ang-2 in rats. International journal of clinical and experimental medicine 24 26885006
2011 The Caenorhabditis elegans GARP complex contains the conserved Vps51 subunit and is required to maintain lysosomal morphology. Molecular biology of the cell 23 21613545
2020 Nintedanib and a bi-specific anti-VEGF/Ang2 nanobody selectively prevent brain metastases of lung adenocarcinoma cells. Clinical & experimental metastasis 22 32918638
2019 VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report. European journal of medical genetics 22 31207318
2019 Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock. Scandinavian journal of immunology 22 31489646
2021 Long noncoding TUG1 promotes angiogenesis of HUVECs in PE via regulating the miR-29a-3p/VEGFA and Ang2/Tie2 pathways. Microvascular research 20 34352236
2019 2,7-Dibromocarbazole interferes with tube formation in HUVECs by altering Ang2 promoter DNA methylation status. The Science of the total environment 20 32380619
2023 ANG2 Blockade Diminishes Proangiogenic Cerebrovascular Defects Associated With Models of Hereditary Hemorrhagic Telangiectasia. Arteriosclerosis, thrombosis, and vascular biology 18 37288572
2022 Ang2-Targeted Combination Therapy for Cancer Treatment. Frontiers in immunology 18 35874764
2019 PRSS21/testisin inhibits ovarian tumor metastasis and antagonizes proangiogenic angiopoietins ANG2 and ANGPTL4. Journal of molecular medicine (Berlin, Germany) 18 30911775
2013 Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2. Chinese journal of natural medicines 18 23725836
2020 LncRNA EPIC1 promotes tumor angiogenesis via activating the Ang2/Tie2 axis in non-small cell lung cancer. Life sciences 17 33359744
2008 Vascular dynamics in relation to immunolocalisation of VEGF-A, VEGFR-2 and Ang-2 in the bovine corpus luteum. Acta histochemica 17 18541291
2021 Targeting the Ang2/Tie2 Axis with Tanshinone IIA Elicits Vascular Normalization in Ischemic Injury and Colon Cancer. Oxidative medicine and cellular longevity 16 34804370
2021 BMAL1 may be involved in angiogenesis and peritumoral cerebral edema of human glioma by regulating VEGF and ANG2. Aging 16 34815366
2012 Over-expression of VEGF in marrow stromal cells promotes angiogenesis in rats with cerebral infarction via the synergistic effects of VEGF and Ang-2. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban 16 23073804
2009 Association of Ang-2 with integrin beta 2 controls Ang-2/PDGF-BB-dependent upregulation of human peripheral blood monocyte fibrinolysis. Inflammation 16 19728062
2021 Real-world clinical and cost analysis of CT coronary angiography and CT coronary angiography-derived fractional flow reserve (FFRCT)-guided care in the National Health Service. Clinical radiology 15 34261595
2010 Real-time PCR study of Ang1, Ang2, Tie-2, VEGF, and KDR expression in human erectile tissue during aging. The journal of sexual medicine 14 21091880
2004 Differential regulation of ANG2 and VEGF-A in human granulosa lutein cells by choriogonadotropin. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 13 15127326
2022 Biochemical and genomic identification of novel biomarkers in progressive sarcoidosis: HBEGF, eNAMPT, and ANG-2. Frontiers in medicine 12 36388923
2019 Propranolol inhibits proliferation and induces apoptosis of hemangioma-derived endothelial cells via Akt pathway by down-regulating Ang-2 expression. Chemico-biological interactions 12 31838054
2016 Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1. Scientific reports 12 27784899
2015 Delayed vasculogenesis and impaired angiogenesis due to altered Ang-2 and VE-cadherin levels in the chick embryo model following exposure to cadmium. Pediatric surgery international 12 26628413
2009 The ang3 mutation identified the ribosomal protein gene RPL5B with a role in cell expansion during organ growth. Physiologia plantarum 12 19878482
2007 Ang-2 and PDGF-BB cooperatively stimulate human peripheral blood monocyte fibrinolysis. Journal of leukocyte biology 12 17395886
2023 The impact of early RPE cell junction loss on VEGF, Ang-2, and TIMP secretion in vitro. Molecular vision 11 37859808
2020 Effect of Chitosan Magnetic Nanoparticles Loaded with Ang2-siRNA Plasmids on the Growth of Melanoma Xenografts in Nude Mice. Cancer management and research 11 32904466
2006 Angiopoietin-1, 2 and Tie2 expressions in endometrial adenocarcinoma--the Ang2 dominant balance up-regulates tumor angiogenesis in the presence of VEGF. European journal of gynaecological oncology 11 16620053
2025 Clematichinenoside AR alleviates rheumatoid arthritis by inhibiting synovial angiogenesis through the HIF-1α/VEGFA/ANG2 axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 10 40020629
2020 Role of the Ang2-Tie2 Axis in Vascular Damage Driven by High Glucose or Nucleoside Diphosphate Kinase B Deficiency. International journal of molecular sciences 10 32466219
2016 A bispecific antibody (ScBsAbAgn-2/TSPO) target for Ang-2 and TSPO resulted in therapeutic effects against glioblastomas. Biochemical and biophysical research communications 10 26898800
2011 VEGF-A not Ang2 mediates endothelial-like differentiation of immature DCs by ERK1/2 signaling in the microenvironment of human colon adenocarcinoma. International journal of oncology 9 21455573
2010 VEGF, Ang-2 and SRIF associated abnormal postnatal development of the retinal capillary network in the Royal College of Surgeons rat. Experimental eye research 9 21147101
2023 The expression analyses of GSK3B, VEGF, ANG1, and ANG2 in human brain microvascular endothelial cells treated with the synthetic cannabinoid XLR-11. Gene 8 37355149
2021 IL-8, MSPa, MIF, FGF-9, ANG-2 and AgRP collection were identified for the diagnosis of colorectal cancer based on the support vector machine model. Cell cycle (Georgetown, Tex.) 8 33779485
2021 Intrinsic differences in the mechanisms of Tie2 binding to angiopoietins exploited by directed evolution to create an Ang2-selective ligand trap. The Journal of biological chemistry 8 34153320
2018 Development of an Orthogonal Tie2 Ligand Resistant to Inhibition by Ang2. Molecular pharmaceutics 8 30036484
2016 Safety and toxicology of the intravenous administration of Ang2‑siRNA plasmid chitosan magnetic nanoparticles. Molecular medicine reports 8 28035391
2013 Forward mandibular positioning enhances the expression of Ang-1 and Ang-2 in rabbit condylar chondrocytes. Molecular medicine reports 8 23934380
2012 Plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer. European cytokine network 8 22449617
2012 Expression and regulation of Ang-2 in murine ovaries during sexual maturation and development of corpus luteum. Molekuliarnaia biologiia 8 23350236
2008 Differential expression of VEGFA, TIE2, and ANG2 but not ADAMTS1 in rat mesenteric microvascular arteries and veins. Physiological research 8 18380533
2023 miR-221-3p targets Ang-2 to inhibit the transformation of HCMECs to tip cells. Journal of cellular and molecular medicine 7 37525394
2023 Ang-2 is a potential molecular marker for lymphatic metastasis and better response to bevacizumab therapy in ovarian cancer. Journal of cancer research and clinical oncology 7 37684509
2022 Anti-angiogenic effects of aqueous extract from Agrostemma githago L. seed in human umbilical vein endothelial cells via regulating Notch/VEGF, MMP2/9, ANG2, and VEGFR2. Environmental science and pollution research international 7 36287364
2018 Immunohistochemical determination of Ang-1, Ang-2 and Tie-2 in placentas of sows at 30, 60 and 114 days of gestation and validation through a bioinformatic approach. Animal reproduction science 7 29885854
2023 The synthetic cannabinoid 5F-MDMB-PICA enhances the metabolic activity and angiogenesis in human brain microvascular endothelial cells by upregulation of VEGF, ANG-1, and ANG-2. Toxicology research 6 37915478
2022 Newly-established in vitro inner BRB spheroids to elucidate retinal Ang2-linked substance transfer. Journal of controlled release : official journal of the Controlled Release Society 6 36122894
2022 Vitreous protein networks around ANG2 and VEGF in proliferative diabetic retinopathy and the differential effects of aflibercept versus bevacizumab pre-treatment. Scientific reports 6 36473885
2016 Reduced Ang2 expression in aging endothelial cells. Biochemical and biophysical research communications 6 27137842
2015 Combined Ang-2 and VEGF serum levels: holding hands as a new integral biomarker in non-small-cell lung cancers. Future oncology (London, England) 6 26562248
2010 Minimally invasive colorectal resection for cancer is associated with a short-lived decrease in soluble Tie-2 receptor levels, which may transiently inhibit VEGF-mediated angiogenesis (via altered blood levels of free Ang-1 and Ang-2). Surgical endoscopy 6 20354881
2017 Evaluation of Plasma Growth Factors (VEGF, PDGF, EGF, ANG1, and ANG2) in Patients with Varicose Veins Before and After Treatment with Endovenous Laser Ablation. Photomedicine and laser surgery 5 29173075
2016 T3 enhances Ang2 in rat aorta in myocardial I/R: comparison with left ventricle. Journal of molecular endocrinology 5 27444191
2010 Characterization of the expression of Ang1, Ang2, and Tie2 in the Corpus Cavernosum of the rat during aging. Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada 5 20969813