Affinage

HGS

Hepatocyte growth factor-regulated tyrosine kinase substrate · UniProt O14964

Length
777 aa
Mass
86.2 kDa
Annotated
2026-06-10
71 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HGS (mammalian Vps27/Hrs) is the core ESCRT-0 component that initiates sorting of ubiquitinated transmembrane cargo into multivesicular bodies (MVBs) at the early/prevacuolar endosome (PMID:12900393, PMID:7593183). It achieves compartmental specificity through a FYVE domain that binds phosphatidylinositol 3-phosphate (PI3P), couples this to ubiquitin recognition via tandem UIMs that each fold as autonomous helices engaging the Ile44 hydrophobic patch of ubiquitin, and recruits downstream ESCRT-I through PSDP/PTVP C-terminal motifs that contact Vps23 (PMID:12900393, PMID:12970172, PMID:14581452). HGS partners with Hse1 to form a barbell-like scaffold built from intertwined GAT domains and an antiparallel coiled coil that juxtaposes the cargo-, ubiquitin-, and deubiquitinase-binding surfaces for cooperative recognition of ubiquitinated membrane proteins (PMID:14581452, PMID:17543868). PI3P-dependent recruitment and PDK1-family (Pkh1/Pkh2) phosphorylation at a conserved serine gate the membrane recruitment of HGS and downstream ESCRT-I assembly, linking HGS function to both MVB sorting and microautophagy (PMID:22918958, PMID:34798133). Beyond cargo degradation, HGS scaffolds TGF-β/activin and BMP signaling by recruiting Smad2 and Smad5 and by localizing TAK1 to early endosomes for activation, with a C-terminal-deletion knock-in being embryonic lethal (PMID:11094085, PMID:21953618, PMID:16516194). HGS also directs endosome-to-ER cholesterol transport independently of other ESCRT subunits, controls exosome size downstream of TP53, and is required for myoblast differentiation and cardiac proteostasis through autophagy and lysosomal homeostasis (PMID:22832105, PMID:27312428, PMID:34330273, PMID:35342336). A point mutation in mouse Hgs (teetering) disrupts neuromuscular junction structure and synaptic transmission, establishing an in vivo neuronal requirement (PMID:26115514). HGS is exploited during infection: it traffics the coronavirus M protein to the ERGIC and forms enlarged HGS+ compartments that serve as virion assembly sites, and a small molecule disrupting the HGS–M interaction blocks assembly (PMID:41401029).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Established that the HGS ortholog Vps27 is a functional gatekeeper of the prevacuolar/endosomal compartment used by both biosynthetic and endocytic traffic, defining the cellular compartment at which HGS acts.

    Evidence temperature-sensitive VPS27 allele with trafficking and restoration assays in yeast

    PMID:7593183

    Open questions at the time
    • Did not define the molecular interactions through which Vps27 acts
    • Mammalian relevance not yet established
  2. 2000 High

    Showed HGS is not solely an endosomal sorting factor but a signaling scaffold that recruits Smad2 to TGF-β/activin receptors, with in vivo essentiality demonstrated by an embryonic-lethal knock-in.

    Evidence Co-IP, knock-in mouse genetics, and reporter assays

    PMID:11094085

    Open questions at the time
    • Spatial coupling of Smad recruitment to endosomes not yet shown
    • Whether scaffolding and ESCRT functions are separable unresolved
  3. 2001 Medium

    Extended HGS scaffolding to stress/MAPK signaling by linking it to TAK1 and Pak1 and to IL-2-induced c-fos promoter activation.

    Evidence Co-IP and SRE/CRE reporter assays with dominant-negative constructs

    PMID:11397816

    Open questions at the time
    • Single lab, no structural mapping of interactions
    • Endosomal dependence of TAK1/Pak1 activation not tested here
  4. 2002 Medium

    Defined the molecular basis of HGS membrane targeting (FYVE/PI3P) and revealed a UIM-dependent autoregulatory loop in which HGS recruits Nedd4 to self-ubiquitylate and limit receptor degradation.

    Evidence Co-IP, domain deletion, dominant-negative overexpression, endosome fractionation

    PMID:12230472

    Open questions at the time
    • Single lab
    • Stoichiometry and physiological scope of self-ubiquitylation unresolved
  5. 2003 High

    Resolved the atomic logic of cargo capture: tandem UIMs independently bind ubiquitin, the C-terminal PTVP/PSDP motifs directly recruit ESCRT-I, and Vps27 forms a ubiquitin-sorting receptor with Hse1, with FYVE-PI3P providing compartmental specificity.

    Evidence NMR structures, mutagenesis, lipid-binding and MVB sorting assays in yeast

    PMID:12900393 PMID:12970172 PMID:14581452

    Open questions at the time
    • Higher-order architecture of the assembled receptor not yet resolved
    • Quantitative cargo handoff kinetics to ESCRT-I not defined
  6. 2003 Low

    Showed HGS acts as an inhibitor of TGF-β1 signaling in primary T cells, indicating context-dependent signaling outcomes.

    Evidence mRNA quantification, reporter assays, overexpression in primary CD4+ T cells

    PMID:12554698

    Open questions at the time
    • No direct biochemical mechanism beyond reduced reporter output
    • Single lab, not independently confirmed
  7. 2006 Medium

    Identified Smad5 as a direct HGS partner and positioned HGS as a negative regulator of BMP transcriptional responses.

    Evidence cDNA library screen, Co-IP, BMP reporter assays

    PMID:16516194

    Open questions at the time
    • Inhibitory versus required role for BMP signaling not reconciled with later in vivo data
    • Single lab
  8. 2007 High

    Provided the structural scaffold model: the Vps27/Hse1 core forms intertwined GAT domains joined by a coiled coil into a barbell that positions cargo- and DUB-binding modules for cooperative recognition.

    Evidence 3.0 Å crystal structure, sedimentation equilibrium, Monte Carlo simulations

    PMID:17543868

    Open questions at the time
    • Membrane-bound assembly not captured experimentally
    • Dynamics of cooperative ubiquitin/lipid binding inferred from simulation
  9. 2007 Medium

    Demonstrated conservation of HGS function in membrane biogenesis beyond MVB sorting, showing the fission yeast ortholog is required for forespore membrane formation in a FYVE/PI3K- and Hse1-dependent manner.

    Evidence GFP localization, two-hybrid/Co-IP, UIM mutants, spore viability assays

    PMID:17951524

    Open questions at the time
    • Mammalian counterpart of sporulation role undefined
    • Single organism
  10. 2011 Medium

    Connected HGS scaffolding to developmental BMP output in vivo by showing HGS localizes TAK1 to early endosomes to enable SMAD1/5/8 and TAK1/p38 phosphorylation.

    Evidence mouse knockout, phospho-immunoblotting, TAK1 localization imaging

    PMID:21953618

    Open questions at the time
    • Reconciliation with HGS as a BMP inhibitor not addressed
    • Direct kinase-scaffold contacts at endosome not structurally mapped
  11. 2012 Medium

    Separated HGS's cholesterol-transport role from its degradative role, showing HGS specifically routes LDL-derived cholesterol from endosomes to the ER.

    Evidence siRNA knockdown, filipin staining, fractionation in mammalian cells

    PMID:22832105

    Open questions at the time
    • Molecular machinery linking HGS to ER cholesterol delivery unknown
    • Single lab
  12. 2012 Medium

    Established phospho-regulation and a PI3P-dependent recruitment axis for HGS recruitment and ESCRT-I assembly, extending its role to microautophagy.

    Evidence in vitro kinase assays, S613A mutant, forced-membrane-targeting rescue in yeast

    PMID:22918958 PMID:34798133

    Open questions at the time
    • Mammalian HGS phosphosite regulation not demonstrated
    • Direct kinase identity in mammals unknown
  13. 2015 High

    Demonstrated an in vivo neuronal requirement: a point mutation in mouse Hgs disrupts NMJ structure, synaptic transmission, and protein/myelin homeostasis.

    Evidence positional cloning, EM, NMJ electrophysiology, western blot

    PMID:26115514

    Open questions at the time
    • Which HGS cargo defects drive the synaptic phenotype unresolved
    • Cell-autonomous versus systemic contributions not separated
  14. 2015 Medium

    Revealed tissue-specific physiological roles and a cancer-context dependency, showing HGS is required for esophageal smooth-muscle motility and is synthetic lethal with oncogenic CTNNB1.

    Evidence SMC-specific KO with contractility assays; kinome siRNA screen with isogenic CTNNB1 pairs

    PMID:26078721 PMID:26715116

    Open questions at the time
    • Mechanism linking HGS loss to apoptosis in β-catenin-active cells undefined
    • Single labs
  15. 2015 Medium

    Identified a ubiquitin-independent role for HGS in viral egress, promoting HBV naked-capsid secretion while suppressing HBV replication.

    Evidence siRNA/overexpression, in vivo hydrodynamic delivery, Co-IP, confocal microscopy

    PMID:26431433

    Open questions at the time
    • Molecular basis of the ubiquitin-independent HBc association unclear
    • Single lab
  16. 2016 Medium

    Linked HGS expression to exosome biogenesis under TP53 control, showing HGS levels set exosome size downstream of TP53 status.

    Evidence iTRAQ proteomics, HGS knockdown/overexpression, nanoparticle tracking in isogenic TP53 cells

    PMID:27312428

    Open questions at the time
    • Direct transcriptional regulation of HGS by TP53 not shown
    • Functional consequence of altered exosome size undefined
  17. 2021 Medium

    Connected HGS to muscle differentiation and proteostasis, showing HGS depletion blocks myogenesis via MEK/ERK, Akt2, FOXO1/GSK3β dysregulation and impaired autophagy, with pathway inhibitors rescuing differentiation.

    Evidence knockdown with pharmacological rescue in C2C12 and human myoblasts

    PMID:34330273

    Open questions at the time
    • How loss of endosomal sorting feeds into these signaling changes unclear
    • Single lab
  18. 2022 Medium

    Demonstrated that cardiomyocyte HGS maintains lysosomal homeostasis and proteostasis, with loss causing a restrictive-cardiomyopathy phenotype reversible by suppressing protein aggregation.

    Evidence cardiomyocyte-specific KO, proteomics, EM, doxycycline rescue, cardiac function assays

    PMID:35342336

    Open questions at the time
    • Causal hierarchy between cholesterol/lysosomal defects and aggregation not resolved
    • Single lab
  19. 2025 High

    Established HGS as a host factor co-opted for coronavirus assembly, trafficking the M protein to the ERGIC and forming enlarged HGS+ compartments as virion assembly sites, druggable by disrupting the HGS–M interaction.

    Evidence genome-wide CRISPRi screen, Co-IP, fractionation/imaging, APEX2-EM/cryo-CLEM, in vivo antiviral and drug/peptide assays (one report a preprint)

    PMID:41401029 PMID:bio_10.1101_2025.10.25.684511

    Open questions at the time
    • Whether ESCRT-0 sorting activity is required for M trafficking unresolved
    • Origin/membrane identity of HGS+ assembly compartments only partly defined
  20. 2025 Low

    Reported HGS as a target of pathogen effectors, with Salmonella SopB binding HGS ubiquitin-binding domains and recruiting ESCRT-0 to the Salmonella-containing vacuole.

    Evidence Virotrap mass spectrometry, Co-IP with UIM constructs, colocalization (preprint)

    PMID:bio_10.1101_2025.08.19.669813

    Open questions at the time
    • Single preprint; functional consequence on intracellular survival not established
    • Pathway placement proposed rather than demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how HGS's single biochemical core (PI3P/ubiquitin/ESCRT-I recognition) is partitioned among its many cellular outputs — MVB sorting, Smad/TAK1 signaling, cholesterol transport, exosome biogenesis, and viral assembly — and whether these reflect separable molecular activities or one shared mechanism deployed in different compartments.
  • No study dissects which HGS molecular surface drives each non-canonical role
  • Mammalian structural model of the assembled cargo receptor on membranes lacking
  • Mechanistic basis of context-dependent signaling (activating vs inhibitory) unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005768 endosome 3 GO:0005764 lysosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9612973 Autophagy 3 R-HSA-1643685 Disease 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
NEDD4PAK1SMAD2SMAD5STAMTAK1TSG101
Complex memberships
ESCRT-0 (HGS/Hse1-STAM)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Vps27 (HGS ortholog) recruits ESCRT-I to endosomal membranes through direct binding via a PTVP-containing motif in its C-terminus; FYVE domain-mediated binding to phosphatidylinositol 3-phosphate provides compartmental specificity for the MVB sorting reaction, and both interactions are required for ubiquitinated cargo sorting into MVBs. Yeast genetics, in vivo binding assays, mutational analysis of PTVP motif, lipid-binding assays The Journal of cell biology High 12900393
1995 Vps27 controls membrane trafficking through the prevacuolar/endosomal compartment: rapid inactivation of Vps27p causes Golgi recycling proteins (Vps10p) and endocytosed proteins (Ste3p) to accumulate in a class E compartment, and restoration of Vps27p function allows transit to resume, establishing the prevacuolar compartment as a functional intermediate for both biosynthetic and endocytic pathways. Temperature-sensitive allele of VPS27, fluorescence microscopy, protein trafficking assays The Journal of cell biology High 7593183
2003 The individual UIMs of Vps27 fold as autonomous alpha-helices that each independently bind ubiquitin via the Leu8-Ile44-Val70 hydrophobic patch; both UIMs are required for efficient ubiquitin interactions and MVB cargo sorting. The binding surface is conserved with other ubiquitin-binding endocytic proteins (S5a, CUE, UBA domains). NMR solution structure, mutagenesis, in vitro binding assays The EMBO journal High 12970172
2003 Vps27 forms a complex with Hse1; together they act as a ubiquitin-sorting receptor at endosomes. Vps27 binds Vps23 (ESCRT-I) directly via two PSDP motifs in its C-terminus. Disruption of Vps27-Hse1 interaction causes severe MVB sorting defects, while loss of Vps27-Vps23 interaction reduces sorting efficiency without abolishing MVB formation. Both the Vps27 and Vps23 ubiquitin-binding surfaces contact the same cargo ubiquitin. NMR spectroscopy, mutagenesis, yeast genetics, MVB sorting assays The Journal of cell biology High 14581452
2007 Crystal structure of the Vps27/Hse1 complex core at 3.0 Å resolution reveals two intertwined GAT domains (each formed by two helices from one subunit and one from the other) connected by an antiparallel coiled coil forming a 90 Å barbell-like scaffold. This architecture positions domains that recruit ubiquitinated cargo and deubiquitinating enzymes in proximity; Monte Carlo simulations show cooperative binding to lipids and ubiquitinated membrane proteins. X-ray crystallography (3.0 Å), sedimentation equilibrium, coarse-grained Monte Carlo simulations Developmental cell High 17543868
2000 HGS (Hgs) binds Smad2 via its C-terminal half and cooperates with SARA to stimulate activin receptor-mediated signaling by efficiently recruiting Smad2 to the TGF-β/activin receptor complex. A C-terminal deletion knock-in mouse is embryonic lethal (E8.5–10.5) and mutant cells show significantly decreased responses to activin and TGF-β stimulation. Co-immunoprecipitation, gene targeting (knock-in), reporter assays, cell stimulation assays Molecular and cellular biology High 11094085
2002 HGS localizes to early endosomes via its FYVE/lipid-binding domain, which is necessary for constitutive EGFR endocytosis. The ubiquitin-interacting motif (UIM) of HGS has dual function: it binds ubiquitylated proteins AND recruits Nedd4 ubiquitin ligase to promote self-ubiquitylation of HGS, thereby negatively regulating receptor degradation. Co-immunoprecipitation, dominant-negative overexpression, immunofluorescence/endosome fractionation, domain deletion analysis Traffic (Copenhagen, Denmark) Medium 12230472
2001 HGS physically associates with TAK1 (TGF-β-activated kinase 1) and Pak1 (p21-activated kinase 1), and is required for IL-2-induced activation of the serum-response element and CRE of the c-fos promoter through the TAK1-JNK and Pak1-SRF pathways. Co-immunoprecipitation, reporter gene assays (SRE, CRE of c-fos), dominant-negative constructs The Journal of biological chemistry Medium 11397816
2011 HGS is required for phosphorylation of SMAD1/5/8 and TAK1/p38 to transduce BMP signaling during early mouse embryo development. HGS functions to localize TAK1 to the early endosome for its activation; Hgs-mutant embryos show highly down-regulated BMP target genes. Mouse knockout genetics, western blot (phospho-SMAD1/5/8, phospho-TAK1/p38), immunofluorescence localization of TAK1 Developmental dynamics Medium 21953618
2006 HGS (Hgs) directly interacts with Smad5 (identified via cDNA library screen and confirmed by co-immunoprecipitation) and overexpression of Hgs attenuates BMP-dependent transcriptional responses, establishing HGS as an inhibitor of BMP signaling. cDNA expression library screen, co-immunoprecipitation, BMP-responsive reporter gene assay Experimental cell research Medium 16516194
2012 Pkh1/Pkh2 kinases (yeast orthologs of PDK1) directly phosphorylate Vps27 at serine 613 both in vivo and in vitro; this phosphorylation is required for proper ESCRT-I (Vps28) recruitment to endosomes. vps27-S613A mutant cells show impaired MVB sorting of Cps1 and Ste2, and ESCRT-I remains mainly cytoplasmic. In vitro kinase assay, site-directed mutagenesis (S613A), GFP-tagging/fluorescence microscopy, MVB sorting assays Molecular biology of the cell High 22918958
2012 HRS (HGS) is required for transport of LDL-derived cholesterol from endosomes to the endoplasmic reticulum. This function is distinct from its role in lysosomal receptor degradation: knockdown of other ESCRT proteins does not cause prominent endosomal cholesterol accumulation, and NPC1/NPC2 localization and biochemical properties are unchanged upon HRS knockdown. siRNA knockdown, filipin staining (cholesterol), fractionation, fluorescence microscopy Cell reports Medium 22832105
2021 PI3K complex II-generated PI3P on vacuolar membranes is required for Vps27 recruitment and ESCRT-0 complex formation during microautophagy induction after TORC1 inactivation; forced recruitment of Vps27 to vacuolar membranes rescues microautophagy defects in PI3KCII-deficient cells, establishing the PI3KCII-PI3P-Vps27 axis as critical for microautophagy. Yeast genetics (deletion mutants), fluorescence microscopy, forced membrane targeting constructs, survival assays under nutrient stress Journal of molecular biology Medium 34798133
2015 The teetering (tn) neurological mutation is a single nucleotide substitution in Hgs/HGS. Loss of HGS causes structural alterations at the neuromuscular junction (swellings, ultra-terminal sprouting, increased endosomes/MVBs), a reduction in spontaneous and evoked acetylcholine release, elevated ubiquitinated proteins in synaptosomes, and both hypermyelinated and dysmyelinated axons. TrkB levels were only modestly decreased in sciatic nerve, and RTK levels in CNS were unchanged. Positional cloning, electron microscopy, electrophysiology (NMJ recordings), western blot, immunofluorescence PLoS genetics High 26115514
2015 HGS plays a dual role in HBV biology: it suppresses HBV transcription/replication at aberrant levels, and promotes secretion of naked capsids through a ubiquitin-independent association with HBV core protein (HBc). HBc colocalizes with HGS near the cell periphery rather than at punctate endosomes. Mutant core (HBc 1-147 lacking ARD) can still secrete empty naked capsids promoted by HGS, but not empty virions. siRNA knockdown, overexpression, hydrodynamic delivery in mouse model, co-immunoprecipitation, confocal microscopy, virion/capsid quantification PLoS pathogens Medium 26431433
2021 HRS/HGS depletion in myoblasts impairs differentiation by (1) upregulating MEK/ERK signaling, (2) downregulating Akt2 signaling, (3) activating myogenic repressors FOXO1 and GSK3β, and (4) inhibiting functional autophagy required for myogenesis. Pharmacological inhibition of MEK/ERK (U0126) or GSK3β (azakenpaullone) significantly restores differentiation in Hrs-depleted cells. siRNA/shRNA knockdown, pharmacological rescue experiments, western blot, differentiation assays in C2C12 and human myoblasts BMC biology Medium 34330273
2022 Cardiomyocyte-specific Hgs knockout mice develop restrictive cardiomyopathy (RCM)-like phenotype. HGS deficiency impairs lysosomal homeostasis, disrupts cholesterol transport and lysosomal integrity causing lysosomal storage disorder, and leads to aberrant autophagosome accumulation and protein aggregation. Suppression of protein aggregation by doxycycline treatment attenuates cardiac fibrosis and diastolic dysfunction. Conditional gene knockout (Cre/lox), proteomic analysis, electron microscopy, doxycycline pharmacological rescue, cardiac function measurements International journal of biological sciences Medium 34330273 35342336
2015 HGS depletion selectively induces apoptosis in hepatoblastoma and colorectal cancer cells with active oncogenic β-catenin signaling (CTNNB1 mutation) but spares cells with low β-catenin activity, establishing a synthetic lethal relationship between HGS function and oncogenic CTNNB1 in two independent cancer cell contexts. Kinome-wide siRNA screen, isogenic cell line pairs with inducible shRNA against CTNNB1, apoptosis measurement by flow cytometry and immunoblotting BMC cancer Medium 26715116
2015 Smooth muscle-specific Hgs deficiency causes progressive esophageal dilation with thinning muscle layer, decreased contractile responsiveness to KCl and acetylcholine, increased inhibitory neurites, T lymphocyte infiltration, and altered expression of neurotrophin and inflammation genes, indicating that HGS in SMCs is required for normal esophageal motility. Conditional knockout (SMC-specific), organ bath contractility assays, immunohistochemistry, gene expression analysis International journal of biological sciences Medium 26078721
2016 TP53 regulates HGS expression, and HGS levels control exosome size: low HGS (in TP53-KO or TP53-mutant R273H cells) leads to smaller exosomes compared to TP53-WT cells. Functional studies demonstrate that HGS-dependent exosome formation is downstream of TP53 status. iTRAQ-2D-LC-MS/MS proteomics, HGS knockdown/overexpression, nanoparticle tracking analysis, isogenic TP53 cell lines Scientific reports Medium 27312428
2025 HGS interacts with the coronavirus membrane (M) protein and facilitates M protein trafficking to the ER-Golgi intermediate compartment (ERGIC) for virion assembly. HGS deficiency causes M protein retention in the ER and blocks virion assembly. M-derived peptides and the drug riboflavin tetrabutyrate (RTB) bind HGS and disrupt HGS-M protein interaction, blocking coronavirus assembly. Genome-wide CRISPRi screen, co-immunoprecipitation, subcellular fractionation/immunofluorescence, in vitro and in vivo antiviral assays, peptide design and drug screening The Journal of clinical investigation High 41401029
2025 Coronavirus infection induces HGS to form enlarged vesicular compartments (distinct from normal endosomes) that serve as sites of virion assembly at later infection stages. Viral structural proteins colocalize with these HGS+ compartments. APEX2-EM and cryo-CLEM confirm assembled virions within HGS+ compartments. HGS deficiency abolishes these compartments and markedly reduces assembled virions. HGS+ vesicular compartments are rearranged from Golgi and endosome/lysosome by coronavirus infection. Confocal microscopy, live-cell super-resolution microscopy, APEX2-based electron microscopy, immuno-EM, cryo-CLEM, whole-cell volume EM, HGS knockdown bioRxivpreprint Medium bio_10.1101_2025.10.25.684511
2025 Salmonella effector SopB directly interacts with the ubiquitin-binding domains of the ESCRT-0 subunit HGS, and promotes ESCRT-0 recruitment to the Salmonella-containing vacuole (SCV) where HGS colocalizes with SopB. Virotrap mass spectrometry, co-immunoprecipitation with ubiquitin-binding domain constructs, immunofluorescence colocalization bioRxivpreprint Low bio_10.1101_2025.08.19.669813
2007 Sst4p (fission yeast Vps27/HGS ortholog) localizes adjacent to forespore membranes during sporulation in a FYVE domain- and PI3-kinase-dependent manner, interacts with Hse1p, and is required for proper spore formation. UIM mutations in the Sst4p/Hse1p complex cause abnormal spore morphology. Fluorescence microscopy of GFP fusions, yeast two-hybrid/co-immunoprecipitation, deletion and UIM mutant analysis, spore viability assays Eukaryotic cell Medium 17951524
2025 HGS overexpression induces epithelial-mesenchymal transition (EMT) and anchorage-independent growth in MDCK and cancer cells, while overexpression of the HGS coiled-coil domain suppresses HGF-induced EMT and anchorage-independent growth. An oligopeptide from the coiled-coil domain (OP12-462) suppresses tumor growth in vivo. Overexpression in MDCK/B16/COLO205 cells, soft agar colony formation assay, mouse xenograft tumor growth assay International journal of molecular sciences Medium 39859488
2024 Sit4 (yeast PP2A-like phosphatase) genetically interacts with Vps27 in a negative manner: sit4Δvps27Δ double mutants have shortened lifespan compared to single mutants. Vps27 is critical for iron homeostasis and mitochondrial function in sit4Δ cells, as double mutants show high iron levels and impaired mitochondrial respiration. Yeast genetics (double mutant analysis), proteomic analysis of vacuolar fractions, mitochondrial respiration assays, chronological lifespan measurement Cells Low 38667270
2003 SARA and HGS (Hgs) attenuate TGF-β1 susceptibility in human CD4+ T cells: both molecules are down-regulated in antigen-stimulated T cells, and overexpression of SARA or HGS dose-dependently decreases TGF-β1-responsive reporter gene expression, demonstrating an inhibitory function on TGF-β1 signaling in T cells. mRNA quantification, reporter gene assay, overexpression experiments in primary T cells FASEB journal Low 12554698

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Vps27 recruits ESCRT machinery to endosomes during MVB sorting. The Journal of cell biology 371 12900393
1995 VPS27 controls vacuolar and endocytic traffic through a prevacuolar compartment in Saccharomyces cerevisiae. The Journal of cell biology 347 7593183
2014 Development of the Horse Grimace Scale (HGS) as a pain assessment tool in horses undergoing routine castration. PloS one 311 24647606
2005 HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. British journal of cancer 262 15846298
2003 Solution structure of Vps27 UIM-ubiquitin complex important for endosomal sorting and receptor downregulation. The EMBO journal 171 12970172
2003 Vps27-Hse1 and ESCRT-I complexes cooperate to increase efficiency of sorting ubiquitinated proteins at the endosome. The Journal of cell biology 166 14581452
2000 Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Molecular and cellular biology 146 11094085
2002 Ligand-independent degradation of epidermal growth factor receptor involves receptor ubiquitylation and Hgs, an adaptor whose ubiquitin-interacting motif targets ubiquitylation by Nedd4. Traffic (Copenhagen, Denmark) 127 12230472
2009 Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Annals of oncology : official journal of the European Society for Medical Oncology 123 19633048
2013 Effect of dissolved organic matter source and character on microbial Hg methylation in Hg-S-DOM solutions. Environmental science & technology 112 23634978
2006 Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose-dependent growth delay in vivo. Oncogene 94 16636678
2016 Using the Horse Grimace Scale (HGS) to Assess Pain Associated with Acute Laminitis in Horses (Equus caballus). Animals : an open access journal from MDPI 73 27527224
2015 The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion. PLoS pathogens 66 26431433
2007 The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent sorting. Developmental cell 63 17543868
2006 Mcl-1L cleavage is involved in TRAIL-R1- and TRAIL-R2-mediated apoptosis induced by HGS-ETR1 and HGS-ETR2 human mAbs in myeloma cells. Blood 57 16638930
2016 A novel TP53 pathway influences the HGS-mediated exosome formation in colorectal cancer. Scientific reports 54 27312428
2012 Protein-directed synthesis of NIR-emitting, tunable HgS quantum dots and their applications in metal-ion sensing. Small (Weinheim an der Bergstrasse, Germany) 48 22826036
2012 An essential role of Hrs/Vps27 in endosomal cholesterol trafficking. Cell reports 45 22832105
2018 Spectroscopic and Microscopic Evidence of Biomediated HgS Species Formation from Hg(II)-Cysteine Complexes: Implications for Hg(II) Bioavailability. Environmental science & technology 38 30078312
2018 Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder. Epigenomics 38 30456986
2021 The underappreciated role of natural organic matter bond Hg(II) and nanoparticulate HgS as substrates for methylation in paddy soils across a Hg concentration gradient. Environmental pollution (Barking, Essex : 1987) 33 34634402
2003 SARA and Hgs attenuate susceptibility to TGF-beta1-mediated T cell suppression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 12554698
2012 Pkh1/2-dependent phosphorylation of Vps27 regulates ESCRT-I recruitment to endosomes. Molecular biology of the cell 28 22918958
2017 Zuotai and HgS differ from HgCl2 and methyl mercury in Hg accumulation and toxicity in weanling and aged rats. Toxicology and applied pharmacology 25 28536007
2008 Ototoxicity induced by cinnabar (a naturally occurring HgS) in mice through oxidative stress and down-regulated Na(+)/K(+)-ATPase activities. Neurotoxicology 25 18329716
2020 Does Thirty-Minute Standardised Training Improve the Inter-Observer Reliability of the Horse Grimace Scale (HGS)? A Case Study. Animals : an open access journal from MDPI 24 32365927
2015 Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS. PLoS genetics 21 26115514
2019 HgS and Zuotai differ from HgCl2 and methyl mercury in intestinal Hg absorption, transporter expression and gut microbiome in mice. Toxicology and applied pharmacology 20 31175882
2016 Association between targeted somatic mutation (TSM) signatures and HGS-OvCa progression. Cancer medicine 20 27485054
1999 TOM1 genes map to human chromosome 22q13.1 and mouse chromosome 8C1 and encode proteins similar to the endosomal proteins HGS and STAM. Genomics 20 10329004
2011 Metacinnabar (β-HgS): a strong 3D topological insulator with highly anisotropic surface states. Physical review letters 16 21770536
2023 Direct Uptake and Intracellular Dissolution of HgS Nanoparticles: Evidence from a Bacterial Biosensor Approach. Environmental science & technology 14 37755700
2010 Initial testing (stage 1) of mapatumumab (HGS-ETR1) by the pediatric preclinical testing program. Pediatric blood & cancer 14 19856388
2022 Single-Molecule Force Spectroscopy Reveals the Dynamic HgS Coordination Site in the De Novo-Designed Metalloprotein α3DIV. The journal of physical chemistry letters 12 35678420
2015 A kinome siRNA screen identifies HGS as a potential target for liver cancers with oncogenic mutations in CTNNB1. BMC cancer 12 26715116
2001 Involvement of Hgs/Hrs in signaling for cytokine-mediated c-fos induction through interaction with TAK1 and Pak1. The Journal of biological chemistry 12 11397816
2021 The ESCRT-0 subcomplex component Hrs/Hgs is a master regulator of myogenesis via modulation of signaling and degradation pathways. BMC biology 11 34330273
2013 Microbially enhanced dissolution of HgS in an acid mine drainage system in the California Coast Range. Geobiology 11 24224806
2021 The PI3 Kinase Complex II-PI3P-Vps27 Axis on Vacuolar Membranes is Critical for Microautophagy Induction and Nutrient Stress Adaptation. Journal of molecular biology 10 34798133
2015 The Vps27/Hrs/STAM (VHS) Domain of the Signal-transducing Adaptor Molecule (STAM) Directs Associated Molecule with the SH3 Domain of STAM (AMSH) Specificity to Longer Ubiquitin Chains and Dictates the Position of Cleavage. The Journal of biological chemistry 10 26601948
2007 Schizosaccharomyces pombe Sst4p, a conserved Vps27/Hrs homolog, functions downstream of phosphatidylinositol 3-kinase Pik3p to mediate proper spore formation. Eukaryotic cell 9 17951524
2019 HgS Inhibits Oxidative Stress Caused by Hypoxia through Regulation of 5-HT Metabolism Pathway. International journal of molecular sciences 8 30889910
2015 Ultra-bright near-infrared-emitting HgS/ZnS core/shell nanocrystals for in vitro and in vivo imaging. Journal of materials chemistry. B 8 32262542
2006 Hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) and guanylate kinase 1 (GUK1) are differentially expressed in GH-secreting adenomas. Pituitary 8 16832584
2020 Adaptive mechanisms induced by sparingly soluble mercury sulfide (HgS) in zebrafish: Behavioural and proteomics analysis. Chemosphere 7 33429232
2025 Targeting the host factor HGS-viral membrane protein interaction in coronavirus infection. The Journal of clinical investigation 6 41401029
2022 Effects of Tibetan medicine metacinnabar (β-HgS) combined with imipramine or sertraline on depression-like symptoms in mice. Frontiers in pharmacology 6 36120298
2021 Zuotai (β-HgS)-containing 70 Wei Zhen-Zhu-Wan differs from mercury chloride and methylmercury on hepatic cytochrome P450 in mice. F1000Research 6 34249337
2021 Amperometric biosensors for L-arginine and creatinine assay based on recombinant deiminases and ammonium-sensitive Cu/Zn(Hg)S nanoparticles. Talanta 6 34857329
2021 StarD13 negatively regulates invadopodia formation and invasion in high-grade serous (HGS) ovarian adenocarcinoma cells by inhibiting Cdc42. European journal of cell biology 6 34958986
2015 Smooth Muscle Hgs Deficiency Leads to Impaired Esophageal Motility. International journal of biological sciences 6 26078721
2011 Hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs) is involved in BMP signaling through phosphorylation of SMADS and TAK1 in early mouse embryo. Developmental dynamics : an official publication of the American Association of Anatomists 6 21953618
2006 Hgs physically interacts with Smad5 and attenuates BMP signaling. Experimental cell research 6 16516194
2023 Stability Investigations on a Pt@HGS Catalyst as a Model Material for Fuel Cell Applications: The Role of the Local pH. Angewandte Chemie (International ed. in English) 5 37846806
2022 Hgs Deficiency Caused Restrictive Cardiomyopathy via Disrupting Proteostasis. International journal of biological sciences 5 35342336
2019 Neurotoxicity of β-HgS differs from environmental mercury pollutants (MeHgCl and HgCl2) in Neuro-2a cell. International journal of environmental health research 5 31793343
2024 Enhancing the Horse Grimace Scale (HGS): Proposed updates and anatomical descriptors for pain assessment. Veterinary journal (London, England : 1997) 4 39142376
2023 Carboxypeptidase A4 negatively regulates HGS-ETR1/2-induced pyroptosis by forming a positive feedback loop with the AKT signalling pathway. Cell death & disease 4 38049405
2007 Autometallographic tracing of Hg-S quantum dots in frogs exposed to inorganic mercury. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 4 17929145
2024 A study on the effects of metacinnabar (β-HgS) on weight and appetite recovery in stressed mice. Journal of ethnopharmacology 3 39128797
2024 Viscoelastic Fluid Focusing Chip-ICP-MS Single-Cell Analysis Enables Elucidating the Effect of Extracellular Polymeric Substances on Bioaccumulation of Hg2+/HgS in Microcystis aeruginosa Cell. Analytical chemistry 3 39436158
2021 Biological Synthesis of PbS, As3S4, HgS, CdS Nanoparticles using Pseudomonas aeruginosa and their Structural, Morphological, Photoluminescence as well as Whole Cell Protein Profiling Studies. Journal of fluorescence 3 34268653
2019 Rapid, simplified microscale quantitative analysis of lignin H/G/S composition with GC-MS in glass ampules and glass capillaries. MethodsX 3 31763191
2013 Target-stimulated metallic HgS nanostructures on a DNA-based polyion complex membrane for highly efficient impedimetric detection of dissolved hydrogen sulfide. Chemical communications (Cambridge, England) 3 24150530
2013 Evaluation of reduced point charge models of proteins through Molecular Dynamics simulations: application to the Vps27 UIM-1-Ubiquitin complex. Journal of molecular graphics & modelling 2 24316938
2025 HGS Promotes Tumor Growth, Whereas the Coiled-Coil Domain and Its Oligopeptide of HGS Suppress It. International journal of molecular sciences 1 39859488
2025 Thermal Decomposition of Metacinnabar (β-HgS) during Monoethylene Glycol Regeneration in Natural Gas Processing. Energy & fuels : an American Chemical Society journal 1 40303971
2024 Sit4 Genetically Interacts with Vps27 to Regulate Mitochondrial Function and Lifespan in Saccharomyces cerevisiae. Cells 1 38667270
2023 Development and Validation of Hindu Gratitude Scale (HGS-15): A Rnas Perspective. Journal of religion and health 1 37204652
2020 Effects of β-HgS on cell viability and intracellular oxidative stress in PC-12 cells. Metallomics : integrated biometal science 1 32638798
2026 Unveiling HgS nanoparticle formation in Hg(II)-dissolved organic matter systems at low nanomolar to submicromolar levels: A comprehensive characterization via combined liquid chromatography-ICP-MS and single particle ICP-MS. Journal of hazardous materials 0 42235392

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