STAT5B is a latent cytoplasmic signal transducer and sequence-specific transcription factor of the STAT family. It is composed of an N-terminal domain, a coiled-coil domain, a DNA-binding domain, a linker, an SH2 domain, and a C-terminal transactivation domain. STAT5B is activated downstream of numerous cytokine and hormone receptors: it is the principal signal transducer for growth hormone (via JAK2), is activated by the common gamma-chain cytokines IL-2, IL-7, IL-9, IL-15 and IL-21 (via JAK1/JAK3), and is also activated by prolactin, erythropoietin and thrombopoietin (via JAK2), GM-CSF/IL-3/IL-5, G-CSF, and oncostatin-M. Receptor-associated JAK kinases phosphorylate STAT5B on Tyr-699; phosphorylated STAT5B dimerizes through reciprocal SH2-phosphotyrosine interactions (and can form heterodimers with STAT5A or STAT3), translocates to the nucleus, and binds gamma-activated sequence (GAS) DNA elements to activate transcription of target genes. STAT5B drives transcriptional programs controlling postnatal growth (induction of IGF1 downstream of growth hormone), lymphocyte development and immune homeostasis (including regulatory T cells and NK cells), and erythroid/hematopoietic differentiation. Loss-of-function variants cause growth hormone insensitivity syndrome with immune dysregulation (short stature with low IGF1 and normal/elevated growth hormone), while somatic activating mutations such as the SH2-domain N642H substitution drive T-cell and NK-cell leukemias and lymphomas. STAT5B is highly similar to and largely functionally overlapping with, but non-redundant from, its paralog STAT5A.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is active in the nucleus, where activated dimers bind GAS DNA elements and regulate transcription. Strongly supported phylogenetically and by direct experimental evidence. Reason: Core localization for STAT5B's transcription factor activity; consistent with IDA evidence (PMID:29844444) and the entire STAT mechanism. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is a latent cytoplasmic factor prior to phosphorylation, where it docks to activated receptors and is phosphorylated by JAKs before nuclear translocation. Reason: Core dual localization (cytoplasm/nucleus) of STAT proteins; supported by IDA (PMID:29844444). |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5B regulates RNA Pol II transcription of GAS-element target genes. Correct but general; the activator-specific terms (GO:0045944) and MF 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:0006952 defense response | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reflects STAT5B's role in immunity downstream of gamma-chain cytokines. This is a very general process term inferred phylogenetically across the family. Reason: Captures the immune role at too high a level; lymphocyte differentiation / cytokine signaling terms are more informative. |
| GO:0019221 cytokine-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is a central transducer of cytokine signaling (IL-2/7/9/15/21, EPO, GM-CSF, etc.). Core process annotation, well supported by experiment and phylogeny. Reason: Core biological process for STAT5B as a cytokine signal transducer. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B binds GAS elements in cis-regulatory regions of Pol II target genes. Supported experimentally by EMSA against the GHRE/GAS probe (PMID:29844444). Reason: Core sequence-specific DNA-binding molecular function of STAT5B. |
| GO:0042127 regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5B promotes proliferation/survival of hematopoietic and lymphoid cells downstream of cytokines, and constitutive activation is oncogenic. General downstream process. Reason: A downstream consequence of STAT5B target-gene programs rather than its direct molecular function. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is a defining component of JAK-STAT signaling downstream of cell surface cytokine/hormone receptors. Core process, strongly supported. Reason: Core biological process; STAT5B is by definition a JAK-STAT pathway effector. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is a sequence-specific RNA Pol II transcription factor. This is the core molecular function, also supported by ISA (TFClass) and IDA for the activator-specific child term (PMID:29844444). Reason: Core molecular function of STAT5B. |
| GO:0090575 RNA polymerase II transcription regulator complex | IBA GO_REF:0000033 | ACCEPT | Summary: Activated STAT5B dimers act within Pol II transcription regulator complexes at GAS-element promoters/enhancers, recruiting coactivators (e.g. CBP/p300 via NMI; NCOA1/SRC-1). Reason: Consistent with STAT5B function as part of a transcription regulator complex; also supported by NAS (PMID:24058793). |
| GO:0043434 response to peptide hormone | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: STAT5B mediates responses to peptide hormones including growth hormone and prolactin. General parent of the more specific GH receptor signaling term. Reason: Accurate but subsumed by the more specific GH receptor signaling pathway annotation. |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IBA GO_REF:0000033 | ACCEPT | Summary: STAT5B is the principal signal transducer for growth hormone; GH-GHR-JAK2 signaling activates STAT5B to induce IGF1. Core process, also supported by IDA (PMID:12552091) and disease genetics (PMID:29844444). Reason: Core, signature biological process for STAT5B (GH/IGF1 axis). |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: STAT5B binds DNA. General parent of the sequence-specific GAS-binding MF; InterPro-based electronic inference is consistent with experimental evidence. Reason: Correct but a general parent of the specific RNA Pol II cis-regulatory DNA binding annotation. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: STAT5B is a DNA-binding transcription factor. Correct but general; the RNA Pol II-specific child term (GO:0000981) is the precise core MF. Reason: General term; the RNA Pol II-specific transcription factor activity term (GO:0000981, already annotated) should be used. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization of activated STAT5B. Consistent with IDA evidence (PMID:29844444). Reason: Core localization, redundant with the IBA/IDA nucleus annotations. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization of latent STAT5B. Consistent with IDA evidence (PMID:29844444). Reason: Core localization, redundant with IBA/IDA cytoplasm annotations. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: STAT5B regulates transcription. Very general InterPro-derived process term; subsumed by the Pol II-specific regulation/activation terms. Reason: General parent term; more specific Pol II transcription terms are present. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: STAT5B is part of signal transduction. Very general; 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:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: Duplicate (ARBA electronic) of the cytokine-mediated signaling pathway annotation; core process for STAT5B. Reason: Core process; redundant with the IBA annotation to the same term. |
| GO:1903706 regulation of hemopoiesis | IEA GO_REF:0000117 | ACCEPT | Summary: STAT5B regulates hematopoiesis, including erythroid differentiation (PMID:20702587) and lymphoid development. Accurate process annotation. Reason: Supported by experimental erythroid-differentiation evidence and broad hematopoietic role. |
| GO:0005515 protein binding | IPI PMID:21106534 The tumor suppressor hTid1 inhibits STAT5b activity via func... | MARK AS OVER ANNOTATED | Summary: Interaction with the DnaJ tumor suppressor hTid1/DNAJA3, a negative regulator that binds the STAT5B transactivation domain (PMID:21106534). The bare 'protein binding' term is uninformative about function. Reason: GO:0005515 'protein binding' is uninformative; per guidelines a specific MF should be used. The interaction itself is real but does not define STAT5B's core function. |
| GO:0005515 protein binding | IPI PMID:31175292 Structural and functional consequences of the STAT5B(N642H) ... | MARK AS OVER ANNOTATED | Summary: Interaction with ABL1 (P00519) reported in the STAT5B(N642H) study. Bare 'protein binding' term is uninformative. Reason: GO:0005515 'protein binding' is uninformative; a specific MF is preferred. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: High-throughput binary interactome (HuRI) interactions. Bare 'protein binding' is uninformative and these HT partners do not inform core function. Reason: GO:0005515 'protein binding' is uninformative; high-throughput partners add no functional resolution. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Affinity-capture interactome (BioPlex) interaction. Bare 'protein binding' is uninformative. Reason: GO:0005515 'protein binding' is uninformative; high-throughput partner. |
| GO:0005515 protein binding | IPI PMID:9989503 Functional association of Nmi with Stat5 and Stat1 in IL-2- ... | MARK AS OVER ANNOTATED | Summary: Interaction with NMI (Q13287), identified via yeast two-hybrid using the STAT5b coiled-coil region; NMI enhances CBP/p300 recruitment to STAT5 (PMID:9989503). Real and functionally relevant, but 'protein binding' is uninformative. Reason: GO:0005515 'protein binding' is uninformative; the coactivator-recruitment role is captured by transcription regulator complex membership. |
| GO:0042802 identical protein binding | IPI PMID:31175292 Structural and functional consequences of the STAT5B(N642H) ... | KEEP AS NON CORE | Summary: STAT5B self-association (homodimerization), consistent with the activated STAT5B homodimer. The IDA-supported GO:0042803 protein homodimerization activity (PMID:29844444) captures this more precisely. Reason: Reflects the functionally important homodimer but is captured more specifically by GO:0042803 (homodimerization activity). |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: GAS-element binding inferred from mouse ortholog. Core MF, duplicate of the IBA annotation to the same term. Reason: Core DNA-binding MF; redundant with IBA annotation. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: STAT5B is a transcriptional activator at GAS elements. Core MF, also supported by IDA (PMID:29844444; luciferase reporter transactivation). Reason: Core molecular function; STAT5B is a sequence-specific transcriptional activator. |
| GO:0040014 regulation of multicellular organism growth | IEA GO_REF:0000107 | ACCEPT | Summary: STAT5B regulates organismal growth via the GH/IGF1 axis; loss of function causes short stature (PMID:29844444). Core organism-level outcome. Reason: Well-supported by human disease genetics (GH insensitivity / short stature). |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000107 | MODIFY | Summary: Activated STAT5B dimerizes. General dimerization term; the IDA-supported homodimerization activity (GO:0042803) is more specific. Reason: General term; the specific homodimerization activity (GO:0042803, IDA from PMID:29844444) better represents the function. Proposed replacements: protein homodimerization activity |
| GO:0060397 growth hormone receptor signaling pathway via JAK-STAT | IEA GO_REF:0000107 | ACCEPT | Summary: GH receptor signaling via JAK-STAT, inferred from mouse ortholog. Duplicate of the IBA/IDA annotations; core process. Reason: Core process, redundant with IBA and IDA (PMID:12552091) annotations. |
| GO:0071363 cellular response to growth factor stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: STAT5B mediates cellular responses to growth factors/cytokines. General term subsumed by specific JAK-STAT and GH receptor signaling annotations. Reason: General process term; specific cytokine/GH signaling terms are present. |
| 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: STAT5B 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 IBA/TAS annotations to the same term. |
| 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: STAT5B positively regulates transcription of GAS-element target genes. Core process; also supported by ISS and the IDA activator MF. Reason: Core process for STAT5B as a transcriptional activator. |
| 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 STAT5B acts within Pol II transcription regulator complexes (including STAT5A/STAT5B and STAT3/STAT5B complexes; ComplexPortal CPX-6044/6045). Reason: Consistent with STAT5B function in transcription regulator complexes; redundant with IBA annotation. |
| GO:0038162 erythropoietin-mediated signaling pathway | IDA PMID:9657743 Erythropoietin induces tyrosine phosphorylation of Jak2, STA... | ACCEPT | Summary: EPO induces tyrosine phosphorylation of JAK2, STAT5A and STAT5B in primary human erythroid precursors, with nuclear translocation of activated STAT5 (PMID:9657743). Direct experimental support. Reason: Well-supported core process; EPO/JAK2/STAT5B signaling drives erythropoiesis. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:29844444 Dominant-negative STAT5B mutations cause growth hormone inse... | ACCEPT | Summary: WT STAT5B bound the STAT5B-specific GHRE DNA probe under GH stimulation and drove luciferase reporter transactivation; DBD variants abolished both (PMID:29844444). Direct evidence for sequence-specific transcriptional activator activity. Reason: Core molecular function with strong direct experimental support. |
| GO:0005634 nucleus | IDA PMID:29844444 Dominant-negative STAT5B mutations cause growth hormone inse... | ACCEPT | Summary: GH-stimulated WT STAT5B translocates to the nucleus (immunofluorescence; the Q177P variant fails to enter the nucleus) (PMID:29844444). Direct support. Reason: Core localization with direct experimental evidence. |
| GO:0005737 cytoplasm | IDA PMID:29844444 Dominant-negative STAT5B mutations cause growth hormone inse... | ACCEPT | Summary: Latent and Q177P-mutant STAT5B localize to the cytoplasm/nuclear membrane (PMID:29844444). Direct support. Reason: Core localization with direct experimental evidence. |
| GO:0042803 protein homodimerization activity | IDA PMID:29844444 Dominant-negative STAT5B mutations cause growth hormone inse... | ACCEPT | Summary: Co-IP experiments showed STAT5B homodimerization (and heterodimerization with WT) upon activation (PMID:29844444). Activated STAT5B functions as a homodimer. Reason: Core, mechanistically essential molecular function (dimerization precedes nuclear import and DNA binding). |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: As a sequence-specific TF, STAT5B associates with chromatin at target loci. TFClass-based inference, consistent with function. Reason: Consistent with DNA-binding TF activity and nuclear localization. |
| 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 TF activity. Duplicate of the IBA annotation; core MF. Reason: Core molecular function; redundant with IBA annotation. |
| 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). Indirect, organism/context-specific and far from the core function. Reason: Highly indirect, narrowly-scoped ISS transfer; not representative of STAT5B's core transcription-factor function. |
| GO:0040014 regulation of multicellular organism growth | ISS GO_REF:0000024 | ACCEPT | Summary: Growth regulation via the GH/IGF1 axis; duplicate of the Ensembl IEA annotation. Supported by human disease genetics (PMID:29844444). Reason: Core organism-level outcome of GH/STAT5B signaling. |
| GO:0045648 positive regulation of erythrocyte differentiation | IDA PMID:20702587 ZFP36L1 negatively regulates erythroid differentiation of CD... | ACCEPT | Summary: STAT5B promotes erythroid differentiation; ZFP36L1-mediated down-regulation of Stat5b mRNA drastically decreases erythroid colony formation in human hematopoietic progenitors (PMID:20702587). Reason: Supported by direct experimental (loss-of-function) evidence in human erythroid progenitors. |
| GO:0003682 chromatin binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: STAT5B binds chromatin at target loci. General MF transferred by similarity; the sequence-specific GAS-binding terms are more precise. Reason: General DNA/chromatin-binding term subsumed by the specific cis-regulatory DNA binding annotation. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: Nuclear localization, transferred by similarity. Core localization, redundant with IDA/IBA/IEA annotations. Reason: Core localization; redundant. |
| GO:0005737 cytoplasm | ISS GO_REF:0000024 | ACCEPT | Summary: Cytoplasmic localization, transferred by similarity. Core localization, redundant with IDA/IBA/IEA annotations. Reason: Core localization; redundant. |
| GO:0046983 protein dimerization activity | ISS GO_REF:0000024 | MODIFY | Summary: Dimerization activity transferred by similarity. General; the specific homodimerization activity (GO:0042803, IDA) is preferred. Reason: General term; replace with the specific homodimerization activity supported by IDA. Proposed replacements: protein homodimerization activity |
| GO:0071363 cellular response to growth factor stimulus | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: General response-to-growth-factor process, transferred by similarity. Subsumed by specific cytokine/GH signaling terms. Reason: General process term; specific signaling annotations are present. |
| GO:0071364 cellular response to epidermal growth factor stimulus | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: EGF-response annotation transferred from STAT5A (P52632). STAT5 can be activated downstream of EGFR in some contexts, but this is a narrow, similarity-based, non-core annotation for STAT5B. Reason: Narrow ISS transfer from the paralog; EGF response is not a core, well-established STAT5B function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1470012 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8983379 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9012671 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9670426 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698016 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698021 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698033 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698041 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9698754 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9978250 | KEEP AS NON CORE | Summary: Nucleoplasmic localization of activated STAT5B within Reactome cytokine/hormone signaling pathways. Consistent with the IDA nucleus annotation; one of many pathway-specific Reactome localization records. Reason: Correct localization but a pathway-specific Reactome duplicate of the core nucleus annotation. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1168894 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of Pol II transcription, transferred by similarity. Core process; duplicate of the NAS annotation to the same term. Reason: Core process for STAT5B as a transcriptional activator; redundant. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1433456 | KEEP AS NON CORE | Summary: Cytosolic localization of latent STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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 STAT5B within a Reactome cytokine/hormone signaling pathway. Consistent with the IDA 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:0060397 growth hormone receptor signaling pathway via JAK-STAT | IDA PMID:12552091 Estrogen inhibits GH signaling by suppressing GH-induced JAK... | ACCEPT | Summary: GH stimulated STAT5-dependent reporter activity in 293GHR/HuH7/T-47D cells, with GH-induced JAK2 phosphorylation (PMID:12552091). Supports STAT5B in GH receptor JAK-STAT signaling. Core process, redundant with the IBA/IEA annotations. Reason: Core process with direct experimental support; defer to curator (BHF-UCL) full-text reading. |
| GO:0032355 response to estradiol | IDA PMID:12552091 Estrogen inhibits GH signaling by suppressing GH-induced JAK... | KEEP AS NON CORE | Summary: Estradiol (via ER-alpha and SOCS-2) suppresses GH-induced JAK2/STAT5 signaling (PMID:12552091). Captures STAT5B's modulation by estrogen rather than a core function; a context-specific crosstalk process. Reason: Reflects upstream regulation of STAT5B signaling by estradiol, not a core STAT5B function. Defer to curator who read the full text. |
| GO:0032870 cellular response to hormone stimulus | IDA PMID:12552091 Estrogen inhibits GH signaling by suppressing GH-induced JAK... | KEEP AS NON CORE | Summary: STAT5B mediates cellular responses to hormones (GH, estradiol context; PMID:12552091). Very general process term subsumed by the specific GH receptor signaling annotation. Reason: General hormone-response term; specific GH receptor signaling annotation is more informative. |
| GO:0035259 nuclear glucocorticoid receptor binding | IPI PMID:12552091 Estrogen inhibits GH signaling by suppressing GH-induced JAK... | UNDECIDED | Summary: Annotation of STAT5B binding the glucocorticoid receptor (NR3C1, P04150), consistent with UniProt SUBUNIT 'Binds NR3C1 (By similarity)'. The cached abstract of PMID:12552091 is an estrogen/SOCS-2 GH-signaling study and does not itself describe GR binding; this is curator (BHF-UCL) judgment from full text (not cached). Cannot independently verify the supporting evidence. Reason: Per guidelines, cannot verify an experimental IPI annotation whose full text is not in the cache and whose cached abstract does not mention GR binding; do not overrule the curator. |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | MODIFY | Summary: STAT5B is a DNA-binding transcription factor (cloning/characterization paper, PMID:8631883). General; the RNA Pol II-specific child term is the precise core MF. Reason: General term; the RNA Pol II-specific transcription factor activity term (GO:0000981) is preferred. Proposed replacements: DNA-binding transcription factor activity, RNA polymerase II-specific |
| 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: STAT5B regulates Pol II transcription of target genes (PMID:8631883). Correct but general; duplicate of the IBA annotation. Reason: General process subsumed by the specific positive-regulation annotation. |
| GO:0007259 cell surface receptor signaling pathway via JAK-STAT | TAS PMID:8631883 Cloning of human Stat5B. Reconstitution of interleukin-2-ind... | ACCEPT | Summary: STAT5B was shown to be activated by IL-2 via JAK1/JAK3 and the IL-2R beta/gamma chains, requiring Tyr-699 for dimerization (PMID:8631883). Core JAK-STAT process with direct support. Reason: Core process; supported by the original IL-2/JAK-STAT reconstitution study. |
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Download this section (compressed HTML)Q: Which target-gene programs are uniquely dependent on STAT5B versus STAT5A in human cells, given their high sequence identity and largely overlapping but non-redundant functions?
Q: How do STAT5B heterodimers (e.g. STAT5A/STAT5B, STAT3/STAT5B) differ from homodimers in DNA-element preference and target-gene output in lymphocytes?
Q: What distinguishes the transcriptional consequences of germline loss-of-function STAT5B variants (growth/immune phenotypes) from somatic gain-of-function variants (e.g. N642H) in leukemia?
Experiment: ChIP-seq for endogenous STAT5B (with STAT5A-specific controls) in cytokine- or GH-stimulated primary human T cells and erythroid progenitors to define the STAT5B-specific GAS-element cistrome and target genes.
Experiment: Paired RNA-seq after STAT5B-specific versus STAT5A-specific degron/knockdown to quantify non-redundant target-gene programs downstream of IL-2, GH and EPO.
Experiment: Structure-function and EMSA/reporter assays of additional CCD, DBD and SH2 variants to map how each domain contributes to dimerization, nuclear import and DNA binding, extending the dominant-negative analyses of PMID:29844444.
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