Affinage

ITSN2

Intersectin-2 · UniProt Q9NZM3

Length
1697 aa
Mass
193.5 kDa
Annotated
2026-06-10
96 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ITSN2 is a multimodular scaffold/adaptor that couples membrane trafficking to actin cytoskeletal remodeling by functioning as a guanine nucleotide exchange factor (GEF) for the Rho-family GTPase Cdc42 (PMID:12192056, PMID:21530493). Generated as short and long splice isoforms, the protein combines EH domains, a coiled-coil, and SH3 domains with an additional DH-PH-C2 module in the long isoform; GEF activity toward Cdc42 resides in the DH-PH tandem and strictly requires the PH domain, as the isolated DH domain is inactive (PMID:10922467, PMID:31469028). Through its SH3 domains ITSN2 engages proline-rich ligands including WIP and RhoU, and via its coiled-coil it binds Eps8 and promotes its lysosomal degradation, linking the protein to clathrin-mediated endocytosis, Cdc42-WASP/Arp2/3-driven actin assembly, and RhoU-dependent fast endosomal recycling on Rab4-positive endosomes (PMID:22449706, PMID:25797047, PMID:32737221); ITSN2 overexpression inhibits transferrin internalization and it co-localizes with the endocytic component Eps15 (PMID:10922467). This Cdc42-actin axis underlies its physiological roles: ITSN2 is required upstream of Cdc42-WASP-Arp2/3 for cortical actin cap formation, spindle assembly, and meiotic progression in oocytes (PMID:28626024, PMID:30478952), and supports adaptive immunity, driving germinal-center B-cell responses through Cdc42/WASp/WIP-dependent actin remodeling downstream of the B-cell receptor and regulating T-cell effector functions downstream of TCR engagement (PMID:29337666, PMID:32618424). ITSN2 also acts as a podocyte Cdc42 GEF essential for glomerular function, and loss-of-function mutations that impair its GEF activity cause partially treatment-sensitive nephrotic syndrome in humans, recapitulated by Itsn2-L knockout mice (PMID:29773874). Beyond trafficking and actin, ITSN2 is a major downstream effector of ING1a-induced cellular senescence, inducing the cyclin-dependent kinase inhibitors p16 and p57KIP2 to block Rb inactivation (PMID:23472054), negatively regulates ENaC-mediated Na+ transport under aldosterone/miR-27 control (PMID:27636893), and together with ITSN1 maintains cortico-striatal NMDA receptor function and plasticity (PMID:37603735). Its expression is tuned post-transcriptionally by m6A-mediated mRNA stabilization via METTL3 and an RBM15B-IGF2BP1 axis (PMID:34689175, PMID:41795047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 Medium

    Established ITSN2 as a multidomain endocytic protein and predicted, from its long-isoform DH-PH-C2 architecture, that it acts as a GEF for Rho-family GTPases.

    Evidence cDNA/domain characterization, transferrin internalization assay, and co-localization with Eps15

    PMID:10922467

    Open questions at the time
    • GEF activity inferred from domain content, not yet measured
    • Which Rho GTPase substrate not identified
  2. 2002 Medium

    Identified Cdc42 as the GTPase substrate of ITSN2, converting the domain-based prediction into a measured catalytic activity.

    Evidence FRET-based Raichu-Cdc42 GEF activity assay in living cells

    PMID:12192056

    Open questions at the time
    • Domain requirements for activity not dissected
    • Physiological context of Cdc42 activation untested
  3. 2011 Medium

    Placed ITSN2 GEF activity in a developmental and cytoskeletal context, showing the DH-PH tandem activates Cdc42 to control actin and morphogenesis in vivo.

    Evidence Domain overexpression in Xenopus embryos with dominant-negative/constitutively active Cdc42 epistasis

    PMID:21530493

    Open questions at the time
    • Endogenous requirement not tested (gain-of-function only)
    • Direct molecular partners in embryo unknown
  4. 2012 Medium

    Defined ITSN2 protein-protein interactions and signaling roles, linking it to Eps8 turnover and to receptor-proximal JAK2 activation at clathrin-coated structures.

    Evidence Yeast two-hybrid, co-IP, GST pull-down, lysosomal stability assay (Eps8); RNAi and receptor mutants (GMR/JAK2)

    PMID:22449706 PMID:22935703

    Open questions at the time
    • Mechanism connecting GEF activity to Eps8 degradation unclear
    • Generality of JAK2 role across receptors untested
  5. 2013 High

    Revealed two distinct ITSN2 functions: a senescence-effector role downstream of ING1a via the Rb-E2F pathway, and isoform-specific tyrosine phosphorylation creating SH2-domain docking sites that distinguish ITSN2 from ITSN1.

    Evidence Reciprocal overexpression/knockdown with senescence markers (p16/p57/Rb); phosphorylation analysis and SH2 domain binding arrays

    PMID:23472054 PMID:23936226

    Open questions at the time
    • How ITSN2 induces p16/p57 mechanistically not resolved
    • Functional consequence of each SH2-mediated interaction untested
  6. 2015 Medium

    Connected ITSN2 SH3 domains to actin machinery by demonstrating WIP binding and localization to invadopodia, embedding it in the Cdc42-WASP/Arp2/3 network.

    Evidence Co-IP, GST pull-down domain mapping, immunofluorescence in invasive cancer cells

    PMID:25797047

    Open questions at the time
    • Functional requirement of ITSN2 at invadopodia not directly tested
    • Trimeric complex shown for ITSN1, not explicitly ITSN2
  7. 2017 High

    Demonstrated an endogenous, physiological requirement for ITSN2 as a Cdc42 GEF in oocyte meiosis, regulating actin cap formation, spindle, and chromosome alignment via WASP/Arp2/3, and identified miR-27/ENaC regulation in kidney.

    Evidence Morpholino knockdown with dominant-positive Cdc42 rescue and ZCL278 inhibitor (oocytes); 3'-UTR reporter, knockdown/overexpression with ENaC electrophysiology (kidney)

    PMID:27636893 PMID:28161632 PMID:28626024

    Open questions at the time
    • Direct GEF measurement in oocytes not performed
    • CR16 interaction (idx 11) lacks functional rescue
  8. 2018 High

    Established ITSN2 as a physiological Cdc42 GEF in immunity and in the kidney, with human disease relevance: it drives B-cell germinal-center responses and its loss-of-function mutations cause nephrotic syndrome through deficient podocyte GEF activity.

    Evidence ITSN2 knockout mice (immune phenotyping, B-T conjugates); human genetics, GEF assay with patient mutants, Itsn2-L KO mouse, podocyte migration assay; ZCL278 in porcine oocytes

    PMID:29337666 PMID:29773874 PMID:30478952

    Open questions at the time
    • Cell-type-specific GEF substrates beyond Cdc42 not excluded
    • Genotype-phenotype correlation for individual mutations limited
  9. 2019 Medium

    Pinned down the structural basis of GEF activity, showing the PH domain is obligatory for Cdc42 activation by ITSN2 in primary human cells.

    Evidence Single-cell FRET biosensor assays with full-length versus truncated GEF constructs in endothelial cells

    PMID:31469028

    Open questions at the time
    • Atomic mechanism of PH-domain contribution unresolved
    • Regulation of GEF activity in cells not addressed
  10. 2020 Medium

    Extended ITSN2's immune function to T cells, linking TCR-induced phosphorylation of ITSN2 to T-cell effector responses.

    Evidence Time-resolved phosphoproteomics and fast-track CRISPR inactivation in primary lymphocytes

    PMID:32618424

    Open questions at the time
    • Phosphorylation sites and upstream kinase not defined
    • Mechanistic link to Cdc42/actin in T cells untested
  11. 2020 Medium

    Defined an isoform-selective trafficking role: RhoU binds ITSN2 (not ITSN1) SH3 domains, and ITSN2 is required for fast vesicle recycling on Rab4-positive endosomes.

    Evidence Co-IP, isoform-specific siRNA, transferrin recycling assay, co-localization

    PMID:32737221

    Open questions at the time
    • Whether GEF activity is required for recycling untested
    • Functional consequence of RhoU-ITSN2 binding beyond recycling unclear
  12. 2021 Medium

    Identified post-transcriptional control of ITSN2 by m6A, stabilizing its mRNA via METTL3 to support oocyte maturation, and placed ITSN2 in the CBL/CBLB EGFR-signaling network.

    Evidence Oocyte Mettl3 KO with MeRIP-seq and mRNA stability assays; AP-MS with co-IP validation (CBL/CBLB)

    PMID:34134489 PMID:34689175

    Open questions at the time
    • CBL/CBLB interaction lacks functional follow-up (idx 18, Low)
    • Reader proteins for oocyte m6A not defined here
  13. 2023 High

    Revealed a neuronal role: combined ITSN1/2 loss disrupts cortico-striatal neurotransmission and NMDA receptor maintenance, producing ASD/OCD-like behavior.

    Evidence ITSN1/2 double knockout mice with behavior, morphology, electrophysiology, and receptor immunostaining

    PMID:37603735

    Open questions at the time
    • ITSN2-specific contribution versus ITSN1 not separated
    • Molecular link from ITSN to NMDA receptor maintenance unresolved
  14. 2026 Medium

    Extended m6A regulation of ITSN2 to cancer, defining an RBM15B-IGF2BP1-ITSN2 axis that stabilizes ITSN2 mRNA to promote hepatocellular carcinoma growth.

    Evidence MeRIP-seq, RIP-qRT-PCR, and ITSN2-depletion rescue in HCC proliferation/migration and tumor assays

    PMID:41795047

    Open questions at the time
    • Downstream effector mechanism of ITSN2 in HCC not defined
    • Whether Cdc42 GEF activity drives the tumor phenotype untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ITSN2's catalytic GEF function, its scaffold/SH3-mediated trafficking interactions, and its non-GEF roles (senescence induction, NMDA receptor maintenance) are integrated and selectively deployed across tissues remains unresolved.
  • No structural model of full-length ITSN2 or its substrate complex
  • Whether GEF activity is required for each phenotype not systematically tested
  • Mechanism switching ITSN2 between trafficking, actin, and transcriptional/senescence outputs unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CBLCBLBCDC42EPS15EPS8ITSN1RHOUWIP

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ITSN2 was characterized as a new multimodular human protein involved in clathrin-mediated endocytosis. It has two isoforms generated by alternative splicing: a short isoform with two EH domains, a coiled-coil region, and five SH3 domains, and a long isoform containing additional DH, PH, and C2 domains suggesting GEF activity for Rho-like GTPases. Overexpression of ITSN2 isoforms inhibits transferrin internalization, and ITSN2 co-localizes with Eps15, a component of the endocytic machinery. cDNA characterization, domain analysis, transferrin internalization assay, immunofluorescence co-localization FEBS letters Medium 10922467
2002 KIAA1256 (ITSN2) was identified as a guanine nucleotide exchange factor (GEF) for Cdc42 using a FRET-based single-molecule probe (Raichu-Cdc42) assay in living cells. FRET-based GTPase activity assay (Raichu-Cdc42 probe) in live cells Molecular and cellular biology Medium 12192056
2007 The K15 protein of Kaposi's sarcoma-associated herpesvirus selectively binds the SH3-C domain of ITSN2 via a conserved PPLP proline-rich motif in its cytoplasmic tail. This interaction was identified by mass spectrometry, domain and peptide arrays, and surface plasmon resonance, and confirmed by co-localization of K15 and ITSN2 to discrete compartments within B cells. Mass spectrometry, domain/peptide arrays, surface plasmon resonance, co-immunoprecipitation, immunofluorescence co-localization Biochemistry High 17696407
2011 The DH-PH tandem of ITSN2-L acts as a nucleotide exchange factor for Cdc42 during Xenopus early embryonic development. Overexpression of this domain in embryos caused hyperpigmentation and gastrulation failure affecting the actin cytoskeleton, phenotypes dependent on Cdc42 (partially rescued by dominant-negative Cdc42 and phenocopied by constitutively active Cdc42). Overexpression of functional domains in Xenopus embryos, genetic epistasis with dominant-negative and constitutively active Cdc42, phenotypic analysis Biochemical and biophysical research communications Medium 21530493
2012 ITSN2 binds Eps8 protein via its coiled-coil domain interacting with amino acids 260–306 of Eps8, and overexpression of ITSN2 promotes lysosomal degradation of Eps8. The interaction was demonstrated by yeast two-hybrid, co-immunoprecipitation, co-localization, and GST pull-down assays. Yeast two-hybrid, co-immunoprecipitation, GST pull-down, immunofluorescence, protein stability assay with lysosome inhibitor BMB reports Medium 22449706
2012 ITSN2 is required for GM-CSF receptor (GMR)-mediated activation of JAK2 at clathrin-coated structures (CCSs). Knockdown of ITSN2 attenuated GMR-mediated JAK2 activation, and an ITSN2-non-binding mutant of GMR that failed to target to CCSs also failed to activate JAK2. Ligand treatment enhanced JAK2/GMR association at CCSs and induced a conformational change in JAK2 required for CCS-localized CK2-mediated activation. RNAi knockdown, dominant-negative dynamin, receptor binding mutants, co-immunoprecipitation, subcellular fractionation/co-localization Cell cycle Medium 22935703
2013 ITSN2 expression is induced >25-fold by the ING1a tumor suppressor during cellular senescence. ITSN2 overexpression independently induces p16 and p57KIP2 cyclin-dependent kinase inhibitors that block Rb inactivation. Knockdown of ITSN2 blocks ING1a-induced senescence, establishing ITSN2 as a major downstream effector of ING1a-induced senescence via the Rb-E2F pathway. ITSN2 is also induced in normally senescing cells. Gene expression profiling, ITSN2 overexpression, siRNA knockdown, senescence assays (β-galactosidase, morphology, SAHF), Western blotting for p16/p57/Rb PLoS biology High 23472054
2013 ITSN2 SH3 domains bind the same proline-rich ligands as ITSN1, but ITSN2 (unlike ITSN1 short isoform) is specifically tyrosine-phosphorylated in various cell lines, and EGF stimulation enhances this phosphorylation, enabling recognition of ITSN2 by SH2 domains of Fyn, Fgr, Abl1, PI3K regulatory subunit, Grb2, Crk, and PLCγ. Endogenous ITSN1 and ITSN2 co-localize and form a complex in cells. Co-immunoprecipitation, SH3 domain binding assays, phosphorylation analysis, SH2 domain array/binding assays, immunofluorescence PloS one Medium 23936226
2015 ITSN2 (and ITSN1) interact with the actin-regulating protein WIP via the SH3 domains of ITSNs and the proline-rich region of WIP. Endogenous ITSN1 and ITSN2 localize to invadopodia of MDA-MB-231 breast cancer cells, and ITSN1, WIP, and N-WASP can form a trimeric complex in cells. Co-immunoprecipitation, GST pull-down (SH3 domain mapping), immunofluorescence in invasive cancer cell lines Cellular signalling Medium 25797047
2017 ITSN2 depletion in mouse oocytes causes delayed meiotic resumption, defective cytokinesis, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap. ITSN2 depletion reduces Cdc42 activity, and forced expression of dominant-positive Cdc42 partially rescues actin cap formation. The downstream effectors WASP and Arp2 are mislocalized upon ITSN2 knockdown, supporting a model in which ITSN2 acts upstream of Cdc42 to regulate WASP/Arp2/3 and actin dynamics in oocyte meiosis. Morpholino-mediated knockdown, dominant-positive Cdc42 rescue, small molecule ZCL278 (ITSN-Cdc42 interaction inhibitor), immunofluorescence, Cdc42 activity assay FASEB journal High 28626024
2017 ITSN2 is a target of aldosterone-regulated miR-27a/b in the distal kidney nephron. miR-27a/b binds the 3'-UTR of ITSN2 mRNA; aldosterone stimulation decreases ITSN2 mRNA and protein. Depletion of ITSN2 increases ENaC-mediated Na+ transport, while ITSN2 overexpression reduces ENaC function, demonstrating that ITSN2 negatively regulates epithelial sodium channel activity. 3'-UTR reporter assay, siRNA knockdown, overexpression, ENaC electrophysiology (Na+ transport assay), Western blot Journal of cellular physiology Medium 27636893
2017 Mammalian verprolin CR16 forms complexes with ITSN1 and ITSN2 in human cell lines. CR16 modulates ITSN association with β-actin, and overexpressed CR16 promotes co-localization of ITSN1 with F-actin in MCF-7 cells. Co-immunoprecipitation, immunofluorescence, Western blot Biochemical and biophysical research communications Low 28161632
2018 ITSN2-deficient mice show increased mortality during primary influenza infection, incomplete protection after flu vaccination, reduced germinal centre formation, and impaired antibody responses. These defects are intrinsic to the B cell compartment. In vivo, ITSN2-deficient B cells show reduced SLAM, CD84, and ICOSL expression, diminished ability to form long-term T cell conjugates, reduced proliferation, and impaired germinal centre differentiation, demonstrating ITSN2 as a key regulator of adaptive B cell immunity via Cdc42/WASp/WIP-dependent actin remodeling downstream of BCR engagement. ITSN2 knockout mice, viral infection, vaccination, flow cytometry, in vivo B-T cell conjugate assays, germinal centre analysis eLife High 29337666
2018 Loss-of-function mutations in ITSN2 (along with ITSN1, MAGI2, TNS2, DLC1, CDK20) cause partially treatment-sensitive nephrotic syndrome (NS) in humans. ITSN1 and ITSN2 function as podocytic guanine nucleotide exchange factors for Cdc42, and patient-derived ITSN2 mutants show deficient GEF activity. Itsn2-L knockout mice recapitulate the mild NS phenotype. Knockdown of ITSN2 in podocytes reduces migration rate. Human genetic analysis, GEF activity assay with patient mutants, Itsn2-L knockout mouse model with NS phenotype, podocyte knockdown migration assay Nature communications High 29773874
2018 Inhibition of the ITSN2-Cdc42 interaction using the small molecule ZCL278 prevents porcine oocytes from completing meiosis, causes spindle defects, chromosomal congression failure, and impairs actin polymerization, supporting ITSN2 function upstream of Cdc42 in meiotic apparatus assembly. Small molecule inhibitor (ZCL278) targeting ITSN-Cdc42 interaction, spindle and chromosome immunofluorescence, actin staining Journal of cellular physiology Medium 30478952
2019 The DHPH domain of ITSN2 (together with ITSN1 and PLEKHG1) activates Cdc42 in primary human endothelial cells, whereas the isolated DH domain alone does not activate Cdc42, establishing that the PH domain is required for ITSN2 GEF activity toward Cdc42. Single-cell FRET measurements with Rho GTPase biosensors, overexpression of full-length and truncated GEF constructs in primary human endothelial cells Small GTPases Medium 31469028
2020 ITSN2 is phosphorylated following TCR stimulation in primary T cells, and gene inactivation of ITSN2 in primary lymphocytes using a fast-track approach impairs T-cell effector functions, demonstrating that ITSN2 regulates T-cell responses downstream of TCR engagement. Time-resolved phosphoproteomics, fast-track CRISPR gene inactivation in primary lymphocytes, T-cell effector function assays Molecular systems biology Medium 32618424
2020 RhoU binds ITSN2 (but not ITSN1) via its N-terminal PxxP motif interacting with the SH3 domains of ITSN2. Silencing of ITSN2 (but not ITSN1) increases transferrin accumulation in early endosomes, indicating a defect in fast vesicle recycling. RhoU and ITSN2 co-localize on Rab4-positive fast recycling endosomes. Co-immunoprecipitation, siRNA knockdown, fluorescent transferrin uptake assay, immunofluorescence co-localization Journal of cell science Medium 32737221
2021 EPS15L1 and ITSN2 were validated as stable binding partners of both CBL and CBLB (ubiquitin E3 ligases) through biochemical assays (AP-MS and co-IP validation), placing ITSN2 in the EGFR signaling network. Affinity purification–mass spectrometry (AP-MS), biochemical co-IP validation Journal of proteome research Low 34134489
2021 METTL3-mediated m6A modification targets Itsn2 mRNA in mouse oocytes to enhance its stability, and this stabilization influences oocyte meiosis. Loss of METTL3 in oocytes (Gdf9-Cre) reduces Itsn2 expression and is associated with defective oocyte maturation. Oocyte-specific Mettl3 knockout, MeRIP-seq (m6A immunoprecipitation sequencing), RNA-seq, mRNA stability assay Cell death & disease Medium 34689175
2023 Deletion of both ITSN1 and ITSN2 in mice leads to ASD/OCD-like behavioral alterations and defective cortico-striatal neurotransmission. The striatum is decreased in size, striatal neurons show reduced dendritic complexity and spine density, and NMDA receptor currents are reduced due to postsynaptic NMDA receptor depletion, establishing ITSN1/2 as regulators of cortico-striatal plasticity and NMDA receptor maintenance. ITSN1/2 double knockout mice, behavioral testing (ASD/OCD-like behaviors), morphological analysis, electrophysiology (NMDA receptor currents), immunostaining Proceedings of the National Academy of Sciences of the United States of America High 37603735
2026 RBM15B promotes m6A modification of ITSN2 mRNA and, through the m6A reader IGF2BP1, stabilizes ITSN2 mRNA in hepatocellular carcinoma (HCC), enhancing ITSN2 expression. ITSN2 depletion rescues the tumor-promoting phenotype induced by RBM15B overexpression, establishing a RBM15B-IGF2BP1-ITSN2 regulatory axis in HCC. MeRIP-seq, RNA immunoprecipitation (RIP)-qRT-PCR, rescue assays (cell proliferation and migration), in vitro and in vivo tumor assays Journal of cancer research and clinical oncology Medium 41795047

Source papers

Stage 0 corpus · 96 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Activation of rac and cdc42 video imaged by fluorescent resonance energy transfer-based single-molecule probes in the membrane of living cells. Molecular and cellular biology 473 12192056
2019 Reduced non-rapid eye movement sleep is associated with tau pathology in early Alzheimer's disease. Science translational medicine 282 30626715
2013 Sex differences in circadian timing systems: implications for disease. Frontiers in neuroendocrinology 273 24287074
1997 Sleep and sleep regulation in normal and prion protein-deficient mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 217 9030645
2018 Slow-wave sleep: From the cell to the clinic. Sleep medicine reviews 185 29490885
2008 Sleep homeostasis: a role for adenosine in humans? Biochemical pharmacology 185 18384754
2007 Exploratory behavior, cortical BDNF expression, and sleep homeostasis. Sleep 160 17326538
2009 Control and function of the homeostatic sleep response by adenosine A1 receptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 150 19193874
2018 Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment. Nature communications 99 29773874
2011 Involvement of cytokines in slow wave sleep. Progress in brain research 96 21854954
2023 Sleep and circadian rhythmicity as entangled processes serving homeostasis. Nature reviews. Neuroscience 88 38040815
2000 Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis. FEBS letters 81 10922467
2021 METTL3-mediated mRNA N6-methyladenosine is required for oocyte and follicle development in mice. Cell death & disease 78 34689175
2003 Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Transactions of the Royal Society of Tropical Medicine and Hygiene 73 12886815
2005 Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. Journal of clinical pathology 72 15858124
2002 Brain-immune interactions in sleep. International review of neurobiology 70 12498102
2017 The adenosine-mediated, neuronal-glial, homeostatic sleep response. Current opinion in neurobiology 61 28633050
2011 Functional Anatomy of Non-REM Sleep. Frontiers in neurology 59 22110467
2013 Ketamine, sleep, and depression: current status and new questions. Current psychiatry reports 56 23949569
2019 Strengthening sleep-autonomic interaction via acoustic enhancement of slow oscillations. Sleep 52 30753650
2001 The human intersectin genes and their spliced variants are differentially expressed. Biochimica et biophysica acta 52 11690630
2001 Additional complexity on human chromosome 15q: identification of a set of newly recognized duplicons (LCR15) on 15q11-q13, 15q24, and 15q26. Genome research 50 11156619
1997 Multiple pathways for toluene degradation in Burkholderia sp. strain JS150. Applied and environmental microbiology 48 9327568
2020 An essential role for MEF2C in the cortical response to loss of sleep in mice. eLife 40 32851972
2023 Sleep restoration by optogenetic targeting of GABAergic neurons reprograms microglia and ameliorates pathological phenotypes in an Alzheimer's disease model. Molecular neurodegeneration 38 38041158
2021 Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors. JCO precision oncology 37 34036223
2011 Mutability of prions. EMBO reports 34 21997293
2024 Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases. EBioMedicine 33 38471395
2008 Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy. Breast cancer research and treatment 33 18925433
2015 Sustained sleep fragmentation induces sleep homeostasis in mice. Sleep 28 25325477
2013 The ING1a tumor suppressor regulates endocytosis to induce cellular senescence via the Rb-E2F pathway. PLoS biology 28 23472054
2022 DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation. Frontiers in genetics 26 35518360
2024 BDNF-TrkB signaling orchestrates the buildup process of local sleep. Cell reports 23 39046880
2021 Electrophysiological signatures of acute systemic lipopolysaccharide-induced inflammation: potential implications for delirium science. British journal of anaesthesia 23 33648701
2010 Hypothalamic versus neocortical control of sleep. Current opinion in pulmonary medicine 23 20739890
2007 The K15 protein of Kaposi's sarcoma-associated herpesvirus recruits the endocytic regulator intersectin 2 through a selective SH3 domain interaction. Biochemistry 23 17696407
2022 High-density EEG power topography and connectivity during confusional arousal. Cortex; a journal devoted to the study of the nervous system and behavior 20 35985125
2020 LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions. Molecular systems biology 19 32618424
2019 An Integrated Model of Slow-Wave Activity and Neuroplasticity Impairments in Major Depressive Disorder. Current psychiatry reports 19 30880367
2017 A MicroRNA Cluster miR-23-24-27 Is Upregulated by Aldosterone in the Distal Kidney Nephron Where it Alters Sodium Transport. Journal of cellular physiology 19 27636893
2015 Intersectin adaptor proteins are associated with actin-regulating protein WIP in invadopodia. Cellular signalling 19 25797047
2017 Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 18 28626024
2019 Identification of guanine nucleotide exchange factors that increase Cdc42 activity in primary human endothelial cells. Small GTPases 17 31469028
2018 Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity. eLife 17 29337666
2021 Granulocytic myeloid-derived suppressor cells inhibit T follicular helper cells during experimental Schistosoma japonicum infection. Parasites & vectors 16 34565440
2014 Substance P and the neurokinin-1 receptor regulate electroencephalogram non-rapid eye movement sleep slow-wave activity locally. Neuroscience 15 25301750
2023 Activation of the nociceptin/orphanin-FQ receptor promotes NREM sleep and EEG slow wave activity. Proceedings of the National Academy of Sciences of the United States of America 14 36947514
2018 Cortistatin-expressing interneurons require TrkB signaling to suppress neural hyper-excitability. Brain structure & function 13 30377803
2013 The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis. Psychiatric genetics 11 23811784
2013 Adaptor proteins intersectin 1 and 2 bind similar proline-rich ligands but are differentially recognized by SH2 domain-containing proteins. PloS one 11 23936226
2011 Intersectin 2 nucleotide exchange factor regulates Cdc42 activity during Xenopus early development. Biochemical and biophysical research communications 11 21530493
2024 OVO positively regulates essential maternal pathways by binding near the transcriptional start sites in the Drosophila female germline. eLife 10 39291827
2022 Noradrenergic Signaling in Astrocytes Influences Mammalian Sleep Homeostasis. Clocks & sleep 10 35892990
2020 Time- and population-dependent genetic patterns underlie bovine milk somatic cell count. Journal of dairy science 10 32622601
2024 Intersectin - many facets of a scaffold protein. Biochemical Society transactions 9 38174740
2023 Intersectin deficiency impairs cortico-striatal neurotransmission and causes obsessive-compulsive behaviors in mice. Proceedings of the National Academy of Sciences of the United States of America 9 37603735
2022 Cold exposure induces browning of bovine subcutaneous white fat in vivo and in vitro. Journal of thermal biology 9 36796901
2019 TLR7 Modulated T Cell Response in the Mesenteric Lymph Node of Schistosoma japonicum-Infected C57BL/6 Mice. Journal of immunology research 9 31930147
2012 Identification of a novel function of the clathrin-coated structure at the plasma membrane in facilitating GM-CSF receptor-mediated activation of JAK2. Cell cycle (Georgetown, Tex.) 9 22935703
2024 Therapeutic effect of Micro-Implant Anchorage in orthodontics. Pakistan journal of medical sciences 8 39554669
2021 Generation of Tetracycline and Rifamycin Resistant Chlamydia Suis Recombinants. Frontiers in microbiology 8 34276577
2021 Lipocalin 2 Is a Regulator During Macrophage Polarization Induced by Soluble Worm Antigens. Frontiers in cellular and infection microbiology 8 34616693
2024 Clinicopathologic Features and Cytologic Correlation of ALK-Rearranged Papillary Thyroid Carcinoma: A Series of Eight Cases. Endocrine pathology 7 38642308
2013 Maternal dietary restriction alters offspring's sleep homeostasis. PloS one 7 23741310
2012 Human intersectin 2 (ITSN2) binds to Eps8 protein and enhances its degradation. BMB reports 7 22449706
2005 The neuro-biomolecular basis of alertness in sleep disorders. Sleep medicine 7 16140244
2000 Distinctive Swann blood group genotypes: molecular investigations. Vox sanguinis 7 11155072
2020 The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways. Journal of cell science 6 32737221
2007 Expression analysis of human intersectin 2 gene (ITSN2) minor splice variants showing differential expression in normal human brain. Oncology reports 6 17390067
2023 Shear wave elastography can stratify rectal cancer response to short-course radiation therapy. Scientific reports 5 37752156
2018 Intersectin-Cdc42 interaction is required for orderly meiosis in porcine oocytes. Journal of cellular physiology 5 30478952
2016 Fluorescence and phosphorescence of tryptophan in peptides of different length and sequence. Journal of photochemistry and photobiology. B, Biology 5 26916609
2024 Slow wave activity disruptions and memory impairments in a mouse model of aging. Neurobiology of aging 4 38701647
2023 Sleep and the sleep electroencephalogram in C57BL/6 and C3H/HeN mice. Journal of sleep research 4 37803888
2022 Correlating electroconvulsive therapy response to electroencephalographic markers: Study protocol. Frontiers in psychiatry 4 36405897
2021 Stable and EGF-Induced Temporal Interactome Profiling of CBL and CBLB Highlights Their Signaling Complex Diversity. Journal of proteome research 4 34134489
2021 Pain sensitivity increases with sleep disturbance under predictable chronic mild stress in mice. Scientific reports 4 34244555
2019 Evaluating global and local sequence alignment methods for comparing patient medical records. BMC medical informatics and decision making 4 31856819
2017 Long-Distance Travellers: Phylogeography of a Generalist Parasite, Pholeter gastrophilus, from Cetaceans. PloS one 4 28085945
2017 Mammalian verprolin CR16 acts as a modulator of ITSN scaffold proteins association with actin. Biochemical and biophysical research communications 4 28161632
2024 Multi-tissue transcriptome profiling linked the association between tissue-specific circRNAs and the heterosis for feed intake and efficiency in chicken. Poultry science 3 38713987
2023 Case of hereditary kidney disease presenting thin basement membrane with a single heterozygous variant of Intersectin 2. Journal of rural medicine : JRM 3 37032986
2019 Infraslow coordination of slow wave activity through altered neuronal synchrony. Sleep 3 31353415
2014 Contribution of transcriptional and translational mechanisms to the recovery aspect of sleep regulation. Annals of medicine 3 24428734
2025 Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice. Current biology : CB 2 40118064
2025 Dim light at night disrupts the sleep-wake cycle and exacerbates abnormal EEG activity in Cntnap2 knockout mice: implications for autism spectrum disorders. Molecular autism 2 41408339
2019 Cortical zeta-inhibitory peptide injection reduces local sleep need. Sleep 2 30722054
2025 Chronic chemogenetic slow-wave-sleep enhancement in mice. bioRxiv : the preprint server for biology 1 39896659
2024 Arbuscular mycorrhizal fungi increased biomass, nutritional value, and cochineal resistance of Opuntia ficus-indica plants. BMC plant biology 1 39054409
2024 Serodiagnosis of urogenital schistosomiasis and profiling of immunoreactive protein(s) in Schistosoma haematobium soluble egg and adult worm antigens. Journal of vector borne diseases 1 39468931
2023 Reassignment of NMR spectroscopic data of oleana-9(11),12-diene-3β-ol isolated from Jeffreycia zeylanica and its wound healing potential in terms of cell migration and proangiogenic activity1. Natural product research 1 36938871
2026 RBM15B promotes hepatocellular carcinoma progression via IGF2BP1-mediated ITSN2 mRNA stabilization. Journal of cancer research and clinical oncology 0 41795047
2025 Prime editing of the β1 adrenoceptor in the brain restores physiological REM sleep in a mouse model of Alzheimer's disease. Nature communications 0 41365977
2025 Serodiagnosis of urogenital schistosomiasis and profiling of immunoreactive protein(s) in Schistosoma haematobium soluble egg and adult worm antigens. Journal of vector borne diseases 0 42041245
2024 OVO Positively Regulates Essential Maternal Pathways by Binding Near the Transcriptional Start Sites in the Drosophila Female Germline. bioRxiv : the preprint server for biology 0 38076814
2023 A rare phytosterol, stigmast-5-en-3β,7α,22α-triol and other secondary metabolites from Leea indica showing enhanced in vitro cell migration and proangiogenic activity. Natural product research 0 37590092

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