LDLRAP1 (ARH) is a cargo-selective clathrin-associated sorting protein (CLASP) that couples the low-density lipoprotein receptor and other LDLR-family receptors (VLDLR, LRP2/megalin) to the clathrin endocytic machinery. Its N-terminal PID/PTB domain binds the FxNPxY internalization motif in the receptor cytoplasmic tail, while separate C-terminal motifs bind clathrin and the beta2-adaptin subunit of the AP-2 complex, and it binds phosphatidylinositol-4,5-bisphosphate; together these couple cargo capture to clathrin-coated pit assembly at the plasma membrane. It is required for efficient LDLR endocytosis in the liver and other polarized cells, and loss-of-function mutations cause autosomal recessive hypercholesterolemia.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001540 amyloid-beta binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Binds APP; peripheral to the core LDL endocytosis function. Reason: LDLRAP1 interacts with APP (P05067) and regulates its trafficking (PMID:12805363), a real but peripheral activity distinct from its core LDL-receptor endocytic-adaptor role; retained as non-core. Note the partner is full-length APP rather than the amyloid-beta peptide the term names. |
| GO:0001540 amyloid-beta binding | IPI PMID:12805363 Autosomal recessive hypercholesterolemia protein interacts w... | KEEP AS NON CORE | Summary: Binds APP; peripheral to the core LDL endocytosis function. Reason: LDLRAP1 interacts with APP (P05067) and regulates its trafficking (PMID:12805363), a real but peripheral activity distinct from its core LDL-receptor endocytic-adaptor role; retained as non-core. Note the partner is full-length APP rather than the amyloid-beta peptide the term names. |
| GO:0001784 phosphotyrosine residue binding | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | KEEP AS NON CORE | Summary: ARH PTB domain binds the UNphosphorylated NPxY motif (phospho-independent); phosphotyrosine residue binding is an imprecise fit, kept non-core by deference to the curator IDA. Reason: The ARH/Dab2-class PID/PTB domain recognises the FxNPxY (NPVY) internalization motif in a phosphorylation-INDEPENDENT manner (PMID:12451172: "PTB domains bind to the consensus sequence FXNPXY"), so GO:0001784 phosphotyrosine residue binding - which names binding to a phosphorylated tyrosine - is a loose fit. The IDA row is retained by deference to the curator, but as non-core; the precise cargo-recognition MF is GO:0050750 LDL particle receptor binding. Supporting Evidence: PMID:12451172 PTB domains bind to the consensus sequence FXNPXY |
| GO:0005515 protein binding | IPI PMID:12221107 ARH is a modular adaptor protein that interacts with the LDL... | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005515 protein binding | IPI PMID:27107012 Pooled-matrix protein interaction screens using Barcode Fusi... | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Uninformative high-throughput protein-binding row; removed per policy. Reason: Bare protein binding (GO:0005515) from a high-throughput interactome/two-hybrid screen; uninformative about LDLRAP1's molecular function and removed under the protein-binding policy. The specific endocytic-adaptor contacts (LDLR, clathrin, AP-2) are captured by dedicated terms elsewhere in this review. |
| GO:0005515 protein binding | IPI PMID:39526800 A comprehensive two-hybrid analysis to explore the Legionell... | MODIFY | Summary: Interactor is AP2B1 (beta2-adaptin); recast as AP-2 adaptor complex binding. Reason: The interaction partner is AP2B1 (beta2-adaptin, UniProtKB:P63010), a subunit of the AP-2 adaptor complex; LDLRAP1's C-terminal beta2-appendage-binding motif is well characterised, so the informative MF is AP-2 adaptor complex binding rather than bare protein binding. Proposed replacements: AP-2 adaptor complex binding Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0005546 phosphatidylinositol-4,5-bisphosphate binding | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | ACCEPT | Summary: PIP2 binding couples the adaptor to coated-pit assembly. Reason: LDLRAP1 binds PtdIns(4,5)P2 via its PTB domain, coupling cargo capture to clathrin-coated bud assembly at the plasma membrane; supported by direct assay and contributes to the core adaptor mechanism. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Refine cytoplasm to the supported cytosol term. Reason: Cytoplasm is correct but less specific than warranted; the gene carries cytosol (GO:0005829) by direct assay. Refine to the specific supported location. Proposed replacements: cytosol |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Early endosome localisation; consistent across IDA/IBA/IEA. Reason: LDLRAP1 localises to early endosomes, consistent with its role escorting internalised LDLR/megalin through the endocytic pathway (PMID:14528014). |
| GO:0005769 early endosome | IDA PMID:14528014 The adaptor protein ARH escorts megalin to and through endos... | ACCEPT | Summary: Early endosome localisation; consistent across IDA/IBA/IEA. Reason: LDLRAP1 localises to early endosomes, consistent with its role escorting internalised LDLR/megalin through the endocytic pathway (PMID:14528014). |
| GO:0005769 early endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Early endosome localisation; consistent across IDA/IBA/IEA. Reason: LDLRAP1 localises to early endosomes, consistent with its role escorting internalised LDLR/megalin through the endocytic pathway (PMID:14528014). |
| GO:0005829 cytosol | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | ACCEPT | Summary: Cytosol localisation (IDA). Reason: Cytosolic pool of the adaptor prior to membrane recruitment; accurate direct-assay localisation. |
| GO:0005883 neurofilament | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Neurofilament localisation unsupported by function; over-annotated. Reason: Neurofilament localisation derives from brain-expression/sequence studies and is not supported by LDLRAP1's characterised function as a plasma-membrane/endosomal endocytic adaptor; likely an over-annotation. |
| GO:0005883 neurofilament | ISS PMID:17727637 Characterization of the adaptor protein ARH expression in th... | MARK AS OVER ANNOTATED | Summary: Neurofilament localisation unsupported by function; over-annotated. Reason: Neurofilament localisation derives from brain-expression/sequence studies and is not supported by LDLRAP1's characterised function as a plasma-membrane/endosomal endocytic adaptor; likely an over-annotation. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-350168 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8863471 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9759202 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9759209 | ACCEPT | Summary: Plasma membrane; site of cargo capture. Reason: Plasma membrane is where LDLRAP1 nucleates clathrin-mediated endocytosis of LDLR; core location (Reactome CLASP models). |
| GO:0006898 receptor-mediated endocytosis | IDA PMID:14528014 The adaptor protein ARH escorts megalin to and through endos... | ACCEPT | Summary: Receptor-mediated endocytosis; core, multi-cargo. Reason: LDLRAP1 directly mediates receptor-mediated endocytosis (of LDLR and, per PMID:14528014, megalin/LRP2); core process. The general term is apt because the adaptor serves multiple LDLR-family cargoes, not only cholesterol-related receptors. |
| GO:0008203 cholesterol metabolic process | NAS PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | KEEP AS NON CORE | Summary: Broad downstream metabolic process; non-core. Reason: Cholesterol metabolic process is a broad downstream consequence of LDLRAP1's endocytic-adaptor activity (NAS); true but peripheral relative to the specific LDL-clearance/endocytosis terms. Non-core. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:14528014 The adaptor protein ARH escorts megalin to and through endos... | ACCEPT | Summary: Cytoplasmic side of plasma membrane. Reason: The adaptor acts on the cytoplasmic face of the plasma membrane; accurate, specific localisation (IDA). |
| GO:0009925 basal plasma membrane | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | ACCEPT | Summary: Basal plasma membrane in polarized cells. Reason: In polarized cells LDLRAP1 acts at the basolateral surface where LDLR is internalised; accurate direct-assay localisation. |
| GO:0030159 signaling receptor complex adaptor activity | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | MODIFY | Summary: Recast 'signaling receptor complex adaptor' as clathrin-cargo adaptor activity. Reason: LDLR is an endocytic cargo receptor, not a signaling receptor; the IMP evidence (PMID:15166224) shows LDLRAP1 is required for LDLR internalization, i.e. clathrin-cargo adaptor activity. Lateral correction to the mechanistically correct MF. Proposed replacements: clathrin-cargo adaptor activity |
| GO:0030276 clathrin binding | IDA PMID:12221107 ARH is a modular adaptor protein that interacts with the LDL... | ACCEPT | Summary: Direct clathrin binding; core. Reason: LDLRAP1 binds clathrin directly (clathrin-box motif; Kd~44 nM), a core contact of the cargo adaptor. Supporting Evidence: PMID:12221107 Recombinant ARH bound purified bovine clathrin with high affinity (K(D), approximately 44 nm). |
| GO:0030276 clathrin binding | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | ACCEPT | Summary: Direct clathrin binding; core. Reason: LDLRAP1 binds clathrin directly (clathrin-box motif; Kd~44 nM), a core contact of the cargo adaptor. |
| GO:0030301 cholesterol transport | NAS PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | KEEP AS NON CORE | Summary: Broad cholesterol transport; non-core. Reason: Cholesterol transport is a broad downstream role (NAS); the specific endocytosis/LDL-clearance terms are the core framing. Non-core. |
| GO:0030424 axon | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS axon localisation; unsupported, over-annotated. Reason: Axon localisation is an ISS-propagated, brain-context annotation not supported by LDLRAP1's characterised endocytic function; likely an over-annotation. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: Clathrin-coated endocytic vesicle membrane. Reason: Clathrin-coated endocytic vesicle membrane is where the adaptor operates; core location (Reactome). |
| GO:0031623 receptor internalization | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: Receptor internalization; core. Reason: Loss-of-function abolishes LDLR internalization (PMID:15166224); LDLRAP1 directly effects receptor internalization. Core. |
| GO:0034383 low-density lipoprotein particle clearance | IMP PMID:12417523 Molecular mechanisms of autosomal recessive hypercholesterol... | ACCEPT | Summary: LDL particle clearance; core. Reason: LDLRAP1 is required for LDL particle clearance; loss causes autosomal recessive hypercholesterolemia. Core physiological process. |
| GO:0034383 low-density lipoprotein particle clearance | IMP PMID:12464675 Restoration of LDL receptor function in cells from patients ... | ACCEPT | Summary: LDL particle clearance; core. Reason: LDLRAP1 is required for LDL particle clearance; loss causes autosomal recessive hypercholesterolemia. Core physiological process. |
| GO:0034383 low-density lipoprotein particle clearance | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: LDL particle clearance; core. Reason: LDLRAP1 is required for LDL particle clearance; loss causes autosomal recessive hypercholesterolemia. Core physiological process. |
| GO:0035591 signaling adaptor activity | IDA PMID:12221107 ARH is a modular adaptor protein that interacts with the LDL... | MODIFY | Summary: Recast 'signaling adaptor activity' as clathrin-cargo adaptor activity. Reason: PMID:12221107 characterises LDLRAP1 as coupling LDLR to the endocytic machinery, i.e. an endocytic/clathrin-cargo adaptor, not a signaling adaptor; LDLR endocytosis is not a signaling event. Lateral correction to the correct MF. Proposed replacements: clathrin-cargo adaptor activity Supporting Evidence: PMID:12221107 These data are consistent with the hypothesis that ARH functions as an adaptor protein that couples LDLR to the endocytic machinery. |
| GO:0035612 AP-2 adaptor complex binding | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | ACCEPT | Summary: AP-2 adaptor complex binding; core. Reason: LDLRAP1's C-terminal motif binds the beta2-adaptin subunit of AP-2; core adaptor contact. Supporting Evidence: PMID:12221107 A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2. |
| GO:0035612 AP-2 adaptor complex binding | IDA PMID:15728179 Functional dissection of an AP-2 beta2 appendage-binding seq... | ACCEPT | Summary: AP-2 adaptor complex binding confirmed; core. Reason: Independent dissection of the ARH beta2-appendage-binding sequence confirms direct AP-2 binding (PMID:15728179); core contact. |
| GO:0035615 clathrin-cargo adaptor activity | IDA PMID:15728179 Functional dissection of an AP-2 beta2 appendage-binding seq... | ACCEPT | Summary: Clathrin-cargo adaptor activity; the core function. Reason: Clathrin-cargo adaptor activity is LDLRAP1's defining molecular function: it couples the LDL receptor to the clathrin machinery via PTB (cargo), clathrin-box (clathrin) and beta2-appendage (AP-2) contacts. Core. Supporting Evidence: PMID:15728179 The carboxyl-terminal half of ARH contains a clathrin-binding sequence and a separate AP-2 adaptor binding region providing a plausible mechanism for how ARH can act as an endocytic adaptor or CLASP (clathrin-associated sorting protein) to couple LDL receptors with the clathrin machinery. |
| GO:0035650 AP-1 adaptor complex binding | IDA PMID:12451172 The autosomal recessive hypercholesterolemia (ARH) protein i... | KEEP AS NON CORE | Summary: AP-1 binding; secondary to AP-2-mediated endocytosis. Reason: AP-1 adaptor complex binding (PMID:12451172) is a real direct contact but relates to TGN/basolateral sorting rather than the plasma-membrane LDLR endocytosis that is the core role; retained as non-core. |
| GO:0042632 cholesterol homeostasis | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: Cholesterol homeostasis; core. Reason: By mediating hepatic LDLR endocytosis, LDLRAP1 maintains cholesterol homeostasis; its loss causes hypercholesterolemia. Core physiological role. |
| GO:0042982 amyloid precursor protein metabolic process | IMP PMID:12805363 Autosomal recessive hypercholesterolemia protein interacts w... | KEEP AS NON CORE | Summary: APP metabolic process; peripheral, non-core. Reason: Regulation of APP metabolism (PMID:12805363) is a peripheral activity distinct from the core LDL endocytic-adaptor role. Non-core. |
| GO:0043393 regulation of protein binding | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | MARK AS OVER ANNOTATED | Summary: Vague 'regulation of protein binding'; over-annotated. Reason: 'Regulation of protein binding' is a vague process term that does not capture a specific LDLRAP1 activity; over-annotation of what is mechanistically its adaptor/scaffolding of the endocytic machinery. |
| GO:0048260 positive regulation of receptor-mediated endocytosis | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | KEEP AS NON CORE | Summary: Positive regulation of RME; non-core framing. Reason: True (LDLRAP1 promotes receptor-mediated endocytosis) but framed as regulation; the participant terms (receptor internalization, RME) carry the core role. Non-core. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:12221107 ARH is a modular adaptor protein that interacts with the LDL... | ACCEPT | Summary: LDL receptor binding (cargo recognition); core. Reason: LDLRAP1 binds the LDL receptor (P01130) via its PTB domain reading the NPVY motif; the cargo-recognition contact and core to function. Supporting Evidence: PMID:12221107 The phosphotyrosine binding domain of ARH interacted with the internalization sequence (NPVY) in the cytoplasmic tail of LDLR in a sequence-specific manner. |
| GO:0050750 low-density lipoprotein particle receptor binding | IPI PMID:14528014 The adaptor protein ARH escorts megalin to and through endos... | ACCEPT | Summary: LRP2/megalin binding; LDLR-family cargo. Reason: LDLRAP1 also binds the LDLR-family receptor megalin/LRP2 (P98158), escorting it through endosomes (PMID:14528014); extends the cargo-recognition role. Core/near-core. |
| GO:0055037 recycling endosome | IDA PMID:14528014 The adaptor protein ARH escorts megalin to and through endos... | ACCEPT | Summary: Recycling endosome localisation. Reason: Recycling endosome localisation reflects megalin trafficking (PMID:14528014); accurate direct-assay localisation. |
| GO:0071345 cellular response to cytokine stimulus | IMP PMID:28257760 Induction of MiR133a expression by IL-19 targets LDLRAP1 and... | MARK AS OVER ANNOTATED | Summary: Indirect (LDLRAP1 is the miRNA target); over-annotated. Reason: From a study where IL-19-induced miR-133a targets LDLRAP1 (PMID:28257760): this makes LDLRAP1 a target of cytokine-driven regulation, not a participant performing a cytokine response. Over-annotation of an indirect relationship. |
| GO:0090118 receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:12417523 Molecular mechanisms of autosomal recessive hypercholesterol... | ACCEPT | Summary: RME in cholesterol transport; core. Reason: Receptor-mediated endocytosis involved in cholesterol transport is the specific process LDLRAP1 executes for LDLR; core. |
| GO:0090118 receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:12464675 Restoration of LDL receptor function in cells from patients ... | ACCEPT | Summary: RME in cholesterol transport; core. Reason: Receptor-mediated endocytosis involved in cholesterol transport is the specific process LDLRAP1 executes for LDLR; core. |
| GO:0090118 receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: RME in cholesterol transport; core. Reason: Receptor-mediated endocytosis involved in cholesterol transport is the specific process LDLRAP1 executes for LDLR; core. |
| GO:0090205 positive regulation of cholesterol metabolic process | IC PMID:15166224 The modular adaptor protein ARH is required for low density ... | KEEP AS NON CORE | Summary: Broad regulatory process (IC); non-core. Reason: Curator-inferred (IC) positive regulation of cholesterol metabolic process; a broad downstream framing of the core endocytic role. Non-core. |
| GO:1903076 regulation of protein localization to plasma membrane | IMP PMID:12805363 Autosomal recessive hypercholesterolemia protein interacts w... | KEEP AS NON CORE | Summary: Regulation of PM protein localization; non-core. Reason: Regulation of protein localization to plasma membrane (PMID:12805363) relates to LDLRAP1's effect on partner (e.g. APP/LDLR) surface levels; peripheral/indirect relative to the core adaptor MF. Non-core. |
| GO:1904707 positive regulation of vascular associated smooth muscle cell proliferation | IMP PMID:28257760 Induction of MiR133a expression by IL-19 targets LDLRAP1 and... | MARK AS OVER ANNOTATED | Summary: Downstream VSMC-proliferation effect; over-annotated. Reason: Positive regulation of vascular smooth muscle cell proliferation (PMID:28257760) is a downstream disease-context effect of altered LDL handling, not a direct LDLRAP1 function. Over-annotation. |
| GO:1905581 positive regulation of low-density lipoprotein particle clearance | IMP PMID:28257760 Induction of MiR133a expression by IL-19 targets LDLRAP1 and... | KEEP AS NON CORE | Summary: Positive regulation of LDL clearance; non-core (participant term is core). Reason: Positive regulation of LDL particle clearance is true and consistent with core function, but the participant term LDL particle clearance (GO:0034383) already captures the core role; retained as non-core to avoid a regulator/participant duplication. |
| GO:1905602 positive regulation of receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:12417523 Molecular mechanisms of autosomal recessive hypercholesterol... | ACCEPT | Summary: Positive regulation of RME in cholesterol transport; core. Reason: LDLRAP1 is required for and promotes receptor-mediated endocytosis in cholesterol transport; specific and central to its physiology. Core. |
| GO:1905602 positive regulation of receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:12464675 Restoration of LDL receptor function in cells from patients ... | ACCEPT | Summary: Positive regulation of RME in cholesterol transport; core. Reason: LDLRAP1 is required for and promotes receptor-mediated endocytosis in cholesterol transport; specific and central to its physiology. Core. |
| GO:1905602 positive regulation of receptor-mediated endocytosis involved in cholesterol transport | IMP PMID:15166224 The modular adaptor protein ARH is required for low density ... | ACCEPT | Summary: Positive regulation of RME in cholesterol transport; core. Reason: LDLRAP1 is required for and promotes receptor-mediated endocytosis in cholesterol transport; specific and central to its physiology. Core. |
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