ANG encodes angiogenin/RNase 5, a secreted RNase A-family endoribonuclease. Its core activity is regulated RNA cleavage, especially ribosome-activated cleavage of mature cytoplasmic tRNAs under stress to generate tiRNA/tsRNA halves, together with nucleolar stimulation of rRNA transcription and established proangiogenic functions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004540 RNA nuclease activity | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0005615 obsolete extracellular space | IBA GO_REF:0000033 | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0019731 antibacterial humoral response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kept as non-core. This immune/antimicrobial IBA annotation may reflect secreted RNase biology, but ANG is better characterized by RNase/stress and angiogenic functions. |
| GO:0045087 innate immune response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kept as non-core. Recent evidence supports ANG-derived tsRNAs in innate immune/inflammasome regulation, but this is context-specific. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated **5′ tsRNAs** are anti-inflammatory effectors that suppress **NLRP3 inflammasome** activation and pyroptosis by promoting **DDX3X recruitment into SGs**, reducing DDX3X-NLRP3 interaction. |
| GO:0050830 defense response to Gram-positive bacterium | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kept as non-core. This immune/antimicrobial IBA annotation may reflect secreted RNase biology, but ANG is better characterized by RNase/stress and angiogenic functions. |
| GO:0061844 antimicrobial humoral immune response mediated by antimicrobial peptide | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Kept as non-core. This immune/antimicrobial IBA annotation may reflect secreted RNase biology, but ANG is better characterized by RNase/stress and angiogenic functions. |
| GO:0001525 angiogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Generic nucleic acid binding does not describe the catalytic RNA-cleavage function. |
| GO:0004540 RNA nuclease activity | IEA GO_REF:0000117 | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0010494 cytoplasmic stress granule | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0005515 protein binding | IPI PMID:10413501 Superadditive and subadditive effects of "hot spot" mutation... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:15737636 Alpha-actinin-2, a cytoskeletal protein, binds to angiogenin... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:17991437 Identification and characterization of follistatin as a nove... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:24457100 Angiogenin interacts with the plasminogen activation system ... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:28777577 Proteomic Analysis of Human Angiogenin Interactions Reveals ... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005730 nucleolus | IDA GO_REF:0000052 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0004521 RNA endonuclease activity | TAS Reactome:R-HSA-9708327 | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0007165 signal transduction | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Broad signaling is less informative than receptor ligand, angiogenesis, and RNase/stress-response terms. |
| GO:0048018 receptor ligand activity | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | KEEP AS NON CORE | Summary: Supported but non-core. Receptor-mediated signaling or uptake is relevant to ANG trafficking and extracellular activity, but not the central RNase mechanism. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0004540 RNA nuclease activity | IDA PMID:23047679 Structural and molecular insights into the mechanism of acti... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0005615 obsolete extracellular space | IDA PMID:23047679 Structural and molecular insights into the mechanism of acti... | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IDA PMID:23047679 Structural and molecular insights into the mechanism of acti... | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005737 cytoplasm | IDA PMID:23047679 Structural and molecular insights into the mechanism of acti... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Prefer specific cytosol, stress granule, nuclear, nucleolar, and extracellular localization terms. |
| GO:0034063 stress granule assembly | IDA PMID:23047679 Structural and molecular insights into the mechanism of acti... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:27518564 Angiogenin Promotes Hematopoietic Regeneration by Dichotomou... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:32510170 Myeloid cells protect intestinal epithelial barrier integrit... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:38718836 Structural mechanism of angiogenin activation by the ribosom... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0009303 rRNA transcription | IDA PMID:27518564 Angiogenin Promotes Hematopoietic Regeneration by Dichotomou... | ACCEPT | Summary: Correct. In nucleoli, ANG promotes rRNA transcription and ribosome biogenesis under growth conditions. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0009303 rRNA transcription | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | ACCEPT | Summary: Correct. In nucleoli, ANG promotes rRNA transcription and ribosome biogenesis under growth conditions. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0009303 rRNA transcription | IDA PMID:32510170 Myeloid cells protect intestinal epithelial barrier integrit... | ACCEPT | Summary: Correct. In nucleoli, ANG promotes rRNA transcription and ribosome biogenesis under growth conditions. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0010494 cytoplasmic stress granule | IDA PMID:27518564 Angiogenin Promotes Hematopoietic Regeneration by Dichotomou... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0010494 cytoplasmic stress granule | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:27518564 Angiogenin Promotes Hematopoietic Regeneration by Dichotomou... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:29100074 Plexin-B2 Mediates Physiologic and Pathologic Functions of A... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:32510170 Myeloid cells protect intestinal epithelial barrier integrit... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:38718836 Structural mechanism of angiogenin activation by the ribosom... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0043022 ribosome binding | IDA PMID:38718836 Structural mechanism of angiogenin activation by the ribosom... | ACCEPT | Summary: Correct and informative. Ribosome binding activates ANG and positions tRNA substrate for efficient anticodon-loop cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A key unresolved question in the field has been why ANG is a weak RNase as a free protein yet is biologically potent in cells. Loveland et al. (bioRxiv, posted 2023-12; version/availability in 2024) provide structural and biochemical evidence that the **cytosolic 80S ribosome is the activator and specificity factor for ANG**. |
| GO:0071425 hematopoietic stem cell proliferation | IDA PMID:27518564 Angiogenin Promotes Hematopoietic Regeneration by Dichotomou... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0004540 RNA nuclease activity | IDA PMID:3289612 Base cleavage specificity of angiogenin with Saccharomyces c... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:19332886 Angiogenin cleaves tRNA and promotes stress-induced translat... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:20129916 Angiogenin-induced tRNA-derived stress-induced RNAs promote ... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:21855800 Angiogenin-induced tRNA fragments inhibit translation initia... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:31582561 Angiogenin generates specific stress-induced tRNA halves and... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:19332886 Angiogenin cleaves tRNA and promotes stress-induced translat... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:20129916 Angiogenin-induced tRNA-derived stress-induced RNAs promote ... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:21855800 Angiogenin-induced tRNA fragments inhibit translation initia... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0032055 negative regulation of translation in response to stress | IDA PMID:31582561 Angiogenin generates specific stress-induced tRNA halves and... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0034063 stress granule assembly | IDA PMID:20129916 Angiogenin-induced tRNA-derived stress-induced RNAs promote ... | ACCEPT | Summary: Correct. ANG-derived tiRNAs/tsRNAs repress translation and participate in stress granule-linked stress responses. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported as a non-core survival/stress-response outcome of ANG-derived tiRNAs rather than a direct molecular function. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG-generated tiRNAs/tsRNAs repress protein synthesis and help organize the stress response. |
| GO:0001525 angiogenesis | IDA PMID:3470787 Human placental ribonuclease inhibitor abolishes both angiog... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0004540 RNA nuclease activity | IDA PMID:11919285 Diversifying selection of the tumor-growth promoter angiogen... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:3470787 Human placental ribonuclease inhibitor abolishes both angiog... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004549 tRNA-specific ribonuclease activity | IDA PMID:29748193 Human angiogenin is a potent cytotoxin in the absence of rib... | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0005615 obsolete extracellular space | IDA PMID:29748193 Human angiogenin is a potent cytotoxin in the absence of rib... | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IDA PMID:23843625 Ribonuclease/angiogenin inhibitor 1 regulates stress-induced... | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005737 cytoplasm | IDA PMID:23843625 Ribonuclease/angiogenin inhibitor 1 regulates stress-induced... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Prefer specific cytosol, stress granule, nuclear, nucleolar, and extracellular localization terms. |
| GO:0030139 endocytic vesicle | IDA PMID:29748193 Human angiogenin is a potent cytotoxin in the absence of rib... | KEEP AS NON CORE | Summary: Supported but non-core. Receptor-mediated signaling or uptake is relevant to ANG trafficking and extracellular activity, but not the central RNase mechanism. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0004540 RNA nuclease activity | IDA PMID:2459697 Mutagenesis of aspartic acid-116 enhances the ribonucleolyti... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:3122207 Ribonucleolytic activity of angiogenin: essential histidine,... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:8159680 Role of glutamine-117 in the ribonucleolytic activity of hum... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:8570639 A combined kinetic and modeling study of the catalytic cente... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:8622921 The C-terminal region of human angiogenin has a dual role in... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0001525 angiogenesis | IDA PMID:4074709 Isolation and characterization of angiogenin, an angiogenic ... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0023052 signaling | IDA PMID:2457905 Angiogenin activates endothelial cell phospholipase C. | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Broad signaling is less informative than receptor ligand, angiogenesis, and RNase/stress-response terms. |
| GO:0016078 tRNA decay | TAS Reactome:R-HSA-9708296 | ACCEPT | Summary: Correct and core. ANG cleaves mature cytoplasmic tRNAs in the anticodon loop to generate tiRNA/tsRNA halves. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md A central, repeatedly supported substrate in stress biology is **mature cytoplasmic tRNA**, cleaved **within the anticodon loop** to yield **5′ and 3′ tRNA halves** (often called **tiRNAs/tsRNAs**), typically ~**30–40 nt**. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9708327 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-5692437 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IDA PMID:25372031 Computational and functional characterization of Angiogenin ... | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0042803 protein homodimerization activity | IDA PMID:25372031 Computational and functional characterization of Angiogenin ... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001525 angiogenesis | IDA PMID:8448182 Characterization and sequencing of rabbit, pig and mouse ang... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001556 oocyte maturation | NAS PMID:11438326 Concentrations of angiogenic factors in follicular fluid and... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001666 response to hypoxia | IDA PMID:10999833 Evidence for the presence of angiogenin in human follicular ... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0009725 response to hormone | IDA PMID:10999833 Evidence for the presence of angiogenin in human follicular ... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0030426 growth cone | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0042277 peptide binding | IDA PMID:11782452 Antiplasmin activity of a peptide that binds to the receptor... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Peptide binding is too generic for ANG-specific curation. |
| GO:0043025 neuronal cell body | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001525 angiogenesis | IMP PMID:17125737 Angiogenin-induced protein kinase B/Akt activation is necess... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0016477 cell migration | IMP PMID:17125737 Angiogenin-induced protein kinase B/Akt activation is necess... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0042327 positive regulation of phosphorylation | IDA PMID:17125737 Angiogenin-induced protein kinase B/Akt activation is necess... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0032311 angiogenin-PRI complex | IDA PMID:3470787 Human placental ribonuclease inhibitor abolishes both angiog... | KEEP AS NON CORE | Summary: Supported but non-core. The angiogenin-PRI/RNH1 complex is a specific inhibitory regulatory complex for ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **RNH1/RI** is the principal intracellular inhibitor that restrains ANG activity and trafficking. |
| GO:0032311 angiogenin-PRI complex | IPI PMID:3470787 Human placental ribonuclease inhibitor abolishes both angiog... | KEEP AS NON CORE | Summary: Supported but non-core. The angiogenin-PRI/RNH1 complex is a specific inhibitory regulatory complex for ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **RNH1/RI** is the principal intracellular inhibitor that restrains ANG activity and trafficking. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:9707554 Neomycin inhibits angiogenin-induced angiogenesis. | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0005730 nucleolus | ISS GO_REF:0000024 | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0030041 actin filament polymerization | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0050714 positive regulation of protein secretion | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001525 angiogenesis | IMP PMID:2479414 Site-directed mutagenesis of histidine-13 and histidine-114 ... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0003677 DNA binding | IC PMID:10649442 Human angiogenin is rapidly translocated to the nucleus of h... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: DNA binding is too generic relative to nucleolar rRNA-transcription and RNase annotations. |
| GO:0004519 endonuclease activity | TAS PMID:10103013 Expression of receptors for human angiogenin in vascular smo... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Use RNA endonuclease and tRNA-specific ribonuclease terms rather than generic endonuclease activity. |
| GO:0004540 RNA nuclease activity | IDA PMID:2424496 Characteristic ribonucleolytic activity of human angiogenin. | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0004540 RNA nuclease activity | IDA PMID:2730651 Characterization of ribonucleolytic activity of angiogenin t... | ACCEPT | Summary: Correct. ANG is an RNase A-family RNA endoribonuclease that catalyzes RNA backbone cleavage. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md **Reaction class**: ANG is an RNase A-family **phosphodiesterase** (EC 3.1.27.- in UniProt context), catalyzing RNA backbone cleavage via the canonical RNase A catalytic architecture. |
| GO:0005507 copper ion binding | IDA PMID:9245697 Interaction of human angiogenin with copper modulates angiog... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0005515 protein binding | IPI PMID:2742853 Binding of placental ribonuclease inhibitor to the active si... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005515 protein binding | IPI PMID:3470787 Human placental ribonuclease inhibitor abolishes both angiog... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Retain interaction evidence conceptually, but replace generic protein binding with specific binding, complex, receptor, ribosome, and RNase annotations. |
| GO:0005604 basement membrane | IDA PMID:15166501 Angiogenin distribution in human term placenta, and expressi... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0005615 obsolete extracellular space | IDA PMID:3663649 Isolation of angiogenin from normal human plasma. | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IDA PMID:10649442 Human angiogenin is rapidly translocated to the nucleus of h... | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0007154 cell communication | NAS PMID:10103013 Expression of receptors for human angiogenin in vascular smo... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Generic cell communication should not be used when specific ANG functions are available. |
| GO:0008201 heparin binding | IDA PMID:10103013 Expression of receptors for human angiogenin in vascular smo... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0019843 rRNA binding | TAS PMID:2457905 Angiogenin activates endothelial cell phospholipase C. | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0042592 homeostatic process | NAS PMID:15166501 Angiogenin distribution in human term placenta, and expressi... | MARK AS OVER ANNOTATED | Summary: Correct or plausible but too broad for useful ANG annotation. Reason: Homeostatic process is not informative for ANG curation. |
| GO:0050714 positive regulation of protein secretion | IDA PMID:2646638 Angiogenin stimulates endothelial cell prostacyclin secretio... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001938 positive regulation of endothelial cell proliferation | IDA PMID:9122172 A putative angiogenin receptor in angiogenin-responsive huma... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0003779 actin binding | IDA PMID:7679494 Actin is a binding protein for angiogenin. | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0005102 signaling receptor binding | IDA PMID:9122172 A putative angiogenin receptor in angiogenin-responsive huma... | KEEP AS NON CORE | Summary: Supported but non-core. Receptor-mediated signaling or uptake is relevant to ANG trafficking and extracellular activity, but not the central RNase mechanism. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0048662 negative regulation of smooth muscle cell proliferation | IDA PMID:10103013 Expression of receptors for human angiogenin in vascular smo... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001525 angiogenesis | TAS PMID:16567967 Influence of angiogenin on the growth of A375 human melanoma... | ACCEPT | Summary: Correct. ANG is a canonical proangiogenic factor, with angiogenic outcomes linked to its secreted/nuclear RNase biology. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001541 ovarian follicle development | NAS PMID:12770725 Production of vascular endothelial growth factor and angioge... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0001666 response to hypoxia | NAS PMID:15776477 Angiogenin is up-regulated in the nucleus and cytoplasm in h... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001666 response to hypoxia | IDA PMID:15979542 Hypoxia up-regulated angiogenin and down-regulated vascular ... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001666 response to hypoxia | IDA PMID:16490744 Hypoxic conditions stimulate the production of angiogenin an... | KEEP AS NON CORE | Summary: Supported as a non-core angiogenic or vascular cell-response context downstream of ANG activity. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG remains a canonical **proangiogenic** factor and tumor-associated RNase. |
| GO:0001890 placenta development | NAS PMID:11984825 Expression and localization of angiogenin in placenta: enhan... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0003779 actin binding | IDA PMID:11782452 Antiplasmin activity of a peptide that binds to the receptor... | KEEP AS NON CORE | Summary: Supported or plausible for ANG, but non-core relative to regulated RNase activity, tRNA cleavage, nucleolar rRNA transcription, and angiogenesis. This context-specific annotation should not drive the core function summary. |
| GO:0005615 obsolete extracellular space | IDA PMID:16461950 Assessment of some tools for the characterization of the hum... | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005615 obsolete extracellular space | IDA PMID:16490744 Hypoxic conditions stimulate the production of angiogenin an... | MODIFY | Summary: The biological localization is extracellular, but this GO term is obsolete and should be replaced by extracellular region. Reason: GO:0005615 is obsolete; GO:0005576 extracellular region is the current supported localization term. Proposed replacements: extracellular region Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0005634 nucleus | IDA PMID:15735021 Angiogenin is translocated to the nucleus of HeLa cells and ... | ACCEPT | Summary: Correct. ANG has compartment-dependent function across extracellular, nuclear/nucleolar, and cytosolic stress-response pools. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
| GO:0009303 rRNA transcription | IMP PMID:15735021 Angiogenin is translocated to the nucleus of HeLa cells and ... | ACCEPT | Summary: Correct. In nucleoli, ANG promotes rRNA transcription and ribosome biogenesis under growth conditions. Supporting Evidence: file:human/ANG/ANG-deep-research-falcon.md ANG is secreted and can be re-internalized by cells through receptor-mediated uptake; once internalized, its localization determines function. **Nucleolar ANG** promotes rRNA transcription and ribosome biogenesis, whereas **cytosolic ANG** under stress cleaves tRNAs and participates in translational arrest/SG programs. |
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Download this section (compressed HTML)Q: Which ANG functions require ribosome-activated tRNA cleavage versus nucleolar rRNA transcription in specific human cell types?
Q: Which receptor-mediated uptake routes determine ANG partitioning between extracellular signaling, cytosolic stress responses, and nucleolar growth programs?
Experiment: Use ANG variants defective in ribosome association or catalytic residues, then compare tRNA-half production, translation rates, and stress granule assembly after oxidative stress.
Hypothesis: Ribosome binding is required for stress-induced ANG tRNA cleavage and translation repression in cells.
Experiment: Rescue ANG-depleted endothelial cells with localization-biased ANG variants and measure rRNA transcription, endothelial proliferation/migration, and stress-induced tiRNA production.
Hypothesis: ANG angiogenic outputs are separable from cytosolic stress-response outputs by altering nuclear localization or receptor-mediated uptake.
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