STAT5A

UniProt ID: P42229
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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.
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).
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).
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).
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).
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).
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.
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).
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).
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

Core Functions

Cytokine/hormone-receptor-activated, sequence-specific RNA polymerase II transcription factor: upon JAK-mediated phosphorylation at Tyr-694 and SH2-dependent dimerization, activated STAT5A binds gamma-activated sequence (GAS) elements in cis-regulatory regions of target genes and activates their transcription, recruiting coactivators (NCOA1/SRC-1, CBP/p300).

Supporting Evidence:
  • PMID:8631883
    human Stat5 activation is also dependent on Tyr-694 in Stat5A and Tyr-699 in Stat5B
  • PMID:15534001
    both proteins bind to the endogenous beta-casein promoter
  • file:human/STAT5A/STAT5A-deep-research-falcon.md
    STAT5A is a nucleocytoplasmic, cytokine-responsive transcription factor

Phosphotyrosine-dependent signal transduction: the SH2 domain of latent cytoplasmic STAT5A recognizes phosphotyrosine residues on activated cytokine/hormone receptors and, reciprocally, on the partner STAT5 monomer (Tyr-694), forming the activated dimer that couples receptor-associated JAK activation to nuclear translocation and DNA binding.

Supporting Evidence:

References

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Deep Research

Falcon

(STAT5A-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(STAT5A-notes.md)

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