CLTC encodes clathrin heavy chain 1 (CHC17), the major structural component of clathrin-coated vesicles. CHC17 forms triskelia composed of three heavy chains and three light chains that polymerize into polyhedral lattices at the plasma membrane and trans-Golgi network. The protein contains an N-terminal WD40-like beta-propeller domain (terminal domain) that serves as the primary adaptor binding site, seven clathrin heavy-chain repeat (CHCR) domains forming the leg, and a C-terminal hub/trimerization domain. Core functions include: (1) clathrin-mediated endocytosis at the plasma membrane via AP-2 adaptor interaction; (2) intracellular trafficking at the TGN via AP-1 and GGA adaptors; (3) mitotic spindle stabilization through TACC3/ch-TOG/clathrin complex formation at kinetochore fibers. Recent evidence (2024) suggests clathrin also actively constricts membrane pores during fission, beyond its traditional coat function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0071439 clathrin complex | IBA GO_REF:0000033 | ACCEPT | Summary: CHC17 is the defining component of the clathrin complex, forming triskelia with three heavy chains and three clathrin light chains. Cryo-EM studies confirm the conserved hub structure for trimerization and variable leg conformations enabling different cage architectures [PMID:31611653 morris2019cryoemofmultiple]. Reason: This is a core structural annotation. CHC17 assembles with light chains (CLTA/CLTB) into triskelia that are the fundamental building blocks of clathrin coats. UniProt confirms "Clathrin triskelions, composed of 3 heavy chains and 3 light chains, are the basic subunits of the clathrin coat." Supporting Evidence: file:human/CLTC/CLTC-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0006898 receptor-mediated endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Receptor-mediated endocytosis (RME) is the canonical function of CHC17-containing clathrin coats at the plasma membrane. The N-terminal domain binds AP-2 adaptors that recruit cargo receptors. Deep research confirms CHC17 drives clathrin-mediated endocytosis in all cells [greig2024chc22clathrinrecruitment]. Reason: This is the core biological process for CLTC. RME via clathrin-coated pits is essential for nutrient uptake, signaling receptor downregulation, and pathogen entry. Experimental evidence includes siRNA knockdown reducing transferrin uptake (PMID:14985334) and EGF receptor internalization defects. |
| GO:0005819 spindle | IBA GO_REF:0000033 | ACCEPT | Summary: CHC17 localizes to the mitotic spindle where it forms a complex with TACC3 and ch-TOG (CKAP5) that stabilizes kinetochore fibers through inter-microtubule bridging [PMID:15858577, PMID:21297582]. Reason: Non-endocytic spindle function is well-documented. PMID:15858577 showed clathrin is required for mitotic spindle function via direct localization studies. UniProt confirms localization to "Cytoplasm, cytoskeleton, spindle." |
| GO:0000278 mitotic cell cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: CHC17 participates in mitosis through spindle stabilization. The TACC3/ch-TOG/clathrin complex maintains kinetochore fiber tension required for proper chromosome segregation [PMID:23532825]. Reason: While the mitotic function is genuine, it is secondary to the primary vesicle trafficking role. The term is appropriately general for this moonlighting function, which occurs in dividing cells but is not the defining activity of clathrin. |
| GO:0032051 clathrin light chain binding | IBA GO_REF:0000033 | ACCEPT | Summary: CHC17 binds clathrin light chains (CLTA and CLTB) through the proximal leg region (residues 1213-1522 per UniProt). This interaction is essential for triskelion assembly and coat stability. Reason: Core molecular function. UniProt explicitly defines the light chain binding region and notes that "hub assembly is influenced by both the pH and the concentration of calcium" in the presence of light chains. |
| GO:0045334 clathrin-coated endocytic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: CHC17 is the defining coat protein of clathrin-coated endocytic vesicles formed at the plasma membrane. These vesicles internalize cargo from the cell surface. Reason: Core cellular component annotation. Clathrin-coated vesicles at the plasma membrane are the functional units of clathrin-mediated endocytosis, and CHC17 is their essential structural component. |
| GO:0048268 clathrin coat assembly | IBA GO_REF:0000033 | ACCEPT | Summary: CHC17 polymerizes to form the clathrin lattice during coat assembly. The universal mode of self-assembly involves hexagonal and pentagonal tiling enabled by leg flexibility [morris2019cryoemofmultiple]. Reason: Core biological process. Coat assembly is the fundamental activity of clathrin heavy chain, driven by triskelia self-association into polyhedral lattices. |
| GO:0005198 structural molecule activity | IEA GO_REF:0000002 | ACCEPT | Summary: CHC17 provides the structural scaffold for clathrin-coated pits and vesicles. The heavy chain repeat domains form the arms of the triskelion that polymerize into cage-like structures. Reason: Appropriate molecular function annotation. The primary activity of clathrin heavy chain is structural - providing the scaffold for vesicle formation. This is complementary to more specific binding functions. |
| GO:0005802 trans-Golgi network | IEA GO_REF:0000117 | ACCEPT | Summary: CHC17 localizes to the trans-Golgi network where it participates in vesicle formation for lysosomal and secretory pathways via AP-1 and GGA adaptors. Reason: Core localization. TGN trafficking is a well-established function of CHC17, distinct from but parallel to its plasma membrane endocytic function. UniProt lists "trans-Golgi network membrane" as a confirmed location. |
| GO:0005819 spindle | IEA GO_REF:0000044 | ACCEPT | Summary: Duplicate of IBA annotation. CHC17 localizes to the mitotic spindle as part of the TACC3/ch-TOG/clathrin complex [PMID:15858577, PMID:21297582]. Reason: Valid localization supported by multiple experimental studies. IEA annotation is consistent with IBA and IDA evidence for spindle localization. |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000043 | ACCEPT | Summary: CHC17 is the defining structural component of clathrin-coated pits at the plasma membrane. These are the sites of cargo concentration and vesicle budding during CME. Reason: Core localization. UniProt confirms "Cytoplasmic face of coated pits and vesicles." Clathrin-coated pits are the assembly sites where clathrin coats form on the plasma membrane before vesicle scission. |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: CHC17 mediates intracellular protein transport via clathrin-coated vesicles at both the plasma membrane and TGN. This includes receptor recycling and lysosomal enzyme targeting. Reason: Appropriate parent term for clathrin's trafficking functions. While more specific terms exist (receptor-mediated endocytosis, retrograde transport), this captures the general role in vesicular transport. |
| GO:0006898 receptor-mediated endocytosis | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate annotation of the core CME function via ARBA machine learning. Consistent with the IBA annotation and experimental evidence. Reason: Core function annotation. Redundant with IBA but correctly identifies the primary biological process. |
| GO:0006914 autophagy | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: This annotation derives from UniProt keyword mapping. UniProt notes interaction with ATG16L1 and "a role in early autophagosome formation" based on PMID:20639872. However, this represents an indirect/accessory role rather than a core autophagy function. Reason: The deep research review found no direct autophagy function for CLTC. While clathrin may contribute plasma membrane to early autophagosomes (PMID:20639872), this is peripheral to clathrin's core endocytic function. The primary role of CHC17 is vesicular trafficking, not autophagy. This annotation could mislead users into thinking autophagy is a core function. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHC17 associates with membranes as a peripheral membrane protein during coat formation. It localizes to the cytoplasmic face of coated pits and vesicles. Reason: General but accurate localization. More specific membrane compartment terms are also present (plasma membrane, TGN membrane, etc.), but this general term captures the membrane association. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000002 | ACCEPT | Summary: CHC17 is essential for clathrin-mediated vesicular transport pathways including endocytosis and TGN-to-lysosome trafficking. Reason: Appropriate parent term for clathrin's transport functions. This captures the general role in vesicle-based trafficking. |
| GO:0030130 clathrin coat of trans-Golgi network vesicle | IEA GO_REF:0000002 | ACCEPT | Summary: CHC17 forms the coat of clathrin-coated vesicles at the TGN, working with AP-1 and GGA adaptors for lysosomal enzyme sorting and secretory pathway trafficking. Reason: Core localization for TGN function. This is a well-established site of clathrin coat formation distinct from plasma membrane CME. |
| GO:0030132 clathrin coat of coated pit | IEA GO_REF:0000002 | ACCEPT | Summary: CHC17 is the structural component of the clathrin coat that forms at coated pits during vesicle budding. Reason: Core cellular component. This is precisely where clathrin performs its primary structural function during endocytosis. |
| GO:0030136 clathrin-coated vesicle | IEA GO_REF:0000117 | ACCEPT | Summary: CHC17 is the defining structural component of clathrin-coated vesicles, the transport carriers formed by clathrin coat assembly. Reason: Core localization. Clathrin-coated vesicles are the product of clathrin coat assembly and the transport units for CME and TGN trafficking. |
| GO:0030659 cytoplasmic vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: CHC17 associates with cytoplasmic vesicle membranes as a peripheral membrane protein forming the coat structure. Reason: Appropriate general localization term for clathrin's association with intracellular vesicular membranes. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000043 | ACCEPT | Summary: CHC17 localizes to cytoplasmic vesicles as the coat protein of clathrin-coated vesicles. Reason: Appropriate general localization. More specific clathrin-coated vesicle terms are also present but this captures the general vesicular association. |
| GO:0032051 clathrin light chain binding | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of IBA annotation. CHC17 binds clathrin light chains through the proximal leg region (residues 1213-1522). Reason: Core molecular function. IEA annotation is consistent with IBA evidence. |
| GO:0042147 retrograde transport, endosome to Golgi | IEA GO_REF:0000117 | ACCEPT | Summary: CHC17 participates in retrograde transport pathways. This is supported by experimental evidence (PMID:20065094). Reason: Secondary trafficking function. While not as prominent as anterograde endocytic trafficking, clathrin does participate in retrograde pathways. |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: CHC17 was identified in melanosome fractions by mass spectrometry (PMID:17081065). UniProt notes identification "in melanosome fractions from stage I to stage IV." Reason: Tissue/cell-type specific localization. Melanosomes are specialized lysosome-related organelles, and clathrin's presence likely reflects its role in cargo trafficking to these organelles rather than a melanosome-specific function. |
| GO:0051301 cell division | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: CHC17 participates in cell division through its role in mitotic spindle stabilization via the TACC3/ch-TOG/clathrin complex. Reason: Secondary function. The mitotic spindle role is genuine but represents a moonlighting function distinct from the core vesicular trafficking activities. |
| GO:0071439 clathrin complex | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of IBA annotation. CHC17 is the heavy chain component of the clathrin complex/triskelion. Reason: Core cellular component. IEA annotation is consistent with IBA evidence. |
| GO:0005515 protein binding | IPI PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kapp... | MODIFY | Summary: High-throughput protein-protein interaction study mapping the TNF-alpha/NF-kappa B signaling pathway. Reason: The term "protein binding" is uninformative for GO annotation purposes. More specific binding terms should be used based on the interaction partners identified. Unable to access publication for specific details on binding partners. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:14743216 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. |
| GO:0005515 protein binding | IPI PMID:16137687 SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 e... | MODIFY | Summary: Study on SNX9 as adaptor linking synaptojanin-1 to Cdc42 effector ACK1. Clathrin interaction with SNX9 is relevant to endocytosis regulation. Reason: "Protein binding" is too general. The interaction with SNX9 relates to CME regulation and could be annotated more specifically. Proposed replacements: clathrin binding Supporting Evidence: PMID:16137687 SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1. |
| GO:0005515 protein binding | IPI PMID:16169070 A human protein-protein interaction network: a resource for ... | MODIFY | Summary: Large-scale human protein-protein interaction network study. Reason: High-throughput study with generic "protein binding" term. Without specific binding partner context, this should be replaced with more informative terms based on known clathrin interactions. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:16169070 A human protein-protein interaction network: a resource for annotating the proteome. |
| GO:0005515 protein binding | IPI PMID:16902405 Membrane targeting and activation of the Lowe syndrome prote... | MODIFY | Summary: Study on OCRL1 membrane targeting by Rab GTPases. OCRL interacts with clathrin via its PH domain. Reason: More specific term available. The OCRL-clathrin interaction is relevant to clathrin-mediated endocytosis regulation. Proposed replacements: clathrin binding Supporting Evidence: PMID:16902405 Aug 10. Membrane targeting and activation of the Lowe syndrome protein OCRL1 by rab GTPases. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | MODIFY | Summary: Large-scale protein-protein interaction mapping by mass spectrometry. Reason: High-throughput study with generic term. Should be replaced with more specific binding annotations based on validated interactions. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:18548008 A B-Myb complex containing clathrin and filamin is required ... | MODIFY | Summary: Study on B-Myb complex containing clathrin and filamin required for mitotic spindle function. Documents clathrin interaction with TACC3. Reason: Important interaction for spindle function. More specific binding term should be used. Proposed replacements: tau protein binding Supporting Evidence: PMID:18548008 A B-Myb complex containing clathrin and filamin is required for mitotic spindle function. |
| GO:0005515 protein binding | IPI PMID:19536138 A PH domain within OCRL bridges clathrin-mediated membrane t... | MODIFY | Summary: Study on OCRL PH domain bridging clathrin-mediated membrane trafficking to phosphoinositide metabolism. Reason: More specific term available for OCRL interaction. Proposed replacements: clathrin binding Supporting Evidence: PMID:19536138 A PH domain within OCRL bridges clathrin-mediated membrane trafficking to phosphoinositide metabolism. |
| GO:0005515 protein binding | IPI PMID:19798056 Participation of Tom1L1 in EGF-stimulated endocytosis of EGF... | MODIFY | Summary: Study on Tom1L1 participation in EGF-stimulated EGFR endocytosis. Documents clathrin interaction with Tom1L1. Reason: Tom1L1 interaction is relevant to cargo recruitment during CME. More specific term should be used. Proposed replacements: clathrin binding Supporting Evidence: PMID:19798056 Participation of Tom1L1 in EGF-stimulated endocytosis of EGF receptor. |
| GO:0005515 protein binding | IPI PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibre... | MODIFY | Summary: Study showing TACC3/ch-TOG/clathrin complex stabilizes kinetochore fibers by inter-microtubule bridging. Key evidence for spindle function. Reason: Well-characterized interaction with TACC3. More specific binding annotation appropriate. Proposed replacements: clathrin binding Supporting Evidence: PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. |
| GO:0005515 protein binding | IPI PMID:25107275 A role of OCRL in clathrin-coated pit dynamics and uncoating... | MODIFY | Summary: Study on OCRL role in clathrin-coated pit dynamics and uncoating in Lowe syndrome cells. Reason: OCRL-clathrin interaction relevant to CME. More specific term available. Proposed replacements: clathrin binding Supporting Evidence: PMID:25107275 A role of OCRL in clathrin-coated pit dynamics and uncoating revealed by studies of Lowe syndrome cells. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MODIFY | Summary: Human interactome study organized by stoichiometries and abundances. Reason: High-throughput study with generic term. More specific annotations should be used based on validated interactions. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Crosslinking mass spectrometry study of histone interactions in cell nuclei. Clathrin interaction with histones is likely an artifact or non-functional. Reason: Clathrin is a cytoplasmic/membrane-associated protein; histone interactions detected by crosslinking are likely non-specific or artifactual. Not relevant to clathrin function. Supporting Evidence: PMID:30021884 Epub 2018 Jul 18. Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Dual proteome-scale networks revealing cell-specific interactome remodeling. Reason: High-throughput study with generic term. More specific annotations appropriate. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ... | MODIFY | Summary: Proteome-scale mapping of binding sites in unstructured regions. Reason: High-throughput study with generic term. More specific annotations should be used. Proposed replacements: disordered domain specific binding Supporting Evidence: PMID:35044719 Proteome-scale mapping of binding sites in the unstructured regions of the human proteome. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MODIFY | Summary: OpenCell endogenous tagging study for cellular organization cartography. Reason: High-throughput localization/interaction study. Generic "protein binding" should be replaced with specific terms. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | MODIFY | Summary: Phage-based screening for pan-viral mimicry of host short linear motifs. Reason: Study identifies viral mimicry of host SLiMs. More specific annotation based on interaction type is appropriate. Proposed replacements: disordered domain specific binding Supporting Evidence: PMID:37100772 Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs. |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | MODIFY | Summary: Phosphomimetic screening for phospho-modulated motif-based protein interactions. Reason: Study on phospho-regulated interactions. More specific binding term appropriate. Proposed replacements: disordered domain specific binding Supporting Evidence: PMID:37219487 2023 May 23. Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Multimodal cell maps as foundation for structural and functional genomics. Reason: High-throughput study with generic term. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics. |
| GO:0005764 lysosome | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based localization to lysosomes. Clathrin participates in TGN-to-lysosome trafficking. Reason: Valid localization reflecting clathrin's role in lysosomal enzyme delivery via AP-1/GGA-mediated TGN sorting. |
| GO:0005768 endosome | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based localization to endosomes. Clathrin-coated vesicles deliver cargo to endosomes. Reason: Valid localization. Endosomes are the destination of clathrin-coated vesicles from the plasma membrane. |
| GO:0072686 mitotic spindle | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence-based localization to the mitotic spindle. Supported by multiple experimental studies [PMID:15858577, PMID:21297582]. Reason: Well-documented localization for clathrin's mitotic function. Consistent with TACC3/ch-TOG/clathrin complex formation at kinetochore fibers. |
| GO:0072318 clathrin coat disassembly | ISS GO_REF:0000024 | ACCEPT | Summary: CHC17 is the substrate for uncoating by HSPA8/Hsc70 recruited via auxilin (DNAJC6). ATP-driven Hsc70 action destabilizes the lattice [sengupta2024 structuralinsightsinto]. Reason: Core function. Coat disassembly is essential for clathrin recycling after vesicle formation. UniProt describes interaction with DNAJC6 mediating HSPA8 recruitment for uncoating. |
| GO:0005515 protein binding | IPI PMID:29735704 LRRK2 phosphorylation of auxilin mediates synaptic defects i... | MODIFY | Summary: Study on LRRK2 phosphorylation of auxilin (DNAJC6) mediating synaptic defects in Parkinson's disease. Documents clathrin-DNAJC6 interaction. Reason: Important interaction for the uncoating mechanism: the IPI partner is auxilin (DNAJC6, UniProtKB:O75061), the J-domain co-chaperone that recruits HSC70 to clathrin cages. The binding partner is a chaperone, not an unfolded protein (the previously proposed GO:0051082 unfolded protein binding was wrong for a folded clathrin lattice, and is now obsolete), so protein-folding chaperone binding is the more specific term. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:29735704 phosphorylation of auxilin led to differential clathrin binding |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700131 | ACCEPT | Summary: Reactome pathway annotation for ALK mutants binding TKIs. Cytosolic localization reflects clathrin pool available for coat assembly. Reason: Valid localization. Clathrin triskelia cycle between cytosol and membrane-bound coats. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700179 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization for cytosolic clathrin pool. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9700181 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712078 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712079 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712083 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712084 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9712085 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9850958 | ACCEPT | Summary: Reactome pathway annotation. Duplicate cytosol localization. Reason: Valid localization. |
| GO:0005515 protein binding | IPI PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | MODIFY | Summary: Study on PICALM role in amyloid-beta blood-brain barrier transcytosis. Documents clathrin interaction with PICALM. Reason: PICALM is a clathrin adaptor. More specific binding term appropriate. Proposed replacements: clathrin binding Supporting Evidence: PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier transcytosis and clearance. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: Study on PICALM-mediated clathrin-dependent transcytosis. Clathrin interacts with LRP1 receptor for amyloid-beta clearance. Reason: Specific receptor interaction relevant to transcytosis pathway. This is a tissue-specific function (blood-brain barrier) rather than core clathrin activity. Supporting Evidence: PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier transcytosis and clearance. |
| GO:0072583 clathrin-dependent endocytosis | IMP PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | ACCEPT | Summary: Study demonstrates clathrin-dependent endocytosis mediates amyloid-beta transcytosis across the blood-brain barrier. Reason: Core biological process. This is a specific example of clathrin-mediated endocytosis validated by mutant phenotype analysis. Supporting Evidence: PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier transcytosis and clearance. |
| GO:0150093 amyloid-beta clearance by transcytosis | IMP PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier tra... | KEEP AS NON CORE | Summary: CLTC knockdown reduced amyloid-beta transcytosis across brain endothelial cells. Reason: Tissue-specific application of clathrin's core endocytic function. This is relevant to Alzheimer's disease pathophysiology but represents a specialized instance of CME rather than a defining clathrin function. Supporting Evidence: PMID:26005850 Central role for PICALM in amyloid-Ξ² blood-brain barrier transcytosis and clearance. |
| GO:0032991 protein-containing complex | IDA PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | ACCEPT | Summary: Study on RFTN1 involvement in TLR3 activation nucleocapture complex. Clathrin identified as part of a multi-protein complex. Reason: Clathrin functions as part of multi-protein complexes including triskelia and TACC3/ch-TOG/clathrin spindle complex. Supporting Evidence: PMID:21266579 2011 Jan 25. Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. |
| GO:0001649 osteoblast differentiation | HDA PMID:16210410 Differential expression profiling of membrane proteins by qu... | MARK AS OVER ANNOTATED | Summary: High-throughput proteomic study of mesenchymal stem cell differentiation to osteoblasts. CLTC identified as differentially expressed. Reason: Differential expression during osteoblast differentiation does not imply a functional role in the differentiation process. This likely reflects increased endocytic activity in differentiating cells rather than a specific osteoblast function. Supporting Evidence: PMID:16210410 Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation. |
| GO:0016020 membrane | HDA PMID:16210410 Differential expression profiling of membrane proteins by qu... | ACCEPT | Summary: Same proteomic study. Membrane association detected. Reason: Valid general localization consistent with clathrin's membrane-associated function. Supporting Evidence: PMID:16210410 Differential expression profiling of membrane proteins by quantitative proteomics in a human mesenchymal stem cell line undergoing osteoblast differentiation. |
| GO:1990381 ubiquitin-specific protease binding | IPI PMID:26756164 USP2-45 Is a Circadian Clock Output Effector Regulating Calc... | ACCEPT | Summary: Study on USP2-45 as circadian clock output effector. Documents clathrin interaction with USP2 isoform 4. UniProt confirms this interaction. Reason: Specific molecular function annotation. USP2 interaction may regulate clathrin stability or function. Supporting Evidence: PMID:26756164 eCollection 2016. USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level. |
| GO:0045334 clathrin-coated endocytic vesicle | NAS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: Study on CALM regulation of clathrin-coated vesicle size and maturation. Clathrin is the defining component of CCVs. Reason: Core localization annotation consistent with IBA evidence. Supporting Evidence: PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. |
| GO:0030118 clathrin coat | IMP PMID:11756460 Unusual structural organization of the endocytic proteins AP... | ACCEPT | Summary: Study on structural organization of AP180 and epsin 1 showing their disordered domains interact with clathrin. Clathrin forms the coat. Reason: Core cellular component. CHC17 is the structural component of the clathrin coat. Supporting Evidence: PMID:11756460 2001 Dec 26. Unusual structural organization of the endocytic proteins AP180 and epsin 1. |
| GO:0048268 clathrin coat assembly | IMP PMID:11756460 Unusual structural organization of the endocytic proteins AP... | ACCEPT | Summary: Study demonstrates coat assembly promoted by AP180/epsin interactions with clathrin. Reason: Core biological process supported by experimental evidence. Supporting Evidence: PMID:11756460 2001 Dec 26. Unusual structural organization of the endocytic proteins AP180 and epsin 1. |
| GO:0097718 disordered domain specific binding | IPI PMID:11756460 Unusual structural organization of the endocytic proteins AP... | ACCEPT | Summary: Study shows clathrin terminal domain binds disordered regions of AP180 and epsin 1 containing clathrin-box motifs. Reason: Specific molecular function. The N-terminal domain of clathrin binds multiple adaptor proteins through their disordered regions containing clathrin-binding motifs. Supporting Evidence: PMID:11756460 2001 Dec 26. Unusual structural organization of the endocytic proteins AP180 and epsin 1. |
| GO:0060236 regulation of mitotic spindle organization | IMP PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibre... | ACCEPT | Summary: Study showing TACC3/ch-TOG/clathrin complex stabilizes kinetochore fibers by inter-microtubule bridging. Reason: Well-documented mitotic function. Clathrin depletion disrupts spindle organization. Supporting Evidence: PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. |
| GO:1990498 mitotic spindle microtubule | IDA PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibre... | ACCEPT | Summary: Direct imaging showed clathrin localizes to kinetochore fiber microtubules as part of TACC3/ch-TOG/clathrin complex. Reason: Specific localization within spindle supported by direct experimental evidence. Supporting Evidence: PMID:21297582 A TACC3/ch-TOG/clathrin complex stabilises kinetochore fibres by inter-microtubule bridging. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856808 | ACCEPT | Summary: Reactome pathway: Recruitment of AP-2 complex and clathrin. Reason: Valid localization for cytosolic clathrin pool recruited to membranes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856813 | ACCEPT | Summary: Reactome pathway: AAK1 phosphorylates AP-2 mu subunit. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8862280 | ACCEPT | Summary: Reactome pathway: FCHo proteins bind nascent clathrin-coated pit. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866283 | ACCEPT | Summary: Reactome pathway: ARRB recruits GPCRs into clathrin-coated pits. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Reactome pathway: F- and N-BAR domain proteins bind clathrin-coated pit. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Reactome pathway: CLASP proteins and cargo recruitment. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Reactome pathway: Clathrin recruits PIK3C2A. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Reactome pathway: Clathrin-associated PIK3C2A phosphorylates PI(4)P. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Reactome pathway: SNX9 recruits actin polymerizing machinery. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Reactome pathway: BAR domain proteins recruit dynamin. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Reactome pathway: SYNJ hydrolyzes PI(4,5)P2. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Reactome pathway: Endophilins recruit synaptojanins. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: Reactome pathway: HSPA8-mediated ATP hydrolysis promotes uncoating. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: Reactome pathway: Clathrin recruits auxilins. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: Reactome pathway: Auxilin recruits HSPA8:ATP. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Reactome pathway: Dynamin-mediated vesicle scission. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: Reactome pathway: Dissociation of clathrin-associated proteins. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: Reactome pathway: Dissociation of AAK1 and dephosphorylation of AP-2. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: Reactome pathway: RAB5 and GAPVD1 bind AP-2. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871196 | ACCEPT | Summary: Reactome pathway: Initial binding of AP-2 and clathrin to PI(4,5)P2. Reason: Valid localization. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130486 | ACCEPT | Summary: Reactome pathway: Uncoating of clathrin-coated vesicles and fusion with endosomes. Reason: Valid localization for clathrin-coated vesicle destination. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130725 | ACCEPT | Summary: Reactome pathway: Internalization of MHC II:Ii clathrin coated vesicle. Reason: Valid localization. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784729 | ACCEPT | Summary: Reactome pathway: PCSK9:LDLR:Clathrin-coated vesicle transport. Reason: Valid localization. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784738 | ACCEPT | Summary: Reactome pathway: Degradation of PCSK9:LDLR complex. Reason: Valid localization. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-8855130 | ACCEPT | Summary: Reactome pathway: VLDLR:PCSK9:Clathrin-coated vesicle transport. Reason: Valid localization. |
| GO:0070062 extracellular exosome | HDA PMID:12519789 Proteomic and biochemical analyses of human B cell-derived e... | KEEP AS NON CORE | Summary: Proteomic analysis of B cell-derived exosomes identified clathrin. Reason: Clathrin presence in exosomes likely reflects its abundance in endocytic pathway rather than a specific exosome function. This is not a core function of clathrin. Supporting Evidence: PMID:12519789 2003 Jan 7. Proteomic and biochemical analyses of human B cell-derived exosomes. |
| GO:0042147 retrograde transport, endosome to Golgi | IMP PMID:20065094 The clathrin heavy chain isoform CHC22 functions in a novel ... | ACCEPT | Summary: Study on CHC22 clathrin in novel endosomal sorting step. While focused on CHC22, may have implications for CHC17 in retrograde transport. Reason: Valid biological process. Clathrin participates in retrograde pathways in addition to anterograde endocytic transport. Supporting Evidence: PMID:20065094 The clathrin heavy chain isoform CHC22 functions in a novel endosomal sorting step. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: Proteomic analysis of cerebrospinal fluid extracellular vesicles. Reason: Clathrin presence in extracellular vesicles reflects endocytic pathway involvement rather than a specific EV function. Supporting Evidence: PMID:24769233 2014 Apr 24. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset. |
| GO:1903077 negative regulation of protein localization to plasma membrane | IMP PMID:19581412 Quantitative proteomics identifies a Dab2/integrin module re... | ACCEPT | Summary: Study on Dab2/integrin module regulating cell migration. Clathrin-mediated endocytosis removes proteins from plasma membrane. Reason: This is a natural consequence of clathrin-mediated endocytosis - removing receptors/proteins from the cell surface. Valid biological process. Supporting Evidence: PMID:19581412 Jul 6. Quantitative proteomics identifies a Dab2/integrin module regulating cell migration. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: Analysis of myosin-II-responsive focal adhesion proteome. Reason: Clathrin may be involved in integrin endocytosis at focal adhesions but this is not a core clathrin function. Detection in focal adhesion proteome may reflect transient association during receptor turnover. Supporting Evidence: PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for Ξ²-Pix in negative regulation of focal adhesion maturation. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Proteomic analysis of prostatic secretion exosomes. Reason: Same reasoning as other exosome annotations - reflects clathrin abundance in endocytic pathway rather than specific function. Supporting Evidence: PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: Proteomic study defining NK cell membrane proteome. Reason: Valid general localization. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. |
| GO:0019901 protein kinase binding | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence similarity-based annotation for protein kinase binding. Clathrin may interact with kinases involved in CME regulation (e.g., AAK1). Reason: Valid molecular function. Multiple kinases regulate clathrin-mediated endocytosis through direct or indirect interactions with clathrin. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-5333658 | ACCEPT | Summary: Reactome pathway: CLAT:AP1:CLVS bind PI(3,5)P2. Reason: Core localization for TGN trafficking function. |
| GO:1900126 negative regulation of hyaluronan biosynthetic process | IMP PMID:23509262 KIAA1199, a deafness gene of unknown function, is a new hyal... | KEEP AS NON CORE | Summary: Study on KIAA1199/CEMIP as hyaluronan binding protein. Clathrin involvement may relate to receptor internalization. Reason: This is an indirect effect of clathrin's endocytic function on hyaluronan metabolism, not a direct regulatory function of clathrin. Supporting Evidence: PMID:23509262 KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization. |
| GO:1900126 negative regulation of hyaluronan biosynthetic process | IDA PMID:24251095 Murine homologue of the human KIAA1199 is implicated in hyal... | KEEP AS NON CORE | Summary: Study on murine KIAA1199 in hyaluronan depolymerization. Reason: Same reasoning - indirect effect via endocytic pathway. Supporting Evidence: PMID:24251095 eCollection 2013. Murine homologue of the human KIAA1199 is implicated in hyaluronan binding and depolymerization. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: mRNA-bound proteome study. Clathrin identified in RNA-protein complexes. Reason: High-throughput study identifying many proteins associated with mRNA. No established function for clathrin in RNA binding or metabolism. Likely reflects non-specific or indirect association. Supporting Evidence: PMID:22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. |
| GO:0032051 clathrin light chain binding | IPI PMID:4066749 Clathrin structure characterized with monoclonal antibodies.... | ACCEPT | Summary: Early study characterizing clathrin structure with monoclonal antibodies, identifying in vivo clathrin forms. Documents heavy-light chain interaction. Reason: Classic structural study confirming heavy-light chain interaction. Supporting Evidence: PMID:4066749 Clathrin structure characterized with monoclonal antibodies. |
| GO:0071439 clathrin complex | IDA PMID:4066749 Clathrin structure characterized with monoclonal antibodies.... | ACCEPT | Summary: Same study directly showing clathrin complex/triskelion structure. Reason: Direct evidence for clathrin complex formation. Supporting Evidence: PMID:4066749 Clathrin structure characterized with monoclonal antibodies. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-177479 | ACCEPT | Summary: Reactome pathway: Axonal transport of NGF:Trk complexes. Reason: Core localization for endocytic clathrin function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130640 | ACCEPT | Summary: Reactome pathway: Recruitment of clathrin coated vesicle by Ii. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130725 | ACCEPT | Summary: Reactome pathway: MHC II:Ii clathrin coated vesicle internalization. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392748 | ACCEPT | Summary: Reactome pathway: L1 binds to AP-2 Clathrin complex. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392749 | ACCEPT | Summary: Reactome pathway: Transport of L1 into endosomes. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445071 | ACCEPT | Summary: Reactome pathway: Reinsertion of L1 into plasma membrane. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445079 | ACCEPT | Summary: Reactome pathway: Phosphorylation of L1 by ERK. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5138433 | ACCEPT | Summary: Reactome pathway: DVL2 recruits AP-2 and beta-arrestin 2. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5138459 | ACCEPT | Summary: Reactome pathway: WNT5A:FZD4 endocytosis. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-555065 | ACCEPT | Summary: Reactome pathway: Formation of clathrin coated vesicle. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784729 | ACCEPT | Summary: Reactome pathway: PCSK9:LDLR transport. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784735 | ACCEPT | Summary: Reactome pathway: PCSK9:LDLR bind Clathrin. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855130 | ACCEPT | Summary: Reactome pathway: VLDLR:PCSK9 transport. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855131 | ACCEPT | Summary: Reactome pathway: VLDLR:PCSK9 binds clathrin. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: Reactome pathway: Epsin binds ubiquitinated cargo. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Reactome pathway: BAR domain proteins bind clathrin-coated pit. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Reactome pathway: CLASP proteins and cargo recruitment. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Reactome pathway: Clathrin recruits PIK3C2A. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Reactome pathway: PIK3C2A phosphorylates PI(4)P. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Reactome pathway: SNX9 recruits actin machinery. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Reactome pathway: BAR proteins recruit dynamin. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Reactome pathway: SYNJ hydrolyzes PI(4,5)P2. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Reactome pathway: Endophilins recruit synaptojanins. Reason: Valid localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Reactome pathway: Dynamin-mediated vesicle scission. Reason: Valid localization. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-5138459 | ACCEPT | Summary: Reactome pathway: WNT5A:FZD4 endocytosis. Reason: Core localization. CHC17 is the defining coat protein of these vesicles. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Proteomic analysis of parotid gland exosomes. Reason: Exosome presence reflects endocytic pathway abundance, not specific function. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Large-scale proteomics of urinary exosomes. Reason: Same reasoning as other exosome annotations. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0003725 double-stranded RNA binding | IDA PMID:21266579 Raftlin is involved in the nucleocapture complex to induce p... | MARK AS OVER ANNOTATED | Summary: Study on RFTN1 involvement in TLR3 activation by poly(I:C). Clathrin was part of the nucleocapture complex that binds dsRNA. Reason: This appears to be an indirect association via the RFTN1 complex rather than direct dsRNA binding by clathrin. No established mechanism for clathrin to directly bind nucleic acids. The study implicates clathrin in the complex but dsRNA binding is likely mediated by other components. Supporting Evidence: PMID:21266579 2011 Jan 25. Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Proteomic analysis of MHC class II-associated proteins in B-cell exosomes. Reason: Same reasoning as other exosome annotations. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2130619 | ACCEPT | Summary: Reactome pathway: TGN-lysosomal vesicle coat assembly. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-2213236 | ACCEPT | Summary: Reactome pathway: TGN-lysosome vesicle uncoating. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-421831 | ACCEPT | Summary: Reactome pathway: trans-Golgi Network Coat Assembly. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-421835 | ACCEPT | Summary: Reactome pathway: trans-Golgi Network Vesicle Scission. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-421836 | ACCEPT | Summary: Reactome pathway: trans-Golgi Network Derived Vesicle Uncoating. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432688 | ACCEPT | Summary: Reactome pathway: TGN Derived Lysosomal Vesicle Uncoating. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432706 | ACCEPT | Summary: Reactome pathway: TGN Lysosome Vesicle Coat Assembly. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-432707 | ACCEPT | Summary: Reactome pathway: TGN Lysosomal Vesicle Scission. Reason: Valid localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8951498 | ACCEPT | Summary: Reactome pathway: Dissociation of Arf1:GDP, AP-1 Clathrin coated complex. Reason: Valid localization. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2130641 | ACCEPT | Summary: Reactome pathway: Translocation of TGN-lysosome vesicle. Reason: Core localization for TGN trafficking function. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-2213236 | ACCEPT | Summary: Reactome pathway: TGN-lysosome vesicle uncoating. Reason: Valid localization. |
| GO:0032588 trans-Golgi network membrane | TAS Reactome:R-HSA-8951498 | ACCEPT | Summary: Reactome pathway: Dissociation of AP-1 clathrin complex. Reason: Valid localization. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | KEEP AS NON CORE | Summary: Proteomic analysis of trabecular meshwork cell exosomes. Reason: Same reasoning as other exosome annotations. Supporting Evidence: PMID:21362503 Epub 2011 Mar 8. Protein profile of exosomes from trabecular meshwork cells. |
| GO:0005515 protein binding | IPI PMID:12429846 Clint: a novel clathrin-binding ENTH-domain protein at the G... | MODIFY | Summary: Study on Clint (ENTH-domain protein) at the Golgi. Documents clathrin interaction with CLINT1. Reason: More specific binding term available. CLINT1 is a clathrin-interacting protein. Proposed replacements: clathrin binding Supporting Evidence: PMID:12429846 Clint: a novel clathrin-binding ENTH-domain protein at the Golgi. |
| GO:0000278 mitotic cell cycle | IMP PMID:15858577 Clathrin is required for the function of the mitotic spindle... | KEEP AS NON CORE | Summary: Key study showing clathrin is required for mitotic spindle function. Clathrin depletion causes mitotic defects. Reason: Important experimental evidence for mitotic function. However, this remains a secondary function compared to vesicular trafficking. Supporting Evidence: PMID:15858577 Clathrin is required for the function of the mitotic spindle. |
| GO:0005515 protein binding | IPI PMID:19478182 A role for the CHC22 clathrin heavy-chain isoform in human g... | MODIFY | Summary: Study on CHC22 role in human glucose metabolism. While focused on CHC22, documents clathrin interactions. Reason: Generic term should be replaced with more specific annotation. Proposed replacements: clathrin light chain binding Supporting Evidence: PMID:19478182 A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. |
| GO:0005819 spindle | IDA PMID:15858577 Clathrin is required for the function of the mitotic spindle... | ACCEPT | Summary: Key study directly demonstrating clathrin localization to the mitotic spindle by immunofluorescence. Reason: Direct experimental evidence for spindle localization. This is the primary reference establishing clathrin's mitotic function. Supporting Evidence: PMID:15858577 Clathrin is required for the function of the mitotic spindle. |
| GO:0006898 receptor-mediated endocytosis | IMP PMID:15858577 Clathrin is required for the function of the mitotic spindle... | ACCEPT | Summary: Same study also demonstrated clathrin role in receptor-mediated endocytosis through knockdown experiments. Reason: Core function validated by experimental evidence. Supporting Evidence: PMID:15858577 Clathrin is required for the function of the mitotic spindle. |
| GO:0030136 clathrin-coated vesicle | IDA PMID:19478182 A role for the CHC22 clathrin heavy-chain isoform in human g... | ACCEPT | Summary: Study on CHC22 showing clathrin-coated vesicle localization. Reason: Valid localization consistent with other evidence. Supporting Evidence: PMID:19478182 A role for the CHC22 clathrin heavy-chain isoform in human glucose metabolism. |
| GO:0031623 receptor internalization | IMP PMID:14985334 Analysis of clathrin-mediated endocytosis of epidermal growt... | ACCEPT | Summary: Study on clathrin-mediated EGFR endocytosis using RNA interference. Clathrin knockdown reduced receptor internalization. Reason: Core function. Receptor internalization via clathrin-mediated endocytosis is a primary activity of CHC17. Supporting Evidence: PMID:14985334 2004 Feb 25. Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. |
| GO:0033572 transferrin transport | IMP PMID:14985334 Analysis of clathrin-mediated endocytosis of epidermal growt... | ACCEPT | Summary: Same study showed clathrin knockdown reduced transferrin uptake, the classic marker for CME. Reason: Canonical experimental readout for clathrin-mediated endocytosis. Transferrin-transferrin receptor is the classic CME cargo. Supporting Evidence: PMID:14985334 2004 Feb 25. Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. |
| GO:0030118 clathrin coat | NAS PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning... | ACCEPT | Summary: Early study on partial cloning of human CLTC, mapping to chromosome 17. Established clathrin coat localization. Reason: Historical reference establishing core localization. Supporting Evidence: PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter. |
| GO:0005198 structural molecule activity | NAS PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning... | ACCEPT | Summary: Same study establishing clathrin as structural component of coated vesicles. Reason: Core molecular function - clathrin provides structural scaffold for coated pits and vesicles. Supporting Evidence: PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter. |
| GO:0006886 intracellular protein transport | NAS PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning... | ACCEPT | Summary: Same study describing clathrin function in intracellular transport. Reason: Core biological process for clathrin function. Supporting Evidence: PMID:1765375 Human clathrin heavy chain (CLTC): partial molecular cloning, expression, and mapping of the gene to human chromosome 17q11-qter. |
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Download this section (compressed HTML)Q: What is the relative contribution of membrane fission activity (recently described Wei et al. 2024) versus coat scaffolding in CHC17 function?
Q: Are there tissue-specific differences in CHC17 function beyond the CHC17/CHC22 isoform distinction?
Q: What regulates the partitioning of clathrin between endocytic and mitotic spindle pools during cell division?
Experiment: Cryo-ET analysis of CHC17 at membrane constriction sites to validate the fission function proposed by Wei et al. 2024
Experiment: Proximity labeling (BioID/APEX) to identify the full complement of CHC17 interactors at different cellular locations
Experiment: Structure-function analysis of CHC17 variants found in neurodevelopmental disorders to understand domain-specific requirements
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