Affinage

STAMBP

STAM-binding protein · UniProt O95630

Length
424 aa
Mass
48.1 kDa
Annotated
2026-06-10
51 papers in source corpus 34 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

STAMBP (AMSH) is a JAMM-domain zinc metalloprotease deubiquitinase that functions in endosomal cargo sorting by cleaving polyubiquitin from membrane receptors, with strict preference for K63-linked chains in its activated state (PMID:15314065, PMID:16431367, PMID:24151880). Catalysis depends on a conserved active site, and an inactivating D348A mutation causes ubiquitin to accumulate on endosomes and stabilizes ubiquitinated STAM (PMID:15314065). Its activity is gated by intramolecular autoinhibition: the N-terminal MIT domain binds the catalytic domain and occludes the distal ubiquitin-binding site, an inhibition relieved specifically by STAM binding but not by CHMP3 (PMID:40441142). STAM stimulation underlies the enzyme's K63 specificity by supplying a ubiquitin-interaction module that engages the proximal ubiquitin while the catalytic domain binds the distal ubiquitin, stabilizing the chain in a productive orientation and biasing cleavage toward distal isopeptide bonds in longer chains (PMID:24151880, PMID:17078930, PMID:26601948, PMID:27725184). STAMBP is embedded in the multivesicular-body machinery: a clathrin-binding site on its N-terminus anchors it to early endosomes independently of STAM (PMID:16716190), while interaction with ESCRT-III subunits including CHMP3 (via a high-affinity MIM4–MIT interface) is required for in vivo deubiquitination of cargo rather than for localization or catalysis per se (PMID:16431367, PMID:16760479, PMID:17261583, PMID:17159328, PMID:21827950). Through these activities STAMBP controls the lysosomal fate of multiple surface receptors and substrates, including EGFR, CXCR4, connexin-43, and the calcium-sensing receptor, and restrains NLRP3 inflammasome activation by removing K63 chains from NLRP3 (PMID:15314065, PMID:20159979, PMID:25070368, PMID:16854379, PMID:17426287, PMID:33253913, PMID:34102455). STAMBP protein level is itself controlled by an RNF11/Smurf2 axis that ubiquitinates it for proteasomal degradation (PMID:14755250). Loss-of-function mutations in STAMBP cause microcephaly-capillary malformation (MIC-CAP) syndrome, with patient cells showing ubiquitin-conjugated protein aggregates, elevated apoptosis, and constitutive RAS-MAPK and PI3K-AKT-mTOR signaling (PMID:23542699); this neuronal requirement is reinforced by knockout mice that develop hippocampal and cortical neuronal death with ubiquitinated aggregate accumulation, a phenotype rescuable by brain-directed STAMBP gene supplementation (PMID:11713295, PMID:21531206, PMID:39169623).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Medium

    Established STAMBP/AMSH as a STAM-associated molecule functionally linked to cytokine signaling, framing it as more than an isolated protein.

    Evidence Yeast two-hybrid against the STAM SH3 domain plus dominant-negative proliferation/signaling assays

    PMID:10383417

    Open questions at the time
    • No enzymatic activity defined
    • Mechanism downstream of STAM unresolved
  2. 2001 High

    Defined a tissue-specific essential role by showing AMSH loss selectively kills hippocampal CA1 and cortical neurons, distinguishing neuronal dependence from a general housekeeping function.

    Evidence Gene-targeted knockout mouse with histopathology and in vitro neuronal survival assays

    PMID:11713295

    Open questions at the time
    • Molecular basis of neuron-selective death not established
    • No link to enzymatic activity yet
  3. 2004 High

    Identified STAMBP as a ubiquitin isopeptidase acting on endosomal cargo, and revealed it is itself degraded via an RNF11/Smurf2 ubiquitination axis, establishing both its catalytic identity and its turnover.

    Evidence In vitro isopeptidase assay with active-site mutagenesis (D348A), siRNA, plus Co-IP and in vitro ubiquitination assays for RNF11/Smurf2

    PMID:14755250 PMID:15314065

    Open questions at the time
    • Chain-linkage specificity in cells not yet resolved
    • Regulation of the RNF11/Smurf2 axis unknown
  4. 2006 Medium

    Determined how STAMBP is recruited and activated: clathrin anchors it to early endosomes, ESCRT-III subunits provide cargo-proximal positioning, and STAM binding markedly stimulates K63-chain cleavage.

    Evidence RNAi, deletion mutants, fluorescence colocalization, in vitro reconstitution with purified STAM, and reciprocal Co-IP with CHMP1A/1B/2A/3

    PMID:16431367 PMID:16716190 PMID:16760479 PMID:16854379 PMID:17078930 PMID:17426287

    Open questions at the time
    • Separation of localization vs. catalytic requirements still incomplete
    • Structural basis of activation not yet known
  5. 2007 Medium

    Demonstrated that endosomal localization via CHMP3 is functionally required, separating receptor degradation from internalization.

    Evidence Dominant-negative CHMP3 mislocalization with EGFR degradation assays and Co-IP

    PMID:17159328 PMID:17261583

    Open questions at the time
    • Whether CHMP3 contributes catalytically or only positionally needed clarification
  6. 2011 High

    Provided the structural and disease framework: crystal structures of the catalytic domain and the MIT–CHMP3 interface explained the high-affinity ESCRT engagement, while knockout mice showed ubiquitinated aggregate accumulation with co-trapped TDP-43, glutamate receptors, and p62.

    Evidence X-ray crystallography, ITC/SPR, thermodynamic unfolding, HIV-1 budding assay, and knockout-mouse immunohistochemistry

    PMID:21531206 PMID:21827950 PMID:21888914

    Open questions at the time
    • Autoinhibitory role of the MIT domain not yet recognized
    • In vivo substrate hierarchy in neurons unresolved
  7. 2013 High

    Connected enzyme mechanism to human disease, showing proximal-ubiquitin recognition drives K63 specificity and that the MIC-CAP mutation T313I abolishes catalysis, while patient cells reveal aggregate accumulation, apoptosis, and constitutive RAS-MAPK/PI3K-AKT-mTOR signaling.

    Evidence Kinetic and mutational analyses with purified STAM, plus whole-exome sequencing and patient cell-line pathway/apoptosis assays

    PMID:23542699 PMID:24151880

    Open questions at the time
    • How catalytic loss drives pathway hyperactivation mechanistically unclear
    • Capillary malformation phenotype mechanism unaddressed
  8. 2015 Medium

    Refined the activation model by showing the STAM VHS domain tunes chain-length preference and directs distal-bond cleavage, lowering Km for longer K63 chains.

    Evidence In vitro cleavage kinetics with STAM domain truncations and chain-length panels

    PMID:25070368 PMID:26601948

    Open questions at the time
    • Physiological chain lengths on real cargo not measured
  9. 2017 Medium

    Extended STAMBP function to innate immunity by showing it stabilizes NALP7 and controls IL-1β release, and that a small-molecule inhibitor reproduces loss of function.

    Evidence siRNA, Co-IP, ubiquitination assays, BC-1471 inhibitor treatment, and IL-1β ELISA

    PMID:28492230

    Open questions at the time
    • Linkage specificity on NALP7 not defined
    • Inhibitor selectivity not fully characterized
  10. 2020 Medium

    Defined STAMBP as a negative regulator of the NLRP3 inflammasome acting by removing K63 chains from NLRP3 without changing its abundance.

    Evidence CRISPR/Cas9 knockout in monocytes, ubiquitination assays, and inflammasome/cytokine readouts

    PMID:33253913

    Open questions at the time
    • Recruitment to NLRP3 not mapped
    • In vivo inflammatory role untested
  11. 2021 High

    Established pharmacological tractability and EGFR regulation, developing ubiquitin-variant inhibitors with a JAMM–UbV crystal structure and showing STAMBP stabilizes EGFR to sustain MAPK/ERK signaling.

    Evidence Phage display, X-ray crystallography of STAMBPL1-UbV, in vitro inhibition assays, plus siRNA and EGFR stability/xenograft assays

    PMID:34102455 PMID:34425109

    Open questions at the time
    • Cellular efficacy of UbV inhibitors not shown
    • EGFR linkage type in this context not detailed
  12. 2022 Medium

    Broadened substrate scope beyond K63 by showing STAMBP removes K48 chains from RAI14 to block proteasomal degradation, supporting tumor growth.

    Evidence IP-mass spectrometry, Co-IP, ubiquitination assays, siRNA, and xenograft model

    PMID:36434041

    Open questions at the time
    • Reconciliation of K48 activity with reported K63 specificity unaddressed
  13. 2024 High

    Cemented the brain-specific requirement and therapeutic potential, with CNS-specific knockout phenocopying microcephaly and AAV9 gene supplementation rescuing defects, while human models linked catalytic function to neurogenesis via NSC proliferation and CFLAR-dependent survival.

    Evidence Conditional knockout mice with AAV9 rescue, hESC cortical organoid KO with wild-type vs. mutant rescue, and NPC expansion/CFLAR rescue assays

    PMID:36033615 PMID:38951308 PMID:39169623

    Open questions at the time
    • Direct neuronal substrates driving death not pinpointed
    • How catalytic loss lowers CFLAR mechanistically unknown
  14. 2025 High

    Resolved the activation switch and expanded oncogenic substrate networks, showing the MIT domain autoinhibits the catalytic domain (relieved by STAM but not CHMP3) and that IKKα phosphorylation at Ser2 activates substrate-specific deubiquitination of BAG3, with additional cancer substrates ERα, CXCR4, and YY1.

    Evidence X-ray crystallography of the MIT-CD complex with biochemical validation, mass spectrometry, Co-IP, site-specific ubiquitination assays, and xenograft models

    PMID:40441142 PMID:41301420 PMID:41456274 PMID:41559433 PMID:41611844

    Open questions at the time
    • Mix of K48 and K63 substrate claims not mechanistically unified
    • Several cancer-substrate findings rest on single-lab Co-IP without structural validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how STAMBP's endosomal/ESCRT-coupled K63 deubiquitination relates mechanistically to its reported K48-cleaving, proteasome-sparing roles on cytosolic and nuclear substrates, and how catalytic loss produces the specific neuronal death and pathway hyperactivation of MIC-CAP.
  • No unified model linking linkage specificity to substrate localization
  • Direct disease-relevant neuronal substrates uncharacterized
  • Mechanism of constitutive RAS-MAPK/PI3K-AKT-mTOR activation unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016787 hydrolase activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005768 endosome 4 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2
Partners
CHMP1ACHMP1BCHMP2ACHMP3CLTCRNF11SMURF2STAM
Complex memberships
ESCRT-III

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 AMSH (STAMBP) is a ubiquitin isopeptidase with activity against K48-linked tetraubiquitin and K63-linked polyubiquitin chains in vitro. An inactivating mutation (D348A) causes accumulation of ubiquitin on endosomes and stabilization of ubiquitinated STAM. AMSH knockdown enhances EGFR degradation rate, and ubiquitinated EGFR serves as an in vitro substrate. In vitro isopeptidase assay, active-site mutagenesis (D348A), siRNA knockdown, immunofluorescence The Journal of cell biology High 15314065
2006 AMSH is activated by coincubation with STAM, showing marked stimulation of K63-linked polyubiquitin chain cleavage in vitro. AMSH directly binds clathrin and ESCRT-III component mVps24/CHMP3; simultaneous STAM binding reinforces the CHMP3 interaction. These interactions embed AMSH within the MVB-sorting machinery. In vitro enzymatic assay with purified components, direct binding assays, Co-IP Current biology : CB High 16431367
1999 AMSH (STAMBP) was identified as a novel molecule interacting with the SH3 domain of STAM. A dominant-negative C-terminal deletion mutant of AMSH inhibits IL-2- and GM-CSF-mediated signaling for DNA synthesis and c-myc induction, placing AMSH downstream of the Jak2/Jak3·STAM complex. Yeast two-hybrid, dominant-negative mutant overexpression, cell proliferation and signaling assays The Journal of biological chemistry Medium 10383417
2006 AMSH interacts with ESCRT-III subunits CHMP1A, CHMP1B, CHMP2A, and CHMP3. Catalytically inactive AMSH acts as a dominant negative, inhibiting retroviral budding and causing accumulation of ubiquitinated endosomal cargo. VPS4 and AMSH compete for binding to C-terminal regions of CHMP1A and CHMP1B. Co-IP, dominant-negative overexpression, retroviral budding assay, competition binding assay The Journal of biological chemistry Medium 16760479
2007 AMSH interacts with CHMP3 (ESCRT-III) in cells; a dominant-negative CHMP3 that prevents AMSH targeting to endosomes inhibits EGFR degradation but not internalization, demonstrating that endosomal localization of AMSH is required for its function in the MVB pathway. Co-IP, dominant-negative CHMP3 overexpression, EGFR degradation assay, fluorescence microscopy The Journal of biological chemistry Medium 17261583
2006 AMSH and AMSH-LP are anchored to early endosomes via a novel clathrin-binding site on the terminal domain of clathrin heavy chain. Deletion of this site or RNAi depletion of clathrin heavy chain abolishes endosomal localization of AMSH, whereas loss of STAM-binding does not affect endosomal localization. RNAi knockdown, deletion mutants, fluorescence co-localization microscopy, fractionation Genes to cells : devoted to molecular & cellular mechanisms Medium 16716190
2006 AMSH-mediated deubiquitination of endosomal cargo in vivo requires both its catalytic DUB activity and its CHMP3-binding ability; an AMSH mutant lacking CHMP3-binding localizes normally to endosomes but causes accumulation of ubiquitinated cargo, indicating CHMP3 interaction is needed for in vivo substrate access rather than localization or catalytic activity per se. Mutant overexpression, immunofluorescence, in vitro DUB assay Cell structure and function Medium 17159328
2004 RNF11 binds AMSH in mammalian cells independently of the RNF11 RING domain and PY motif, and recruits AMSH to the HECT-type E3 ligase Smurf2, which ubiquitinates AMSH leading to its proteasomal degradation. Yeast two-hybrid, Co-IP in mammalian cells, in vitro ubiquitination assay Oncogene Medium 14755250
2010 AMSH loss-of-function or catalytic inactivity increases basal steady-state CXCR4 levels, and catalytically inactive AMSH causes basal hyperubiquitination of ESCRT-0 components STAM1 and Hrs in an RXXK-motif-dependent manner. The RXXK motif mediates high-affinity interaction with SH3 domains of STAM and Grb2 families. RNAi knockdown, catalytic mutant overexpression, co-IP, CXCR4 trafficking/degradation assays The Journal of biological chemistry Medium 20159979
2011 Crystal structure of the AMSH catalytic domain (JAMM motif) was determined; the catalytic domain of AMSH is nearly identical to that of AMSH-LP but is thermodynamically less stable. An active-site mutant (E280A) retains zinc coordination via compensatory aspartate repositioning, indicating structural plasticity. A modeled AMSH-diubiquitin complex reveals a distinct distal ubiquitin interface compared to AMSH-LP. X-ray crystallography, guanidine-HCl unfolding (thermodynamic stability), structural modeling Journal of molecular biology High 21888914
2011 Crystal structure of the AMSH N-terminal fragment in complex with CHMP3 C-terminal region reveals that the AMSH N-terminus folds into an elongated helical assembly containing an unusual MIT domain. CHMP3 is unstructured in solution but forms a helix upon binding AMSH via a novel MIM4 motif with unusually high affinity. The N-terminal helical segment of AMSH has a regulatory role: its destabilization causes loss of function during HIV-1 budding. X-ray crystallography, ITC, SPR, HIV-1 budding functional assay Structure (London, England : 1993) High 21827950
2013 Kinetic and mutational analysis established that proximal ubiquitin recognition is critical for AMSH's K63-linkage specificity and catalytic efficiency. The MIC-CAP disease mutation T313I causes substantial loss of catalytic activity without altering thermodynamic stability. STAM activates AMSH by providing its UIM to bind the proximal ubiquitin while AMSH catalytic domain binds the distal ubiquitin, stabilizing the chain in a productive orientation. Kinetic assays, site-directed mutagenesis, biochemical/biophysical analyses (thermal stability), in vitro reconstitution with purified STAM Biochemistry High 24151880
2001 AMSH-deficient mice generated by gene targeting show selective postnatal death of hippocampal CA1 neurons and cerebral cortex atrophy, with AMSH-deficient hippocampal neurons unable to survive in vitro. Neurons from other regions (cerebellum) and other cell types (thymocytes, fibroblasts) survive normally, establishing a tissue-specific essential role for AMSH in neuronal survival. Gene-targeted knockout mouse, histopathology, in vitro neuronal culture survival assay Molecular and cellular biology High 11713295
2011 AMSH-deficient mice accumulate ubiquitinated protein aggregates in the brain beginning at embryonic day 10. TDP-43, glutamate receptors, and p62 co-accumulate with ubiquitinated aggregates in the brain, indicating AMSH is required for degradation of ubiquitinated proteins and glutamate receptors in the CNS in vivo. AMSH knockout mouse, immunohistochemistry, immunofluorescence co-localization Biochemical and biophysical research communications Medium 21531206
2013 Loss-of-function mutations in STAMBP cause microcephaly-capillary malformation (MIC-CAP) syndrome. Patient cell lines show reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis, and insensitive (constitutive) activation of RAS-MAPK and PI3K-AKT-mTOR signaling pathways. Whole-exome sequencing, patient cell line analysis, western blotting for pathway activation, apoptosis assays Nature genetics High 23542699
2014 AMSH interacts with Cx43 (connexin-43), mediates its deubiquitination, and is recruited to gap junction plaque sites at the plasma membrane. Cx43 is modified with K63-linked polyubiquitin chains. siRNA depletion or catalytically inactive AMSH overexpression increases both the internalization and degradation rate of Cx43, indicating that AMSH-mediated deubiquitination protects gap junctions from degradation. Co-IP, siRNA knockdown, catalytic mutant overexpression, fluorescence microscopy, ubiquitin linkage-specific analysis FASEB journal Medium 25070368
2006 AMSH interacts with the carboxyl terminus of the calcium-sensing receptor (CaR) and causes a decrease in CaR signaling properties. AMSH overexpression redirects CaR from slow recycling (Rab11a-dependent) to down-regulation, reducing CaR expression and PTHrP secretion. Yeast two-hybrid/co-IP, dominant-negative Rab11a, PTHrP secretion assay, CaR signaling assays Biochemical and biophysical research communications; Molecular endocrinology Medium 16854379 17426287
2006 STAM binding to AMSH via the SH3 domain (requiring a PxVDRxxKP motif in AMSH) facilitates the deubiquitination activity of the isolated AMSH C-terminal domain in vitro, with specificity toward K63-linked ubiquitin chains, by enabling simultaneous STAM-ubiquitin and AMSH-ubiquitin engagement. In vitro DUB assay with purified components, binding affinity measurement, mutagenesis Biochemical and biophysical research communications Medium 17078930
2015 The VHS (Vps27/Hrs/STAM) domain of STAM directs AMSH to preferentially cleave longer K63-linked ubiquitin chains by lowering Km without changing kcat for tri-ubiquitin vs. di-ubiquitin. STAM also directs AMSH cleavage toward the distal isopeptide bond in tri-ubiquitin chains. This effect requires homogenous K63-linkages. In vitro cleavage kinetics, STAM domain truncation mutants, structural modeling The Journal of biological chemistry Medium 26601948
2016 NMR analysis shows that the SH3-binding motif (SBM) of AMSH outcompetes K63-linked diubiquitin for binding to the SH3 domain of STAM2. The NMR solution structure of the AMSH-SBM/STAM2-SH3 complex was determined, revealing how AMSH binding to STAM2 positions AMSH for polyubiquitin chain cleavage. NMR spectroscopy, solution structure determination, binding competition experiments Journal of molecular biology High 27725184
2017 STAMBP deubiquitinates NALP7, impeding its trafficking to lysosomes and thereby stabilizing NALP7 protein upon TLR ligation by LPS or Pam3CSK4. STAMBP knockdown abrogates TLR agonist-induced NALP7 accumulation. A small-molecule STAMBP inhibitor (BC-1471) decreases NALP7 levels and suppresses IL-1β release. siRNA knockdown, Co-IP, ubiquitination assay, small-molecule inhibitor treatment, IL-1β ELISA Nature communications Medium 28492230
2020 STAMBP deubiquitinates NLRP3 by removing K63-linked polyubiquitin chains, acting as a negative regulator of NLRP3 inflammasome activation. CRISPR/Cas9 knockout of STAMBP in monocytes increases NLRP3 K63-polyubiquitination, inflammasome activation, and IL-1β release after TLR ligation, without altering NLRP3 protein abundance. CRISPR/Cas9 knockout, ubiquitination assay, ELISA for cytokines, inflammasome activation assay Cellular signalling Medium 33253913
2021 Ubiquitin variant (UbV) inhibitors UbVSP.1 and UbVSP.3 were developed that bind STAMBP with high affinity and potently inhibit its isopeptidase activity. The crystal structure of the STAMBPL1-UbVSP.1 complex was determined by X-ray crystallography, revealing hotspots of the JAMM-UbV interaction relevant to STAMBP. Phage display, X-ray crystallography, in vitro isopeptidase inhibition assays, affinity measurements The Journal of biological chemistry High 34425109
2022 STAMBP stabilizes the actin-binding protein RAI14 by deubiquitinating K48-linked polyubiquitin chains on RAI14, thereby preventing its proteasomal degradation. Knockdown of STAMBP reduces RAI14 protein levels and suppresses TNBC tumor growth in vitro and in vivo. IP-mass spectrometry, Co-IP, ubiquitination assay, siRNA knockdown, xenograft mouse model Experimental & molecular medicine Medium 36434041
2025 The MIT domain of STAMBP autoinhibits its catalytic domain by binding tightly to it and occupying a large portion of the distal ubiquitin-binding site. The crystal structure of the MIT-CD complex reveals this mechanism. STAM1 binding to STAMBP relieves this autoinhibition and enhances activity, whereas CHMP3 binding does not relieve autoinhibition. X-ray crystallography, biochemical activity assays with domain fragments, mutational analysis, binding assays Structure (London, England : 1993) High 40441142
2021 STAMBP deubiquitinates EGFR to promote its membrane stabilization and prevents its degradation in lung adenocarcinoma cells. STAMBP localizes to early endosomes where it acts on EGFR, and its knockdown reduces EGFR stability and attenuates MAPK/ERK signaling after EGF treatment. siRNA knockdown, immunofluorescence, EGFR stability and ubiquitination assay, western blotting for ERK, xenograft mouse model Neoplasia Medium 34102455
2025 STAMBP deubiquitinates ERα by removing K48-linked polyubiquitin chains, thereby enhancing ERα protein stability and promoting ERα-dependent oncogenic signaling. STAMBP knockdown reduces ERα stability and restores tamoxifen sensitivity in endocrine-resistant breast cancer cells. siRNA knockdown, Co-IP, ubiquitination assay, drug sensitivity assay Biomolecules Low 41301420
2025 STAMBP is phosphorylated by IKKα at Ser2, and this phosphorylation activates STAMBP to deubiquitinate BAG3 by removing K63-linked polyubiquitin chains at Lys29 and Lys60, stabilizing BAG3 and promoting PDAC progression. STAMBP deficiency increases cisplatin/oxaliplatin sensitivity. Mass spectrometry substrate identification, Co-IP, ubiquitination assay with site-specific mutants, phosphorylation assay, xenograft mouse model Cell death and differentiation Medium 41611844
2025 STAMBP deubiquitinates CXCR4 to stabilize its protein expression in colorectal cancer cells, promoting CRC proliferation and MDSC recruitment. Silencing CXCR4 reversed both STAMBP-driven tumor growth and MDSC infiltration. siRNA knockdown, Co-IP, ubiquitination assay, functional proliferation and immune cell recruitment assays Genes and immunity Low 41559433
2025 NOL6 recruits STAMBP to deubiquitinate YY1 by removing K48-linked polyubiquitin chains at lysine 339, preventing YY1 proteasomal degradation and enhancing c-Myc transcription in colorectal cancer. Co-IP, ubiquitination assay with site-specific mutants, reporter assay for c-Myc transcription Cell reports Low 41456274
2024 CNS-specific Stambp knockout mice phenocopy null mice with microcephaly, growth retardation, and preweaning death. Early-onset neuronal death occurs specifically in hippocampus and cortex with ubiquitinated protein aggregation and neuroinflammation. AAV9-mediated postnatal Stambp gene supplementation to the brain rescues neurological defects, sustains growth, and prolongs lifespan. Conditional knockout mouse, histopathology, AAV9 gene therapy rescue experiment Molecular therapy High 39169623
2024 STAMBP knockout in human cortical organoids reduces neural stem cell (NSC) proliferation, yielding smaller organoids characteristic of microcephaly. Re-expression of wild-type STAMBP rescues impaired NSC proliferation, but known pathogenic mutants do not, directly linking STAMBP catalytic function to cortical neurogenesis. hESC-derived cortical organoids with STAMBP KO, rescue by wild-type vs. mutant re-expression, proliferation assays Frontiers in neuroscience Medium 36033615
2024 STAMBP-deficient neural progenitor cells (NPCs) derived from hESCs fail to maintain long-term in vitro expansion. The anti-apoptotic protein CFLAR is downregulated in STAMBP-deficient NPCs, and ectopic CFLAR expression rescues NPC defects, placing STAMBP upstream of the death receptor apoptosis pathway in NPCs. hESC differentiation, STAMBP KO, protein expression analysis, CFLAR rescue experiment Stem cell reviews and reports Medium 38951308

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 AMSH is an endosome-associated ubiquitin isopeptidase. The Journal of cell biology 319 15314065
2006 Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Current biology : CB 170 16431367
1999 Possible involvement of a novel STAM-associated molecule "AMSH" in intracellular signal transduction mediated by cytokines. The Journal of biological chemistry 116 10383417
2006 Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo. The Journal of biological chemistry 111 16760479
2013 Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome. Nature genetics 89 23542699
2017 Targeting the deubiquitinase STAMBP inhibits NALP7 inflammasome activity. Nature communications 69 28492230
2007 Targeting of AMSH to endosomes is required for epidermal growth factor receptor degradation. The Journal of biological chemistry 68 17261583
2010 AMSH interacts with ESCRT-0 to regulate the stability and trafficking of CXCR4. The Journal of biological chemistry 60 20159979
2004 An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein. Oncogene 57 14755250
2020 The deubiquitinase STAMBP modulates cytokine secretion through the NLRP3 inflammasome. Cellular signalling 54 33253913
2006 AMSH, an ESCRT-III associated enzyme, deubiquitinates cargo on MVB/late endosomes. Cell structure and function 51 17159328
2011 Structural and thermodynamic comparison of the catalytic domain of AMSH and AMSH-LP: nearly identical fold but different stability. Journal of molecular biology 45 21888914
2011 Structural basis for ESCRT-III CHMP3 recruitment of AMSH. Structure (London, England : 1993) 42 21827950
2001 Loss of neurons in the hippocampus and cerebral cortex of AMSH-deficient mice. Molecular and cellular biology 41 11713295
2014 AMSH-mediated deubiquitination of Cx43 regulates internalization and degradation of gap junctions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 25070368
2007 Calcium-sensing receptor endocytosis links extracellular calcium signaling to parathyroid hormone-related peptide secretion via a Rab11a-dependent and AMSH-sensitive mechanism. Molecular endocrinology (Baltimore, Md.) 36 17426287
2004 Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor beta signaling. BMC cell biology 34 14728725
2013 Mechanism of recruitment and activation of the endosome-associated deubiquitinase AMSH. Biochemistry 33 24151880
2006 Clathrin anchors deubiquitinating enzymes, AMSH and AMSH-like protein, on early endosomes. Genes to cells : devoted to molecular & cellular mechanisms 33 16716190
2022 The deubiquitinating enzyme STAMBP is a newly discovered driver of triple-negative breast cancer progression that maintains RAI14 protein stability. Experimental & molecular medicine 28 36434041
2003 Identification of AMSH-LP containing a Jab1/MPN domain metalloenzyme motif. Biochemical and biophysical research communications 28 12810066
2006 STAM-AMSH interaction facilitates the deubiquitination activity in the C-terminal AMSH. Biochemical and biophysical research communications 26 17078930
2021 STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway. Neoplasia (New York, N.Y.) 24 34102455
2011 AMSH is required to degrade ubiquitinated proteins in the central nervous system. Biochemical and biophysical research communications 24 21531206
2012 Recycling of EGFR and ErbB2 is associated with impaired Hrs tyrosine phosphorylation and decreased deubiquitination by AMSH. Cellular signalling 23 22800866
2006 AMSH regulates calcium-sensing receptor signaling through direct interactions. Biochemical and biophysical research communications 20 16854379
2021 Structural and functional characterization of ubiquitin variant inhibitors for the JAMM-family deubiquitinases STAMBP and STAMBPL1. The Journal of biological chemistry 17 34425109
2016 Microcephaly-capillary malformation syndrome: Brothers with a homozygous STAMBP mutation, uncovered by exome sequencing. American journal of medical genetics. Part A 16 27531570
2015 Novel STAMBP mutation and additional findings in an Arabic family. American journal of medical genetics. Part A 12 25692795
2013 High-throughput compatible fluorescence resonance energy transfer-based assay to identify small molecule inhibitors of AMSH deubiquitinase activity. Analytical biochemistry 12 23747283
2018 A novel homozygous missense mutation in the SH3-binding motif of STAMBP causing microcephaly-capillary malformation syndrome. Journal of human genetics 11 29907875
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
2019 Early‑onset epilepsy and microcephaly‑capillary malformation syndrome caused by a novel STAMBP mutation in a Chinese boy. Molecular medicine reports 9 31638258
2022 Serum alpha-melanocyte-stimulating hormone (a-MSH), brain-derived neurotrophic factor (BDNF), and agouti-related protein (AGRP) levels in children with Prader-Willi or Bardet-Biedl syndromes. Journal of endocrinological investigation 8 35098494
2022 Novel compound heterozygous mutation in STAMBP causes a neurodevelopmental disorder by disrupting cortical proliferation. Frontiers in neuroscience 6 36033615
2016 NMR Reveals the Interplay among the AMSH SH3 Binding Motif, STAM2, and Lys63-Linked Diubiquitin. Journal of molecular biology 6 27725184
2023 Novel STAMBP mutations in a Chinese girl with rare symptoms of microcephaly-capillary malformation syndrome and Mowat-Wilson syndrome. Heliyon 5 38058451
2011 Nipped in the bud: how the AMSH MIT domain helps deubiquitinate lysosome-bound cargo. Structure (London, England : 1993) 5 21827939
2025 Gut Escherichia coli promotes lung cancer by increasing circulating STAMBP production. Discover oncology 4 40180620
2024 AAV-mediated Stambp gene replacement therapy rescues neurological defects in a mouse model of microcephaly-capillary malformation syndrome. Molecular therapy : the journal of the American Society of Gene Therapy 4 39169623
2022 The expression and clinical significance of STAMBP in breast cancer. Molecular biology reports 4 36309616
2003 A newly identified AMSH-family protein is specifically expressed in haploid stages of testicular germ cells. Biochemical and biophysical research communications 3 12943674
2025 The MIT domain of STAMBP autoinhibits its deubiquitination activity. Structure (London, England : 1993) 1 40441142
2025 PEZO-1 is not required for AMsh glial responses to mechanical stimulation and does not play a major role in nose touch avoidance in C. elegans. microPublication biology 1 40625671
2025 AXIN1, STAMBP, ST1A1, CDCP1, and SIRT2 Validated as Myasthenia Gravis Biomarkers: A Comparative Proteomic Study With MS, CIDP, and Controls. European journal of neurology 1 41235764
2025 Lactylation-stabilized NOL6 promotes colorectal cancer progression via STAMBP-mediated YY1 deubiquitination and c-Myc transcription upregulation. Cell reports 1 41456274
2026 STAMBP drives colorectal cancer progression via CXCR4 deubiquitination and bone marrow-derived suppressor cell recruitment. Genes and immunity 0 41559433
2026 Expanding the Phenotype of STAMBP-Related Microcephaly-Capillary Malformation Syndrome. American journal of medical genetics. Part A 0 41603106
2026 Phosphorylation-dependent STAMBP drives the progression of pancreatic ductal adenocarcinoma by deubiquitinating and stabilizing BAG3. Cell death and differentiation 0 41611844
2025 STAMBP Accelerates Progression and Tamoxifen Resistance of Breast Cancer Through Deubiquitinating ERα. Biomolecules 0 41301420
2024 STAMBP is Required for Long-Term Maintenance of Neural Progenitor Cells Derived from hESCs. Stem cell reviews and reports 0 38951308

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