Affinage

STAM

Signal transducing adapter molecule 1 · UniProt Q92783

Length
540 aa
Mass
59.2 kDa
Annotated
2026-06-10
54 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STAM (STAM1) is an endosomal adaptor that partners with Hrs to form the ESCRT-0 complex, which sorts ubiquitinated membrane cargo into the multivesicular body/lysosomal degradation pathway (PMID:12551915, PMID:25564854). STAM binds ubiquitin and K63-ubiquitinated cargo through its tandem VHS domain and ubiquitin-interacting motif (UIM), which cooperate to enhance ubiquitin affinity, and reconstitution on lipid bilayers shows that the ubiquitin-binding domains of both Hrs and STAM must be intact for ESCRT-0 to stably engage cargo (PMID:12972556, PMID:21187078, PMID:25564854). STAM is recruited to and stabilized on early endosomes by direct binding to Hrs via its coiled-coil region; loss of Hrs mislocalizes STAM to the cytosol, lowers STAM levels, and impairs EGFR degradation (PMID:12551915, PMID:15113837). Through its SH3 domain STAM recruits the K63-specific deubiquitinase AMSH, whose activity is allosterically stimulated upon STAM binding, with the STAM VHS domain dictating chain-length specificity and cleavage position; STAM similarly recruits the deubiquitinase USP8 via RXXK motifs to control endosomal ubiquitin dynamics and slow EGFR turnover (PMID:16431367, PMID:17078930, PMID:26601948, PMID:20736164). Beyond cargo degradation, STAM functions in cytokine and receptor signaling: it associates with the JAK2/JAK3 kinases via its ITAM and SH3 regions to transduce IL-2 and GM-CSF signals driving DNA synthesis and c-myc induction (PMID:9133424, PMID:10899310), and it constitutively scaffolds IFNAR1/TYK2 at the plasma membrane to suppress TYK2 until IFN-α-driven endocytosis delivers the complex to Hrs on endosomes to license signaling (PMID:36797476). STAM also directs activated STING into extracellular vesicles to dampen innate immunity (PMID:36946680). Genetically, STAM is required for T-cell survival downstream of cytokine receptors, for hippocampal CA3 neuron survival, and for maintenance of neuromuscular junction structure (PMID:12446783, PMID:11340172, PMID:39280771).

Mechanistic history

Synthesis pass · year-by-year structured walk · 26 steps
  1. 1997 High

    Established STAM as a JAK-associated signaling adaptor, defining its earliest known role in cytokine-driven proliferation before any endosomal function was known.

    Evidence Co-IP, dominant-negative SH3/ITAM mutants, and DNA synthesis/c-myc assays in IL-2 and GM-CSF stimulated cells

    PMID:9133424

    Open questions at the time
    • Did not place STAM in endosomal trafficking
    • Direct kinase substrate relationship within the complex not resolved
  2. 1997 High

    Identified Hrs as a direct STAM partner that counteracts STAM-driven proliferation, the first link between the two future ESCRT-0 subunits.

    Evidence Cloning, reciprocal Co-IP, deletion mutagenesis, and DNA synthesis rescue/loss assays

    PMID:9407053

    Open questions at the time
    • Endosomal localization of the complex not yet shown
    • Mechanism of growth suppression undefined
  3. 1999 Medium

    Placed AMSH downstream of the JAK-STAM complex via the STAM SH3 domain, foreshadowing deubiquitinase recruitment.

    Evidence Yeast two-hybrid, Co-IP, and dominant-negative AMSH in DNA synthesis/c-myc assays

    PMID:10383417

    Open questions at the time
    • AMSH enzymatic activity and ubiquitin specificity not yet established
    • Single lab
  4. 2000 Medium

    Showed STAM2 is a functionally redundant paralog, establishing the STAM family with compensatory roles in cytokine signaling.

    Evidence cDNA cloning, Co-IP with JAK2/JAK3, additive dominant-negative DNA synthesis assays

    PMID:10899310

    Open questions at the time
    • Degree of functional overlap in vivo not addressed
    • Single lab
  5. 2003 High

    Reframed STAM as an endosomal ubiquitin-sorting factor by demonstrating ternary Hrs-STAM-Eps15 assembly and VHS/UIM-dependent binding of ubiquitinated cargo and EGFR on early endosomes.

    Evidence Recombinant ternary complex reconstitution, in vitro ubiquitin-binding, siRNA, confocal microscopy, EGFR assays

    PMID:12551915 PMID:12972556

    Open questions at the time
    • Quantitative ubiquitin affinities not measured
    • Cooperativity between domains not yet structurally defined
  6. 2003 Medium

    Identified DDP/TIMM8a as a binding partner mapping to the STAM coiled-coil/ITAM overlap region used by JAK and Hrs, implying competing or shared interaction surfaces.

    Evidence Yeast two-hybrid, Co-IP, pulldowns, Zn2+-dependent binding and nuclear redistribution assays

    PMID:12745081

    Open questions at the time
    • Functional consequence of the interaction unclear
    • Single lab
  7. 2004 High

    Defined Hrs binding via the STAM coiled-coil as the determinant of endosomal localization and STAM protein stability, linking complex assembly to sorting function.

    Evidence Deletion mutagenesis, RNAi, fractionation, microscopy, EGFR degradation assays

    PMID:15113837

    Open questions at the time
    • Mechanism of STAM destabilization upon Hrs loss unresolved
  8. 2005 Medium

    Showed Hrs-STAM phosphorylation is endocytosis- and ubiquitin-dependent and signal-specific, coupling receptor activation to combinatorial complex modification.

    Evidence Kinase inhibitor profiling, phospho-antibodies, dominant-negative c-Cbl, UIM mutagenesis

    PMID:15828871

    Open questions at the time
    • Specific phosphosites and their functional roles not mapped
    • Single lab
  9. 2006 High

    Established the catalytic logic of STAM-AMSH coupling: STAM allosterically activates AMSH, which is K63-selective and links to ESCRT-III, integrating deubiquitination with cargo sorting.

    Evidence In vitro DUB activity reconstitution, K63/K48 specificity, Co-IP/pulldown with CHMP3 and clathrin; affinity-mapped RXXK/PxVDRxxKP motif binding

    PMID:16431367 PMID:17078930

    Open questions at the time
    • Structural basis of activation not yet determined
    • In vivo timing of deubiquitination vs sorting unresolved
  10. 2006 High

    In yeast, demonstrated that the Hse1-Vps27 (STAM-Hrs ortholog) complex coordinates both ubiquitin ligases and peptidases to set cargo ubiquitination status for MVB sorting.

    Evidence Yeast two-hybrid and genetic epistasis with MVB cargo sorting readouts

    PMID:17079730

    Open questions at the time
    • Direct extrapolation to mammalian STAM not tested
    • PY/Hua1 module conservation unclear
  11. 2007 High

    Connected STAM to receptor turnover beyond EGFR by showing STAM-Hrs sorts the polycystin LOV-1/PKD-2 complex for lysosomal degradation in cilia, with sensory phenotypes.

    Evidence C. elegans stam-1 loss-of-function, overexpression, ciliary localization microscopy, behavioral assays

    PMID:17581863

    Open questions at the time
    • Mammalian polycystin sorting by STAM not demonstrated
  12. 2007 Medium

    Identified Rin1 as an SH3-domain partner that cooperates with STAM to accelerate EGFR degradation, expanding the endosomal sorting machinery.

    Evidence Co-IP, deletion mutagenesis, confocal colocalization, EGFR degradation and siRNA assays

    PMID:17403676

    Open questions at the time
    • Mechanistic role of Rin1 GEF activity in this complex unclear
    • Single lab
  13. 2008 Medium

    Extended STAM function to early exocytic trafficking, showing STAM associates with COPII at ER exit sites and influences Golgi integrity and secretory transport.

    Evidence Co-IP with COPII, Sar1-dependence, siRNA/overexpression, VSVg-GFP live imaging, Brefeldin A recovery

    PMID:19054391

    Open questions at the time
    • Whether this is independent of ESCRT-0 function unclear
    • Single lab
  14. 2010 High

    Defined USP8 as a second deubiquitinase recruited to STAM via RXXK motifs that, in opposition to Hrs, controls endosomal ubiquitin dynamics and slows EGFR progression.

    Evidence Co-IP, single/double siRNA, catalytic mutant, EGFR ubiquitination assays, Hrs-rescue epistasis

    PMID:20736164

    Open questions at the time
    • Interplay/competition between AMSH and USP8 on STAM not resolved
  15. 2010 Medium

    Revealed context-dependent positive and negative regulation of RTK signaling by Stam-Hrs in Drosophila, complicating a purely degradative view.

    Evidence stam/hrs loss-of-function, EM endosome morphology, receptor localization, epistasis

    PMID:20422006

    Open questions at the time
    • Molecular basis of signal-promoting role undefined
    • Single lab, ortholog system
  16. 2010 Medium

    Provided structural and thermodynamic basis for STAM ubiquitin recognition, showing the UIM helix and cooperative VHS-UIM binding.

    Evidence NMR structure of UIM, ITC of tandem VHS-UIM, mutagenesis

    PMID:21187078

    Open questions at the time
    • Full-length ESCRT-0 cargo-binding structure not solved
    • Single lab
  17. 2015 High

    Demonstrated ESCRT-0 cooperativity directly: only Hrs+STAM together, with both ubiquitin-binding domains intact, stably bind cargo in a lipid bilayer.

    Evidence In vitro reconstitution on lipid bilayer with VAMP2-ubiquitin cargo and UBD mutagenesis

    PMID:25564854

    Open questions at the time
    • Behavior with polyubiquitinated and clustered cargo not addressed
  18. 2015 Medium

    Showed the STAM VHS domain confers chain-length and linkage selectivity onto AMSH cleavage, refining the enzymatic specificity of the complex.

    Evidence In vitro DUB kinetics on di/tri-ubiquitin, mutagenesis, structural modeling

    PMID:26601948

    Open questions at the time
    • Experimental high-resolution structure of AMSH-STAM-chain complex lacking
    • Single lab
  19. 2014 Medium

    Revealed a dynamic membrane binding/dissociation cycle for ESCRT-0 in which STAM1 promotes Hrs release from endosomes, indicating regulated complex turnover.

    Evidence Fluorescent protein reconstitution/microinjection, blue-native PAGE, STAM1 co-expression, EGFR assays

    PMID:25296754

    Open questions at the time
    • Physiological trigger for the cycle unclear
    • Single lab
  20. 2016 Medium

    Linked STAM1 to GPCR-driven cell motility through a β-arrestin1-STAM1 complex required for CXCR4-dependent FAK activation and chemotaxis.

    Evidence Co-IP, minigene disruption, RNAi, FAK autophosphorylation, chemotaxis assays

    PMID:27789711

    Open questions at the time
    • How endosomal adaptor function relates to FAK signaling unclear
    • Single lab
  21. 2016 Medium

    Placed STAM1 in a developmental gene-regulatory circuit as an ISL1-LHX3 target that sets CXCR4 levels controlling motor axon trajectory.

    Evidence Transactivation/ChIP, in ovo shRNA and overexpression, axon projection immunofluorescence

    PMID:27161150

    Open questions at the time
    • Mechanism by which STAM1 sets CXCR4 protein level not dissected
    • Single lab
  22. 2002 High

    Showed via T-cell double knockout that STAMs are required for lymphocyte survival, not proximal cytokine signaling, decoupling the in vivo role from the early biochemical model.

    Evidence Conditional STAM1/STAM2 double knockout, flow cytometry, proliferation, STAT5/ERK/Akt analysis, viability assays

    PMID:12446783

    Open questions at the time
    • Molecular link between STAM and apoptosis suppression undefined
  23. 2001 High

    Established a cytokine-independent neuronal survival role, showing STAM1 protects hippocampal CA3 neurons from excitotoxicity.

    Evidence STAM1 knockout mice, histology, primary neuron excitotoxicity/NO-donor viability assays

    PMID:11340172

    Open questions at the time
    • Mechanism connecting endosomal sorting to neuronal survival unknown
  24. 2023 High

    Defined a spatial signaling switch in which STAM constitutively suppresses TYK2 at the plasma membrane and IFN-α-driven endocytosis to Hrs+ endosomes licenses IFNAR signaling.

    Evidence Co-IP, live-cell/single-molecule imaging, siRNA epistasis, phospho-STAT and endosomal fractionation

    PMID:36797476

    Open questions at the time
    • Structural basis of TYK2 inhibition by STAM not resolved
    • IFN-β endosomal subdomain identity unclear
  25. 2023 Medium

    Showed STAM directs activated STING into extracellular vesicles as a degradative route that dampens innate immune signaling.

    Evidence Co-IP, EV isolation, STING activation and innate immune readouts

    PMID:36946680

    Open questions at the time
    • Relationship to ESCRT-driven ILV/MVB sorting of STING unclear
    • Single lab
  26. 2024 Medium

    Identified an HGS/STAM1 requirement for neuromuscular junction maintenance, with progressive endplate degeneration and loss of presynaptic SNAREs.

    Evidence STAM1 knockout mouse histology, endplate immunofluorescence, motor performance, SNARE/AChR Western blots

    PMID:39280771

    Open questions at the time
    • Causal link between cargo sorting and SNARE loss undefined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How STAM coordinates its competing deubiquitinases (AMSH vs USP8), its multiple signaling roles, and the molecular basis of its survival functions in neurons and T cells into one regulated program remains unresolved.
  • No unified model linking ESCRT-0 sorting to apoptosis suppression
  • Switch governing AMSH vs USP8 recruitment unknown
  • No human Mendelian disease link established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0031386 protein tag activity 3 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0038024 cargo receptor activity 2
Localization
GO:0005768 endosome 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
AMSH (STAMBP)HGSIFNAR1JAK2JAK3STING1TYK2USP8
Complex memberships
ESCRT-0 (Hrs-STAM)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 STAM is associated with Jak3 and Jak2 tyrosine kinases via its ITAM region and is phosphorylated by Jak3 and Jak2 upon stimulation with IL-2 and GM-CSF, respectively. An SH3 deletion mutant of STAM confers a dominant-negative effect on DNA synthesis, and wild-type STAM (but not SH3 or ITAM deletion mutants) enhances c-myc induction mediated by IL-2 and GM-CSF. Co-immunoprecipitation, dominant-negative mutant overexpression, DNA synthesis assay, c-myc induction assay Immunity High 9133424
1997 Hrs (the human counterpart of mouse Hrs) associates with STAM via coiled-coil sequences. Tyrosine phosphorylation of Hrs is induced by IL-2, GM-CSF, and HGF. Exogenous wild-type Hrs suppresses DNA synthesis upon IL-2 and GM-CSF stimulation, while the Hrs mutant lacking the STAM-binding site loses this suppressive ability, indicating that Hrs counteracts STAM function through direct interaction. Molecular cloning, co-immunoprecipitation, deletion mutagenesis, DNA synthesis assay The Journal of biological chemistry High 9407053
1999 AMSH (associated molecule with the SH3 domain of STAM) is a novel protein that interacts with the SH3 domain of STAM. An AMSH C-terminal deletion mutant confers dominant-negative effects on DNA synthesis and c-myc induction mediated by IL-2 and GM-CSF, placing AMSH downstream of the Jak2/Jak3-STAM complex. Yeast two-hybrid, co-immunoprecipitation, dominant-negative mutant overexpression, DNA synthesis assay The Journal of biological chemistry Medium 10383417
2000 STAM2 (a new STAM family member containing SH3 and ITAM domains) associates with Jak2 and Jak3 and is involved in signaling for DNA synthesis and c-myc induction mediated by IL-2 and GM-CSF. Co-expression of SH3 deletion mutants of STAM1 and STAM2 produces additive suppression of DNA synthesis, indicating compensatory roles. cDNA cloning, co-immunoprecipitation, dominant-negative mutant overexpression, DNA synthesis assay FEBS letters Medium 10899310
2003 STAM1 and STAM2 interact directly with Hrs via the same coiled-coil domain that targets Hrs to endosomes. STAM1, STAM2, and Eps15 can be co-immunoprecipitated with Hrs from membrane and cytosolic fractions, and recombinant Hrs, STAM1/STAM2, and Eps15 form a ternary complex in vitro. Overexpression of Hrs recruits STAM2 to endosome membranes. STAM2, Hrs, and Eps15 colocalize with ubiquitinated proteins in clathrin-containing endosomal microdomains. Hrs depletion by siRNA reduces STAM2 endosomal recruitment and impairs EGFR degradation. Co-immunoprecipitation, recombinant protein reconstitution, siRNA knockdown, confocal microscopy, EGFR degradation assay The Journal of biological chemistry High 12551915
2003 STAM proteins (STAM1 and STAM2) bind ubiquitin and ubiquitinated proteins via their tandemly located VHS domain and ubiquitin-interacting motif (UIM). STAM proteins colocalize with Hrs on the early endosome. Overexpression of STAM, but not ubiquitin-binding-deficient mutants, causes accumulation of ubiquitinated proteins and ligand-activated EGFR on the early endosome. In vitro ubiquitin-binding assay, deletion mutagenesis, confocal microscopy, EGFR accumulation assay Molecular biology of the cell High 12972556
2003 DDP/TIMM8a (the deafness-dystonia protein) directly interacts with STAM1, as identified by yeast two-hybrid screening and confirmed by co-immunoprecipitation, fusion protein pulldowns, and nuclear redistribution assays. Zn2+ stimulates the DDP-STAM1 interaction in vitro. The interaction requires a coiled-coil region in STAM1 that overlaps with the ITAM, the same region important for Jak2/3 and Hrs interactions. Yeast two-hybrid, co-immunoprecipitation, pulldown assay, nuclear redistribution assay, in vitro binding assay Biochemical and biophysical research communications Medium 12745081
2004 STAM localization to the early endosome requires binding to Hrs via its coiled-coil region; STAM2 mutants lacking the coiled-coil region mislocalize to the cytoplasm. Depletion of endogenous Hrs by RNAi causes STAM2 mislocalization to the cytoplasm and drastically reduces endogenous STAM protein levels, indicating Hrs binding stabilizes STAM. Hrs-binding-deficient STAM2 mutants fail to cause endosome enlargement, accumulate ubiquitinated proteins, or inhibit EGFR degradation. Deletion mutagenesis, siRNA knockdown, confocal microscopy, subcellular fractionation, EGFR degradation assay Journal of biochemistry High 15113837
2005 Phosphorylation of the Hrs-STAM complex requires receptor endocytosis and an intact UIM in Hrs. A dominant-negative c-Cbl (E3 ubiquitin ligase) inhibits EGF- and HGF-dependent Hrs phosphorylation. Distinct non-receptor tyrosine kinases couple EGF, HGF, and PDGF to generate a signal-specific, combinatorial phosphorylation profile of the Hrs-STAM complex. Kinase inhibitor profiling, phospho-specific antibodies, dominant-negative c-Cbl expression, UIM mutagenesis The Biochemical journal Medium 15828871
2006 AMSH directly binds the SH3 domain of STAM and is markedly stimulated in deubiquitinating activity by co-incubation with STAM in vitro. AMSH shows specificity for K63- over K48-linked polyubiquitin chains. AMSH also binds clathrin and interacts with mVps24/CHMP3 (ESCRT-III), with the latter interaction reinforced by simultaneous STAM binding. In vitro deubiquitinase activity assay, co-immunoprecipitation, pulldown assay Current biology : CB High 16431367
2006 In yeast, the STAM homolog Hse1 interacts with ubiquitin peptidases (Ubp2, Ubp7) and the ubiquitin ligase Rsp5 via a PY element in its C-terminus and through a novel protein Hua1. The SH3 domain of Hse1 binds the deubiquitinating protein Ubp7. Disruption of both Rsp5-association modes blocks MVB sorting of ubiquitination-dependent cargo, whereas further deletion of Ubp7 restores sorting, establishing that both ubiquitin ligases and peptidases associate with the Hse1-Vps27 complex to control ubiquitination status and cargo sorting efficiency. Yeast two-hybrid, genetic epistasis (double/triple mutant analysis), MVB cargo sorting assay Molecular biology of the cell High 17079730
2006 AMSH requires the Px(V/I)(D/N)RxxKP sequence motif to bind the SH3 domain of STAM with ~7 µM affinity. The isolated C-terminal domain of AMSH contains isopeptidase activity. Deubiquitination by AMSH is facilitated when ubiquitin chains are simultaneously bound to STAM, with specificity for K63-linked ubiquitins. In vitro binding assay (affinity measurement), in vitro deubiquitinase activity assay, domain deletion analysis Biochemical and biophysical research communications Medium 17078930
2007 In C. elegans, STAM-1A interacts with the polycystin PC1 (LOV-1), and STAM functions with Hrs on early endosomes to direct the LOV-1–PKD-2 complex for lysosomal degradation. In a stam-1 mutant, both LOV-1 and PKD-2 improperly accumulate at the ciliary base. Conversely, overexpression of STAM or Hrs promotes removal of PKD-2 from cilia, causing sensory behavioral defects. Genetic loss-of-function (stam-1 mutant), transgenic overexpression, fluorescence microscopy (ciliary localization), behavioral assay Molecular biology of the cell High 17581863
2007 Rin1 interacts with STAM2 through the SH3 domain of STAM2 and the proline-rich domain (PRD) of Rin1, as demonstrated by co-immunoprecipitation. GFP-Rin1 co-localizes with HA-STAM2 and endogenous Hrs. Rin1ΔPRD, lacking the PRD, does not interact with STAM2 and fails to accelerate EGFR degradation, indicating Rin1 regulates EGFR degradation in cooperation with STAM. Co-immunoprecipitation, deletion mutagenesis, confocal microscopy, EGFR degradation assay, siRNA knockdown The Journal of biological chemistry Medium 17403676
2008 STAM proteins localize prominently to early exocytic compartments and interact with COPII proteins, probably at ER exit sites; Sar1 activity is required to maintain STAM localization at discrete ER exit sites. STAM overexpression causes Golgi fragmentation; STAM depletion causes Golgi condensation. Both scenarios inhibit VSVg-GFP trafficking to the plasma membrane and impair Golgi recovery after Brefeldin A treatment. Co-immunoprecipitation (STAM-COPII interaction), siRNA knockdown, overexpression, live-cell imaging (VSVg-GFP trafficking), Brefeldin A recovery assay, confocal microscopy Traffic (Copenhagen, Denmark) Medium 19054391
2010 USP8 directly interacts with the SH3 domain(s) of STAM1/2 through three extended RXXK motifs in its central region. USP8 depletion accelerates EGFR turnover; this is rescued by co-depletion of Hrs. Catalytic inactivation of USP8 causes EGFR hyperubiquitination and promotes receptor localization to high-ubiquitin endosomes. The USP8·STAM complex regulates ubiquitin dynamics on EGFR-positive endosomes, slowing EGFR progression past the early-to-recycling endosome circuit in a manner dependent on the RXXK motifs. Co-immunoprecipitation, siRNA knockdown (single and double), catalytic mutant analysis, EGFR ubiquitination assay, confocal microscopy, epistasis (Hrs rescue) The Journal of biological chemistry High 20736164
2010 In Drosophila, Hrs and Stam are both required for efficient FGFR signaling during tracheal cell migration and terminal cell cytoplasmic extension formation. stam and hrs mutant cells display altered FGFR/Btl localization. While stam and hrs together downregulate EGFR signaling in the embryo, they are required for full activation of EGFR signaling during wing development, demonstrating context-dependent positive and negative regulation of RTK signaling. Genetic loss-of-function (stam and hrs mutants), electron microscopy (endosome morphology), confocal microscopy (receptor localization), epistasis analysis PloS one Medium 20422006
2010 The STAM1 UIM adopts an α-helical structure with amphipathic character, determined by NMR. The central hydrophobic residues provide the ubiquitin-binding surface. The tandem VHS domain and UIM of STAM1 show cooperative ubiquitin binding with affinities of 52.4 µM and 94.9 µM respectively, with 1.5–2.2-fold enhancement over isolated domains. NMR structure determination, ITC (isothermal titration calorimetry), mutagenesis Biochemical and biophysical research communications Medium 21187078
2014 Hrs can be targeted to endosomes independently of STAM; co-expression of STAM1 promotes dissociation of Hrs from endosomal membranes. Fluorescently labeled Hrs introduced by membrane permeabilization or microinjection shows endosomal localization in the absence of STAM1 but dissociates upon sequential addition of recombinant STAM1. Blue-native PAGE reveals membrane-associated Hrs exists partly as a monomer and not only in STAM1-bound form, indicating a membrane binding/dissociation cycle of ESCRT-0 proteins. Fluorescent protein reconstitution/microinjection, blue-native PAGE, STAM1 co-expression, confocal microscopy, EGFR degradation assay The Journal of biological chemistry Medium 25296754
2015 ESCRT-0 (Hrs and STAM together), but not ESCRT-I or ESCRT-II, can stably associate with mono-ubiquitinated membrane cargo (VAMP2-ubiquitin) reconstituted in a lipid bilayer. Both ubiquitin-binding domains in Hrs and STAM must be intact to enable cargo binding, demonstrating that the two ESCRT-0 subunits function cooperatively. In vitro reconstitution in lipid bilayer, ubiquitin-binding domain mutagenesis, cargo-binding assay Biophysical journal High 25564854
2015 The VHS domain of STAM directs AMSH specificity toward longer K63-linked ubiquitin chains and dictates the position of cleavage (distal isopeptide bond in tri-ubiquitin). The kcat for di- versus tri-ubiquitin cleavage is comparable, but the Km is lower for tri-ubiquitin in a VHS-domain-dependent and K63-linkage-homogeneity-dependent manner. A structural model of the AMSH-STAM complex was generated to show how the complex binds K63-linked chains. In vitro deubiquitinase kinetics, deletion mutagenesis, chain-linkage specificity assay, structural modeling The Journal of biological chemistry Medium 26601948
2016 The β-arrestin1·STAM1 complex mediates CXCR4-dependent chemotaxis. Expression of minigene fragments from β-arrestin1 or STAM1 (to disrupt the complex) and RNAi against either protein attenuates CXCL12-induced chemotaxis. The β-arrestin1·STAM1 complex is necessary for promoting autophosphorylation of focal adhesion kinase (FAK); FAK associates with and co-localizes with β-arrestin1 and STAM1 in a CXCL12-dependent manner. Co-immunoprecipitation, minigene dominant-negative expression, RNAi knockdown, FAK autophosphorylation assay, confocal microscopy, chemotaxis assay The Journal of biological chemistry Medium 27789711
2016 STAM1 is a direct transcriptional target of the ISL1-LHX3 complex in spinal motor neurons. STAM1 knockdown in the developing chick spinal cord downregulates CXCR4 expression and causes dorsally projecting motor axons. Overexpression of STAM1 also results in dorsal projection, indicating that precise CXCR4 protein level controlled by STAM1 is necessary for proper ventral motor axon trajectory. Chromatin immunoprecipitation/transactivation assay (ISL1-LHX3 → Stam1), in ovo shRNA knockdown, overexpression, immunofluorescence (axon projection) Development (Cambridge, England) Medium 27161150
2023 STAM constitutively associates with IFNAR1 and TYK2 kinase at the plasma membrane, preventing TYK2 activation by type I IFNs. IFN-α-stimulated IFNAR endocytosis delivers the STAM-IFNAR complex to early endosomes where it interacts with Hrs, relieving TYK2 inhibition and triggering IFNAR signaling at the endosome. In contrast, IFN-β-stimulated IFNAR signaling occurs independently of Hrs as IFNAR is sorted to a distinct endosomal subdomain. Co-immunoprecipitation, live-cell fluorescence imaging, siRNA knockdown, JAK-STAT signaling readout (phospho-STAT), endosomal fractionation, FRAP/single-molecule imaging Nature cell biology High 36797476
2023 STAM directly interacts with STING and facilitates transport of STING oligomers into extracellular vesicles (EVs) upon STING activation. STING translocation into EVs serves as a degradation mechanism that suppresses the innate immune response. Co-immunoprecipitation, EV isolation and characterization, STING activation assays, innate immune signaling readout Journal of extracellular vesicles Medium 36946680
2002 T-cell-specific double knockout of STAM1 and STAM2 causes significant reduction in thymocytes and peripheral mature T cells, with defective proliferative response to TCR stimulation and IL-2/IL-7. Downstream signaling (STAT5, ERK, PKB/Akt, c-myc) remains normal in double mutant thymocytes, but double mutant thymocytes exhibit accelerated cell death in culture, indicating STAMs are required for T-cell survival through prevention of apoptosis but are dispensable for proximal cytokine receptor signaling. Conditional double knockout (Cre/loxP), flow cytometry, proliferation assay, signaling analysis (STAT5/ERK/Akt phosphorylation), cell viability assay Molecular and cellular biology High 12446783
2001 STAM1 knockout mice develop normally but lose hippocampal CA3 pyramidal neurons. Primary hippocampal neurons from STAM1-/- mice are more vulnerable to cell death induced by excitotoxic amino acids or an NO donor, demonstrating a role for STAM1 in neuronal survival independent of its cytokine signaling role in lymphocytes. Homologous recombination knockout, histology, primary neuron culture, excitotoxicity assay (NMDA/NO donor treatment), cell viability measurement Molecular and cellular biology High 11340172
2024 Loss of STAM1 in knockout mice causes reduced muscle mass, strength, and motor performance by 3 months of age. The motor endplate structure is altered from 1 month of age with progressive degeneration, increased embryonic γ-AChR subunit expression, and significant reduction of presynaptic SNARE proteins VTI1A and VAMP2 in motor neurons, indicating the HGS/STAM1 complex maintains synaptic structure and function. STAM1 knockout mouse analysis, histology, immunofluorescence (motor endplate morphology), grip strength/motor performance tests, Western blot (SNARE proteins), AChR subunit expression Current research in neurobiology Medium 39280771

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. The Journal of biological chemistry 260 12551915
2006 Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Current biology : CB 170 16431367
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
2001 Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. The Journal of biological chemistry 161 11390366
1997 STAM, signal transducing adaptor molecule, is associated with Janus kinases and involved in signaling for cell growth and c-myc induction. Immunity 133 9133424
1999 Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines. The Journal of biological chemistry 116 10383417
2003 STAM proteins bind ubiquitinated proteins on the early endosome via the VHS domain and ubiquitin-interacting motif. Molecular biology of the cell 101 12972556
2010 Regulation of epidermal growth factor receptor ubiquitination and trafficking by the USP8·STAM complex. The Journal of biological chemistry 89 20736164
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
2000 STAM2, a new member of the STAM family, binding to the Janus kinases. FEBS letters 65 10899310
2007 STAM and Hrs down-regulate ciliary TRP receptors. Molecular biology of the cell 60 17581863
2002 Signal-transducing adaptor molecules STAM1 and STAM2 are required for T-cell development and survival. Molecular and cellular biology 51 12446783
2001 Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1. Molecular and cellular biology 46 11340172
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
2001 STAM/EAST/Hbp adapter proteins--integrators of signalling pathways. FEBS letters 43 11728436
2010 The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development. PloS one 42 20422006
2004 Association with Hrs is required for the early endosomal localization, stability, and function of STAM. Journal of biochemistry 37 15113837
2007 Rin1 interacts with signal-transducing adaptor molecule (STAM) and mediates epidermal growth factor receptor trafficking and degradation. The Journal of biological chemistry 33 17403676
1999 The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial. Gene 31 10231582
2016 β-Arrestin1 and Signal-transducing Adaptor Molecule 1 (STAM1) Cooperate to Promote Focal Adhesion Kinase Autophosphorylation and Chemotaxis via the Chemokine Receptor CXCR4. The Journal of biological chemistry 30 27789711
2023 STAM transports STING oligomers into extracellular vesicles, down-regulating the innate immune response. Journal of extracellular vesicles 28 36946680
2020 The Role of the Histone Methyltransferase EZH2 in Liver Inflammation and Fibrosis in STAM NASH Mice. Biology 28 32370249
2006 STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH. Biochemical and biophysical research communications 26 17078930
2018 Gemcabene downregulates inflammatory, lipid-altering and cell-signaling genes in the STAM™ model of NASH. PloS one 23 29847555
2015 Hrs and STAM function synergistically to bind ubiquitin-modified cargoes in vitro. Biophysical journal 22 25564854
2008 STAM adaptor proteins interact with COPII complexes and function in ER-to-Golgi trafficking. Traffic (Copenhagen, Denmark) 21 19054391
2020 Omaveloxolone and TX63682 are hepatoprotective in the STAM mouse model of nonalcoholic steatohepatitis. Journal of biochemical and molecular toxicology 20 32410268
2017 Pathophysiological analysis of the progression of hepatic lesions in STAM mice. Physiological research 20 28730823
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
2018 STAM-binding protein regulates melanoma metastasis through SLUG stabilization. Biochemical and biophysical research communications 19 30454887
2023 STAM and Hrs interact sequentially with IFN-α Receptor to control spatiotemporal JAK-STAT endosomal activation. Nature cell biology 18 36797476
2014 ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation. The Journal of biological chemistry 16 25296754
2022 Characterization and Genomic Analysis of a Novel Jumbo Bacteriophage vB_StaM_SA1 Infecting Staphylococcus aureus With Two Lysins. Frontiers in microbiology 14 35572667
2003 Interaction of the deafness-dystonia protein DDP/TIMM8a with the signal transduction adaptor molecule STAM1. Biochemical and biophysical research communications 14 12745081
2004 STAM: simple transmembrane alignment method. Bioinformatics (Oxford, England) 12 14751993
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
2010 Solution structure of UIM and interaction of tandem ubiquitin binding domains in STAM1 with ubiquitin. Biochemical and biophysical research communications 10 21187078
2022 STAM binding protein regulated by hsa_circ_0007334 exerts oncogenic potential in pancreatic cancer. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 9 36089485
2024 Identification of STAM-binding protein as a target for the treatment of gemcitabine resistance pancreatic cancer in a nutrient-poor microenvironment. Cell death & disease 7 39242557
2018 Identification of unique glycoisoforms of vitamin D-binding protein and haptoglobin as biomarker candidates in hepatocarcinogenesis of STAM mice. Glycoconjugate journal 7 30194503
2023 STAM-binding Protein-like 1 Promotes Growth and Migration of Colorectal Cancer by NF-κB Pathway. Protein and peptide letters 4 38008943
2020 sTAM: An Online Tool for the Discovery of miRNA-Set Level Disease Biomarkers. Molecular therapy. Nucleic acids 4 32750560
2023 LncRNA MAGI2-AS3 inhibites tumor progression by up-regulating STAM via interacting with miR-142-3p in clear cell renal cell carcinoma. Cellular signalling 3 38084836
2021 STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion. Frontiers in oncology 3 33959493
2016 Identification of STAM1 as a novel effector of ventral projection of spinal motor neurons. Development (Cambridge, England) 3 27161150
2024 Periodontitis promotes hepatocellular carcinoma in Stelic Animal model (STAM) mice. Scientific reports 2 39080409
2023 Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice. Scientific reports 2 37264108
2021 Corrigendum: STAM Prolongs Clear Cell Renal Cell Carcinoma Patients' Survival via Inhibiting Cell Growth and Invasion. Frontiers in oncology 2 34568056
2005 stam--a Bioconductor compliant R package for structured analysis of microarray data. BMC bioinformatics 2 16122395
2024 Analysis of the neuromuscular deficits caused by STAM1 deficiency. Current research in neurobiology 1 39280771
2026 STAM1-deficient mice exhibit an attention-deficit/hyperactivity disorder-like phenotype. Biochemical and biophysical research communications 0 41520568
2026 Cholesterol-rich diet exacerbates steatohepatitis in the STAM mouse model. Scientific reports 0 41922430
2025 Sequencing Trait-Associated Mutations (STAM) to Clone Rust Resistance Genes. Methods in molecular biology (Clifton, N.J.) 0 40198565

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