Affinage

CLTC

Clathrin heavy chain 1 · UniProt Q00610

Round 2 corrected
Length
1675 aa
Mass
191.6 kDa
Annotated
2026-04-28
130 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLTC encodes the major structural subunit of clathrin triskelions that polymerize into lattice coats on budding vesicles, and is essential for clathrin-coated pit formation and receptor-mediated endocytosis of diverse cargoes including transferrin, EGF receptor, and GPCRs internalized via a β-arrestin–AP-2–clathrin axis (PMID:12952941, PMID:10097102). Beyond canonical endocytosis, CLTC interacts directly with Atg16L1 to drive plasma-membrane-derived autophagosome precursor formation and mediates autophagosome fusion with pathogen-containing vacuoles (PMID:20639872, PMID:29973118). The CLTC locus at 17q23 is a recurrent chromosomal translocation partner generating oncogenic fusions (CLTC-ALK, CLTC-TFE3, CLTC-FOSB) across multiple tumor types including inflammatory myofibroblastic tumor and large B-cell lymphoma (PMID:11485898, PMID:12750159, PMID:32749039). De novo loss-of-function and dominant-negative CLTC variants cause a variable neurodevelopmental syndrome with intellectual disability, reflecting the protein's critical role in synaptic vesicle recycling (PMID:31776469).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1999 High

    Establishing that clathrin-coated pit endocytosis of GPCRs depends on a β-arrestin–AP-2 axis answered how activated receptors are coupled to the clathrin coat machinery.

    Evidence Yeast two-hybrid, co-IP, and dominant-negative minigene inhibition of β2-adrenergic receptor internalization in cultured cells

    PMID:10097102

    Open questions at the time
    • Whether all GPCRs use the same β-arrestin–AP-2 route to clathrin
    • Structural basis of β-arrestin–clathrin heavy chain interaction
  2. 2000 High

    Demonstrating that CLTC is part of the core coated-vesicle budding machinery across organelles provided a unified framework for clathrin's role in intracellular membrane trafficking.

    Evidence Synthesis of in vitro reconstitution and structural studies of clathrin, COPI, and COPII coats

    PMID:11252894

    Open questions at the time
    • Regulation of coat assembly/disassembly kinetics in vivo
    • Relative contributions of clathrin vs. other coats at specific organelles
  3. 2003 High

    RNAi depletion of CLTC abolished clathrin-coated pits and blocked uptake of transferrin, EGF, and LDL receptor chimeras, proving CLTC is non-redundant for clathrin-mediated endocytosis at the plasma membrane.

    Evidence siRNA knockdown to undetectable levels in HeLaM cells with electron microscopy and multiple cargo uptake assays

    PMID:12952941

    Open questions at the time
    • Whether clathrin light chains or CHC2 can partially compensate under different conditions
    • Long-term consequences of CLTC loss in vivo
  4. 2001 High

    Discovery of the CLTC-ALK fusion in inflammatory myofibroblastic tumor revealed CLTC as a chromosomal translocation partner capable of activating oncogenic kinases, opening a new disease dimension for the gene.

    Evidence Cytogenetics, FISH, RT-PCR, and sequencing of the t(2;17)(p23;q23) fusion transcript in IMT

    PMID:11485898

    Open questions at the time
    • Whether the clathrin portion contributes dimerization or localization signals to fusion oncoproteins
    • Frequency of CLTC-ALK among all IMT cases
  5. 2003 High

    Identification of CLTC-ALK in large B-cell lymphoma and CLTC-TFE3 in renal carcinoma established CLTC as a recurrent fusion partner across histologically distinct malignancies, with the clathrin portion dictating subcellular localization of the fusion product.

    Evidence FISH, RT-PCR, immunohistochemistry in multiple DLBCL cases and molecular cloning of CLTC-TFE3 in pediatric renal carcinoma

    PMID:12750159 PMID:12917640

    Open questions at the time
    • Whether CLTC-driven oligomerization is required for constitutive kinase activation
    • Functional significance of CLTC-TFE3 retaining TFE3 DNA-binding but lacking CLTC multimerization domain
  6. 2010 High

    Direct CLTC–Atg16L1 interaction and the requirement of clathrin-mediated internalization for autophagosome precursor formation linked clathrin to autophagy, revealing a non-canonical function beyond endocytosis.

    Evidence Reciprocal co-IP, live-cell imaging of Atg16L1-positive precursors, and siRNA knockdown with autophagosome quantification

    PMID:20639872

    Open questions at the time
    • Whether CLTC's autophagy role is independent of adaptor proteins used in endocytosis
    • Structural basis of the CLTC–Atg16L1 interaction
  7. 2011 Medium

    ALK inhibitor treatment of CLTC-ALK-positive DLBCL cells induced apoptosis and tumor regression, demonstrating that the kinase activity of the fusion is required for tumor maintenance and is therapeutically targetable.

    Evidence NVP-TAE684 treatment of LM1 cells with signaling pathway analysis and xenograft regression model

    PMID:21494621

    Open questions at the time
    • Clinical efficacy of ALK inhibitors in patients with CLTC-ALK fusions
    • Resistance mechanisms specific to CLTC-ALK
  8. 2018 High

    CLTC enrichment on Coxiella-containing vacuoles and its requirement for autophagosome–vacuole fusion extended CLTC's autophagy role to pathogen defense, showing clathrin mediates membrane fusion events beyond vesicle budding.

    Evidence siRNA silencing of CLTC with LC3B localization, CCV fusion assays, and starvation-induced autophagy in infected cells

    PMID:29973118

    Open questions at the time
    • Whether CLTC promotes membrane fusion directly or via recruitment of SNARE/tethering factors
    • Generalizability to other intracellular pathogens
  9. 2019 Medium

    A cohort of 27 individuals with de novo CLTC variants established a neurodevelopmental syndrome spectrum, with missense variants producing dominant-negative effects (more severe phenotype) and truncating variants causing haploinsufficiency, linking clathrin's synaptic vesicle recycling function to brain development.

    Evidence Exome sequencing, molecular modeling, and genotype–phenotype correlation across 27 affected individuals

    PMID:31776469

    Open questions at the time
    • No direct cellular functional assays validating dominant-negative mechanism
    • Whether variant-specific endocytic defects correlate with clinical severity
    • Animal models recapitulating the human phenotype
  10. 2020 Medium

    Discovery of CLTC-FOSB fusion in pseudomyogenic hemangioendothelioma expanded the oncogenic fusion repertoire beyond kinase partners, showing the CLTC locus participates in fusions that deregulate transcription factors.

    Evidence RNA sequencing and RT-PCR confirmation of CLTC exon 17–FOSB exon 2 in-frame fusion

    PMID:32749039

    Open questions at the time
    • Functional consequences of CLTC-FOSB on transcriptional programs
    • Whether the clathrin N-terminal portion provides a promoter or stabilization advantage

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CLTC's autophagy functions, whether dominant-negative CLTC variants impair specific cargo-selective endocytic pathways in neurons, and the precise contribution of the clathrin portion to the oncogenic activity of CLTC fusion proteins.
  • No structural model of CLTC–Atg16L1 complex
  • No neuron-specific functional studies of disease-associated CLTC variants
  • Clathrin's contribution to fusion oncoprotein dimerization/localization not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 2 R-HSA-9612973 Autophagy 2
Partners
ALKAP2B1ARRB2ATG16L1FOSBTFE3
Complex memberships
Clathrin triskelion

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 The clathrin heavy chain (CLTC) interacts directly with the Atg16L1 autophagy protein and is involved in the formation of Atg16L1-positive early autophagosome precursors; inhibition of clathrin-mediated internalization decreased formation of both Atg16L1-positive precursors and mature autophagosomes, and the plasma membrane contributes directly to early autophagosome precursor formation in a clathrin-dependent manner. Co-immunoprecipitation, live-cell imaging, siRNA knockdown with autophagosome quantification Nature cell biology High 20639872
1999 The beta2-adrenergic receptor/beta-arrestin complex recruits the clathrin adaptor AP-2 during endocytosis; AP-2 beta2-adaptin subunit binds beta-arrestin 2 and co-immunoprecipitates with beta-arrestins and beta2AR in an agonist-dependent manner, and expression of beta-arrestin 2 minigene constructs containing the beta2-adaptin interacting region inhibits beta2AR endocytosis, demonstrating that clathrin-coated pits mediate GPCR internalization via a betaarrestin-AP2-clathrin heavy chain axis. Co-immunoprecipitation, yeast two-hybrid, dominant-negative minigene inhibition, confocal colocalization Proceedings of the National Academy of Sciences of the United States of America High 10097102
2003 RNA interference knockdown of clathrin heavy chain to undetectable levels in HeLaM cells abolished all clathrin-coated pits and vesicles at the plasma membrane, swelled post-Golgi membrane compartments, and severely inhibited receptor-mediated endocytosis of transferrin, EGF receptor, and an LDL receptor chimera, establishing CLTC as essential for clathrin-coated vesicle formation and cargo endocytosis. RNAi knockdown, electron microscopy, transferrin/EGF uptake assays The Journal of cell biology High 12952941
2000 A comprehensive review established that clathrin, together with COPI and COPII coat proteins, executes a programmed set of sequential protein interactions leading to vesicle budding between organelles, defining CLTC as a core component of the coated-vesicle formation machinery. Biochemical reconstitution and structural review of coated vesicle assembly Nature reviews. Molecular cell biology High 11252894
2001 CLTC (clathrin heavy chain gene on chromosome 17q23) fuses with the ALK tyrosine kinase gene (chromosome 2p23) via t(2;17)(p23;q23) translocation in inflammatory myofibroblastic tumor (IMT), generating a CLTC-ALK fusion oncoprotein in which the ALK C-terminal kinase domain is fused to the N-terminal portion of clathrin heavy chain. Cytogenetics, RT-PCR, FISH, molecular cloning of fusion transcript The American journal of pathology High 11485898
2003 CLTC forms a novel fusion with TFE3 via t(X;17)(p11.2;q23) in pediatric renal carcinoma; the predicted CLTC-TFE3 fusion product retains the nuclear localization and DNA-binding domains of TFE3 but lacks the multimerization domain of CLTC, and CLTC is identified as a recurrent fusion partner for multiple oncogenes due to its chromosomal location at 17q23. Molecular cloning, RT-PCR, sequencing of fusion transcript, immunohistochemistry Oncogene Medium 12917640
2003 CLTC-ALK fusion is a recurrent event in ALK-positive large B-cell lymphoma (LBCL); the t(2;17)(p23;q23) encoding a CLTC-ALK fusion protein results in granular cytoplasmic ALK staining (consistent with clathrin lattice localization) rather than the nuclear/cytoplasmic pattern of NPM-ALK, and CLTC-ALK drives a plasmablastic LBCL phenotype distinct from T/null-cell ALCL. FISH, RT-PCR, immunohistochemistry, karyotyping Blood High 12750159
2007 CLTC is confirmed as an ALK fusion partner in inflammatory myofibroblastic tumors via cloning of a novel ALK-CLTC breakpoint junction; FISH analysis of IMT cases identified CLTC as the fusion partner in multiple additional cases, establishing CLTC-ALK as a recurrent but variant rearrangement in IMT with diverse fusion partners. FISH, breakpoint cloning, RT-PCR Cancer genetics and cytogenetics Medium 17656252
2008 Clathrin (CLTC) is present at tubulobulbar complexes in the rat testis seminiferous epithelium; immunofluorescence and immunoelectron microscopy localized clathrin-positive structures to the ends of tubulobulbar complexes alongside N-WASP and cortactin, suggesting clathrin initiates formation of these podosome-like endocytic structures that internalize intact intercellular junctions during sperm release. Immunofluorescence microscopy, immunoelectron microscopy, fixed tissue sections Biology of reproduction Medium 18799755
2011 ALK inhibition by NVP-TAE684 in CLTC-ALK-positive DLBCL cells (LM1 cell line) repressed ALK-activated signaling pathways and induced apoptosis in vitro at nanomolar concentrations, and caused sustained tumor regression in a xenotransplant model, demonstrating that deregulated ALK kinase activity driven by the CLTC-ALK fusion is required for maintenance of the malignant phenotype. Cell line establishment, ALK inhibitor treatment, signaling pathway analysis (Western blot), xenograft mouse model PloS one Medium 21494621
2013 CLTC-ALK fusion gene was identified as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm (BPDCN) originating in utero; analysis of neonatal blood spots confirmed the fusion arose prenatally, and lineage distribution showed the fusion was present in monocytes, neutrophils, and T cells, indicating CLTC-ALK originated in a multipotent hematopoietic progenitor. Karyotyping, RT-PCR, FISH, neonatal blood spot PCR, lineage-specific PCR Genes, chromosomes & cancer Medium 24142740
2016 De novo heterozygous frameshift mutation in CLTC (c.2737_2738dupGA, p.D913Efs*59 in exon 17) causes a syndrome of multiple malformations and global developmental delay in a child; CHC1 (clathrin heavy chain 1) plays an important role in the brain for vesicle recycling and neurotransmitter release at pre-synaptic nerve terminals and in placental development. Whole-exome sequencing, bioinformatic filtering, de novo mutation verification American journal of medical genetics. Part A Medium 26822784
2018 CLTC (clathrin heavy chain) is enriched on the Coxiella-containing vacuole (CCV) membrane and is required for autophagosome-CCV fusion; siRNA silencing of CLTC prevented CCV-CCV fusion and excluded MAP1LC3B/LC3B from CCVs, and starvation-induced autophagy expanded CCV size in a CLTC-dependent manner, establishing a functional link between CLTC and autophagy in intracellular trafficking. siRNA knockdown, immunofluorescence, LC3B localization assay, starvation-induced autophagy, CCV size measurement Autophagy High 29973118
2019 De novo CLTC variants (missense, in-frame, nonsense, frameshift) cause a variable neurodevelopmental syndrome; combining 27 affected individuals, all had intellectual disability, and missense/in-frame variants were more frequently associated with microcephaly, hypoplasia of the corpus callosum, and epilepsy than nonsense/frameshift variants, suggesting missense variants exert dominant-negative effects while nonsense/frameshift variants cause haploinsufficiency of CLTC function. Exome sequencing, molecular modeling, tolerance landscape analysis, genotype-phenotype correlation across 27 individuals Genetics in medicine Medium 31776469
2020 A novel CLTC-FOSB gene fusion (exon 17 of CLTC joined in-frame to exon 2 of FOSB) was identified in pseudomyogenic hemangioendothelioma of bone by RNA sequencing and confirmed by RT-PCR, expanding CLTC as a recurrent fusion partner oncogene beyond ALK and TFE3 fusions. RNA sequencing, RT-PCR, direct sequencing of fusion product Genes, chromosomes & cancer Medium 32749039
2022 CLTC was identified as a novel ALK fusion partner in epithelioid fibrous histiocytoma (EFH) by next-generation sequencing; the two CLTC-rearranged EFH cases involved exon 19 of ALK (rather than the typical exon 20), further expanding the repertoire of CLTC fusion configurations in human tumors. Next-generation sequencing (RNA-seq), FISH, IHC Genes, chromosomes & cancer Medium 35289445
2003 Proteomic characterization of human B cell-derived exosomes by mass spectrometry identified clathrin (CLTC) as an abundant component, suggesting a role for clathrin in protein sorting at multivesicular bodies during exosome biogenesis. Mass spectrometry proteomics of purified exosomes, immunoblotting The Journal of biological chemistry Low 12519789
2011 Proteomic analysis of isolated focal adhesions identified clathrin heavy chain (CLTC) as a component of the myosin-II-responsive focal adhesion proteome; CLTC abundance in focal adhesions was enhanced by myosin II-mediated contractility, linking clathrin-dependent endocytosis to focal adhesion disassembly. Focal adhesion isolation, quantitative mass spectrometry proteomics, myosin II inhibition Nature cell biology Low 21423176

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nature neuroscience 977 10862698
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2003 Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. The Journal of biological chemistry 708 12519789
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2010 Plasma membrane contributes to the formation of pre-autophagosomal structures. Nature cell biology 704 20639872
2012 A census of human soluble protein complexes. Cell 689 22939629
2003 P1/HC-Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA unction. Developmental cell 670 12586064
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2003 Clathrin-mediated endocytosis in AP-2-depleted cells. The Journal of cell biology 563 12952941
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
1999 The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis. Proceedings of the National Academy of Sciences of the United States of America 527 10097102
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1988 Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature 435 2841611
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2000 Three ways to make a vesicle. Nature reviews. Molecular cell biology 410 11252894
2008 HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Molecular pain 376 18954467
2022 The BlueScreen HC assay to predict the genotoxic potential of fragrance materials. Mutagenesis 361 35302169
2001 Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. The American journal of pathology 250 11485898
2003 A novel CLTC-TFE3 gene fusion in pediatric renal adenocarcinoma with t(X;17)(p11.2;q23). Oncogene 215 12917640
1992 Diagnostic value of analysis of cystatin C and protein HC in biological fluids. Clinical nephrology 204 1284235
2008 EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung cancer (Amsterdam, Netherlands) 135 18242762
2006 HC-toxin. Phytochemistry 134 16839576
2003 ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 134 12750159
2003 Substrate complexes of hepatitis C virus RNA polymerase (HC-J4): structural evidence for nucleotide import and de-novo initiation. Journal of molecular biology 124 12589751
2006 High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutation research 121 16781187
2003 Structural characterization of HC-Pro, a plant virus multifunctional protein. The Journal of biological chemistry 117 12684502
2016 HC-HA/PTX3 Purified From Amniotic Membrane as Novel Regenerative Matrix: Insight Into Relationship Between Inflammation and Regeneration. Investigative ophthalmology & visual science 114 27116665
2009 Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. The Journal of biological chemistry 113 19491101
2018 Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice. PloS one 108 29385160
2016 A novel long noncoding RNA Lnc-HC binds hnRNPA2B1 to regulate expressions of Cyp7a1 and Abca1 in hepatocytic cholesterol metabolism. Hepatology (Baltimore, Md.) 107 26663205
1992 Alpha 1-microglobulin (protein HC): features of a promising indicator of proximal tubular dysfunction. European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies 86 1283528
2002 C-F...H-C hydrogen bonds in ribonucleic acids. Journal of the American Chemical Society 83 12010039
1986 Human protein HC and its IgA complex are inhibitors of neutrophil chemotaxis. Proceedings of the National Academy of Sciences of the United States of America 78 2419908
2008 HC-Pro protein of sugar cane mosaic virus interacts specifically with maize ferredoxin-5 in vitro and in planta. The Journal of general virology 73 18632977
2008 Cortactin (CTTN), N-WASP (WASL), and clathrin (CLTC) are present at podosome-like tubulobulbar complexes in the rat testis. Biology of reproduction 68 18799755
1986 The molecular organization of the protein HC-IgA complex (HC-IgA). The Journal of biological chemistry 63 2429955
2007 The HC-pro protein of potato virus Y interacts with NtMinD of tobacco. Molecular plant-microbe interactions : MPMI 62 17990958
2000 Analysis of mutants of tetanus toxin Hc fragment: ganglioside binding, cell binding and retrograde axonal transport properties. Molecular microbiology 60 10972823
1995 Requirement for HC-Pro processing during genome amplification of tobacco etch potyvirus. Virology 60 7747479
2014 Constitutive expression of pentraxin 3 (PTX3) protein by human amniotic membrane cells leads to formation of the heavy chain (HC)-hyaluronan (HA)-PTX3 complex. The Journal of biological chemistry 58 24652286
2005 Ectopic DICER-LIKE1 expression in P1/HC-Pro Arabidopsis rescues phenotypic anomalies but not defects in microRNA and silencing pathways. The Plant cell 56 16214897
2007 RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors. Cancer genetics and cytogenetics 55 17656252
2016 Structural basis of TRPA1 inhibition by HC-030031 utilizing species-specific differences. Scientific reports 53 27874100
2006 Immunogenicity of recombinant hepatitis B vaccine (rHBV) in recipients of unrelated or related allogeneic hematopoietic cell (HC) transplants. Blood 53 16763208
2010 Discriminating mutations of HC-Pro of zucchini yellow mosaic virus with differential effects on small RNA pathways involved in viral pathogenicity and symptom development. Molecular plant-microbe interactions : MPMI 52 19958135
2019 Long Noncoding RNA lnc-HC Regulates PPARγ-Mediated Hepatic Lipid Metabolism through miR-130b-3p. Molecular therapy. Nucleic acids 50 31770672
2006 The phylogenetically conserved molluscan chitinase-like protein 1 (Cg-Clp1), homologue of human HC-gp39, stimulates proliferation and regulates synthesis of extracellular matrix components of mammalian chondrocytes. The Journal of biological chemistry 50 16882657
2005 Structural analysis of tobacco etch potyvirus HC-pro oligomers involved in aphid transmission. Journal of virology 49 15731269
1999 Non-viral neuronal gene delivery mediated by the HC fragment of tetanus toxin. European journal of biochemistry 47 10092862
2008 Contrasting effects of HC-Pro and 2b viral suppressors from Sugarcane mosaic virus and Tomato aspermy cucumovirus on the accumulation of siRNAs. Virology 45 18280529
2018 Interaction between autophagic vesicles and the Coxiella-containing vacuole requires CLTC (clathrin heavy chain). Autophagy 44 29973118
2009 Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). International journal for parasitology 44 19796644
2008 Histone deacetylase inhibitor Helminthosporium carbonum (HC)-toxin suppresses the malignant phenotype of neuroblastoma cells. International journal of cancer 44 18074352
2019 The selective TRPV4 channel antagonist HC-067047 attenuates mechanical allodynia in diabetic mice. European journal of pharmacology 42 31129158
2011 Inhibition of anaplastic lymphoma kinase (ALK) activity provides a therapeutic approach for CLTC-ALK-positive human diffuse large B cell lymphomas. PloS one 42 21494621
2000 Transformation of BALB3T3 cells caused by over-expression of rat CD98 heavy chain (HC) requires its association with light chain: mis-sense mutation in a cysteine residue of CD98HC eliminates its transforming activity. International journal of cancer 42 10897033
2003 HC gp-39 gene is upregulated in glioblastomas. Cancer letters 40 12957359
2000 Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions. Rheumatology (Oxford, England) 40 11136874
2001 Resistance of RNA-mediated TGS to HC-Pro, a viral suppressor of PTGS, suggests alternative pathways for dsRNA processing. Current biology : CB 39 11509235
2017 Recombinant Botulinum Neurotoxin Hc Subunit (BoNT Hc) and Catalytically Inactive Clostridium botulinum Holoproteins (ciBoNT HPs) as Vaccine Candidates for the Prevention of Botulism. Toxins 37 28869522
1994 Human protein HC (alpha 1-microglobulin) and inter-alpha-trypsin inhibitor in connective tissue. The Histochemical journal 37 7533752
2019 25-HC decreases the sensitivity of human gastric cancer cells to 5-fluorouracil and promotes cells invasion via the TLR2/NF-κB signaling pathway. International journal of oncology 36 30664194
1988 Identification of the protein HC receptor. FEBS letters 36 2457516
2020 HC-HA/PTX3 Purified From Human Amniotic Membrane Reverts Human Corneal Fibroblasts and Myofibroblasts to Keratocytes by Activating BMP Signaling. Investigative ophthalmology & visual science 35 32462202
2016 CLTC as a clinically novel gene associated with multiple malformations and developmental delay. American journal of medical genetics. Part A 34 26822784
2006 Recombinant C fragment of botulinum neurotoxin B serotype (rBoNTB (HC)) immune response and protection in the rhesus monkey. Toxicon : official journal of the International Society on Toxinology 34 16730042
1990 Location and characterization of the three carbohydrate prosthetic groups of human protein HC. FEBS letters 33 1694784
2010 Helper component-proteinase (HC-Pro) protein of Papaya ringspot virus interacts with papaya calreticulin. Molecular plant pathology 32 20447282
2009 Correlated dynamics between protein HN and HC bonds observed by NMR cross relaxation. Journal of the American Chemical Society 32 19235934
2006 HC-gp39 contributes to chondrocyte differentiation by inducing SOX9 and type II collagen expressions. Osteoarthritis and cartilage 30 16949314
2013 CLTC-ALK fusion as a primary event in congenital blastic plasmacytoid dendritic cell neoplasm. Genes, chromosomes & cancer 26 24142740
2009 Compensatory molecular evolution of HC-Pro, an RNA-silencing suppressor from a plant RNA virus. Molecular biology and evolution 26 19906792
2007 Expression of a RING-HC protein from rice improves resistance to Pseudomonas syringae pv. tomato DC3000 in transgenic Arabidopsis thaliana. Journal of experimental botany 26 18182423
2022 Adhesion and Colonization of the Probiotic Lactobacillus plantarum HC-2 in the Intestine of Litopenaeus Vannamei Are Associated With Bacterial Surface Proteins. Frontiers in microbiology 25 35535252
2021 The ApiAP2 factor PfAP2-HC is an integral component of heterochromatin in the malaria parasite Plasmodium falciparum. iScience 25 33997710
2011 ALK-positive extramedullary plasmacytoma with expression of the CLTC-ALK fusion transcript. Pathology, research and practice 25 21855232
2020 A novel CLTC-FOSB gene fusion in pseudomyogenic hemangioendothelioma of bone. Genes, chromosomes & cancer 24 32749039
2015 On the Role of Interfaces in Planar-Structured HC(NH2 )2 PbI3 Perovskite Solar Cells. ChemSusChem 24 25881766
2006 Biochemical and pre-steady-state kinetic characterization of the hepatitis C virus RNA polymerase (NS5BDelta21, HC-J4). Biochemistry 24 16533043
2005 High-resolution aliphatic side-chain assignments in 3D HCcoNH experiments with joint H-C evolution and non-uniform sampling. Journal of biomolecular NMR 24 16041483
2004 Stress and transcriptional regulation of tick ferritin HC. Insect molecular biology 24 15271215
2003 Role of HPV DNA testing in predicting cervical intraepithelial lesions: comparison of HC HPV and ISH HPV. Diagnostic cytopathology 24 12951683
1999 A putative branched-chain-amino-acid transaminase gene required for HC-toxin biosynthesis and pathogenicity in Cochliobolus carbonum. Microbiology (Reading, England) 24 10627051
1987 Structural homology of human complement component C8 gamma and plasma protein HC: identity of the cysteine bond pattern. Biochemical and biophysical research communications 23 2447883
2023 PERK Inhibition by HC-5404 Sensitizes Renal Cell Carcinoma Tumor Models to Antiangiogenic Tyrosine Kinase Inhibitors. Clinical cancer research : an official journal of the American Association for Cancer Research 22 37733811
2020 The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation by Sequestering hsa-miR-183-5p. Molecular therapy. Nucleic acids 22 32278306
2012 The GADD45a-GFP GreenScreen HC assay. Methods in molecular biology (Clifton, N.J.) 22 22147576
2020 Investigation of the effects of P1 on HC-pro-mediated gene silencing suppression through genetics and omics approaches. Botanical studies 21 32748085
2010 Mapping the self-interacting domains of TuMV HC-Pro and the subcellular localization of the protein. Virus genes 21 20938729
1988 Identification of retinol as one of the protein HC chromophores. Biochemical and biophysical research communications 21 2460097
2010 HC-Pro, a potyvirus RNA silencing suppressor, cancels cycling of Cucumber mosaic virus in Nicotiana benthamiana plants. Virus genes 20 20162445
2006 Reduction of the ganglioside binding activity of the tetanus toxin HC fragment destroys immunogenicity: implications for development of novel tetanus vaccines. Infection and immunity 20 16861677
2021 Hyaluronic acid synthesis, degradation, and crosslinking in equine osteoarthritis: TNF-α-TSG-6-mediated HC-HA formation. Arthritis research & therapy 19 34416923
2021 Investigating the Viral Suppressor HC-Pro Inhibiting Small RNA Methylation through Functional Comparison of HEN1 in Angiosperm and Bryophyte. Viruses 19 34578418
2020 A Novel Vibriophage vB_VcaS_HC Containing Lysogeny-Related Gene Has Strong Lytic Ability against Pathogenic Bacteria. Virologica Sinica 19 32767211
2020 Niche regulation of limbal epithelial stem cells: HC-HA/PTX3 as surrogate matrix niche. Experimental eye research 19 32795525
2020 Synthesis of Full-Length cDNA Infectious Clones of Soybean Mosaic Virus and Functional Identification of a Key Amino Acid in the Silencing Suppressor Hc-Pro. Viruses 19 32823665
2019 De novo CLTC variants are associated with a variable phenotype from mild to severe intellectual disability, microcephaly, hypoplasia of the corpus callosum, and epilepsy. Genetics in medicine : official journal of the American College of Medical Genetics 18 31776469
2011 High level expression of recombinant BoNT/A-Hc by high cell density cultivation of Escherichia coli. Bioprocess and biosystems engineering 18 21833619
2009 Prevalence of hepatitis C and B infection and HC V genotypes among hemodialysis patients in Khuzestan province, southwest Iran. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 18 19587521
2003 A multi-domain protein system based on the HC fragment of tetanus toxin for targeting DNA to neuronal cells. Journal of drug targeting 18 14668054
2000 Age-related reference limits for urine levels of albumin, orosomucoid, immunoglobulin G and protein HC in children. Scandinavian journal of clinical and laboratory investigation 18 10757455
2014 Hc-fau, a novel gene regulating diapause in the nematode parasite Haemonchus contortus. International journal for parasitology 17 25058511
2010 Enhanced expression of soluble recombinant tetanus neurotoxin Hc in Escherichia coli as a tetanus vaccine candidate. Immunobiology 17 20888666
2002 Molecular studies of the synergistic interactions between plum pox virus HC-Pro protein and potato virus X. Archives of virology 17 12491099
2022 Molecular investigation of ALK-rearranged epithelioid fibrous histiocytomas identifies CLTC as a novel fusion partner and evidence of fusion-independent transcription activation. Genes, chromosomes & cancer 16 35289445
2021 Phase I clinical trial of HC-1119: A deuterated form of enzalutamide. International journal of cancer 16 34109624
2016 Structural and functional characterization of a novel gene, Hc-daf-22, from the strongylid nematode Haemonchus contortus. Parasites & vectors 16 27472920
1984 Conformational studies of the human complex-forming glycoprotein, heterogeneous in charge: protein HC. Biochemistry 16 6201192
2012 Characterisation of the cell line HC-AFW1 derived from a pediatric hepatocellular carcinoma. PloS one 15 22666492
2002 Fluorescent probes DPH, TMA-DPH and C17-HC induce erythrocyte exovesiculation. The Journal of membrane biology 15 12422273
2015 HC toxin (a HDAC inhibitor) enhances IRS1-Akt signalling and metabolism in mouse myotubes. Journal of molecular endocrinology 14 26373795
2006 Indirect NMR spin-spin coupling constants 3J(P,C) and 2J(P,H) across the P-O...H-C link can be used for structure determination of nucleic acids. Journal of the American Chemical Society 14 16719462