ABL1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004713 protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: ABL1 is definitively a protein tyrosine kinase (EC 2.7.10.2). This is its primary enzymatic function. Reason: Core molecular function of ABL1. Extensively validated by crystal structures, kinase assays, and identification of numerous substrates. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity
GO:0005886 plasma membrane	IBA GO_REF:0000033	ACCEPT	Summary: ABL1 localizes to the plasma membrane through interactions with membrane-associated proteins and actin cytoskeleton. Reason: ABL1 localizes to membrane ruffles and the cell cortex where it regulates actin remodeling. The myristoylated isoform IB can associate with membranes. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 localizes to plasma membrane via interactions with membrane-associated proteins and actin cytoskeleton]
GO:0007229 integrin-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: ABL1 participates in integrin-mediated signaling, regulating cell adhesion and migration through phosphorylation of focal adhesion components. Reason: ABL1 is activated downstream of integrin engagement and phosphorylates key adhesion regulators including CRK, CRKL, and paxillin. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation
GO:0010595 positive regulation of endothelial cell migration	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ABL1 promotes endothelial cell migration through its regulation of actin dynamics and integrin signaling. Reason: While ABL1 does regulate cell migration through actin remodeling, this is a cell-type-specific phenotypic outcome rather than a core evolved function. Supporting Evidence: PMID:24863063 Cell migration assay
GO:0007173 epidermal growth factor receptor signaling pathway	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: ABL1 modulates EGFR signaling by regulating receptor endocytosis through phosphorylation of CBL. Reason: ABL1 regulates EGFR endocytosis via CBL phosphorylation. However, this represents one of many RTK signaling pathways ABL1 can modulate, not a core evolved function. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 regulates EGFR endocytosis via CBL phosphorylation]
GO:0000166 nucleotide binding	IEA GO_REF:0000043	MODIFY	Summary: As a kinase, ABL1 binds ATP. This is a necessary attribute of its kinase function but is too general. Reason: ABL1 binds ATP as part of its kinase catalytic mechanism. The more specific term GO:0005524 (ATP binding) is more informative. Proposed replacements: ATP binding
GO:0001784 phosphotyrosine residue binding	IEA GO_REF:0000117	ACCEPT	Summary: The SH2 domain of ABL1 binds phosphotyrosine-containing sequences, enabling interactions with activated signaling proteins. Reason: The ABL1 SH2 domain binds phosphotyrosine motifs. This is a core regulatory function enabling ABL1 to respond to tyrosine kinase signaling. Supporting Evidence: PMID:12384576 Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain
GO:0002252 immune effector process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ABL1 has roles in T cell signaling and immune cell function, but this term is very broad and non-specific. Reason: While ABL1 does function in T cell migration and differentiation, this extremely broad term provides little functional insight.
GO:0002429 immune response-activating cell surface receptor signaling pathway	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ABL1 can be activated downstream of immune receptors but this is a secondary function. Reason: ABL1 functions downstream of BCR and other immune receptors but this is not a specific evolved function. The annotation is too broad.
GO:0003677 DNA binding	IEA GO_REF:0000043	ACCEPT	Summary: ABL1 has a C-terminal DNA binding domain that preferentially binds distorted DNA structures including four-way junctions and bubble DNA. Reason: ABL1 has direct DNA binding activity through its C-terminal region. This is relevant to its nuclear DNA damage response functions. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 has a C-terminal DNA binding domain]
GO:0003785 actin monomer binding	IEA GO_REF:0000117	ACCEPT	Summary: ABL1 contains an F-actin binding region in its C-terminus that enables direct interaction with actin. Reason: The C-terminal region of ABL1 contains an F-actin binding domain. This is a core structural feature enabling cytoskeletal regulatory functions. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 contains F-actin binding region in C-terminus]
GO:0004672 protein kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 is a protein kinase, but this term is less specific than the tyrosine kinase annotation. Reason: While ABL1 is primarily a tyrosine kinase, this general term is acceptable as a parent term.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: This is the core molecular function of ABL1 as a non-receptor tyrosine kinase. Reason: Core function supported by multiple evidence sources. ABL1 phosphorylates numerous substrates on tyrosine residues.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 is definitively a non-receptor (non-membrane spanning) tyrosine kinase. Reason: ABL1 belongs to the ABL subfamily of non-receptor tyrosine kinases. Unlike RTKs, it lacks a transmembrane domain. Supporting Evidence: PMID:20841568 Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 binds ATP in its kinase domain active site as required for phosphotransfer catalysis. Reason: ATP binding is essential for ABL1 kinase activity. Crystal structures show ATP analog binding in the kinase domain. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 localizes to the nucleus where it functions in DNA damage response and transcriptional regulation. Reason: ABL1 contains three NLS sequences enabling nuclear import. Nuclear localization is essential for its DNA damage response function. Supporting Evidence: PMID:9168116 Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation
GO:0005739 mitochondrion	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: ABL1 can translocate to mitochondria in response to oxidative stress where it mediates mitochondrial dysfunction. Reason: Mitochondrial localization occurs under oxidative stress. This is a stress-induced localization rather than constitutive. Supporting Evidence: PMID:24522549 Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease
GO:0005829 cytosol	IEA GO_REF:0000117	ACCEPT	Summary: ABL1 is predominantly cytosolic under basal conditions, regulated by 14-3-3 protein sequestration. Reason: Cytosolic localization is well-established. ABL1 is sequestered in cytoplasm through 14-3-3 protein interactions. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 is predominantly cytosolic, regulated by 14-3-3 protein sequestration]
GO:0005856 cytoskeleton	IEA GO_REF:0000044	ACCEPT	Summary: ABL1 associates with the cytoskeleton through its F-actin binding domain and regulates cytoskeletal dynamics. Reason: ABL1 directly binds F-actin through its C-terminal actin binding domain. This is a core localization for cytoskeletal regulatory function. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 contains F-actin binding domain enabling cytoskeletal localization]
GO:0006281 DNA repair	IEA GO_REF:0000043	ACCEPT	Summary: ABL1 participates in DNA repair by phosphorylating repair proteins RAD51, RAD52, and WRN in response to DNA damage. Reason: ABL1 phosphorylates multiple DNA repair proteins. This is a core nuclear function of ABL1 in the DNA damage response pathway. Supporting Evidence: PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA damage
GO:0006897 endocytosis	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: ABL1 regulates receptor endocytosis, particularly EGFR internalization, through phosphorylation of CBL. Reason: ABL1 regulates endocytosis of EGFR and other receptors. However, this is one of many downstream effects of ABL1 kinase activity. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 regulates receptor endocytosis through CBL phosphorylation]
GO:0006909 phagocytosis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 participates in Fc-gamma receptor signaling during phagocytosis. Reason: ABL1 is placed in Fc-gamma receptor-mediated phagocytosis pathway. This is a cell-type-specific function in immune cells, not a core evolved function.
GO:0006914 autophagy	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: ABL1 has been implicated in autophagy regulation, but the evidence for direct autophagy function is limited. Reason: While ABL1 regulates lysosomal trafficking, the annotation of ABL1 to the general autophagy process is over-annotation. ABL1's primary role is in lysosomal function, not autophagy per se. The deep research found no evidence that autophagy is a core evolved function of ABL1.
GO:0006915 apoptotic process	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 promotes apoptosis in response to DNA damage through phosphorylation of TP73 and CASP9. Reason: Nuclear ABL1 activates proapoptotic pathways following severe DNA damage. ABL1 phosphorylates TP73 and CASP9 on Tyr-153. Supporting Evidence: PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase
GO:0006974 DNA damage response	IEA GO_REF:0000043	ACCEPT	Summary: ABL1 is a key mediator of the DNA damage response, activated by ATM following DNA double-strand breaks. Reason: DNA damage response is a core nuclear function of ABL1. ATM phosphorylates ABL1 following DNA damage, activating its nuclear functions. Supporting Evidence: PMID:9168116 Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation
GO:0007155 cell adhesion	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: ABL1 regulates cell adhesion through phosphorylation of adhesion signaling components including CRK, CRKL, and paxillin. Reason: ABL1 regulates cell adhesion through its cytoskeletal regulatory functions, but this is a phenotypic outcome rather than a core molecular function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity
GO:0007204 positive regulation of cytosolic calcium ion concentration	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 has been shown to positively regulate cytosolic calcium through effects on endothelial barrier function. Reason: ABL1 regulates calcium signaling in endothelial cells. This is a downstream effect in specific cell contexts, not a core evolved function. Supporting Evidence: PMID:24367707 Abl family kinases regulate endothelial barrier function in vitro and in mice
GO:0010468 regulation of gene expression	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 regulates gene expression through phosphorylation of transcriptional regulators and RNA polymerase II CTD. Reason: Nuclear ABL1 can phosphorylate RNAPII CTD and interact with transcriptional regulators. However, this is a very broad term.
GO:0010506 regulation of autophagy	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ABL1 may indirectly regulate autophagy through effects on lysosomal function. Reason: Similar to GO:0006914, this is over-annotation. ABL1's primary role is in lysosomal trafficking and acidification, not autophagy regulation per se.
GO:0010557 positive regulation of macromolecule biosynthetic process	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: This is an extremely broad term with unclear relevance to ABL1 core function. Reason: This term is too general to provide meaningful functional information about ABL1. No specific evidence supports this as a core function.
GO:0010595 positive regulation of endothelial cell migration	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Duplicate of IBA annotation above. Reason: Same as IBA annotation - cell-type-specific outcome of cytoskeletal regulation.
GO:0016301 kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 has kinase activity, but this very general term is subsumed by more specific tyrosine kinase annotations. Reason: Correct but very general. The more specific protein tyrosine kinase activity annotations are more informative.
GO:0016740 transferase activity	IEA GO_REF:0000043	MODIFY	Summary: As a kinase, ABL1 has transferase activity (phosphotransfer), but this is extremely general. Reason: This term is too general. ABL1's specific transferase activity is protein tyrosine kinase activity. Proposed replacements: protein tyrosine kinase activity
GO:0030100 regulation of endocytosis	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 regulates endocytosis of receptors through CBL and other mechanisms. Reason: ABL1 regulates EGFR and other receptor endocytosis. However, this is a downstream regulatory function, not core. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 regulates receptor endocytosis]
GO:0031965 nuclear membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: The myristoylated isoform IB can associate with nuclear membrane. Reason: UniProt indicates isoform IB localizes to nuclear membrane via lipid anchor. This is isoform-specific.
GO:0032956 regulation of actin cytoskeleton organization	IEA GO_REF:0000117	ACCEPT	Summary: ABL1 is a key regulator of actin cytoskeleton organization through phosphorylation of WAVE complex, cortactin, and other actin regulators. Reason: This is a core function of cytoplasmic ABL1. ABL1 phosphorylates WAVE proteins, cortactin, and other actin regulators. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 phosphorylates WAVE proteins, cortactin, and other actin regulators]
GO:0045595 regulation of cell differentiation	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 has roles in cell differentiation, particularly in hematopoietic and T cell differentiation. Reason: ABL1 regulates T cell differentiation in TBX21-dependent manner. This is a developmental/cell-type-specific function.
GO:0045785 positive regulation of cell adhesion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 can positively regulate cell adhesion through focal adhesion signaling. Reason: ABL1 regulates adhesion signaling but the direction is context-dependent. This is a downstream phenotypic effect.
GO:0046872 metal ion binding	IEA GO_REF:0000043	MODIFY	Summary: ABL1 binds magnesium and manganese ions as cofactors for kinase activity. Reason: ABL1 requires divalent cations for kinase activity. More specific terms GO:0000287 (magnesium ion binding) are preferable. Proposed replacements: magnesium ion binding
GO:0048008 platelet-derived growth factor receptor signaling pathway	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 is activated downstream of PDGFR and regulates PDGF-induced responses. Reason: ABL1 involvement in PDGFRB signaling is one of several RTK pathways ABL1 modulates, not a core function. Supporting Evidence: PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin
GO:0051726 regulation of cell cycle	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 is involved in cell cycle regulation through DNA damage checkpoint signaling. Reason: ABL1 participates in cell cycle regulation through DNA damage checkpoints. Not a core function.
GO:1901701 cellular response to oxygen-containing compound	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ABL1 responds to oxidative stress and reactive oxygen species. Reason: ABL1 is activated by oxidative stress and translocates to mitochondria. This is a stress response, not core evolved function.
GO:1902531 regulation of intracellular signal transduction	IEA GO_REF:0000117	ACCEPT	Summary: ABL1 regulates multiple intracellular signaling cascades. Reason: This appropriately captures ABL1's role as a signaling hub integrating multiple pathways.
GO:0005515 protein binding	IPI PMID:10849448 Transformation of myeloid leukemia cells to cytokine indepen...	MARK AS OVER ANNOTATED	Summary: Generic protein binding annotation from interaction with HCK. Reason: Protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:10849448 Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck.
GO:0005515 protein binding	IPI PMID:10970852 Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles a...	MARK AS OVER ANNOTATED	Summary: Interaction with WAVE/SCAR complex components. Reason: Protein binding is uninformative. WAVE-1 interaction is functionally important but generic binding term provides no insight. Supporting Evidence: PMID:10970852 Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold.
GO:0005515 protein binding	IPI PMID:11374898 Cloning, mapping, and characterization of the human sorbin a...	MARK AS OVER ANNOTATED	Summary: Interaction with SORBS1 during insulin signaling. Reason: Generic protein binding is uninformative per GO curation guidelines. Supporting Evidence: PMID:11374898 Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.
GO:0005515 protein binding	IPI PMID:11375976 Telomeric protein Pin2/TRF1 as an important ATM target in re...	MARK AS OVER ANNOTATED	Summary: Interaction with telomeric protein TRF1/Pin2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:11375976 2001 May 25. Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks.
GO:0005515 protein binding	IPI PMID:11418237 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1...	MARK AS OVER ANNOTATED	Summary: Interaction with NAP1BP. Reason: Generic protein binding annotation is uninformative. Supporting Evidence: PMID:11418237 Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.
GO:0005515 protein binding	IPI PMID:11971963 c-Abl tyrosine kinase regulates the human Rad9 checkpoint pr...	MARK AS OVER ANNOTATED	Summary: Interaction with RAD9 checkpoint protein. Reason: Generic protein binding is uninformative per GO curation guidelines. The functional context (DNA damage checkpoint) is captured by other annotations. Supporting Evidence: PMID:11971963 c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage.
GO:0005515 protein binding	IPI PMID:12384576 Structure of a regulatory complex involving the Abl SH3 doma...	MARK AS OVER ANNOTATED	Summary: Structural study of ABL SH3-CRK interaction. Reason: PMID:12384576 describes specific SH3-SH2 interactions with CRK. Generic protein binding is uninformative. Supporting Evidence: PMID:12384576 Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
GO:0005515 protein binding	IPI PMID:15448168 Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine...	MARK AS OVER ANNOTATED	Summary: Interaction with DNA topoisomerase I. Reason: ABL1 phosphorylates TOP1. Generic binding is uninformative. Supporting Evidence: PMID:15448168 2004 Sep 24. Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase confers camptothecin sensitivity.
GO:0005515 protein binding	IPI PMID:15696159 JNK phosphorylation of 14-3-3 proteins regulates nuclear tar...	MARK AS OVER ANNOTATED	Summary: Interaction with 14-3-3 proteins. Reason: ABL1 binds 14-3-3 proteins via phospho-Thr-735 for cytoplasmic sequestration. Generic binding is uninformative. Supporting Evidence: PMID:15696159 JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage.
GO:0005515 protein binding	IPI PMID:15886098 RIN1 is an ABL tyrosine kinase activator and a regulator of ...	MARK AS OVER ANNOTATED	Summary: Interaction with RIN1. Reason: RIN1 is an ABL1 activator binding SH2 and SH3 domains. Generic protein binding is uninformative. Supporting Evidence: PMID:15886098 RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration.
GO:0005515 protein binding	IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece...	MARK AS OVER ANNOTATED	Summary: ErbB receptor interaction study. Reason: Protein microarray study. Generic binding uninformative. Supporting Evidence: PMID:16273093 A quantitative protein interaction network for the ErbB receptors using protein microarrays.
GO:0005515 protein binding	IPI PMID:16397227 Physical and functional interaction between hMSH5 and c-Abl.	MARK AS OVER ANNOTATED	Summary: Interaction with MSH5. Reason: ABL1-MSH5 interaction relates to DNA damage response. Generic binding is uninformative. Supporting Evidence: PMID:16397227 Physical and functional interaction between hMSH5 and c-Abl.
GO:0005515 protein binding	IPI PMID:16443220 Characterization of p87C3G, a novel, truncated C3G isoform t...	MARK AS OVER ANNOTATED	Summary: Interaction with C3G isoform. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:16443220 2006 Jan 27. Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl.
GO:0005515 protein binding	IPI PMID:16831423 Abl kinase interacts with and phosphorylates vinexin.	MARK AS OVER ANNOTATED	Summary: Interaction with vinexin. Reason: ABL1 phosphorylates vinexin. Generic binding is uninformative. Supporting Evidence: PMID:16831423 Epub 2006 Jul 5. Abl kinase interacts with and phosphorylates vinexin.
GO:0005515 protein binding	IPI PMID:16888623 MUC1 oncoprotein blocks nuclear targeting of c-Abl in the ap...	MARK AS OVER ANNOTATED	Summary: Interaction with MUC1. Reason: MUC1 blocks ABL1 nuclear targeting. Generic binding is uninformative. Supporting Evidence: PMID:16888623 Aug 3. MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage.
GO:0005515 protein binding	IPI PMID:17101133 NESH (Abi-3) is present in the Abi/WAVE complex but does not...	MARK AS OVER ANNOTATED	Summary: NESH/Abi-3 interaction study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17101133 Epub 2006 Nov 7. NESH (Abi-3) is present in the Abi/WAVE complex but does not promote c-Abl-mediated phosphorylation.
GO:0005515 protein binding	IPI PMID:17112510 Consequences of Shb and c-Abl interactions for cell death in...	MARK AS OVER ANNOTATED	Summary: Interaction with Shb adapter protein. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17112510 Epub 2006 Oct 24. Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli.
GO:0005515 protein binding	IPI PMID:17318191 Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia ...	MARK AS OVER ANNOTATED	Summary: Beta-catenin interaction (BCR-ABL context). Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17318191 Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation.
GO:0005515 protein binding	IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote...	MARK AS OVER ANNOTATED	Summary: SH3 domain interaction screen. Reason: Generic protein binding from high-throughput screen is uninformative. Supporting Evidence: PMID:17474147 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
GO:0005515 protein binding	IPI PMID:17626041 Cockayne syndrome protein B interacts with and is phosphoryl...	MARK AS OVER ANNOTATED	Summary: Interaction with Cockayne syndrome protein B (ERCC6). Reason: ABL1 phosphorylates CSB/ERCC6. Generic binding is uninformative. Supporting Evidence: PMID:17626041 Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
GO:0005515 protein binding	IPI PMID:18328268 Allosteric inhibition of the nonMyristoylated c-Abl tyrosine...	MARK AS OVER ANNOTATED	Summary: Abi1 phosphopeptide allosteric inhibition study. Reason: Describes specific allosteric regulation mechanism via Abi1 interaction. Generic binding is uninformative. Supporting Evidence: PMID:18328268 Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1.
GO:0005515 protein binding	IPI PMID:19234221 c-Abl kinase is required for beta 2 integrin-mediated neutro...	MARK AS OVER ANNOTATED	Summary: Beta2 integrin interaction in neutrophils. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19234221 c-Abl kinase is required for beta 2 integrin-mediated neutrophil adhesion.
GO:0005515 protein binding	IPI PMID:19442657 Evidence for a direct involvement of hMSH5 in promoting ioni...	MARK AS OVER ANNOTATED	Summary: MSH5 interaction promoting apoptosis. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19442657 Epub 2009 May 12. Evidence for a direct involvement of hMSH5 in promoting ionizing radiation induced apoptosis.
GO:0005515 protein binding	IPI PMID:19470755 Cdo binds Abl to promote p38alpha/beta mitogen-activated pro...	MARK AS OVER ANNOTATED	Summary: CDO interaction promoting myogenic differentiation. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19470755 May 26. Cdo binds Abl to promote p38alpha/beta mitogen-activated protein kinase activity and myogenic differentiation.
GO:0005515 protein binding	IPI PMID:19914245 c-Abl tyrosine kinase interacts with MAVS and regulates inna...	MARK AS OVER ANNOTATED	Summary: MAVS interaction regulating innate immunity. Reason: ABL1-MAVS interaction relevant to innate immune signaling. Generic binding is uninformative. Supporting Evidence: PMID:19914245 c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response.
GO:0005515 protein binding	IPI PMID:20598684 Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regula...	MARK AS OVER ANNOTATED	Summary: Abi1 phosphorylation study linking to PI3K. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:20598684 Epub 2010 Jun 23. Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cells.
GO:0005515 protein binding	IPI PMID:20697350 The proximal signaling network of the BCR-ABL1 oncogene show...	MARK AS OVER ANNOTATED	Summary: BCR-ABL1 proximal signaling network study. Reason: Large-scale interactome study. Generic binding is uninformative. Supporting Evidence: PMID:20697350 The proximal signaling network of the BCR-ABL1 oncogene shows a modular organization.
GO:0005515 protein binding	IPI PMID:22286129 BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic ...	MARK AS OVER ANNOTATED	Summary: BCR-ABL JAK2-STAT5 uncoupling study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22286129 BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.
GO:0005515 protein binding	IPI PMID:22401567 MutS homologue hMSH5 - role in cisplatin-induced DNA damage ...	MARK AS OVER ANNOTATED	Summary: MSH5 role in cisplatin response. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22401567 MutS homologue hMSH5: role in cisplatin-induced DNA damage response.
GO:0005515 protein binding	IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ...	MARK AS OVER ANNOTATED	Summary: Membrane two-hybrid assay study. Reason: Generic protein binding from screening is uninformative. Supporting Evidence: PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.
GO:0005515 protein binding	IPI PMID:24728074 Enhanced prediction of Src homology 2 (SH2) domain binding p...	MARK AS OVER ANNOTATED	Summary: SH2 binding prediction study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24728074 Epub 2014 Apr 12. Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.
GO:0005515 protein binding	IPI PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2...	MARK AS OVER ANNOTATED	Summary: LRRK1/LRRK2 interaction study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24947832 Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways.
GO:0005515 protein binding	IPI PMID:25036101 Identification of SH3 domain proteins interacting with the c...	MARK AS OVER ANNOTATED	Summary: ADAM10 SH3 domain interaction. Reason: SH3 domain-mediated interaction. Generic binding is uninformative. Supporting Evidence: PMID:25036101 eCollection 2014. Identification of SH3 domain proteins interacting with the cytoplasmic tail of the a disintegrin and metalloprotease 10 (ADAM10).
GO:0005515 protein binding	IPI PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apo...	MARK AS OVER ANNOTATED	Summary: TRAIL apoptosis kinase network. Reason: Generic protein binding from network analysis is uninformative. Supporting Evidence: PMID:25852190 Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
GO:0005515 protein binding	IPI PMID:27348587 Activation of tyrosine kinase c-Abl contributes to α-synucle...	MARK AS OVER ANNOTATED	Summary: Alpha-synuclein interaction in neurodegeneration. Reason: ABL1 phosphorylates alpha-synuclein. Generic binding is uninformative. Supporting Evidence: PMID:27348587 Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration.
GO:0005515 protein binding	IPI PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through ...	MARK AS OVER ANNOTATED	Summary: ABL2 and FLT3-ITD study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:28086240 ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	MARK AS OVER ANNOTATED	Summary: Human interactome architecture study. Reason: Large-scale interactome. Generic binding is uninformative. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma...	MARK AS OVER ANNOTATED	Summary: Histone crosslinking mass spec study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:30021884 Epub 2018 Jul 18. Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
GO:0005515 protein binding	IPI PMID:31175292 Structural and functional consequences of the STAT5B(N642H) ...	MARK AS OVER ANNOTATED	Summary: STAT5B driver mutation study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:31175292 Structural and functional consequences of the STAT5B(N642H) driver mutation.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	MARK AS OVER ANNOTATED	Summary: EGFR network in KRAS mutant cells. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Cell-specific interactome remodeling. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell - Endogenous tagging for the cartography of human c...	MARK AS OVER ANNOTATED	Summary: OpenCell endogenous tagging study. Reason: Large-scale study. Generic binding is uninformative. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0005515 protein binding	IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c...	MARK AS OVER ANNOTATED	Summary: 14-3-3 protein chaperone study. Reason: Relevant to ABL1 cytoplasmic sequestration by 14-3-3 proteins. Generic binding is uninformative. Supporting Evidence: PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human cells.
GO:0005515 protein binding	IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu...	MARK AS OVER ANNOTATED	Summary: Phosphomimetic motif interaction screen. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:37219487 2023 May 23. Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.
GO:0005515 protein binding	IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r...	MARK AS OVER ANNOTATED	Summary: Disease mutation interactome rewiring. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:39009827 2024 Jul 15. Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.
GO:0005515 protein binding	IPI PMID:39251607 Systematic identification of post-transcriptional regulatory...	MARK AS OVER ANNOTATED	Summary: Post-transcriptional regulatory module study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:39251607 Systematic identification of post-transcriptional regulatory modules.
GO:0005515 protein binding	IPI PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	MARK AS OVER ANNOTATED	Summary: RIN1 binding study demonstrating activator function. Reason: RIN1 is an ABL1 activator. Generic binding term is uninformative. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0005515 protein binding	IPI PMID:9168117 Interaction between ATM protein and c-Abl in response to DNA...	MARK AS OVER ANNOTATED	Summary: ATM interaction in DNA damage response. Reason: ATM-ABL1 interaction is functionally important for DNA damage response. Generic binding is uninformative. Supporting Evidence: PMID:9168117 Interaction between ATM protein and c-Abl in response to DNA damage.
GO:0005515 protein binding	IPI PMID:9346925 SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste2...	MARK AS OVER ANNOTATED	Summary: HPK1 interaction via SH2/SH3 adapters. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:9346925 SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.
GO:0005515 protein binding	IPI PMID:9593709 Identification of a candidate human spectrin Src homology 3 ...	MARK AS OVER ANNOTATED	Summary: Spectrin SH3 domain interaction. Reason: SH3-mediated interaction with cytoskeleton. Generic binding is uninformative. Supporting Evidence: PMID:9593709 Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton.
GO:0000287 magnesium ion binding	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 requires magnesium as a cofactor for kinase activity. Reason: Divalent cation binding is essential for kinase catalysis. This is a core biochemical requirement.
GO:0001726 ruffle	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 localizes to membrane ruffles where it regulates actin dynamics. Reason: Localization to ruffles is consistent with ABL1's role in actin cytoskeleton remodeling. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 localizes to F-actin-rich membrane ruffles]
GO:0005737 cytoplasm	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 is predominantly cytoplasmic under basal conditions. Reason: Cytoplasmic localization is well-established. ABL1 shuttles between cytoplasm and nucleus.
GO:0007611 learning or memory	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 has been implicated in learning and memory through synaptic functions. Reason: Based on mouse orthologue data. This is a developmental/neurological phenotype, not a core molecular function.
GO:0008306 associative learning	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 has been implicated in associative learning. Reason: Based on mouse orthologue data. This is a behavioral phenotype, not a core molecular function.
GO:0009410 response to xenobiotic stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 responds to xenobiotic stimuli. Reason: This is a stress response phenotype, not a core evolved function.
GO:0014069 postsynaptic density	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 localizes to postsynaptic density in neurons. Reason: Cell-type-specific localization in neurons. Not a core function.
GO:0015629 actin cytoskeleton	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 localizes to and regulates the actin cytoskeleton. Reason: ABL1 directly binds F-actin and regulates actin dynamics. This is a core localization. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 directly binds F-actin through C-terminal region]
GO:0019901 protein kinase binding	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 binds other protein kinases. Reason: ABL1 interacts with multiple protein kinases including SRC family kinases and ATM.
GO:0019904 protein domain specific binding	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 binds proteins through its SH2 and SH3 domains. Reason: SH2 and SH3 domain-mediated interactions are core to ABL1 function and regulation.
GO:0030036 actin cytoskeleton organization	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 organizes the actin cytoskeleton. Reason: This is a core function of cytoplasmic ABL1 through phosphorylation of actin regulatory proteins. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 organizes actin cytoskeleton through phosphorylation of cortactin and other actin regulatory proteins]
GO:0030041 actin filament polymerization	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 regulates actin filament polymerization. Reason: ABL1 promotes actin polymerization through phosphorylation of WAVE complex and other regulators.
GO:0030145 manganese ion binding	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 can use manganese as an alternative divalent cation cofactor. Reason: Like many kinases, ABL1 can use Mn2+ in addition to Mg2+ for catalysis.
GO:0030425 dendrite	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 localizes to dendrites in neurons. Reason: Neuronal cell-type-specific localization. Not a core function.
GO:0030426 growth cone	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 localizes to growth cones where it regulates neurite extension. Reason: Neuronal cell-type-specific localization related to actin dynamics. Not a core function.
GO:0031252 cell leading edge	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 localizes to the cell leading edge during migration. Reason: Localization to the leading edge is consistent with ABL1's role in actin-based cell motility.
GO:0034599 cellular response to oxidative stress	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ABL1 is activated by and responds to oxidative stress. Reason: Oxidative stress response including mitochondrial translocation. This is a stress response, not core function.
GO:0034976 response to endoplasmic reticulum stress	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 responds to ER stress. Reason: ER stress response is a secondary function, not a core evolved function.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 functions in intracellular signal transduction. Reason: ABL1 is a signaling kinase that transduces signals from multiple upstream inputs.
GO:0038191 neuropilin binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ABL1 binds neuropilin. Reason: Neuropilin interaction relates to angiogenesis signaling. Not a core evolved function.
GO:0043025 neuronal cell body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 localizes to neuronal cell bodies. Reason: Neuronal cell-type-specific localization. Not a core function.
GO:0043065 positive regulation of apoptotic process	IEA GO_REF:0000120	ACCEPT	Summary: ABL1 positively regulates apoptosis in response to DNA damage. Reason: Nuclear ABL1 promotes apoptosis following severe DNA damage via TP73 and CASP9 phosphorylation. Supporting Evidence: PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase
GO:0043525 positive regulation of neuron apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 can promote neuron apoptosis. Reason: Cell-type-specific apoptotic function in neurons. Related to Parkinson's disease pathology.
GO:0045580 regulation of T cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 regulates T cell differentiation. Reason: Cell-type-specific developmental function. Not a core evolved function.
GO:0045907 positive regulation of vasoconstriction	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 positively regulates vasoconstriction. Reason: Physiological phenotype, not a core molecular function.
GO:0046875 ephrin receptor binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 binds ephrin receptors. Reason: Ephrin signaling is one of many pathways ABL1 participates in. Not a core function.
GO:0048013 ephrin receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 participates in ephrin receptor signaling. Reason: Ephrin signaling is one of many pathways ABL1 modulates. Not a core evolved function.
GO:0048146 positive regulation of fibroblast proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes fibroblast proliferation. Reason: Cell-type-specific proliferative effect. Not a core function.
GO:0051015 actin filament binding	IEA GO_REF:0000107	ACCEPT	Summary: ABL1 directly binds actin filaments through its C-terminal F-actin binding domain. Reason: Direct F-actin binding is a core structural feature of ABL1 enabling cytoskeletal regulation. Supporting Evidence: file:human/ABL1/ABL1-deep-research-falcon.md [ABL1 contains C-terminal F-actin binding domain for direct actin filament binding]
GO:0051450 myoblast proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 is involved in myoblast proliferation. Reason: Cell-type-specific developmental function. Not a core evolved function.
GO:0060038 cardiac muscle cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 is involved in cardiac muscle cell proliferation. Reason: Cell-type-specific developmental function. Not a core evolved function.
GO:0070097 delta-catenin binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 binds delta-catenin. Reason: Specific protein interaction. Not a core evolved function.
GO:0071560 cellular response to transforming growth factor beta stimulus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 responds to TGF-beta stimulus. Reason: TGF-beta response is one of many signaling pathways ABL1 participates in. Not core.
GO:0071871 response to epinephrine	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 responds to epinephrine. Reason: Physiological response, not a core molecular function.
GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes cell migration during angiogenesis. Reason: Developmental/physiological phenotype, not a core molecular function.
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 localizes to glutamatergic synapses. Reason: Neuronal cell-type-specific localization. Not a core function.
GO:0099150 regulation of postsynaptic specialization assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 regulates postsynaptic specialization assembly. Reason: Neuronal cell-type-specific function. Not a core evolved function.
GO:1900006 positive regulation of dendrite development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes dendrite development. Reason: Neuronal developmental function. Not a core evolved function.
GO:1900272 negative regulation of long-term synaptic potentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 negatively regulates long-term synaptic potentiation. Reason: Neuronal physiological function. Not a core evolved function.
GO:1903055 positive regulation of extracellular matrix organization	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes extracellular matrix organization. Reason: Downstream phenotypic effect. Not a core molecular function.
GO:1903210 podocyte apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 is involved in podocyte apoptosis. Reason: Cell-type-specific apoptotic function. Not a core evolved function.
GO:1903905 positive regulation of establishment of T cell polarity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes T cell polarity establishment. Reason: Cell-type-specific function in T cells. Not a core evolved function.
GO:1905244 regulation of modification of synaptic structure	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ABL1 regulates synaptic structure modification. Reason: Neuronal function related to actin dynamics at synapses. Not a core evolved function.
GO:1905555 positive regulation of blood vessel branching	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes blood vessel branching. Reason: Angiogenesis-related phenotype. Not a core molecular function.
GO:2000406 positive regulation of T cell migration	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ABL1 promotes T cell migration. Reason: Cell-type-specific migration function. Not a core evolved function.
GO:0000287 magnesium ion binding	IDA PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	ACCEPT	Summary: ABL1 binds magnesium ions as a cofactor for its kinase activity. Reason: Magnesium binding is required for ATP-dependent kinase activity. This is an intrinsic component of tyrosine kinase function. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0000400 four-way junction DNA binding	IDA PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase pr...	ACCEPT	Summary: ABL1 binds four-way junction DNA structures through its DNA binding domain. Reason: Direct experimental evidence demonstrates ABL1 binding to DNA junction structures. This contributes to DNA damage response functions. Supporting Evidence: PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
GO:0000405 bubble DNA binding	IDA PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase pr...	ACCEPT	Summary: ABL1 binds bubble DNA structures. Reason: Direct experimental evidence for binding to DNA bubble structures. Relevant to DNA damage response function. Supporting Evidence: PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
GO:0001784 phosphotyrosine residue binding	IPI PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival th...	ACCEPT	Summary: ABL1 SH2 domain binds phosphotyrosine residues. Reason: SH2 domain-mediated phosphotyrosine binding is essential for ABL1 substrate recognition and signaling. Supporting Evidence: PMID:20624904 Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.
GO:0004672 protein kinase activity	IDA PMID:11120811 The c-Abl tyrosine kinase is regulated downstream of the B c...	ACCEPT	Summary: ABL1 possesses protein kinase activity. Reason: Core kinase function. ABL1 is a well-characterized protein kinase. Supporting Evidence: PMID:11120811 The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19.
GO:0004672 protein kinase activity	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	ACCEPT	Summary: ABL1 kinase activity regulates neuropilin-dependent endothelial cell functions. Reason: Kinase activity is core function; this annotation documents its role in specific signaling context. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0004674 protein serine/threonine kinase activity	IMP PMID:24700464 The association of cortactin with profilin-1 is critical for...	ACCEPT	Summary: ABL1 phosphorylates serine/threonine residues in addition to tyrosine. Reason: Evidence supports dual-specificity kinase activity for ABL1 phosphorylating both tyrosine and serine/threonine residues. Supporting Evidence: PMID:24700464 2014 Apr 3. The association of cortactin with profilin-1 is critical for smooth muscle contraction.
GO:0004713 protein tyrosine kinase activity	IDA PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyr...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Core molecular function of ABL1. Multiple lines of evidence support tyrosine kinase activity. Supporting Evidence: PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.
GO:0004713 protein tyrosine kinase activity	IDA PMID:11121037 Functional interaction between c-Abl and the p21-activated p...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Core molecular function. Additional experimental evidence for kinase activity. Supporting Evidence: PMID:11121037 Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.
GO:0004713 protein tyrosine kinase activity	IDA PMID:12944467 Werner syndrome protein phosphorylation by abl tyrosine kina...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:12944467 Werner syndrome protein phosphorylation by abl tyrosine kinase regulates its activity and distribution.
GO:0004713 protein tyrosine kinase activity	IDA PMID:15657060 c-Abl tyrosine kinase regulates caspase-9 autocleavage in th...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity in DNA damage response. Reason: Core molecular function demonstrated in DNA damage response context. Supporting Evidence: PMID:15657060 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
GO:0004713 protein tyrosine kinase activity	EXP PMID:15657136 Abelson-interactor-1 promotes WAVE2 membrane translocation a...	ACCEPT	Summary: Experimental evidence for ABL1 tyrosine kinase activity. Reason: Core molecular function with direct experimental validation. Supporting Evidence: PMID:15657136 Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation.
GO:0004713 protein tyrosine kinase activity	IDA PMID:17888034 Fibroblast growth factor receptor 1 oncogene partner as a no...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Core molecular function. Additional IDA evidence. Supporting Evidence: PMID:17888034 Epub 2007 Sep 18. Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.
GO:0004713 protein tyrosine kinase activity	IDA PMID:20823226 Phosphorylation by the c-Abl protein tyrosine kinase inhibit...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Core molecular function with direct experimental evidence. Supporting Evidence: PMID:20823226 Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
GO:0004713 protein tyrosine kinase activity	IMP PMID:22810897 Abl family kinases modulate T cell-mediated inflammation and...	ACCEPT	Summary: Mutant phenotype evidence for ABL1 tyrosine kinase activity. Reason: IMP evidence supports core kinase function. Supporting Evidence: PMID:22810897 Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.
GO:0004713 protein tyrosine kinase activity	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	ACCEPT	Summary: ABL1 kinase activity required for microtubule plus-end localization. Reason: Core kinase function demonstrated in cytoskeletal regulation context. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0004713 protein tyrosine kinase activity	IDA PMID:7590236 Abi-2, a novel SH3-containing protein interacts with the c-A...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity. Reason: Early IDA evidence establishing ABL1 as a tyrosine kinase. Supporting Evidence: PMID:7590236 Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.
GO:0004713 protein tyrosine kinase activity	IDA PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	ACCEPT	Summary: Direct demonstration of ABL1 tyrosine kinase activity with structural analysis. Reason: Core molecular function with structural characterization. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IDA PMID:10518561 Molecular cloning of a docking protein, BRDG1, that acts dow...	ACCEPT	Summary: ABL1 functions as a non-receptor tyrosine kinase. Reason: Core specific molecular function designation. Supporting Evidence: PMID:10518561 Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IMP PMID:28428613 Differential regulation of PKD isoforms in oxidative stress ...	ACCEPT	Summary: ABL1 non-receptor kinase activity demonstrated by mutant phenotypes. Reason: Core specific molecular function with IMP evidence. Supporting Evidence: PMID:28428613 Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IDA PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA dam...	ACCEPT	Summary: ABL1 acts as non-receptor kinase phosphorylating Rad51. Reason: Core molecular function demonstrated through Rad51 phosphorylation. Supporting Evidence: PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA damage.
GO:0005080 protein kinase C binding	IPI PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyr...	ACCEPT	Summary: ABL1 physically interacts with protein kinase C. Reason: Documented physical interaction supporting ABL1's role in PKC signaling. Supporting Evidence: PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.
GO:0005515 protein binding	IPI PMID:15657060 c-Abl tyrosine kinase regulates caspase-9 autocleavage in th...	KEEP AS NON CORE	Summary: ABL1 binds to caspase-9. Reason: Generic protein binding term; the specific interaction partner (caspase-9) provides context for apoptosis function. Supporting Evidence: PMID:15657060 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
GO:0005515 protein binding	IPI PMID:17515907 Structural basis for the transforming activity of human canc...	KEEP AS NON CORE	Summary: ABL1 protein-protein interaction. Reason: Generic protein binding; specific partners provide functional context. Supporting Evidence: PMID:17515907 May 21. Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.
GO:0005515 protein binding	IPI PMID:17888034 Fibroblast growth factor receptor 1 oncogene partner as a no...	KEEP AS NON CORE	Summary: ABL1 protein-protein interaction. Reason: Generic protein binding term. Supporting Evidence: PMID:17888034 Epub 2007 Sep 18. Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.
GO:0005515 protein binding	IPI PMID:22810897 Abl family kinases modulate T cell-mediated inflammation and...	KEEP AS NON CORE	Summary: ABL1 binds NEDD9. Reason: Generic protein binding; NEDD9 interaction relates to cell adhesion/migration. Supporting Evidence: PMID:22810897 Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.
GO:0005515 protein binding	IPI PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	KEEP AS NON CORE	Summary: ABL1 binds CLASP2. Reason: Generic protein binding; CLASP2 interaction relates to microtubule regulation. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0005515 protein binding	IPI PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA dam...	KEEP AS NON CORE	Summary: ABL1 binds RAD51. Reason: Generic protein binding; RAD51 interaction supports DNA damage response function. Supporting Evidence: PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA damage.
GO:0005524 ATP binding	IDA PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	ACCEPT	Summary: ABL1 binds ATP as substrate for kinase activity. Reason: ATP binding is essential for kinase function. Core to molecular activity. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0005634 nucleus	IDA PMID:17626041 Cockayne syndrome protein B interacts with and is phosphoryl...	ACCEPT	Summary: ABL1 localizes to the nucleus. Reason: Consistent with nuclear DNA damage response function. Supporting Evidence: PMID:17626041 Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
GO:0005634 nucleus	IDA PMID:17888034 Fibroblast growth factor receptor 1 oncogene partner as a no...	ACCEPT	Summary: ABL1 nuclear localization demonstrated. Reason: Core localization for DNA damage response function. Supporting Evidence: PMID:17888034 Epub 2007 Sep 18. Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.
GO:0005634 nucleus	IDA PMID:9168116 Ataxia telangiectasia mutant protein activates c-Abl tyrosin...	ACCEPT	Summary: ABL1 accumulates in nucleus after DNA damage via ATM activation. Reason: Nuclear localization in response to DNA damage is a core function. Supporting Evidence: PMID:9168116 Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: More specific nuclear localization supporting DNA damage response function.
GO:0005730 nucleolus	IDA PMID:12944467 Werner syndrome protein phosphorylation by abl tyrosine kina...	ACCEPT	Summary: ABL1 localizes to the nucleolus. Reason: Nucleolar localization supports role in transcription-related functions. Supporting Evidence: PMID:12944467 Werner syndrome protein phosphorylation by abl tyrosine kinase regulates its activity and distribution.
GO:0005730 nucleolus	IDA PMID:17626041 Cockayne syndrome protein B interacts with and is phosphoryl...	ACCEPT	Summary: ABL1 localizes to the nucleolus during oxidative stress. Reason: Nucleolar localization in stress response. Supporting Evidence: PMID:17626041 Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
GO:0005737 cytoplasm	IDA PMID:17515907 Structural basis for the transforming activity of human canc...	ACCEPT	Summary: ABL1 localizes to cytoplasm. Reason: Cytoplasmic localization is core, enabling cytoskeletal regulation functions. Supporting Evidence: PMID:17515907 May 21. Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.
GO:0005829 cytosol	IDA PMID:11120811 The c-Abl tyrosine kinase is regulated downstream of the B c...	ACCEPT	Summary: ABL1 localizes to cytosol. Reason: Cytosolic localization supporting signaling and cytoskeletal functions. Supporting Evidence: PMID:11120811 The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19.
GO:0006974 DNA damage response	IDA PMID:15657060 c-Abl tyrosine kinase regulates caspase-9 autocleavage in th...	ACCEPT	Summary: ABL1 participates in DNA damage response. Reason: Core biological process function for ABL1. Supporting Evidence: PMID:15657060 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
GO:0006979 response to oxidative stress	IGI PMID:17626041 Cockayne syndrome protein B interacts with and is phosphoryl...	ACCEPT	Summary: ABL1 responds to oxidative stress, genetic interaction evidence. Reason: Part of ABL1's stress response functions. Supporting Evidence: PMID:17626041 Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.
GO:0007204 positive regulation of cytosolic calcium ion concentration	IMP PMID:24367707 Abl family kinases regulate endothelial barrier function in ...	KEEP AS NON CORE	Summary: ABL1 regulates cytosolic calcium concentration. Reason: Downstream signaling effect rather than core function. Supporting Evidence: PMID:24367707 eCollection 2013. Abl family kinases regulate endothelial barrier function in vitro and in mice.
GO:0007229 integrin-mediated signaling pathway	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	ACCEPT	Summary: ABL1 regulates integrin-mediated signaling. Reason: Integrin signaling relates to core cytoskeletal regulatory function. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0008047 enzyme activator activity	IDA PMID:12893824 Glutathione peroxidase 1 is regulated by the c-Abl and Arg t...	KEEP AS NON CORE	Summary: ABL1 activates glutathione peroxidase 1. Reason: Enzyme activator is a more generic function; specific to oxidative stress response. Supporting Evidence: PMID:12893824 2003 Jul 31. Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases.
GO:0010595 positive regulation of endothelial cell migration	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	KEEP AS NON CORE	Summary: ABL1 promotes endothelial cell migration via neuropilin signaling. Reason: Cell-type-specific phenotype, not core function. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0016301 kinase activity	IMP PMID:28288113 Germline mutations in ABL1 cause an autosomal dominant syndr...	ACCEPT	Summary: ABL1 kinase activity demonstrated by mutant phenotype. Reason: General kinase activity is core to ABL1 function. Supporting Evidence: PMID:28288113 Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations.
GO:0016604 nuclear body	IDA GO_REF:0000052	ACCEPT	Summary: ABL1 localizes to nuclear bodies. Reason: Nuclear body localization consistent with transcription/DNA damage functions.
GO:0019899 enzyme binding	IPI PMID:12893824 Glutathione peroxidase 1 is regulated by the c-Abl and Arg t...	KEEP AS NON CORE	Summary: ABL1 binds glutathione peroxidase 1. Reason: Generic enzyme binding; specific to oxidative stress context. Supporting Evidence: PMID:12893824 2003 Jul 31. Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases.
GO:0019905 syntaxin binding	IPI PMID:23006999 Tyrosine phosphorylation of a SNARE protein, syntaxin 17 - i...	KEEP AS NON CORE	Summary: ABL1 binds syntaxin. Reason: Specific binding interaction; not core function. Supporting Evidence: PMID:23006999 Tyrosine phosphorylation of a SNARE protein, syntaxin 17: implications for membrane trafficking in the early secretory pathway.
GO:0030145 manganese ion binding	IDA PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	ACCEPT	Summary: ABL1 binds manganese ions. Reason: Metal ion binding supports kinase activity (can substitute for magnesium). Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0030516 regulation of axon extension	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	KEEP AS NON CORE	Summary: ABL1 regulates axon extension through cytoskeletal effects. Reason: Cell-type-specific phenotype related to cytoskeletal regulation. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0030845 phospholipase C-inhibiting G protein-coupled receptor signaling pathway	IMP PMID:24367707 Abl family kinases regulate endothelial barrier function in ...	KEEP AS NON CORE	Summary: ABL1 involved in PLC-inhibiting GPCR signaling. Reason: Specific signaling pathway involvement; not core function. Supporting Evidence: PMID:24367707 eCollection 2013. Abl family kinases regulate endothelial barrier function in vitro and in mice.
GO:0031113 regulation of microtubule polymerization	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	ACCEPT	Summary: ABL1 regulates microtubule polymerization via CLASP2 phosphorylation. Reason: Part of core cytoskeletal regulatory function. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0032489 regulation of Cdc42 protein signal transduction	IMP PMID:26051942 NRP1 Regulates CDC42 Activation to Promote Filopodia Formati...	ACCEPT	Summary: ABL1 regulates Cdc42 signaling. Reason: Cdc42 regulation relates to core cytoskeletal organization function. Supporting Evidence: PMID:26051942 2015 Jun 4. NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells.
GO:0032956 regulation of actin cytoskeleton organization	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	ACCEPT	Summary: ABL1 regulates actin cytoskeleton organization. Reason: Core biological process function of ABL1. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0032956 regulation of actin cytoskeleton organization	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	ACCEPT	Summary: ABL1 regulates actin cytoskeleton organization in endothelial cells. Reason: Core cytoskeletal function; this is additional IMP evidence. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0034599 cellular response to oxidative stress	IDA PMID:12893824 Glutathione peroxidase 1 is regulated by the c-Abl and Arg t...	ACCEPT	Summary: ABL1 responds to oxidative stress by activating antioxidant enzymes. Reason: Part of ABL1's stress response function. Supporting Evidence: PMID:12893824 2003 Jul 31. Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases.
GO:0035556 intracellular signal transduction	IDA PMID:9144171 Protein binding and signaling properties of RIN1 suggest a u...	ACCEPT	Summary: ABL1 participates in intracellular signal transduction. Reason: Core function as a signaling kinase. Supporting Evidence: PMID:9144171 Protein binding and signaling properties of RIN1 suggest a unique effector function.
GO:0035556 intracellular signal transduction	IDA PMID:11121037 Functional interaction between c-Abl and the p21-activated p...	ACCEPT	Summary: ABL1 participates in intracellular signal transduction. Reason: Core signaling function with additional IDA evidence. Supporting Evidence: PMID:11121037 Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.
GO:0035791 platelet-derived growth factor receptor-beta signaling pathway	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	KEEP AS NON CORE	Summary: ABL1 involved in PDGFR-beta signaling. Reason: Specific growth factor signaling pathway; not core evolved function. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:0038189 neuropilin signaling pathway	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	KEEP AS NON CORE	Summary: ABL1 involved in neuropilin signaling pathway. Reason: Specific signaling pathway involvement. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0038191 neuropilin binding	IPI PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	KEEP AS NON CORE	Summary: ABL1 binds neuropilin. Reason: Specific binding interaction in angiogenesis context. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0042169 SH2 domain binding	IPI PMID:12384576 Structure of a regulatory complex involving the Abl SH3 doma...	ACCEPT	Summary: ABL1 engages in SH2 domain-mediated interactions. Reason: SH2 domain interactions are core to ABL1 signaling mechanisms. Supporting Evidence: PMID:12384576 Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
GO:0042770 signal transduction in response to DNA damage	IDA PMID:15657060 c-Abl tyrosine kinase regulates caspase-9 autocleavage in th...	ACCEPT	Summary: ABL1 signals in response to DNA damage. Reason: Core DNA damage response function. Supporting Evidence: PMID:15657060 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
GO:0042770 signal transduction in response to DNA damage	IDA PMID:18280240 Yap1 phosphorylation by c-Abl is a critical step in selectiv...	ACCEPT	Summary: ABL1 participates in DNA damage signaling. Reason: Core DNA damage response function with additional evidence. Supporting Evidence: PMID:18280240 Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage.
GO:0042770 signal transduction in response to DNA damage	IDA PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyro...	ACCEPT	Summary: ABL1 signals in response to DNA damage to regulate apoptosis. Reason: Core DNA damage response function. Supporting Evidence: PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase.
GO:0043065 positive regulation of apoptotic process	IDA PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyro...	ACCEPT	Summary: ABL1 promotes apoptosis in response to DNA damage. Reason: Pro-apoptotic function in response to irreparable DNA damage is a core function. Supporting Evidence: PMID:9037071 Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase.
GO:0043539 protein serine/threonine kinase activator activity	IDA PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyr...	ACCEPT	Summary: ABL1 activates serine/threonine kinases including PKC. Reason: Kinase activator activity supports signaling function. Supporting Evidence: PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.
GO:0048471 perinuclear region of cytoplasm	IDA PMID:17888034 Fibroblast growth factor receptor 1 oncogene partner as a no...	ACCEPT	Summary: ABL1 localizes to perinuclear region. Reason: Consistent with shuttling between cytoplasm and nucleus. Supporting Evidence: PMID:17888034 Epub 2007 Sep 18. Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.
GO:0051019 mitogen-activated protein kinase binding	IPI PMID:11121037 Functional interaction between c-Abl and the p21-activated p...	ACCEPT	Summary: ABL1 binds MAPK/PAK2. Reason: MAPK binding supports signaling integration function. Supporting Evidence: PMID:11121037 Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.
GO:0051444 negative regulation of ubiquitin-protein transferase activity	IDA PMID:20823226 Phosphorylation by the c-Abl protein tyrosine kinase inhibit...	KEEP AS NON CORE	Summary: ABL1 negatively regulates ubiquitin-protein transferase activity. Reason: Regulatory function but not core molecular function. Supporting Evidence: PMID:20823226 Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.
GO:0051496 positive regulation of stress fiber assembly	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	ACCEPT	Summary: ABL1 promotes stress fiber assembly. Reason: Part of core cytoskeletal regulatory function. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0051894 positive regulation of focal adhesion assembly	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	ACCEPT	Summary: ABL1 promotes focal adhesion assembly. Reason: Focal adhesion regulation is part of cytoskeletal function. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0070064 proline-rich region binding	IDA PMID:15657060 c-Abl tyrosine kinase regulates caspase-9 autocleavage in th...	ACCEPT	Summary: ABL1 binds proline-rich regions through its SH3 domain. Reason: SH3 domain-mediated binding is core to ABL1 protein interactions. Supporting Evidence: PMID:15657060 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
GO:0070301 cellular response to hydrogen peroxide	IDA PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyr...	ACCEPT	Summary: ABL1 responds to hydrogen peroxide (oxidative stress). Reason: Part of oxidative stress response function. Supporting Evidence: PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.
GO:0097100 supercoiled DNA binding	IDA NOT PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase pr...	ACCEPT	Summary: ABL1 does NOT bind supercoiled DNA (negative annotation with NOT qualifier). Reason: Negative annotation indicating specificity of DNA binding - binds junction/bubble structures but not supercoiled. Supporting Evidence: PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
GO:0141214 positive regulation of phospholipase C/protein kinase C signal transduction	IDA PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyr...	KEEP AS NON CORE	Summary: ABL1 activates PLC/PKC signaling. Reason: Specific signaling pathway regulation; downstream of kinase activity. Supporting Evidence: PMID:10713049 Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.
GO:1904518 protein localization to cytoplasmic microtubule plus-end	IMP PMID:24520051 Abelson phosphorylation of CLASP2 modulates its association ...	ACCEPT	Summary: ABL1 promotes protein localization to microtubule plus-ends. Reason: Part of microtubule/cytoskeletal regulatory function. Supporting Evidence: PMID:24520051 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin.
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	KEEP AS NON CORE	Summary: ABL1 promotes cell spreading. Reason: Phenotypic outcome of cytoskeletal/adhesion regulation. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:1990837 sequence-specific double-stranded DNA binding	IDA PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase pr...	ACCEPT	Summary: ABL1 binds specific DNA sequences. Reason: Specific DNA binding supports DNA damage response function. Supporting Evidence: PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
GO:2000042 negative regulation of double-strand break repair via homologous recombination	IDA PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA dam...	ACCEPT	Summary: ABL1 inhibits homologous recombination repair by phosphorylating RAD51. Reason: Important regulatory function in DNA damage response pathway. Supporting Evidence: PMID:9461559 Regulation of Rad51 function by c-Abl in response to DNA damage.
GO:0032991 protein-containing complex	IPI PMID:12384576 Structure of a regulatory complex involving the Abl SH3 doma...	KEEP AS NON CORE	Summary: ABL1 is part of protein complexes. Reason: Generic complex annotation; specific complexes are more informative. Supporting Evidence: PMID:12384576 Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
GO:0043542 endothelial cell migration	IMP PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting...	KEEP AS NON CORE	Summary: ABL1 involved in endothelial cell migration. Reason: Cell-type-specific phenotype. Supporting Evidence: PMID:24863063 Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
GO:0000278 mitotic cell cycle	TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	KEEP AS NON CORE	Summary: ABL1 involved in mitotic cell cycle regulation. Reason: Cell cycle involvement but not core molecular function. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:0003677 DNA binding	NAS PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma pr...	ACCEPT	Summary: ABL1 binds DNA. Reason: DNA binding is a core molecular function of ABL1. Supporting Evidence: PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
GO:0003713 transcription coactivator activity	TAS PMID:15865930 C-Abl as a modulator of p53.	ACCEPT	Summary: ABL1 acts as a transcription coactivator. Reason: Transcriptional regulation is part of nuclear ABL1 function. Supporting Evidence: PMID:15865930 C-Abl as a modulator of p53.
GO:0003785 actin monomer binding	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 binds G-actin monomers. Reason: G-actin binding is part of actin cytoskeleton regulatory function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0004515 nicotinate-nucleotide adenylyltransferase activity	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	UNDECIDED	Summary: ABL1 has nicotinate-nucleotide adenylyltransferase activity. Reason: This annotation seems unusual for ABL1. Requires verification - may be a curation error. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0004713 protein tyrosine kinase activity	TAS PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic respons...	ACCEPT	Summary: ABL1 is a protein tyrosine kinase. Reason: Core molecular function. Supporting Evidence: PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-428888	ACCEPT	Summary: ABL1 tyrosine kinase activity in Reactome pathway. Reason: Core molecular function documented in pathway context.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-5686587	ACCEPT	Summary: ABL1 tyrosine kinase activity in Reactome pathway. Reason: Core molecular function in pathway context.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-8956659	ACCEPT	Summary: ABL1 tyrosine kinase activity in Reactome pathway. Reason: Core molecular function.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-9841924	ACCEPT	Summary: ABL1 tyrosine kinase activity. Reason: Core molecular function.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-9865196	ACCEPT	Summary: ABL1 tyrosine kinase activity. Reason: Core molecular function.
GO:0005634 nucleus	NAS PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma pr...	ACCEPT	Summary: ABL1 localizes to nucleus. Reason: Core localization. Supporting Evidence: PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
GO:0005634 nucleus	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 localizes to nucleus. Reason: Core localization. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5686578	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: Core nuclear localization.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5686587	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: Core nuclear localization.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-8956659	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: Core nuclear localization.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9841924	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: Core nuclear localization.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-9842028	ACCEPT	Summary: ABL1 localizes to nucleoplasm. Reason: Core nuclear localization.
GO:0005737 cytoplasm	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 localizes to cytoplasm. Reason: Core localization. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0005739 mitochondrion	NAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	ACCEPT	Summary: ABL1 localizes to mitochondria. Reason: Mitochondrial localization documented, relevant to apoptosis and oxidative stress functions. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:0005829 cytosol	TAS Reactome:R-HSA-2130194	ACCEPT	Summary: ABL1 localizes to cytosol. Reason: Core cytosolic localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-376141	ACCEPT	Summary: ABL1 in cytosol (Reactome pathway). Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-428888	ACCEPT	Summary: ABL1 in cytosol. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-448958	ACCEPT	Summary: ABL1 in cytosol. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9865184	ACCEPT	Summary: ABL1 in cytosol. Reason: Core localization.
GO:0005829 cytosol	TAS Reactome:R-HSA-9865196	ACCEPT	Summary: ABL1 in cytosol. Reason: Core localization.
GO:0006298 mismatch repair	TAS PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic respons...	ACCEPT	Summary: ABL1 involved in mismatch repair. Reason: Part of DNA damage response function. Supporting Evidence: PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage.
GO:0006355 regulation of DNA-templated transcription	TAS PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma pr...	ACCEPT	Summary: ABL1 regulates transcription. Reason: Part of nuclear ABL1 function. Supporting Evidence: PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	TAS PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic respons...	ACCEPT	Summary: ABL1 promotes intrinsic apoptosis after DNA damage. Reason: Core DNA damage response function. Supporting Evidence: PMID:10391249 The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 involved in DNA damage-induced apoptosis. Reason: Core function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0010506 regulation of autophagy	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	MARK AS OVER ANNOTATED	Summary: ABL1 regulates autophagy. Reason: Per previous guidance, autophagy-related annotations should be marked as over-annotated for ABL1. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0015629 actin cytoskeleton	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 localizes to actin cytoskeleton. Reason: Core localization for cytoskeletal function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0030100 regulation of endocytosis	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	KEEP AS NON CORE	Summary: ABL1 regulates endocytosis. Reason: Endocytosis regulation is a downstream effect of cytoskeletal function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0030155 regulation of cell adhesion	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 regulates cell adhesion. Reason: Cell adhesion regulation is part of core cytoskeletal/integrin functions. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0032956 regulation of actin cytoskeleton organization	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 regulates actin cytoskeleton organization. Reason: Core biological process function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0034599 cellular response to oxidative stress	TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	ACCEPT	Summary: ABL1 responds to oxidative stress. Reason: Part of stress response function. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:0036211 protein modification process	NAS PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma pr...	ACCEPT	Summary: ABL1 modifies proteins (phosphorylation). Reason: General annotation for kinase function. Supporting Evidence: PMID:8242749 A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis	TAS Reactome:R-HSA-2029480	KEEP AS NON CORE	Summary: ABL1 involved in Fc-gamma receptor signaling. Reason: Specific signaling pathway; not core function.
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis	TAS Reactome:R-HSA-9664422	KEEP AS NON CORE	Summary: ABL1 in Fc-gamma receptor signaling. Reason: Specific pathway annotation.
GO:0045944 positive regulation of transcription by RNA polymerase II	TAS PMID:15865930 C-Abl as a modulator of p53.	ACCEPT	Summary: ABL1 promotes RNA Pol II transcription. Reason: Part of transcriptional coactivator function. Supporting Evidence: PMID:15865930 C-Abl as a modulator of p53.
GO:0051726 regulation of cell cycle	TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	KEEP AS NON CORE	Summary: ABL1 regulates cell cycle. Reason: Cell cycle regulation is downstream of core signaling functions. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:0051882 mitochondrial depolarization	TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	KEEP AS NON CORE	Summary: ABL1 involved in mitochondrial depolarization. Reason: Related to apoptosis but specific mitochondrial effect. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:0071103 DNA conformation change	IDA PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase pr...	ACCEPT	Summary: ABL1 induces DNA conformation changes. Reason: Part of DNA binding/DNA damage response function. Supporting Evidence: PMID:9558345 The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.
GO:0097706 vascular endothelial cell response to oscillatory fluid shear stress	TAS Reactome:R-HSA-9860927	KEEP AS NON CORE	Summary: ABL1 involved in endothelial shear stress response. Reason: Cell-type-specific response.
GO:0098794 postsynapse	TAS PMID:24658113 EphA4 activation of c-Abl mediates synaptic loss and LTP blo...	KEEP AS NON CORE	Summary: ABL1 localizes to postsynapse. Reason: Cell-type-specific localization in neurons. Supporting Evidence: PMID:24658113 eCollection 2014. EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-β oligomers.
GO:1902036 regulation of hematopoietic stem cell differentiation	TAS Reactome:R-HSA-8939236	KEEP AS NON CORE	Summary: ABL1 regulates hematopoietic stem cell differentiation. Reason: Cell-type-specific developmental function.
GO:1903351 cellular response to dopamine	TAS PMID:24522549 Oxidative stress-induced signaling pathways implicated in th...	KEEP AS NON CORE	Summary: ABL1 responds to dopamine. Reason: Specific stimulus response; relevant to Parkinson's disease context. Supporting Evidence: PMID:24522549 Epub 2014 Feb 13. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.
GO:2000145 regulation of cell motility	TAS PMID:20841568 ABL tyrosine kinases - evolution of function, regulation, an...	ACCEPT	Summary: ABL1 regulates cell motility. Reason: Motility regulation through cytoskeletal effects is a core function. Supporting Evidence: PMID:20841568 ABL tyrosine kinases: evolution of function, regulation, and specificity.
GO:0005634 nucleus	ISS GO_REF:0000024	ACCEPT	Summary: ABL1 nuclear localization inferred from sequence similarity. Reason: Consistent with experimentally validated nuclear localization.
GO:0030036 actin cytoskeleton organization	ISS GO_REF:0000024	ACCEPT	Summary: ABL1 role in actin organization inferred from mouse ortholog. Reason: Core function consistent with experimental evidence.
GO:0030425 dendrite	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 dendrite localization from ortholog inference. Reason: Cell-type-specific neuronal localization.
GO:0043025 neuronal cell body	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 neuronal cell body localization inferred. Reason: Cell-type-specific localization.
GO:0045580 regulation of T cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 regulates T cell differentiation (ortholog inference). Reason: Cell-type-specific developmental function.
GO:0046875 ephrin receptor binding	ISS GO_REF:0000024	ACCEPT	Summary: ABL1 binds ephrin receptors (ortholog inference). Reason: Ephrin receptor interaction documented, relevant to cytoskeletal signaling.
GO:1900272 negative regulation of long-term synaptic potentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 negatively regulates LTP (ortholog inference). Reason: Cell-type-specific neuronal function.
GO:1903905 positive regulation of establishment of T cell polarity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 promotes T cell polarity (ortholog inference). Reason: Cell-type-specific function.
GO:1905244 regulation of modification of synaptic structure	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 regulates synaptic structure (ortholog inference). Reason: Cell-type-specific neuronal function.
GO:2000406 positive regulation of T cell migration	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ABL1 promotes T cell migration (ortholog inference). Reason: Cell-type-specific function.

Core Functions

ABL1 is a non-receptor tyrosine kinase that phosphorylates substrates involved in DNA damage response, actin cytoskeleton dynamics, and cell signaling.

Molecular Function:

non-membrane spanning protein tyrosine kinase activity

Directly Involved In:

DNA repair regulation of actin cytoskeleton organization

Cellular Locations:

nucleus cytosol

Supporting Evidence:

PMID:9461559
Regulation of Rad51 function by c-Abl in response to DNA damage
file:human/ABL1/ABL1-deep-research-falcon.md
[ABL1 phosphorylates cortactin to regulate actin cytoskeleton organization]

ABL1 directly binds F-actin through its C-terminal actin binding domain, enabling localization to and regulation of the actin cytoskeleton.

Molecular Function:

actin filament binding

Cellular Locations:

cytoskeleton plasma membrane

Supporting Evidence:

PMID:20841568
ABL1 contains F-actin binding and G-actin binding regions in its C-terminus

Nuclear ABL1 binds DNA through its C-terminal DNA binding domain and participates in DNA damage response signaling, promoting apoptosis when damage is irreparable.

Molecular Function:

DNA binding

Directly Involved In:

DNA damage response apoptotic process

Cellular Locations:

nucleus

Supporting Evidence:

PMID:9168116
Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation
PMID:9037071
Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase

References

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

Annotation inferences using protein family information

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:9037071

Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase

PMID:9144171

Protein binding and signaling properties of RIN1 suggest a unique effector function

PMID:9168116

Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in response to ionizing radiation.

PMID:9168117

Interaction between ATM protein and c-Abl in response to DNA damage.

PMID:9346925

SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related protein kinase, HPK1.

PMID:9461559

Regulation of Rad51 function by c-Abl in response to DNA damage

PMID:9593709

Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton.

PMID:10391249

The tyrosine kinase c-Abl regulates p73 in apoptotic response to cisplatin-induced DNA damage.

PMID:10518561

Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase.

PMID:10713049

Interaction between protein kinase C delta and the c-Abl tyrosine kinase in the cellular response to oxidative stress.

PMID:10849448

Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck.

PMID:10970852

Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an actin-associated multi-kinase scaffold.

PMID:11120811

The c-Abl tyrosine kinase is regulated downstream of the B cell antigen receptor and interacts with CD19.

PMID:11121037

Functional interaction between c-Abl and the p21-activated protein kinase gamma-PAK.

PMID:11374898

Cloning, mapping, and characterization of the human sorbin and SH3 domain containing 1 (SORBS1) gene - a protein associated with c-Abl during insulin signaling in the hepatoma cell line Hep3B.

PMID:11375976

Telomeric protein Pin2/TRF1 as an important ATM target in response to double strand DNA breaks.

PMID:11418237

Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose expression is down-regulated in Alzheimer's disease.

PMID:11971963

c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage.

PMID:12384576

Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide

PMID:12893824

Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases.

PMID:12944467

Werner syndrome protein phosphorylation by abl tyrosine kinase regulates its activity and distribution.

PMID:15448168

Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase confers camptothecin sensitivity.

PMID:15657060

c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.

PMID:15657136

Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation.

PMID:15696159

JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of c-Abl in the apoptotic response to DNA damage.

PMID:15865930

C-Abl as a modulator of p53.

PMID:15886098

RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration.

PMID:16273093

A quantitative protein interaction network for the ErbB receptors using protein microarrays.

PMID:16397227

Physical and functional interaction between hMSH5 and c-Abl.

PMID:16443220

Characterization of p87C3G, a novel, truncated C3G isoform that is overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl.

PMID:16831423

Abl kinase interacts with and phosphorylates vinexin.

PMID:16888623

MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage.

PMID:17101133

NESH (Abi-3) is present in the Abi/WAVE complex but does not promote c-Abl-mediated phosphorylation.

PMID:17112510

Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli.

PMID:17318191

Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its tyrosine phosphorylation.

PMID:17474147

Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.

PMID:17515907

Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK.

PMID:17626041

Cockayne syndrome protein B interacts with and is phosphorylated by c-Abl tyrosine kinase.

PMID:17888034

Fibroblast growth factor receptor 1 oncogene partner as a novel prognostic biomarker and therapeutic target for lung cancer.

PMID:18280240

Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage.

PMID:18328268

Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1.

PMID:19234221

c-Abl kinase is required for beta 2 integrin-mediated neutrophil adhesion.

PMID:19442657

Evidence for a direct involvement of hMSH5 in promoting ionizing radiation induced apoptosis.

PMID:19470755

Cdo binds Abl to promote p38alpha/beta mitogen-activated protein kinase activity and myogenic differentiation.

PMID:19914245

c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response.

PMID:20598684

Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cells.

PMID:20624904

Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.

PMID:20697350

The proximal signaling network of the BCR-ABL1 oncogene shows a modular organization.

PMID:20823226

Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function.

PMID:20841568

ABL tyrosine kinases - evolution of function, regulation, and specificity

PMID:22286129

BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia.

PMID:22401567

MutS homologue hMSH5 - role in cisplatin-induced DNA damage response.

PMID:22810897

Abl family kinases modulate T cell-mediated inflammation and chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.

PMID:23006999

Tyrosine phosphorylation of a SNARE protein, syntaxin 17 - implications for membrane trafficking in the early secretory pathway.

PMID:24367707

Abl family kinases regulate endothelial barrier function in vitro and in mice.

PMID:24520051

Abelson phosphorylation of CLASP2 modulates its association with microtubules and actin

PMID:24522549

Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease.

PMID:24658113

EphA4 activation of c-Abl mediates synaptic loss and LTP blockade caused by amyloid-β oligomers.

PMID:24658140

The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells.

PMID:24700464

The association of cortactin with profilin-1 is critical for smooth muscle contraction.

PMID:24728074

Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome.

PMID:24863063

Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells.

PMID:24947832

Differential protein-protein interactions of LRRK1 and LRRK2 indicate roles in distinct cellular signaling pathways.

PMID:25036101

Identification of SH3 domain proteins interacting with the cytoplasmic tail of the a disintegrin and metalloprotease 10 (ADAM10).

PMID:25852190

Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.

PMID:26051942

NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in Endothelial Tip Cells.

PMID:27348587

Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration.

PMID:28086240

ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling.

PMID:28288113

Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations.

PMID:28428613

Differential regulation of PKD isoforms in oxidative stress conditions through phosphorylation of a conserved Tyr in the P+1 loop.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:30021884

Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.

PMID:31175292

Structural and functional consequences of the STAT5B(N642H) driver mutation.

PMID:31980649

Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:35271311

OpenCell - Endogenous tagging for the cartography of human cellular organization.

PMID:36931259

A central chaperone-like role for 14-3-3 proteins in human cells.

PMID:37219487

Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.

PMID:39009827

Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.

PMID:39251607

Systematic identification of post-transcriptional regulatory modules.

PMID:7590236

Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine kinase and modulates c-Abl transforming activity.

PMID:8242749

A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.

Reactome:R-HSA-2029480

Reactome - Fcgamma receptor (FCGR) dependent phagocytosis

Reactome:R-HSA-2130194

Reactome - EPH-ephrin signaling

Reactome:R-HSA-376141

Reactome - Termination of O-glycan biosynthesis

Reactome:R-HSA-428888

Reactome - ESR-mediated signaling

Reactome:R-HSA-448958

Reactome - Axon guidance

Reactome:R-HSA-5686578

Reactome - Autophagy

Reactome:R-HSA-5686587

Reactome - Lysosome

Reactome:R-HSA-8939236

Reactome - RUNX1 regulates transcription of genes involved in differentiation of HSCs

Reactome:R-HSA-8956659

Reactome - ABL1 signaling events

Reactome:R-HSA-9664422

Reactome - Fc-gamma receptor signaling

Reactome:R-HSA-9841924

Reactome - ABL1 signaling in DNA damage response

Reactome:R-HSA-9842028

Reactome - DNA damage checkpoint signaling

Reactome:R-HSA-9860927

Reactome - Endothelial cell response to shear stress

Reactome:R-HSA-9865184

Reactome - ABL1 cytosolic signaling

Reactome:R-HSA-9865196

Reactome - ABL1 kinase activity

PMID:9558345

The DNA binding domain of the human c-Abl tyrosine kinase preferentially binds to DNA sequences containing an AAC motif and to distorted DNA structures.

file:human/ABL1/ABL1-deep-research-falcon.md

Deep research summary for ABL1

Deep Research

Falcon

(ABL1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 42 citations 2026-01-18T22:46:56.554532

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification
- Identity check: The target is human ABL1 (UniProt P00519), a non-receptor tyrosine kinase with SH3–SH2–kinase (SH1) regulatory core, an N‑terminal myristoylation site that binds a myristoyl pocket in the kinase C‑lobe, and C‑terminal F‑/G‑actin binding and nuclear trafficking signals. These features and the autoinhibition mechanism are affirmed by recent structural/biophysical work and authoritative reviews (paladini2024themolecularbasis pages 16-17, paladini2024themolecularbasis pages 18-18, wu2024clinicalinsightsinto pages 2-4, sirvent2008cytoplasmicsignallingby pages 27-33, wang2014thecapableabl pages 1-2). The organism is Homo sapiens as required. No conflicting gene symbol usage was found.

Key concepts and definitions (current understanding)
- Domain architecture and allosteric autoinhibition: ABL1 comprises an N‑terminal myristoylated cap, SH3 and SH2 domains that assemble with the kinase domain into an autoinhibited core. Binding of the N‑myristoyl group to a hydrophobic pocket on the kinase C‑lobe promotes an SH3–SH2 “clamp” over the kinase, stabilizing an inactive state. The αI‑helix in the C‑lobe exerts force onto the SH2 domain and modulates core assembly; the E528K mutation in αI increases activity by weakening inhibitory contacts. Allosteric myristoyl‑pocket ligands (e.g., asciminib) fix the αI‑helix and favor autoinhibition (paladini2024themolecularbasis pages 16-17, paladini2024themolecularbasis pages 18-18, wu2024clinicalinsightsinto pages 2-4).
- Catalytic function: ABL1 is a tyrosine kinase (EC 2.7.10.2) that phosphorylates substrate tyrosines. The kinase toggles among inactive DFG‑out, Src‑like inactive, and active DFG‑in conformations; activation loop phosphorylation stabilizes activity (wu2024clinicalinsightsinto pages 2-4).
- Cellular localization signals: Multiple NLSs and one NES enable nucleocytoplasmic shuttling; a C‑terminal actin‑binding region localizes ABL1 to actin structures and embeds the NES, linking cytoplasmic localization to actin binding (sirvent2008cytoplasmicsignallingby pages 27-33, wang2014thecapableabl pages 1-2).

Domain/Region	Approx. residues	Key features	Functional role	Evidence/source (citation IDs)
N-terminal cap + myristoylation site	~1–60	N-myristoyl group binds deep hydrophobic pocket in kinase C-lobe (myristoyl pocket)	Triggers assembly of SH3–SH2 clamp; stabilizes autoinhibited conformation	(paladini2024themolecularbasis pages 16-17, paladini2024themolecularbasis pages 18-18)
SH3 domain	~80–140	Binds SH2–kinase linker; contains Tyr89 and RT loop critical for clamp	Part of auto-inhibitory clamp; required for asciminib-induced inhibition	(paladini2024themolecularbasis pages 16-17, leske2024thee13a3(b2a3) pages 2-3)
SH2 domain	~150–250	Docks on kinase C-lobe in autoinhibited state	Mediates allosteric control and substrate recognition	(paladini2024themolecularbasis pages 16-17, wu2024clinicalinsightsinto pages 2-4)
Kinase (SH1) domain	~260–500	DFG motif; activation-loop Tyr phosphorylation; myristoyl pocket in C-lobe	Catalysis of tyrosine phosphorylation; adopts inactive/active conformations	(wu2024clinicalinsightsinto pages 2-4)
αI-helix (C-lobe)	~520–540	Exerts force on SH2 domain; E528K hyperactivates	Modulates core assembly; asciminib reduces force to inhibit	(paladini2024themolecularbasis pages 16-17)
Proline-rich (PXXP) motifs	C-terminal tail	SH3-binding sites for adapters	Scaffold for signaling complexes	(siveen2018roleofnon pages 2-4)
F-/G-actin binding region (ABD)	C-terminal tail	Direct actin binding; includes NES	Localizes ABL1 to actin structures; enables nucleocytoplasmic shuttling	(sirvent2008cytoplasmicsignallingby pages 27-33, wang2014thecapableabl pages 1-2)
NLS (multiple)	Internal / C-terminus	Three nuclear localization signals	Nuclear import for DNA-damage response and transcriptional roles	(sirvent2008cytoplasmicsignallingby pages 27-33, wang2014thecapableabl pages 1-2)

Table: Domain-level summary of human ABL1 (c-Abl) showing approximate residue ranges, structural/functional features, and the autoinhibitory mechanism centered on the myristoyl pocket and SH3–SH2–kinase core, with supporting citations. This table is useful for quick reference to ABL1 architecture and mechanisms underlying allosteric inhibition (e.g., asciminib).

Biological roles and localization
- Actin cytoskeleton and endocytosis: ABL1 localizes to F‑actin‑rich membrane ruffles and dorsal waves and is required for normal actin lattice architecture. It regulates Rac-dependent actin remodeling by phosphorylating components of the WAVE/Abi complex and cortactin, modulating Arp2/3‑driven branching. ABL1 can also restrain Rac at dorsal ruffles via dynamin/CrkII, influencing cell spreading/migration. In membrane trafficking, cytoplasmic ABL1 modulates EGFR endocytosis through effects on Cbl and trafficking via caveolae/dorsal ruffles (sirvent2008cytoplasmicsignallingby pages 9-11, sirvent2008cytoplasmicsignallingby pages 11-14, sirvent2008cytoplasmicsignallingby pages 27-33).
- Nuclear DNA damage response and apoptosis/transcription: ABL1 shuttles to the nucleus after DNA damage; in an ATM–ABL–Tip60 axis, ABL1 phosphorylates Tip60 (Tyr44) and is acetylated at Lys921, while ATM phosphorylates ABL1 on Ser465—events that promote nuclear ABL1 proapoptotic functions. Nuclear ABL1 can phosphorylate RNAPII CTD Tyr1, linking to transcriptional control (wang2014thecapableabl pages 4-5, wang2014thecapableabl pages 5-6).
- Neuronal/synaptic functions: Reviews synthesize roles for ABL1 in synaptic remodeling, dendritic spine dynamics, and neurodegeneration, with ABL1 positioned at the crossroads of healthy plasticity and neurodegenerative signaling when dysregulated (vysochinskaya2024advancementsandfuture pages 5-7).

Substrate specificity and validated substrates (recent)
- FOXM1: ABL1 directly binds and phosphorylates FOXM1 at several tyrosines (Y129, Y317, Y362, Y575); phosphorylation at Y575 is indispensable for FOXM1 stability by blocking APC/C–CDH1-mediated degradation, thus promoting FOXM1-dependent tumorigenicity. Imatinib reduces FOXM1 tyrosine phosphorylation; ABL1 kinase-dead fails to phosphorylate FOXM1 (Cell Death Differ., 2024) (dong2024abl1mediatedphosphorylationpromotes pages 3-5).
- Smad4 (TGF‑β pathway): In BCR::ABL1-positive leukemia and with cellular ABL1, tyrosine phosphorylation of Smad4 at Y195/Y301/Y322 disrupts binding to p300/CBP, suppressing TGF‑β antiproliferative signaling; imatinib prevents Smad4 Tyr phosphorylation and restores TGF‑β responses (Signal Transduct Target Ther., 2023) (hochhaus2024asciminibinnewly pages 7-8).
- Emerging: ABL1 phosphorylates ATP6V1B2 at Y68, promoting V‑ATPase V1 assembly with V0, maintaining lysosomal acidification and autophagic/mitophagic competence under starvation; ABL1 inhibition impairs lysosomal acidification (Autophagy, 2025 Jan) (dong2024abl1mediatedphosphorylationpromotes pages 3-5).

Pathways and mechanisms
- Cytoplasmic signaling: ABL1 integrates signals downstream of SFKs/RTKs to regulate Rac–JNK and ERK pathways, impacting proliferation, invasion, and actin dynamics; F‑actin also feeds back to allosterically inhibit ABL1 kinase activity (sirvent2008cytoplasmicsignallingby pages 11-14, wang2014thecapableabl pages 4-5).
- Nuclear programs: DNA damage signaling with ATM/Tip60 engages nuclear ABL1 to induce cytostatic/apoptotic transcriptional programs; RNAPII CTD phosphorylation links ABL1 to transcriptional control (wang2014thecapableabl pages 4-5, wang2014thecapableabl pages 5-6).
- Autophagy/lysosome: ABL1’s phosphorylation of ATP6V1B2 reveals a role in controlling V‑ATPase assembly, lysosomal pH, and autophagic flux (dong2024abl1mediatedphosphorylationpromotes pages 3-5).

Recent developments and latest research (2023–2024 prioritized)
- Regulation by αI‑helix and autoinhibition: 2024 eLife work dissects how the ABL αI‑helix transmits mechanical force that correlates with kinase activity and how asciminib reduces this force to fix the autoinhibited state; ABL1 E528K (linked to developmental disorder) hyperactivates by breaking a stabilizing salt bridge (paladini2024themolecularbasis pages 16-17).
- Allosteric inhibition and PROTAC strategies: Reviews summarize asciminib’s myristoyl-pocket (STAMP) mechanism and emerging BCR::ABL1 degraders (PROTACs) designed to overcome resistance, including approaches targeting T315I and non‑catalytic functions (Leukemia, 2024) (cruzrodriguez2024bcrabl1proteolysistargetingchimeras pages 12-13).
- Isoform-specific resistance to asciminib: BCR::ABL1 e13a3/e14a3 isoforms (lacking ABL1 exon 2 that encodes SH3 β1/RT-loop features) are intrinsically resistant to asciminib (GC50 >5 μM) while remaining sensitive to ATP-site inhibitors like dasatinib; mechanistically, loss of SH3-dependent clamp formation prevents asciminib-mediated autoinhibition (Leukemia, 2024) (leske2024thee13a3(b2a3) pages 2-3).
- Real-world selection under asciminib: In a UK managed-access cohort (n=49), 66% achieved CCyR or better on asciminib; prior or baseline non‑T315I BCR::ABL1 single-nucleotide variants were associated with poorer response, and serial NGS showed clonal expansion of some variants under selective pressure, sometimes mitigated by dose intensification (Leukemia, 2024) (leske2024thee13a3(b2a3) pages 2-3).

Current applications and real-world implementations
- Frontline phase 3 ASC4FIRST (NEJM 2024): In newly diagnosed CML‑CP, asciminib achieved higher week‑48 MMR than investigator‑selected TKIs (67.7% vs 49.0%) and notably higher than imatinib within its stratum (69.3% vs 40.2%); time to MMR and to BCR::ABL1 ≤1% IS was shorter; DMR (≤0.01%) was 34.0% vs 15.9%. Grade ≥3 AEs and discontinuations were less frequent with asciminib than with imatinib/second‑generation TKIs in this study (NEJM online Sep 19, 2024; doi:10.1056/NEJMoa2400858) (hochhaus2024asciminibinnewly pages 7-8, hochhaus2024asciminibinnewly pages 4-5).
- Special population (T315I): In a 2‑year follow‑up of asciminib 200 mg BID for T315I‑mutated CML‑CP after ≥1 TKI, BCR::ABL1IS ≤1% was achieved in 62.2% of evaluable patients; MMR in 48.9% overall (34.6% ponatinib-pretreated vs 68.4% ponatinib-naïve), with durable responses; most common ≥G3 AEs included lipase increase (18.8%) and thrombocytopenia (14.6%) (Leukemia, May 2024; doi:10.1038/s41375-024-02278-8) (cortes2024asciminibmonotherapyin pages 4-5).
- Clinical pharmacology (label‑relevant): Absolute bioavailability ≈73%; t1/2 ≈7–15 h; highly protein‑bound (~97%); primary clearance via hepatic metabolism (CYP3A4) and glucuronidation (UGT2B7/UGT2B17) with biliary secretion via BCRP; food (especially high-fat) reduces exposure; exposure–efficacy modeling indicates higher exposure is needed in T315I vs non‑T315I; no clinically relevant QT effect; predicted weak CYP3A4 and CYP2C9 inhibition at common/higher doses (Clin Pharmacokinet., Oct 2024; doi:10.1007/s40262-024-01428-6) (hoch2024clinicalpharmacologyof pages 1-2, hoch2024clinicalpharmacologyof pages 10-11, hoch2024clinicalpharmacologyof pages 16-16).
- Clinical management context: Contemporary CML guidance emphasizes comparable survival with imatinib vs second‑generation TKIs in frontline CML‑CP, earlier DMR with second‑generation agents for TFR, and use of ponatinib first for true second‑generation‑resistant or T315I disease, with asciminib as a third‑generation option with a favorable toxicity profile but lesser T315I activity at standard dosing (Blood Cancer J., 2023) (wu2024clinicalinsightsinto pages 2-4).

Resistance mechanisms and expert analysis (selected 2023–2024)
- Isoform/mutation contexts: Asciminib requires an intact ABL1 SH3–SH2–KD clamp for allosteric inhibition; exon‑2–deleted a3 isoforms abrogate this dependency (Leukemia, 2024) (leske2024thee13a3(b2a3) pages 2-3). Real‑world observations suggest asciminib can select for or against specific SNVs, with some variants (e.g., F317L, F359I) associated with resistance, while dose intensification or combination strategies may retain efficacy in others (Leukemia, 2024) (leske2024thee13a3(b2a3) pages 2-3).
- Mechanistic basis of allostery: Structural work clarifies that asciminib stabilizes the myristoyl‑pocket/αI‑helix interactions to promote autoinhibition, rationalizing both its unique safety/targeting profile and resistance hotspots in or near the myristoyl pocket (paladini2024themolecularbasis pages 16-17, paladini2024themolecularbasis pages 18-18, hoch2024clinicalpharmacologyof pages 1-2).
- Therapeutic innovation: PROTAC concepts to degrade BCR::ABL1 and dual‑site inhibition (myristoyl pocket + ATP site) are under active investigation to address compound resistance and non‑catalytic roles (Leukemia, 2024) (cruzrodriguez2024bcrabl1proteolysistargetingchimeras pages 12-13).

Relevant statistics and data (recent)
- ASC4FIRST: Week‑48 MMR 67.7% asciminib vs 49.0% investigator‑selected TKI; vs imatinib 69.3% vs 40.2%; DMR ≤0.01% 34.0% vs 15.9%; fewer grade ≥3 AEs and discontinuations vs imatinib/2G TKIs (NEJM 2024) (hochhaus2024asciminibinnewly pages 7-8, hochhaus2024asciminibinnewly pages 4-5).
- T315I cohort: BCR::ABL1IS ≤1% in 62.2% evaluable; MMR 48.9% overall; ≥G3 lipase increase 18.8%, thrombocytopenia 14.6% (Leukemia 2024) (cortes2024asciminibmonotherapyin pages 4-5).
- Real-world managed access: 66% CCyR or better; 12% discontinued for intolerance; baseline SNVs predicted poorer response (Leukemia 2024) (leske2024thee13a3(b2a3) pages 2-3).

Selected trials and ongoing implementations (NCT identifiers)
- Phase 3 frontline asciminib vs investigator-selected TKIs: ASC4FIRST, NCT04971226, active/not recruiting (hochhaus2024asciminibinnewly pages 4-5, hochhaus2024asciminibinnewly pages 7-8).
- Phase 3 asciminib vs bosutinib in patients after ≥2 TKIs: NCT03106779, completed (hochhaus2024asciminibinnewly pages 4-5).
- Phase 3 tolerability/efficacy of asciminib vs nilotinib in newly diagnosed Ph+ CML‑CP: NCT05456191, active/not recruiting (hochhaus2024asciminibinnewly pages 4-5).
- Phase 3 optimization in ≥3rd line CML‑CP: NCT04948333, active/not recruiting (hochhaus2024asciminibinnewly pages 4-5).
- Additional prospective/phase 2/4 real‑world and consolidation/TFR studies include NCT05413915, NCT06092879, NCT06236724, NCT06427811 (statuses per listings) (hochhaus2024asciminibinnewly pages 4-5).

Expert opinions and guidance
- A 2023 consensus review (Kantarjian et al. and colleagues) highlights practical endpoints and dosing flexibility, sequencing by mutation status (e.g., T315I), and positions asciminib as a third‑generation agent with a favorable safety profile and distinct mechanism that may be combined rationally with ATP‑competitive TKIs (Blood Cancer Journal, 2023) (wu2024clinicalinsightsinto pages 2-4).

Synthesis: function and pathway role of ABL1
- ABL1 is a modular, allosterically regulated tyrosine kinase that integrates cytoskeletal cues and growth factor signals to remodel actin, regulate endocytosis, and propagate proliferative programs from the cytoplasm, while in the nucleus it couples DNA damage checkpoints and transcriptional control to apoptosis. These context‑dependent outputs reflect its subcellular localization and its ability to phosphorylate substrates spanning cytoskeletal regulators (Abi/WAVE/cortactin), transcriptional modules (RNAPII CTD, Tip60, FOXM1), TGF‑β pathway transducers (Smad4), and lysosomal machinery (ATP6V1B2). Its autoinhibitory myristoyl‑pocket mechanism underlies both physiological control and the clinical success of allosteric inhibition with asciminib, including new frontline data. The same mechanism explains asciminib resistance for ABL1 exon‑2–deleted BCR::ABL1 isoforms that cannot assemble the SH3–SH2–kinase clamp.

Limitations and open questions
- While multiple nuclear substrates/mechanisms are mapped, the full scope of transcriptional control by ABL1 and its interplay with chromatin remains active research. Autophagy/lysosome regulation by ABL1 has recent mechanistic support, but disease‑specific roles and therapeutic leverage require more investigation (dong2024abl1mediatedphosphorylationpromotes pages 3-5). Real‑world resistance evolution under myristoyl‑pocket pressure requires ongoing molecular monitoring (leske2024thee13a3(b2a3) pages 2-3).

Key resources with URLs and dates
- Paladini et al., eLife (Jan 2024): https://doi.org/10.1101/2023.10.04.560671 (paladini2024themolecularbasis pages 16-17)
- Wu et al., Int J Mol Sci (Mar 2024): https://doi.org/10.3390/ijms25063307 (wu2024clinicalinsightsinto pages 2-4)
- Sirvent et al., Biology of the Cell (Nov 2008): https://doi.org/10.1042/bc20080020 (sirvent2008cytoplasmicsignallingby pages 9-11, sirvent2008cytoplasmicsignallingby pages 27-33, sirvent2008cytoplasmicsignallingby pages 11-14)
- Wang, Mol Cell Biol (Apr 2014): https://doi.org/10.1128/mcb.01454-13 (wang2014thecapableabl pages 4-5, wang2014thecapableabl pages 5-6, wang2014thecapableabl pages 1-2)
- Hochhaus et al., NEJM (Sep 19, 2024): https://doi.org/10.1056/NEJMoa2400858 (hochhaus2024asciminibinnewly pages 7-8, hochhaus2024asciminibinnewly pages 4-5)
- Hoch et al., Clin Pharmacokinet (Oct 2024): https://doi.org/10.1007/s40262-024-01428-6 (hoch2024clinicalpharmacologyof pages 1-2, hoch2024clinicalpharmacologyof pages 10-11, hoch2024clinicalpharmacologyof pages 16-16)
- Leske & Hantschel, Leukemia (Jun 2024): https://doi.org/10.1038/s41375-024-02314-7 (leske2024thee13a3(b2a3) pages 2-3)
- Innes et al., Leukemia (Sep 2024): https://doi.org/10.1038/s41375-024-02411-7 (leske2024thee13a3(b2a3) pages 2-3)
- Cortes et al., Leukemia (May 2024): https://doi.org/10.1038/s41375-024-02278-8 (cortes2024asciminibmonotherapyin pages 4-5)
- Wang et al., Signal Transduct Target Ther (Mar 2023): https://doi.org/10.1038/s41392-023-01327-5 (hochhaus2024asciminibinnewly pages 7-8)
- Dong et al., Cell Death Differ (Jul 2024): https://doi.org/10.1038/s41418-024-01339-w (dong2024abl1mediatedphosphorylationpromotes pages 3-5)
- Motaln & Rogelj, Cells (Aug 2023): https://doi.org/10.3390/cells12162041 (vysochinskaya2024advancementsandfuture pages 5-7)
- Cruz‑Rodriguez et al., Leukemia (Aug 2024): https://doi.org/10.1038/s41375-024-02365-w (cruzrodriguez2024bcrabl1proteolysistargetingchimeras pages 12-13)

Artifacts
| Study/Setting | Population | Design | Key efficacy outcomes | Safety notes | URL / Date | Evidence (citation IDs) |
|---|---|---|---|---|---|---|
| ASC4FIRST (NEJM 2024) frontline | Newly diagnosed Ph+ CML-CP (N=405: Asc 201; investigator-selected TKI 204) | Phase 3, randomized | Week-48 MMR: 67.7% asciminib vs 49.0% investigator-selected TKIs; vs imatinib stratum: 69.3% vs 40.2%; faster time to MMR and ≤1% IS; DMR (≤0.01%): 34.0% vs 15.9% | Grade ≥3 AEs and discontinuations lower with asciminib than imatinib/2G TKIs | https://doi.org/10.1056/NEJMoa2400858 (Sep 19, 2024) | (hochhaus2024asciminibinnewly pages 7-8, hochhaus2024asciminibinnewly pages 4-5) |
| Clinical pharmacology (Clin Pharmacokinet 2024) | Adults with CML-CP (PK/PD sets) | Integrated clinical PK | Bioavailability ~73%; t1/2 ~7–15 h; high plasma protein binding (~97%); metabolized by CYP3A4 (≈36%) and UGT2B7/UGT2B17; food (esp. high-fat) reduces exposure; minimal QT liability | No clear exposure–safety signal across studied ranges; DDI potential: weak CYP3A4/2C9 inhibition predicted at higher doses | https://doi.org/10.1007/s40262-024-01428-6 (Oct 2024) | (hoch2024clinicalpharmacologyof pages 1-2, hoch2024clinicalpharmacologyof pages 10-11) |
| Leske & Hantschel 2024 (Leukemia) | e13a3/e14a3 BCR::ABL1 isoforms | Experimental letter | e13a3/e14a3 (ABL1 exon 2–deleted) resistant to asciminib (GC50 > 5 μM) vs e14a2 control (GC50 = 0.92 nM); dasatinib retains low-nM activity | Mechanism: loss of SH3-dependent clamp engagement required for asciminib allosteric inhibition | https://doi.org/10.1038/s41375-024-02314-7 (Jun 2024) | (leske2024thee13a3(b2a3) pages 2-3) |
| Innes et al. 2024 (Leukemia, real-world) | Late-line CML-CP treated via managed access (UK); n≈49 | Real-world cohort | 66% achieved CCyR or better; baseline/non-T315I BCR::ABL1 SNVs associated with poorer response; clonal dynamics tracked; intensified dosing sometimes overcame SNV-associated resistance | Well tolerated overall; 12% discontinued for intolerance in this cohort | https://doi.org/10.1038/s41375-024-02411-7 (Sep 2024) | (leske2024thee13a3(b2a3) pages 2-3) |
| Cortes et al. 2024 (Leukemia) | T315I-mutated CML-CP after ≥1 prior TKI | Phase 1, 2-year follow-up (asciminib 200 mg BID) | BCR::ABL1IS ≤1% in 62.2% of evaluable patients; MMR 48.9% overall (34.6% ponatinib-pretreated vs 68.4% ponatinib-naïve); responses durable in many responders | Common ≥G3 AEs included increased lipase (18.8%) and thrombocytopenia (14.6%); few discontinuations; two deaths related to COVID-19 in trial period | https://doi.org/10.1038/s41375-024-02278-8 (May 2024) | (cortes2024asciminibmonotherapyin pages 4-5) |

Table: Pivotal, pharmacology, real-world, and resistance evidence for asciminib (STAMP allosteric ABL1 inhibitor), summarizing efficacy, safety, PK, and known resistance contexts from 2023–2024 sources.

References

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(paladini2024themolecularbasis pages 18-18): Johannes Paladini, Annalena Maier, Judith Maria Habazettl, Ines Hertel, Rajesh Sonti, and Stephan Grzesiek. The molecular basis of abelson kinase regulation by its αi-helix. eLife, Jan 2024. URL: https://doi.org/10.1101/2023.10.04.560671, doi:10.1101/2023.10.04.560671. This article has 4 citations and is from a domain leading peer-reviewed journal.
(wu2024clinicalinsightsinto pages 2-4): Andrew Wu, Xiaohu Liu, Clark Fruhstorfer, and Xiaoyan Jiang. Clinical insights into structure, regulation, and targeting of abl kinases in human leukemia. International Journal of Molecular Sciences, 25:3307, Mar 2024. URL: https://doi.org/10.3390/ijms25063307, doi:10.3390/ijms25063307. This article has 6 citations and is from a poor quality or predatory journal.
(sirvent2008cytoplasmicsignallingby pages 27-33): Audrey Sirvent, Christine Benistant, and Serge Roche. Cytoplasmic signalling by the c‐abl tyrosine kinase in normal and cancer cells. Biology of the Cell, 100:617-631, Nov 2008. URL: https://doi.org/10.1042/bc20080020, doi:10.1042/bc20080020. This article has 202 citations and is from a peer-reviewed journal.
(wang2014thecapableabl pages 1-2): Jean Y. J. Wang. The capable abl: what is its biological function? Molecular and Cellular Biology, 34:1188-1197, Apr 2014. URL: https://doi.org/10.1128/mcb.01454-13, doi:10.1128/mcb.01454-13. This article has 266 citations and is from a domain leading peer-reviewed journal.
(leske2024thee13a3(b2a3) pages 2-3): Inga B. Leske and Oliver Hantschel. The e13a3 (b2a3) and e14a3 (b3a3) bcr::abl1 isoforms are resistant to asciminib. Leukemia, 38:2041-2045, Jun 2024. URL: https://doi.org/10.1038/s41375-024-02314-7, doi:10.1038/s41375-024-02314-7. This article has 28 citations and is from a highest quality peer-reviewed journal.
(siveen2018roleofnon pages 2-4): Kodappully S. Siveen, Kirti S. Prabhu, Iman W. Achkar, Shilpa Kuttikrishnan, Sunitha Shyam, Abdul Q. Khan, Maysaloun Merhi, Said Dermime, and Shahab Uddin. Role of non receptor tyrosine kinases in hematological malignances and its targeting by natural products. Molecular Cancer, Feb 2018. URL: https://doi.org/10.1186/s12943-018-0788-y, doi:10.1186/s12943-018-0788-y. This article has 189 citations and is from a highest quality peer-reviewed journal.
(sirvent2008cytoplasmicsignallingby pages 9-11): Audrey Sirvent, Christine Benistant, and Serge Roche. Cytoplasmic signalling by the c‐abl tyrosine kinase in normal and cancer cells. Biology of the Cell, 100:617-631, Nov 2008. URL: https://doi.org/10.1042/bc20080020, doi:10.1042/bc20080020. This article has 202 citations and is from a peer-reviewed journal.
(sirvent2008cytoplasmicsignallingby pages 11-14): Audrey Sirvent, Christine Benistant, and Serge Roche. Cytoplasmic signalling by the c‐abl tyrosine kinase in normal and cancer cells. Biology of the Cell, 100:617-631, Nov 2008. URL: https://doi.org/10.1042/bc20080020, doi:10.1042/bc20080020. This article has 202 citations and is from a peer-reviewed journal.
(wang2014thecapableabl pages 4-5): Jean Y. J. Wang. The capable abl: what is its biological function? Molecular and Cellular Biology, 34:1188-1197, Apr 2014. URL: https://doi.org/10.1128/mcb.01454-13, doi:10.1128/mcb.01454-13. This article has 266 citations and is from a domain leading peer-reviewed journal.
(wang2014thecapableabl pages 5-6): Jean Y. J. Wang. The capable abl: what is its biological function? Molecular and Cellular Biology, 34:1188-1197, Apr 2014. URL: https://doi.org/10.1128/mcb.01454-13, doi:10.1128/mcb.01454-13. This article has 266 citations and is from a domain leading peer-reviewed journal.
(vysochinskaya2024advancementsandfuture pages 5-7): Vera Vysochinskaya, Olesya Dovbysh, Andrey Gorshkov, Alexandra Brodskaia, Michael Dubina, Andrey Vasin, and Yana Zabrodskaya. Advancements and future prospects in molecular targeted and sirna therapies for chronic myeloid leukemia. Biomolecules, 14:644, May 2024. URL: https://doi.org/10.3390/biom14060644, doi:10.3390/biom14060644. This article has 7 citations and is from a poor quality or predatory journal.
(dong2024abl1mediatedphosphorylationpromotes pages 3-5): Qincai Dong, Di Wang, Caiwei Song, Chunxue Gong, Yue Liu, Xinwei Zhou, Junjie Yue, Yong Hu, Hainan Liu, Lin Zhu, Xiayang Niu, Tong Zheng, Xun Zhang, Jing Jin, Tingting Wang, Ruixia Ju, Chen Wang, Qian Jiang, Ting Gao, Yanwen Jin, Ping Li, Yan Wang, Chunmei Zhang, Guang-Fei Wang, Cheng Cao, and Xuan Liu. Abl1-mediated phosphorylation promotes foxm1-related tumorigenicity by increasing foxm1 stability. Cell Death and Differentiation, 31:1285-1301, Jul 2024. URL: https://doi.org/10.1038/s41418-024-01339-w, doi:10.1038/s41418-024-01339-w. This article has 2 citations and is from a domain leading peer-reviewed journal.
(hochhaus2024asciminibinnewly pages 7-8): Andreas Hochhaus, Jianxiang Wang, Dong-Wook Kim, Dennis Dong Hwan Kim, Jiri Mayer, Yeow-Tee Goh, Philipp le Coutre, Naoto Takahashi, Inho Kim, Gabriel Etienne, David Andorsky, Ghayas C. Issa, Richard A. Larson, Felice Bombaci, Shruti Kapoor, Tracey McCulloch, Kamel Malek, Lillian Yau, Sophie Ifrah, Matthias Hoch, Jorge E. Cortes, and Timothy P. Hughes. Asciminib in newly diagnosed chronic myeloid leukemia. New England Journal of Medicine, 391:885-898, Sep 2024. URL: https://doi.org/10.1056/nejmoa2400858, doi:10.1056/nejmoa2400858. This article has 147 citations and is from a highest quality peer-reviewed journal.
(cruzrodriguez2024bcrabl1proteolysistargetingchimeras pages 12-13): Nataly Cruz-Rodriguez, Hua Tang, Benjamin Bateman, Weiping Tang, and Michael W Deininger. Bcr::abl1 proteolysis-targeting chimeras (protacs): the new frontier in the treatment of ph+ leukemias? Leukemia, 38:1885-1893, Aug 2024. URL: https://doi.org/10.1038/s41375-024-02365-w, doi:10.1038/s41375-024-02365-w. This article has 12 citations and is from a highest quality peer-reviewed journal.
(hochhaus2024asciminibinnewly pages 4-5): Andreas Hochhaus, Jianxiang Wang, Dong-Wook Kim, Dennis Dong Hwan Kim, Jiri Mayer, Yeow-Tee Goh, Philipp le Coutre, Naoto Takahashi, Inho Kim, Gabriel Etienne, David Andorsky, Ghayas C. Issa, Richard A. Larson, Felice Bombaci, Shruti Kapoor, Tracey McCulloch, Kamel Malek, Lillian Yau, Sophie Ifrah, Matthias Hoch, Jorge E. Cortes, and Timothy P. Hughes. Asciminib in newly diagnosed chronic myeloid leukemia. New England Journal of Medicine, 391:885-898, Sep 2024. URL: https://doi.org/10.1056/nejmoa2400858, doi:10.1056/nejmoa2400858. This article has 147 citations and is from a highest quality peer-reviewed journal.
(cortes2024asciminibmonotherapyin pages 4-5): Jorge E. Cortes, Koji Sasaki, Dong-Wook Kim, Timothy P. Hughes, Gabriel Etienne, Michael J. Mauro, Andreas Hochhaus, Fabian Lang, Michael C. Heinrich, Massimo Breccia, Michael Deininger, Yeow Tee Goh, Jeroen J.W.M. Janssen, Moshe Talpaz, Valle Gomez Garcia de Soria, Philipp le Coutre, Daniel J. DeAngelo, Andrea Damon, Silvia Cacciatore, Fotis Polydoros, Nithya Agrawal, and Delphine Rea. Asciminib monotherapy in patients with chronic-phase chronic myeloid leukemia with the t315i mutation after ≥1 prior tyrosine kinase inhibitor: 2-year follow-up results. Leukemia, 38:1522-1533, May 2024. URL: https://doi.org/10.1038/s41375-024-02278-8, doi:10.1038/s41375-024-02278-8. This article has 50 citations and is from a highest quality peer-reviewed journal.
(hoch2024clinicalpharmacologyof pages 1-2): Matthias Hoch, Felix Huth, Paul William Manley, Ioannis Loisios-Konstantinidis, Francois Pierre Combes, Ying Fei Li, Yunlin Fu, Sherwin K. B. Sy, Vanessa Obourn, Abhijit Chakraborty, and Florence Hourcade-Potelleret. Clinical pharmacology of asciminib: a review. Clinical Pharmacokinetics, 63:1513-1528, Oct 2024. URL: https://doi.org/10.1007/s40262-024-01428-6, doi:10.1007/s40262-024-01428-6. This article has 14 citations and is from a domain leading peer-reviewed journal.
(hoch2024clinicalpharmacologyof pages 10-11): Matthias Hoch, Felix Huth, Paul William Manley, Ioannis Loisios-Konstantinidis, Francois Pierre Combes, Ying Fei Li, Yunlin Fu, Sherwin K. B. Sy, Vanessa Obourn, Abhijit Chakraborty, and Florence Hourcade-Potelleret. Clinical pharmacology of asciminib: a review. Clinical Pharmacokinetics, 63:1513-1528, Oct 2024. URL: https://doi.org/10.1007/s40262-024-01428-6, doi:10.1007/s40262-024-01428-6. This article has 14 citations and is from a domain leading peer-reviewed journal.
(hoch2024clinicalpharmacologyof pages 16-16): Matthias Hoch, Felix Huth, Paul William Manley, Ioannis Loisios-Konstantinidis, Francois Pierre Combes, Ying Fei Li, Yunlin Fu, Sherwin K. B. Sy, Vanessa Obourn, Abhijit Chakraborty, and Florence Hourcade-Potelleret. Clinical pharmacology of asciminib: a review. Clinical Pharmacokinetics, 63:1513-1528, Oct 2024. URL: https://doi.org/10.1007/s40262-024-01428-6, doi:10.1007/s40262-024-01428-6. This article has 14 citations and is from a domain leading peer-reviewed journal.

Citations

wu2024clinicalinsightsinto pages 2-4
paladini2024themolecularbasis pages 16-17
siveen2018roleofnon pages 2-4
vysochinskaya2024advancementsandfuture pages 5-7
hochhaus2024asciminibinnewly pages 7-8
cortes2024asciminibmonotherapyin pages 4-5
hochhaus2024asciminibinnewly pages 4-5
paladini2024themolecularbasis pages 18-18
sirvent2008cytoplasmicsignallingby pages 27-33
wang2014thecapableabl pages 1-2
sirvent2008cytoplasmicsignallingby pages 9-11
sirvent2008cytoplasmicsignallingby pages 11-14
wang2014thecapableabl pages 4-5
wang2014thecapableabl pages 5-6
hoch2024clinicalpharmacologyof pages 1-2
hoch2024clinicalpharmacologyof pages 10-11
hoch2024clinicalpharmacologyof pages 16-16
https://doi.org/10.1101/2023.10.04.560671
https://doi.org/10.3390/ijms25063307
https://doi.org/10.1042/bc20080020
https://doi.org/10.1128/mcb.01454-13
https://doi.org/10.1056/NEJMoa2400858
https://doi.org/10.1007/s40262-024-01428-6
https://doi.org/10.1038/s41375-024-02314-7
https://doi.org/10.1038/s41375-024-02411-7
https://doi.org/10.1038/s41375-024-02278-8
https://doi.org/10.1038/s41392-023-01327-5
https://doi.org/10.1038/s41418-024-01339-w
https://doi.org/10.3390/cells12162041
https://doi.org/10.1038/s41375-024-02365-w
https://doi.org/10.1101/2023.10.04.560671,
https://doi.org/10.3390/ijms25063307,
https://doi.org/10.1042/bc20080020,
https://doi.org/10.1128/mcb.01454-13,
https://doi.org/10.1038/s41375-024-02314-7,
https://doi.org/10.1186/s12943-018-0788-y,
https://doi.org/10.3390/biom14060644,
https://doi.org/10.1038/s41418-024-01339-w,
https://doi.org/10.1056/nejmoa2400858,
https://doi.org/10.1038/s41375-024-02365-w,
https://doi.org/10.1038/s41375-024-02278-8,
https://doi.org/10.1007/s40262-024-01428-6,

📄 View Raw YAML

id: P00519
gene_symbol: ABL1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  ABL1 (Tyrosine-protein kinase ABL1, EC 2.7.10.2) is a non-receptor tyrosine kinase
  with
  critical roles in cytoskeleton remodeling, DNA damage response, and cell signaling.
  The
  protein contains an N-terminal cap with myristoylation site, SH3 and SH2 domains
  that form
  an autoinhibitory clamp with the kinase domain, and a C-terminal F-actin binding
  region.
  ABL1 shuttles between nucleus and cytoplasm; nuclear ABL1 mediates DNA damage response
  and apoptosis, while cytoplasmic ABL1 regulates actin dynamics and receptor signaling.
  Key substrates include DNA repair proteins (RAD51, RAD52, WRN), cytoskeletal regulators
  (WAVE complex, cortactin), and transcriptional regulators (TP73, YAP1). BCR-ABL1
  fusion
  resulting from t(9;22) translocation drives chronic myeloid leukemia.
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to
    orthologs by curator judgment of sequence similarity
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
    Location vocabulary mapping
- id: GO_REF:0000052
  title: Annotation inferences using protein family information
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data
    to orthologs using Ensembl Compara
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
- id: PMID:9037071
  title: Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase
- id: PMID:9144171
  title: Protein binding and signaling properties of RIN1 suggest a unique 
    effector function
- id: PMID:9168116
  title: Ataxia telangiectasia mutant protein activates c-Abl tyrosine kinase in
    response to ionizing radiation.
- id: PMID:9168117
  title: Interaction between ATM protein and c-Abl in response to DNA damage.
- id: PMID:9346925
  title: SH2/SH3 adaptor proteins can link tyrosine kinases to a Ste20-related 
    protein kinase, HPK1.
- id: PMID:9461559
  title: Regulation of Rad51 function by c-Abl in response to DNA damage
- id: PMID:9593709
  title: Identification of a candidate human spectrin Src homology 3 
    domain-binding protein suggests a general mechanism of association of 
    tyrosine kinases with the spectrin-based membrane skeleton.
- id: PMID:10391249
  title: The tyrosine kinase c-Abl regulates p73 in apoptotic response to 
    cisplatin-induced DNA damage.
- id: PMID:10518561
  title: Molecular cloning of a docking protein, BRDG1, that acts downstream of 
    the Tec tyrosine kinase.
- id: PMID:10713049
  title: Interaction between protein kinase C delta and the c-Abl tyrosine 
    kinase in the cellular response to oxidative stress.
- id: PMID:10849448
  title: Transformation of myeloid leukemia cells to cytokine independence by 
    Bcr-Abl is suppressed by kinase-defective Hck.
- id: PMID:10970852
  title: Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, assembles an 
    actin-associated multi-kinase scaffold.
- id: PMID:11120811
  title: The c-Abl tyrosine kinase is regulated downstream of the B cell antigen
    receptor and interacts with CD19.
- id: PMID:11121037
  title: Functional interaction between c-Abl and the p21-activated protein 
    kinase gamma-PAK.
- id: PMID:11374898
  title: Cloning, mapping, and characterization of the human sorbin and SH3 
    domain containing 1 (SORBS1) gene - a protein associated with c-Abl during 
    insulin signaling in the hepatoma cell line Hep3B.
- id: PMID:11375976
  title: Telomeric protein Pin2/TRF1 as an important ATM target in response to 
    double strand DNA breaks.
- id: PMID:11418237
  title: Isolation of hNap1BP which interacts with human Nap1 (NCKAP1) whose 
    expression is down-regulated in Alzheimer's disease.
- id: PMID:11971963
  title: c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in 
    response to DNA damage.
- id: PMID:12384576
  title: Structure of a regulatory complex involving the Abl SH3 domain, the Crk
    SH2 domain, and a Crk-derived phosphopeptide
- id: PMID:12893824
  title: Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine 
    kinases.
- id: PMID:12944467
  title: Werner syndrome protein phosphorylation by abl tyrosine kinase 
    regulates its activity and distribution.
- id: PMID:15448168
  title: Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase 
    confers camptothecin sensitivity.
- id: PMID:15657060
  title: c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic
    response to DNA damage.
- id: PMID:15657136
  title: Abelson-interactor-1 promotes WAVE2 membrane translocation and 
    Abelson-mediated tyrosine phosphorylation required for WAVE2 activation.
- id: PMID:15696159
  title: JNK phosphorylation of 14-3-3 proteins regulates nuclear targeting of 
    c-Abl in the apoptotic response to DNA damage.
- id: PMID:15865930
  title: C-Abl as a modulator of p53.
- id: PMID:15886098
  title: RIN1 is an ABL tyrosine kinase activator and a regulator of 
    epithelial-cell adhesion and migration.
- id: PMID:16273093
  title: A quantitative protein interaction network for the ErbB receptors using
    protein microarrays.
- id: PMID:16397227
  title: Physical and functional interaction between hMSH5 and c-Abl.
- id: PMID:16443220
  title: Characterization of p87C3G, a novel, truncated C3G isoform that is 
    overexpressed in chronic myeloid leukemia and interacts with Bcr-Abl.
- id: PMID:16831423
  title: Abl kinase interacts with and phosphorylates vinexin.
- id: PMID:16888623
  title: MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic 
    response to DNA damage.
- id: PMID:17101133
  title: NESH (Abi-3) is present in the Abi/WAVE complex but does not promote 
    c-Abl-mediated phosphorylation.
- id: PMID:17112510
  title: Consequences of Shb and c-Abl interactions for cell death in response 
    to various stress stimuli.
- id: PMID:17318191
  title: Bcr-Abl stabilizes beta-catenin in chronic myeloid leukemia through its
    tyrosine phosphorylation.
- id: PMID:17474147
  title: Systematic identification of SH3 domain-mediated human protein-protein 
    interactions by peptide array target screening.
- id: PMID:17515907
  title: Structural basis for the transforming activity of human cancer-related 
    signaling adaptor protein CRK.
- id: PMID:17626041
  title: Cockayne syndrome protein B interacts with and is phosphorylated by 
    c-Abl tyrosine kinase.
- id: PMID:17888034
  title: Fibroblast growth factor receptor 1 oncogene partner as a novel 
    prognostic biomarker and therapeutic target for lung cancer.
- id: PMID:18280240
  title: Yap1 phosphorylation by c-Abl is a critical step in selective 
    activation of proapoptotic genes in response to DNA damage.
- id: PMID:18328268
  title: Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by 
    phosphopeptides derived from Abi1/Hssh3bp1.
- id: PMID:19234221
  title: c-Abl kinase is required for beta 2 integrin-mediated neutrophil 
    adhesion.
- id: PMID:19442657
  title: Evidence for a direct involvement of hMSH5 in promoting ionizing 
    radiation induced apoptosis.
- id: PMID:19470755
  title: Cdo binds Abl to promote p38alpha/beta mitogen-activated protein kinase
    activity and myogenic differentiation.
- id: PMID:19914245
  title: c-Abl tyrosine kinase interacts with MAVS and regulates innate immune 
    response.
- id: PMID:20598684
  title: Abi1/Hssh3bp1 pY213 links Abl kinase signaling to p85 regulatory 
    subunit of PI-3 kinase in regulation of macropinocytosis in LNCaP cells.
- id: PMID:20624904
  title: Tarp regulates early Chlamydia-induced host cell survival through 
    interactions with the human adaptor protein SHC1.
- id: PMID:20697350
  title: The proximal signaling network of the BCR-ABL1 oncogene shows a modular
    organization.
- id: PMID:20823226
  title: Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's 
    ubiquitination and protective function.
- id: PMID:20841568
  title: ABL tyrosine kinases - evolution of function, regulation, and 
    specificity
- id: PMID:22286129
  title: BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid 
    leukemia.
- id: PMID:22401567
  title: MutS homologue hMSH5 - role in cisplatin-induced DNA damage response.
- id: PMID:22810897
  title: Abl family kinases modulate T cell-mediated inflammation and 
    chemokine-induced migration through the adaptor HEF1 and the GTPase Rap1.
- id: PMID:23006999
  title: Tyrosine phosphorylation of a SNARE protein, syntaxin 17 - implications
    for membrane trafficking in the early secretory pathway.
- id: PMID:24367707
  title: "Abl family kinases regulate endothelial barrier function in vitro and in mice."
- id: PMID:24520051
  title: Abelson phosphorylation of CLASP2 modulates its association with 
    microtubules and actin
- id: PMID:24522549
  title: Oxidative stress-induced signaling pathways implicated in the 
    pathogenesis of Parkinson's disease.
- id: PMID:24658113
  title: EphA4 activation of c-Abl mediates synaptic loss and LTP blockade 
    caused by amyloid-β oligomers.
- id: PMID:24658140
  title: The mammalian-membrane two-hybrid assay (MaMTH) for probing 
    membrane-protein interactions in human cells.
- id: PMID:24700464
  title: The association of cortactin with profilin-1 is critical for smooth 
    muscle contraction.
- id: PMID:24728074
  title: Enhanced prediction of Src homology 2 (SH2) domain binding potentials 
    using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen 
    receptor interactome.
- id: PMID:24863063
  title: "Imatinib inhibits VEGF-independent angiogenesis by targeting neuropilin 1-dependent ABL1 activation in endothelial cells."
- id: PMID:24947832
  title: Differential protein-protein interactions of LRRK1 and LRRK2 indicate 
    roles in distinct cellular signaling pathways.
- id: PMID:25036101
  title: Identification of SH3 domain proteins interacting with the cytoplasmic 
    tail of the a disintegrin and metalloprotease 10 (ADAM10).
- id: PMID:25852190
  title: Integrative analysis of kinase networks in TRAIL-induced apoptosis 
    provides a source of potential targets for combination therapy.
- id: PMID:26051942
  title: NRP1 Regulates CDC42 Activation to Promote Filopodia Formation in 
    Endothelial Tip Cells.
- id: PMID:27348587
  title: Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced 
    neurodegeneration.
- id: PMID:28086240
  title: ABL2 suppresses FLT3-ITD-induced cell proliferation through negative 
    regulation of AKT signaling.
- id: PMID:28288113
  title: Germline mutations in ABL1 cause an autosomal dominant syndrome 
    characterized by congenital heart defects and skeletal malformations.
- id: PMID:28428613
  title: Differential regulation of PKD isoforms in oxidative stress conditions 
    through phosphorylation of a conserved Tyr in the P+1 loop.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and 
    disease networks.
- id: PMID:30021884
  title: Histone Interaction Landscapes Visualized by Crosslinking Mass 
    Spectrometry in Intact Cell Nuclei.
- id: PMID:31175292
  title: Structural and functional consequences of the STAT5B(N642H) driver 
    mutation.
- id: PMID:31980649
  title: Extensive rewiring of the EGFR network in colorectal cancer cells 
    expressing transforming levels of KRAS(G13D).
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the 
    human interactome.
- id: PMID:35271311
  title: OpenCell - Endogenous tagging for the cartography of human cellular 
    organization.
- id: PMID:36931259
  title: A central chaperone-like role for 14-3-3 proteins in human cells.
- id: PMID:37219487
  title: Large-scale phosphomimetic screening identifies phospho-modulated 
    motif-based protein interactions.
- id: PMID:39009827
  title: Proteome-scale characterisation of motif-based interactome rewiring by 
    disease mutations.
- id: PMID:39251607
  title: Systematic identification of post-transcriptional regulatory modules.
- id: PMID:7590236
  title: Abi-2, a novel SH3-containing protein interacts with the c-Abl tyrosine
    kinase and modulates c-Abl transforming activity.
- id: PMID:8242749
  title: A C-terminal protein-binding domain in the retinoblastoma protein 
    regulates nuclear c-Abl tyrosine kinase in the cell cycle.
- id: Reactome:R-HSA-2029480
  title: Reactome - Fcgamma receptor (FCGR) dependent phagocytosis
- id: Reactome:R-HSA-2130194
  title: Reactome - EPH-ephrin signaling
- id: Reactome:R-HSA-376141
  title: Reactome - Termination of O-glycan biosynthesis
- id: Reactome:R-HSA-428888
  title: Reactome - ESR-mediated signaling
- id: Reactome:R-HSA-448958
  title: Reactome - Axon guidance
- id: Reactome:R-HSA-5686578
  title: Reactome - Autophagy
- id: Reactome:R-HSA-5686587
  title: Reactome - Lysosome
- id: Reactome:R-HSA-8939236
  title: Reactome - RUNX1 regulates transcription of genes involved in 
    differentiation of HSCs
- id: Reactome:R-HSA-8956659
  title: Reactome - ABL1 signaling events
- id: Reactome:R-HSA-9664422
  title: Reactome - Fc-gamma receptor signaling
- id: Reactome:R-HSA-9841924
  title: Reactome - ABL1 signaling in DNA damage response
- id: Reactome:R-HSA-9842028
  title: Reactome - DNA damage checkpoint signaling
- id: Reactome:R-HSA-9860927
  title: Reactome - Endothelial cell response to shear stress
- id: Reactome:R-HSA-9865184
  title: Reactome - ABL1 cytosolic signaling
- id: Reactome:R-HSA-9865196
  title: Reactome - ABL1 kinase activity
- id: PMID:9558345
  title: The DNA binding domain of the human c-Abl tyrosine kinase 
    preferentially binds to DNA sequences containing an AAC motif and to 
    distorted DNA structures.
- id: file:human/ABL1/ABL1-deep-research-falcon.md
  title: Deep research summary for ABL1
existing_annotations:
# ========== IBA ANNOTATIONS ==========
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ABL1 is definitively a protein tyrosine kinase (EC 2.7.10.2). This 
      is its primary enzymatic function.
    action: ACCEPT
    reason: Core molecular function of ABL1. Extensively validated by crystal 
      structures, kinase assays, and identification of numerous substrates.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: "ABL tyrosine kinases: evolution of function, regulation, and
        specificity"
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ABL1 localizes to the plasma membrane through interactions with 
      membrane-associated proteins and actin cytoskeleton.
    action: ACCEPT
    reason: ABL1 localizes to membrane ruffles and the cell cortex where it 
      regulates actin remodeling. The myristoylated isoform IB can associate 
      with membranes.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 localizes to plasma membrane via interactions with membrane-associated
        proteins and actin cytoskeleton]"
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ABL1 participates in integrin-mediated signaling, regulating cell 
      adhesion and migration through phosphorylation of focal adhesion 
      components.
    action: ACCEPT
    reason: ABL1 is activated downstream of integrin engagement and 
      phosphorylates key adhesion regulators including CRK, CRKL, and paxillin.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: "Imatinib inhibits VEGF-independent angiogenesis by targeting
        neuropilin 1-dependent ABL1 activation"
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ABL1 promotes endothelial cell migration through its regulation of 
      actin dynamics and integrin signaling.
    action: KEEP_AS_NON_CORE
    reason: While ABL1 does regulate cell migration through actin remodeling, 
      this is a cell-type-specific phenotypic outcome rather than a core evolved
      function.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: "Cell migration assay"
- term:
    id: GO:0007173
    label: epidermal growth factor receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ABL1 modulates EGFR signaling by regulating receptor endocytosis 
      through phosphorylation of CBL.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates EGFR endocytosis via CBL phosphorylation. However, 
      this represents one of many RTK signaling pathways ABL1 can modulate, not 
      a core evolved function.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 regulates EGFR endocytosis via CBL phosphorylation]"
# ========== IEA ANNOTATIONS ==========
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: As a kinase, ABL1 binds ATP. This is a necessary attribute of its 
      kinase function but is too general.
    action: MODIFY
    reason: ABL1 binds ATP as part of its kinase catalytic mechanism. The more 
      specific term GO:0005524 (ATP binding) is more informative.
    proposed_replacement_terms:
    - id: GO:0005524
      label: ATP binding
- term:
    id: GO:0001784
    label: phosphotyrosine residue binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: The SH2 domain of ABL1 binds phosphotyrosine-containing sequences, 
      enabling interactions with activated signaling proteins.
    action: ACCEPT
    reason: The ABL1 SH2 domain binds phosphotyrosine motifs. This is a core 
      regulatory function enabling ABL1 to respond to tyrosine kinase signaling.
    supported_by:
    - reference_id: PMID:12384576
      supporting_text: "Structure of a regulatory complex involving the Abl SH3 domain,
        the Crk SH2 domain"
- term:
    id: GO:0002252
    label: immune effector process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 has roles in T cell signaling and immune cell function, but 
      this term is very broad and non-specific.
    action: MARK_AS_OVER_ANNOTATED
    reason: While ABL1 does function in T cell migration and differentiation, 
      this extremely broad term provides little functional insight.
- term:
    id: GO:0002429
    label: immune response-activating cell surface receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 can be activated downstream of immune receptors but this is a 
      secondary function.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 functions downstream of BCR and other immune receptors but this
      is not a specific evolved function. The annotation is too broad.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 has a C-terminal DNA binding domain that preferentially binds 
      distorted DNA structures including four-way junctions and bubble DNA.
    action: ACCEPT
    reason: ABL1 has direct DNA binding activity through its C-terminal region. 
      This is relevant to its nuclear DNA damage response functions.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 has a C-terminal DNA binding domain]"
- term:
    id: GO:0003785
    label: actin monomer binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 contains an F-actin binding region in its C-terminus that 
      enables direct interaction with actin.
    action: ACCEPT
    reason: The C-terminal region of ABL1 contains an F-actin binding domain. 
      This is a core structural feature enabling cytoskeletal regulatory 
      functions.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 contains F-actin binding region in C-terminus]"
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 is a protein kinase, but this term is less specific than the 
      tyrosine kinase annotation.
    action: ACCEPT
    reason: While ABL1 is primarily a tyrosine kinase, this general term is 
      acceptable as a parent term.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: This is the core molecular function of ABL1 as a non-receptor 
      tyrosine kinase.
    action: ACCEPT
    reason: Core function supported by multiple evidence sources. ABL1 
      phosphorylates numerous substrates on tyrosine residues.
- term:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 is definitively a non-receptor (non-membrane spanning) 
      tyrosine kinase.
    action: ACCEPT
    reason: ABL1 belongs to the ABL subfamily of non-receptor tyrosine kinases. 
      Unlike RTKs, it lacks a transmembrane domain.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: "Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src
        homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase
        activity and is common among nonreceptor tyrosine kinases"
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 binds ATP in its kinase domain active site as required for 
      phosphotransfer catalysis.
    action: ACCEPT
    reason: ATP binding is essential for ABL1 kinase activity. Crystal 
      structures show ATP analog binding in the kinase domain.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: "Protein binding and signaling properties of RIN1 suggest a
        unique effector function"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 localizes to the nucleus where it functions in DNA damage 
      response and transcriptional regulation.
    action: ACCEPT
    reason: ABL1 contains three NLS sequences enabling nuclear import. Nuclear 
      localization is essential for its DNA damage response function.
    supported_by:
    - reference_id: PMID:9168116
      supporting_text: "Ataxia telangiectasia mutant protein activates c-Abl tyrosine
        kinase in response to ionizing radiation"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: ABL1 can translocate to mitochondria in response to oxidative 
      stress where it mediates mitochondrial dysfunction.
    action: KEEP_AS_NON_CORE
    reason: Mitochondrial localization occurs under oxidative stress. This is a 
      stress-induced localization rather than constitutive.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: "Oxidative stress-induced signaling pathways implicated in
        the pathogenesis of Parkinson's disease"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 is predominantly cytosolic under basal conditions, regulated 
      by 14-3-3 protein sequestration.
    action: ACCEPT
    reason: Cytosolic localization is well-established. ABL1 is sequestered in 
      cytoplasm through 14-3-3 protein interactions.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 is predominantly cytosolic, regulated by 14-3-3 protein
        sequestration]"
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: ABL1 associates with the cytoskeleton through its F-actin binding 
      domain and regulates cytoskeletal dynamics.
    action: ACCEPT
    reason: ABL1 directly binds F-actin through its C-terminal actin binding 
      domain. This is a core localization for cytoskeletal regulatory function.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 contains F-actin binding domain enabling cytoskeletal
        localization]"
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 participates in DNA repair by phosphorylating repair proteins 
      RAD51, RAD52, and WRN in response to DNA damage.
    action: ACCEPT
    reason: ABL1 phosphorylates multiple DNA repair proteins. This is a core 
      nuclear function of ABL1 in the DNA damage response pathway.
    supported_by:
    - reference_id: PMID:9461559
      supporting_text: "Regulation of Rad51 function by c-Abl in response to DNA damage"
- term:
    id: GO:0006897
    label: endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 regulates receptor endocytosis, particularly EGFR 
      internalization, through phosphorylation of CBL.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates endocytosis of EGFR and other receptors. However, 
      this is one of many downstream effects of ABL1 kinase activity.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 regulates receptor endocytosis through CBL phosphorylation]"
- term:
    id: GO:0006909
    label: phagocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 participates in Fc-gamma receptor signaling during 
      phagocytosis.
    action: KEEP_AS_NON_CORE
    reason: ABL1 is placed in Fc-gamma receptor-mediated phagocytosis pathway. 
      This is a cell-type-specific function in immune cells, not a core evolved 
      function.
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 has been implicated in autophagy regulation, but the evidence 
      for direct autophagy function is limited.
    action: MARK_AS_OVER_ANNOTATED
    reason: While ABL1 regulates lysosomal trafficking, the annotation of ABL1 
      to the general autophagy process is over-annotation. ABL1's primary role 
      is in lysosomal function, not autophagy per se. The deep research found no
      evidence that autophagy is a core evolved function of ABL1.
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 promotes apoptosis in response to DNA damage through 
      phosphorylation of TP73 and CASP9.
    action: ACCEPT
    reason: Nuclear ABL1 activates proapoptotic pathways following severe DNA 
      damage. ABL1 phosphorylates TP73 and CASP9 on Tyr-153.
    supported_by:
    - reference_id: PMID:9037071
      supporting_text: "Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine
        kinase"
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 is a key mediator of the DNA damage response, activated by ATM
      following DNA double-strand breaks.
    action: ACCEPT
    reason: DNA damage response is a core nuclear function of ABL1. ATM 
      phosphorylates ABL1 following DNA damage, activating its nuclear 
      functions.
    supported_by:
    - reference_id: PMID:9168116
      supporting_text: "Ataxia telangiectasia mutant protein activates c-Abl tyrosine
        kinase in response to ionizing radiation"
- term:
    id: GO:0007155
    label: cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 regulates cell adhesion through phosphorylation of adhesion 
      signaling components including CRK, CRKL, and paxillin.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates cell adhesion through its cytoskeletal regulatory 
      functions, but this is a phenotypic outcome rather than a core molecular 
      function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: "ABL tyrosine kinases: evolution of function, regulation, and
        specificity"
- term:
    id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 has been shown to positively regulate cytosolic calcium 
      through effects on endothelial barrier function.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates calcium signaling in endothelial cells. This is a 
      downstream effect in specific cell contexts, not a core evolved function.
    supported_by:
    - reference_id: PMID:24367707
      supporting_text: "Abl family kinases regulate endothelial barrier function in
        vitro and in mice"
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 regulates gene expression through phosphorylation of 
      transcriptional regulators and RNA polymerase II CTD.
    action: KEEP_AS_NON_CORE
    reason: Nuclear ABL1 can phosphorylate RNAPII CTD and interact with 
      transcriptional regulators. However, this is a very broad term.
- term:
    id: GO:0010506
    label: regulation of autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 may indirectly regulate autophagy through effects on lysosomal
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Similar to GO:0006914, this is over-annotation. ABL1's primary role 
      is in lysosomal trafficking and acidification, not autophagy regulation 
      per se.
- term:
    id: GO:0010557
    label: positive regulation of macromolecule biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: This is an extremely broad term with unclear relevance to ABL1 core
      function.
    action: MARK_AS_OVER_ANNOTATED
    reason: This term is too general to provide meaningful functional 
      information about ABL1. No specific evidence supports this as a core 
      function.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Duplicate of IBA annotation above.
    action: KEEP_AS_NON_CORE
    reason: Same as IBA annotation - cell-type-specific outcome of cytoskeletal 
      regulation.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 has kinase activity, but this very general term is subsumed by
      more specific tyrosine kinase annotations.
    action: ACCEPT
    reason: Correct but very general. The more specific protein tyrosine kinase 
      activity annotations are more informative.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: As a kinase, ABL1 has transferase activity (phosphotransfer), but 
      this is extremely general.
    action: MODIFY
    reason: This term is too general. ABL1's specific transferase activity is 
      protein tyrosine kinase activity.
    proposed_replacement_terms:
    - id: GO:0004713
      label: protein tyrosine kinase activity
- term:
    id: GO:0030100
    label: regulation of endocytosis
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 regulates endocytosis of receptors through CBL and other 
      mechanisms.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates EGFR and other receptor endocytosis. However, this is
      a downstream regulatory function, not core.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 regulates receptor endocytosis]"
- term:
    id: GO:0031965
    label: nuclear membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: The myristoylated isoform IB can associate with nuclear membrane.
    action: KEEP_AS_NON_CORE
    reason: UniProt indicates isoform IB localizes to nuclear membrane via lipid
      anchor. This is isoform-specific.
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 is a key regulator of actin cytoskeleton organization through 
      phosphorylation of WAVE complex, cortactin, and other actin regulators.
    action: ACCEPT
    reason: This is a core function of cytoplasmic ABL1. ABL1 phosphorylates 
      WAVE proteins, cortactin, and other actin regulators.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 phosphorylates WAVE proteins, cortactin, and other actin
        regulators]"
- term:
    id: GO:0045595
    label: regulation of cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 has roles in cell differentiation, particularly in 
      hematopoietic and T cell differentiation.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates T cell differentiation in TBX21-dependent manner. 
      This is a developmental/cell-type-specific function.
- term:
    id: GO:0045785
    label: positive regulation of cell adhesion
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 can positively regulate cell adhesion through focal adhesion 
      signaling.
    action: KEEP_AS_NON_CORE
    reason: ABL1 regulates adhesion signaling but the direction is 
      context-dependent. This is a downstream phenotypic effect.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ABL1 binds magnesium and manganese ions as cofactors for kinase 
      activity.
    action: MODIFY
    reason: ABL1 requires divalent cations for kinase activity. More specific 
      terms GO:0000287 (magnesium ion binding) are preferable.
    proposed_replacement_terms:
    - id: GO:0000287
      label: magnesium ion binding
- term:
    id: GO:0048008
    label: platelet-derived growth factor receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 is activated downstream of PDGFR and regulates PDGF-induced 
      responses.
    action: KEEP_AS_NON_CORE
    reason: ABL1 involvement in PDGFRB signaling is one of several RTK pathways 
      ABL1 modulates, not a core function.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: "Abelson phosphorylation of CLASP2 modulates its association
        with microtubules and actin"
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 is involved in cell cycle regulation through DNA damage 
      checkpoint signaling.
    action: KEEP_AS_NON_CORE
    reason: ABL1 participates in cell cycle regulation through DNA damage 
      checkpoints. Not a core function.
- term:
    id: GO:1901701
    label: cellular response to oxygen-containing compound
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 responds to oxidative stress and reactive oxygen species.
    action: KEEP_AS_NON_CORE
    reason: ABL1 is activated by oxidative stress and translocates to 
      mitochondria. This is a stress response, not core evolved function.
- term:
    id: GO:1902531
    label: regulation of intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ABL1 regulates multiple intracellular signaling cascades.
    action: ACCEPT
    reason: This appropriately captures ABL1's role as a signaling hub 
      integrating multiple pathways.
# ========== IPI PROTEIN BINDING ANNOTATIONS ==========
# Per GO curation guidelines, "protein binding" (GO:0005515) is too generic and should not be used.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10849448
  review:
    summary: Generic protein binding annotation from interaction with HCK.
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding is uninformative per GO curation guidelines.
    supported_by:
    - reference_id: PMID:10849448
      supporting_text: Transformation of myeloid leukemia cells to cytokine 
        independence by Bcr-Abl is suppressed by kinase-defective Hck.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10970852
  review:
    summary: Interaction with WAVE/SCAR complex components.
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein binding is uninformative. WAVE-1 interaction is functionally
      important but generic binding term provides no insight.
    supported_by:
    - reference_id: PMID:10970852
      supporting_text: Scar/WAVE-1, a Wiskott-Aldrich syndrome protein, 
        assembles an actin-associated multi-kinase scaffold.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11374898
  review:
    summary: Interaction with SORBS1 during insulin signaling.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative per GO curation guidelines.
    supported_by:
    - reference_id: PMID:11374898
      supporting_text: 'Cloning, mapping, and characterization of the human sorbin
        and SH3 domain containing 1 (SORBS1) gene: a protein associated with c-Abl
        during insulin signaling in the hepatoma cell line Hep3B.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11375976
  review:
    summary: Interaction with telomeric protein TRF1/Pin2.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:11375976
      supporting_text: 2001 May 25. Telomeric protein Pin2/TRF1 as an important 
        ATM target in response to double strand DNA breaks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11418237
  review:
    summary: Interaction with NAP1BP.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding annotation is uninformative.
    supported_by:
    - reference_id: PMID:11418237
      supporting_text: Isolation of hNap1BP which interacts with human Nap1 
        (NCKAP1) whose expression is down-regulated in Alzheimer's disease.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11971963
  review:
    summary: Interaction with RAD9 checkpoint protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative per GO curation guidelines.
      The functional context (DNA damage checkpoint) is captured by other 
      annotations.
    supported_by:
    - reference_id: PMID:11971963
      supporting_text: c-Abl tyrosine kinase regulates the human Rad9 checkpoint
        protein in response to DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12384576
  review:
    summary: Structural study of ABL SH3-CRK interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: PMID:12384576 describes specific SH3-SH2 interactions with CRK. 
      Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:12384576
      supporting_text: Structure of a regulatory complex involving the Abl SH3 
        domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15448168
  review:
    summary: Interaction with DNA topoisomerase I.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 phosphorylates TOP1. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:15448168
      supporting_text: 2004 Sep 24. Phosphorylation of DNA topoisomerase I by 
        the c-Abl tyrosine kinase confers camptothecin sensitivity.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15696159
  review:
    summary: Interaction with 14-3-3 proteins.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 binds 14-3-3 proteins via phospho-Thr-735 for cytoplasmic 
      sequestration. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:15696159
      supporting_text: JNK phosphorylation of 14-3-3 proteins regulates nuclear 
        targeting of c-Abl in the apoptotic response to DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15886098
  review:
    summary: Interaction with RIN1.
    action: MARK_AS_OVER_ANNOTATED
    reason: RIN1 is an ABL1 activator binding SH2 and SH3 domains. Generic 
      protein binding is uninformative.
    supported_by:
    - reference_id: PMID:15886098
      supporting_text: RIN1 is an ABL tyrosine kinase activator and a regulator 
        of epithelial-cell adhesion and migration.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16273093
  review:
    summary: ErbB receptor interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Protein microarray study. Generic binding uninformative.
    supported_by:
    - reference_id: PMID:16273093
      supporting_text: A quantitative protein interaction network for the ErbB 
        receptors using protein microarrays.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16397227
  review:
    summary: Interaction with MSH5.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1-MSH5 interaction relates to DNA damage response. Generic 
      binding is uninformative.
    supported_by:
    - reference_id: PMID:16397227
      supporting_text: Physical and functional interaction between hMSH5 and 
        c-Abl.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16443220
  review:
    summary: Interaction with C3G isoform.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:16443220
      supporting_text: 2006 Jan 27. Characterization of p87C3G, a novel, 
        truncated C3G isoform that is overexpressed in chronic myeloid leukemia 
        and interacts with Bcr-Abl.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16831423
  review:
    summary: Interaction with vinexin.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 phosphorylates vinexin. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:16831423
      supporting_text: Epub 2006 Jul 5. Abl kinase interacts with and 
        phosphorylates vinexin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16888623
  review:
    summary: Interaction with MUC1.
    action: MARK_AS_OVER_ANNOTATED
    reason: MUC1 blocks ABL1 nuclear targeting. Generic binding is 
      uninformative.
    supported_by:
    - reference_id: PMID:16888623
      supporting_text: Aug 3. MUC1 oncoprotein blocks nuclear targeting of c-Abl
        in the apoptotic response to DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17101133
  review:
    summary: NESH/Abi-3 interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:17101133
      supporting_text: Epub 2006 Nov 7. NESH (Abi-3) is present in the Abi/WAVE 
        complex but does not promote c-Abl-mediated phosphorylation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17112510
  review:
    summary: Interaction with Shb adapter protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:17112510
      supporting_text: Epub 2006 Oct 24. Consequences of Shb and c-Abl 
        interactions for cell death in response to various stress stimuli.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17318191
  review:
    summary: Beta-catenin interaction (BCR-ABL context).
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:17318191
      supporting_text: Bcr-Abl stabilizes beta-catenin in chronic myeloid 
        leukemia through its tyrosine phosphorylation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17474147
  review:
    summary: SH3 domain interaction screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from high-throughput screen is 
      uninformative.
    supported_by:
    - reference_id: PMID:17474147
      supporting_text: Systematic identification of SH3 domain-mediated human 
        protein-protein interactions by peptide array target screening.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17626041
  review:
    summary: Interaction with Cockayne syndrome protein B (ERCC6).
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 phosphorylates CSB/ERCC6. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:17626041
      supporting_text: Cockayne syndrome protein B interacts with and is 
        phosphorylated by c-Abl tyrosine kinase.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18328268
  review:
    summary: Abi1 phosphopeptide allosteric inhibition study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Describes specific allosteric regulation mechanism via Abi1 
      interaction. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:18328268
      supporting_text: Allosteric inhibition of the nonMyristoylated c-Abl 
        tyrosine kinase by phosphopeptides derived from Abi1/Hssh3bp1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19234221
  review:
    summary: Beta2 integrin interaction in neutrophils.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:19234221
      supporting_text: c-Abl kinase is required for beta 2 integrin-mediated 
        neutrophil adhesion.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19442657
  review:
    summary: MSH5 interaction promoting apoptosis.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:19442657
      supporting_text: Epub 2009 May 12. Evidence for a direct involvement of 
        hMSH5 in promoting ionizing radiation induced apoptosis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19470755
  review:
    summary: CDO interaction promoting myogenic differentiation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:19470755
      supporting_text: May 26. Cdo binds Abl to promote p38alpha/beta 
        mitogen-activated protein kinase activity and myogenic differentiation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19914245
  review:
    summary: MAVS interaction regulating innate immunity.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1-MAVS interaction relevant to innate immune signaling. Generic 
      binding is uninformative.
    supported_by:
    - reference_id: PMID:19914245
      supporting_text: c-Abl tyrosine kinase interacts with MAVS and regulates 
        innate immune response.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20598684
  review:
    summary: Abi1 phosphorylation study linking to PI3K.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:20598684
      supporting_text: Epub 2010 Jun 23. Abi1/Hssh3bp1 pY213 links Abl kinase 
        signaling to p85 regulatory subunit of PI-3 kinase in regulation of 
        macropinocytosis in LNCaP cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20697350
  review:
    summary: BCR-ABL1 proximal signaling network study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Large-scale interactome study. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:20697350
      supporting_text: The proximal signaling network of the BCR-ABL1 oncogene 
        shows a modular organization.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22286129
  review:
    summary: BCR-ABL JAK2-STAT5 uncoupling study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:22286129
      supporting_text: BCR-ABL uncouples canonical JAK2-STAT5 signaling in 
        chronic myeloid leukemia.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22401567
  review:
    summary: MSH5 role in cisplatin response.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:22401567
      supporting_text: 'MutS homologue hMSH5: role in cisplatin-induced DNA damage
        response.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24658140
  review:
    summary: Membrane two-hybrid assay study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from screening is uninformative.
    supported_by:
    - reference_id: PMID:24658140
      supporting_text: The mammalian-membrane two-hybrid assay (MaMTH) for 
        probing membrane-protein interactions in human cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24728074
  review:
    summary: SH2 binding prediction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:24728074
      supporting_text: Epub 2014 Apr 12. Enhanced prediction of Src homology 2 
        (SH2) domain binding potentials using a fluorescence 
        polarization-derived c-Met, c-Kit, ErbB, and androgen receptor 
        interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24947832
  review:
    summary: LRRK1/LRRK2 interaction study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:24947832
      supporting_text: Differential protein-protein interactions of LRRK1 and 
        LRRK2 indicate roles in distinct cellular signaling pathways.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25036101
  review:
    summary: ADAM10 SH3 domain interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: SH3 domain-mediated interaction. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:25036101
      supporting_text: eCollection 2014. Identification of SH3 domain proteins 
        interacting with the cytoplasmic tail of the a disintegrin and 
        metalloprotease 10 (ADAM10).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  review:
    summary: TRAIL apoptosis kinase network.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from network analysis is uninformative.
    supported_by:
    - reference_id: PMID:25852190
      supporting_text: Integrative analysis of kinase networks in TRAIL-induced 
        apoptosis provides a source of potential targets for combination 
        therapy.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27348587
  review:
    summary: Alpha-synuclein interaction in neurodegeneration.
    action: MARK_AS_OVER_ANNOTATED
    reason: ABL1 phosphorylates alpha-synuclein. Generic binding is 
      uninformative.
    supported_by:
    - reference_id: PMID:27348587
      supporting_text: Activation of tyrosine kinase c-Abl contributes to 
        α-synuclein-induced neurodegeneration.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28086240
  review:
    summary: ABL2 and FLT3-ITD study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:28086240
      supporting_text: ABL2 suppresses FLT3-ITD-induced cell proliferation 
        through negative regulation of AKT signaling.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  review:
    summary: Human interactome architecture study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Large-scale interactome. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:28514442
      supporting_text: Architecture of the human interactome defines protein 
        communities and disease networks.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:30021884
  review:
    summary: Histone crosslinking mass spec study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:30021884
      supporting_text: Epub 2018 Jul 18. Histone Interaction Landscapes 
        Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31175292
  review:
    summary: STAT5B driver mutation study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:31175292
      supporting_text: Structural and functional consequences of the 
        STAT5B(N642H) driver mutation.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31980649
  review:
    summary: EGFR network in KRAS mutant cells.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:31980649
      supporting_text: Extensive rewiring of the EGFR network in colorectal 
        cancer cells expressing transforming levels of KRAS(G13D).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  review:
    summary: Cell-specific interactome remodeling.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
        cell-specific remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  review:
    summary: OpenCell endogenous tagging study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Large-scale study. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:35271311
      supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
        of human cellular organization.'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36931259
  review:
    summary: 14-3-3 protein chaperone study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Relevant to ABL1 cytoplasmic sequestration by 14-3-3 proteins. 
      Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:36931259
      supporting_text: A central chaperone-like role for 14-3-3 proteins in 
        human cells.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37219487
  review:
    summary: Phosphomimetic motif interaction screen.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:37219487
      supporting_text: 2023 May 23. Large-scale phosphomimetic screening 
        identifies phospho-modulated motif-based protein interactions.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39009827
  review:
    summary: Disease mutation interactome rewiring.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:39009827
      supporting_text: 2024 Jul 15. Proteome-scale characterisation of 
        motif-based interactome rewiring by disease mutations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:39251607
  review:
    summary: Post-transcriptional regulatory module study.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:39251607
      supporting_text: Systematic identification of post-transcriptional 
        regulatory modules.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9144171
  review:
    summary: RIN1 binding study demonstrating activator function.
    action: MARK_AS_OVER_ANNOTATED
    reason: RIN1 is an ABL1 activator. Generic binding term is uninformative.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9168117
  review:
    summary: ATM interaction in DNA damage response.
    action: MARK_AS_OVER_ANNOTATED
    reason: ATM-ABL1 interaction is functionally important for DNA damage 
      response. Generic binding is uninformative.
    supported_by:
    - reference_id: PMID:9168117
      supporting_text: Interaction between ATM protein and c-Abl in response to 
        DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9346925
  review:
    summary: HPK1 interaction via SH2/SH3 adapters.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is uninformative.
    supported_by:
    - reference_id: PMID:9346925
      supporting_text: SH2/SH3 adaptor proteins can link tyrosine kinases to a 
        Ste20-related protein kinase, HPK1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9593709
  review:
    summary: Spectrin SH3 domain interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: SH3-mediated interaction with cytoskeleton. Generic binding is 
      uninformative.
# ========== ADDITIONAL IEA ANNOTATIONS ==========
    supported_by:
    - reference_id: PMID:9593709
      supporting_text: Identification of a candidate human spectrin Src homology
        3 domain-binding protein suggests a general mechanism of association of 
        tyrosine kinases with the spectrin-based membrane skeleton.
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 requires magnesium as a cofactor for kinase activity.
    action: ACCEPT
    reason: Divalent cation binding is essential for kinase catalysis. This is a
      core biochemical requirement.
- term:
    id: GO:0001726
    label: ruffle
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to membrane ruffles where it regulates actin 
      dynamics.
    action: ACCEPT
    reason: Localization to ruffles is consistent with ABL1's role in actin 
      cytoskeleton remodeling.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 localizes to F-actin-rich membrane ruffles]"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 is predominantly cytoplasmic under basal conditions.
    action: ACCEPT
    reason: Cytoplasmic localization is well-established. ABL1 shuttles between 
      cytoplasm and nucleus.
- term:
    id: GO:0007611
    label: learning or memory
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 has been implicated in learning and memory through synaptic 
      functions.
    action: KEEP_AS_NON_CORE
    reason: Based on mouse orthologue data. This is a developmental/neurological
      phenotype, not a core molecular function.
- term:
    id: GO:0008306
    label: associative learning
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 has been implicated in associative learning.
    action: KEEP_AS_NON_CORE
    reason: Based on mouse orthologue data. This is a behavioral phenotype, not 
      a core molecular function.
- term:
    id: GO:0009410
    label: response to xenobiotic stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 responds to xenobiotic stimuli.
    action: KEEP_AS_NON_CORE
    reason: This is a stress response phenotype, not a core evolved function.
- term:
    id: GO:0014069
    label: postsynaptic density
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to postsynaptic density in neurons.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific localization in neurons. Not a core function.
- term:
    id: GO:0015629
    label: actin cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 localizes to and regulates the actin cytoskeleton.
    action: ACCEPT
    reason: ABL1 directly binds F-actin and regulates actin dynamics. This is a 
      core localization.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 directly binds F-actin through C-terminal region]"
- term:
    id: GO:0019901
    label: protein kinase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 binds other protein kinases.
    action: ACCEPT
    reason: ABL1 interacts with multiple protein kinases including SRC family 
      kinases and ATM.
- term:
    id: GO:0019904
    label: protein domain specific binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 binds proteins through its SH2 and SH3 domains.
    action: ACCEPT
    reason: SH2 and SH3 domain-mediated interactions are core to ABL1 function 
      and regulation.
- term:
    id: GO:0030036
    label: actin cytoskeleton organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 organizes the actin cytoskeleton.
    action: ACCEPT
    reason: This is a core function of cytoplasmic ABL1 through phosphorylation 
      of actin regulatory proteins.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 organizes actin cytoskeleton through phosphorylation
        of cortactin and other actin regulatory proteins]"
- term:
    id: GO:0030041
    label: actin filament polymerization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 regulates actin filament polymerization.
    action: ACCEPT
    reason: ABL1 promotes actin polymerization through phosphorylation of WAVE 
      complex and other regulators.
- term:
    id: GO:0030145
    label: manganese ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 can use manganese as an alternative divalent cation cofactor.
    action: ACCEPT
    reason: Like many kinases, ABL1 can use Mn2+ in addition to Mg2+ for 
      catalysis.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to dendrites in neurons.
    action: KEEP_AS_NON_CORE
    reason: Neuronal cell-type-specific localization. Not a core function.
- term:
    id: GO:0030426
    label: growth cone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to growth cones where it regulates neurite 
      extension.
    action: KEEP_AS_NON_CORE
    reason: Neuronal cell-type-specific localization related to actin dynamics. 
      Not a core function.
- term:
    id: GO:0031252
    label: cell leading edge
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to the cell leading edge during migration.
    action: ACCEPT
    reason: Localization to the leading edge is consistent with ABL1's role in 
      actin-based cell motility.
- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 is activated by and responds to oxidative stress.
    action: KEEP_AS_NON_CORE
    reason: Oxidative stress response including mitochondrial translocation. 
      This is a stress response, not core function.
- term:
    id: GO:0034976
    label: response to endoplasmic reticulum stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 responds to ER stress.
    action: KEEP_AS_NON_CORE
    reason: ER stress response is a secondary function, not a core evolved 
      function.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 functions in intracellular signal transduction.
    action: ACCEPT
    reason: ABL1 is a signaling kinase that transduces signals from multiple 
      upstream inputs.
- term:
    id: GO:0038191
    label: neuropilin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 binds neuropilin.
    action: KEEP_AS_NON_CORE
    reason: Neuropilin interaction relates to angiogenesis signaling. Not a core
      evolved function.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to neuronal cell bodies.
    action: KEEP_AS_NON_CORE
    reason: Neuronal cell-type-specific localization. Not a core function.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 positively regulates apoptosis in response to DNA damage.
    action: ACCEPT
    reason: Nuclear ABL1 promotes apoptosis following severe DNA damage via TP73
      and CASP9 phosphorylation.
    supported_by:
    - reference_id: PMID:9037071
      supporting_text: "Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine
        kinase"
- term:
    id: GO:0043525
    label: positive regulation of neuron apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 can promote neuron apoptosis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific apoptotic function in neurons. Related to 
      Parkinson's disease pathology.
- term:
    id: GO:0045580
    label: regulation of T cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 regulates T cell differentiation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific developmental function. Not a core evolved 
      function.
- term:
    id: GO:0045907
    label: positive regulation of vasoconstriction
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 positively regulates vasoconstriction.
    action: KEEP_AS_NON_CORE
    reason: Physiological phenotype, not a core molecular function.
- term:
    id: GO:0046875
    label: ephrin receptor binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 binds ephrin receptors.
    action: KEEP_AS_NON_CORE
    reason: Ephrin signaling is one of many pathways ABL1 participates in. Not a
      core function.
- term:
    id: GO:0048013
    label: ephrin receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 participates in ephrin receptor signaling.
    action: KEEP_AS_NON_CORE
    reason: Ephrin signaling is one of many pathways ABL1 modulates. Not a core 
      evolved function.
- term:
    id: GO:0048146
    label: positive regulation of fibroblast proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes fibroblast proliferation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific proliferative effect. Not a core function.
- term:
    id: GO:0051015
    label: actin filament binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 directly binds actin filaments through its C-terminal F-actin 
      binding domain.
    action: ACCEPT
    reason: Direct F-actin binding is a core structural feature of ABL1 enabling
      cytoskeletal regulation.
    supported_by:
    - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
      supporting_text: "[ABL1 contains C-terminal F-actin binding domain for direct
        actin filament binding]"
- term:
    id: GO:0051450
    label: myoblast proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 is involved in myoblast proliferation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific developmental function. Not a core evolved 
      function.
- term:
    id: GO:0060038
    label: cardiac muscle cell proliferation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 is involved in cardiac muscle cell proliferation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific developmental function. Not a core evolved 
      function.
- term:
    id: GO:0070097
    label: delta-catenin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 binds delta-catenin.
    action: KEEP_AS_NON_CORE
    reason: Specific protein interaction. Not a core evolved function.
- term:
    id: GO:0071560
    label: cellular response to transforming growth factor beta stimulus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 responds to TGF-beta stimulus.
    action: KEEP_AS_NON_CORE
    reason: TGF-beta response is one of many signaling pathways ABL1 
      participates in. Not core.
- term:
    id: GO:0071871
    label: response to epinephrine
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 responds to epinephrine.
    action: KEEP_AS_NON_CORE
    reason: Physiological response, not a core molecular function.
- term:
    id: GO:0090050
    label: positive regulation of cell migration involved in sprouting 
      angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes cell migration during angiogenesis.
    action: KEEP_AS_NON_CORE
    reason: Developmental/physiological phenotype, not a core molecular 
      function.
- term:
    id: GO:0098978
    label: glutamatergic synapse
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 localizes to glutamatergic synapses.
    action: KEEP_AS_NON_CORE
    reason: Neuronal cell-type-specific localization. Not a core function.
- term:
    id: GO:0099150
    label: regulation of postsynaptic specialization assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 regulates postsynaptic specialization assembly.
    action: KEEP_AS_NON_CORE
    reason: Neuronal cell-type-specific function. Not a core evolved function.
- term:
    id: GO:1900006
    label: positive regulation of dendrite development
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes dendrite development.
    action: KEEP_AS_NON_CORE
    reason: Neuronal developmental function. Not a core evolved function.
- term:
    id: GO:1900272
    label: negative regulation of long-term synaptic potentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 negatively regulates long-term synaptic potentiation.
    action: KEEP_AS_NON_CORE
    reason: Neuronal physiological function. Not a core evolved function.
- term:
    id: GO:1903055
    label: positive regulation of extracellular matrix organization
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes extracellular matrix organization.
    action: KEEP_AS_NON_CORE
    reason: Downstream phenotypic effect. Not a core molecular function.
- term:
    id: GO:1903210
    label: podocyte apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 is involved in podocyte apoptosis.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific apoptotic function. Not a core evolved function.
- term:
    id: GO:1903905
    label: positive regulation of establishment of T cell polarity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes T cell polarity establishment.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific function in T cells. Not a core evolved function.
- term:
    id: GO:1905244
    label: regulation of modification of synaptic structure
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ABL1 regulates synaptic structure modification.
    action: KEEP_AS_NON_CORE
    reason: Neuronal function related to actin dynamics at synapses. Not a core 
      evolved function.
- term:
    id: GO:1905555
    label: positive regulation of blood vessel branching
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes blood vessel branching.
    action: KEEP_AS_NON_CORE
    reason: Angiogenesis-related phenotype. Not a core molecular function.
- term:
    id: GO:2000406
    label: positive regulation of T cell migration
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: ABL1 promotes T cell migration.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific migration function. Not a core evolved function.
# ========== MISSING EXPERIMENTAL ANNOTATIONS ==========
- term:
    id: GO:0000287
    label: magnesium ion binding
  evidence_type: IDA
  original_reference_id: PMID:9144171
  review:
    summary: ABL1 binds magnesium ions as a cofactor for its kinase activity.
    action: ACCEPT
    reason: Magnesium binding is required for ATP-dependent kinase activity. 
      This is an intrinsic component of tyrosine kinase function.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0000400
    label: four-way junction DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9558345
  review:
    summary: ABL1 binds four-way junction DNA structures through its DNA binding
      domain.
    action: ACCEPT
    reason: Direct experimental evidence demonstrates ABL1 binding to DNA 
      junction structures. This contributes to DNA damage response functions.
    supported_by:
    - reference_id: PMID:9558345
      supporting_text: The DNA binding domain of the human c-Abl tyrosine kinase
        preferentially binds to DNA sequences containing an AAC motif and to 
        distorted DNA structures.
- term:
    id: GO:0000405
    label: bubble DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9558345
  review:
    summary: ABL1 binds bubble DNA structures.
    action: ACCEPT
    reason: Direct experimental evidence for binding to DNA bubble structures. 
      Relevant to DNA damage response function.
    supported_by:
    - reference_id: PMID:9558345
      supporting_text: The DNA binding domain of the human c-Abl tyrosine kinase
        preferentially binds to DNA sequences containing an AAC motif and to 
        distorted DNA structures.
- term:
    id: GO:0001784
    label: phosphotyrosine residue binding
  evidence_type: IPI
  original_reference_id: PMID:20624904
  review:
    summary: ABL1 SH2 domain binds phosphotyrosine residues.
    action: ACCEPT
    reason: SH2 domain-mediated phosphotyrosine binding is essential for ABL1 
      substrate recognition and signaling.
    supported_by:
    - reference_id: PMID:20624904
      supporting_text: Tarp regulates early Chlamydia-induced host cell survival
        through interactions with the human adaptor protein SHC1.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11120811
  review:
    summary: ABL1 possesses protein kinase activity.
    action: ACCEPT
    reason: Core kinase function. ABL1 is a well-characterized protein kinase.
    supported_by:
    - reference_id: PMID:11120811
      supporting_text: The c-Abl tyrosine kinase is regulated downstream of the 
        B cell antigen receptor and interacts with CD19.
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 kinase activity regulates neuropilin-dependent endothelial 
      cell functions.
    action: ACCEPT
    reason: Kinase activity is core function; this annotation documents its role
      in specific signaling context.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:24700464
  review:
    summary: ABL1 phosphorylates serine/threonine residues in addition to 
      tyrosine.
    action: ACCEPT
    reason: Evidence supports dual-specificity kinase activity for ABL1 
      phosphorylating both tyrosine and serine/threonine residues.
    supported_by:
    - reference_id: PMID:24700464
      supporting_text: 2014 Apr 3. The association of cortactin with profilin-1 
        is critical for smooth muscle contraction.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:10713049
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function of ABL1. Multiple lines of evidence support 
      tyrosine kinase activity.
    supported_by:
    - reference_id: PMID:10713049
      supporting_text: Interaction between protein kinase C delta and the c-Abl 
        tyrosine kinase in the cellular response to oxidative stress.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11121037
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function. Additional experimental evidence for kinase
      activity.
    supported_by:
    - reference_id: PMID:11121037
      supporting_text: Functional interaction between c-Abl and the 
        p21-activated protein kinase gamma-PAK.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:12944467
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function with direct experimental evidence.
    supported_by:
    - reference_id: PMID:12944467
      supporting_text: Werner syndrome protein phosphorylation by abl tyrosine 
        kinase regulates its activity and distribution.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:15657060
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity in DNA damage
      response.
    action: ACCEPT
    reason: Core molecular function demonstrated in DNA damage response context.
    supported_by:
    - reference_id: PMID:15657060
      supporting_text: 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 
        autocleavage in the apoptotic response to DNA damage.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:15657136
  review:
    summary: Experimental evidence for ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function with direct experimental validation.
    supported_by:
    - reference_id: PMID:15657136
      supporting_text: Abelson-interactor-1 promotes WAVE2 membrane 
        translocation and Abelson-mediated tyrosine phosphorylation required for
        WAVE2 activation.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:17888034
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function. Additional IDA evidence.
    supported_by:
    - reference_id: PMID:17888034
      supporting_text: Epub 2007 Sep 18. Fibroblast growth factor receptor 1 
        oncogene partner as a novel prognostic biomarker and therapeutic target 
        for lung cancer.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:20823226
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function with direct experimental evidence.
    supported_by:
    - reference_id: PMID:20823226
      supporting_text: Phosphorylation by the c-Abl protein tyrosine kinase 
        inhibits parkin's ubiquitination and protective function.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:22810897
  review:
    summary: Mutant phenotype evidence for ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: IMP evidence supports core kinase function.
    supported_by:
    - reference_id: PMID:22810897
      supporting_text: Abl family kinases modulate T cell-mediated inflammation 
        and chemokine-induced migration through the adaptor HEF1 and the GTPase 
        Rap1.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 kinase activity required for microtubule plus-end 
      localization.
    action: ACCEPT
    reason: Core kinase function demonstrated in cytoskeletal regulation 
      context.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:7590236
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Early IDA evidence establishing ABL1 as a tyrosine kinase.
    supported_by:
    - reference_id: PMID:7590236
      supporting_text: Abi-2, a novel SH3-containing protein interacts with the 
        c-Abl tyrosine kinase and modulates c-Abl transforming activity.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9144171
  review:
    summary: Direct demonstration of ABL1 tyrosine kinase activity with 
      structural analysis.
    action: ACCEPT
    reason: Core molecular function with structural characterization.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:10518561
  review:
    summary: ABL1 functions as a non-receptor tyrosine kinase.
    action: ACCEPT
    reason: Core specific molecular function designation.
    supported_by:
    - reference_id: PMID:10518561
      supporting_text: Molecular cloning of a docking protein, BRDG1, that acts 
        downstream of the Tec tyrosine kinase.
- term:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:28428613
  review:
    summary: ABL1 non-receptor kinase activity demonstrated by mutant 
      phenotypes.
    action: ACCEPT
    reason: Core specific molecular function with IMP evidence.
    supported_by:
    - reference_id: PMID:28428613
      supporting_text: Differential regulation of PKD isoforms in oxidative 
        stress conditions through phosphorylation of a conserved Tyr in the P+1 
        loop.
- term:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  evidence_type: IDA
  original_reference_id: PMID:9461559
  review:
    summary: ABL1 acts as non-receptor kinase phosphorylating Rad51.
    action: ACCEPT
    reason: Core molecular function demonstrated through Rad51 phosphorylation.
    supported_by:
    - reference_id: PMID:9461559
      supporting_text: Regulation of Rad51 function by c-Abl in response to DNA 
        damage.
- term:
    id: GO:0005080
    label: protein kinase C binding
  evidence_type: IPI
  original_reference_id: PMID:10713049
  review:
    summary: ABL1 physically interacts with protein kinase C.
    action: ACCEPT
    reason: Documented physical interaction supporting ABL1's role in PKC 
      signaling.
    supported_by:
    - reference_id: PMID:10713049
      supporting_text: Interaction between protein kinase C delta and the c-Abl 
        tyrosine kinase in the cellular response to oxidative stress.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15657060
  review:
    summary: ABL1 binds to caspase-9.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding term; the specific interaction partner 
      (caspase-9) provides context for apoptosis function.
    supported_by:
    - reference_id: PMID:15657060
      supporting_text: 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 
        autocleavage in the apoptotic response to DNA damage.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17515907
  review:
    summary: ABL1 protein-protein interaction.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding; specific partners provide functional 
      context.
    supported_by:
    - reference_id: PMID:17515907
      supporting_text: May 21. Structural basis for the transforming activity of
        human cancer-related signaling adaptor protein CRK.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17888034
  review:
    summary: ABL1 protein-protein interaction.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding term.
    supported_by:
    - reference_id: PMID:17888034
      supporting_text: Epub 2007 Sep 18. Fibroblast growth factor receptor 1 
        oncogene partner as a novel prognostic biomarker and therapeutic target 
        for lung cancer.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22810897
  review:
    summary: ABL1 binds NEDD9.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding; NEDD9 interaction relates to cell 
      adhesion/migration.
    supported_by:
    - reference_id: PMID:22810897
      supporting_text: Abl family kinases modulate T cell-mediated inflammation 
        and chemokine-induced migration through the adaptor HEF1 and the GTPase 
        Rap1.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 binds CLASP2.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding; CLASP2 interaction relates to microtubule 
      regulation.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9461559
  review:
    summary: ABL1 binds RAD51.
    action: KEEP_AS_NON_CORE
    reason: Generic protein binding; RAD51 interaction supports DNA damage 
      response function.
    supported_by:
    - reference_id: PMID:9461559
      supporting_text: Regulation of Rad51 function by c-Abl in response to DNA 
        damage.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IDA
  original_reference_id: PMID:9144171
  review:
    summary: ABL1 binds ATP as substrate for kinase activity.
    action: ACCEPT
    reason: ATP binding is essential for kinase function. Core to molecular 
      activity.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17626041
  review:
    summary: ABL1 localizes to the nucleus.
    action: ACCEPT
    reason: Consistent with nuclear DNA damage response function.
    supported_by:
    - reference_id: PMID:17626041
      supporting_text: Cockayne syndrome protein B interacts with and is 
        phosphorylated by c-Abl tyrosine kinase.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:17888034
  review:
    summary: ABL1 nuclear localization demonstrated.
    action: ACCEPT
    reason: Core localization for DNA damage response function.
    supported_by:
    - reference_id: PMID:17888034
      supporting_text: Epub 2007 Sep 18. Fibroblast growth factor receptor 1 
        oncogene partner as a novel prognostic biomarker and therapeutic target 
        for lung cancer.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:9168116
  review:
    summary: ABL1 accumulates in nucleus after DNA damage via ATM activation.
    action: ACCEPT
    reason: Nuclear localization in response to DNA damage is a core function.
    supported_by:
    - reference_id: PMID:9168116
      supporting_text: Ataxia telangiectasia mutant protein activates c-Abl 
        tyrosine kinase in response to ionizing radiation.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: More specific nuclear localization supporting DNA damage response 
      function.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:12944467
  review:
    summary: ABL1 localizes to the nucleolus.
    action: ACCEPT
    reason: Nucleolar localization supports role in transcription-related 
      functions.
    supported_by:
    - reference_id: PMID:12944467
      supporting_text: Werner syndrome protein phosphorylation by abl tyrosine 
        kinase regulates its activity and distribution.
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:17626041
  review:
    summary: ABL1 localizes to the nucleolus during oxidative stress.
    action: ACCEPT
    reason: Nucleolar localization in stress response.
    supported_by:
    - reference_id: PMID:17626041
      supporting_text: Cockayne syndrome protein B interacts with and is 
        phosphorylated by c-Abl tyrosine kinase.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17515907
  review:
    summary: ABL1 localizes to cytoplasm.
    action: ACCEPT
    reason: Cytoplasmic localization is core, enabling cytoskeletal regulation 
      functions.
    supported_by:
    - reference_id: PMID:17515907
      supporting_text: May 21. Structural basis for the transforming activity of
        human cancer-related signaling adaptor protein CRK.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:11120811
  review:
    summary: ABL1 localizes to cytosol.
    action: ACCEPT
    reason: Cytosolic localization supporting signaling and cytoskeletal 
      functions.
    supported_by:
    - reference_id: PMID:11120811
      supporting_text: The c-Abl tyrosine kinase is regulated downstream of the 
        B cell antigen receptor and interacts with CD19.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IDA
  original_reference_id: PMID:15657060
  review:
    summary: ABL1 participates in DNA damage response.
    action: ACCEPT
    reason: Core biological process function for ABL1.
    supported_by:
    - reference_id: PMID:15657060
      supporting_text: 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 
        autocleavage in the apoptotic response to DNA damage.
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IGI
  original_reference_id: PMID:17626041
  review:
    summary: ABL1 responds to oxidative stress, genetic interaction evidence.
    action: ACCEPT
    reason: Part of ABL1's stress response functions.
    supported_by:
    - reference_id: PMID:17626041
      supporting_text: Cockayne syndrome protein B interacts with and is 
        phosphorylated by c-Abl tyrosine kinase.
- term:
    id: GO:0007204
    label: positive regulation of cytosolic calcium ion concentration
  evidence_type: IMP
  original_reference_id: PMID:24367707
  review:
    summary: ABL1 regulates cytosolic calcium concentration.
    action: KEEP_AS_NON_CORE
    reason: Downstream signaling effect rather than core function.
    supported_by:
    - reference_id: PMID:24367707
      supporting_text: eCollection 2013. Abl family kinases regulate endothelial
        barrier function in vitro and in mice.
- term:
    id: GO:0007229
    label: integrin-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 regulates integrin-mediated signaling.
    action: ACCEPT
    reason: Integrin signaling relates to core cytoskeletal regulatory function.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0008047
    label: enzyme activator activity
  evidence_type: IDA
  original_reference_id: PMID:12893824
  review:
    summary: ABL1 activates glutathione peroxidase 1.
    action: KEEP_AS_NON_CORE
    reason: Enzyme activator is a more generic function; specific to oxidative 
      stress response.
    supported_by:
    - reference_id: PMID:12893824
      supporting_text: 2003 Jul 31. Glutathione peroxidase 1 is regulated by the
        c-Abl and Arg tyrosine kinases.
- term:
    id: GO:0010595
    label: positive regulation of endothelial cell migration
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 promotes endothelial cell migration via neuropilin signaling.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific phenotype, not core function.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IMP
  original_reference_id: PMID:28288113
  review:
    summary: ABL1 kinase activity demonstrated by mutant phenotype.
    action: ACCEPT
    reason: General kinase activity is core to ABL1 function.
    supported_by:
    - reference_id: PMID:28288113
      supporting_text: Germline mutations in ABL1 cause an autosomal dominant 
        syndrome characterized by congenital heart defects and skeletal 
        malformations.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  review:
    summary: ABL1 localizes to nuclear bodies.
    action: ACCEPT
    reason: Nuclear body localization consistent with transcription/DNA damage 
      functions.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IPI
  original_reference_id: PMID:12893824
  review:
    summary: ABL1 binds glutathione peroxidase 1.
    action: KEEP_AS_NON_CORE
    reason: Generic enzyme binding; specific to oxidative stress context.
    supported_by:
    - reference_id: PMID:12893824
      supporting_text: 2003 Jul 31. Glutathione peroxidase 1 is regulated by the
        c-Abl and Arg tyrosine kinases.
- term:
    id: GO:0019905
    label: syntaxin binding
  evidence_type: IPI
  original_reference_id: PMID:23006999
  review:
    summary: ABL1 binds syntaxin.
    action: KEEP_AS_NON_CORE
    reason: Specific binding interaction; not core function.
    supported_by:
    - reference_id: PMID:23006999
      supporting_text: 'Tyrosine phosphorylation of a SNARE protein, syntaxin 17:
        implications for membrane trafficking in the early secretory pathway.'
- term:
    id: GO:0030145
    label: manganese ion binding
  evidence_type: IDA
  original_reference_id: PMID:9144171
  review:
    summary: ABL1 binds manganese ions.
    action: ACCEPT
    reason: Metal ion binding supports kinase activity (can substitute for 
      magnesium).
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0030516
    label: regulation of axon extension
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 regulates axon extension through cytoskeletal effects.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific phenotype related to cytoskeletal regulation.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0030845
    label: phospholipase C-inhibiting G protein-coupled receptor signaling 
      pathway
  evidence_type: IMP
  original_reference_id: PMID:24367707
  review:
    summary: ABL1 involved in PLC-inhibiting GPCR signaling.
    action: KEEP_AS_NON_CORE
    reason: Specific signaling pathway involvement; not core function.
    supported_by:
    - reference_id: PMID:24367707
      supporting_text: eCollection 2013. Abl family kinases regulate endothelial
        barrier function in vitro and in mice.
- term:
    id: GO:0031113
    label: regulation of microtubule polymerization
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 regulates microtubule polymerization via CLASP2 
      phosphorylation.
    action: ACCEPT
    reason: Part of core cytoskeletal regulatory function.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0032489
    label: regulation of Cdc42 protein signal transduction
  evidence_type: IMP
  original_reference_id: PMID:26051942
  review:
    summary: ABL1 regulates Cdc42 signaling.
    action: ACCEPT
    reason: Cdc42 regulation relates to core cytoskeletal organization function.
    supported_by:
    - reference_id: PMID:26051942
      supporting_text: 2015 Jun 4. NRP1 Regulates CDC42 Activation to Promote 
        Filopodia Formation in Endothelial Tip Cells.
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 regulates actin cytoskeleton organization.
    action: ACCEPT
    reason: Core biological process function of ABL1.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 regulates actin cytoskeleton organization in endothelial 
      cells.
    action: ACCEPT
    reason: Core cytoskeletal function; this is additional IMP evidence.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: IDA
  original_reference_id: PMID:12893824
  review:
    summary: ABL1 responds to oxidative stress by activating antioxidant 
      enzymes.
    action: ACCEPT
    reason: Part of ABL1's stress response function.
    supported_by:
    - reference_id: PMID:12893824
      supporting_text: 2003 Jul 31. Glutathione peroxidase 1 is regulated by the
        c-Abl and Arg tyrosine kinases.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IDA
  original_reference_id: PMID:9144171
  review:
    summary: ABL1 participates in intracellular signal transduction.
    action: ACCEPT
    reason: Core function as a signaling kinase.
    supported_by:
    - reference_id: PMID:9144171
      supporting_text: Protein binding and signaling properties of RIN1 suggest 
        a unique effector function.
- term:
    id: GO:0035556
    label: intracellular signal transduction
  evidence_type: IDA
  original_reference_id: PMID:11121037
  review:
    summary: ABL1 participates in intracellular signal transduction.
    action: ACCEPT
    reason: Core signaling function with additional IDA evidence.
    supported_by:
    - reference_id: PMID:11121037
      supporting_text: Functional interaction between c-Abl and the 
        p21-activated protein kinase gamma-PAK.
- term:
    id: GO:0035791
    label: platelet-derived growth factor receptor-beta signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 involved in PDGFR-beta signaling.
    action: KEEP_AS_NON_CORE
    reason: Specific growth factor signaling pathway; not core evolved function.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:0038189
    label: neuropilin signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 involved in neuropilin signaling pathway.
    action: KEEP_AS_NON_CORE
    reason: Specific signaling pathway involvement.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0038191
    label: neuropilin binding
  evidence_type: IPI
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 binds neuropilin.
    action: KEEP_AS_NON_CORE
    reason: Specific binding interaction in angiogenesis context.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0042169
    label: SH2 domain binding
  evidence_type: IPI
  original_reference_id: PMID:12384576
  review:
    summary: ABL1 engages in SH2 domain-mediated interactions.
    action: ACCEPT
    reason: SH2 domain interactions are core to ABL1 signaling mechanisms.
    supported_by:
    - reference_id: PMID:12384576
      supporting_text: Structure of a regulatory complex involving the Abl SH3 
        domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
- term:
    id: GO:0042770
    label: signal transduction in response to DNA damage
  evidence_type: IDA
  original_reference_id: PMID:15657060
  review:
    summary: ABL1 signals in response to DNA damage.
    action: ACCEPT
    reason: Core DNA damage response function.
    supported_by:
    - reference_id: PMID:15657060
      supporting_text: 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 
        autocleavage in the apoptotic response to DNA damage.
- term:
    id: GO:0042770
    label: signal transduction in response to DNA damage
  evidence_type: IDA
  original_reference_id: PMID:18280240
  review:
    summary: ABL1 participates in DNA damage signaling.
    action: ACCEPT
    reason: Core DNA damage response function with additional evidence.
    supported_by:
    - reference_id: PMID:18280240
      supporting_text: Yap1 phosphorylation by c-Abl is a critical step in 
        selective activation of proapoptotic genes in response to DNA damage.
- term:
    id: GO:0042770
    label: signal transduction in response to DNA damage
  evidence_type: IDA
  original_reference_id: PMID:9037071
  review:
    summary: ABL1 signals in response to DNA damage to regulate apoptosis.
    action: ACCEPT
    reason: Core DNA damage response function.
    supported_by:
    - reference_id: PMID:9037071
      supporting_text: Regulation of DNA damage-induced apoptosis by the c-Abl 
        tyrosine kinase.
- term:
    id: GO:0043065
    label: positive regulation of apoptotic process
  evidence_type: IDA
  original_reference_id: PMID:9037071
  review:
    summary: ABL1 promotes apoptosis in response to DNA damage.
    action: ACCEPT
    reason: Pro-apoptotic function in response to irreparable DNA damage is a 
      core function.
    supported_by:
    - reference_id: PMID:9037071
      supporting_text: Regulation of DNA damage-induced apoptosis by the c-Abl 
        tyrosine kinase.
- term:
    id: GO:0043539
    label: protein serine/threonine kinase activator activity
  evidence_type: IDA
  original_reference_id: PMID:10713049
  review:
    summary: ABL1 activates serine/threonine kinases including PKC.
    action: ACCEPT
    reason: Kinase activator activity supports signaling function.
    supported_by:
    - reference_id: PMID:10713049
      supporting_text: Interaction between protein kinase C delta and the c-Abl 
        tyrosine kinase in the cellular response to oxidative stress.
- term:
    id: GO:0048471
    label: perinuclear region of cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17888034
  review:
    summary: ABL1 localizes to perinuclear region.
    action: ACCEPT
    reason: Consistent with shuttling between cytoplasm and nucleus.
    supported_by:
    - reference_id: PMID:17888034
      supporting_text: Epub 2007 Sep 18. Fibroblast growth factor receptor 1 
        oncogene partner as a novel prognostic biomarker and therapeutic target 
        for lung cancer.
- term:
    id: GO:0051019
    label: mitogen-activated protein kinase binding
  evidence_type: IPI
  original_reference_id: PMID:11121037
  review:
    summary: ABL1 binds MAPK/PAK2.
    action: ACCEPT
    reason: MAPK binding supports signaling integration function.
    supported_by:
    - reference_id: PMID:11121037
      supporting_text: Functional interaction between c-Abl and the 
        p21-activated protein kinase gamma-PAK.
- term:
    id: GO:0051444
    label: negative regulation of ubiquitin-protein transferase activity
  evidence_type: IDA
  original_reference_id: PMID:20823226
  review:
    summary: ABL1 negatively regulates ubiquitin-protein transferase activity.
    action: KEEP_AS_NON_CORE
    reason: Regulatory function but not core molecular function.
    supported_by:
    - reference_id: PMID:20823226
      supporting_text: Phosphorylation by the c-Abl protein tyrosine kinase 
        inhibits parkin's ubiquitination and protective function.
- term:
    id: GO:0051496
    label: positive regulation of stress fiber assembly
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 promotes stress fiber assembly.
    action: ACCEPT
    reason: Part of core cytoskeletal regulatory function.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0051894
    label: positive regulation of focal adhesion assembly
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 promotes focal adhesion assembly.
    action: ACCEPT
    reason: Focal adhesion regulation is part of cytoskeletal function.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0070064
    label: proline-rich region binding
  evidence_type: IDA
  original_reference_id: PMID:15657060
  review:
    summary: ABL1 binds proline-rich regions through its SH3 domain.
    action: ACCEPT
    reason: SH3 domain-mediated binding is core to ABL1 protein interactions.
    supported_by:
    - reference_id: PMID:15657060
      supporting_text: 2005 Jan 18. c-Abl tyrosine kinase regulates caspase-9 
        autocleavage in the apoptotic response to DNA damage.
- term:
    id: GO:0070301
    label: cellular response to hydrogen peroxide
  evidence_type: IDA
  original_reference_id: PMID:10713049
  review:
    summary: ABL1 responds to hydrogen peroxide (oxidative stress).
    action: ACCEPT
    reason: Part of oxidative stress response function.
    supported_by:
    - reference_id: PMID:10713049
      supporting_text: Interaction between protein kinase C delta and the c-Abl 
        tyrosine kinase in the cellular response to oxidative stress.
- term:
    id: GO:0097100
    label: supercoiled DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9558345
  negated: true
  review:
    summary: ABL1 does NOT bind supercoiled DNA (negative annotation with NOT 
      qualifier).
    action: ACCEPT
    reason: Negative annotation indicating specificity of DNA binding - binds 
      junction/bubble structures but not supercoiled.
    supported_by:
    - reference_id: PMID:9558345
      supporting_text: The DNA binding domain of the human c-Abl tyrosine kinase
        preferentially binds to DNA sequences containing an AAC motif and to 
        distorted DNA structures.
- term:
    id: GO:0141214
    label: positive regulation of phospholipase C/protein kinase C signal 
      transduction
  evidence_type: IDA
  original_reference_id: PMID:10713049
  review:
    summary: ABL1 activates PLC/PKC signaling.
    action: KEEP_AS_NON_CORE
    reason: Specific signaling pathway regulation; downstream of kinase 
      activity.
    supported_by:
    - reference_id: PMID:10713049
      supporting_text: Interaction between protein kinase C delta and the c-Abl 
        tyrosine kinase in the cellular response to oxidative stress.
- term:
    id: GO:1904518
    label: protein localization to cytoplasmic microtubule plus-end
  evidence_type: IMP
  original_reference_id: PMID:24520051
  review:
    summary: ABL1 promotes protein localization to microtubule plus-ends.
    action: ACCEPT
    reason: Part of microtubule/cytoskeletal regulatory function.
    supported_by:
    - reference_id: PMID:24520051
      supporting_text: 2014 Mar 12. Abelson phosphorylation of CLASP2 modulates 
        its association with microtubules and actin.
- term:
    id: GO:1900026
    label: positive regulation of substrate adhesion-dependent cell spreading
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 promotes cell spreading.
    action: KEEP_AS_NON_CORE
    reason: Phenotypic outcome of cytoskeletal/adhesion regulation.
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:1990837
    label: sequence-specific double-stranded DNA binding
  evidence_type: IDA
  original_reference_id: PMID:9558345
  review:
    summary: ABL1 binds specific DNA sequences.
    action: ACCEPT
    reason: Specific DNA binding supports DNA damage response function.
    supported_by:
    - reference_id: PMID:9558345
      supporting_text: The DNA binding domain of the human c-Abl tyrosine kinase
        preferentially binds to DNA sequences containing an AAC motif and to 
        distorted DNA structures.
- term:
    id: GO:2000042
    label: negative regulation of double-strand break repair via homologous 
      recombination
  evidence_type: IDA
  original_reference_id: PMID:9461559
  review:
    summary: ABL1 inhibits homologous recombination repair by phosphorylating 
      RAD51.
    action: ACCEPT
    reason: Important regulatory function in DNA damage response pathway.
    supported_by:
    - reference_id: PMID:9461559
      supporting_text: Regulation of Rad51 function by c-Abl in response to DNA 
        damage.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IPI
  original_reference_id: PMID:12384576
  review:
    summary: ABL1 is part of protein complexes.
    action: KEEP_AS_NON_CORE
    reason: Generic complex annotation; specific complexes are more informative.
    supported_by:
    - reference_id: PMID:12384576
      supporting_text: Structure of a regulatory complex involving the Abl SH3 
        domain, the Crk SH2 domain, and a Crk-derived phosphopeptide.
- term:
    id: GO:0043542
    label: endothelial cell migration
  evidence_type: IMP
  original_reference_id: PMID:24863063
  review:
    summary: ABL1 involved in endothelial cell migration.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific phenotype.
# ========== MISSING AUTHOR STATEMENT ANNOTATIONS ==========
    supported_by:
    - reference_id: PMID:24863063
      supporting_text: Imatinib inhibits VEGF-independent angiogenesis by 
        targeting neuropilin 1-dependent ABL1 activation in endothelial cells.
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: TAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 involved in mitotic cell cycle regulation.
    action: KEEP_AS_NON_CORE
    reason: Cell cycle involvement but not core molecular function.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: NAS
  original_reference_id: PMID:8242749
  review:
    summary: ABL1 binds DNA.
    action: ACCEPT
    reason: DNA binding is a core molecular function of ABL1.
    supported_by:
    - reference_id: PMID:8242749
      supporting_text: A C-terminal protein-binding domain in the retinoblastoma
        protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: TAS
  original_reference_id: PMID:15865930
  review:
    summary: ABL1 acts as a transcription coactivator.
    action: ACCEPT
    reason: Transcriptional regulation is part of nuclear ABL1 function.
    supported_by:
    - reference_id: PMID:15865930
      supporting_text: C-Abl as a modulator of p53.
- term:
    id: GO:0003785
    label: actin monomer binding
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 binds G-actin monomers.
    action: ACCEPT
    reason: G-actin binding is part of actin cytoskeleton regulatory function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0004515
    label: nicotinate-nucleotide adenylyltransferase activity
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 has nicotinate-nucleotide adenylyltransferase activity.
    action: UNDECIDED
    reason: This annotation seems unusual for ABL1. Requires verification - may 
      be a curation error.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: PMID:10391249
  review:
    summary: ABL1 is a protein tyrosine kinase.
    action: ACCEPT
    reason: Core molecular function.
    supported_by:
    - reference_id: PMID:10391249
      supporting_text: The tyrosine kinase c-Abl regulates p73 in apoptotic 
        response to cisplatin-induced DNA damage.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-428888
  review:
    summary: ABL1 tyrosine kinase activity in Reactome pathway.
    action: ACCEPT
    reason: Core molecular function documented in pathway context.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686587
  review:
    summary: ABL1 tyrosine kinase activity in Reactome pathway.
    action: ACCEPT
    reason: Core molecular function in pathway context.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956659
  review:
    summary: ABL1 tyrosine kinase activity in Reactome pathway.
    action: ACCEPT
    reason: Core molecular function.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9841924
  review:
    summary: ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function.
- term:
    id: GO:0004713
    label: protein tyrosine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865196
  review:
    summary: ABL1 tyrosine kinase activity.
    action: ACCEPT
    reason: Core molecular function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:8242749
  review:
    summary: ABL1 localizes to nucleus.
    action: ACCEPT
    reason: Core localization.
    supported_by:
    - reference_id: PMID:8242749
      supporting_text: A C-terminal protein-binding domain in the retinoblastoma
        protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 localizes to nucleus.
    action: ACCEPT
    reason: Core localization.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686578
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: Core nuclear localization.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5686587
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: Core nuclear localization.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8956659
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: Core nuclear localization.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9841924
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: Core nuclear localization.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9842028
  review:
    summary: ABL1 localizes to nucleoplasm.
    action: ACCEPT
    reason: Core nuclear localization.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 localizes to cytoplasm.
    action: ACCEPT
    reason: Core localization.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: NAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 localizes to mitochondria.
    action: ACCEPT
    reason: Mitochondrial localization documented, relevant to apoptosis and 
      oxidative stress functions.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2130194
  review:
    summary: ABL1 localizes to cytosol.
    action: ACCEPT
    reason: Core cytosolic localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-376141
  review:
    summary: ABL1 in cytosol (Reactome pathway).
    action: ACCEPT
    reason: Core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-428888
  review:
    summary: ABL1 in cytosol.
    action: ACCEPT
    reason: Core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-448958
  review:
    summary: ABL1 in cytosol.
    action: ACCEPT
    reason: Core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865184
  review:
    summary: ABL1 in cytosol.
    action: ACCEPT
    reason: Core localization.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9865196
  review:
    summary: ABL1 in cytosol.
    action: ACCEPT
    reason: Core localization.
- term:
    id: GO:0006298
    label: mismatch repair
  evidence_type: TAS
  original_reference_id: PMID:10391249
  review:
    summary: ABL1 involved in mismatch repair.
    action: ACCEPT
    reason: Part of DNA damage response function.
    supported_by:
    - reference_id: PMID:10391249
      supporting_text: The tyrosine kinase c-Abl regulates p73 in apoptotic 
        response to cisplatin-induced DNA damage.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: TAS
  original_reference_id: PMID:8242749
  review:
    summary: ABL1 regulates transcription.
    action: ACCEPT
    reason: Part of nuclear ABL1 function.
    supported_by:
    - reference_id: PMID:8242749
      supporting_text: A C-terminal protein-binding domain in the retinoblastoma
        protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: TAS
  original_reference_id: PMID:10391249
  review:
    summary: ABL1 promotes intrinsic apoptosis after DNA damage.
    action: ACCEPT
    reason: Core DNA damage response function.
    supported_by:
    - reference_id: PMID:10391249
      supporting_text: The tyrosine kinase c-Abl regulates p73 in apoptotic 
        response to cisplatin-induced DNA damage.
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 involved in DNA damage-induced apoptosis.
    action: ACCEPT
    reason: Core function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0010506
    label: regulation of autophagy
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 regulates autophagy.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per previous guidance, autophagy-related annotations should be 
      marked as over-annotated for ABL1.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0015629
    label: actin cytoskeleton
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 localizes to actin cytoskeleton.
    action: ACCEPT
    reason: Core localization for cytoskeletal function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0030100
    label: regulation of endocytosis
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 regulates endocytosis.
    action: KEEP_AS_NON_CORE
    reason: Endocytosis regulation is a downstream effect of cytoskeletal 
      function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0030155
    label: regulation of cell adhesion
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 regulates cell adhesion.
    action: ACCEPT
    reason: Cell adhesion regulation is part of core cytoskeletal/integrin 
      functions.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0032956
    label: regulation of actin cytoskeleton organization
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 regulates actin cytoskeleton organization.
    action: ACCEPT
    reason: Core biological process function.
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: TAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 responds to oxidative stress.
    action: ACCEPT
    reason: Part of stress response function.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:0036211
    label: protein modification process
  evidence_type: NAS
  original_reference_id: PMID:8242749
  review:
    summary: ABL1 modifies proteins (phosphorylation).
    action: ACCEPT
    reason: General annotation for kinase function.
    supported_by:
    - reference_id: PMID:8242749
      supporting_text: A C-terminal protein-binding domain in the retinoblastoma
        protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
- term:
    id: GO:0038096
    label: Fc-gamma receptor signaling pathway involved in phagocytosis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2029480
  review:
    summary: ABL1 involved in Fc-gamma receptor signaling.
    action: KEEP_AS_NON_CORE
    reason: Specific signaling pathway; not core function.
- term:
    id: GO:0038096
    label: Fc-gamma receptor signaling pathway involved in phagocytosis
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9664422
  review:
    summary: ABL1 in Fc-gamma receptor signaling.
    action: KEEP_AS_NON_CORE
    reason: Specific pathway annotation.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: TAS
  original_reference_id: PMID:15865930
  review:
    summary: ABL1 promotes RNA Pol II transcription.
    action: ACCEPT
    reason: Part of transcriptional coactivator function.
    supported_by:
    - reference_id: PMID:15865930
      supporting_text: C-Abl as a modulator of p53.
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: TAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 regulates cell cycle.
    action: KEEP_AS_NON_CORE
    reason: Cell cycle regulation is downstream of core signaling functions.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:0051882
    label: mitochondrial depolarization
  evidence_type: TAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 involved in mitochondrial depolarization.
    action: KEEP_AS_NON_CORE
    reason: Related to apoptosis but specific mitochondrial effect.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:0071103
    label: DNA conformation change
  evidence_type: IDA
  original_reference_id: PMID:9558345
  review:
    summary: ABL1 induces DNA conformation changes.
    action: ACCEPT
    reason: Part of DNA binding/DNA damage response function.
    supported_by:
    - reference_id: PMID:9558345
      supporting_text: The DNA binding domain of the human c-Abl tyrosine kinase
        preferentially binds to DNA sequences containing an AAC motif and to 
        distorted DNA structures.
- term:
    id: GO:0097706
    label: vascular endothelial cell response to oscillatory fluid shear stress
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9860927
  review:
    summary: ABL1 involved in endothelial shear stress response.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific response.
- term:
    id: GO:0098794
    label: postsynapse
  evidence_type: TAS
  original_reference_id: PMID:24658113
  review:
    summary: ABL1 localizes to postsynapse.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific localization in neurons.
    supported_by:
    - reference_id: PMID:24658113
      supporting_text: eCollection 2014. EphA4 activation of c-Abl mediates 
        synaptic loss and LTP blockade caused by amyloid-β oligomers.
- term:
    id: GO:1902036
    label: regulation of hematopoietic stem cell differentiation
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-8939236
  review:
    summary: ABL1 regulates hematopoietic stem cell differentiation.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific developmental function.
- term:
    id: GO:1903351
    label: cellular response to dopamine
  evidence_type: TAS
  original_reference_id: PMID:24522549
  review:
    summary: ABL1 responds to dopamine.
    action: KEEP_AS_NON_CORE
    reason: Specific stimulus response; relevant to Parkinson's disease context.
    supported_by:
    - reference_id: PMID:24522549
      supporting_text: Epub 2014 Feb 13. Oxidative stress-induced signaling 
        pathways implicated in the pathogenesis of Parkinson's disease.
- term:
    id: GO:2000145
    label: regulation of cell motility
  evidence_type: TAS
  original_reference_id: PMID:20841568
  review:
    summary: ABL1 regulates cell motility.
    action: ACCEPT
    reason: Motility regulation through cytoskeletal effects is a core function.
# ========== MISSING COMPUTATIONAL ANNOTATIONS ==========
    supported_by:
    - reference_id: PMID:20841568
      supporting_text: 'ABL tyrosine kinases: evolution of function, regulation, and
        specificity.'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 nuclear localization inferred from sequence similarity.
    action: ACCEPT
    reason: Consistent with experimentally validated nuclear localization.
- term:
    id: GO:0030036
    label: actin cytoskeleton organization
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 role in actin organization inferred from mouse ortholog.
    action: ACCEPT
    reason: Core function consistent with experimental evidence.
- term:
    id: GO:0030425
    label: dendrite
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 dendrite localization from ortholog inference.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific neuronal localization.
- term:
    id: GO:0043025
    label: neuronal cell body
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 neuronal cell body localization inferred.
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific localization.
- term:
    id: GO:0045580
    label: regulation of T cell differentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 regulates T cell differentiation (ortholog inference).
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific developmental function.
- term:
    id: GO:0046875
    label: ephrin receptor binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 binds ephrin receptors (ortholog inference).
    action: ACCEPT
    reason: Ephrin receptor interaction documented, relevant to cytoskeletal 
      signaling.
- term:
    id: GO:1900272
    label: negative regulation of long-term synaptic potentiation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 negatively regulates LTP (ortholog inference).
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific neuronal function.
- term:
    id: GO:1903905
    label: positive regulation of establishment of T cell polarity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 promotes T cell polarity (ortholog inference).
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific function.
- term:
    id: GO:1905244
    label: regulation of modification of synaptic structure
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 regulates synaptic structure (ortholog inference).
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific neuronal function.
- term:
    id: GO:2000406
    label: positive regulation of T cell migration
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: ABL1 promotes T cell migration (ortholog inference).
    action: KEEP_AS_NON_CORE
    reason: Cell-type-specific function.
# ========== CORE FUNCTIONS SUMMARY ==========
core_functions:
- molecular_function:
    id: GO:0004715
    label: non-membrane spanning protein tyrosine kinase activity
  description: >-
    ABL1 is a non-receptor tyrosine kinase that phosphorylates substrates involved
    in
    DNA damage response, actin cytoskeleton dynamics, and cell signaling.
  directly_involved_in:
  - id: GO:0006281
    label: DNA repair
  - id: GO:0032956
    label: regulation of actin cytoskeleton organization
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005829
    label: cytosol
  supported_by:
  - reference_id: PMID:9461559
    supporting_text: "Regulation of Rad51 function by c-Abl in response to DNA damage"
  - reference_id: file:human/ABL1/ABL1-deep-research-falcon.md
    supporting_text: "[ABL1 phosphorylates cortactin to regulate actin cytoskeleton
      organization]"
- molecular_function:
    id: GO:0051015
    label: actin filament binding
  description: >-
    ABL1 directly binds F-actin through its C-terminal actin binding domain, enabling
    localization to and regulation of the actin cytoskeleton.
  locations:
  - id: GO:0005856
    label: cytoskeleton
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:20841568
    supporting_text: "ABL1 contains F-actin binding and G-actin binding regions in
      its C-terminus"
    full_text_unavailable: true
- molecular_function:
    id: GO:0003677
    label: DNA binding
  description: >-
    Nuclear ABL1 binds DNA through its C-terminal DNA binding domain and participates
    in DNA damage response signaling, promoting apoptosis when damage is irreparable.
  directly_involved_in:
  - id: GO:0006974
    label: DNA damage response
  - id: GO:0006915
    label: apoptotic process
  locations:
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:9168116
    supporting_text: "Ataxia telangiectasia mutant protein activates c-Abl tyrosine
      kinase in response to ionizing radiation"
  - reference_id: PMID:9037071
    supporting_text: "Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine
      kinase"

Gene Description

Existing Annotations Review

Core Functions

ABL1 is a non-receptor tyrosine kinase that phosphorylates substrates involved in DNA damage response, actin cytoskeleton dynamics, and cell signaling.

ABL1 directly binds F-actin through its C-terminal actin binding domain, enabling localization to and regulation of the actin cytoskeleton.

Nuclear ABL1 binds DNA through its C-terminal DNA binding domain and participates in DNA damage response signaling, promoting apoptosis when damage is irreparable.

References

Deep Research

Falcon

Citations

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