Affinage

ITCH

E3 ubiquitin-protein ligase Itchy homolog · UniProt Q96J02

Length
903 aa
Mass
102.8 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITCH (AIP4) is a HECT-domain E3 ubiquitin ligase that uses its WW domains to engage substrates and partners and its catalytic HECT domain to build polyubiquitin chains controlling receptor down-regulation, signal-pathway tuning, apoptosis, and organelle quality control (PMID:14602072, PMID:17463226, PMID:20504295). A recurrent theme is endosomal-to-lysosomal sorting of membrane receptors: ITCH ubiquitinates the chemokine receptor CXCR4 and the sorting factor Hrs to coordinate lysosomal degradation (PMID:14602072), and targets Notch1 and Deltex for lysosomal turnover by assembling non-canonical K29-linked chains (PMID:17028573, PMID:18628966), while also ubiquitinating TRPV4/TRPC4 channels and ErbB-4/HER3 to reduce their surface abundance and stability (PMID:17110928, PMID:17463226). ITCH activity is gated by autoinhibition and by activating inputs: JNK-mediated phosphorylation and deubiquitination by USP8/USP9X stimulate substrate ubiquitination (e.g., cFLIP and HER3), whereas the adaptor SPG20/Spartin binds the WW region to relieve autoinhibition and recruits ITCH to specific membranes (PMID:20504295, PMID:20484045, PMID:27203743). Beyond degradation, ITCH acts as a ubiquitination-independent scaffold for Smad7 at the TGF-β type I receptor to inhibit TGF-β signaling (PMID:15946939), and it controls apoptosis by degrading cFLIP in concert with TGIF, which it monoubiquitinates to form a feedback loop (PMID:20064471). At organelles, Spartin-activated ITCH ubiquitinates adipophilin on lipid droplets and marks damaged lysosomes with K63-linked chains to initiate lysophagy (PMID:20504295, PMID:38503285); it also K48-ubiquitinates influenza M1 to restrict viral replication (PMID:30328013). Genetic loss of Itch in mice produces an itchy, multi-organ inflammatory phenotype reflecting its broad role in immune regulation and T-cell tolerance (PMID:26085204).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 Medium

    Established that ITCH engages receptor down-regulation machinery, showing it interacts with the RING ligase CBLC via WW-domain/proline-rich binding and cooperatively dampens EGFR signaling.

    Evidence Yeast two-hybrid, GST pulldown, Co-IP, and dominant-negative EGFR ubiquitination assays

    PMID:12226085

    Open questions at the time
    • Direct chain linkage on EGFR not defined
    • Single lab; physiological context of CBLC cooperation untested
  2. 2003 High

    Defined ITCH as a plasma-membrane and endosomal ligase coordinating lysosomal receptor sorting by ubiquitinating both the cargo CXCR4 and the sorting machine Hrs.

    Evidence Co-IP, colocalization, dominant-negative and siRNA experiments with Hrs/Vps4

    PMID:14602072

    Open questions at the time
    • Chain-type on CXCR4 not specified
    • Recruitment mechanism to the receptor not resolved
  3. 2005 High

    Revealed that ITCH has a catalysis-independent function, scaffolding Smad7 onto the TGF-β type I receptor to inhibit signaling separately from Smad7 degradation.

    Evidence Yeast two-hybrid, catalytic-dead mutant, Co-IP, and TGF-β reporter assays

    PMID:15946939

    Open questions at the time
    • Structural basis of the scaffold not determined
    • In vivo relevance of scaffolding vs degradation unquantified
  4. 2006 High

    Showed ITCH builds non-canonical K29-linked chains to route Deltex to lysosomes and degrades TRP channels and p63, establishing substrate diversity and chain-type specificity.

    Evidence K29-specific ubiquitin mutants, surface biotinylation/electrophysiology, Co-IP, and degradation assays

    PMID:16861923 PMID:17028573 PMID:17110928

    Open questions at the time
    • How chain-type selection is achieved mechanistically is unknown
    • p63 finding is Medium confidence/single lab
  5. 2007 Medium

    Extended ITCH receptor regulation to ErbB-4/HER4, showing WW-domain binding drives ubiquitination and degradation that limits nuclear access of the ErbB-4 intracellular domain.

    Evidence Phage display, Co-IP, in vivo ubiquitination, degradation, and nuclear fractionation

    PMID:17463226

    Open questions at the time
    • Proteasomal vs lysosomal route not cleanly separated
    • Single lab
  6. 2008 High

    Demonstrated ligand-independent Notch1 degradation by ITCH requires a bridging factor or modification rather than direct binding, refining how ITCH recognizes Notch.

    Evidence Itch−/− fibroblast reconstitution, lysosomal rescue, K29-chain analysis, negative in vitro binding

    PMID:18628966

    Open questions at the time
    • Identity of the bridging factor/modification not established
    • Mechanism of Notch recruitment unresolved
  7. 2009 High

    Connected ITCH to TNF-α-induced apoptosis, showing TGIF association exposes cFLIP(L) for degradation while ITCH monoubiquitinates TGIF at K259 to create positive feedback.

    Evidence TNF-α-inducible Co-IP, ubiquitination assays, K259R mutagenesis, apoptosis assays

    PMID:20064471

    Open questions at the time
    • Direct vs adaptor-mediated cFLIP recognition not separated
    • Stoichiometry of the feedback loop unclear
  8. 2010 Medium

    Identified upstream regulators of ITCH activity: Spartin relieves WW/HECT autoinhibition to activate the ligase at lipid droplets, USP8 deubiquitinates ITCH to enhance cFLIP(S) degradation, and AKT/JNK status controls JUNB degradation.

    Evidence ELISA binding affinity, self-ubiquitination, colocalization, siRNA rescue epistasis, promoter-reporter and apoptosis assays

    PMID:20484045 PMID:20504295 PMID:21135252

    Open questions at the time
    • Each axis from a single lab
    • Integration of competing kinase/DUB inputs not modeled
  9. 2015 Medium

    Consolidated ITCH's broad immune role, linking its loss to T-cell tolerance failure and multi-organ inflammation in the itchy mouse.

    Evidence Review of Itch−/− mouse genetics and substrate ubiquitination studies

    PMID:26085204

    Open questions at the time
    • Review consolidation rather than new primary data
    • Substrate-to-phenotype causality not dissected here
  10. 2016 Medium

    Showed antibody-induced HER3 degradation operates through ITCH activated by JNK1/2 phosphorylation and USP8/USP9X, with N4BP1 acting as an inhibitor, integrating multiple regulatory inputs at one substrate.

    Evidence siRNA knockdown, N4BP1 overexpression, Co-IP, ubiquitination, JNK inhibition

    PMID:27203743

    Open questions at the time
    • Relative contribution of each activator not quantified
    • Single lab/therapeutic-antibody context
  11. 2018 Medium

    Defined an antiviral role for ITCH, K48-ubiquitinating influenza M1 at K102/K104 for proteasomal degradation, with Cyclophilin A antagonizing the interaction to control M1 nuclear export.

    Evidence Lysine-specific ubiquitin mutants, K102R/K104R mutagenesis, recombinant virus rescue, localization assays

    PMID:30328013

    Open questions at the time
    • In vivo relevance to infection not established
    • Single lab
  12. 2024 High

    Established ITCH as an effector of lysosomal quality control, recruited and activated by Spartin's lipid-damage-sensing amphipathic helices to deposit K63-linked ubiquitin on damaged lysosomes and initiate lysophagy.

    Evidence Proximity ligation, Co-IP, K63-specific linkage analysis, amphipathic-helix mutagenesis, live imaging, autophagy flux in human cells

    PMID:38503285

    Open questions at the time
    • Downstream lysophagy receptors recognizing the K63 mark not detailed here
    • How repair (IST1) vs destruction decision is set quantitatively

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ITCH selects substrate-specific chain linkages (K29 vs K48 vs K63) and integrates competing kinase/DUB/adaptor inputs to dictate proteasomal versus lysosomal versus signaling outcomes remains unresolved.
  • No structural model linking activator binding to chain-type output
  • Substrate recruitment codes for direct vs bridged binding not generalized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005886 plasma membrane 2 GO:0005811 lipid droplet 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-168256 Immune System 1 R-HSA-9609507 Protein localization 1 R-HSA-9612973 Autophagy 1
Partners
CBLCHRSN4BP1SMAD7SPG20TGIFUSP8USP9X

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 AIP4/ITCH (HECT E3 ubiquitin ligase) mediates ubiquitination of the chemokine receptor CXCR4 at the plasma membrane, and also ubiquitinates the endosomal ubiquitin-binding protein Hrs, coordinating lysosomal sorting of CXCR4 together with Hrs and Vps4. Co-immunoprecipitation, colocalization, dominant-negative and siRNA experiments in cells Developmental cell High 14602072
2006 ITCH/AIP4 generates K29-linked polyubiquitin chains (rather than canonical K48 chains) on Deltex (DTX), targeting it for lysosomal degradation; ITCH and DTX interact and partially colocalize on endocytic vesicles. Co-immunoprecipitation, colocalization, in vivo ubiquitin linkage analysis (lysine-29-specific mutant ubiquitin), lysosomal inhibitor rescue EMBO reports High 17028573
2008 ITCH/AIP4 controls ligand-independent degradation of Notch1 receptor by targeting it to lysosomes after early endocytosis, generating K29-linked polyubiquitin chains on Notch; ITCH is not required for Notch activation. The Notch–ITCH interaction requires either a post-translational modification or a bridging factor (not detectable by direct in vitro interaction). Itch−/− fibroblasts reconstituted with Notch1, lysosomal inhibitor rescue, ubiquitin chain-linkage analysis, in vitro binding assays (negative for direct interaction) PloS one High 18628966
2006 AIP4/ITCH promotes ubiquitination and lysosomal degradation of TRP channels TRPV4 and TRPC4, reducing their plasma membrane abundance and basal channel activity; ubiquitination promotes endocytosis of TRPV4 without degrading the total protein pool. This regulation is selective: several other TRP channels are not affected by AIP4. Overexpression of AIP4 in cells, surface biotinylation, electrophysiology (basal current measurement), ubiquitination assays The EMBO journal High 17110928
2006 ITCH/AIP4 promotes ubiquitin-dependent degradation of the transcription factor p63; two specific lysine residues in p63 (associated with Split-Hand and Foot Malformation-4 syndrome) are required for ITCH-mediated degradation. Co-immunoprecipitation, overexpression/deletion mutagenesis of p63, ubiquitination assay, pulse-chase degradation assay Cell cycle (Georgetown, Tex.) Medium 16861923
2007 AIP4/ITCH interacts with ErbB-4 (HER4) via its WW domains, ubiquitinates ErbB-4 in vivo, and promotes polyubiquitination and proteasomal/lysosomal degradation of ErbB-4, thereby reducing receptor stability and nuclear access of the ErbB-4 intracellular domain. Phage display library panning, Co-immunoprecipitation, in vivo ubiquitination assay, degradation assay, nuclear fractionation FASEB journal Medium 17463226
2005 AIP4 targets Smad7 for ubiquitin-dependent degradation via a two-hybrid-identified interaction; paradoxically, AIP4 inhibits TGF-β signaling by enhancing Smad7 association with the activated TGF-β type I receptor (TβRI). A catalytically inactive AIP4 mutant (unable to ubiquitinate Smad7) still stabilizes the TβRI–Smad7 complex and inhibits TGF-β signaling, demonstrating a ubiquitination-independent scaffolding mechanism. Yeast two-hybrid, Co-immunoprecipitation, catalytic-dead AIP4 mutant, TGF-β reporter assays, degradation assays The Journal of biological chemistry High 15946939
2002 AIP4/ITCH physically interacts with CBLC (a RING-type E3 ligase) via its WW domains binding proline-rich regions; co-expression of CBLC and AIP4 cooperatively down-regulates EGFR signaling. Both AIP4 and CBLC become tyrosine-phosphorylated after EGF stimulation. Expression of WW domains of AIP4 exerts a dominant-negative effect on EGFR ubiquitination. Yeast two-hybrid, GST pulldown, Co-immunoprecipitation, colocalization, EGFR ubiquitination assay, dominant-negative overexpression The Journal of biological chemistry Medium 12226085
2010 Spartin binds the WW region of AIP4/ITCH with ~7-fold higher affinity than the WW region binds the HECT domain (disrupting AIP4 autoinhibition), thereby activating AIP4 E3 ligase activity. Spartin recruits AIP4 to lipid droplets, where AIP4 ubiquitinates adipophilin, regulating lipid droplet turnover. Spartin itself is not a substrate for AIP4. ELISA-based binding affinity measurement, self-ubiquitination assay, colocalization to lipid droplets (fluorescence microscopy), ubiquitination assay of adipophilin BMC biology Medium 20504295
2010 USP8 (a deubiquitinase downstream of Akt) links the PTEN-Akt pathway to AIP4 activity: USP8 deubiquitinates AIP4, increasing AIP4-mediated ubiquitination and degradation of cFLIP(S), thereby decreasing TRAIL resistance in glioblastoma cells. siRNA knockdown of AIP4 reverses the effects of USP8 overexpression on FLIP(S) levels. siRNA knockdown, overexpression, ubiquitination assay, half-life (pulse-chase), co-immunoprecipitation, TRAIL apoptosis assay Cancer research Medium 20484045
2010 AIP4/ITCH-dependent JUNB protein degradation is markedly reduced in cells with active AKT; JNK-mediated AIP4 activity is required for rapamycin-induced repression of cyclin D1 and c-MYC transcription via JUNB degradation. Silencing AIP4 or inhibiting JNK abrogates the rapamycin-induced transcriptional effects. siRNA knockdown of AIP4, JNK inhibition, promoter-reporter assays, protein stability assays, ChIP Molecular cancer research : MCR Medium 21135252
2009 TNF-α signaling induces association of the homeodomain protein TGIF with ITCH/AIP4, increasing accessibility of cFLIP(L) for ITCH-mediated ubiquitination and degradation, thereby promoting TNF-α-induced apoptosis. Additionally, ITCH monoubiquitinates TGIF at K259 in response to TNF-α, stabilizing TGIF and creating a positive feedback loop. Co-immunoprecipitation (TNF-α-inducible), ubiquitination assays, site-directed mutagenesis (K259R), apoptosis assays Molecular cell High 20064471
2016 The anti-HER3 antibody 9F7-F11 induces HER3 ubiquitination and degradation mainly through ITCH/AIP4, activated by JNK1/2 phosphorylation; deubiquitinases USP8 and USP9X activate ITCH/AIP4 activity in this context. Overexpression of the ITCH inhibitor N4BP1 or siRNA knockdown of ITCH blocks 9F7-F11-induced HER3 ubiquitination/degradation. siRNA knockdown of ITCH, N4BP1 overexpression, ubiquitination assays, Co-immunoprecipitation, JNK inhibitor treatment, PI3K/AKT signaling assays Oncotarget Medium 27203743
2018 AIP4/ITCH promotes K48-linked ubiquitination of influenza A virus matrix protein M1 at K102 and K104, targeting it for proteasome-mediated degradation; Cyclophilin A (CypA) inhibits AIP4-mediated M1 ubiquitination by impairing the AIP4–M1 interaction, thereby modulating nuclear export of M1 and viral replication. Ubiquitination assays with lysine-specific ubiquitin mutants, Co-immunoprecipitation, site-directed mutagenesis of M1 (K102R/K104R), recombinant virus rescue assay, subcellular localization assay Virologica Sinica Medium 30328013
2024 SPG20 (Spartin) detects lipid-packing defects in the limiting membrane of damaged lysosomes via sensory amphipathic helices before membrane rupture, then recruits and activates ITCH to mark damaged lysosomes with K63-linked ubiquitin chains, initiating lysophagy. SPG20 binds the repair factor IST1 on damaged lysosomes and integrates repair status with lipid damage detection; if damage is extensive (e.g., lipid peroxidation), ITCH is recruited for lysosomal destruction. Proximity ligation, Co-immunoprecipitation, ubiquitin chain linkage analysis (K63-specific), amphipathic helix mutagenesis, fluorescence live imaging of lysosomal damage, autophagy flux assays in human cells Molecular cell High 38503285
2015 ITCH E3 ubiquitin ligase is involved in multiple immune regulatory contexts: it controls T-cell activation and tolerance, T-helper cell differentiation, and various signaling pathways through substrate ubiquitylation; its deletion in mice causes an itchy phenotype with multi-organ inflammation. Genetic deletion (Itch−/− mice), immune phenotyping, multiple substrate ubiquitination studies (review consolidation of primary experiments) Immunological reviews Medium 26085204

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell 764 24094650
2009 Cellular basis of itch sensation. Science (New York, N.Y.) 469 19661382
2019 Astrocytes in chronic pain and itch. Nature reviews. Neuroscience 394 31537912
2003 The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. Developmental cell 323 14602072
2018 Peripheral and Central Mechanisms of Itch. Neuron 291 29723501
2003 Itch: scratching more than the surface. QJM : monthly journal of the Association of Physicians 262 12509645
2014 Sensory neurons and circuits mediating itch. Nature reviews. Neuroscience 240 24356071
2018 Mast cell-neural interactions contribute to pain and itch. Immunological reviews 226 29431216
2015 Gate control of mechanical itch by a subpopulation of spinal cord interneurons. Science (New York, N.Y.) 217 26516282
2021 A basophil-neuronal axis promotes itch. Cell 210 33450207
2017 A central neural circuit for itch sensation. Science (New York, N.Y.) 203 28818946
2013 Neural processing of itch. Neuroscience 192 23891755
2017 Spinal Circuits for Touch, Pain, and Itch. Annual review of physiology 187 28961064
2021 Structure, function and pharmacology of human itch GPCRs. Nature 179 34789874
2006 Itch/AIP4 mediates Deltex degradation through the formation of K29-linked polyubiquitin chains. EMBO reports 165 17028573
2013 New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? Pflugers Archiv : European journal of physiology 149 23636773
2015 HTR7 Mediates Serotonergic Acute and Chronic Itch. Neuron 147 26074006
2021 Structure, function and pharmacology of human itch receptor complexes. Nature 129 34789875
2015 G Protein-Coupled Receptors: Dynamic Machines for Signaling Pain and Itch. Neuron 121 26590341
2018 The vicious cycle of itch and anxiety. Neuroscience and biobehavioral reviews 120 29374516
2008 AIP4/Itch regulates Notch receptor degradation in the absence of ligand. PloS one 120 18628966
2008 Neuropathic and psychogenic itch. Dermatologic therapy 118 18318883
2013 The neurology of itch. Brain : a journal of neurology 102 23794605
2006 Chronic itch and pain--similarities and differences. European journal of pain (London, England) 101 16678456
2021 Itch: Pathogenesis and treatment. Journal of the American Academy of Dermatology 99 34648873
2019 Pathophysiologic mechanisms of itch in bullous pemphigoid. Journal of the American Academy of Dermatology 93 31351883
2021 Itch: Epidemiology, clinical presentation, and diagnostic workup. Journal of the American Academy of Dermatology 88 34428534
2010 Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets. BMC biology 82 20504295
2023 Basic mechanisms of itch. The Journal of allergy and clinical immunology 81 37201903
2018 Clinical presentation, management, and pathophysiology of neuropathic itch. The Lancet. Neurology 79 30033061
2021 Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition. Brain : a journal of neurology 76 33367648
2021 A neuropeptide code for itch. Nature reviews. Neuroscience 76 34663954
2006 The HECT ubiquitin ligase AIP4 regulates the cell surface expression of select TRP channels. The EMBO journal 75 17110928
2002 Interaction between two ubiquitin-protein isopeptide ligases of different classes, CBLC and AIP4/ITCH. The Journal of biological chemistry 73 12226085
2022 Mechanisms of pruritus in cholestasis: understanding and treating the itch. Nature reviews. Gastroenterology & hepatology 72 36307649
2015 Molecular and cellular mechanisms that initiate pain and itch. Cellular and molecular life sciences : CMLS 72 25894692
2015 Trp channels and itch. Seminars in immunopathology 72 26385480
2011 Itch signaling in the nervous system. Physiology (Bethesda, Md.) 72 21841076
2019 Circular RNA ITCH: A novel tumor suppressor in multiple cancers. Life sciences 70 31843532
2010 Ubiquitin-specific protease 8 links the PTEN-Akt-AIP4 pathway to the control of FLIPS stability and TRAIL sensitivity in glioblastoma multiforme. Cancer research 69 20484045
2006 Itch/AIP4 associates with and promotes p63 protein degradation. Cell cycle (Georgetown, Tex.) 68 16861923
2015 Neuroimmune interactions in itch: Do chronic itch, chronic pain, and chronic cough share similar mechanisms? Pulmonary pharmacology & therapeutics 66 26351759
2011 Pathophysiology of itch and new treatments. Current opinion in allergy and clinical immunology 65 21772138
2007 The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 17463226
2022 Transient Receptor Potential Channels and Itch. International journal of molecular sciences 61 36613861
2015 The E3 ligase Itch in immune regulation and beyond. Immunological reviews 61 26085204
2020 New and emerging treatments for inflammatory itch. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 60 32497711
2016 The cell biology of acute itch. The Journal of cell biology 60 27114499
2024 Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH. Molecular cell 58 38503285
2017 Infection, Pain, and Itch. Neuroscience bulletin 58 28144843
2018 Anatomical and functional dichotomy of ocular itch and pain. Nature medicine 56 29988128
2010 AP-1 regulates cyclin D1 and c-MYC transcription in an AKT-dependent manner in response to mTOR inhibition: role of AIP4/Itch-mediated JUNB degradation. Molecular cancer research : MCR 55 21135252
2023 Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice. Nature communications 53 37137899
2015 The role of the Mrgpr receptor family in itch. Handbook of experimental pharmacology 51 25861775
2022 Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit. Brain : a journal of neurology 49 35598161
2005 AIP4 restricts transforming growth factor-beta signaling through a ubiquitination-independent mechanism. The Journal of biological chemistry 49 15946939
2015 Protease-activated receptors and itch. Handbook of experimental pharmacology 47 25861783
2021 Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons. Proceedings of the National Academy of Sciences of the United States of America 45 34234018
2021 Periostin, an Emerging Player in Itch Sensation. The Journal of investigative dermatology 44 34023128
2020 Mechanisms and Management of Itch in Dry Skin. Acta dermato-venereologica 44 31940044
2023 Sensory neuronal STAT3 is critical for IL-31 receptor expression and inflammatory itch. Cell reports 43 38029739
2015 NK-1 Antagonists and Itch. Handbook of experimental pharmacology 41 25861784
2012 Peripheral mechanisms of itch. Neuroscience bulletin 41 22466121
2023 IL-33 potentiates histaminergic itch. The Journal of allergy and clinical immunology 39 37984799
2010 Itch in ethnic populations. Acta dermato-venereologica 36 20526537
2023 Itch and Janus Kinase Inhibitors. Acta dermato-venereologica 34 36789757
2020 A New Generation of Treatments for Itch. Acta dermato-venereologica 34 31940047
2019 Itch Processing in the Skin. Frontiers in medicine 34 31380380
2023 Similarities and differences in peripheral itch and pain pathways in atopic dermatitis. The Journal of allergy and clinical immunology 31 38103700
2022 Update on mosquito bite reaction: Itch and hypersensitivity, pathophysiology, prevention, and treatment. Frontiers in immunology 31 36211437
2020 The Challenge of Basic Itch Research. Acta dermato-venereologica 31 31940043
2019 Spinal somatostatin-positive interneurons transmit chemical itch. Pain 31 30913166
2019 Neuropathic itch. Pain 31 31008844
2015 Evolving understanding on the aetiology of thermally provoked itch. European journal of pain (London, England) 31 26415614
2011 The itch of liver disease. Seminars in cutaneous medicine and surgery 31 21767769
2018 Neuropathic Pain and Itch Mechanisms Underlying Allergic Conjunctivitis. Journal of investigational allergology & clinical immunology 30 30222114
2015 Molecular dissection of itch. Current opinion in neurobiology 29 25700248
2015 Neuraxial opioid-induced itch and its pharmacological antagonism. Handbook of experimental pharmacology 29 25861787
2023 Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 28 37023756
2021 TRPV1 in Pain and Itch. Advances in experimental medicine and biology 28 35138618
2018 Itch and psyche: psychiatric aspects of pruritus. International journal of dermatology 28 29917231
2017 Spinal Mechanisms of Itch Transmission. Neuroscience bulletin 27 28365862
2011 Intracellular signaling and the origins of the sensations of itch and pain. Science signaling 26 21868356
2015 Transient receptor potential channels and itch: how deep should we scratch? Handbook of experimental pharmacology 25 25861776
2022 Critical Players and Therapeutic Targets in Chronic Itch. International journal of molecular sciences 24 36077340
2021 Intractable Itch in Atopic Dermatitis: Causes and Treatments. Biomedicines 23 33668714
2016 The anti-HER3 (ErbB3) therapeutic antibody 9F7-F11 induces HER3 ubiquitination and degradation in tumors through JNK1/2- dependent ITCH/AIP4 activation. Oncotarget 23 27203743
2021 Connections between Immune-Derived Mediators and Sensory Nerves for Itch Sensation. International journal of molecular sciences 22 34830245
2018 TRPV1 gain-of-function mutation impairs pain and itch sensations in mice. Molecular pain 22 29424270
2015 Protein kinase Cδ mediates histamine-evoked itch and responses in pruriceptors. Molecular pain 22 25558916
2013 Updated neurophysiology of itch. Biological & pharmaceutical bulletin 22 23902966
2018 Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch. Protein & cell 21 30413999
2022 Circular RNA ITCH: An Emerging Multifunctional Regulator. Biomolecules 20 35327551
2022 A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior. Cell reports 20 36198265
2022 Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice. Journal of cellular physiology 20 36436135
2018 CypA Regulates AIP4-Mediated M1 Ubiquitination of Influenza A Virus. Virologica Sinica 20 30328013
2005 Itch and pain. Dermatologic therapy 20 16297001
2016 Cell transplants to treat the "disease" of neuropathic pain and itch. Pain 19 26780378
2009 A model of partnership co-opted by the homeodomain protein TGIF and the Itch/AIP4 ubiquitin ligase for effective execution of TNF-alpha cytotoxicity. Molecular cell 19 20064471
2020 Substance use disorders and chronic itch. Journal of the American Academy of Dermatology 18 32891774

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