Affinage

CC2D1A

Coiled-coil and C2 domain-containing protein 1A · UniProt Q6P1N0

Length
951 aa
Mass
104.1 kDa
Annotated
2026-06-09
100 papers in source corpus 21 papers cited in narrative 21 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

CC2D1A (Freud-1/TAPE/Aki1) is a multifunctional DM14- and C2-domain scaffold that operates as both a calcium-regulated transcriptional repressor and a cytoplasmic signaling regulator across neuronal, immune, and membrane-trafficking contexts (PMID:12917378, PMID:20529849, PMID:22406677). As a transcriptional repressor it binds a 14-bp repressor element in the 5-HT1A receptor promoter and an intronic element in the dopamine D2 receptor gene, mediating calcium-sensitive repression through its C2/CalB domain; calcium signaling and CaM/CaMK activity relieve this repression (PMID:12917378, PMID:17535813). The predominant long isoform is nuclear and shuttles via CRM1-dependent export (PMID:17714190). In the cytoplasm CC2D1A scaffolds the PDK1/Akt complex downstream of activated EGFR (PMID:18662999), activates canonical NF-κB through a TRAF2/Ubc13/TAK1/IKK cascade requiring its C2 domain (PMID:20529849), and—localizing to endolysosomes—links TLR3, endocytic TLR4, and RIG-I-like receptors (RIG-I, MDA5) to IFN-β induction upstream of TRIF and IPS-1/MAVS (PMID:21189260, PMID:22833682). Through its DM14 domains CC2D1A directly binds the N-terminal hairpin of the ESCRT-III subunit CHMP4B with nanomolar affinity, preventing CHMP4B polymerization and thereby restraining intraluminal-vesicle sorting and lysosomal degradation of receptors such as EGFR and TLR4 (PMID:22406677, PMID:22258254, PMID:27769858). In neurons CC2D1A controls dendritic complexity, synaptic maturation, and plasticity: it maintains homeostatic NF-κB levels, and its loss drives Rac1 hyperactivation through reduced SENP1/SENP3-mediated de-SUMOylation, with pharmacological inhibition of NF-κB or Rac1 rescuing the resulting deficits (PMID:21273312, PMID:25066123, PMID:30992372). Conditional knockout mice recapitulate human CC2D1A loss-of-function neurodevelopmental phenotypes including impaired learning, reduced sociability, repetitive grooming, and altered excitation/inhibition balance (PMID:26826102, PMID:34132974). CC2D1A loss also causes heterotaxy and ciliary defects in zebrafish via a loss-of-function mechanism (PMID:33196317).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established CC2D1A's founding identity as a sequence-specific, calcium-regulated transcriptional repressor, explaining how 5-HT1A receptor levels are set.

    Evidence DNA-binding, promoter-reporter, antisense knockdown, and CalB-domain mutagenesis on the 5-HT1A promoter

    PMID:12917378

    Open questions at the time
    • Mechanism coupling calcium/CaMK signaling to loss of FRE binding not structurally defined
    • Did not address non-transcriptional functions
  2. 2007 High

    Extended the repressor role to a second neurotransmitter receptor gene (DRD2) and showed allele-specific regulation, establishing CC2D1A as a broader regulator of monoaminergic receptor expression.

    Evidence EMSA, ChIP, siRNA, and reporter assays on the DRD2 intronic D2-DRE plus SNP analysis

    PMID:17535813

    Open questions at the time
    • Shared sequence determinants of FRE vs D2-DRE recognition not defined
  3. 2007 Medium

    Resolved isoform usage and showed the nuclear long isoform is the chromatin-engaged repressor with CRM1-dependent export, clarifying where repression occurs.

    Evidence Subcellular fractionation, CRM1 inhibition, in vitro DNA binding, isoform-specific ChIP

    PMID:17714190

    Open questions at the time
    • Single lab
    • Functional role of nuclear export in regulating repression not established
  4. 2008 High

    Revealed a cytoplasmic scaffolding function distinct from transcription, coupling CC2D1A to EGFR-driven PDK1/Akt survival signaling.

    Evidence Reciprocal Co-IP, kinase assays, siRNA with apoptosis and clonogenic readouts

    PMID:18662999

    Open questions at the time
    • Domain required for PDK1/Akt scaffolding not mapped
    • Basis of EGF- vs IGF-1 selectivity unknown
  5. 2010 High

    Defined CC2D1A as a C2-domain-dependent activator of canonical NF-κB and placed it within a defined ubiquitin-kinase cascade.

    Evidence Reporter assays with domain mutagenesis and genetic epistasis across Ubc13/TRAF2/TAK1/IKK plus CYLD

    PMID:20529849

    Open questions at the time
    • Direct molecular target of CC2D1A within the cascade not identified
    • How C2 domain engages the pathway unclear
  6. 2010 High

    Identified CC2D1A/TAPE as an endolysosomal innate immune adaptor linking endosomal TLRs to IFN-β upstream of TRIF.

    Evidence Rab5/LAMP1 co-localization, TRIF Co-IP, siRNA epistasis with cytokine readouts

    PMID:21189260

    Open questions at the time
    • Direct binding interface with TRIF not mapped
    • Relationship to NF-κB scaffolding role not integrated
  7. 2011 High

    Demonstrated organismal essentiality and a C2-domain-dependent role in controlling the pace of synaptic functional maturation.

    Evidence Cc2d1a knockout mice with cortical-neuron electrophysiology and full-length vs C2-deletion rescue

    PMID:21273312

    Open questions at the time
    • Molecular link between C2 domain and synaptic maturation not defined
    • Cause of neonatal respiratory failure unresolved
  8. 2012 High

    Provided the structural and biochemical mechanism for CC2D1A as a negative regulator of ESCRT-III, binding the CHMP4B hairpin to block polymerization.

    Evidence SPR affinity mapping, crystal structure of CHMP4B hairpin, in vitro polymerization, HIV-1 budding mutagenesis (corroborated by Co-IP/domain mapping in cells)

    PMID:22258254 PMID:22406677

    Open questions at the time
    • How CC2D1A release permits CHMP4B polymerization in vivo not defined
    • Regulation of CC2D1A-CHMP4B binding unknown
  9. 2012 High

    Extended the innate-immune adaptor role to cytosolic RNA sensing, placing CC2D1A upstream of IPS-1 in the RIG-I/MDA5 pathway.

    Evidence Co-IP with RIG-I/MDA5/IPS-1, siRNA/KO epistasis, viral infection assays

    PMID:22833682

    Open questions at the time
    • How an endolysosomal protein engages cytosolic RLR signaling not reconciled
  10. 2013 Medium

    Linked CC2D1A to cAMP homeostasis via DM14-dependent control of PDE4D localization and PKA-mediated phosphorylation.

    Evidence Co-localization, phospho-PDE4D blots, rolipram rescue in CC2D1A-mutant MEFs

    PMID:23826796

    Open questions at the time
    • Single lab
    • Whether CC2D1A binds PDE4D directly not established
  11. 2014 High

    Reframed CC2D1A's NF-κB role in neurons as homeostatic and established NF-κB dysregulation as the cause of dendritic deficits.

    Evidence Neuronal gain/loss-of-function, NF-κB reporter, morphology, pharmacological NF-κB inhibition rescue

    PMID:25066123

    Open questions at the time
    • Mechanism by which both gain and loss elevate NF-κB not resolved
  12. 2016 High

    Showed CC2D1A cycles to endosomal membranes and is required for endosomal morphogenesis, while excluding Notch involvement.

    Evidence Conditional KO, EM endosome morphometry, VPS4-perturbation localization, Notch reporter

    PMID:26720614

    Open questions at the time
    • Centrosomal function not confirmed
    • Trigger for cytosol-to-endosome cycling unknown
  13. 2016 Medium

    Connected the ESCRT-regulatory role to receptor signaling kinetics, showing CC2D1A restrains EGFR/TLR4 ILV sorting and ERK termination.

    Evidence siRNA with receptor degradation and ERK1/2 signaling readouts

    PMID:27769858

    Open questions at the time
    • No rescue experiment
    • Single lab
  14. 2017 High

    Demonstrated in vivo that 5-HT1A autoreceptor upregulation mediates the affective consequences of CC2D1A loss, formally validating the transcriptional repressor model.

    Evidence 5-HT-neuron conditional KO with autoradiography, neurochemistry, behavior, and double-KO epistasis

    PMID:29101244

    Open questions at the time
    • Relationship to non-serotonergic CC2D1A functions not addressed
  15. 2017 High

    Established that forebrain CC2D1A loss recapitulates human neurodevelopmental disease phenotypes spanning morphology, plasticity, and behavior.

    Evidence CamKIIa-Cre conditional KO with morphology, LTP, and behavioral battery

    PMID:26826102

    Open questions at the time
    • Causal molecular pathway not dissected in this study
  16. 2019 High

    Identified a SENP1/SENP3–SUMO–Rac1 axis as the downstream mechanism linking CC2D1A loss to plasticity and memory deficits.

    Evidence Conditional KO, LTP, Rac1 activity pull-down, SENP/SUMO blots, Rac1-inhibitor rescue

    PMID:30992372

    Open questions at the time
    • How CC2D1A controls SENP1/SENP3 expression unknown
    • Relationship to NF-κB homeostasis pathway unclear
  17. 2019 Medium

    Implicated CC2D1A in chemotherapy resistance, indicating its survival-signaling functions are relevant in cancer.

    Evidence shRNA knockdown with clonogenic assays and xenograft survival

    PMID:31632917

    Open questions at the time
    • Mechanistic pathway not defined
    • Single lab
  18. 2020 Medium

    Established a ciliary/left-right patterning role and confirmed a loss-of-function disease mechanism through allele-specific rescue.

    Evidence TALEN zebrafish KO with acetylated α-tubulin staining and wild-type vs patient-mutant mRNA rescue

    PMID:33196317

    Open questions at the time
    • Single lab/ortholog model
    • Molecular role of CC2D1A at cilia not defined
  19. 2021 Medium

    Tied CC2D1A loss to CREB/BDNF signaling alongside serotonergic dysregulation in vivo.

    Evidence AAV-shRNA hippocampal knockdown with western blot, qRT-PCR, HPLC, behavior

    PMID:34948116

    Open questions at the time
    • No rescue
    • Causal ordering relative to 5-HT1A and cAMP/PDE4D not resolved
  20. 2021 High

    Linked CC2D1A loss in glutamatergic neurons to autistic-like phenotypes via E/I imbalance amenable to anti-inflammatory rescue.

    Evidence Emx1-Cre conditional KO with morphology, E/I electrophysiology, behavior, minocycline rescue

    PMID:34132974

    Open questions at the time
    • Molecular target of minocycline action not identified
    • Integration with Rac1 and NF-κB mechanisms not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CC2D1A's diverse functions—nuclear repression, cytoplasmic kinase/immune scaffolding, and ESCRT-III regulation—are coordinated within a single protein, and which is primary in each disease context, remains unresolved.
  • No unified structural model integrating DM14 and C2 functions
  • Mechanism switching CC2D1A between nuclear, cytosolic, and endosomal pools unknown
  • Causal hierarchy among NF-κB, Rac1, cAMP, and serotonergic pathways in neurodevelopmental disease not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005768 endosome 3 GO:0005634 nucleus 1 GO:0005764 lysosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-112316 Neuronal System 5 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-74160 Gene expression (Transcription) 2
Partners
AKTCHMP4BEGFRIPS-1PDE4DPDK1RIG-ITRIF
Complex memberships
CC2D1A-CHMP4B (ESCRT-III) complexPDK1/Akt complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Freud-1 (CC2D1A) was cloned as a novel DNA-binding protein that binds a 14 bp 5'-repressor element (FRE) in the 5-HT1A receptor gene promoter and mediates transcriptional repression. An intact C2/CalB calcium/phospholipid-binding domain was required for repression. Calcium-dependent signaling blocked Freud-1–FRE binding, and inhibitors of calmodulin or CaM-dependent protein kinase reversed this calcium-mediated inhibition. Overexpression repressed the 5-HT1A promoter and decreased 5-HT1A receptor protein, while antisense to Freud-1 derepressed it. DNA-binding assays, promoter-reporter assays, antisense knockdown, CalB domain mutagenesis, immunofluorescence co-localization The Journal of Neuroscience High 12917378
2007 Freud-1/CC2D1A binds a conserved intronic element (D2-DRE) in the human dopamine D2 receptor (DRD2) gene and represses its transcription. Recombinant Freud-1 bound D2-DRE specifically; endogenous Freud-1 occupancy was confirmed by chromatin immunoprecipitation. siRNA knockdown of Freud-1 upregulated DRD2 mRNA and binding sites. A SNP (rs2734836) adjacent to D2-DRE conferred allele-specific Freud-1 binding and differential repression. Electrophoretic mobility shift assay, chromatin immunoprecipitation, siRNA knockdown, transcriptional reporter assay, receptor-binding assay The Journal of Biological Chemistry High 17535813
2007 Human CC2D1A/Freud-1 encodes short and long isoforms; the long isoform (Freud-1L) is predominant in human cells and is enriched in the nuclear fraction. Nuclear export of Freud-1L is CRM1/exportin-1-dependent. Freud-1L binds the 5-HT1A dual repressor element in vitro and is bound to it in chromatin as shown by ChIP with isoform-specific antibodies. Subcellular fractionation, CRM1-inhibitor treatment, in vitro DNA-binding assay, chromatin immunoprecipitation The European Journal of Neuroscience Medium 17714190
2008 Freud-1/Aki1 (CC2D1A) functions as a receptor-selective scaffold for the PDK1/Akt pathway. It associates with PDK1 and Akt, induces PDK1/Akt complex formation, and regulates Akt activation in a concentration-dependent biphasic manner. It also associates with EGF receptor upon EGF stimulation. Freud-1/Aki1 gene silencing decreased Akt kinase activity, induced apoptosis, and increased chemosensitivity. The scaffold function was selective for EGF, not IGF-1, signaling. Co-immunoprecipitation, siRNA knockdown, kinase activity assay, apoptosis assay, clonogenic assay Molecular and Cellular Biology High 18662999
2010 CC2D1A activates NF-κB through the canonical IKK pathway. Activation requires its C2 domain. The pathway dependence was defined by genetic epistasis: CC2D1A-induced NF-κB activation required Ubc13, TRAF2, TAK1, and the IKK complex. The deubiquitinase CYLD negatively regulates CC2D1A-mediated NF-κB activation. Transcriptional reporter assay, domain deletion/mutagenesis, dominant-negative and siRNA epistasis experiments The Journal of Biological Chemistry High 20529849
2010 TAPE/CC2D1A is an innate immune regulator that colocalizes with endosomal marker Rab5 and lysosomal marker LAMP1, placing it in endolysosomes. It activates TBK1, NF-κB, and ERK pathways leading to IFN-β and inflammatory cytokine induction. Knockdown selectively impairs TLR3 and endocytic TLR4 pathways to IFN-β. TAPE physically interacts and synergizes with TRIF; TAPE acts upstream of TRIF in TLR3 signaling. Immunofluorescence co-localization, co-immunoprecipitation, siRNA knockdown, reporter assay, cytokine ELISA The Journal of Biological Chemistry High 21189260
2011 Cc2d1a knockout mice die soon after birth apparently due to respiratory failure not explained by peripheral structural defects. Cc2d1a-deficient cortical neurons show a robust increase in the pace of maturation of evoked synaptic responses and synaptic vesicle trafficking. Reintroduction of full-length Cc2d1a, but not a C2-domain-deletion mutant, rescued these synaptic anomalies, demonstrating that the C2 domain is required for Cc2d1a's role in controlling synaptic functional maturation. Knockout mouse generation, electrophysiology of cortical neurons, rescue by lentiviral expression of full-length vs. C2-deletion mutant Journal of Neurophysiology High 21273312
2012 CC2D1A directly binds CHMP4B (ESCRT-III) with nanomolar affinity forming a 1:1 complex. The binding site on CC2D1A maps to a short linear sequence within the third DM14 domain; the binding site on CHMP4B maps to its N-terminal helical hairpin as defined by crystal structure and surface plasmon resonance mutagenesis. CC2D1A binding prevents CHMP4B polymerization in vitro, suggesting CC2D1A acts as a negative regulator of CHMP4B function. Mutations disrupting the CC2D1A-binding surface on CHMP4B abolished the dominant-negative effect of CHMP4B C-terminal truncation on HIV-1 budding. Pulldown, surface plasmon resonance (affinity measurement), crystal structure of CHMP4B helical hairpin, in vitro polymerization assay, HIV-1 budding assay with mutagenesis Journal of Molecular Biology High 22406677
2012 CC2D1A and CC2D1B bind to the core domain of CHMP4B proteins in human cells and are found in high-molecular-weight complexes with CHMP4 in vivo. The DM14 domains constitute novel CHMP4-binding modules; the highest-affinity DM14 domain alone inhibits ALIX-dependent HIV-1 budding by sequestering CHMP4. Overexpression of CC2D1A inhibited HIV-1 release; siRNA against CC2D1A or CC2D1B increased budding under certain conditions, consistent with a role in restraining CHMP4 polymerization. Co-immunoprecipitation from human cells, domain mapping, HIV-1 budding assay, siRNA knockdown Journal of Virology High 22258254
2012 TAPE/CC2D1A physically interacts with RIG-I, MDA5, and IPS-1 (MAVS) and activates the IFN-β promoter. TAPE knockdown impairs IFN-β activation induced by RLRs but not by IPS-1 overexpression, placing TAPE upstream of IPS-1 in the RIG-I-like receptor pathway. TAPE-deficient cells show defective cytokine production and antiviral responses upon RNA virus infection. Co-immunoprecipitation, siRNA knockdown and knockout, reporter assay, cytokine measurement, viral infection assay The Journal of Biological Chemistry High 22833682
2013 CC2D1A co-localizes with PDE4D in the cytosol before cAMP stimulation and at the cell periphery after stimulation; full-length CC2D1A is required for this translocation. In CC2D1A mutant cells lacking three of four DM14 domains, the complex fails to translocate and PDE4D Ser126 is constitutively phosphorylated by PKA, leading to PDE4D hyperactivity and defective downstream CREB phosphorylation. Rolipram (PDE4 inhibitor) restored CREB phosphorylation in mutant cells. Immunofluorescence co-localization, phospho-specific western blot, pharmacological rescue with rolipram, mouse embryonic fibroblasts from CC2D1A mutant mice Cell Communication and Signaling Medium 23826796
2014 Cc2d1a gain- and loss-of-function both increase NF-κB activation in neurons, revealing a homeostatic role. Cc2d1a knockdown in neurons reduces dendritic complexity and increases NF-κB activity. Inhibiting NF-κB activity rescued the dendritic complexity defect caused by Cc2d1a depletion, establishing NF-κB dysregulation as the pathway mechanism downstream of CC2D1A loss in neurons. siRNA knockdown in neurons, NF-κB reporter assay, neuronal morphology analysis, pharmacological NF-κB inhibition rescue Cell Reports High 25066123
2015 CC2D1A (mammalian ortholog of Drosophila Lgd) and its interaction partner CHMP4B localize to endosomes in MEF cells when VPS4 activity is reduced, indicating CC2D1A cycles between cytosol and endosomal membrane. Cc2d1a knockout MEF cells show increased average endosome size, indicating a defect in endosomal morphogenesis. However, CC2D1A loss does not affect Notch signaling in intestinal-specific knockout mice, and centrosomal function was not confirmed. Conditional knockout mice, electron microscopy of endosomes, immunofluorescence co-localization with VPS4 dominant-negative, Notch reporter (Hes1-emGFP) analysis PLoS Genetics High 26720614
2016 CC2D1A binds to CHMP4B polymers formed on endosomes and regulates the endosomal sorting pathway. Depletion of CC2D1A and CC2D1B accelerates lysosomal degradation of EGFR and TLR4 by promoting their sorting to intraluminal vesicles (ILVs), and rapidly terminates ERK1/2 downstream signaling. siRNA knockdown, receptor degradation assay, western blot for downstream signaling (ERK1/2), immunofluorescence Biochemical and Biophysical Research Communications Medium 27769858
2017 Conditional knockout of Freud-1/Cc2d1a specifically in 5-HT neurons in adult mice (cF1ko) increases 5-HT1A autoreceptor protein, binding, and hypothermic response, reduces 5-HT content and raphe neuronal activity, and produces anxiety- and depression-like behavior resistant to fluoxetine. Conditional double knockout removing both Freud-1 and 5-HT1A in 5-HT neurons abolished the anxiety/depression-like phenotype of Freud-1 knockout, demonstrating that the behavioral effects of Freud-1 loss are mediated through 5-HT1A autoreceptor upregulation. Conditional knockout mouse (Cre/loxP in 5-HT neurons), receptor autoradiography, 5-HT neurochemistry, behavioral testing, conditional double knockout epistasis The Journal of Neuroscience High 29101244
2017 Forebrain-specific postnatal conditional deletion of Cc2d1a (CamKIIa-Cre) in mice produces abnormal cortical dendrite organization, reduced dendritic spine density, deficits in LTP/neuronal plasticity, and impaired spatial learning and memory, as well as reduced sociability, hyperactivity, anxiety, and excessive grooming, recapitulating human CC2D1A loss-of-function phenotypes. Conditional knockout mouse, neuronal morphology analysis (Golgi/immunofluorescence), electrophysiology (LTP), behavioral battery Cerebral Cortex High 26826102
2019 Conditional deletion of Cc2d1a from excitatory neurons impairs LTP at CA1 synapses and object location memory. Loss of CC2D1A results in reduced SENP1 and SENP3 expression, increasing Rac1 SUMOylation and thereby elevating basal Rac1 activity. Partial pharmacological blockade of Rac1 rescued both LTP and memory deficits in Cc2d1a cKO mice, establishing Rac1 hyperactivation as a downstream mechanism. Conditional knockout mouse (CamKIIa-Cre), LTP electrophysiology, Rac1 activity pull-down assay, western blot for SENP1/SENP3/SUMOylated Rac1, pharmacological rescue with Rac1 inhibitor The Journal of Neuroscience High 30992372
2019 CC2D1A promotes chemotherapy resistance in ovarian cancer cells. shRNA-mediated knockdown of CC2D1A in cisplatin-resistant ovarian cancer cell lines increased sensitivity to cisplatin and paclitaxel in clonogenic assays, and xenograft mice with CC2D1A knockdown survived significantly longer under chemotherapy treatment. shRNA knockdown, cell viability/clonogenic assay, xenograft mouse model Frontiers in Oncology Medium 31632917
2020 Monoallelic loss-of-function mutations in CC2D1A are associated with heterotaxy and ciliary dysfunction. In zebrafish, TALEN-mediated somatic and germline cc2d1a knockout produced heterotaxy of cardiovascular and gastrointestinal organs and defective cilia (reduced acetylated α-tubulin staining). Phenotypes were rescued by wild-type cc2d1a mRNA but not by mRNA encoding the patient mutations, confirming a loss-of-function mechanism for CC2D1A in left-right patterning and ciliogenesis. TALEN zebrafish knockout, whole-mount immunostaining of acetylated α-tubulin, mRNA rescue experiment Circulation: Genomic and Precision Medicine Medium 33196317
2021 Cc2d1a/Freud-1 hippocampal knockdown via AAV-shRNA upregulates 5-HT and 5-HIAA levels, reduces CREB mRNA and CREB phosphorylation, upregulates cFos mRNA, and enhances proBDNF protein expression, placing CC2D1A in a pathway that regulates CREB and BDNF signaling in addition to 5-HT1A receptor control. AAV-mediated shRNA knockdown in vivo, western blot, qRT-PCR, HPLC for serotonin metabolites, behavioral tests International Journal of Molecular Sciences Medium 34948116
2021 Loss of CC2D1A in glutamatergic neurons (Emx1-Cre) in mice leads to autistic-like phenotypes including self-injurious repetitive grooming and aberrant social interactions, decreased complexity of mPFC pyramidal neuron dendritic arbors, and increased synaptic excitation/inhibition (E/I) ratio. Chronic minocycline treatment rescued behavioral, morphological, and E/I ratio abnormalities, identifying inflammatory/E/I imbalance as a mechanistic pathway. Emx1-Cre conditional knockout, dendritic morphology analysis, electrophysiology (E/I ratio in mPFC), behavioral battery, pharmacological rescue with minocycline Neurotherapeutics High 34132974

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 Evaluating Protein Transfer Learning with TAPE. Advances in neural information processing systems 448 33390682
2018 Contingency and determinism in evolution: Replaying life's tape. Science (New York, N.Y.) 384 30409860
2020 Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis. The Journal of allergy and clinical immunology 179 32709423
2019 Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis. JAMA dermatology 156 31596431
2001 Physical and physiological effects of stratum corneum tape stripping. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 149 11301640
2005 The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation. Journal of medical genetics 127 16033914
2015 The phage tail tape measure protein, an inner membrane protein and a periplasmic chaperone play connected roles in the genome injection process of E. coli phage HK97. Molecular microbiology 111 25532427
2018 Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2-high atopic dermatitis disease endotype. The Journal of allergy and clinical immunology 96 29309794
2007 Efficient and simple quantification of stratum corneum proteins on tape strippings by infrared densitometry. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 96 17610645
2020 Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin. Allergy 91 32639640
2016 Functional and structural dissection of the tape measure protein of lactococcal phage TP901-1. Scientific reports 82 27824135
2003 Freud-1: A neuronal calcium-regulated repressor of the 5-HT1A receptor gene. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 12917378
2021 Replaying the evolutionary tape to investigate subgenome dominance in allopolyploid Brassica napus. The New phytologist 74 33280122
2016 Tape Stripping Technique for Stratum Corneum Protein Analysis. Scientific reports 70 26817661
2014 CC2D1A regulates human intellectual and social function as well as NF-κB signaling homeostasis. Cell reports 70 25066123
2008 Freud-1/Aki1, a novel PDK1-interacting protein, functions as a scaffold to activate the PDK1/Akt pathway in epidermal growth factor signaling. Molecular and cellular biology 62 18662999
2021 Tape strips in dermatology research. The British journal of dermatology 59 33370449
2018 Photo-tearable tape close-wrapped upconversion nanocapsules for near-infrared modulated efficient siRNA delivery and therapy. Biomaterials 54 29452948
2012 Portable self-contained cultures for phage and bacteria made of paper and tape. Lab on a chip 53 22895550
2015 Replaying the tape of life in the twenty-first century. Interface focus 51 26640652
2012 CC2D1A is a regulator of ESCRT-III CHMP4B. Journal of molecular biology 51 22406677
2009 Induction of eosinophil- and Th2-attracting epidermal chemokines and cutaneous late-phase reaction in tape-stripped skin. Experimental dermatology 51 19558500
2022 Junctional epithelium and hemidesmosomes: Tape and rivets for solving the "percutaneous device dilemma" in dental and other permanent implants. Bioactive materials 50 35387164
2006 Laser capture microdissection of plant cells from tape-transferred paraffin sections promotes recovery of structurally intact RNA for global gene profiling. The Plant journal : for cell and molecular biology 49 17026538
2004 Use of RT-PCR and DNA microarrays to characterize RNA recovered by non-invasive tape harvesting of normal and inflamed skin. The Journal of investigative dermatology 48 15191556
2020 Skin tape sampling technique identifies proinflammatory cytokines in atopic dermatitis skin. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 45 32896640
2021 Assessment of biomarkers in pediatric atopic dermatitis by tape strips and skin biopsies. Allergy 44 34695223
2021 Transcriptomic Profiling of Tape-Strips From Moderate to Severe Atopic Dermatitis Patients Treated With Dupilumab. Dermatitis : contact, atopic, occupational, drug 43 34405829
2017 Cc2d1a Loss of Function Disrupts Functional and Morphological Development in Forebrain Neurons Leading to Cognitive and Social Deficits. Cerebral cortex (New York, N.Y. : 1991) 42 26826102
2019 Advancement through epidermis using tape stripping technique and Reflectance Confocal Microscopy. Scientific reports 41 31434955
2017 Abrogated Freud-1/Cc2d1a Repression of 5-HT1A Autoreceptors Induces Fluoxetine-Resistant Anxiety/Depression-Like Behavior. The Journal of neuroscience : the official journal of the Society for Neuroscience 41 29101244
2023 Intrapatient comparison of atopic dermatitis skin transcriptome shows differences between tape-strips and biopsies. Allergy 37 37577841
2009 Chronic social defeat downregulates the 5-HT1A receptor but not Freud-1 or NUDR in the rat prefrontal cortex. Neuroscience letters 37 20026183
2012 Identifying biological landmarks using a novel cell measuring image analysis tool: Cell-o-Tape. Plant methods 36 22385537
2016 Recovery of Trace DNA on Clothing: A Comparison of Mini-tape Lifting and Three Other Forensic Evidence Collection Techniques. Journal of forensic sciences 35 27864934
2010 Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression. The international journal of neuropsychopharmacology 35 20392296
2007 Differential repression by freud-1/CC2D1A at a polymorphic site in the dopamine-D2 receptor gene. The Journal of biological chemistry 35 17535813
2010 CC2D1A, a DM14 and C2 domain protein, activates NF-kappaB through the canonical pathway. The Journal of biological chemistry 34 20529849
2022 TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor. Nature communications 33 36581624
2004 Osteoblast responses to tape-cast and sintered bioactive glass ceramics. Journal of biomedical materials research. Part A 32 15162403
2011 The evolution of the tape measure protein: units, duplications and losses. BMC bioinformatics 31 22151602
2010 TBK1-associated protein in endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways. The Journal of biological chemistry 31 21189260
1995 Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping. The Journal of investigative dermatology 31 7636313
2011 Cc2d1a, a C2 domain containing protein linked to nonsyndromic mental retardation, controls functional maturation of central synapses. Journal of neurophysiology 30 21273312
2000 Fingerprints and DNA: STR typing of DNA extracted from adhesive tape after processing for fingerprints. Journal of forensic sciences 30 10855979
2015 The Mammalian Orthologs of Drosophila Lgd, CC2D1A and CC2D1B, Function in the Endocytic Pathway, but Their Individual Loss of Function Does Not Affect Notch Signalling. PLoS genetics 29 26720614
2018 Stomata Tape-Peel: An Improved Method for Guard Cell Sample Preparation. Journal of visualized experiments : JoVE 28 30059032
2012 Regulation of CHMP4/ESCRT-III function in human immunodeficiency virus type 1 budding by CC2D1A. Journal of virology 28 22258254
2012 TBK1-associated protein in endolysosomes (TAPE)/CC2D1A is a key regulator linking RIG-I-like receptors to antiviral immunity. The Journal of biological chemistry 28 22833682
2021 The transcriptome of hand eczema assessed by tape stripping. Contact dermatitis 27 34812515
1977 Indonesian tapé ketan fermentation. Applied and environmental microbiology 27 16345243
2019 Conditional Deletion of CC2D1A Reduces Hippocampal Synaptic Plasticity and Impairs Cognitive Function through Rac1 Hyperactivation. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 30992372
2023 The Proteome of Hand Eczema Assessed by Tape Stripping. The Journal of investigative dermatology 25 36773646
2014 Stress-induced alterations in 5-HT1A receptor transcriptional modulators NUDR and Freud-1. The international journal of neuropsychopharmacology 25 24946016
2006 Toll-like receptor-9 expression induced by tape-stripping triggers on effective immune response with CpG-oligodeoxynucleotides. Vaccine 25 17049678
2007 The Freud-1/CC2D1A family: transcriptional regulators implicated in mental retardation. Journal of neuroscience research 24 17394259
2017 Tape-Assisted Photolithographic-Free Microfluidic Chip Cell Patterning for Tumor Metastasis Study. Analytical chemistry 23 29191012
2021 Who Packed the Drugs? Application of Bayesian Networks to Address Questions of DNA Transfer, Persistence, and Recovery from Plastic Bags and Tape. Genes 21 35052357
2020 The stratum corneum transcriptome in atopic dermatitis can be assessed by tape stripping. Journal of dermatological science 21 33218696
1997 Tape stripping induces marked epidermal proliferation and altered TGF-alpha expression in non-lesional psoriatic skin. Journal of dermatological science 21 9039979
2019 Disregulation of Autophagy in the Transgenerational Cc2d1a Mouse Model of Autism. Neuromolecular medicine 20 31721010
2021 Effects of Kinesio Tape on Delayed Onset Muscle Soreness: A Systematic Review and Meta-analysis. BioMed research international 19 34159201
2018 Loss of the Intellectual Disability and Autism Gene Cc2d1a and Its Homolog Cc2d1b Differentially Affect Spatial Memory, Anxiety, and Hyperactivity. Frontiers in genetics 19 29552027
2007 The mental retardation gene CC2D1A/Freud-1 encodes a long isoform that binds conserved DNA elements to repress gene transcription. The European journal of neuroscience 19 17714190
2021 Noninvasive Tape-Stripping with High-Resolution RNA Profiling Effectively Captures a Preinflammatory State in Nonlesional Psoriatic Skin. The Journal of investigative dermatology 18 34808239
2020 An assessment of tape-lifts. Forensic science international. Genetics 18 32248081
2019 Barrier-disrupted skin: Quantitative analysis of tape and cyanoacrylate stripping efficiency by multiphoton tomography. International journal of pharmaceutics 18 31759105
2013 Phosphodiesterase activity is regulated by CC2D1A that is implicated in non-syndromic intellectual disability. Cell communication and signaling : CCS 18 23826796
2010 Analysis of free and protein-bound ceramides by tape stripping of stratum corneum from dogs. Archives of dermatological research 18 20361334
2024 Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities. Allergy 17 38375886
2022 Transdermal Drug Delivery: Determining Permeation Parameters Using Tape Stripping and Numerical Modeling. Pharmaceutics 17 36145628
2021 Tape stripping and lipidomics reveal skin surface lipid abnormity in female melasma. Pigment cell & melanoma research 17 33974351
2015 Combining tape stripping and non-invasive reflectance confocal microscopy : an in vivo model to study skin damage. Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 17 25773201
2013 Aberrant distribution patterns of corneodesmosomal components of tape-stripped corneocytes in atopic dermatitis and related skin conditions (ichthyosis vulgaris, Netherton syndrome and peeling skin syndrome type B). Journal of dermatological science 17 23810772
2004 Iso[7]LGD2-protein adducts are abundant in vivo and free radical-induced oxidation of an arachidonyl phospholipid generates this D series isolevuglandin in vitro. Chemical research in toxicology 17 15144218
2023 Continuous removal of single cell layers by tape stripping the stratum corneum - a histological study. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 16 37149231
2023 Digital data storage on DNA tape using CRISPR base editors. Nature communications 16 37833288
2023 Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa. Journal of the American Academy of Dermatology 16 38049071
2020 DNA recovery from unfired and fired cartridge cases: A comparison of swabbing, tape lifting, vacuum filtration, and direct PCR. Forensic science international 16 32977300
2021 Touch DNA recovery from unfired and fired cartridges: Comparison of swabbing, tape lifting and soaking. Forensic science international 15 34801815
2018 The Tape Measure Protein Is Involved in the Heat Stability of Lactococcus lactis Phages. Applied and environmental microbiology 15 29150509
2020 Monoallelic Mutations in CC2D1A Suggest a Novel Role in Human Heterotaxy and Ciliary Dysfunction. Circulation. Genomic and precision medicine 14 33196317
1979 Comparative ultrastructure and cytochemistry of epidermal responses to tape stripping, ethanol and vitamin A acid in hairless mice. The Journal of investigative dermatology 14 224115
2025 Tape-strip profiling identifies unique immune and lipid dysregulation in patients with seborrheic dermatitis. Journal of the American Academy of Dermatology 13 39900186
2020 The Role of Tape Measure Protein in Nucleocytoplasmic Large DNA Virus Capsid Assembly. Viral immunology 13 33074779
2020 Novel alterations of CC2D1A as a candidate gene in a Turkish sample of patients with autism spectrum disorder. The International journal of neuroscience 13 33287601
2016 CC2D1A and CC2D1B regulate degradation and signaling of EGFR and TLR4. Biochemical and biophysical research communications 13 27769858
2009 Effect of tape stripping and adjuvants on immune response after intradermal DNA electroporation. Pharmaceutical research 13 19384465
2021 RNA tape sampling in cutaneous lupus erythematosus discriminates affected from unaffected and healthy volunteer skin. Lupus science & medicine 12 33658303
2021 Loss of CC2D1A in Glutamatergic Neurons Results in Autistic-Like Features in Mice. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 12 34132974
2021 Effects of a Cc2d1a/Freud-1 Knockdown in the Hippocampus on Behavior, the Serotonin System, and BDNF. International journal of molecular sciences 12 34948116
2017 Comparison of suction blistering and tape stripping for analysis of epidermal genes, proteins and lipids. Archives of dermatological research 12 28905096
2017 Kinesiology tape modestly increases skin blood flow regardless of tape application technique. Journal of performance health research 12 34527888
2012 17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells. Cellular and molecular neurobiology 12 22328058
2012 Isotretinoin-loaded nanocapsules: stability and cutaneous penetration by tape stripping in human and pig skin. Journal of biomedical nanotechnology 12 22515077
2025 Skin Tape Stripping Reveals Distinct Biomarker Profiles in Chronic Hand Eczema of Patients With and Without Comorbid Atopic Dermatitis. Allergy 11 39760239
2023 Mussel Foot Protein Inspired Tape-Type Adhesive with Water-Responsive, High Conformal, Tough, and On-Demand Detachable Adhesion to Wet Tissue. Advanced healthcare materials 11 36912388
2022 Inflammation Self-Limiting Electrospun Fibrous Tape via Regional Immunity for Deep Soft Tissue Repair. Small (Weinheim an der Bergstrasse, Germany) 11 36031400
2019 Tape-Stripping Electrochemical Detection of Melanoma. Analytical chemistry 11 31529964
2019 Coiled-Coil and C2 Domain-Containing Protein 1A (CC2D1A) Promotes Chemotherapy Resistance in Ovarian Cancer. Frontiers in oncology 11 31632917

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