Affinage

HGS

Hepatocyte growth factor-regulated tyrosine kinase substrate · UniProt O14964

Length
777 aa
Mass
86.2 kDa
Annotated
2026-04-28
100 papers in source corpus 58 papers cited in narrative 58 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HGS (Hrs) is the core scaffold of the ESCRT-0 complex that initiates ubiquitin-dependent sorting of endocytic cargo into multivesicular bodies for lysosomal degradation. On early endosomes, Hrs binds phosphatidylinositol 3-phosphate via its FYVE domain, recognizes monoubiquitinated receptors through a double-sided UIM that simultaneously engages two ubiquitin molecules, assembles with STAM and Eps15b into flat clathrin-coated microdomains, and recruits ESCRT-I via a PSAP motif interaction with Tsg101, thereby driving degradation of receptors such as EGFR, connexin-43, and ENaC (PMID:11988742, PMID:16462748, PMID:12802020, PMID:12551915, PMID:16720641, PMID:19808888). Beyond degradative sorting, Hrs promotes sequence-directed receptor recycling (via its VHS domain for β2-adrenergic and TrkB receptors), WASH-complex-dependent constitutive recycling of EGFR/MT1-MMP, phagosomal and autophagosomal maturation, exosome biogenesis including ERK-phosphorylation-dependent loading of PD-L1 into exosomes, and participates in TGF-β/Smad2 signaling (PMID:15944737, PMID:29891722, PMID:15121875, PMID:17624298, PMID:35835783, PMID:11094085). Hrs-null mice die at mid-gestation with ventral folding defects, and neuron-specific deletion causes ubiquitinated protein accumulation, hippocampal neurodegeneration, and behavioral deficits, underscoring its essential role in membrane protein quality control in vivo (PMID:10364163, PMID:19008375).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 High

    Identification of HGS as a growth-factor-responsive phosphoprotein with a FYVE zinc-finger domain established it as a candidate signaling/trafficking regulator, but its function was unknown.

    Evidence Anti-phosphotyrosine purification and cDNA cloning from HGF/EGF/PDGF-stimulated cells

    PMID:7565774

    Open questions at the time
    • No function assigned
    • Subcellular localization incompletely resolved
    • Phosphorylation sites and responsible kinases unknown
  2. 1997 High

    Localization of Hrs to early endosomal membranes and identification of its STAM interaction established it as an endosomal adaptor rather than a nuclear signaling molecule, and linked it to cytokine-driven proliferation.

    Evidence Immunoelectron microscopy, co-immunoprecipitation, and thymidine incorporation assays with domain deletions

    PMID:9252367 PMID:9407053

    Open questions at the time
    • How Hrs reaches endosomes mechanistically unclear
    • Cargo substrates unidentified
    • Relationship to endosomal sorting machinery unknown
  3. 1999 High

    Hrs knockout mouse embryonic lethality with enlarged early endosomes demonstrated that Hrs is essential for endosomal vesicular transport in vivo, not merely an accessory adaptor.

    Evidence Gene targeting in mice, histology, and wortmannin perturbation of PI3K-dependent localization

    PMID:10364163

    Open questions at the time
    • Precise molecular cargo handled by Hrs unknown
    • Whether PI3P binding is direct or indirect unclear
    • How Hrs cooperates with downstream sorting machinery unresolved
  4. 2000 High

    Discovery that Hrs interacts with SNX1 on endosomes and is required for ligand-induced EGFR degradation, plus its role in TGF-β/Smad2 signaling via SARA cooperation, revealed that Hrs functions in both degradative receptor sorting and signal transduction pathways.

    Evidence Co-immunoprecipitation/domain mapping with EGFR degradation assays; knock-in mice with C-terminal deletions showing activin/TGF-β signaling defects

    PMID:11094085 PMID:11110793

    Open questions at the time
    • Ubiquitin recognition mechanism unknown
    • Connection to ESCRT machinery not yet established
    • Whether sorting and signaling functions are separable unclear
  5. 2002 High

    Identification of the UIM as the ubiquitin-recognition element and demonstration that the FYVE domain directly binds PI3P with membrane penetration solved how Hrs recognizes both the endosomal membrane and its ubiquitinated cargo.

    Evidence UIM mutant genetic sorting assays in yeast (Vps27); surface plasmon resonance and monolayer penetration for FYVE-PI3P binding

    PMID:11988742 PMID:12006563

    Open questions at the time
    • How UIM engages multiple ubiquitin moieties structurally unknown
    • Connection to downstream ESCRT-I recruitment unresolved
    • Regulatory phosphorylation of Hrs poorly characterized
  6. 2003 High

    Mapping the PSAP motif–Tsg101 UEV interaction and demonstrating that Hrs recruits ESCRT-I to endosomes established the sequential ESCRT recruitment cascade, placing Hrs/ESCRT-0 as the initiating step; simultaneously, the Hrs–STAM–Eps15 multivalent ubiquitin-binding complex was defined.

    Evidence Co-immunoprecipitation with domain mutagenesis, HIV Gag budding rescue, siRNA of Hrs reducing STAM2 recruitment, NMR structures of UIM–ubiquitin complexes

    PMID:12551915 PMID:12802020 PMID:12900394 PMID:12970172 PMID:14581452

    Open questions at the time
    • Structural basis of the double-sided UIM not yet resolved
    • Role of clathrin in organizing Hrs microdomains unclear
    • Recycling functions of Hrs not yet recognized
  7. 2004 High

    Discovery that Hrs is recruited to phagosomes in a PI3P-dependent manner and is required for phagosomal maturation extended its function beyond receptor sorting to innate immune defense; pathogenic mycobacteria evade this pathway.

    Evidence siRNA depletion of Hrs with phagosomal maturation markers and mycobacterial infection model

    PMID:15121875

    Open questions at the time
    • How mycobacteria block Hrs recruitment mechanistically unknown
    • Whether Hrs phagosomal function requires ESCRT-I unclear
    • Hrs role in autophagy not yet examined
  8. 2005 High

    Demonstration that Hrs promotes VHS-domain-dependent, ubiquitin-independent recycling of GPCRs (β2AR) and assembles a distinct CART complex for constitutive transferrin receptor recycling revealed that Hrs operates in recycling pathways separable from its degradative sorting function.

    Evidence siRNA knockdown with receptor recycling assays and cAMP signaling readouts; co-immunoprecipitation of CART complex (Hrs–actinin-4–BERP–myosin V) with transferrin recycling assays

    PMID:15772161 PMID:15944737

    Open questions at the time
    • How VHS domain recognizes recycling sequences structurally unknown
    • Whether CART and ESCRT-0 complexes coexist on the same endosome unclear
    • Neuronal recycling function not yet tested
  9. 2006 High

    The 1.7-Å crystal structure of the Hrs UIM revealed a double-sided ubiquitin-binding helix engaging two ubiquitin molecules simultaneously, and clathrin was shown to cluster Hrs into dynamic endosomal microdomains essential for sorting; together these findings explained how a limited pool of Hrs achieves efficient cargo concentration.

    Evidence X-ray crystallography with mutagenesis and degradative sorting assays; siRNA of clathrin and FRAP live imaging of Hrs microdomains

    PMID:16462748 PMID:16720641

    Open questions at the time
    • How clathrin flat lattice is nucleated on endosomes unclear
    • Stoichiometry of Hrs in microdomains not determined
    • Regulation of microdomain dynamics unknown
  10. 2007 Medium

    Hrs was shown to be required for autophagosome–lysosome fusion, extending its maturation function to the autophagy pathway independently of primary autophagosome formation.

    Evidence siRNA knockdown with LC3/LAMP-1 colocalization and Streptococcus degradation assays

    PMID:17624298

    Open questions at the time
    • Whether Hrs acts directly on autophagosomal membranes or indirectly via endosomal fusion unclear
    • ESCRT component requirements for autophagosomal maturation not compared
    • Mechanism of Hrs recruitment to autophagosomes unknown
  11. 2008 High

    Neuron-specific Hrs deletion caused ubiquitinated protein accumulation, hippocampal neurodegeneration, and behavioral deficits, establishing Hrs as essential for neuronal protein quality control and demonstrating that ESCRT-0 dysfunction phenocopies aspects of neurodegenerative disease.

    Evidence Conditional knockout mice (Hrs flox/flox; SynI-Cre) with histology, ubiquitin immunostaining, and behavioral testing

    PMID:19008375

    Open questions at the time
    • Which specific neuronal substrates accumulate is not fully cataloged
    • Whether Hrs loss causes neurodegeneration through failed degradation, failed recycling, or both is unknown
    • Glial contributions not assessed
  12. 2010 High

    Hrs was shown to control exosome secretion from dendritic cells and to sort ENaC between degradation and recycling in a Nedd4-2-dependent manner, expanding the functional repertoire to exosome biogenesis and epithelial ion channel regulation.

    Evidence siRNA with exosome quantification and antigen-presentation assays; co-immunoprecipitation of Hrs–ENaC with electrophysiology and ubiquitination assays

    PMID:20673754 PMID:20675381

    Open questions at the time
    • Cargo selectivity of Hrs-dependent exosome loading unknown
    • Whether Hrs directly recognizes ENaC ubiquitin or adaptor-mediated unclear
    • Phosphorylation-dependent regulation of exosome loading not yet examined
  13. 2012 High

    Hrs/ESCRT-0 was found to have a unique role in endosome-to-ER cholesterol transport distinct from other ESCRT subunits, revealing a non-canonical lipid trafficking function.

    Evidence Comparative siRNA knockdown of Hrs versus ESCRT-I/II/III with cholesterol trafficking assays

    PMID:22832105

    Open questions at the time
    • Molecular mechanism of cholesterol handoff from Hrs-containing endosomes to ER unknown
    • Whether NPC1/NPC2 cooperate with Hrs in this context not resolved
    • Not confirmed in in vivo models
  14. 2014 High

    The deubiquitinase UBPY/USP8 was shown to protect Hrs itself from ubiquitin-dependent lysosomal degradation, establishing a writer–eraser circuit that maintains ESCRT-0 complex integrity.

    Evidence Ubpy-null Drosophila genetics with co-immunoprecipitation and deubiquitylation assays

    PMID:24574010

    Open questions at the time
    • Identity of the E3 ligase(s) ubiquitinating Hrs in vivo not fully resolved (POSH implicated but not confirmed in Drosophila)
    • Whether UBPY regulation is conserved in mammalian neurons unknown
    • Structural basis of UBPY–Hrs interaction not determined
  15. 2018 High

    Hrs was shown to support WASH complex endosomal recruitment, enabling constitutive recycling of EGFR and MT1-MMP and promoting cancer cell invasion, linking Hrs recycling function to tumor biology.

    Evidence siRNA knockdown with proximity ligation assay, chimeric receptor trafficking, matrix degradation, and invasion assays in triple-negative breast cancer cells

    PMID:29891722

    Open questions at the time
    • How Hrs physically communicates with WASH complex unclear
    • Whether this axis operates in non-cancer cells not shown
    • Relative contribution of recycling versus degradation to invasion phenotype not dissected
  16. 2022 High

    ERK-mediated phosphorylation of Hrs was found to drive selective PD-L1 loading into exosomes that suppress anti-tumor CD8+ T cell responses, directly connecting Hrs post-translational modification to immune evasion and anti-PD-1 therapy resistance.

    Evidence ERK–HRS phosphorylation assays, co-immunoprecipitation of phospho-HRS–PD-L1, exosome proteomics, murine tumor models, and patient melanoma immunofluorescence

    PMID:35835783 PMID:36484721

    Open questions at the time
    • Specific ERK phosphorylation site(s) on Hrs not mapped to residue level
    • Whether other immune checkpoint ligands are loaded via the same mechanism unknown
    • Therapeutic targeting of Hrs phosphorylation not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of Hrs VHS-domain-mediated recycling sequence recognition, how Hrs coordinates its simultaneous roles in degradation, recycling, exosome loading, and cholesterol transport on the same endosome, and whether Hrs phosphorylation events can be therapeutically targeted to modulate immune checkpoint evasion.
  • No high-resolution structure of full-length Hrs or Hrs–STAM heterodimer in a membrane context
  • Cargo selectivity rules for exosomal versus lysosomal sorting by Hrs not defined
  • In vivo validation of ERK–Hrs–PD-L1 axis in human tumors lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0042393 histone binding 3 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 7 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 8 R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-9612973 Autophagy 1
Partners
CD274EPS15L1SMAD2SNX1STAMSTAM2TSG101USP8
Complex memberships
CART complex (Hrs-actinin-4-BERP-myosin V)ESCRT-0 (Hrs-STAM)Hrs-Eps15b-STAM

Evidence

Reading pass · 58 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 HGS (Hrs) was identified as a novel 115-kDa protein rapidly tyrosine-phosphorylated in cells stimulated with hepatocyte growth factor, epidermal growth factor, and platelet-derived growth factor, containing a conserved zinc finger (FYVE) domain and proline-rich regions, and localized to the cytoplasm. Anti-phosphotyrosine immunoaffinity chromatography, cDNA cloning, subcellular fractionation, polyclonal antibody characterization Molecular and cellular biology High 7565774
1997 HGS (Hrs) is localized to the cytoplasmic surface of early endosomes (colocalizing with transferrin receptor but not late endosomal CD63), and is peripherally membrane-associated, extractable by alkali treatment; the zinc finger domain is not required for endosomal localization. Immunofluorescence staining, immunoelectron microscopy, subcellular fractionation, alkaline extraction The Journal of biological chemistry High 9252367
1997 HGS (Hrs) associates with STAM (signal-transducing adaptor molecule) through their coiled-coil domains; overexpression of Hrs suppresses DNA synthesis upon IL-2 and GM-CSF stimulation, and this suppressive ability requires the STAM-binding site. Co-immunoprecipitation, yeast two-hybrid, domain deletion mutagenesis, [3H]-thymidine incorporation assay The Journal of biological chemistry High 9407053
1999 Hrs null mice die around E11 with ventral folding morphogenesis defects and cardia bifida; Hrs-deficient cells show abnormally enlarged early endosomes, indicating Hrs is required for normal vesicular transport through early endosomes. Wortmannin treatment disrupts Hrs vesicular localization, implicating Hrs in PI3-kinase-dependent membrane trafficking. Gene targeting (knockout mouse), histology, immunofluorescence, wortmannin pharmacological inhibition Genes & development High 10364163
2000 HGS (Hrs) binds to SNAP-25 via coiled-coil interactions and is localized to large dense-core secretory granules and synaptic-like microvesicles in PC12 cells; Hrs overexpression inhibits Ca2+-dependent exocytosis. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence/confocal microscopy, subcellular fractionation, exocytosis assay in PC12 cells Journal of cell science Medium 10825299
2000 HGS (Hrs) interacts with sorting nexin 1 (SNX1) on early endosomal membranes (not in cytosol), forming an ~550 kDa complex; Hrs and SNX1 co-localize on early endosomes; overexpression of Hrs or its SNX1-binding domain inhibits ligand-induced EGFR degradation without affecting endocytosis. Co-immunoprecipitation, subcellular fractionation, immunofluorescence, deletion mapping, EGFR degradation assay The Journal of biological chemistry High 11110793
2000 The deubiquitinating enzyme UBPY interacts with the SH3 domain of Hrs-binding protein (Hbp/STAM2) via a novel PX(V/I)(D/N)RXXKP motif; this interaction is distinct from the canonical PXXP SH3-binding motif. Far Western screening, mutagenesis, co-immunoprecipitation The Journal of biological chemistry Medium 10982817
2000 Hrs-binding protein (Hbp), which associates with Hrs through coiled-coil motifs and co-localizes with Hrs on early endosomes, is required for intracellular degradation of growth factor/receptor complexes but not for their internalization; dominant-negative Hbp mutants block degradation. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence, dominant-negative overexpression, degradation assay Genes to cells Medium 10651905
2000 HGS (Hgs) binds Smad2 at its C-terminal half and cooperates with SARA (another FYVE domain protein) to stimulate activin receptor-mediated TGF-β/activin signaling by recruiting Smad2 to the receptor; C-terminal deletion knock-in mice die between E8.5-10.5 with severely decreased responses to activin and TGF-β. Co-immunoprecipitation, gene targeting (knock-in mouse), reporter assay, domain deletion analysis Molecular and cellular biology High 11094085
2001 HGS (Hrs) localizes to early endosomes via two required domains: the FYVE domain (PI3P-binding; point mutation R183A abolishes membrane targeting) and the second coiled-coil domain (which binds SNAP-25); endosomal targeting of Hrs is independent of Rab5. Immunofluorescence, domain deletion and point mutation analysis, dominant-negative Rab5 expression Journal of cell science High 11493665
2002 The UIM (ubiquitin-interacting motif) domains of Vps27p (yeast ortholog of Hrs) bind ubiquitin and are required for sorting endocytic cargo into multivesicular bodies at the late endosome; monoubiquitin functions as a sorting signal recognized by UIM-containing machinery. Genetic assays (UIM mutants), in vitro ubiquitin binding, protein transport assays in yeast Nature cell biology High 11988742
2002 The FYVE domains of Vps27p and Drosophila Hrs specifically bind phosphatidylinositol 3-phosphate (PI3P) and undergo PI3P-induced membrane penetration; hydrophobic residues near the PI3P-binding pocket and an Arg residue critical for PI3P binding are essential for membrane insertion. Surface plasmon resonance, monolayer penetration analysis, mutagenesis, electrostatic potential calculation The Journal of biological chemistry High 12006563
2002 HGS (Hrs) is phosphorylated downstream of EGFR activation by a non-receptor tyrosine kinase (including Src in vitro), at multiple tyrosine residues; only 10-20% of cellular Hrs is phosphorylated following EGF stimulation; Src, Yes, and Fyn are not the sole kinases responsible. In vitro kinase assay, cells from Src/Yes/Fyn-null backgrounds, phosphotyrosine immunoblotting European journal of biochemistry Medium 12180964
2003 TSG101 (ESCRT-I) interacts with HGS (Hrs) via the TSG101 UEV domain binding to two proline-rich regions in Hrs (including PSAP motif); disruption of this interaction prevents EGFR delivery to late endosomes, causes accumulation of ubiquitinated EGFR in early endosomes, and inhibits ligand-induced EGFR downregulation. Co-immunoprecipitation, dominant-negative mutant expression, EGFR trafficking and degradation assays, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 12802020
2003 HGS (Hrs) recruits ESCRT-I to endosomal membranes via its COOH-terminal PSAP motif (residues 348-351) binding to Tsg101 UEV domain; Hrs222-777 can rescue budding of Gag particles lacking native late domains, showing Hrs normally recruits Tsg101 to endosomes. Hrs FYVE domain mediates PI3P-dependent endosomal localization. Co-immunoprecipitation, HIV Gag budding complementation assay, domain mapping The Journal of cell biology High 12900394
2003 Vps27p (yeast Hrs ortholog) is recruited to endosomes via its FYVE domain binding PI3P; it then recruits ESCRT-I via a PTVP motif in its C-terminus that binds Vps23/Tsg101, establishing the sequential ESCRT recruitment mechanism. Protein-lipid binding assays, co-immunoprecipitation, endosomal recruitment assays, mutagenesis in yeast The Journal of cell biology High 12900393
2003 HGS (Hrs) forms a multivalent ubiquitin-binding complex on early endosomes together with STAM1/STAM2 and Eps15; STAM2 binds ubiquitin; Hrs overexpression recruits STAM2 to endosomal membranes; siRNA depletion of Hrs strongly reduces STAM2 endosomal recruitment and impairs EGFR degradation. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, overexpression, EGFR degradation assay The Journal of biological chemistry High 12551915
2003 The UIM domains of Vps27 (Hrs ortholog) adopt autonomously folded alpha-helices that bind the Leu8-Ile44-Val70 hydrophobic patch of ubiquitin independently and non-cooperatively; two UIMs act serially on the same monoubiquitylated cargo during endosomal transport. NMR solution structure, in vitro binding assays, mutagenesis The EMBO journal High 12970172
2003 Vps27-Hse1 (yeast Hrs-STAM complex) and ESCRT-I cooperate for efficient ubiquitinated cargo sorting at the endosome; Vps27 directly binds Vps23 (Tsg101 ortholog) via two PSDP motifs; loss of Vps27-Vps23 association reduces sorting efficiency but Vps27-Hse1 disruption causes severe MVB formation defects. NMR spectroscopy, mutagenesis, genetic sorting assays in yeast, Co-IP The Journal of cell biology High 14581452
2003 HGS (Hrs) UIM domain is required for EGF-stimulated tyrosine phosphorylation of Hrs; Hrs concentrates ubiquitinated receptors in clathrin-coated endosomal regions via UIM; overexpression of Hrs (but not UIM mutants) inhibits internal vesicle formation within MVBs and retards EGFR degradation. Mutagenesis, overexpression, EGFR trafficking/degradation assays, immunofluorescence Journal of cell science High 12953068
2004 HGS (Hrs) associates with phagosomes in a FYVE domain/PI3P-dependent manner and via additional attachment sites; siRNA depletion of Hrs impairs phagosomal maturation (blocks acquisition of lysobisphosphatidic acid and luminal acidification); pathogenic mycobacteria fail to recruit Hrs to phagosomes, explaining their maturation arrest. siRNA knockdown, immunofluorescence, phagosomal maturation assays, mycobacterial infection model Molecular and cellular biology High 15121875
2004 STAM2 endosomal localization requires binding to Hrs via coiled-coil domains; Hrs depletion by RNAi causes STAM2 mislocalization to cytoplasm and rapid STAM degradation; STAM2 mutants lacking Hrs-binding activity fail to enlarge endosomes, accumulate ubiquitinated proteins, or inhibit EGFR degradation. RNAi knockdown, mutagenesis, immunofluorescence, co-immunoprecipitation, EGFR degradation assay Journal of biochemistry High 15113837
2004 HGS (Hrs) overexpression inhibits EGFR trafficking from early endosomes in both ligand-stimulated and unstimulated cells; FYVE domain deletion or point mutation (abrogating PI3P binding) abolishes this effect, indicating the FYVE domain and endosomal microdomain residency are essential for Hrs sorting function. Overexpression, FYVE domain mutagenesis, immunofluorescence, EGFR trafficking assay Experimental cell research Medium 15212941
2005 Hrs forms a complex (CART) with actinin-4, BERP, and myosin V required for efficient constitutive transferrin receptor (TfR) recycling but not for EGFR degradation; the complex assembles linearly, and disruption of any member-to-member interaction inhibits TfR recycling, shunting it to a slower recycling endosome pathway. Co-immunoprecipitation, siRNA, overexpression, transferrin recycling assays Molecular biology of the cell High 15772161
2005 HGS (Hrs) promotes rapid sequence-directed recycling of endocytosed signaling receptors (e.g., β2-adrenergic receptor) to the plasma membrane in a mechanism distinct from MVB/lysosomal sorting; this function requires the VHS domain of Hrs, is ubiquitin-independent, and does not require other Class E proteins; disrupting this recycling converts GPCR signaling from sustained to transient. siRNA knockdown, dominant-negative overexpression, receptor recycling assays, signaling (cAMP) assays, mutagenesis The EMBO journal High 15944737
2005 Hrs and STAM form a heterodimeric complex that is tyrosine-phosphorylated downstream of EGF, HGF, and PDGF receptors; phosphorylation requires both receptor endocytosis and an intact Hrs UIM, and is dependent on c-Cbl E3 ligase activity; distinct non-receptor tyrosine kinases mediate signal-specific phosphorylation patterns on the complex. Phospho-specific antibodies, kinase inhibitors, dominant-negative c-Cbl, endocytosis inhibition, Co-IP The Biochemical journal Medium 15828871
2005 Met receptor ubiquitination by Cbl is required for phosphorylation of Hrs; fusion of monoubiquitin to ubiquitination-deficient Met (Y1003F) rescues Hrs phosphorylation, decreases Met stability, prevents sustained MEK1/2 activation, and decreases transformation; Met Y1003F localizes with Hrs but fails to induce Hrs phosphorylation. Mutagenesis (Y1003F Met), monoubiquitin fusion, co-localization, phosphorylation assays, focus-forming assays, in vivo tumorigenicity Molecular and cellular biology High 16227611
2005 NF2 tumor suppressor schwannomin requires interaction with HRS to inhibit Stat3 and Stat5 activation; pathogenic schwannomin missense mutant Q538P fails to bind HRS and does not inhibit Stat5 phosphorylation. Co-immunoprecipitation, reporter assays, pathogenic mutant analysis, overexpression in schwannoma cell lines Human molecular genetics Medium 12444102
2005 HRS interacts with PELP1 via yeast two-hybrid/Co-IP and sequesters PELP1 in the cytoplasm, activating MAPK/ERK signaling in an EGFR-dependent but estrogen receptor-independent manner; HRS-stimulated MAPK activation requires endogenous PELP1. Yeast two-hybrid, co-immunoprecipitation, MAPK activation assays, dominant-negative/overexpression, compartment localization studies The Journal of biological chemistry Medium 16352611
2005 POSH (a RING-finger/SH3 scaffold) colocalizes with Hrs on early endosomes and acts as an E3 ubiquitin ligase for Hrs, targeting it for ubiquitin-proteasomal degradation; JNK1 competes with Hrs for POSH binding and reduces POSH-mediated Hrs ubiquitination. Co-immunoprecipitation, ubiquitination assay, immunofluorescence, RING domain mutagenesis Cellular signalling Medium 16084064
2006 HGS (Hrs) Tsg101 depletion causes distinct phenotypes: Tsg101 loss inhibits MVB formation and causes early endosome tubulation; Hrs depletion causes enlarged MVBs without tubulation; both are needed for EGF/EGFR degradation; indicating Tsg101 is required for stable vacuolar endosomal domains and Hrs for accumulation of internal vesicles. siRNA knockdown of Hrs and Tsg101, electron microscopy, EGFR/EGF degradation assays, MVB morphometry Molecular biology of the cell High 16707569
2006 The Hrs-UIM crystal structure at 1.7-Å resolution reveals a single alpha-helix that binds two ubiquitin molecules simultaneously on opposite sides (double-sided UIM), both through the Ile44 surface with equal affinity; mutational experiments show both binding sites are required for efficient degradative protein sorting. X-ray crystallography (1.7 Å), mutagenesis, binding assays, degradative sorting assays Nature structural & molecular biology High 16462748
2006 Clathrin and the clathrin-box motif of Hrs are required for clustering Hrs into restricted endosomal microdomains; these microdomains are dynamic (exchange Hrs and clathrin with similar kinetics) and acquire Tsg101; clathrin-mediated clustering is essential for Hrs degradative sorting function. siRNA knockdown of clathrin, FRAP, immunofluorescence, dominant-negative clathrin, EGFR sorting assays Journal of cell science High 16720641
2006 A novel acidic dileucine-like sequence in the β2-adrenergic receptor cytoplasmic tail switches receptor recycling from default to Hrs-dependent; mutation of this sequence makes recycling Hrs-independent and PDZ-ligand-independent. Receptor mutagenesis, recycling assays, siRNA Hrs knockdown The Journal of biological chemistry Medium 17138565
2006 Hrs tyrosine phosphorylation at Y329/Y334 (downstream of Cbl and EGFR) regulates Hrs ubiquitination and protein stability, which in turn controls EGFR degradation; Y329/334F Hrs mutant shows altered Hrs degradation and impaired EGFR degradation. Cbl overexpression, phospho-specific analysis, mutagenesis (Y329/334F), Hrs depletion with rescue, EGFR degradation assays Molecular and cellular biology High 17101784
2006 Eps15b (an endosome-localized isoform of Eps15) specifically binds Hrs in vivo (whereas Eps15 does not), localizes to Hrs-positive endosomal microdomains, and its depletion delays EGFR degradation and promotes recycling, similar to Hrs overexpression; Eps15b overexpression inhibits EGFR degradation. Co-immunoprecipitation in vivo, siRNA knockdown, immunofluorescence, EGFR degradation/recycling assays The Journal of cell biology High 18362181
2006 The Vps27/Hse1 (Hrs/STAM) complex core consists of two intertwined GAT domains in a barbell-like structure (crystal structure at 3.0 Å); this scaffold positions ubiquitin-binding domains, deubiquitinase-recruiting domains, and lipid-binding FYVE domains for coordinated endosomal cargo recognition and ubiquitination reactions. X-ray crystallography (3.0 Å), coarse-grained Monte Carlo membrane simulations Developmental cell High 17543868
2006 Hse1 (yeast STAM ortholog) recruits Rsp5 E3 ubiquitin ligase (via PY element and adaptor Hua1), the deubiquitinase Ubp7 (via SH3 domain), and Ubp2/Rup1 to the Hse1-Vps27 sorting complex; dual association with E3 and deubiquitinases regulates ubiquitination status and sorting efficiency of MVB cargo. Co-immunoprecipitation, genetic sorting assays, domain mapping in yeast Molecular biology of the cell High 17079730
2007 HGS (Hrs) depletion or overexpression in C. elegans directs the STAM-Hrs complex to promote lysosomal degradation of ciliary polycystin LOV-1 (PC1) and PKD-2 (TRPP2) from early endosomes; STAM-1 interacts with LOV-1; loss of stam-1 causes accumulation of LOV-1 and PKD-2 at the ciliary base. C. elegans genetics, interaction assays (co-IP), overexpression, fluorescence localization Molecular biology of the cell Medium 17581863
2007 HGS (Hrs) is required for autophagosome maturation (fusion with lysosomes); Hrs depletion reduces the number of mature autophagolysosomes (LC3+LAMP-1+ structures) without affecting primary autophagosome formation. siRNA knockdown, autophagosome markers (LC3, LAMP-1), immunofluorescence, Streptococcus degradation assay Biochemical and biophysical research communications Medium 17624298
2007 HGS (Hrs) depletion causes enhanced EGFR recycling (not degradation); Hrs and ESCRT-I (Tsg101) are both required for EGFR degradation but not for EGFR internalization or CI-M6PR retrograde trafficking; ESCRT-II and -III depletion does not cause enhanced EGFR recycling. siRNA knockdown of Hrs, Tsg101, Vps22, Vps24; receptor trafficking and degradation assays Experimental cell research High 18031739
2008 HGS (Hrs) is essential for lysosomal targeting of ubiquitinated EGF receptors but is dispensable for multivesicular body biogenesis and transport to late endosomes; SNX3 (also a PI3P-binding protein) is required for MVB formation but not for EGFR degradation, showing complementary roles of two PI3P effectors. siRNA knockdown, electron microscopy, EGFR degradation/trafficking assays, MVB morphological analysis PLoS biology High 18767904
2008 HGS (Hrs) mediates ubiquitin-independent sorting of IL-2Rβ from early to late endosomes via direct binding to the IL-2Rβ C-terminal region through a non-UIM domain; IL-2Rβ mutant lacking the Hrs-binding region is mis-sorted to transferrin receptor-positive compartments and shows attenuated degradation. GST pull-down with bacterially expressed proteins, receptor trafficking/degradation assays, mutagenesis Journal of cell science High 18445679
2008 Neuronal-specific deletion of Hrs (hrs flox/flox; SynI-Cre mice) leads to accumulation of ubiquitinated proteins (glutamate receptors, p62), apoptosis and loss of hippocampal CA3 neurons, and severe reductions in locomotor activity and learning; establishing Hrs is essential for neuronal protein quality control and survival in vivo. Conditional knockout (Cre-lox), histological/immunohistochemical analysis, behavioral testing The American journal of pathology High 19008375
2009 HGS (Hrs) mediates Hrs-dependent recycling of full-length TrkB (TrkB-FL) but not TrkB.T1 after BDNF stimulation; this recycling requires TrkB-FL tyrosine kinase activity but is independent of the Hrs UIM; Hrs-sensitive TrkB-FL recycling sustains BDNF-induced MAPK activation. siRNA knockdown, receptor trafficking assays, UIM mutant Hrs, MAPK signaling assays in neurons The Journal of biological chemistry Medium 19351881
2009 Ubiquitylation of connexin-43 (Cx43) gap junctions triggers Hrs/Tsg101-dependent sorting from early endosomes to lysosomes; siRNA depletion of Hrs or Tsg101 blocks Cx43 lysosomal trafficking and allows Cx43 to return to the plasma membrane and form functional gap junctions; simultaneous depletion causes accumulation of phosphorylated/ubiquitylated Cx43 in early endosomes. siRNA knockdown (Hrs and Tsg101), immunofluorescence, gap junction functional assay, co-localization Journal of cell science High 19808888
2010 HGS (Hrs) is required for exosome secretion in dendritic cells; Hrs depletion significantly decreases exosome secretion following OVA and calcium ionophore stimulation, and suppresses antigen-presentation activity of purified exosomes. siRNA knockdown, ultrastructural analysis, exosome quantification, antigen-presentation assay Biochemical and biophysical research communications Medium 20673754
2010 HGS (Hrs) controls sorting of ENaC between lysosomal degradation and recycling pathways; Nedd4-2 induces binding of ENaC to Hrs and catalyzes Hrs ubiquitination; dominant-negative Hrs (ΔUIM) increases ENaC surface expression by reducing degradation of proteolytically activated ENaC. Co-immunoprecipitation, dominant-negative Hrs expression, ENaC current measurements, ubiquitination assays, mutagenesis The Journal of biological chemistry High 20675381
2010 The Drosophila Hrs/Stam (ESCRT-0) complex acts both positively and negatively on RTK signaling depending on developmental context: hrs and stam mutants show reduced FGFR signaling (with altered FGFR localization) in tracheal system, while together they downregulate EGFR in embryo but are required for full EGFR activation during wing development. Drosophila genetics (mutant alleles), electron microscopy, receptor localization assays, RTK reporter assays PloS one Medium 20422006
2011 HGS (Hrs/ESCRT-0) is required for HIV-1 Vpu-mediated down-regulation of BST-2/tetherin; BST-2 undergoes constitutive ESCRT-dependent lysosomal degradation enhanced by Vpu; Hrs co-precipitates with Vpu and BST-2; HRS knockdown increases BST-2 levels and restricts virus release. siRNA knockdown, Co-immunoprecipitation (Hrs-Vpu-BST-2), HIV release assay, flow cytometry PLoS pathogens High 21304933
2012 HGS (Hrs), as a component of ESCRT-0, is required for transport of LDL-derived cholesterol from endosomes to the endoplasmic reticulum; this function is distinct from its role in lysosomal receptor sorting, as knockdown of other ESCRT components does not cause prominent endosomal cholesterol accumulation. siRNA knockdown of Hrs and other ESCRT components, cholesterol trafficking assays, NPC1/NPC2 localization analysis Cell reports High 22832105
2012 Pkh1/2 kinases (yeast ortholog of PDK1) directly phosphorylate Vps27 (yeast Hrs ortholog) at Ser613 in vitro and in vivo; this phosphorylation is required for ESCRT-I (Vps28) endosomal recruitment and proper MVB cargo sorting. In vitro kinase assay, in vivo phosphorylation mapping, temperature-sensitive pkh mutant, ESCRT-I localization assays, MVB sorting assay in yeast Molecular biology of the cell High 22918958
2014 Ubpy (deubiquitinase) interacts with and deubiquitylates HGS (Hrs); in Ubpy-null Drosophila cells, Hrs becomes ubiquitylated and degraded in lysosomes, disrupting ESCRT-0 integrity, causing accumulation of signaling proteins in enlarged endosomes. Drosophila genetics (null mutants), Co-immunoprecipitation, deubiquitylation assay, endosomal marker analysis Development High 24574010
2015 HGS (an ESCRT-0 component) has a dual role in HBV biology: appropriate HGS levels are required for HBV transcription and virion secretion; overexpression stimulates ubiquitin-independent secretion of naked HBV capsids in a manner dependent on the arginine-rich domain of HBc; HBc preferentially co-localizes with HGS near the cell periphery rather than at punctate endosomes. siRNA screening, overexpression, HBV replication/virion assays, co-localization, domain mutagenesis, hydrodynamic delivery in mice PLoS pathogens Medium 26431433
2017 HRS promotes TLR7 complex formation in early and late endosomes during EV71 infection by interacting with TLR7 and TAB1; HRS is involved in regulation of TLR7/NF-κB/p38 MAPK and TLR7/NF-κB/IRF3 signaling to induce proinflammatory cytokines and interferons. Co-immunoprecipitation (HRS-TLR7-TAB1), siRNA knockdown, NF-κB/IRF3 reporter assays, cytokine measurements PLoS pathogens Medium 28854257
2018 HRS promotes constitutive recycling of EGFR and MT1-MMP by supporting WASH complex endosomal localization in adjacent subdomains; HRS depletion results in defective recycling (accumulation in internal compartments) and impaired matrix degradation and invasion of triple-negative breast cancer cells; direct interaction between endosomal actin and transmembrane cargo can counteract ubiquitin-dependent lysosomal sorting. siRNA knockdown, chimeric receptor trafficking assays, matrix degradation/invasion assay, immunofluorescence, proximity ligation assay The Journal of cell biology High 29891722
2022 ERK-mediated phosphorylation of HRS drives selective loading of PD-L1 into exosomes; phosphorylated HRS interacts with PD-L1 and mediates its incorporation into exosomes, which inhibit CD8+ T cell migration into tumors; overexpression of phosphorylated HRS increases resistance to anti-PD-1 therapy in murine tumor models. Phosphorylation assays (ERK-HRS), Co-immunoprecipitation (HRS-PD-L1), exosome isolation/proteomics, in vivo murine tumor models, immunofluorescence in patient melanoma samples Nature communications High 35835783
2023 HRS (ESCRT-0 component) regulates PD-L1 loading into small extracellular vesicles (sEVs); HRS knockdown markedly reduces PD-L1 in HNSCC cell-derived sEVs and decreases their immunosuppressive effects on CD8+ T cells; HRS knockout inhibits tumor growth in combination with PD-1 blockade in immunocompetent mice. siRNA/shRNA knockdown, CRISPR knockout, sEV isolation/flow cytometry, CD8+ T cell suppression assay, in vivo syngeneic tumor model Cancer immunology research High 36484721

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy. Heart rhythm 571 31078652
2002 Epsins and Vps27p/Hrs contain ubiquitin-binding domains that function in receptor endocytosis. Nature cell biology 373 11988742
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 302 24647606
2003 TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. Proceedings of the National Academy of Sciences of the United States of America 274 12802020
2003 STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. The Journal of biological chemistry 260 12551915
2001 FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. Journal of cell science 254 11493665
2003 HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. The Journal of cell biology 214 12900394
2010 Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochemical and biophysical research communications 210 20673754
2006 Distinct roles for Tsg101 and Hrs in multivesicular body formation and inward vesiculation. Molecular biology of the cell 207 16707569
1999 Hrs, a FYVE finger protein localized to early endosomes, is implicated in vesicular traffic and required for ventral folding morphogenesis. Genes & development 207 10364163
2000 A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP. The Journal of biological chemistry 193 10982817
1980 Expression of leukemogenic recombinant viruses associated with a recessive gene in HRS/J mice. The Journal of experimental medicine 174 7400758
2003 Solution structure of Vps27 UIM-ubiquitin complex important for endosomal sorting and receptor downregulation. The EMBO journal 171 12970172
2000 Hrs interacts with sorting nexin 1 and regulates degradation of epidermal growth factor receptor. The Journal of biological chemistry 170 11110793
1997 Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth. The Journal of biological chemistry 169 9407053
2005 Met/Hepatocyte growth factor receptor ubiquitination suppresses transformation and is required for Hrs phosphorylation. Molecular and cellular biology 166 16227611
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
1997 Hrs, a tyrosine kinase substrate with a conserved double zinc finger domain, is localized to the cytoplasmic surface of early endosomes. The Journal of biological chemistry 155 9252367
2003 The UIM domain of Hrs couples receptor sorting to vesicle formation. Journal of cell science 148 12953068
2000 Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through cooperation with SARA. Molecular and cellular biology 145 11094085
2006 Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nature structural & molecular biology 144 16462748
1995 Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain. Molecular and cellular biology 143 7565774
2019 2019 HRS expert consensus statement on evaluation, risk stratification, and management of arrhythmogenic cardiomyopathy: Executive summary. Heart rhythm 139 31676023
2002 Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. The Journal of biological chemistry 131 12006563
2006 Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. Journal of cell science 129 16720641
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
2006 An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Molecular biology of the cell 113 16407403
2005 Essential role of Hrs in a recycling mechanism mediating functional resensitization of cell signaling. The EMBO journal 109 15944737
2007 Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Experimental cell research 108 18031739
2005 CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. Molecular biology of the cell 104 15772161
2007 Proteomics analysis of Hodgkin lymphoma: identification of new players involved in the cross-talk between HRS cells and infiltrating lymphocytes. Blood 98 18070985
1993 Novel delayed-early and highly insulin-induced growth response genes. Identification of HRS, a potential regulator of alternative pre-mRNA splicing. The Journal of biological chemistry 98 7686911
2011 Regulation of hepatitis C virus secretion by the Hrs-dependent exosomal pathway. Virology 97 22138215
2011 The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS pathogens 91 21304933
2002 Hrs and endocytic sorting of ubiquitinated membrane proteins. Cell structure and function 91 12576633
2009 Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101. Journal of cell science 86 19808888
2008 Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. PLoS biology 84 18767904
2022 HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors. Nature communications 75 35835783
2004 Acquisition of Hrs, an essential component of phagosomal maturation, is impaired by mycobacteria. Molecular and cellular biology 73 15121875
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 72 27527224
2000 A hrs binding protein having a Src homology 3 domain is involved in intracellular degradation of growth factors and their receptors. Genes to cells : devoted to molecular & cellular mechanisms 71 10651905
2008 An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. The Journal of cell biology 67 18362181
2015 The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion. PLoS pathogens 66 26431433
2003 Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation. Biochemical and biophysical research communications 66 13679051
2006 Hse1, a component of the yeast Hrs-STAM ubiquitin-sorting complex, associates with ubiquitin peptidases and a ligase to control sorting efficiency into multivesicular bodies. Molecular biology of the cell 65 17079730
2005 The Hrs/STAM complex in the downregulation of receptor tyrosine kinases. Journal of biochemistry 65 15713877
1997 HRS/SRp40-mediated inclusion of the fibronectin EIIIB exon, a possible cause of increased EIIIB expression in proliferating liver. Molecular and cellular biology 64 9199345
2007 The Vps27/Hse1 complex is a GAT domain-based scaffold for ubiquitin-dependent sorting. Developmental cell 63 17543868
2007 STAM and Hrs down-regulate ciliary TRP receptors. Molecular biology of the cell 60 17581863
2007 Role of Hrs in maturation of autophagosomes in mammalian cells. Biochemical and biophysical research communications 60 17624298
2000 Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. The Journal of biological chemistry 57 10809762
2006 Epidermal growth factor receptor fate is controlled by Hrs tyrosine phosphorylation sites that regulate Hrs degradation. Molecular and cellular biology 55 17101784
2016 A novel TP53 pathway influences the HGS-mediated exosome formation in colorectal cancer. Scientific reports 53 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
2018 Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells. Histopathology 46 29380399
2009 Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. The Journal of biological chemistry 46 19351881
2012 An essential role of Hrs/Vps27 in endosomal cholesterol trafficking. Cell reports 45 22832105
2008 Loss of hrs in the central nervous system causes accumulation of ubiquitinated proteins and neurodegeneration. The American journal of pathology 45 19008375
2018 HRS-WASH axis governs actin-mediated endosomal recycling and cell invasion. The Journal of cell biology 44 29891722
2006 A novel sorting sequence in the beta2-adrenergic receptor switches recycling from default to the Hrs-dependent mechanism. The Journal of biological chemistry 44 17138565
2005 Growth factors induce differential phosphorylation profiles of the Hrs-STAM complex: a common node in signalling networks with signal-specific properties. The Biochemical journal 44 15828871
2010 The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development. PloS one 42 20422006
2002 Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Human molecular genetics 42 12444102
2003 Hrs function: viruses provide the clue. Trends in cell biology 40 14624836
2000 Cultivated H-RS cells are resistant to CD95L-mediated apoptosis despite expression of wild-type CD95. Experimental hematology 40 10658674
2015 Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Journal of the American College of Cardiology 39 26409260
2005 Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) interacts with PELP1 and activates MAPK. The Journal of biological chemistry 39 16352611
2001 Function of Hrs in endocytic trafficking and signalling. Biochemical Society transactions 39 11498011
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
2004 Association with Hrs is required for the early endosomal localization, stability, and function of STAM. Journal of biochemistry 37 15113837
2002 Phosphorylation of Hrs downstream of the epidermal growth factor receptor. European journal of biochemistry 36 12180964
2004 A role for Hrs in endosomal sorting of ligand-stimulated and unstimulated epidermal growth factor receptor. Experimental cell research 35 15212941
2017 HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection. PLoS pathogens 34 28854257
2001 Hrs and hbp: possible regulators of endocytosis and exocytosis. Biochemical and biophysical research communications 34 11243842
2000 Hrs interacts with SNAP-25 and regulates Ca(2+)-dependent exocytosis. Journal of cell science 34 10825299
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
2019 Comparison of urine, self-collected vaginal swab, and cervical swab samples for detecting human papillomavirus (HPV) with Roche Cobas HPV, Anyplex II HPV, and RealTime HR-S HPV assay. Journal of virological methods 33 30998958
2006 GRIF1 binds Hrs and is a new regulator of endosomal trafficking. Journal of cell science 33 17062640
2010 Hrs controls sorting of the epithelial Na+ channel between endosomal degradation and recycling pathways. The Journal of biological chemistry 31 20675381
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
1990 Cultured Reed-Sternberg cells HDLM-1 and KM-H2 can be induced to become histiocytelike cells. H-RS cells are not derived from lymphocytes. The American journal of pathology 31 2167011
2003 After Hrs with HIV. The Journal of cell biology 30 12900390
2005 Novel function of POSH, a JNK scaffold, as an E3 ubiquitin ligase for the Hrs stability on early endosomes. Cellular signalling 29 16084064
2012 Pkh1/2-dependent phosphorylation of Vps27 regulates ESCRT-I recruitment to endosomes. Molecular biology of the cell 28 22918958
2016 ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. Journal of virology 27 26819309
2013 Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: a cell line study in four glioblastoma multiforme (GBM) cell lines. International journal of radiation biology 27 23859266
2006 The endosome-associated protein Hrs is hexameric and controls cargo sorting as a "master molecule". Structure (London, England : 1993) 27 16615908
2006 The C-terminal portion of the Hrs protein interacts with Tsg101 and interferes with human immunodeficiency virus type 1 Gag particle production. Journal of virology 27 17182674
2014 Ubpy controls the stability of the ESCRT-0 subunit Hrs in development. Development (Cambridge, England) 26 24574010
2008 Ubiquitin-independent binding of Hrs mediates endosomal sorting of the interleukin-2 receptor beta-chain. Journal of cell science 26 18445679
1999 The cellular and developmental expression of hrs-2 in rat. The European journal of neuroscience 26 10510169
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
2023 HRS Regulates Small Extracellular Vesicle PD-L1 Secretion and Is Associated with Anti-PD-1 Treatment Efficacy. Cancer immunology research 24 36484721
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
2013 Impact of dose-rate on the low-dose hyper-radiosensitivity and induced radioresistance (HRS/IRR) response. International journal of radiation biology 24 23631649
2009 Proteomic analysis reveals Hrs ubiquitin-interacting motif-mediated ubiquitin signaling in multiple cellular processes. The FEBS journal 24 19019082
2012 Recycling of EGFR and ErbB2 is associated with impaired Hrs tyrosine phosphorylation and decreased deubiquitination by AMSH. Cellular signalling 23 22800866