Affinage

CLIP1

CAP-Gly domain-containing linker protein 1 · UniProt P30622

Length
1438 aa
Mass
162.2 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 34 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLIP1 (CLIP-170) is a microtubule plus-end tracking protein (+TIP) that couples growing microtubule ends to dynein/dynactin-dependent cargo transport, kinetochore–microtubule attachment, and cytoskeletal reorganization during cell division and differentiation. Its N-terminal tandem CAP-Gly domains, together with adjacent serine-rich regions and multiple SXIP motifs, provide multivalent binding to EB1 and tubulin at growing plus ends, while EB1 is necessary and sufficient for CLIP-170's end-tracking specificity (PMID:19126680, PMID:30455356); the C-terminal zinc-finger domain recruits dynactin, LIS1, and dynein to plus ends for retrograde cargo loading, and an intramolecular autoinhibitory fold between the N- and C-terminal domains regulates these interactions (PMID:15381688, PMID:10588646). Phosphorylation by CDK1 (T287), Plk1 (S195), CK2 (S1318), LRRK1 (T1384), and AMPK (S311) coordinates CLIP-170 functions in kinetochore–fiber stability, centrosome duplication, EGFR endosome transport, and cardiomyocyte contractility (PMID:19687009, PMID:20664522, PMID:25413345, PMID:33251722). Loss-of-function mutation in CLIP1 causes autosomal recessive intellectual disability (PMID:24569606).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Establishing that CLIP-170 is a modular protein with a distinct N-terminal MT-binding domain and a C-terminal cargo-anchoring domain resolved how a single protein could bridge microtubules and peripheral structures.

    Evidence Deletion mutant expression in HeLa and Vero cells with colocalization readouts

    PMID:7983157

    Open questions at the time
    • No binding partners for the C-terminal domain were identified
    • Mechanism of N-terminal MT recognition unknown
  2. 1999 High

    Demonstrating that GFP-CLIP-170 treadmills on growing MT plus ends by recognizing newly polymerized tubulin — rather than by transport — established CLIP-170 as a bona fide plus-end tracking protein and defined the +TIP concept.

    Evidence GFP-CLIP-170 live imaging with drug perturbation and speckle dynamics analysis

    PMID:10052454

    Open questions at the time
    • Molecular basis of 'new end' recognition unknown
    • Whether other factors are required for end specificity was not tested
  3. 1999 High

    Showing that CLIP-170 recruits dynactin (and co-resident dynein) to MT plus ends via its C-terminal domain identified plus ends as cargo-loading stations and established the functional logic of CLIP-170's modular architecture.

    Evidence Overexpression of WT and mutant CLIP-170/p150Glued; immunofluorescence colocalization; dynamitin perturbation

    PMID:10212138 PMID:10588646

    Open questions at the time
    • Direct binding interface between CLIP-170 C-terminus and dynactin subunits not mapped
    • Whether CLIP-170 is rate-limiting for dynein cargo loading in vivo was unclear
  4. 1998 High

    Demonstrating that CLIP-170 transiently localizes to prometaphase kinetochores and that a dominant-negative C-terminal fragment delays prometaphase revealed a mitotic function beyond interphase MT organization.

    Evidence Immunofluorescence and C-terminal domain overexpression in mitotic cells

    PMID:9585405

    Open questions at the time
    • Mechanism of kinetochore recruitment unknown
    • Phosphoregulation during mitosis not explored
  5. 2002 High

    Identifying LIS1 as a direct binding partner of the CLIP-170 zinc-finger domain that acts as an adapter between CLIP-170 and dynein at kinetochores provided a mechanistic link between the +TIP system and the lissencephaly pathway.

    Evidence Co-IP, zinc-finger domain mapping, overexpression of LIS1 WD domain displacing CLIP-170 from kinetochores; two-hybrid mapping of LIS1–dynein interface

    PMID:11889140 PMID:11940666

    Open questions at the time
    • Structural basis of LIS1–CLIP-170 zinc-finger interaction not resolved
    • Relative contributions of LIS1 vs. dynactin for CLIP-170 kinetochore targeting not quantified
  6. 2004 High

    Discovery of CLIP-170 intramolecular autoinhibition — the N-terminal CAP-Gly folds back onto C-terminal zinc-finger motifs — explained how MT binding and cargo-loading activities are coordinately regulated, and showed that p150Glued and LIS1 compete for the same C-terminal sites.

    Evidence Scanning force microscopy, intramolecular FRET, co-IP, and RNAi of CLIP-170 reducing dynactin at tips

    PMID:15381688

    Open questions at the time
    • What triggers autoinhibition relief in vivo was unknown
    • Whether phosphorylation regulates the conformational switch was not tested
  7. 2004 High

    Showing that the CLIP-170 H2 domain promotes MT rescue and nucleation in vitro — and induces tubulin rings visible by cryo-EM — suggested a copolymerization mechanism for plus-end targeting.

    Evidence In vitro MT dynamics, centrosome nucleation assay, cryo-EM of tubulin oligomers

    PMID:15589150

    Open questions at the time
    • Copolymerization model later challenged by single-molecule data showing sub-second dwell times
    • Physiological relevance of tubulin rings unclear
  8. 2005 High

    Establishing that EB1/EB3 directly bind CLIPs and control their dwell time at plus ends reframed CLIP-170 end-tracking as EB-dependent rather than autonomous, resolving conflicting models.

    Evidence RNAi of EB proteins, in vitro binding, live imaging, EB1 mutant rescue

    PMID:16148041

    Open questions at the time
    • Multivalent EB1–CLIP binding modes not yet mapped
    • Whether EB-independent tracking occurs under any condition was unresolved
  9. 2009 High

    In vitro reconstitution at single-molecule resolution demonstrated that EB1 is necessary and sufficient for CLIP-170 plus-end tracking, with sub-second dwell times inconsistent with copolymerization, establishing diffusion-and-capture via the GTP cap as the dominant targeting mechanism.

    Evidence Single-molecule TIRF with purified proteins; GMPCPP controls

    PMID:19126680

    Open questions at the time
    • Whether tubulin copolymerization contributes in cellular conditions with higher protein concentrations was not excluded
    • Role of SXIP motifs not yet appreciated
  10. 2009 High

    Identifying CDK1 phosphorylation at T287 as required for proper CLIP-170 localization, G2/M progression, and prevention of centrosome reduplication established the first phosphoregulatory switch linking CLIP-170 to cell cycle control.

    Evidence Phospho-site mapping, T287A mutant expression, centrosome counting, cell cycle profiling

    PMID:19687009

    Open questions at the time
    • Whether T287 phosphorylation modulates autoinhibition was not tested
    • Downstream effectors beyond Plk1 accumulation not identified
  11. 2010 High

    Demonstrating that Plk1 (S195) and CK2 (S1318) sequentially phosphorylate CLIP-170 to promote dynactin binding and kinetochore localization revealed a phosphorylation cascade ensuring timely kinetochore–MT attachment.

    Evidence Kinase identification, phospho-mutant and phospho-mimetic expression, kinetochore-fiber analysis, co-IP

    PMID:20664522

    Open questions at the time
    • Phosphatase(s) reversing these modifications unknown
    • Whether CK2 phosphorylation disrupts autoinhibition was not addressed
  12. 2014 High

    Connecting CDK1-T287 phosphorylation of CLIP-170 to PLK1 recruitment at kinetochores unified two earlier findings and showed that CLIP-170 is a platform for kinase delivery to kinetochores, explaining K-fiber instability upon CLIP-170 depletion.

    Evidence siRNA depletion, T287A non-phosphorylatable mutant rescue, K-fiber cold-stability assay

    PMID:24777477

    Open questions at the time
    • Whether CLIP-170 directly stabilizes K-fibers or acts only through PLK1 was not resolved
  13. 2014 Medium

    Identification of a human CLIP1 nonsense mutation (p.Q1010*) causing complete loss of CLIP-170 and abolished MT plus-end tracking in patient fibroblasts linked CLIP1 to autosomal recessive intellectual disability, providing the first Mendelian disease association.

    Evidence Linkage analysis, NGS, RT-PCR, western blot, and immunofluorescence in patient-derived fibroblasts

    PMID:24569606

    Open questions at the time
    • Single family — independent replication needed
    • Neuronal mechanism of intellectual disability not explored
    • Whether heterozygous carriers have subtle phenotypes unknown
  14. 2014 High

    Showing that LRRK1 phosphorylates CLIP-170 at T1384 in the C-terminal zinc knuckle to promote dynein–dynactin association and EGFR endosome transport connected CLIP-170 phosphoregulation to receptor trafficking in non-mitotic cells.

    Evidence In vitro kinase assay, phospho-site mapping, co-IP, live-cell EGFR endosome tracking

    PMID:25413345

    Open questions at the time
    • Whether T1384 phosphorylation modulates autoinhibition or LIS1 binding was not determined
  15. 2015 High

    Demonstrating that CLIP-170/EB1/DCTN1 at plus ends specifically initiate HSV-1 retrograde transport — while leaving lysosome and mitochondria motility intact — revealed CLIP-170 as a selective cargo-loading factor for pathogen hijacking of dynein.

    Evidence RNAi and dominant-negative in primary human cells; live viral particle tracking with organelle transport controls

    PMID:26504169

    Open questions at the time
    • Viral receptor on CLIP-170 or dynactin not identified
    • Whether other viruses use the same pathway was unknown
  16. 2018 High

    Mapping multiple EB1-binding modules in CLIP-170 — two CAP-Gly domains recognizing the EEY motif plus flanking SXIP motifs engaging the EB homology domain — explained the multivalent avidity that underpins robust plus-end tracking despite sub-second individual dwell times.

    Evidence Isothermal titration calorimetry and size-exclusion chromatography domain mapping

    PMID:30455356

    Open questions at the time
    • No full-length structural model of CLIP-170–EB1 complex exists
    • How autoinhibition masks individual modules is unknown
  17. 2020 High

    Demonstrating that AMPK phosphorylation of CLIP-170 at S311 at cardiomyocyte intercalated disks prevents pathological MT accumulation and preserves cardiac contractility expanded CLIP-170's physiological roles to mechanosensitive cardiac remodeling.

    Evidence CLIP-170 S311A transgenic mice; cardiac contractility measurements; time-lapse imaging

    PMID:33251722

    Open questions at the time
    • Whether S311 phosphorylation alters autoinhibition or EB1 binding is unknown
    • Downstream structural changes at intercalated disks not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structural model of CLIP-170 — including the autoinhibited conformation and how each phosphorylation event remodels domain interactions — remains unresolved, as does the mechanism by which CLIP-170 selectively loads specific cargos (endosomes, viruses, kinetochore components) at plus ends.
  • No high-resolution full-length structure
  • Cargo selectivity mechanism at plus ends uncharacterized
  • Phosphatases controlling CLIP-170 dephosphorylation not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 7 GO:0060090 molecular adaptor activity 4
Localization
GO:0005856 cytoskeleton 5 GO:0005694 chromosome 4 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
CLASP1CLASP2DCTN1LRRK1MAPRE1MAPRE3PAFAH1B1PLK1
Complex memberships
dynein–dynactin complex (recruited, not stable subunit)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 CLIP-170 (CLIP1) has two functional domains: an N-terminal microtubule-binding domain (containing a tandem repeat essential for MT binding in vivo) and a C-terminal domain involved in anchoring microtubules to peripheral cytoplasmic structures. Transient expression of intact and mutant CLIP-170 forms in mammalian cells (HeLa, Vero); domain deletion analysis Journal of cell science High 7983157
1999 GFP-CLIP-170 treadmills on growing microtubule ends by specifically recognizing the structure of newly polymerized tubulin at plus ends, rather than being continuously transported toward these ends. GFP-CLIP170 fusion live imaging; drug perturbation; speckle analysis Cell High 10052454
1999 CLIP-170 recruits dynactin to microtubule plus ends via its cargo-binding (C-terminal) domain; dynactin colocalizes with CLIP-170 at MT plus ends and this colocalization depends on the CLIP-170 C-terminal domain. Overexpression of wild-type and mutant CLIP-170 and p150Glued; immunofluorescence colocalization; perturbation of dynactin function in vivo Molecular biology of the cell High 10588646
1999 Cytoplasmic dynein, dynactin, and CLIP-170 colocalize at distal microtubule plus ends, identifying these regions as cargo-loading sites for minus end-directed organelle transport. Immunofluorescence with six antibodies against dynactin subunits; overexpression of dynamitin; temperature-shift experiments Journal of cell science Medium 10212138
1998 CLIP-170 transiently associates with prometaphase kinetochores, colocalizing with dynein and dynactin; overexpression of the CLIP-170 C-terminal domain at kinetochores displaces endogenous full-length CLIP-170 and causes a delay in prometaphase, demonstrating a role in kinetochore function. Immunofluorescence; transient overexpression of C-terminal domain dominant negative; dynamitin overexpression The Journal of cell biology High 9585405
2000 CLIP-115 (encoded by CLIP2 but related) efficient microtubule binding requires both the conserved CAP-Gly MTB domains AND adjacent basic, serine-rich regions; phosphorylation modulates MT binding. CLIP-115 forms homodimers linked by disulfide bridges, and Cys391 controls MT bundling capacity. Transfection of mutant CLIP-115 in COS-1 cells; in vitro binding assays; dimerization analysis Journal of cell science Medium 10825300
2001 CLASPs bind CLIP-170 and CLIP-115 directly and colocalize with CLIPs at microtubule distal ends; after serum induction, CLASPs relocalize to distal MT segments at the leading edge via PI3-kinase and GSK-3β signaling; CLASP2 is required for orientation of stabilized microtubules toward the leading edge. Pulldown/co-immunoprecipitation; colocalization; antibody microinjection; kinase inhibitor treatment; dominant-negative approaches Cell High 11290329
2002 CLIP-170 interacts directly with LIS1 via the distal zinc finger motif in CLIP-170's C-terminal domain; this interaction mediates recruitment of CLIP-170 to kinetochores. LIS1 acts as a regulated adapter between CLIP-170 and cytoplasmic dynein. Colocalization; co-immunoprecipitation; overexpression studies; domain-mapping with zinc finger mutants Molecular and cellular biology High 11940666
2002 Overexpression of the LIS1 WD-repeat domain displaces CLIP-170 from kinetochores; LIS1 binds dynein heavy chain (first AAA repeat) and intermediate chain, as well as dynamitin, mediating CLIP-170-dynein interactions at kinetochores. Coexpression/co-immunoprecipitation; two-hybrid assays; domain overexpression The Journal of cell biology High 11889140
2004 CLIP-170 forms an intramolecular interaction between its N-terminal (first metal-binding motif) and C-terminal domains, creating a closed/autoinhibited conformation that regulates MT binding. The N-terminus of p150(Glued) binds directly to the C-terminus of CLIP-170 via the second metal-binding motif; p150(Glued) and LIS1 compete for CLIP-170 C-terminus binding. RNAi knockdown of CLIP-170 strongly reduces dynactin accumulation at MT tips. Scanning force microscopy; FRET; co-immunoprecipitation; in vitro binding; RNAi knockdown The Journal of cell biology High 15381688
2004 The N-terminal H2 domain of CLIP-170 (containing MT-binding domains) promotes microtubule rescues and nucleation in vitro; by cryo-EM, H2 induces tubulin rings in solution and curved oligomers at MT ends, suggesting CLIP-170 targets plus ends by copolymerizing with tubulin via oligomeric intermediates. In vitro MT dynamics assay; electron cryomicroscopy; centrosome-based nucleation assay Current biology High 15589150
2005 EB1 and EB3 control CLIP-170 and CLIP-115 dissociation from MT plus ends; CLIPs bind EB proteins directly, and the C-terminal tyrosine of EBs is important for this interaction. Depletion of EB1 and EB3 accelerates CLIP dissociation from tips. RNAi depletion of EB proteins; in vitro binding assays; live imaging of MT tip dynamics; rescue experiments with EB1 mutants Molecular biology of the cell High 16148041
2006 CLIP-170 binds to microtubules through two CAP-Gly domains; each CAP-Gly domain has different activities — CAP-Gly-1 alone cannot mediate plus-end tracking or MT nucleation, while CAP-Gly-2 with adjacent serine-rich region can both track plus ends in vivo and induce tubulin polymerization in vitro. Expression of CLIP-170 fragments in cells (in vivo plus-end tracking); in vitro tubulin polymerization assay The Journal of biological chemistry High 19074770
2008 GFP-CLIP-170 and EB3 turn over rapidly on MT plus ends (seconds timescale); diffusion of CLIP-170 to MT ends is rate-limiting for its binding; CLIP-170 binds growing MT ends with relatively low affinity at multiple sites. FRAP; single-molecule fluorescence; quantitative live imaging of GFP-CLIP-170 The Journal of cell biology High 18283108
2008 CLIP-170 binds both alpha-tubulin and beta-tubulin beyond their acidic C-terminal tails, including the H12 helices; CLIP-170 can utilize multiple tubulin binding sites to bind EB1 and MT simultaneously. EB1's C-terminus mimics tubulin's acidic tail for CLIP-170 binding. Chemical cross-linking and mass spectrometry; binding assays with tubulin fragments; EB1 interaction assays Journal of molecular biology High 19913027
2009 EB1 is necessary and sufficient for CLIP-170 plus-end tracking; in the absence of EB1, CLIP-170 exhibits lattice diffusion and fails to selectively track MT ends. Single-molecule analysis shows both EB1 and CLIP-170 have short dwell times (<1 s) at growing plus ends, inconsistent with copolymerization; GTP hydrolysis is required for end-specificity. In vitro reconstitution; single-molecule TIRF microscopy; GMPCPP tubulin experiments Proceedings of the National Academy of Sciences of the United States of America High 19126680
2008 Dynein, LIS1, and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly; CLIP-170's role in spindle bipolarity is mediated through its interaction with dynein (as depletion of CLIP-115, which lacks the dynein-dynactin interaction domain, does not restore bipolarity). siRNA depletion of CLIP-170, dynein, LIS1; comparison with CLIP-115 depletion; spindle assembly assays The EMBO journal High 19020519
2009 Cdc2 (CDK1) phosphorylates CLIP-170 at Thr287 in vivo; this phosphorylation is required for proper CLIP-170 localization, normal G2/M transition, and inhibition of centrosome reduplication. T287A substitution causes mislocalization, accumulation of Plk1 and cyclin B, and G2/M block. Co-immunoprecipitation; phospho-site mapping; T287A point mutant expression; centrosome counting; cell cycle analysis The Journal of biological chemistry High 19687009
2010 Polo-like kinase 1 (Plk1) phosphorylates CLIP-170 at S195 and casein kinase 2 (CK2) phosphorylates CLIP-170 at S1318; CK2 phosphorylation at S1318 is required for CLIP-170 binding to dynactin and kinetochore localization; Plk1 phosphorylation at S195 enhances CLIP-170 association with CK2. Both phosphorylations are required for timely kinetochore-microtubule attachment formation. Kinase identification; phospho-site mapping; phospho-mutant (S195A, S1318A, S195E, S1318D) expression; kinetochore fiber analysis; co-immunoprecipitation The EMBO journal High 20664522
2011 CLIP-170 CAP-Gly domains interact with EB1 and EB3 C-terminal domains through distinct mechanisms: the p150(Glued) CAP-Gly dually engages the EB1 EEY motif and EB homology domain, whereas CLIP-170 CAP-Gly domains engage only the EEY motif; crystal structure of EB1-EB3 heterodimer C-termini with p150(Glued) CAP-Gly was solved; CLIP-170 and p150(Glued) CAP-Gly domains interact with EBs with differential affinities. Isothermal titration calorimetry; size-exclusion chromatography; crystal structure determination Journal of structural biology High 22119847
2012 EB1 and CLIP-170 (ClipCG12) cooperatively stabilize microtubule dynamics at concentrations below which neither alone is effective; the combination partially depletes stably bound Pi at MT ends, suggesting modification of the stabilizing cap. In vitro MT dynamics assay; SAXS; analytical ultracentrifugation; [γ-32P]GTP pulsing Biochemistry High 22424550
2012 CLIP-170 promotes paclitaxel binding to microtubules and enhances paclitaxel-driven MT assembly; CLIP-170 expression correlates with paclitaxel sensitivity in breast cancer cells. MT sedimentation assay; binding affinity analysis; in vitro tubulin polymerization assay; cell proliferation assays The Journal of pathology Medium 21989536
2014 CLIP-170 localizes to kinetochores during early mitosis and recruits PLK1 to kinetochores; this requires CDK1-dependent phosphorylation of CLIP-170 at T287. Depletion of CLIP-170 reduces PLK1 at kinetochores and causes K-fiber instability and chromosome misalignment; T287A non-phosphorylatable mutant fails to rescue. siRNA depletion; phospho-mutant expression (T287A); immunofluorescence; K-fiber stability assay Journal of cell science High 24777477
2014 Loss-of-function mutation (p.Q1010*, nonsense) in CLIP1 causes absence of CLIP-170 protein in patient cells; patient fibroblasts show absence of MT plus-end staining, establishing CLIP1 as essential for MT plus-end tracking in vivo and linking CLIP1 defects to autosomal recessive intellectual disability. Linkage analysis; NGS; RT-PCR; western blot; immunofluorescence in patient-derived cells European journal of human genetics Medium 24569606
2014 LRRK1 phosphorylates CLIP-170 at Thr1384 in its C-terminal zinc knuckle motif; this phosphorylation promotes CLIP-170 association with dynein-dynactin complexes, causes accumulation of p150(Glued) at MT plus ends, and facilitates migration of EGFR-containing endosomes. In vitro kinase assay; phospho-site mapping; co-immunoprecipitation; live-cell imaging of EGFR endosomes Journal of cell science High 25413345
2015 CLIP-170 at microtubule plus ends initiates HSV-1 retrograde transport in primary human cells; depletion of CLIP-170, EB1, or DCTN1 completely blocks post-entry long-range retrograde transport of herpesvirus particles without affecting dynein-dependent movement of lysosomes or mitochondria. RNAi; dominant-negative; live-cell imaging of viral particles; transferrin and lysosome transport controls The Journal of cell biology High 26504169
2016 Phosphorylation of CLIP-170 and α-tubulin tyrosination combinatorially control initiation of retrograde transport in distal axons: CLIP-170 phosphorylation primarily regulates time to microtubule encounter, while tubulin tyrosination regulates likelihood of dynein binding. In vitro reconstitution with single-molecule resolution; live-cell transport assays in primary neurons; computational image analysis; computer simulations Cell reports High 26972003
2017 CLIP-170 is required for ninein redeployment from centrosome to apical non-centrosomal MTOCs during epithelial differentiation; IQGAP1 and active Rac1 cooperate with CLIP-170 to facilitate MT plus-end cortical targeting and ninein recruitment. Clip1/Clip2 double KO mice confirm requirement for ninein recruitment. siRNA depletion; knockout mouse (Clip1/Clip2); live imaging; immunofluorescence; organoid culture Open biology High 28179500
2017 CLIP-170 interacts with TLR adaptor protein TIRAP and promotes ubiquitination and subsequent degradation of TIRAP, thereby negatively regulating TLR4-mediated proinflammatory signaling (IL-6, TNF-α). Co-immunoprecipitation; overexpression; siRNA knockdown; in vivo siRNA delivery in mice; ELISA Journal of immunology Medium 29222167
2018 CLIP-170 contains multiple EB1-binding modules: two CAP-Gly domains, a bridging SXIP motif, and a unique array of divergent SXIP-like motifs N-terminal to CAP-Gly-1; the CAP-Gly domains engage only the EB1 EEY motif (not the EB homology domain), allowing flanking SXIP motifs to engage the EB homology domain simultaneously, providing multivalent avidity. Isothermal titration calorimetry; size-exclusion chromatography; domain mapping The Journal of biological chemistry High 30455356
2020 AMPK phosphorylates CLIP-170 at Ser311 at intercalated disks in cardiomyocytes; inhibition of this phosphorylation (S311A transgenic mice) leads to MT accumulation at intercalated disks, cardiomyocyte elongation, and progressive decline in cardiac contraction. AMPK localization at intercalated disks is regulated by mechanical stress. Transgenic mouse (CLIP-170 S311A); time-lapse imaging; heart-specific overexpression; cardiac contractility measurement EMBO reports High 33251722
2020 Arsenic trioxide (ATO) displaces zinc from the zinc finger motif of CLIP-170, disrupting the CLIP-170/LIS1/NDEL1/dynein signaling pathway and inhibiting microtubule polymerization; ATO effects are equivalent to siRNA-mediated CLIP-170 knockdown and partially reversed by zinc supplementation. CLIP-170 knockdown (siRNA); zinc supplementation rescue; MT polymerization assays; invasion/migration assays Toxicology and applied pharmacology Medium 32717241
2021 CLIP1-LTK gene fusion results in constitutively activated LTK kinase with transformation potential; CLIP1-LTK-expressing cells show lorlatinib-sensitive proliferation arrest and apoptosis. Whole-transcriptome sequencing for fusion identification; kinase activity assays; Ba/F3 cell transformation assay; lorlatinib treatment Nature High 34819663
2021 Overexpression of CLIP-170 induces large patches containing CLIP-170 and other +TIP proteins with hallmarks of biomolecular condensates/liquid droplets (dynamic exchange by FRAP, exclusion of other condensate markers); intrinsically disordered regions are conserved in key +TIPs. FRAP; video microscopy; immunofluorescence; bioinformatic analysis of IDR conservation PloS one Medium 34890409

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 2303 20371350
2009 Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature 1440 19536157
2008 HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature 1090 18978773
2016 Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nature methods 1054 27018577
2003 CLIP identifies Nova-regulated RNA networks in the brain. Science (New York, N.Y.) 888 14615540
2005 CLIP: a method for identifying protein-RNA interaction sites in living cells. Methods (San Diego, Calif.) 475 16314267
2001 Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell 401 11290329
1999 CLIP-170 highlights growing microtubule ends in vivo. Cell 342 10052454
2011 Mapping in vivo protein-RNA interactions at single-nucleotide resolution from HITS-CLIP data. Nature biotechnology 331 21633356
2010 HITS-CLIP: panoramic views of protein-RNA regulation in living cells. Wiley interdisciplinary reviews. RNA 312 21935890
2014 HITS-CLIP and integrative modeling define the Rbfox splicing-regulatory network linked to brain development and autism. Cell reports 278 24613350
2018 Advances in CLIP Technologies for Studies of Protein-RNA Interactions. Molecular cell 231 29395060
1999 Role of dynactin in endocytic traffic: effects of dynamitin overexpression and colocalization with CLIP-170. Molecular biology of the cell 229 10588646
2002 LIS1, CLIP-170's key to the dynein/dynactin pathway. Molecular and cellular biology 208 11940666
2002 Role of dynein, dynactin, and CLIP-170 interactions in LIS1 kinetochore function. The Journal of cell biology 202 11889140
2015 CLIPdb: a CLIP-seq database for protein-RNA interactions. BMC genomics 184 25652745
1999 Colocalization of cytoplasmic dynein with dynactin and CLIP-170 at microtubule distal ends. Journal of cell science 178 10212138
2020 Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins. Genome biology 173 32252787
2016 Improving microRNA target prediction by modeling with unambiguously identified microRNA-target pairs from CLIP-ligation studies. Bioinformatics (Oxford, England) 172 26743510
2011 Identification of RNA-protein interaction networks using PAR-CLIP. Wiley interdisciplinary reviews. RNA 172 22213601
2005 EB1 and EB3 control CLIP dissociation from the ends of growing microtubules. Molecular biology of the cell 165 16148041
2009 Microtubule plus-end tracking by CLIP-170 requires EB1. Proceedings of the National Academy of Sciences of the United States of America 159 19126680
2016 α-Tubulin Tyrosination and CLIP-170 Phosphorylation Regulate the Initiation of Dynein-Driven Transport in Neurons. Cell reports 154 26972003
2004 Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization. The Journal of cell biology 149 15381688
2017 CLIP Tool Kit (CTK): a flexible and robust pipeline to analyze CLIP sequencing data. Bioinformatics (Oxford, England) 142 27797762
2014 PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity. Nature communications 141 25366541
2011 RNA targets of TDP-43 identified by UV-CLIP are deregulated in ALS. Molecular and cellular neurosciences 141 21421050
2008 Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. The EMBO journal 132 19020519
1998 Evidence for a role of CLIP-170 in the establishment of metaphase chromosome alignment. The Journal of cell biology 130 9585405
2017 PureCLIP: capturing target-specific protein-RNA interaction footprints from single-nucleotide CLIP-seq data. Genome biology 115 29284540
2003 Alteration of microtubule dynamic instability during preprophase band formation revealed by yellow fluorescent protein-CLIP170 microtubule plus-end labeling. The Plant cell 109 12615935
2008 Molecular clip and tweezer introduce new mechanisms of enzyme inhibition. Journal of the American Chemical Society 108 18605724
2000 Functional analysis of CLIP-115 and its binding to microtubules. Journal of cell science 101 10825300
2015 Drosophila melanogaster clip-domain serine proteases: Structure, function and regulation. Biochimie 97 26453810
1994 Molecular characterization of two functional domains of CLIP-170 in vivo. Journal of cell science 97 7983157
2008 Dynamic behavior of GFP-CLIP-170 reveals fast protein turnover on microtubule plus ends. The Journal of cell biology 95 18283108
2013 SNAP-, CLIP- and Halo-tag labelling of budding yeast cells. PloS one 82 24205303
2010 Phosphorylation of CLIP-170 by Plk1 and CK2 promotes timely formation of kinetochore-microtubule attachments. The EMBO journal 82 20664522
2004 CLIP-170/tubulin-curved oligomers coassemble at microtubule ends and promote rescues. Current biology : CB 82 15589150
2020 ALK rearranged renal cell carcinoma (ALK-RCC): a multi-institutional study of twelve cases with identification of novel partner genes CLIP1, KIF5B and KIAA1217. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 78 32467651
2018 Proximity-CLIP provides a snapshot of protein-occupied RNA elements in subcellular compartments. Nature methods 76 30478324
2014 PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis. Genome biology 75 24451213
2019 Chronic Low-grade Inflammatory Phenotype (CLIP) and Senescent Immune Dysregulation. Clinical therapeutics 74 30833113
2004 LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. BioEssays : news and reviews in molecular, cellular and developmental biology 67 14745832
2014 HITS-CLIP reveals key regulators of nuclear receptor signaling in breast cancer. Breast cancer research and treatment 61 24906430
2021 The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer. Nature 58 34819663
2014 CapR: revealing structural specificities of RNA-binding protein target recognition using CLIP-seq data. Genome biology 55 24447569
2002 CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family. The Journal of cell biology 54 11854307
2018 Data Science Issues in Studying Protein-RNA Interactions with CLIP Technologies. Annual review of biomedical data science 50 37123514
2018 The Future of Cross-Linking and Immunoprecipitation (CLIP). Cold Spring Harbor perspectives in biology 48 30068528
2006 CLIP-170 homologue and NUDE play overlapping roles in NUDF localization in Aspergillus nidulans. Molecular biology of the cell 47 16467375
2016 PAR-CLIP: A Method for Transcriptome-Wide Identification of RNA Binding Protein Interaction Sites. Methods in molecular biology (Clifton, N.J.) 46 26463383
2016 Optimization of PAR-CLIP for transcriptome-wide identification of binding sites of RNA-binding proteins. Methods (San Diego, Calif.) 46 27765618
2012 Microtubule-binding protein CLIP-170 is a mediator of paclitaxel sensitivity. The Journal of pathology 46 21989536
2017 Ninein is essential for apico-basal microtubule formation and CLIP-170 facilitates its redeployment to non-centrosomal microtubule organizing centres. Open biology 45 28179500
2014 dCLIP: a computational approach for comparative CLIP-seq analyses. Genome biology 42 24398258
2013 A computational approach for identifying microRNA-target interactions using high-throughput CLIP and PAR-CLIP sequencing. BMC genomics 42 23368412
2006 Microtubule binding proteins CLIP-170, EB1, and p150Glued form distinct plus-end complexes. FEBS letters 40 16455083
2012 CLIP (cross-linking and immunoprecipitation) identification of RNAs bound by a specific protein. Cold Spring Harbor protocols 36 23118367
2011 Interaction of mammalian end binding proteins with CAP-Gly domains of CLIP-170 and p150(glued). Journal of structural biology 36 22119847
2022 Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP. Genome biology 35 36085079
2015 Microtubule plus end-associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells. The Journal of cell biology 35 26504169
2002 Microtubule capture: IQGAP and CLIP-170 expand the repertoire. Current biology : CB 35 12361581
2021 A non-radioactive, improved PAR-CLIP and small RNA cDNA library preparation protocol. Nucleic acids research 34 33503264
2017 Computational analysis of CLIP-seq data. Methods (San Diego, Calif.) 34 28254606
2006 The CLIP-170 orthologue Bik1p and positioning the mitotic spindle in yeast. Current topics in developmental biology 33 17118263
2024 Decoding protein-RNA interactions using CLIP-based methodologies. Nature reviews. Genetics 29 38982239
2015 CLIPSeqTools--a novel bioinformatics CLIP-seq analysis suite. RNA (New York, N.Y.) 29 26577377
2014 CLIP-170 recruits PLK1 to kinetochores during early mitosis for chromosome alignment. Journal of cell science 29 24777477
2018 GoldCLIP: Gel-omitted Ligation-dependent CLIP. Genomics, proteomics & bioinformatics 28 29709556
2014 A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability. European journal of human genetics : EJHG 28 24569606
2008 Minimal plus-end tracking unit of the cytoplasmic linker protein CLIP-170. The Journal of biological chemistry 28 19074770
2018 Recent computational developments on CLIP-seq data analysis and microRNA targeting implications. Briefings in bioinformatics 27 28605404
2014 Leveraging cross-link modification events in CLIP-seq for motif discovery. Nucleic acids research 27 25505146
2009 Probing interactions between CLIP-170, EB1, and microtubules. Journal of molecular biology 27 19913027
2008 Platinated copper(3-clip-phen) complexes as effective DNA-cleaving and cytotoxic agents. Chemistry (Weinheim an der Bergstrasse, Germany) 27 18293353
2013 Transcriptome-wide identification of RNA binding sites by CLIP-seq. Methods (San Diego, Calif.) 26 23545196
2009 Cdc2-mediated phosphorylation of CLIP-170 is essential for its inhibition of centrosome reduplication. The Journal of biological chemistry 25 19687009
2023 Towards in silico CLIP-seq: predicting protein-RNA interaction via sequence-to-signal learning. Genome biology 24 37542318
2018 omniCLIP: probabilistic identification of protein-RNA interactions from CLIP-seq data. Genome biology 24 30384847
2014 LRRK1-phosphorylated CLIP-170 regulates EGFR trafficking by recruiting p150Glued to microtubule plus ends. Journal of cell science 23 25413345
2017 Cytoplasmic Linker Protein CLIP170 Negatively Regulates TLR4 Signaling by Targeting the TLR Adaptor Protein TIRAP. Journal of immunology (Baltimore, Md. : 1950) 22 29222167
2014 HITS-CLIP (CLIP-Seq) for mouse Piwi proteins. Methods in molecular biology (Clifton, N.J.) 22 24178558
2014 HITS-CLIP and PAR-CLIP advance viral miRNA targetome analysis. Critical reviews in eukaryotic gene expression 21 24940765
2012 Cooperative stabilization of microtubule dynamics by EB1 and CLIP-170 involves displacement of stably bound P(i) at microtubule ends. Biochemistry 21 22424550
2020 AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170. EMBO reports 20 33251722
2018 Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons. Genome biology 20 30111345
2020 Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets. Genes 19 31947823
2018 Discovering circRNA-microRNA Interactions from CLIP-Seq Data. Methods in molecular biology (Clifton, N.J.) 19 29322451
2016 Genome-Wide Profiling of RNA-Protein Interactions Using CLIP-Seq. Methods in molecular biology (Clifton, N.J.) 19 26965263
2016 Identification of CELF1 RNA targets by CLIP-seq in human HeLa cells. Genomics data 19 27222809
2009 Myosin V spatially regulates microtubule dynamics and promotes the ubiquitin-dependent degradation of the fission yeast CLIP-170 homologue, Tip1. Journal of cell science 19 19808886
2002 The cytoplasmic linker protein CLIP-170 is a human autoantigen. Clinical and experimental immunology 19 11966772
2023 CLIP: accurate prediction of disordered linear interacting peptides from protein sequences using co-evolutionary information. Briefings in bioinformatics 18 36458437
2019 Identification, characterization, and expression analysis of clip-domain serine protease genes in the silkworm, Bombyx mori. Developmental and comparative immunology 18 31863792
2014 Computational Methods for CLIP-seq Data Processing. Bioinformatics and biology insights 18 25336930
2021 Overexpression of the microtubule-binding protein CLIP-170 induces a +TIP network superstructure consistent with a biomolecular condensate. PloS one 17 34890409
2020 Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer. Toxicology and applied pharmacology 17 32717241
2018 Mapping multivalency in the CLIP-170-EB1 microtubule plus-end complex. The Journal of biological chemistry 17 30455356
2017 Has Sliding-Clip Renorrhaphy Eliminated the Need for Collecting System Repair During Robot-Assisted Partial Nephrectomy? Journal of endourology 17 27960537