STAT5A is a latent cytoplasmic signal transducer and sequence-specific transcription factor of the STAT family, and a close paralog of STAT5B (~90-95% identity). It is built from an N-terminal oligomerization domain, a coiled-coil domain, a p53-like DNA-binding domain, a linker, an SH2 domain, and a C-terminal transactivation domain. STAT5A is activated downstream of numerous cytokine and hormone receptors: the common gamma-chain cytokines IL-2, IL-4, IL-7, IL-9 and IL-15 (via JAK1/JAK3), IL-3/IL-5/GM-CSF, prolactin, growth hormone, erythropoietin and thrombopoietin (via JAK2), and oncogenic tyrosine kinases such as KIT and FLT3. Receptor-associated JAK kinases phosphorylate STAT5A on Tyr-694; the phosphorylated protein dimerizes through reciprocal SH2-phosphotyrosine interactions (forming homodimers, higher-order tetramers, and heterodimers with STAT5B or STAT3), translocates from the cytoplasm to the nucleus, and binds gamma-activated sequence (GAS) DNA elements to activate RNA polymerase II transcription of target genes, recruiting coactivators such as NCOA1/SRC-1 and CBP/p300. Tyrosine phosphorylation is required for DNA binding and dimerization, and serine phosphorylation for maximal transcriptional activity; signaling is terminated by SOCS/CIS proteins, phosphatases, and nuclear export. STAT5A is the mammary-predominant STAT5 paralog and a central effector of prolactin-PRLR-JAK2 signaling driving alveolar differentiation and milk-protein expression during lactation, and it also contributes, largely redundantly with STAT5B, to hematopoietic and lymphoid cell proliferation, survival and differentiation and to immune homeostasis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: As a sequence-specific transcription factor, activated STAT5A dimers associate with chromatin at target loci (GAS elements). TFClass-based inference, consistent with its DNA-binding function. Reason: Consistent with STAT5A's DNA-binding transcription factor activity and nuclear localization. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A binds gamma-activated-sequence (GAS) elements in cis-regulatory regions of RNA Pol II target genes. Strongly supported phylogenetically across the STAT clade and by experiment. Reason: Core sequence-specific DNA-binding molecular function; central to STAT5A's role as a transcription factor. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: GAS-element cis-regulatory DNA binding inferred electronically from the mouse ortholog. Duplicate of the IBA annotation to the same term. Reason: Core DNA-binding molecular function; redundant with the IBA annotation. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A is a sequence-specific RNA Pol II transcription factor. This is the core molecular function, phylogenetically well supported and consistent with direct experimental evidence. Reason: Core molecular function of STAT5A. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based assignment of sequence-specific Pol II transcription factor activity. Duplicate of the IBA annotation; core MF. Reason: Core molecular function; redundant with the IBA annotation. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000120 | ACCEPT | Summary: STAT5A is a sequence-specific transcriptional activator at GAS elements, recruiting coactivators (NCOA1/SRC-1, CBP/p300). Core activator molecular function. Reason: Core molecular function; STAT5A is a sequence-specific transcriptional activator. |
| GO:0001938 positive regulation of endothelial cell proliferation | IMP PMID:20489169 microRNA-222 controls neovascularization by regulating signa... | KEEP AS NON CORE | Summary: miR-222 targeting of STAT5A modulates endothelial cell proliferation during inflammation-driven neovascularization (PMID:20489169). Experimental but a context-specific downstream vascular process, not the core molecular function. Reason: Experimentally supported in a specific neovascularization context; a downstream biological outcome rather than STAT5A's core transcription-factor activity. Supporting Evidence: PMID:20489169 microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: STAT5A binds DNA. General parent of the sequence-specific GAS-binding molecular function; InterPro-based electronic inference consistent with experiment. Reason: Correct but a general parent of the specific RNA Pol II cis-regulatory sequence-specific DNA binding annotation. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:10919676 STAT5 activation is required for interleukin-9-dependent gro... | MODIFY | Summary: STAT5 acts as a DNA-binding transcription factor mediating IL-9-driven proliferation and transformation of lymphoid cells (PMID:10919676). Essence correct but the term is general; STAT5A is specifically an RNA Pol II transcription factor. Reason: The general DNA-binding TF term should be replaced with the RNA Pol II-specific child term (GO:0000981), which precisely captures STAT5A's core activity. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:10919676 STAT5 is an important mediator of IL-9-driven proliferation |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:12393707 Signal transducer and activator of transcription 5a (STAT5a)... | MODIFY | Summary: STAT5a functions as a DNA-binding transcription factor (inducing target genes Bcl-2 and p21) during eosinophil differentiation of human CD34+ cells (PMID:12393707). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:12393707 STAT5 plays a critical role in eosinophil differentiation of primary human |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ... | MODIFY | Summary: STAT5 phosphorylated downstream of TSLP (via JAK1/JAK2) acts as a DNA-binding transcription factor (PMID:20974963). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:20974963 JAK1 and JAK2 in TSLP-mediated STAT5 phosphorylation |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and... | MODIFY | Summary: IL-2 and IL-15 induce tyrosine phosphorylation and activation of STAT5 as a DNA-binding transcription factor (PMID:7568001). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:7568001 IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5 |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:8580378 Activation of JAK3, but not JAK1, is critical for IL-2-induc... | MODIFY | Summary: STAT5 is the predominant STAT transcription factor recruited by IL-2 in human T cells (PMID:8580378). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:8580378 STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:9516478 Prolactin receptor regulates Stat5 tyrosine phosphorylation ... | MODIFY | Summary: Prolactin specifically activates Stat5 as a DNA-binding transcription factor downstream of the prolactin receptor (PMID:9516478). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:9516478 Stat5 is specifically activated by PRL treatment |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: DNA-binding transcription factor activity inferred electronically from STAT-family InterPro signatures. General term; the RNA Pol II-specific child is more precise for STAT5A. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981), which is present and better represents the core function. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:7719937 Identification and purification of human Stat proteins activ... | MODIFY | Summary: Human Stat5 (hStat5), the principal IL-2-inducible DNA-binding transcription factor, was first purified in this study (PMID:7719937). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:7719937 designated hStat5 |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | MODIFY | Summary: STAT5A is a DNA-binding transcription factor whose IL-2-induced DNA-binding activity depends on Tyr-694 phosphorylation (PMID:8631883). General term; the RNA Pol II-specific child is more precise. Reason: Replace with the RNA Pol II-specific transcription factor activity term (GO:0000981). Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:8631883 human Stat5 activation is also dependent on Tyr-694 in Stat5A and Tyr-699 in Stat5B |
| GO:0005515 protein binding | IPI PMID:12237455 The SPOT technique as a tool for studying protein tyrosine p... | REMOVE | Summary: STAT5 phosphopeptides are bound by the PTP-1B (PTPN1) substrate-trapping mutant, i.e. STAT5 is a substrate of this phosphatase (PMID:12237455). The bare 'protein binding' term conveys no functional information about STAT5A. Reason: GO:0005515 'protein binding' is uninformative and the interaction is a phosphatase-substrate relationship that assigns STAT5A no specific molecular function; the interaction is not disputed, but the term should not be retained. Supporting Evidence: PMID:12237455 STAT 5 phosphopeptides |
| GO:0005515 protein binding | IPI PMID:16819511 STAT5 represses BCL6 expression by binding to a regulatory r... | REMOVE | Summary: This IPI annotation (partner BCL6/P41182) actually reflects STAT5 binding inducibly to a regulatory region of the BCL6 gene to repress it, i.e. DNA binding to the BCL6 locus, not a STAT5A-BCL6 protein complex (PMID:16819511). The bare 'protein binding' term is both uninformative and mis-frames the finding. Reason: GO:0005515 'protein binding' is uninformative; the underlying evidence is sequence-specific DNA binding to and transcriptional repression of the BCL6 gene, which is captured by STAT5A's DNA-binding transcription factor activity and transcription-regulation annotations. Supporting Evidence: PMID:16819511 STAT5 can bind inducibly and regulate transcription at one of these regions, identifying BCL6 as a STAT5 target gene |
| GO:0005515 protein binding | IPI PMID:20075866 PIKE-A is required for prolactin-mediated STAT5a activation ... | REMOVE | Summary: PIKE-A (AGAP2) directly associates with STAT5a and the prolactin receptor and is required for PRL-provoked STAT5a activation (PMID:20075866). A real, functionally relevant interaction, but the bare 'protein binding' term gives no molecular-function information. Reason: GO:0005515 'protein binding' is uninformative; the interaction is real but assigns STAT5A no specific molecular function (PIKE-A acts as an upstream activator of STAT5a). Supporting Evidence: PMID:20075866 PIKE-A directly associates with both signal transducer and activator of transcription 5a |
| GO:0005515 protein binding | IPI PMID:24658140 The mammalian-membrane two-hybrid assay (MaMTH) for probing ... | REMOVE | Summary: STAT5A-EGFR interaction detected by the mammalian-membrane two-hybrid (MaMTH) assay (PMID:24658140). The bare 'protein binding' term is uninformative. Reason: GO:0005515 'protein binding' is uninformative; a binary two-hybrid interaction with EGFR adds no functional resolution to STAT5A's role. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: High-throughput binary interactome (HuRI) interaction with TCF12 (PMID:25416956). The bare 'protein binding' term is uninformative. Reason: GO:0005515 'protein binding' is uninformative; a high-throughput binary partner adds no functional resolution. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | REMOVE | Summary: STAT5A-EGFR interaction reported in a high-throughput study of EGFR-network rewiring in colorectal cancer cells (PMID:31980649). The bare 'protein binding' term is uninformative. Reason: GO:0005515 'protein binding' is uninformative; a high-throughput network interaction adds no functional resolution. |
| GO:0005634 nucleus | EXP PMID:15534001 The ERBB4/HER4 receptor tyrosine kinase regulates gene expre... | ACCEPT | Summary: Activated STAT5A accumulates in and functions in the nucleus; ERBB4/4ICD acts as a nuclear chaperone driving STAT5A nuclear localization and beta-casein promoter binding (PMID:15534001). Direct experimental support. Reason: Core localization where STAT5A performs its transcription-factor function. Supporting Evidence: PMID:15534001 both proteins bind to the endogenous beta-casein promoter |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A is active in the nucleus, where activated dimers bind GAS DNA elements and regulate transcription. Phylogenetically supported; STAT5A (P42229) appears in its own WITH/FROM, reflecting experimental grounding on the target itself. Reason: Core localization for STAT5A's transcription-factor activity; consistent with direct experimental evidence. |
| GO:0005634 nucleus | IC PMID:12393707 Signal transducer and activator of transcription 5a (STAT5a)... | ACCEPT | Summary: Nuclear site of action inferred (IC) for activated STAT5a during eosinophil differentiation (PMID:12393707). Consistent with STAT5A's transcription-factor role. Reason: Core nuclear localization of activated STAT5A. |
| GO:0005634 nucleus | IC PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ... | ACCEPT | Summary: Nuclear site of action inferred (IC) for STAT5 activated downstream of TSLP (PMID:20974963). Consistent with STAT5A's transcription-factor role. Reason: Core nuclear localization of activated STAT5A. |
| GO:0005634 nucleus | IC PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and... | ACCEPT | Summary: Nuclear site of action inferred (IC) for STAT5 activated by IL-2/IL-15 (PMID:7568001). Consistent with STAT5A's transcription-factor role. Reason: Core nuclear localization of activated STAT5A. |
| GO:0005634 nucleus | IC PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | ACCEPT | Summary: Nuclear site of action inferred (IC) for STAT5A reconstituting IL-2-induced DNA-binding activity (PMID:8631883). Consistent with STAT5A's transcription-factor role. Reason: Core nuclear localization of activated STAT5A. |
| GO:0005634 nucleus | IDA PMID:9516478 Prolactin receptor regulates Stat5 tyrosine phosphorylation ... | ACCEPT | Summary: Prolactin induces Stat5 nuclear translocation (PMID:9516478). Direct experimental support for nuclear localization. Reason: Core nuclear localization with direct experimental evidence. Supporting Evidence: PMID:9516478 Stat5 is specifically activated by PRL treatment |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization inferred electronically (UniProt SubCell SL-0191 / mouse ortholog). Duplicate of the experimental/IBA nucleus annotations. Reason: Core localization; redundant with the experimental and IBA nucleus annotations. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence localizes STAT5A to the nucleoplasm (GO_REF:0000052). Consistent with its nuclear transcription-factor function; a finer-grained sub-compartment of the core nucleus localization that is already accepted. Reason: Correct localization supported by immunofluorescence (IDA), but a more specific sub-compartment duplicate of the core nucleus annotation (GO:0005634). |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1254285 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1470012 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8954224 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8983379 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9012671 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670426 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698016 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698021 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698033 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698041 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698754 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701903 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9978250 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus/nucleoplasm annotation. |
| GO:0005737 cytoplasm | EXP PMID:15534001 The ERBB4/HER4 receptor tyrosine kinase regulates gene expre... | ACCEPT | Summary: Latent STAT5A resides in the cytoplasm prior to activation (PMID:15534001). Direct experimental support for dual cytoplasm/nucleus localization. Reason: Core localization of latent STAT5A before cytokine-induced nuclear translocation. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A is a latent cytoplasmic factor that docks to activated receptors and is phosphorylated by JAKs before nuclear translocation. Phylogenetically supported; target appears in its own WITH/FROM. Reason: Core dual localization (cytoplasm/nucleus) of STAT proteins. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization inferred electronically (UniProt SubCell SL-0086 / mouse ortholog). Duplicate of the experimental/IBA cytoplasm annotations. Reason: Core localization; redundant with the experimental and IBA cytoplasm annotations. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: HPA immunofluorescence localizes STAT5A to the cytosol (GO_REF:0000052). Consistent with the latent cytoplasmic pool; a finer-grained sub-compartment of the core cytoplasm localization that is already accepted. Reason: Correct localization supported by immunofluorescence (IDA), but a more specific sub-compartment duplicate of the core cytoplasm annotation (GO:0005737). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1168894 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1254285 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1254291 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1295540 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433456 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470009 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470010 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1470012 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1839112 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-380782 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452097 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-452108 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6785165 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-879909 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-879930 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8985929 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8985988 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9025969 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-919404 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-921155 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670412 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670416 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670417 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9670426 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698005 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698013 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698016 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698029 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9698033 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9703432 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9703435 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5A within a Reactome cytokine/hormone signaling pathway. Consistent with the core cytoplasm annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core cytoplasm/cytosol annotation. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: STAT5A regulates transcription. Very general InterPro-derived process term; subsumed by the RNA Pol II-specific regulation/activation terms. Reason: General parent term; more specific RNA Pol II transcription regulation terms are present. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5A regulates RNA Pol II transcription of GAS-element target genes. Correct but general; the activator-specific term (GO:0045944) and the DNA-binding TF activity terms capture the function more precisely. Reason: Accurate but a general parent of the more specific positive-regulation and DNA-binding TF activity annotations that represent the core function. |
| GO:0006357 regulation of transcription by RNA polymerase II | TAS PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | KEEP AS NON CORE | Summary: STAT5A regulates RNA Pol II transcription of target genes following IL-2-induced activation (PMID:8631883). Correct but general; the activator-specific term is more precise. Reason: General process subsumed by the specific positive-regulation-of-transcription annotation. |
| GO:0006952 defense response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reflects STAT5A's role in immunity downstream of gamma-chain cytokines. A very general process term inferred phylogenetically across the family. Reason: Captures the immune role at too high a level; cytokine-signaling / lymphocyte-differentiation terms are more informative. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: STAT5A is part of signal transduction. Very general InterPro-derived term; the JAK-STAT and cytokine-mediated signaling terms are the specific descendants. Reason: Root-level process term subsumed by specific JAK-STAT signaling annotations. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A is a defining component of JAK-STAT signaling downstream of cell surface cytokine/hormone receptors. Core process, strongly supported. Reason: Core biological process; STAT5A is by definition a JAK-STAT pathway effector. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s... | ACCEPT | Summary: STAT5A operates in JAK-STAT signaling, including as part of STAT heterodimers in immunity (PMID:24058793 review). Core process. Reason: Core JAK-STAT process; redundant with the IBA/TAS annotations to the same term. Supporting Evidence: PMID:24058793 Heterodimerization of STAT proteins is one potential mechanism for signals to be modified downstream of the receptor |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | TAS PMID:7719937 Identification and purification of human Stat proteins activ... | ACCEPT | Summary: hStat5 was identified as the principal IL-2-inducible transcription factor acting downstream of JAK kinases (PMID:7719937). Core JAK-STAT process. Reason: Core JAK-STAT process; supported by the original human STAT5/IL-2 identification study. Supporting Evidence: PMID:7719937 designated hStat5 |
| GO:0019221 cytokine-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5A is a central transducer of cytokine signaling (IL-2/3/5/7/9/15, EPO, TPO, GM-CSF, etc.). Core process, well supported by experiment and phylogeny. Reason: Core biological process for STAT5A as a cytokine signal transducer. |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate (ARBA electronic) of the cytokine-mediated signaling pathway annotation; core process for STAT5A. Reason: Core process; redundant with the IBA annotation to the same term. |
| GO:0019530 taurine metabolic process | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Narrow annotation transferred by sequence similarity from mouse Stat5b (acts upstream of taurine metabolism, likely via regulation of a metabolic target gene). Highly indirect, organism/context-specific and far from the core function. Reason: Highly indirect, narrowly-scoped ISS transfer; not representative of STAT5A's core transcription-factor function (matches the STAT5B treatment). |
| GO:0030222 eosinophil differentiation | IDA PMID:12393707 Signal transducer and activator of transcription 5a (STAT5a)... | KEEP AS NON CORE | Summary: STAT5a is required for eosinophil differentiation of human cord blood-derived CD34+ cells; dominant-negative STAT5a blocks differentiation (PMID:12393707). Experimentally supported but a specific hematopoietic differentiation outcome downstream of STAT5A target genes. Reason: Experimentally supported context-specific differentiation process; a downstream biological outcome rather than the core molecular function. Supporting Evidence: PMID:12393707 STAT5 plays a critical role in eosinophil differentiation of primary human |
| GO:0035723 interleukin-15-mediated signaling pathway | IDA PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and... | KEEP AS NON CORE | Summary: IL-15 induces tyrosine phosphorylation and activation of STAT5 (PMID:7568001). A specific cytokine context of STAT5A's core JAK-STAT/transcription-factor activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:7568001 IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5 |
| GO:0035771 interleukin-4-mediated signaling pathway | IDA PMID:17200144 IL-4 induces a wide-spectrum intracellular signaling cascade... | KEEP AS NON CORE | Summary: IL-4 induces Jak3-mediated phosphorylation and nuclear migration of STAT5 in CD8+ T cells (PMID:17200144). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:17200144 IL-4 induces the Jak3-mediated phosphorylation and nuclear migration of STAT1, STAT3, and STAT5 |
| GO:0038026 reelin-mediated signaling pathway | IDA PMID:29581031 IL-7-induced phosphorylation of the adaptor Crk-like and oth... | UNDECIDED | Summary: Annotated to reelin-mediated signaling (acts_upstream_of_or_within) citing PMID:29581031, but the cached publication is abstract-only, concerns IL-7-induced phosphorylation of Crk-like (CrkL)/Stat5, and does not mention reelin in the available text. The reelin link cannot be verified from the cached content. Reason: Per the enum, use UNDECIDED when unable to access relevant publication content: the cached abstract does not support a reelin-signaling role and the full text is unavailable, so the annotation cannot be adjudicated. |
| GO:0038043 interleukin-5-mediated signaling pathway | IDA PMID:12393707 Signal transducer and activator of transcription 5a (STAT5a)... | KEEP AS NON CORE | Summary: IL-5 activates STAT5a during eosinophil differentiation of human hematopoietic cells (PMID:12393707). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:12393707 STAT5 plays a critical role in eosinophil differentiation of primary human |
| GO:0038110 interleukin-2-mediated signaling pathway | IDA PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | KEEP AS NON CORE | Summary: STAT5A is activated by IL-2, reconstituting IL-2-induced DNA-binding activity in a Tyr-694-dependent manner (PMID:8631883). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:8631883 both Stat5A and Stat5B are activated by interleukin-2 |
| GO:0038111 interleukin-7-mediated signaling pathway | IDA PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ... | KEEP AS NON CORE | Summary: STAT5 is activated downstream of IL-7 (JAK1/JAK3), contrasted with TSLP signaling in this study (PMID:20974963). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:20974963 the known activation of JAK1 and JAK3 by the related cytokine, IL-7 |
| GO:0038113 interleukin-9-mediated signaling pathway | IDA PMID:10919676 STAT5 activation is required for interleukin-9-dependent gro... | KEEP AS NON CORE | Summary: STAT5 activation is required for IL-9-dependent growth and transformation of lymphoid cells (PMID:10919676). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:10919676 STAT5 is an important mediator of IL-9-driven proliferation |
| GO:0038156 interleukin-3-mediated signaling pathway | IDA PMID:22102340 STAT5 in human basophils: IL-3 is required for its FcΞ΅RI-med... | KEEP AS NON CORE | Summary: STAT5 in human basophils is phosphorylated in an IL-3-dependent manner (including via FcepsilonRI cross-talk) (PMID:22102340). A specific cytokine context of STAT5A's core activity. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core. Supporting Evidence: PMID:22102340 STAT5 in human basophils |
| GO:0038163 thrombopoietin-mediated signaling pathway | IDA PMID:9122198 Dissecting the thrombopoietin receptor: functional elements ... | KEEP AS NON CORE | Summary: STAT5 is phosphorylated downstream of the thrombopoietin receptor (Mpl) (PMID:9122198). A specific cytokine context of STAT5A's core activity; experimental annotation retained despite the cached abstract focusing on Mpl receptor dissection. Reason: Specific upstream cytokine context of the same core activation mechanism; kept as non-core (do not remove an experimental annotation on abstract-only grounds). Supporting Evidence: PMID:9122198 STAT5 is partially phosphorylated in the absence of any tyrosine residues in the Mpl cytoplasmic domain |
| GO:0040014 regulation of multicellular organism growth | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Organismal growth regulation transferred electronically from the mouse ortholog. Growth regulation via the GH/IGF1 axis is predominantly a STAT5B function; for STAT5A it is a shared/transferred, non-core role. Reason: Predominantly a STAT5B (GH/IGF1) function; for STAT5A this is a transferred, non-core organism-level outcome. |
| GO:0040014 regulation of multicellular organism growth | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Organismal growth regulation transferred by sequence similarity from mouse Stat5b. Duplicate of the IEA annotation; predominantly a STAT5B function for STAT5A. Reason: Predominantly a STAT5B (GH/IGF1) function; non-core, similarity-transferred annotation for STAT5A. |
| GO:0042127 regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5A promotes proliferation/survival of hematopoietic and lymphoid cells downstream of cytokines, and constitutive activation is oncogenic. A general downstream process. Reason: A downstream consequence of STAT5A target-gene programs rather than its direct molecular function. |
| GO:0042301 phosphate ion binding | IEA GO_REF:0000107 | MODIFY | Summary: Annotated as 'phosphate ion binding' by electronic transfer from mouse Stat5b. Biologically this reflects the SH2 domain's recognition of phosphotyrosine (phospho-Tyr on receptors and on the partner monomer at Tyr-694), not binding of free inorganic phosphate. Reason: The intended function is phosphotyrosine recognition by the SH2 domain; replace with the specific and well-supported phosphotyrosine residue binding term. Proposed replacements: phosphotyrosine residue binding Supporting Evidence: PMID:8631883 these tyrosines are required for dimerization |
| GO:0043434 response to peptide hormone | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5A mediates responses to peptide hormones including prolactin and growth hormone. A general parent of the more specific hormone-receptor signaling terms. Reason: Accurate but subsumed by the more specific prolactin/growth-hormone receptor signaling annotations. |
| GO:0043536 positive regulation of blood vessel endothelial cell migration | IMP PMID:20489169 microRNA-222 controls neovascularization by regulating signa... | KEEP AS NON CORE | Summary: miR-222-regulated STAT5A modulates endothelial cell migration during neovascularization (PMID:20489169). Experimental but a context-specific downstream vascular process. Reason: Experimentally supported in a specific neovascularization context; a downstream biological outcome rather than the core molecular function. Supporting Evidence: PMID:20489169 microRNA-222 controls neovascularization by regulating signal transducer and activator of transcription 5A expression |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Sequence-specific DNA binding inferred from the mouse ortholog. A general parent of the RNA Pol II cis-regulatory GAS-element binding term that is already present. Reason: Correct but a general parent of the specific RNA Pol II cis-regulatory sequence-specific DNA binding annotation (GO:0000978). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s... | ACCEPT | Summary: STAT5A positively regulates transcription of GAS-element target genes as a sequence-specific activator (PMID:24058793). Core process, also supported by the IEA activator MF annotation. Reason: Core process for STAT5A as a transcriptional activator. Supporting Evidence: PMID:24058793 Heterodimerization of STAT proteins is one potential mechanism for signals to be modified downstream of the receptor |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5 transduces growth hormone receptor signals via JAK-STAT. The GH/IGF1 axis is predominantly a STAT5B function; for STAT5A this is a shared, non-core context. Reason: Predominantly a STAT5B function (GH/IGF1); for STAT5A it is a shared, non-core signaling context. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: GH receptor signaling via JAK-STAT inferred from the mouse ortholog. Duplicate of the IBA annotation; predominantly a STAT5B function for STAT5A. Reason: Predominantly a STAT5B function; non-core, similarity-based annotation for STAT5A. |
| GO:0090575 RNA polymerase II transcription regulator complex | IBA GO_REF:0000033 | ACCEPT | Summary: Activated STAT5A dimers act within Pol II transcription regulator complexes at GAS-element promoters/enhancers, recruiting coactivators (NCOA1/SRC-1, CBP/p300). Phylogenetically supported. Reason: Consistent with STAT5A functioning as part of a transcription regulator complex. |
| GO:0090575 RNA polymerase II transcription regulator complex | NAS PMID:24058793 STAT heterodimers in immunity: A mixed message or a unique s... | ACCEPT | Summary: Activated STAT5A acts within Pol II transcription regulator complexes, including STAT5A/STAT5B and STAT3/STAT5A complexes (ComplexPortal CPX-6043/6045; PMID:24058793). Core complex membership. Reason: Consistent with STAT5A function in transcription regulator complexes; redundant with the IBA annotation. Supporting Evidence: PMID:24058793 Heterodimerization of STAT proteins is one potential mechanism for signals to be modified downstream of the receptor |
| GO:0140297 DNA-binding transcription factor binding | IPI PMID:35939714 Early B cell factor 4 modulates FAS-mediated apoptosis and p... | KEEP AS NON CORE | Summary: Early B cell factor 4 (EBF4) binds STAT5 (co-IP/interactome in human immune cells) (PMID:35939714). This is an informative transcription-factor-binding annotation (a defined TF partner), unlike bare protein binding. Reason: Informative DNA-binding transcription factor binding annotation supported by a defined interaction; a modulatory interaction rather than STAT5A's core transcription-factor activity. Supporting Evidence: PMID:35939714 EBF4 binding to STAT3, STAT5, and MAP kinase 3 |
| GO:1903706 regulation of hemopoiesis | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: STAT5A regulates hematopoiesis downstream of hematopoietic cytokines, including eosinophil differentiation (PMID:12393707). Accurate but a broad downstream process. Reason: A broad downstream biological process; the specific hematopoietic-differentiation outcomes and the core transcription-factor activity are more precise. |
| GO:1990841 promoter-specific chromatin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT5A binds promoter chromatin at target loci, inferred from the mouse ortholog. Consistent with GAS-element binding at promoters but subsumed by the specific cis-regulatory sequence-specific DNA binding annotation. Reason: Correct but a general chromatin-binding aspect captured more precisely by the sequence-specific cis-regulatory DNA binding molecular function. |
| GO:2000329 negative regulation of T-helper 17 cell lineage commitment | IDA PMID:20696842 CD69 association with Jak3/Stat5 proteins regulates Th17 cel... | KEEP AS NON CORE | Summary: The CD69 cytoplasmic tail associates with the Jak3/Stat5 pathway to limit Th17 differentiation (PMID:20696842). Experimentally supported but a specific immune-regulatory context downstream of STAT5. Reason: Experimentally supported specific immune context; a downstream biological outcome rather than the core molecular function. Supporting Evidence: PMID:20696842 CD69 association with Jak3/Stat5 proteins regulates Th17 cell differentiation |
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