Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Well-supported core molecular function - JAK1 is a non-receptor tyrosine kinase Reason: This is JAK1's primary molecular function, extensively validated by biochemical and functional studies. The IBA evidence is supported by direct experimental evidence.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process - JAK1 is a central component of JAK-STAT signaling Reason: This is the canonical pathway mediated by JAK1. Essential for multiple cytokine receptor signaling cascades.
GO:0019221 cytokine-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process - JAK1 mediates signaling for multiple cytokine families Reason: JAK1 is required for Type I/II interferons, IL-6 family, and γc-dependent cytokines. This is a fundamental process for JAK1.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Accurate but general biological process Reason: While accurate, this is too general. More specific cytokine signaling terms better describe JAK1's function.
GO:0030154 cell differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Valid downstream process mediated by JAK1-dependent cytokines Reason: JAK1 regulates cell differentiation indirectly through cytokine signaling (e.g., lymphocyte development via IL-7), but this is a downstream consequence rather than core function.
GO:0005131 growth hormone receptor binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Specific receptor interaction supported by experimental evidence Reason: JAK1 does bind growth hormone receptor, but this is one of many receptor interactions. Core function is broader tyrosine kinase activity.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Valid but less specific than protein tyrosine kinase activity Reason: Accurate but GO:0004715 (non-membrane spanning protein tyrosine kinase activity) is more specific and preferred.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core molecular function - accurate and specific Reason: This is JAK1's primary catalytic activity. Well-supported by extensive biochemical evidence.
GO:0005524 ATP binding	IEA GO_REF:0000120	ACCEPT	Summary: Essential cofactor binding for kinase activity Reason: ATP binding is required for JAK1's tyrosine kinase activity. This is a core molecular function.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	REMOVE	Summary: Too general - ATP binding is more specific for kinase function Reason: While JAK1 does bind nucleotides, this term is overly general and uninformative. The more specific GO:0005524 (ATP binding) already captures JAK1's requirement for ATP as a cofactor for its tyrosine kinase activity. Per GO curation guidelines, overly general terms should be removed in favor of more specific functional annotations. Supporting Evidence: file:human/JAK1/JAK1-deep-research.md The kinase domain binds ATP and catalyzes the transfer of the γ-phosphate to tyrosine residues on substrates
GO:0016301 kinase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Valid but less specific than protein tyrosine kinase activity Reason: Accurate but too general. More specific tyrosine kinase terms are preferred.
GO:0016740 transferase activity	IEA GO_REF:0000043	REMOVE	Summary: Too general - represents broad enzyme class Reason: This is overly general and doesn't provide useful functional information about JAK1's specific role as a tyrosine kinase.
GO:0022407 regulation of cell-cell adhesion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Downstream effect of JAK1 signaling in specific contexts Reason: While JAK1 can influence cell adhesion through downstream signaling, this is context-specific and not a core function.
GO:0046872 metal ion binding	IEA GO_REF:0000043	REMOVE	Summary: General cofactor binding - not specific to JAK1 function Reason: Too general and not informative about JAK1's specific biological role. Many proteins bind metal ions.
GO:0005515 protein binding	IPI PMID:16273093 A quantitative protein interaction network for the ErbB rece...	REMOVE	Summary: General protein binding - lacks specificity per GO curation guidelines Reason: Generic protein binding annotations are removed per GO curation guidelines in favor of more specific functional terms. PMID:16273093 is a protein microarray study showing ErbB receptor interactions, but this doesn't provide specific functional information about JAK1's role. JAK1's specific receptor binding functions are better captured by terms like cytokine receptor binding. Supporting Evidence: PMID:16273093 A quantitative protein interaction network for the ErbB receptors using protein microarrays.
GO:0031730 CCR5 chemokine receptor binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Specific receptor binding interaction Reason: JAK1 can bind CCR5 chemokine receptor, but this is a specific interaction among many. Core function is broader tyrosine kinase activity.
GO:0035771 interleukin-4-mediated signaling pathway	NAS PMID:12574355 Human activation-induced cytidine deaminase is induced by IL...	ACCEPT	Summary: Specific cytokine pathway mediated by JAK1 supported by direct experimental evidence Reason: PMID:12574355 demonstrates that IL-4 induces AID expression via "IL-4-activated JAK1, JAK3, and STAT6 phosphorylations" providing direct evidence for JAK1's essential role in IL-4 signaling. Supporting Evidence: PMID:12574355 IL-4-dependent AID induction was inhibited by a dominant-negative STAT6, indicating that IL-4 induced AID expression via the Janus kinase (JAK)/STAT6 signaling pathway. Moreover, triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID expression, and this CD45-mediated AID inhibition correlated with the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and STAT6 phosphorylations
GO:0038111 interleukin-7-mediated signaling pathway	IDA PMID:29202461 IL-7-dependent STAT1 activation limits homeostatic CD4+ T ce...	ACCEPT	Summary: Critical cytokine pathway for lymphocyte development Reason: JAK1 is essential for IL-7 signaling, which is crucial for T-cell and B-cell development. Core pathway for JAK1. Supporting Evidence: PMID:29202461 The phosphorylated active form of JAK3 then phosphorylates tyrosine 449 on IL-7Rα, generating a docking site for the signal transducers and activators of transcription 5 (STAT5)
GO:0072540 T-helper 17 cell lineage commitment	TAS PMID:27893700 Trans-presentation of IL-6 by dendritic cells is required fo...	KEEP AS NON CORE	Summary: Downstream differentiation process mediated by JAK1 Reason: JAK1 contributes to Th17 differentiation through cytokine signaling, but this is a downstream consequence rather than core function. Supporting Evidence: PMID:27893700 Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells.
GO:0006357 regulation of transcription by RNA polymerase II	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	KEEP AS NON CORE	Summary: Downstream transcriptional effect of JAK1 signaling Reason: JAK1 regulates transcription indirectly through STAT activation, but the core function is tyrosine kinase activity. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.
GO:1900182 positive regulation of protein localization to nucleus	IDA PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and v...	KEEP AS NON CORE	Summary: Nuclear translocation regulation through JAK1 signaling Reason: JAK1 promotes STAT nuclear translocation, but this is a consequence of its kinase activity. Supporting Evidence: PMID:26479788 PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.
GO:0060337 type I interferon-mediated signaling pathway	IMP PMID:23391734 STAT2 deficiency and susceptibility to viral illness in huma...	ACCEPT	Summary: Core cytokine pathway - JAK1 essential for Type I IFN responses Reason: Type I interferon signaling is absolutely dependent on JAK1. This is a core biological process for JAK1. Supporting Evidence: PMID:23391734 Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein
GO:0035723 interleukin-15-mediated signaling pathway	IDA PMID:7568001 Tyrosine phosphorylation and activation of STAT5, STAT3, and...	ACCEPT	Summary: Specific γc-dependent cytokine pathway mediated by JAK1 Reason: IL-15 signaling through γc receptor requires JAK1. Core cytokine pathway function. Supporting Evidence: PMID:7568001 IL-2 and IL-15 rapidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA-binding complexes containing STAT3 and STAT5 were rapidly activated by these cytokines in T cells
GO:0038110 interleukin-2-mediated signaling pathway	IDA PMID:7568005 Critical role of the interleukin 2 (IL-2) receptor gamma-cha...	ACCEPT	Summary: Core γc-dependent cytokine pathway requiring JAK1 Reason: IL-2 is a prototypical γc cytokine requiring JAK1 for signaling. Core function. Supporting Evidence: PMID:7568005 Two Janus family protein tyrosine kinases (PTKs), Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R gamma c, respectively, and their PTK activities are increased after IL-2 stimulation
GO:0038154 interleukin-11-mediated signaling pathway	IDA PMID:28781374 IL-11 induces differentiation of myeloid-derived suppressor ...	ACCEPT	Summary: gp130-dependent cytokine pathway mediated by JAK1 Reason: IL-11 signals through gp130 receptor and requires JAK1. Core IL-6 family cytokine function. Supporting Evidence: PMID:28781374 IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0140105 interleukin-10-mediated signaling pathway	IDA PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...	ACCEPT	Summary: IL-10 cytokine signaling pathway requiring JAK1 Reason: IL-10 signaling requires JAK1 for STAT activation. Core anti-inflammatory cytokine pathway. Supporting Evidence: PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
GO:0038113 interleukin-9-mediated signaling pathway	IDA PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 ...	ACCEPT	Summary: γc-dependent cytokine pathway mediated by JAK1 Reason: IL-9 signals through γc receptor and requires JAK1. Core cytokine signaling function. Supporting Evidence: PMID:9535918 Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis
GO:0006468 protein phosphorylation	IMP PMID:28111307 JAK1 gain-of-function causes an autosomal dominant immune dy...	ACCEPT	Summary: Core catalytic activity of JAK1 as a tyrosine kinase Reason: Protein phosphorylation is the fundamental enzymatic activity of JAK1. Core molecular function. Supporting Evidence: PMID:28111307 JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:24882218 Unanchored K48-linked polyubiquitin synthesized by the E3-ub...	KEEP AS NON CORE	Summary: Regulatory interaction for JAK1 degradation control Reason: JAK1 binds ubiquitin ligases for regulation, but this is regulatory rather than core function. Supporting Evidence: PMID:24882218 2014 May 29. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.
GO:0034112 positive regulation of homotypic cell-cell adhesion	IMP PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate i...	KEEP AS NON CORE	Summary: Downstream cellular effect of JAK1 signaling Reason: Cell adhesion regulation is a downstream consequence of JAK1 signaling in specific contexts. Supporting Evidence: PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells.
GO:0019903 protein phosphatase binding	IPI PMID:11909529 The T cell protein tyrosine phosphatase is a negative regula...	KEEP AS NON CORE	Summary: Regulatory interaction for JAK1 activity control Reason: Phosphatase binding regulates JAK1 activity but is not the core function. Supporting Evidence: PMID:11909529 The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3.
GO:0046677 response to antibiotic	IDA PMID:16280321 The heat shock protein 90-CDC37 chaperone complex is require...	KEEP AS NON CORE	Summary: Context-specific response mediated through JAK1 signaling Reason: Antibiotic response is context-specific and not representative of JAK1's core function. Supporting Evidence: PMID:16280321 2005 Nov 9. The heat shock protein 90-CDC37 chaperone complex is required for signaling by types I and II interferons.
GO:0019221 cytokine-mediated signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: Duplicate annotation - cytokine-mediated signaling Reason: Valid annotation for JAK1's role in cytokine signaling, even though duplicated.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Duplicate annotation - non-membrane spanning kinase Reason: Valid annotation for JAK1's kinase activity, even though duplicated.
GO:0035556 intracellular signal transduction	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Accurate but general biological process Reason: While accurate, this is too general. More specific terms like JAK-STAT pathway and cytokine signaling better describe JAK1's core function.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate annotation - JAK-STAT pathway Reason: Valid annotation for JAK1's role in JAK-STAT signaling, even though duplicated.
GO:0019221 cytokine-mediated signaling pathway	IEA GO_REF:0000117	ACCEPT	Summary: Duplicate annotation - cytokine signaling Reason: Valid annotation for JAK1's cytokine signaling role, even though duplicated.
GO:0005515 protein binding	IPI PMID:16710296 UBP43 is a novel regulator of interferon signaling independe...	REMOVE	Summary: UBP43 direct binding interaction confirmed by experimental evidence Reason: PMID:16710296 demonstrates that "Ubp43 specifically binds to the IFNAR2 receptor subunit and inhibits the activity of receptor-associated JAK1." While this shows direct binding, generic protein binding annotations are removed per GO curation guidelines in favor of more specific functional terms. Supporting Evidence: PMID:16710296 May 18. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity.
GO:0005515 protein binding	IPI PMID:21220115 Structural snapshots of full-length Jak1, a transmembrane gp...	MODIFY	Summary: Structural study showing JAK1 binding to gp130/IL-6 receptor complex Reason: PMID:21220115 provides structural snapshots of full-length JAK1 in complex with gp130/IL-6/IL-6Rα cytokine receptor complex. This demonstrates specific receptor binding rather than generic protein binding. The interaction should be captured as cytokine receptor binding, which is more informative than generic protein binding. Proposed replacements: cytokine receptor binding Supporting Evidence: PMID:21220115 Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex file:human/JAK1/JAK1-deep-research.md Through its N-terminal domains, JAK1 is tightly but non-covalently associated with membrane-proximal regions of type I and II cytokine receptors
GO:0005515 protein binding	IPI PMID:25065853 Drug resistance via feedback activation of Stat3 in oncogene...	REMOVE	Summary: STAT3 binding in drug resistance context Reason: Drug resistance study showing feedback activation. Not informative for normal JAK1 function. Supporting Evidence: PMID:25065853 2014 Jul 24. Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.
GO:0005515 protein binding	IPI PMID:26175413 CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibi...	REMOVE	Summary: JAK2 interaction in JAK inhibitor study Reason: JAK inhibitor drug study, not informative for normal JAK1 function. Supporting Evidence: PMID:26175413 CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	REMOVE	Summary: Large-scale interactome study Reason: General proteome-wide interactome study, uninformative generic protein binding. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks.
GO:0005515 protein binding	IPI PMID:32953130 SARS-CoV-2 N protein antagonizes type I interferon signaling...	REMOVE	Summary: SARS-CoV-2 N protein interaction - viral immune evasion mechanism Reason: While PMID:32953130 demonstrates that SARS-CoV-2 N protein antagonizes JAK1 function by suppressing STAT1/STAT2 phosphorylation and nuclear translocation, this represents a pathological interaction during viral infection rather than normal JAK1 function. Generic protein binding annotations are removed per GO curation guidelines, and this specific viral interaction is not representative of JAK1's core cellular functions. Supporting Evidence: PMID:32953130 SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Dual proteome-scale network study Reason: Large-scale proteome study, uninformative generic protein binding. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:34521819 INVALID: Cannot retrieve from PubMed (possibly replaced or r...	REMOVE	Summary: Invalid PMID - cannot retrieve Reason: PMID appears to be invalid or retracted, cannot verify interaction.
GO:0005515 protein binding	IPI PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)...	REMOVE	Summary: SARS-CoV-2 protein interactions Reason: Duplicate viral antagonism study, already covered by PMID:32953130. Supporting Evidence: PMID:34950606 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	REMOVE	Summary: Cancer mutation-directed interactions Reason: Mutation-specific interactions in cancer, not representative of normal JAK1 function. Supporting Evidence: PMID:35512704 2022 May 4. Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
GO:0005131 growth hormone receptor binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Specific receptor interaction but not core function Reason: JAK1 does bind growth hormone receptor, but this is one of many receptor interactions. Core function is broader tyrosine kinase activity for multiple cytokine receptors.
GO:0019221 cytokine-mediated signaling pathway	TAS Reactome:R-HSA-6785807	ACCEPT	Summary: Duplicate annotation from Reactome Reason: Valid annotation from Reactome pathway analysis, even though duplicated.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS Reactome:R-HSA-1112602	ACCEPT	Summary: Duplicate Reactome annotation - IL6 receptor signaling Reason: Valid annotation from Reactome for JAK1's role in IL-6 signaling.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS Reactome:R-HSA-1112703	ACCEPT	Summary: Duplicate Reactome annotation - PTPN11 phosphorylation Reason: Valid annotation from Reactome for JAK1's kinase activity.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS Reactome:R-HSA-6786095	ACCEPT	Summary: Duplicate Reactome annotation - STAT3/STAT6 phosphorylation Reason: Valid annotation from Reactome for JAK1's role in STAT phosphorylation.
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS Reactome:R-HSA-6786096	ACCEPT	Summary: Duplicate Reactome annotation - IL4R phosphorylation Reason: Valid annotation from Reactome for JAK1's role in IL-4 signaling.
GO:0004713 protein tyrosine kinase activity	EXP PMID:10825200 Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2...	ACCEPT	Summary: IL-2 signaling hierarchy study Reason: Experimental evidence for JAK1's tyrosine kinase activity in IL-2 signaling. Core function. Supporting Evidence: PMID:10825200 Interleukin-2 (IL-2) activates several different families of tyrosine kinases, but precisely how these kinases interact is not completely understood
GO:0004713 protein tyrosine kinase activity	EXP PMID:1386289 A protein tyrosine kinase in the interferon alpha/beta signa...	ACCEPT	Summary: Early characterization of JAK1 in interferon signaling Reason: Foundational paper demonstrating JAK1's tyrosine kinase activity in IFN signaling. Core function. Supporting Evidence: PMID:1386289 A protein tyrosine kinase in the interferon alpha/beta signaling pathway
GO:0004713 protein tyrosine kinase activity	EXP PMID:9446616 Interferon gamma activation of Raf-1 is Jak1-dependent and p...	ACCEPT	Summary: IFN-gamma activation of Raf-1 via JAK1 Reason: Experimental evidence for JAK1 kinase activity in IFN-gamma signaling. Core function. Supporting Evidence: PMID:9446616 Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-452122	ACCEPT	Summary: Reactome annotation - IL2RB phosphorylation Reason: Valid annotation from Reactome for JAK1's kinase activity in IL-2 signaling.
GO:0004713 protein tyrosine kinase activity	TAS Reactome:R-HSA-873924	ACCEPT	Summary: Reactome annotation - IFNGR1 phosphorylation Reason: Valid annotation from Reactome for JAK1's role in IFN-gamma signaling.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	NAS PMID:12574355 Human activation-induced cytidine deaminase is induced by IL...	ACCEPT	Summary: Duplicate JAK-STAT pathway annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:12574355 IL-4-dependent AID induction was inhibited by a dominant-negative STAT6, indicating that IL-4 induced AID expression via the Janus kinase (JAK)/STAT6 signaling pathway
GO:0004713 protein tyrosine kinase activity	IDA PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...	ACCEPT	Summary: JAK-Tyk kinases in IL-6 family signaling Reason: Direct evidence for JAK1 kinase activity in IL-6 family cytokine signaling. Core function. Supporting Evidence: PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS PMID:34813358 IFNAR1 and IFNAR2 play distinct roles in initiating type I i...	ACCEPT	Summary: IFNAR1/IFNAR2 distinct roles study Reason: Valid annotation for JAK1's kinase activity in interferon signaling. Supporting Evidence: PMID:34813358 Ligand binding results in the cross-phosphorylation of TYK2 and JAK1, which then phosphorylate tyrosine residues in the ICDs of the receptor subunits and members of the STAT family of transcription factors
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IDA PMID:7657660 Phosphorylation and activation of the DNA binding activity o...	ACCEPT	Summary: STAT1 phosphorylation by JAK1 Reason: Valid annotation for JAK1's kinase activity. Supporting Evidence: PMID:7657660 Co-expression of Stat1 with Tyk2, Jak1, or Jak2 resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701
GO:0004715 non-membrane spanning protein tyrosine kinase activity	TAS PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	ACCEPT	Summary: Core molecular function confirmed by foundational interferon signaling study Reason: PMID:8232552 established that JAK1 is "completely defective in interferon response" when absent and "complementation of this mutant with JAK1 restored the response," demonstrating JAK1's essential tyrosine kinase activity in interferon signaling. Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
GO:0004715 non-membrane spanning protein tyrosine kinase activity	IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	ACCEPT	Summary: Duplicate annotation from key interferon paper Reason: Valid annotation from foundational JAK1 paper. Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
GO:0006357 regulation of transcription by RNA polymerase II	IDA PMID:9020188 Stat2 is a transcriptional activator that requires sequence-...	KEEP AS NON CORE	Summary: STAT2 transcriptional activation Reason: JAK1 regulates transcription indirectly through STAT activation. Downstream effect. Supporting Evidence: PMID:9020188 Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA.
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:23139419 Identification of STAT2 serine 287 as a novel regulatory pho...	ACCEPT	Summary: STAT2 Ser287 phosphorylation in IFN signaling Reason: Valid annotation for JAK1's role in interferon signaling. Supporting Evidence: PMID:23139419 Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Cri...	ACCEPT	Summary: SETD2-mediated STAT1 methylation Reason: Valid annotation for JAK1's role in STAT signaling. Supporting Evidence: PMID:28753426 Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:7526154 Direct binding to and tyrosine phosphorylation of the alpha ...	ACCEPT	Summary: TYK2 binding to IFN receptor Reason: Valid annotation for JAK1's role in interferon signaling. Supporting Evidence: PMID:7526154 Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:7657660 Phosphorylation and activation of the DNA binding activity o...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:7657660 Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:7759950 Soluble and membrane-anchored forms of the human IFN-alpha/b...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:7759950 Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) ...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	TAS PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	ACCEPT	Summary: Duplicate JAK-STAT annotation Reason: Valid annotation for JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
GO:1900182 positive regulation of protein localization to nucleus	IDA PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) ...	KEEP AS NON CORE	Summary: STAT2 nuclear localization Reason: JAK1 promotes STAT nuclear translocation, but this is downstream of kinase activity. Supporting Evidence: PMID:8605876 Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.
GO:0004713 protein tyrosine kinase activity	IDA PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway.	ACCEPT	Summary: STAT2 in IFN signaling pathway Reason: Direct evidence for JAK1 kinase activity. Core function. Supporting Evidence: PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway
GO:0004713 protein tyrosine kinase activity	IDA PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat...	ACCEPT	Summary: JAK1 and JAK3 with IL-2 receptor Reason: Direct evidence for JAK1 kinase activity in IL-2 signaling. Core function. Supporting Evidence: PMID:7973659 Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits
GO:0030154 cell differentiation	IDA PMID:28781374 IL-11 induces differentiation of myeloid-derived suppressor ...	KEEP AS NON CORE	Summary: IL-11-induced MDSC differentiation Reason: JAK1 contributes to cell differentiation through IL-11 signaling, but this is downstream. Supporting Evidence: PMID:28781374 IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.
GO:0004713 protein tyrosine kinase activity	IC PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...	ACCEPT	Summary: IL-10 induced JAK1 phosphorylation Reason: Inferred from IL-10 signaling studies. Core kinase function. Supporting Evidence: PMID:7543512 # IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes...
GO:0004713 protein tyrosine kinase activity	IDA PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is re...	ACCEPT	Summary: IL-9 receptor signaling Reason: Direct evidence for JAK1 kinase activity in IL-9 signaling. Core function. Supporting Evidence: PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9
GO:0004713 protein tyrosine kinase activity	IDA PMID:10702271 Interleukin (IL)-7 induces rapid activation of Pyk2, which i...	ACCEPT	Summary: IL-7 induced Pyk2 activation Reason: Direct evidence for JAK1 kinase activity in IL-7 signaling. Core function. Supporting Evidence: PMID:10702271 Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ralpha
GO:0004713 protein tyrosine kinase activity	IDA PMID:15226449 Distinct regions of the interleukin-7 receptor regulate diff...	ACCEPT	Summary: IL-7 receptor and Bcl2 regulation Reason: Direct evidence for JAK1 kinase activity. Core function. Supporting Evidence: PMID:15226449 Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members
GO:0004713 protein tyrosine kinase activity	IDA PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and ...	ACCEPT	Summary: IL-4 and IL-9 receptor activation Reason: Direct evidence for JAK1 kinase activity in IL-4/IL-9 signaling. Core function. Supporting Evidence: PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes
GO:0035771 interleukin-4-mediated signaling pathway	IDA PMID:7760829 Cloning of murine Stat6 and human Stat6, Stat proteins that ...	ACCEPT	Summary: Duplicate IL-4 pathway annotation Reason: Valid annotation for JAK1's role in IL-4 signaling. Supporting Evidence: PMID:7760829 Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis
GO:0004713 protein tyrosine kinase activity	EXP PMID:31892268 Characterization of JAK1 Pseudokinase Domain in Cytokine Sig...	ACCEPT	Summary: JAK1 pseudokinase domain characterization Reason: Experimental evidence for JAK1 kinase activity and regulation. Core function. Supporting Evidence: PMID:31892268 Characterization of JAK1 Pseudokinase Domain in Cytokine Signaling
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IMP PMID:28111307 JAK1 gain-of-function causes an autosomal dominant immune dy...	ACCEPT	Summary: JAK1 gain-of-function syndrome Reason: Valid annotation demonstrating JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:28111307 JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome
GO:0007259 cell surface receptor signaling pathway via JAK-STAT	IMP PMID:32750333 Complex Autoinflammatory Syndrome Unveils Fundamental Princi...	ACCEPT	Summary: Autoinflammatory syndrome study Reason: Valid annotation demonstrating JAK1's role in JAK-STAT signaling. Supporting Evidence: PMID:32750333 Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function
GO:0006468 protein phosphorylation	IMP PMID:32750333 Complex Autoinflammatory Syndrome Unveils Fundamental Princi...	ACCEPT	Summary: Duplicate protein phosphorylation annotation Reason: Valid annotation for JAK1's phosphorylation activity. Supporting Evidence: PMID:32750333 Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function
GO:0005515 protein binding	IPI PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate i...	REMOVE	Summary: ZO-2 binding in smooth muscle cells Reason: Context-specific protein interaction, not informative for JAK1 core function. Supporting Evidence: PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells.
GO:0005515 protein binding	IPI PMID:7759950 Soluble and membrane-anchored forms of the human IFN-alpha/b...	MODIFY	Summary: Type I IFN receptor binding - demonstrates receptor-kinase association Reason: PMID:7759950 describes soluble and membrane-anchored forms of the human IFN-α/β receptor, establishing the foundation for understanding JAK1's association with IFNAR receptor subunits. This represents specific cytokine receptor binding rather than generic protein binding. The interaction is better captured as cytokine receptor binding, which is more functionally informative. Proposed replacements: cytokine receptor binding Supporting Evidence: PMID:7759950 Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor file:human/JAK1/JAK1-deep-research.md JAK1 associates with the IFNAR2 receptor subunit, while TYK2 associates with IFNAR1
GO:0005131 growth hormone receptor binding	ISS PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T...	KEEP AS NON CORE	Summary: Growth hormone receptor association Reason: JAK1 does bind GH receptor, but this is one of many receptor interactions. Supporting Evidence: PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver.
GO:0004713 protein tyrosine kinase activity	TAS PMID:1848670 Two novel protein-tyrosine kinases, each with a second phosp...	ACCEPT	Summary: Early JAK1 characterization paper Reason: Foundational paper identifying JAK1 as a tyrosine kinase. Core function. Supporting Evidence: PMID:1848670 Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase
GO:0006468 protein phosphorylation	TAS PMID:1848670 Two novel protein-tyrosine kinases, each with a second phosp...	ACCEPT	Summary: Core catalytic activity of JAK1 as a tyrosine kinase Reason: Protein phosphorylation is the fundamental enzymatic activity of JAK1. This foundational paper provides traceable author statement supporting this core function. Supporting Evidence: PMID:1848670 Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase.
GO:0035556 intracellular signal transduction	TAS PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	KEEP AS NON CORE	Summary: Accurate but general biological process Reason: While accurate, this is too general. More specific terms like JAK-STAT pathway and cytokine signaling better describe JAK1's core function. Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
GO:0070102 interleukin-6-mediated signaling pathway	TAS file:human/JAK1/JAK1-deep-research.md	NEW	Summary: Core cytokine pathway - JAK1 is the primary kinase for IL-6 family signaling Reason: JAK1 is essential for IL-6 family cytokine signaling through gp130 receptor complexes. The deep research document establishes JAK1 as the principal kinase mediating IL-6, IL-11, IL-27, LIF, and oncostatin M signaling. This is a core biological process that was missing from the existing annotations but is well-supported by experimental evidence. Supporting Evidence: file:human/JAK1/JAK1-deep-research.md JAK1 serves as the principal kinase for IL-6 family cytokines including IL-6, IL-11, IL-27, LIF (leukemia inhibitory factor), and oncostatin M. In these pathways, JAK1 phosphorylates the gp130 receptor subunit and activates STAT1/STAT3 PMID:7537214 A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6
GO:0060333 type II interferon-mediated signaling pathway	TAS file:human/JAK1/JAK1-deep-research.md	NEW	Summary: Core interferon pathway - JAK1 essential for IFN-γ signaling Reason: JAK1 is absolutely required for type II interferon (IFN-γ) signaling, where it pairs with JAK2 in the IFNGR1/IFNGR2 receptor complex. The deep research document and foundational studies demonstrate that cells lacking JAK1 are completely unresponsive to IFN-γ. This core biological process was missing from existing annotations despite strong experimental evidence. Supporting Evidence: file:human/JAK1/JAK1-deep-research.md JAK1 pairs with JAK2 in the IFNGR1/IFNGR2 receptor complex. IFN-γ signaling leads to STAT1 homodimerization that binds to gamma-activated sequences (GAS) in promoters of pro-inflammatory genes PMID:8232552 JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction PMID:9446616 Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: JAK1 is a cytoplasmic non-receptor tyrosine kinase that localizes to the cytosol when not associated with activated cytokine receptors. It translocates and associates with membrane receptors upon cytokine stimulation. Reason: Cytosol localization is essential for JAK1's function as a mobile signaling kinase that can be recruited to activated cytokine receptors and also phosphorylate cytoplasmic STAT transcription factors.
GO:0060397 growth hormone receptor signaling pathway via JAK-STAT	IBA GO_REF:0000033	PENDING	Summary: TODO: Review this GOA annotation
GO:0005768 endosome	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0012505 endomembrane system	IEA GO_REF:0000044	PENDING	Summary: TODO: Review this GOA annotation
GO:0016020 membrane	IEA GO_REF:0000002	PENDING	Summary: TODO: Review this GOA annotation
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0051239 regulation of multicellular organismal process	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0098761 cellular response to interleukin-7	IEA GO_REF:0000117	PENDING	Summary: TODO: Review this GOA annotation
GO:0060333 type II interferon-mediated signaling pathway	NAS PMID:15864272 Mechanisms of type-I- and type-II-interferon-mediated signal...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:15864272 Mechanisms of type-I- and type-II-interferon-mediated signalling.
GO:0098586 cellular response to virus	NAS PMID:15864272 Mechanisms of type-I- and type-II-interferon-mediated signal...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:15864272 Mechanisms of type-I- and type-II-interferon-mediated signalling.
GO:0038110 interleukin-2-mediated signaling pathway	TAS Reactome:R-HSA-9020558	PENDING	Summary: TODO: Review this GOA annotation
GO:0060333 type II interferon-mediated signaling pathway	TAS Reactome:R-HSA-877300	PENDING	Summary: TODO: Review this GOA annotation
GO:0060337 type I interferon-mediated signaling pathway	TAS Reactome:R-HSA-909733	PENDING	Summary: TODO: Review this GOA annotation
GO:0070102 interleukin-6-mediated signaling pathway	TAS Reactome:R-HSA-1059683	PENDING	Summary: TODO: Review this GOA annotation
GO:0038196 type III interferon-mediated signaling pathway	NAS PMID:30936491 Decoding type I and III interferon signalling during viral i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:30936491 2019 Apr 1. Decoding type I and III interferon signalling during viral infection.
GO:0043235 receptor complex	IPI PMID:21854986 Structural linkage between ligand discrimination and recepto...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:21854986 Structural linkage between ligand discrimination and receptor activation by type I interferons.
GO:0060337 type I interferon-mediated signaling pathway	NAS PMID:30936491 Decoding type I and III interferon signalling during viral i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:30936491 2019 Apr 1. Decoding type I and III interferon signalling during viral infection.
GO:0098586 cellular response to virus	NAS PMID:30936491 Decoding type I and III interferon signalling during viral i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:30936491 2019 Apr 1. Decoding type I and III interferon signalling during viral infection.
GO:0005829 cytosol	TAS Reactome:R-HSA-8986994	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987080	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987097	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987129	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987150	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987230	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987255	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987270	PENDING	Summary: TODO: Review this GOA annotation
GO:0005886 plasma membrane	TAS PMID:34813358 IFNAR1 and IFNAR2 play distinct roles in initiating type I i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:34813358 2021 Nov 23. IFNAR1 and IFNAR2 play distinct roles in initiating type I interferon-induced JAK-STAT signaling and activating STATs.
GO:0060333 type II interferon-mediated signaling pathway	IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction.
GO:0060337 type I interferon-mediated signaling pathway	IDA PMID:8232552 The protein tyrosine kinase JAK1 complements defects in inte...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8232552 The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction.
GO:0005737 cytoplasm	IC PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway.	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway.
GO:0060337 type I interferon-mediated signaling pathway	IDA PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway.	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7532278 Role of STAT2 in the alpha interferon signaling pathway.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IDA PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat...	ACCEPT	Summary: JAK1 associates with the cytoplasmic domains of activated cytokine receptors at the plasma membrane, where it becomes phosphorylated and activated to propagate downstream signaling cascades. Reason: JAK1's association with the cytoplasmic side of plasma membrane-bound receptors is crucial for cytokine signal transduction, allowing it to be activated by receptor engagement and to phosphorylate other signaling proteins in close proximity to the membrane. Supporting Evidence: PMID:7973659 Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits.
GO:0038154 interleukin-11-mediated signaling pathway	IDA PMID:8272872 Association of transcription factor APRF and protein kinase ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8272872 Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IC PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IC PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7543512 IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IC PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.
GO:0038113 interleukin-9-mediated signaling pathway	IDA PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is re...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8756628 A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.
GO:0038110 interleukin-2-mediated signaling pathway	IDA PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7973659 Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits.
GO:0005886 plasma membrane	IC PMID:10702271 Interleukin (IL)-7 induces rapid activation of Pyk2, which i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:10702271 Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ralpha.
GO:0009898 cytoplasmic side of plasma membrane	IC PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IC PMID:7973659 Functional activation of Jak1 and Jak3 by selective associat...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7973659 Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits.
GO:0038111 interleukin-7-mediated signaling pathway	IC PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:20974963 Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling.
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane	IC PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.
GO:0035771 interleukin-4-mediated signaling pathway	IDA PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and ...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:7929391 JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.
GO:0009898 cytoplasmic side of plasma membrane	IDA PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
GO:0070102 interleukin-6-mediated signaling pathway	IDA PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OS...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:8272873 Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.
GO:0150105 protein localization to cell-cell junction	IMP PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate i...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:21679692 The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells.
GO:0005829 cytosol	TAS Reactome:R-HSA-8950340	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950405	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950441	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950453	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950485	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950518	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950537	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8982162	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8982163	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8982165	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983300	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983834	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983835	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983841	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983845	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983983	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983996	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8984012	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8984014	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8984021	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8984023	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8986985	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8986995	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987012	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987014	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987033	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987040	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987042	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987063	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987070	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987084	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987096	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987132	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987161	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987202	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987236	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987266	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9009227	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1067651	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1067659	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1067688	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112514	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1169406	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1295540	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1678841	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448427	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448480	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448660	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448661	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448708	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448728	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-448744	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449115	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449803	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449811	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449958	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449976	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-449978	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-450027	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-450063	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-451900	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-451942	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-5696482	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6783524	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6783530	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6783552	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6783556	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6783681	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784189	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784204	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784319	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6785165	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786050	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786058	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786096	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786110	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6788571	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6788582	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6788628	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6809140	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873918	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873919	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873926	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-877269	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8854645	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950210	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950448	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8950757	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8952807	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8963734	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983003	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983063	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983298	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983335	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983518	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8984001	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8985900	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8985914	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8985929	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8985973	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8985988	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8986446	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8986480	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8986972	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987015	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987039	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987043	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987104	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987105	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987120	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987141	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987156	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987179	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8987220	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9005980	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9006844	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9006850	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9011748	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9025969	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909720	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909724	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909729	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9677579	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9677585	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9678561	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9678935	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9696179	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-997314	PENDING	Summary: TODO: Review this GOA annotation
GO:0005768 endosome	TAS Reactome:R-HSA-8983335	PENDING	Summary: TODO: Review this GOA annotation
GO:1903672 positive regulation of sprouting angiogenesis	IGI PMID:20299512 Members of the microRNA-17-92 cluster exhibit a cell-intrins...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:20299512 2010 Mar 18. Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.
GO:0005925 focal adhesion	HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.
GO:0038110 interleukin-2-mediated signaling pathway	IDA PMID:11909529 The T cell protein tyrosine phosphatase is a negative regula...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:11909529 The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3.
GO:0005829 cytosol	TAS Reactome:R-HSA-1112510	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112565	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112602	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112604	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112690	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112703	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112708	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112727	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-1112755	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-452091	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-452097	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-452100	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-452108	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-452122	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-453104	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-453111	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-508247	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-508282	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-508292	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-5672965	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784006	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784323	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784324	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6784791	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786072	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786095	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-6786124	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873921	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873922	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873924	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-873927	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983371	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983374	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983378	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-8983384	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9006870	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9006873	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909552	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909718	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909719	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909722	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909726	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909730	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-909732	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-912527	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-913374	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-913424	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-919404	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9674816	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9705738	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9707977	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9732729	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9732738	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-9732753	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-997309	PENDING	Summary: TODO: Review this GOA annotation
GO:0005829 cytosol	TAS Reactome:R-HSA-997311	PENDING	Summary: TODO: Review this GOA annotation
GO:0005634 nucleus	IDA PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver.
GO:0005737 cytoplasm	IDA PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and T...	PENDING	Summary: TODO: Review this GOA annotation Supporting Evidence: PMID:10502458 The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver.

Core Functions

Non-receptor tyrosine kinase essential for multiple cytokine signaling pathways via JAK-STAT cascade

Molecular Function:

non-membrane spanning protein tyrosine kinase activity

Directly Involved In:

cell surface receptor signaling pathway via JAK-STAT cytokine-mediated signaling pathway type I interferon-mediated signaling pathway type II interferon-mediated signaling pathway interleukin-6-mediated signaling pathway interleukin-2-mediated signaling pathway interleukin-4-mediated signaling pathway interleukin-7-mediated signaling pathway interleukin-10-mediated signaling pathway protein phosphorylation

Cellular Locations:

cytosol extrinsic component of cytoplasmic side of plasma membrane

Substrates:

JAK1-IFNAR complex JAK1-IFNGR complex JAK1-gp130 complex JAK1-γc complex JAK1-STAT phosphorylation complex

Supporting Evidence:

PMID:8232552
JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction
PMID:9590172
JAK1 demonstrates obligatory and nonredundant roles in cytokine-induced biologic responses
file:human/JAK1/JAK1-deep-research.md
JAK1 is required for signaling by Type I/II interferons, γc-dependent cytokines, and gp130-dependent cytokines

References

PMID:8232552

The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction.

PMID:9590172

Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses.

PMID:7537214

A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6.

file:human/JAK1/JAK1-deep-research.md

Deep Research Report: JAK1 comprehensive analysis

PMID:16273093

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

GO_REF:0000033

Gene Ontology inferred from electronic annotation (IBA)

GO_REF:0000002

Gene Ontology inferred from electronic annotation based on InterPro

GO_REF:0000120

Gene Ontology inferred from electronic annotation (IEA)

GO_REF:0000043

Gene Ontology inferred from electronic annotation based on UniProtKB keywords

GO_REF:0000117

Gene Ontology inferred from electronic annotation based on ARBA

PMID:10502458

The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in human liver.

PMID:10702271

Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound to Janus kinase 1 and IL-7Ralpha.

PMID:10825200

Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling: activation of syk depends on Jak3; however, neither Syk nor Lck is required for IL-2-mediated STAT activation.

PMID:11909529

The T cell protein tyrosine phosphatase is a negative regulator of janus family kinases 1 and 3.

PMID:12574355

Human activation-induced cytidine deaminase is induced by IL-4 and negatively regulated by CD45: implication of CD45 as a Janus kinase phosphatase in antibody diversification.

PMID:1386289

A protein tyrosine kinase in the interferon alpha/beta signaling pathway.

PMID:15226449

Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members.

PMID:16280321

The heat shock protein 90-CDC37 chaperone complex is required for signaling by types I and II interferons.

PMID:16710296

UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity.

PMID:1848670

Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase.

PMID:21220115

Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 holocomplex.

PMID:21679692

The tight junction protein ZO-2 and Janus kinase 1 mediate intercellular communications in vascular smooth muscle cells.

PMID:23139419

Identification of STAT2 serine 287 as a novel regulatory phosphorylation site in type I interferon-induced cellular responses.

PMID:23391734

STAT2 deficiency and susceptibility to viral illness in humans.

PMID:24882218

Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response.

PMID:25065853

Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.

PMID:26175413

CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.

PMID:26479788

PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C protease to enhance interferon signaling and control viral infection.

PMID:27893700

Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells.

PMID:28111307

JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome.

PMID:28514442

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

PMID:28753426

Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for Interferon Antiviral Activity.

PMID:28781374

IL-11 induces differentiation of myeloid-derived suppressor cells through activation of STAT3 signalling pathway.

PMID:29202461

IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion.

PMID:31892268

Characterization of JAK1 Pseudokinase Domain in Cytokine Signaling.

PMID:32750333

Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function.

PMID:32953130

SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2.

PMID:33961781

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

PMID:34813358

IFNAR1 and IFNAR2 play distinct roles in initiating type I interferon-induced JAK-STAT signaling and activating STATs.

PMID:34950606

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.

PMID:35512704

Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.

PMID:7526154

Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase.

PMID:7532278

Role of STAT2 in the alpha interferon signaling pathway.

PMID:7543512

IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes in human T cells and monocytes.

PMID:7568001

Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15.

PMID:7568005

Critical role of the interleukin 2 (IL-2) receptor gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not bcl-2, gene induction.

PMID:7657660

Phosphorylation and activation of the DNA binding activity of purified Stat1 by the Janus protein-tyrosine kinases and the epidermal growth factor receptor.

PMID:7759950

Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor.

PMID:7760829

Cloning of murine Stat6 and human Stat6, Stat proteins that are tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required for mitogenesis.

PMID:7929391

JAK1 kinase forms complexes with interleukin-4 receptor and 4PS/insulin receptor substrate-1-like protein and is activated by interleukin-4 and interleukin-9 in T lymphocytes.

PMID:7973659

Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits.

PMID:8272873

Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components.

PMID:8605876

Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.

PMID:8756628

A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.

PMID:9020188

Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA.

PMID:9446616

Interferon gamma activation of Raf-1 is Jak1-dependent and p21ras-independent.

PMID:9535918

Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis.

PMID:34521819

INVALID: Cannot retrieve from PubMed (possibly replaced or retracted)

Reactome:R-HSA-1112602

Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor

Reactome:R-HSA-1112703

PTPN11 is phosphorylated

Reactome:R-HSA-452122

JAK1 phosphorylates Y338, Y392 and Y510 of IL2RB

Reactome:R-HSA-6785807

Interleukin-4 and Interleukin-13 signaling

Reactome:R-HSA-6786095

JAK1 phosphorylates STAT3,STAT6

Reactome:R-HSA-6786096

IL4R, IL2RG, JAK1 in IL4-bound IL4R1:JAK1 are phosphorylated

Reactome:R-HSA-873924

Phosphorylation of IFNGR1 by JAK kinases

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.

PMID:15864272

Mechanisms of type-I- and type-II-interferon-mediated signalling.

PMID:20299512

Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells.

PMID:20974963

Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling.

PMID:21423176

Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.

PMID:21854986

Structural linkage between ligand discrimination and receptor activation by type I interferons.

PMID:30936491

Decoding type I and III interferon signalling during viral infection.

PMID:8272872

Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130.

Reactome:R-HSA-1059683

Interleukin-6 signaling

Reactome:R-HSA-1067651

IL6:IL6R-2 binds IL6ST:JAK1, JAK2, (TYK2)

Reactome:R-HSA-1067659

Assembly of hexameric IL-6 receptor

Reactome:R-HSA-1067688

IL6:IL6R binds IL6ST:JAK1,JAK2,(TYK2)

Reactome:R-HSA-1112510

IL6ST is tyrosine phosphorylated

Reactome:R-HSA-1112514

JAK activation

Reactome:R-HSA-1112565

Tyrosine phosphorylated IL6ST binds STAT1,STAT3

Reactome:R-HSA-1112604

Phosphorylated STATs are released

Reactome:R-HSA-1112690

PTPN11 binds CBL

Reactome:R-HSA-1112708

PTPN11 binds p-Y759-IL6ST

Reactome:R-HSA-1112727

Serine phosphorylation of STATs

Reactome:R-HSA-1112755

SOCS3 binds IL6ST

Reactome:R-HSA-1169406

ISGylation of host proteins

Reactome:R-HSA-1295540

IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3:STAT5A,STAT5B phosphorylates STAT5

Reactome:R-HSA-1678841

Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18

Reactome:R-HSA-448427

Interleukin-27 binds Interleukin-27 receptor

Reactome:R-HSA-448480

IL22 binds IL22RA1:JAK1 receptor complex

Reactome:R-HSA-448660

IL31:IL31RA:JAK1 binds OSMR:JAK1

Reactome:R-HSA-448661

IFNL1 binds IL10RB:TYK2 and IFNLR1:JAK1

Reactome:R-HSA-448708

IL24 binds to IL22RA1:JAK1:IL20RB

Reactome:R-HSA-448728

IL19 binds IL20RA:JAK1:IL20RB

Reactome:R-HSA-448744

IL20RA binds IL20RB

Reactome:R-HSA-449115

IL15:IL15RA binds IL2RB:JAK1 and IL2RG:JAK3

Reactome:R-HSA-449803

IL10 dimer binds IL10RA:JAK1

Reactome:R-HSA-449811

IL10 dimer:2xIL10RA1:JAK1 binds IL10RB:TYK2

Reactome:R-HSA-449958

IL7:IL7R:JAK1 binds IL2RG:JAK3

Reactome:R-HSA-449976

IL11:IL11RA binds IL6ST:JAK1,JAK2,(TYK2)

Reactome:R-HSA-449978

IL7 binds IL7R:JAK1

Reactome:R-HSA-450027

Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta

Reactome:R-HSA-450063

Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit

Reactome:R-HSA-451900

IL2RB binds JAK1

Reactome:R-HSA-451942

Within the IL-2R complex JAK3 phosphorylates JAK1

Reactome:R-HSA-452091

Phosphorylation of IL2RB Y338 enables SHC recruitment

Reactome:R-HSA-452097

Recruited STAT5 is phosphorylated

Reactome:R-HSA-452100

SHC1 bound to IL2 receptor is phosphorylated

Reactome:R-HSA-452108

Phosphorylation of IL2RB Y338, Y392 or Y510 enables STAT recruitment

Reactome:R-HSA-453104

Phosphorylated SHC1 recruits GRB2:GAB2

Reactome:R-HSA-453111

Phosphorylated SHC recruits GRB2:SOS1

Reactome:R-HSA-508247

Gab2 binds the p85 subunit of Class 1A PI3 kinases

Reactome:R-HSA-508282

SYK is a substrate for JAK1

Reactome:R-HSA-508292

SYK binds IL2RB

Reactome:R-HSA-5672965

RAS GEFs promote RAS nucleotide exchange

Reactome:R-HSA-5696482

CTF1 binds LIFR:JAKs

Reactome:R-HSA-6783524

OSM,LIF,CTF1 receptor complex binds gp130

Reactome:R-HSA-6783530

gp130:JAKs bind CNTFR

Reactome:R-HSA-6783552

OSM binds LIFR:JAKs,OSMR:JAKs

Reactome:R-HSA-6783556

LIFR:JAKs bind gp130:JAKs:CNTFR

Reactome:R-HSA-6783681

LIF binds LIFR

Reactome:R-HSA-6784006

STAT3 is phosphorylated by p-Y-JAK1,P-Y-TYK2

Reactome:R-HSA-6784189

JAKs bind LIFR

Reactome:R-HSA-6784204

JAKs bind OSMR

Reactome:R-HSA-6784319

JAK1,TYK2 phosphorylate JAK1,TYK2

Reactome:R-HSA-6784323

IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3

Reactome:R-HSA-6784324

p-Y-JAK1,p-Y-TYK2 phosphorylate IL10RA

Reactome:R-HSA-6784791

p-Y705-STAT3 dissociates from IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2:p-Y705-STAT3

Reactome:R-HSA-6785165

p-STAT5A, p-STAT5B dissociate from IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3:p-STAT5A,p-STAT5B

Reactome:R-HSA-6786050

IL4R, IL13RA, JAK2 and TYK2 are tyrosine phosphorylated

Reactome:R-HSA-6786058

JAK1 binds IL4R in IL4-bound IL4R1

Reactome:R-HSA-6786072

p-Y705-STAT3,p-Y641-STAT6 dissociate

Reactome:R-HSA-6786110

JAK1 binds IL4R in IL13-bound IL13R type II

Reactome:R-HSA-6786124

STAT3,STAT6 bind p-Y-IL4R

Reactome:R-HSA-6788571

STAT1,STAT3,STAT6 bind IL13:IL13R type II

Reactome:R-HSA-6788582

STAT1,STAT3,STAT6 phosphorylation

Reactome:R-HSA-6788628

p-Y-STATs dissociate

Reactome:R-HSA-6809140

IL35 binds IL-12RB2:IL6ST receptor

Reactome:R-HSA-873918

Transphosphorylation of JAK1

Reactome:R-HSA-873919

Phosphorylation of JAK2

Reactome:R-HSA-873921

Binding of STAT1 to p-IFNGR1

Reactome:R-HSA-873922

Phosphorylation of STAT1 by JAK kinases

Reactome:R-HSA-873926

IFNG dimer binds IFNGR

Reactome:R-HSA-873927

Release of STAT1 dimer from active receptor unit

Reactome:R-HSA-877269

SOCS-1 and SOCS-3 binds to p-JAK2

Reactome:R-HSA-877300

Interferon gamma signaling

Reactome:R-HSA-8854645

IL22:IL22RA1:JAK1 binds IL10RB:TYK2

Reactome:R-HSA-8950210

Interleukin-27 dissociates from Interleukin-27 receptor

Reactome:R-HSA-8950340

IL27RA and IL6ST are phosphorylated after IL27:IL27 receptor interaction and JAK's phosphorylation

Reactome:R-HSA-8950405

JAK1/JAK2 bound to IL35:IL6ST:IL12RB2 receptor are phosphorylated

Reactome:R-HSA-8950441

p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor

Reactome:R-HSA-8950448

STAT4 binds to IL12RB2 in Interleukin-12 receptor complex

Reactome:R-HSA-8950453

JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and STAT4

Reactome:R-HSA-8950485

STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R interaction

Reactome:R-HSA-8950518

STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 receptor complex

Reactome:R-HSA-8950537

JAK1, JAK2, TYK2 in IL27:EBI3:IL27RA:JAK1:IL6ST:(JAK1,JAK2,TYK2) are phosphorylated

Reactome:R-HSA-8950757

IL12RB2 in IL12A:IL12RB1:p-Y-TYK2:IL12B:IL12RB2:p-JAK2 is phosphorylated

Reactome:R-HSA-8952807

p-Y693-STAT4 dissociates after IL12:IL12R interaction

Reactome:R-HSA-8963734

IL9 binds IL9R:JAK1 and IL2RG:JAK3

Reactome:R-HSA-8982162

p‑Y705-STAT3 dissociates from IL19:IL20RA:p-JAK1:IL20RB

Reactome:R-HSA-8982163

IL19:IL20RA:p-JAK1:IL20RB:STAT3 phosphorylates STAT3

Reactome:R-HSA-8982165

IL19:IL20RA:p‑JAK1:IL20RB binds STAT3

Reactome:R-HSA-8983003

IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3:PI3K-regulatory subunits binds IRS1,IRS2

Reactome:R-HSA-8983063

JAK3 in IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 is phosphorylated

Reactome:R-HSA-8983298

IL15 binds IL2RB:JAK1 and IL2RG:JAK3

Reactome:R-HSA-8983300

IL15RA:IL15:IL2RB:JAK1:IL2RG:JAK3 phosphorylates JAK3 and JAK1

Reactome:R-HSA-8983335

IL15:IL15RA:IL2RB:JAK1:IL2RG:JAK3 translocates from the plasma membrane to the endosome

Reactome:R-HSA-8983371

IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 phosphorylates STAT3 and STAT5

Reactome:R-HSA-8983374

p-Y-STAT3 and p-STAT5 dissociates from IL15:IL15RA:IL2RB:p-JAK1:IL2RG:p-JAK3:p-Y-STAT3:p-STAT5

Reactome:R-HSA-8983378

IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 binds STAT3 and STAT5

Reactome:R-HSA-8983384

IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3:p-Y-SHC1:GRB2 binds SOS1,SOS2

Reactome:R-HSA-8983518

IL35 binds IL6ST:IL6ST receptor

Reactome:R-HSA-8983834

JAK1/JAK2/TYK2 bound to IL6ST:IL6ST are phosphorylated

Reactome:R-HSA-8983835

JAK1/JAK2/TYK2 bound to IL6ST:IL6ST phosphorylate STAT1

Reactome:R-HSA-8983841

STAT1 associates with IL6ST:IL6ST

Reactome:R-HSA-8983845

p-STAT1 dissociates from IL6ST:IL6ST

Reactome:R-HSA-8983983

p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor

Reactome:R-HSA-8983996

STAT1 and STAT4 associate with IL12RB2:IL6ST receptor

Reactome:R-HSA-8984001

IL35 binds IL27RA:IL12RB2 receptor

Reactome:R-HSA-8984012

JAK1,JAK2 bound to IL27RA:IL12RB2 receptor are phosphorylated

Reactome:R-HSA-8984014

JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3

Reactome:R-HSA-8984021

STAT1,STAT3 associate with IL27RA:IL12RB2 receptor

Reactome:R-HSA-8984023

p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor

Reactome:R-HSA-8985900

p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3

Reactome:R-HSA-8985914

IL9:IL9R:JAK1:IL2RG:JAK3 phosphorylates JAK3

Reactome:R-HSA-8985929

IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A or STAT5B

Reactome:R-HSA-8985973

IL9R is phosphorylated by IL9:IL9R:JAK1:IL2RG:p-Y904,939-JAK3

Reactome:R-HSA-8985988

IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1, STAT3 or STAT5

Reactome:R-HSA-8986446

IL26 binds IL20RA:JAK1

Reactome:R-HSA-8986480

IL26:IL20RA:JAK1 binds IL10RB:TYK2

Reactome:R-HSA-8986972

IL24 binds IL20RA:JAK1:IL20RB

Reactome:R-HSA-8986985

IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates STAT1, STAT2, STAT3, STAT4 and STAT5

Reactome:R-HSA-8986994

IL26:IL20RA:JAK1:IL10RB:TYK2 phosphorylates JAK1, TYK2

Reactome:R-HSA-8986995

IL22:IL22RA1:p-JAK1:IL10RB:p-TYK2 phosphorylates IL22RA

Reactome:R-HSA-8987012

IL24:IL22RA1:JAK1:IL20RB phosphorylates JAK1

Reactome:R-HSA-8987014

IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:PTPN11:IL10RB:p-TYK2 binds STAT3

Reactome:R-HSA-8987015

IL20 binds IL20RA:JAK1:IL20RB

Reactome:R-HSA-8987033

p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5

Reactome:R-HSA-8987039

JAK1 binds IL20RA

Reactome:R-HSA-8987040

IFNL1:IFNLR1:p-JAK1:IL10RB:p-TYK2 phosphorylates IFNLR1

Reactome:R-HSA-8987042

IL22:IL22RA1:JAK1:IL10RB:TYK2 phosphorylates JAK1,TYK2

Reactome:R-HSA-8987043

IL22RA1 binds JAK1

Reactome:R-HSA-8987063

IL24:IL22RA1:p-JAK1:IL20RB binds STAT3

Reactome:R-HSA-8987070

IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:STAT3 phosphorylates STAT3

Reactome:R-HSA-8987080

IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3

Reactome:R-HSA-8987084

IL19:IL20RA:JAK1:IL20RB phosphorylates JAK1

Reactome:R-HSA-8987096

IL24:IL22RA1:p-JAK1:IL20RB:STAT3 phosphorylates STAT3

Reactome:R-HSA-8987097

IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3

Reactome:R-HSA-8987104

IL20:IL20RA:JAK1:IL20RB:p‑JAK2,p‑JAK3 binds STAT3

Reactome:R-HSA-8987105

IFNL2,IFNL3 bind IL10RB:TYK2 and IFNLR1:JAK1

Reactome:R-HSA-8987120

JAK1 binds IFNLR1

Reactome:R-HSA-8987129

JAK1 in IL24:IL20RA:JAK1:IL20RB is phosphorylated

Reactome:R-HSA-8987132

IL22:p‑Y251,p‑Y301‑IL22RA1:p‑JAK1:PTPN11:IL10RB:p‑TYK2 binds PTPN11

Reactome:R-HSA-8987141

IL20:IL20RA:JAK1:IL20RB:p-JAK3,p-JAK2:STAT3 phosphorylates STAT3

Reactome:R-HSA-8987150

IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3

Reactome:R-HSA-8987156

p-STAT3 dissociates from IL20:IL20RA:JAK1:IL20RB:p-Y1007,Y1008-JAK2,p-JAK3

Reactome:R-HSA-8987161

p-STAT3 dissociates from IL24:IL22RA1:p‑JAK1:IL20RB:p‑STAT3

Reactome:R-HSA-8987179

IL20:IL20RA:JAK1:IL20RB:JAK2,JAK3 phosphorylates JAK2,JAK3

Reactome:R-HSA-8987202

IFNL1:IFNLR1:JAK1:IL10RB:TYK2 phosphorylates JAK1,TYK2

Reactome:R-HSA-8987220

IL20:IL20RA:JAK1:IL20RB binds JAK2,JAK3

Reactome:R-HSA-8987230

p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1

Reactome:R-HSA-8987236

p-Y705-STAT3 dissociates from IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:p-Y705-STAT3

Reactome:R-HSA-8987255

IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3 phosphorylates STAT1,STAT3

Reactome:R-HSA-8987266

IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, STAT3, STAT4, STAT5

Reactome:R-HSA-8987270

p-STAT1,p-STAT3 dissociate from IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3

Reactome:R-HSA-9005980

IL21 binds IL21R:JAK1

Reactome:R-HSA-9006844

IL21:IL21R:JAK1 binds IL2RG:JAK3

Reactome:R-HSA-9006850

IL21 receptor JAK phosphorylation

Reactome:R-HSA-9006870

IL21 receptor STAT phosphorylation

Reactome:R-HSA-9006873

IL21 receptor STAT binding

Reactome:R-HSA-9009227

IL20 binds to IL22RA1:JAK1:IL20RB

Reactome:R-HSA-9011748

IL9R binds JAK1

Reactome:R-HSA-9020558

Interleukin-2 signaling

Reactome:R-HSA-9025969

IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3 binds STAT5

Reactome:R-HSA-909552

Phosphorylation of STAT1 at Ser727

Reactome:R-HSA-909718

Formation of p-STAT1 homodimer

Reactome:R-HSA-909719

Recruitment of STAT2 to p-IFNAR1

Reactome:R-HSA-909720

IFN alpha/beta binds to IFNAR2

Reactome:R-HSA-909722

Release of p-STAT2:p-STAT1 dimer

Reactome:R-HSA-909724

Recruitment of IFNAR1

Reactome:R-HSA-909726

Phosphorylation of STAT1

Reactome:R-HSA-909729

Activation of JAK kinases

Reactome:R-HSA-909730

Phosphorylation of INFAR1 by TYK2

Reactome:R-HSA-909732

Phosphorylation of STAT2

Reactome:R-HSA-909733

Interferon alpha/beta signaling

Reactome:R-HSA-912527

SHC1 mediates cytokine-induced phosphorylation of GAB2

Reactome:R-HSA-913374

Phosphorylated SHC1 recruits SHIP

Reactome:R-HSA-913424

The SHC1:SHIP1 complex is stabilized by GRB2

Reactome:R-HSA-919404

Phosphorylated STAT5 is released

Reactome:R-HSA-9674816

p-Y546,Y584-PTPN11 (in CSF3 dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11) dephosphorylates KRAS

Reactome:R-HSA-9677579

CSF3 dimer (GCSF dimer) binds CSF3R:JAK1:LYN

Reactome:R-HSA-9677585

CSF3 dimer:CSFR:LYN:JAK1 binds CSFR:LYN:JAK1

Reactome:R-HSA-9678561

IFNGR1:JAK1:INFGR2:JAK2 binds JAK1,2 inhibitors

Reactome:R-HSA-9678935

IFNAR2:JAK1:STAT2 binds JAK1,2 inhibitors

Reactome:R-HSA-9696179

IFNAR2:JAK1:STAT2 binds type 1 interferon analogs

Reactome:R-HSA-9705738

SOCS1,3 ubiquitinates CSF3R in SOCS1,3:p-4Y-CSF3R:CSF3 dimer:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:CUL5:ELOB:ELOC:RNF7

Reactome:R-HSA-9707977

CSF3 dimer:2xK48polyUb-K655,p-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-Y-SYK:p-HCK:p-TYK2 translocates from the endocytic vesicle membrane to the lysosomal membrane

Reactome:R-HSA-9732729

Activated JAK1 binds RAF1

Reactome:R-HSA-9732738

JAK1-mediated phosphorylation of RAF1

Reactome:R-HSA-9732753

JAK1-activated RAF1 phosphorylates MAPKs

Reactome:R-HSA-997309

Dephosphorylation of STAT1 by SHP2

Reactome:R-HSA-997311

Dephosphorylation of TYK2 by PTP1B

Reactome:R-HSA-997314

Dephosphorylation of JAK1 by SHP1

Suggested Experiments

Experiment: Cryo-EM structures of JAK1 in complex with different cytokine receptors to understand receptor-specific activation mechanisms

Experiment: Single-cell RNA sequencing of immune cells with JAK1 perturbations to map cell-type-specific transcriptional responses

Experiment: Chemical proteomics to identify off-target effects and selectivity profiles of JAK1 inhibitors in development

Experiment: Real-time measurement of JAK1 kinase activity using FRET-based biosensors in response to different cytokines

📚 Additional Documentation

Deep Research

(JAK1-deep-research.md)

Deep Research Report: JAK1 (human)

Generated using OpenAI Deep Research API and enhanced with additional comprehensive research findings (September 2024)

Janus Kinase 1 (JAK1) – Comprehensive Research Report

Gene Function and Molecular Mechanisms

JAK1 is a non-receptor tyrosine kinase that plays a pivotal role in cytokine signaling (kinase-atlas.bu.edu). It is one of four Janus kinases in humans (JAK1, JAK2, JAK3, TYK2) and is constitutively associated with the cytoplasmic domains of various cytokine receptors (pmc.ncbi.nlm.nih.gov). Upon cytokine binding to these receptors, JAK1 becomes activated (often together with a partner JAK) through autophosphorylation and cross-activation, triggering the JAK-STAT signaling cascade (pmc.ncbi.nlm.nih.gov). Activated JAK1 phosphorylates specific tyrosine residues on the receptor’s intracellular tails, creating docking sites for STAT transcription factors, which JAK1 then phosphorylates to induce STAT dimerization and nuclear translocation for gene transcription (pmc.ncbi.nlm.nih.gov). Thus, JAK1’s kinase activity (protein tyrosine kinase activity, GO:0004715) is essential for transmitting signals from extracellular cytokines to changes in gene expression (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In addition to activating STATs, JAK1 can phosphorylate other substrates; for example, it associates with the interleukin-2 receptor β chain and is required for efficient recruitment and phosphorylation of the PI3K p85 subunit, indicating JAK1 also links cytokine receptors to the PI3K-Akt pathway (pubmed.ncbi.nlm.nih.gov). Overall, JAK1 serves as a key signaling node, coupling a wide range of cytokine receptors to intracellular pathways that control immune cell function, proliferation, and survival.

Cellular Localization and Subcellular Components

JAK1 is predominantly an intracellular cytosolic protein localized at the cytoplasmic side of the plasma membrane (GO:0031234) as part of cytokine receptor complexes (pmc.ncbi.nlm.nih.gov). Through its N-terminal domains, JAK1 is tightly but non-covalently associated with membrane-proximal regions of type I and II cytokine receptors, effectively making it an extrinsic component of the cytoplasmic face of the plasma membrane (pmc.ncbi.nlm.nih.gov) (www.informatics.jax.org). Consistent with this, high-throughput localization data indicate JAK1 shows general cytoplasmic distribution in cells (v19.proteinatlas.org). While its main site of action is at the membrane and in the cytosol, there is evidence that JAK1 (and JAK2) can also translocate to the nucleus in certain contexts (www.ncbi.nlm.nih.gov). For example, biochemical and microscopy studies found that both JAK1 and JAK2 are constitutively present in the nucleus of some proliferating cells (www.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). The exact function of nuclear JAK1 is still being explored, but it may phosphorylate nuclear substrates or influence chromatin, indicating that JAK1’s localization is dynamic. Nonetheless, for Gene Ontology annotation, the primary cellular components associated with JAK1 are the cytosol (GO:0005829) and plasma membrane (cytoplasmic side), reflecting its well-established role in membrane-proximal signaling.

Biological Processes Involvement

JAK1 is involved in a broad array of biological processes, predominantly those related to cytokine signaling and immune function. It is a critical mediator of the cytokine-mediated signaling pathway (GO:0019221) and more specifically the JAK-STAT cascade (GO:0007259) across multiple cytokine families (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Notably, JAK1 is required for signaling by certain type I and type II cytokines. For instance, cells lacking JAK1 are completely unresponsive to both type I interferons (IFN-α/β) and type II interferon (IFN-γ), and reintroduction of JAK1 restores these interferon responses (pubmed.ncbi.nlm.nih.gov). This establishes JAK1 as an essential component of the interferon signaling pathways, which are crucial for antiviral defense and immune regulation. JAK1 partners with TYK2 in the type I IFN receptor (IFNAR) complex and with JAK2 in the IFN-γ receptor complex, and both combinations are needed to assemble functional receptor signaling units (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). JAK1 also plays a nonredundant role in signaling via receptors that use the common γ_c chain (type I cytokine receptors such as IL-2, IL-7, IL-9, IL-15) and those that use the gp130 subunit (IL-6 family cytokines) (pubmed.ncbi.nlm.nih.gov). In JAK1-knockout mice, cells fail to respond to class II cytokine receptors (which include interferons and IL-10 family cytokines), to γ_c-dependent cytokines (IL-2/4/7/9/15/21), and to gp130-dependent cytokines (e.g. IL-6, IL-11, LIF), underscoring JAK1's central role in these signaling pathways (pubmed.ncbi.nlm.nih.gov).

Detailed Cytokine Receptor Specificity and Signaling Mechanisms

JAK1 demonstrates remarkable specificity in its cytokine receptor associations, serving as a critical signaling hub for multiple cytokine receptor families:

Type I Interferon Signaling (IFN-α/β): JAK1 associates with the IFNAR2 receptor subunit, while TYK2 associates with IFNAR1. Upon type I IFN binding, JAK1 and TYK2 cross-phosphorylate each other and subsequently phosphorylate STAT1 and STAT2. These STATs form heterodimers that complex with IRF9 to form ISGF3 (interferon-stimulated gene factor 3), which translocates to the nucleus and binds interferon-sensitive response elements (ISRE) to drive antiviral gene expression.

Type II Interferon Signaling (IFN-γ): JAK1 pairs with JAK2 in the IFNGR1/IFNGR2 receptor complex. IFN-γ signaling leads to STAT1 homodimerization that binds to gamma-activated sequences (GAS) in promoters of pro-inflammatory genes, driving immune activation and antimicrobial responses.

Common Gamma Chain (γc) Cytokines: JAK1 is essential for signaling through IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors. The IL-2Rβ subunit is JAK1-associated, while the common γc chain associates with JAK3. This JAK1/JAK3 combination is critical for T cell development, activation, and homeostasis.

GP130-Dependent Cytokines: JAK1 serves as the principal kinase for IL-6 family cytokines including IL-6, IL-11, IL-27, LIF (leukemia inhibitory factor), and oncostatin M. In these pathways, JAK1 phosphorylates the gp130 receptor subunit and activates STAT1/STAT3, driving inflammatory responses and acute-phase protein production.

IL-10 Family Cytokines: JAK1 is involved in IL-10, IL-22, and IL-26 signaling through type II cytokine receptor complexes, typically pairing with TYK2 to phosphorylate STAT1, STAT3, and STAT5, leading to anti-inflammatory and tissue protective responses.

Through these interactions, JAK1 influences many downstream biological outcomes. It acts upstream of processes such as the cellular response to cytokine stimulus (GO:0071345) and positively regulates receptor signaling pathways that utilize STAT transcription factors (www.informatics.jax.org). For example, in the IL-6 pathway, JAK1 is the major kinase that phosphorylates the gp130 receptor subunit and activates STAT1/STAT3; without JAK1, IL-6-induced phosphorylation of gp130 and activation of STAT1/3 are severely impaired (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Consequently, transcription of IL-6 target genes (e.g. IRF1) is abolished in the absence of JAK1 (pubmed.ncbi.nlm.nih.gov). JAK1-dependent signaling pathways control diverse biological processes including immune system development (via IL-7 and other cytokines for lymphocyte development), inflammatory responses (e.g. IL-6, IL-27, IFN-γ in inflammation), and antiviral defense (type I interferon responses). In summary, JAK1 is indispensable for initiating responses to many cytokines and thereby impacts processes like hematopoiesis, antiviral immunity, and general cytokine-driven communication between cells. It essentially acts as a master switch for multiple cytokine-triggered biological processes in both innate and adaptive immunity.

Disease Associations and Phenotypes

Loss-of-function of JAK1: Because JAK1 is required for so many cytokine signals, a complete loss of JAK1 function is deleterious. Knockout studies in mice show that Jak1⁻/⁻ mice are runted, fail to nurse, and die perinatally, reflecting the essential nature of this gene (pubmed.ncbi.nlm.nih.gov). Cells from Jak1-deficient mice can respond to some growth factors, but they cannot respond to cytokines that utilize class II, γ_c, or gp130 receptors (pubmed.ncbi.nlm.nih.gov), leading to severe immunodeficiency and developmental defects. In humans, no individuals with a complete JAK1 deficiency have been described (likely because it would be lethal, as in mice). Notably, unlike JAK3 (where loss-of-function mutations cause severe combined immunodeficiency in humans), germline loss-of-function mutations in JAK1 have not been reported – underscoring that JAK1’s role is so broad that it may not be compatible with postnatal life (pubmed.ncbi.nlm.nih.gov). However, somatic JAK1 mutations have been observed in cancers: for example, some tumors (such as certain melanomas and lymphomas) acquire inactivating mutations in JAK1 to escape immune surveillance. By disabling JAK1, these tumor cells become unresponsive to IFN-γ signaling and can resist the growth-inhibitory and pro-apoptotic effects of the immune system. This mechanism has been linked to primary or acquired resistance to immune checkpoint inhibitor therapies in melanoma, whereby JAK1 or JAK2 loss-of-function leads to lack of PD-L1 upregulation and antigen presentation in response to interferon (pubmed.ncbi.nlm.nih.gov). Thus, JAK1 inactivation in a tumor context can confer an immune-evasive phenotype that promotes disease progression.

Gain-of-function of JAK1: Conversely, hyperactivation of JAK1 is implicated in malignancy and inflammatory conditions. Somatic activating mutations in JAK1 have been identified in subsets of acute lymphoblastic leukemias (especially in T-cell ALL) and other hematological cancers (www.informatics.jax.org). A well-known example is the JAK1 V658F mutation in the pseudokinase domain (analogous to JAK2’s V617F mutation), which removes the pseudokinase’s inhibitory effect and drives constitutive JAK1 signaling (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Such gain-of-function (GOF) mutations lead to unchecked STAT activation and have transforming effects on cells. Beyond cancer, rare germline GOF mutations in JAK1 have recently been shown to cause an immunological disorder: heritable JAK1 hyperactivation can produce a syndrome of severe allergic inflammation and eosinophilia (pmc.ncbi.nlm.nih.gov). In this condition, patients with a germline JAK1 mutation (e.g. JAK1 p.A634D) exhibit extreme atopic dermatitis, asthma, and blood eosinophilia due to heightened signaling through IL-4/IL-13 and other cytokine pathways (pmc.ncbi.nlm.nih.gov). This finding highlights that JAK1’s activity must be tightly regulated for normal immune homeostasis – too little activity causes immunodeficiency, while too much leads to immune overactivity and cancer predisposition.

Given its central role, JAK1 is also a significant drug target in human disease. Small-molecule JAK inhibitors that suppress JAK1 activity have been developed for treating autoimmune and inflammatory diseases. For instance, tofacitinib (a pan-JAK inhibitor with activity on JAK1/JAK3) and more selective JAK1 inhibitors like upadacitinib and filgotinib are now used to treat conditions such as rheumatoid arthritis, ulcerative colitis, and other cytokine-driven disorders (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). These drugs exploit the fact that reducing JAK1-mediated signaling can dampen pathological inflammation. However, due to JAK1’s importance in normal immune function, such therapies must be dosed carefully to avoid immunosuppression (for example, JAK1/3 inhibition can reduce lymphocyte counts because IL-2 family signaling is affected (pmc.ncbi.nlm.nih.gov)). In oncology, JAK1 inhibitors are under investigation for tumors with aberrant JAK-STAT activation. Overall, JAK1’s involvement in disease is double-edged: it is required for immune defense but, if dysregulated, contributes to immune-mediated diseases and cancer. This makes JAK1 a critical focus of both clinical genetics and pharmacological intervention efforts.

Protein Domains and Structural Features

The JAK1 protein is composed of 1154 amino acids and features a multi-domain architecture characteristic of the Janus kinase family. It contains seven JAK homology (JH1–JH7) regions that form four major domains (pmc.ncbi.nlm.nih.gov):

N-terminal FERM domain (JH6–JH7): A band 4.1, ezrin, radixin, moesin (FERM) domain at the N-terminus mediates binding to cytokine receptor cytoplasmic tails (pmc.ncbi.nlm.nih.gov). This domain is crucial for receptor association – deletion of JAK1’s N-terminus abrogates receptor binding (pmc.ncbi.nlm.nih.gov). The FERM domain also plays a regulatory role, as certain mutations in this region can reduce or enhance JAK1’s kinase activity (pmc.ncbi.nlm.nih.gov). In the context of JAK1’s 3D structure, the FERM domain folds together with the next SH2 domain to form a stable receptor-binding module (pmc.ncbi.nlm.nih.gov).
SH2-like domain (JH3–JH5): Adjacent to the FERM region, JAK1 has a Src-homology 2 (SH2) domain that further aids in receptor interaction (pmc.ncbi.nlm.nih.gov). The FERM and SH2 domains are closely associated and together they dock onto specific receptor peptide motifs (pmc.ncbi.nlm.nih.gov). These interactions localize JAK1 to the receptor complex and position the kinase for activation when the receptor chains dimerize.
Pseudokinase domain (JH2): In the middle of JAK1 lies the pseudokinase domain (pmc.ncbi.nlm.nih.gov). This domain resembles a tyrosine kinase domain in sequence but lacks key residues for catalytic activity, so it is kinase-inactive (hence “pseudo”). Despite not catalyzing phosphorylation, JH2 has an essential regulatory function over the adjacent kinase domain (pmc.ncbi.nlm.nih.gov). The pseudokinase exerts an autoinhibitory effect – it maintains JAK1 in an off state until the correct activation signal is received. Mutations in the JH2 domain can disrupt this regulation and lead to constitutive activation (pmc.ncbi.nlm.nih.gov). For example, a single point mutation in JAK2’s pseudokinase (V617F) causes uncontrolled kinase activity in myeloproliferative disease (pmc.ncbi.nlm.nih.gov), and an analogous mutation in JAK1 (V658F) has been found in leukemias (pubmed.ncbi.nlm.nih.gov). These mutations illustrate how the pseudokinase domain normally restrains the kinase domain, acting as a molecular “brake” that can be released by mutation or by receptor-mediated conformational changes.
C-terminal kinase domain (JH1): The C-terminus of JAK1 is a tyrosine kinase domain responsible for its enzymatic activity (pmc.ncbi.nlm.nih.gov). This domain binds ATP and catalyzes the transfer of the γ-phosphate to tyrosine residues on substrates (including the receptor itself, STATs, and other signaling proteins). JAK1’s kinase domain contains the conserved activation loop tyrosines (Tyr^1034 and Tyr^1035 in human JAK1) that must be trans-autophosphorylated for full activation of the kinase. Upon receptor dimerization, two JAK1 molecules (or JAK1 with another JAK) phosphorylate each other’s activation loop, which induces a conformational change that greatly increases catalytic activity (pmc.ncbi.nlm.nih.gov). The kinase domain then phosphorylates downstream targets to propagate the signal. Crystal structure analyses of JAK1 have confirmed the arrangement of these domains and the requirement that the pseudokinase and kinase domains properly interact for normal regulation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Structurally, JAK1 appears as a two-lobed kinase module (pseudokinase + kinase) tethered via a flexible linker to the FERM–SH2 module that grips the receptor (pmc.ncbi.nlm.nih.gov). This modular design allows JAK1 to convert cytokine–receptor binding at the membrane into a kinase activation event. Key structural features of JAK1 also include several autophosphorylation sites outside the activation loop (which modulate its activity and docking interactions) and interaction interfaces for negative regulators (e.g. SOCS1 binds near the kinase domain). Overall, the domain structure of JAK1 underpins its function as a finely tuned switch – the FERM/SH2 domains target JAK1 to receptors, the pseudokinase domain acts as a sensor/regulator, and the kinase domain executes the phosphorylation signaling.

Expression Patterns and Regulation

JAK1 is ubiquitously expressed in human tissues, consistent with its fundamental role in multiple cytokine systems. Transcript and protein profiling indicate low tissue specificity, with JAK1 mRNA detected in all examined tissues and protein present widely at the cellular level (v19.proteinatlas.org). The Human Protein Atlas shows general cytoplasmic expression of JAK1 across numerous cell types and organs (v19.proteinatlas.org). Notably, immune cells and immunological organs (like spleen, lymph nodes, thymus) express high levels of JAK1, as expected given its requirement for lymphocyte growth factor signaling. But JAK1 is also expressed in non-immune tissues (e.g. lung, liver, CNS, etc.), enabling responses to cytokines like growth factors and interferons in those contexts (www.informatics.jax.org). Developmentally, JAK1 is expressed from early stages, and in mice its expression is ubiquitous in the embryo, aligning with the broad developmental defects observed in Jak1 knockout models.

At the regulatory level, JAK1 expression is generally constitutive, but it can be modulated by certain stimuli. Cytokine exposure can induce feedback mechanisms that affect JAK1 stability or transcript levels. One important regulation is via SOCS (Suppressor of Cytokine Signaling) proteins: cytokine-activated STATs induce SOCS1/3, which then bind to JAK1 and target it for ubiquitination and proteasomal degradation, thus providing a negative feedback loop on JAK1 activity. In addition, there is evidence that microRNAs and other post-transcriptional regulators (for instance, miR-15/16 family) can downregulate JAK1 expression in some cell types to modulate sensitivity to cytokines (observed in certain cancers and immune cells). Hormonally, JAK1 levels may be influenced by steroid hormones or stress signals indirectly, though the gene is not known to be strongly inducible. Overall, JAK1’s expression pattern is broad and relatively stable, ensuring that most cells have the capacity to respond to cytokine signals. Fine-tuning of JAK1’s activity is primarily achieved by post-activation mechanisms (phosphatases, SOCS proteins) rather than large changes in expression, with the exception of pathological situations where JAK1 may be overexpressed (e.g. some cancers) or underexpressed due to deletions/mutations.

Evolutionary Conservation

JAK1 and the JAK family are well conserved through evolution among multicellular organisms. Orthologs of JAK1 are found in all vertebrates and even in invertebrates like insects, reflecting an ancient origin of the JAK–STAT signaling mechanism (pmc.ncbi.nlm.nih.gov). The overall domain architecture – FERM, SH2, pseudokinase, kinase – is highly conserved from insects to mammals (pmc.ncbi.nlm.nih.gov). For example, the single JAK homolog in Drosophila melanogaster (the hopscotch gene) contains recognizable FERM, SH2, JH2, and JH1 domains very similar to those of mammalian JAK1, and it performs analogous signaling functions in fly development and immunity. In vertebrates, JAK1 is one of four paralogous JAKs; it shares significant sequence identity with the other family members (especially TYK2 and JAK3 in various domains) and arose from gene duplication events early in vertebrate evolution. Human JAK1 is ~86% identical to mouse Jak1 at the amino acid level, indicating strong conservation among mammals. Key functional residues (such as the lysine in the ATP-binding site of the kinase domain, the activation loop tyrosines, and the inhibitory pseudokinase motifs) are invariant across species (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), underscoring their importance. Evolutionary divergence of JAK family members allowed specialization: for instance, JAK3 evolved to work principally with the γ_c receptor in lymphoid cells, whereas JAK1 and JAK2 took on broader roles. Nonetheless, in lower organisms that lack distinct JAK paralogs, a single JAK can fulfill multiple roles – as seen in flies, where Hopscotch (JAK) transduces signals for various cytokine-like factors in development. No JAK homologs are present in yeasts or plants, suggesting that JAK/STAT signaling is a metazoan (animal-specific) innovation tied to complex intercellular communication. The strong conservation of JAK1 throughout animal evolution highlights its fundamental role: the basic mechanism by which a cytokine binding outside a cell triggers a transcriptional response inside the cell has been preserved. This evolutionary conservation also means findings in model organisms (mice, flies, zebrafish) are highly relevant to understanding human JAK1 function.

Key Experimental Evidence and Literature

Requirement for Interferon Signaling (1993): In a landmark study, Mullers et al. created a mutant human cell line lacking JAK1 and found it was completely unresponsive to interferon-α/β and interferon-γ. Transfecting JAK1 back into these cells restored interferon-driven gene induction, proving that JAK1 is absolutely required for type I and II interferon signal transduction (pubmed.ncbi.nlm.nih.gov). This was the first direct evidence that JAK1 is an essential component of the interferon receptor signaling complexes.
JAK1 Knockout Mouse Phenotype (1998): Rodig et al. (Cell 93:373–383) disrupted the Jak1 gene in mice to investigate its in vivo role. Jak1⁻/⁻ mice were born alive but failed to nurse and died perinatally, and their cells showed selective unresponsiveness to a subset of cytokines. Specifically, Jak1-deficient cells could not respond to IL-2/4/7/9 (γ_c family), IL-6 family cytokines (gp130-dependent), or interferons (pubmed.ncbi.nlm.nih.gov). This study demonstrated non-redundant, essential roles for JAK1 in multiple cytokine pathways and explained the perinatal lethality as a consequence of the loss of numerous cytokine signals (e.g., failure of lymphocyte development due to loss of IL-7 and IL-15 signaling, and nursing defects potentially due to impaired growth hormone or prolactin signaling).
IL-6/GP130 Pathway – JAK1 Dominance (1998): Schaper et al. showed that in human fibrosarcoma cells, IL-6 activates JAK1, JAK2, and TYK2, but JAK1 is uniquely required for downstream signaling. In cells lacking JAK1, IL-6 could not efficiently phosphorylate the gp130 receptor or activate STAT1/STAT3, whereas lack of JAK2 or TYK2 had a lesser effect (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). JAK1’s presence was necessary for induction of IL-6-responsive genes like IRF1. This established that JAK1 is the principal kinase mediating IL-6 family cytokine signaling, and that JAK1 and JAK2 are not functionally redundant in this pathway.
Janus Kinase Name and Structure (Mid-1990s): JAK1 was initially identified in 1992–1993 by two groups using PCR-based strategies to find novel tyrosine kinases. It was named “Janus kinase” because it possesses two kinase-related domains (one active, one pseudo), reminiscent of the two-faced Roman god Janus. Wilks et al. cloned JAK1 (originally called JAK1/JAK1A) and noted the unusual dual-domain structure, predicting its role in cytokine signaling. This prediction was confirmed by functional studies in the same era, linking JAK1 to interferon and interleukin receptor complexes (pubmed.ncbi.nlm.nih.gov). The Janus nomenclature and domain organization were later discussed in reviews, and crystal structures of JAK family members (e.g. JAK1 JH1 domain) were solved in the 2010s, giving structural insight into JAK1’s activation mechanism (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
Oncogenic JAK1 Mutations in Leukemia (2008–2010): With the advent of cancer genomics, activating mutations in JAK1 were discovered in acute leukemias. For example, Hornakova et al. reported somatic JAK1 mutations in T-ALL patients that led to cytokine-independent JAK-STAT activation. One such mutation, JAK1 V658F in the pseudokinase domain, mirrors the JAK2 V617F mutation found in myeloproliferative neoplasms (pubmed.ncbi.nlm.nih.gov). Functional assays showed JAK1 V658F confers constitutive signaling and transforming ability in cells. These findings solidified JAK1 as an oncogene in certain contexts and spurred interest in JAK1 inhibitors for cancer therapy. Additionally, other patient-derived mutations (e.g. JAK1 L910P and C-terminal kinase domain mutants) were characterized, each with varying effects on signaling outputs (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov).
JAK1 in Tumor Cell Invasion and Metastasis (2011): A study by Heidinger et al. (Cancer Cell 20:158–172) revealed a novel role of JAK1 in regulating tumor cell motility. They found that proinflammatory cytokine signaling via gp130–JAK1 triggers RhoA/ROCK-mediated actomyosin contractility in both carcinoma cells and tumor-associated fibroblasts (pubmed.ncbi.nlm.nih.gov). This JAK1-driven contractility enabled cancer cells to adopt an “amoeboid” migration mode, squeezing through extracellular matrix barriers. In experimental models, JAK1 activity was required for efficient metastasis of certain cancers, linking chronic inflammation (IL-6/IL-11 in the tumor microenvironment) to increased invasive potential via a JAK1-STAT3-ROCK pathway. This research expanded the understanding of JAK1 beyond immune signaling, implicating it in the physical processes of cancer dissemination.

These key studies, along with many others, form the evidence base for Gene Ontology annotations of JAK1. They collectively demonstrate JAK1's molecular function as a tyrosine kinase, its cellular location at cytokine receptor complexes, the biological processes it regulates (cytokine signaling, immune responses, etc.), and its involvement in disease phenotypes. Each cited discovery provides experimental support for specific GO terms associated with JAK1, ensuring that annotations are backed by peer-reviewed evidence.

Recent Advances and Therapeutic Developments (2023-2024)

Updated JAK-STAT Pathway Understanding

Recent comprehensive reviews have expanded our understanding of JAK1's role in the JAK-STAT signaling pathway. The pathway is now recognized as controlling more than 50 cytokines that orchestrate hematopoiesis, induce inflammation, and control immune responses PMID:30084503. Updated mechanistic studies demonstrate that SOCS1 is a potent inhibitor of interferon signaling by specifically targeting JAK1, while SHP2 knockout leads to increased JAK1 autophosphorylation and upregulation of interferon signaling. Recent systematic reviews highlight JAK1's central role in autoimmune disorders and cancer through dysregulated JAK-STAT signaling PMID:37202347.

Structural Biology Breakthroughs

Recent cryo-electron microscopy studies have provided detailed structural analysis of the entire JAK1 structure in complex with part of the interferon lambda receptor (IFNλR), with structures deposited as PDB ID: 7T6F. These studies reveal how the FERM and SH2L domains form a single structural unit that engages the Box1 and Box2 cytoplasmic regions of cytokine receptors. Crystal structures show that JAK1 FERM and SH2L domains complex with peptides representing the interferon-λ1 receptor, providing atomic-level detail of receptor recognition mechanisms.

Cytokine Receptor Promiscuity and Signaling Efficiency

Recent research has revealed promiscuous Janus kinase binding to cytokine receptors that modulates signaling efficiencies and contributes to cytokine pleiotropy. Studies demonstrate that TYK2 and JAK1 are recruited to IFN receptor subunits IFNAR1 and IFNAR2, respectively, with cross-phosphorylation between kinases and STAT proteins. Importantly, promiscuous binding of JAK1, JAK2, and TYK2 to IFNAR1 and IFNAR2 correlates with their relative cellular abundances, suggesting that JAK availability in cells influences cytokine response specificity.

Advanced Therapeutic Applications

The landscape of JAK1-targeted therapeutics has significantly expanded since 2023:

Approved JAK1-Selective Inhibitors:
- Upadacitinib: Now approved for rheumatoid arthritis (2019), psoriatic arthritis (2021), atopic dermatitis (2022), and ulcerative colitis (2022). Demonstrates ~60-fold selectivity for JAK1 over JAK2 and >100-fold selectivity over JAK3 in cellular assays.
- Filgotinib: Selective JAK1 inhibitor with expanding indications
- Baricitinib: JAK1/JAK2 inhibitor with established efficacy in multiple autoimmune conditions

Clinical Evidence Base: Current data shows that 12 JAK inhibitors have been approved by the FDA for clinical use against autoimmune inflammatory diseases, including ruxolitinib, pacritinib, fedratinib, tofacitinib, baricitinib, abrocitinib, filgotinib, oclacitinib, peficitinib, upadacitinib, deucravacitinib, and delgocitinib.

Safety Considerations and Risk Management

Recent comprehensive safety analyses have established that JAK1-selective drugs broadly come with the same overarching safety recommendations as other immunosuppressive drugs: caution regarding infection risk and monitoring for laboratory abnormalities including lipids and muscle enzymes. A distinguishing feature of JAK inhibitors is a risk for zoster reactivation, requiring specific monitoring protocols.

Mechanistic Insights into JAK1 Selectivity

Based on current evidence, only JAK1 and TYK2 seem to be involved almost exclusively in inflammatory signal transduction and may represent optimal targets for controlling disease activity in immune-mediated inflammatory diseases. This selectivity profile makes JAK1-selective inhibitors comparable to non-selective ones without the unwanted consequences of JAK2- or JAK3-blockade.

Signal Memory and Post-transcriptional Regulation

Recent research using live-cell microscopy has demonstrated that transient exposure to IFN-γ stimulation induces long-term desensitisation of STAT1 signaling and gene expression responses. This work reveals post-transcriptional regulatory feedback that encodes JAK-STAT signal memory of interferon stimulation, providing new understanding of how cells maintain immune memory through JAK1-dependent pathways.

Disease Association Updates

Recent findings have expanded the understanding of JAK1 in disease:

Autoimmune Diseases: JAK1 inhibitors have proven efficacy in a systematic literature review informing the 2024 update of international consensus statements for immune-mediated inflammatory diseases, confirming their central role in pathological inflammation.

Type 1 Diabetes: Emerging evidence suggests potential applications for JAK inhibitors in type 1 diabetes and immune checkpoint-related diabetes, representing new therapeutic frontiers.

Cancer Immunotherapy: JAK1 continues to be implicated in tumor immune evasion mechanisms, with inactivating mutations leading to resistance to immune checkpoint inhibitors through loss of interferon-γ responsiveness.

These recent advances further solidify JAK1's position as a central hub in cytokine signaling networks and validate its importance as a therapeutic target across multiple disease contexts. The expanding arsenal of JAK1-selective inhibitors, combined with improved understanding of signaling specificity and safety profiles, positions JAK1-targeted therapy as a cornerstone of precision medicine approaches to immune-mediated diseases.

Summary and Core vs Peripheral Functions

Core Molecular Functions (Well-Established)

Protein tyrosine kinase activity (GO:0004715) - JAK1's primary catalytic function, extensively validated
Cytokine receptor binding - Essential for localizing JAK1 to membrane receptor complexes
STAT transcription factor phosphorylation - Direct substrate of JAK1 kinase activity
Interferon signaling - Absolutely required for both type I (IFN-α/β) and type II (IFN-γ) interferon responses
JAK-STAT cascade regulation - Central mediator of this evolutionarily conserved pathway

Core Biological Processes (High-Confidence Annotations)

Type I and II interferon signaling pathways - Essential and non-redundant role
Common γc cytokine signaling (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) - Required for T cell development and function
IL-6 family cytokine signaling - Primary kinase for gp130-dependent pathways
Immune system development - Critical for lymphopoiesis via IL-7 and other cytokines
Cellular response to cytokine stimulus - Broad regulatory role across multiple cytokine families

Peripheral/Contextual Functions (Context-Dependent)

Nuclear translocation and chromatin regulation - Evidence exists but functional significance unclear
Tumor cell invasion and metastasis - Role in cancer cell motility through RhoA/ROCK pathway
Growth factor signaling - Some evidence for non-cytokine growth factor responses
PI3K pathway activation - Indirect coupling to PI3K-Akt signaling via IL-2R

Commonly Over-Annotated Aspects

Protein binding without specificity - JAK1 binds many proteins; specific binding functions should be emphasized
General kinase activity without cytokine context - JAK1's specificity lies in cytokine receptor-associated signaling
Non-specific growth and proliferation - JAK1's role is specifically in cytokine-mediated growth, not general proliferation
Broad developmental processes without mechanistic basis - Focus should be on cytokine-dependent developmental pathways

Key Experimental Validation Requirements

For any JAK1 functional annotation, the following evidence types provide strongest support:
1. JAK1-knockout/knockdown studies showing loss of specific cytokine responses
2. Reconstitution experiments demonstrating restoration of function with JAK1 expression
3. Direct phosphorylation studies identifying specific JAK1 substrates
4. Receptor complex studies showing physical association with cytokine receptors
5. Clinical evidence from JAK1-selective inhibitor studies demonstrating pathway involvement

This comprehensive research establishes JAK1 as a master regulator of cytokine signaling with well-defined core functions in immune regulation, while highlighting the need to distinguish experimentally validated core functions from more peripheral or context-dependent roles.

Notes

(JAK1-notes.md)

JAK1 Gene Review Notes

2025-01-14 - Retired Annotation Fix

Issue: Validation failure due to 15 annotations not found in the current GOA file.

Root Cause: Multiple PMIDs that were referenced in the original annotations have been removed from the current GOA database. These include:
- PMID:29202461 (interleukin-7-mediated signaling pathway)
- PMID:28753426 (regulation of transcription by RNA polymerase II)
- PMID:23391734 (type I interferon-mediated signaling pathway)
- PMID:7568005 (interleukin-2-mediated signaling pathway)
- PMID:28781374 (interleukin-11-mediated signaling pathway)
- PMID:9535918 (interleukin-9-mediated signaling pathway)
- PMID:9020188 (regulation of transcription by RNA polymerase II)
- PMID:23139419, PMID:7526154, PMID:7759950 (JAK-STAT signaling pathway)

Action Taken: Marked annotations with these missing PMIDs as retired: true to exclude them from GOA validation while preserving the annotation review work.

Validation Status: Reduced the number of missing annotations from 15 to potentially 8 or fewer, though some additional ones may need individual attention.

Outstanding Issues:
- Some inconsistent review actions across evidence types for the same GO terms
- Evidence type mismatches with current GOA
- Additional retired annotations may need identification

Note: JAK1 is a key component of the JAK-STAT signaling pathway involved in cytokine signaling, which explains the extensive annotation set and the ongoing changes in the GOA database as curation standards evolve.

📄 View Raw YAML

id: P23458
gene_symbol: JAK1
aliases:
  - JAK1A
  - JAK1B
  - Janus kinase 1
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'JAK1 (Janus Kinase 1) is a non-receptor tyrosine kinase that plays a
  pivotal role in cytokine signal transduction. Contains four major domains: FERM
  domain for receptor binding, SH2-like domain for receptor interaction, pseudokinase
  domain for regulation, and active kinase domain for catalytic activity. Essential
  for Type I/II interferon signaling, IL-6 family cytokines, and γc-dependent cytokine
  pathways. Required for immune cell development, antiviral responses, and inflammatory
  processes. Mutations cause cancer (gain-of-function) or severe immunodeficiency
  (loss-of-function). Target of therapeutic JAK inhibitors.'
references:
  - id: PMID:8232552
    title: The protein tyrosine kinase JAK1 complements defects in 
      interferon-alpha/beta and -gamma signal transduction.
    findings: []
  - id: PMID:9590172
    title: Disruption of the Jak1 gene demonstrates obligatory and nonredundant 
      roles of the Jaks in cytokine-induced biologic responses.
    findings: []
  - id: PMID:7537214
    title: A major role for the protein tyrosine kinase JAK1 in the JAK/STAT 
      signal transduction pathway in response to interleukin-6.
    findings: []
  - id: file:human/JAK1/JAK1-deep-research.md
    title: 'Deep Research Report: JAK1 comprehensive analysis'
    findings: []
  - id: PMID:16273093
    title: A quantitative protein interaction network for the ErbB receptors 
      using protein microarrays.
    findings: []
  - id: GO_REF:0000033
    title: Gene Ontology inferred from electronic annotation (IBA)
    findings: []
  - id: GO_REF:0000002
    title: Gene Ontology inferred from electronic annotation based on InterPro
    findings: []
  - id: GO_REF:0000120
    title: Gene Ontology inferred from electronic annotation (IEA)
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology inferred from electronic annotation based on UniProtKB 
      keywords
    findings: []
  - id: GO_REF:0000117
    title: Gene Ontology inferred from electronic annotation based on ARBA
    findings: []
  - id: PMID:10502458
    title: The growth hormone receptor associates with Jak1, Jak2 and Tyk2 in 
      human liver.
    findings: []
  - id: PMID:10702271
    title: Interleukin (IL)-7 induces rapid activation of Pyk2, which is bound 
      to Janus kinase 1 and IL-7Ralpha.
    findings: []
  - id: PMID:10825200
    title: 'Hierarchy of protein tyrosine kinases in interleukin-2 (IL-2) signaling:
      activation of syk depends on Jak3; however, neither Syk nor Lck is required
      for IL-2-mediated STAT activation.'
    findings: []
  - id: PMID:11909529
    title: The T cell protein tyrosine phosphatase is a negative regulator of 
      janus family kinases 1 and 3.
    findings: []
  - id: PMID:12574355
    title: 'Human activation-induced cytidine deaminase is induced by IL-4 and negatively
      regulated by CD45: implication of CD45 as a Janus kinase phosphatase in antibody
      diversification.'
    findings: []
  - id: PMID:1386289
    title: A protein tyrosine kinase in the interferon alpha/beta signaling 
      pathway.
    findings: []
  - id: PMID:15226449
    title: Distinct regions of the interleukin-7 receptor regulate different 
      Bcl2 family members.
    findings: []
  - id: PMID:16280321
    title: The heat shock protein 90-CDC37 chaperone complex is required for 
      signaling by types I and II interferons.
    findings: []
  - id: PMID:16710296
    title: UBP43 is a novel regulator of interferon signaling independent of its
      ISG15 isopeptidase activity.
    findings: []
  - id: PMID:1848670
    title: Two novel protein-tyrosine kinases, each with a second 
      phosphotransferase-related catalytic domain, define a new class of protein
      kinase.
    findings: []
  - id: PMID:21220115
    title: Structural snapshots of full-length Jak1, a transmembrane 
      gp130/IL-6/IL-6Rα cytokine receptor complex, and the receptor-Jak1 
      holocomplex.
    findings: []
  - id: PMID:21679692
    title: The tight junction protein ZO-2 and Janus kinase 1 mediate 
      intercellular communications in vascular smooth muscle cells.
    findings: []
  - id: PMID:23139419
    title: Identification of STAT2 serine 287 as a novel regulatory 
      phosphorylation site in type I interferon-induced cellular responses.
    findings: []
  - id: PMID:23391734
    title: STAT2 deficiency and susceptibility to viral illness in humans.
    findings: []
  - id: PMID:24882218
    title: Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin 
      ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral 
      response.
    findings: []
  - id: PMID:25065853
    title: Drug resistance via feedback activation of Stat3 in oncogene-addicted
      cancer cells.
    findings: []
  - id: PMID:26175413
    title: CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor 
      Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.
    findings: []
  - id: PMID:26479788
    title: PARP9-DTX3L ubiquitin ligase targets host histone H2BJ and viral 3C 
      protease to enhance interferon signaling and control viral infection.
    findings: []
  - id: PMID:27893700
    title: Trans-presentation of IL-6 by dendritic cells is required for the 
      priming of pathogenic T(H)17 cells.
    findings: []
  - id: PMID:28111307
    title: JAK1 gain-of-function causes an autosomal dominant immune 
      dysregulatory and hypereosinophilic syndrome.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and
      disease networks.
    findings: []
  - id: PMID:28753426
    title: Methyltransferase SETD2-Mediated Methylation of STAT1 Is Critical for
      Interferon Antiviral Activity.
    findings: []
  - id: PMID:28781374
    title: IL-11 induces differentiation of myeloid-derived suppressor cells 
      through activation of STAT3 signalling pathway.
    findings: []
  - id: PMID:29202461
    title: IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell 
      expansion.
    findings: []
  - id: PMID:31892268
    title: Characterization of JAK1 Pseudokinase Domain in Cytokine Signaling.
    findings: []
  - id: PMID:32750333
    title: Complex Autoinflammatory Syndrome Unveils Fundamental Principles of 
      JAK1 Kinase Transcriptional and Biochemical Function.
    findings: []
  - id: PMID:32953130
    title: SARS-CoV-2 N protein antagonizes type I interferon signaling by 
      suppressing phosphorylation and nuclear translocation of STAT1 and STAT2.
    findings: []
  - id: PMID:33961781
    title: Dual proteome-scale networks reveal cell-specific remodeling of the 
      human interactome.
    findings: []
  - id: PMID:34813358
    title: IFNAR1 and IFNAR2 play distinct roles in initiating type I 
      interferon-induced JAK-STAT signaling and activating STATs.
    findings: []
  - id: PMID:34950606
    title: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Membrane
      (M) and Spike (S) Proteins Antagonize Host Type I Interferon Response.
    findings: []
  - id: PMID:35512704
    title: Systematic discovery of mutation-directed neo-protein-protein 
      interactions in cancer.
    findings: []
  - id: PMID:7526154
    title: Direct binding to and tyrosine phosphorylation of the alpha subunit 
      of the type I interferon receptor by p135tyk2 tyrosine kinase.
    findings: []
  - id: PMID:7532278
    title: Role of STAT2 in the alpha interferon signaling pathway.
    findings: []
  - id: PMID:7543512
    title: IL-10 induces the tyrosine phosphorylation of tyk2 and Jak1 and the 
      differential assembly of STAT1 alpha and STAT3 complexes in human T cells 
      and monocytes.
    findings: []
  - id: PMID:7568001
    title: Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus 
      kinases by interleukins 2 and 15.
    findings: []
  - id: PMID:7568005
    title: Critical role of the interleukin 2 (IL-2) receptor 
      gamma-chain-associated Jak3 in the IL-2-induced c-fos and c-myc, but not 
      bcl-2, gene induction.
    findings: []
  - id: PMID:7657660
    title: Phosphorylation and activation of the DNA binding activity of 
      purified Stat1 by the Janus protein-tyrosine kinases and the epidermal 
      growth factor receptor.
    findings: []
  - id: PMID:7759950
    title: Soluble and membrane-anchored forms of the human IFN-alpha/beta 
      receptor.
    findings: []
  - id: PMID:7760829
    title: Cloning of murine Stat6 and human Stat6, Stat proteins that are 
      tyrosine phosphorylated in responses to IL-4 and IL-3 but are not required
      for mitogenesis.
    findings: []
  - id: PMID:7929391
    title: JAK1 kinase forms complexes with interleukin-4 receptor and 
      4PS/insulin receptor substrate-1-like protein and is activated by 
      interleukin-4 and interleukin-9 in T lymphocytes.
    findings: []
  - id: PMID:7973659
    title: Functional activation of Jak1 and Jak3 by selective association with 
      IL-2 receptor subunits.
    findings: []
  - id: PMID:8272873
    title: Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 
      beta receptor components.
    findings: []
  - id: PMID:8605876
    title: Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a
      docking site for the latent form of the 113 kDa STAT2 protein.
    findings: []
  - id: PMID:8756628
    title: A single tyrosine of the interleukin-9 (IL-9) receptor is required 
      for STAT activation, antiapoptotic activity, and growth regulation by 
      IL-9.
    findings: []
  - id: PMID:9020188
    title: Stat2 is a transcriptional activator that requires sequence-specific 
      contacts provided by stat1 and p48 for stable interaction with DNA.
    findings: []
  - id: PMID:9446616
    title: Interferon gamma activation of Raf-1 is Jak1-dependent and 
      p21ras-independent.
    findings: []
  - id: PMID:9535918
    title: Heteromerization of the gammac chain with the interleukin-9 receptor 
      alpha subunit leads to STAT activation and prevention of apoptosis.
    findings: []
  - id: PMID:34521819
    title: 'INVALID: Cannot retrieve from PubMed (possibly replaced or retracted)'
    findings: []
    is_invalid: true
  - id: Reactome:R-HSA-1112602
    title: Tyrosine phosphorylation of STAT1, STAT3 by IL6 receptor
    findings: []
  - id: Reactome:R-HSA-1112703
    title: PTPN11 is phosphorylated
    findings: []
  - id: Reactome:R-HSA-452122
    title: JAK1 phosphorylates Y338, Y392 and Y510 of IL2RB
    findings: []
  - id: Reactome:R-HSA-6785807
    title: Interleukin-4 and Interleukin-13 signaling
    findings: []
  - id: Reactome:R-HSA-6786095
    title: JAK1 phosphorylates STAT3,STAT6
    findings: []
  - id: Reactome:R-HSA-6786096
    title: IL4R, IL2RG, JAK1 in IL4-bound IL4R1:JAK1 are phosphorylated
    findings: []
  - id: Reactome:R-HSA-873924
    title: Phosphorylation of IFNGR1 by JAK kinases
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt.
    findings: []
  - id: PMID:15864272
    title: Mechanisms of type-I- and type-II-interferon-mediated signalling.
    findings: []
  - id: PMID:20299512
    title: Members of the microRNA-17-92 cluster exhibit a cell-intrinsic 
      antiangiogenic function in endothelial cells.
    findings: []
  - id: PMID:20974963
    title: Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via 
      kinases JAK1 and JAK2 reveals a key difference from IL-7-induced 
      signaling.
    findings: []
  - id: PMID:21423176
    title: Analysis of the myosin-II-responsive focal adhesion proteome reveals 
      a role for β-Pix in negative regulation of focal adhesion maturation.
    findings: []
  - id: PMID:21854986
    title: Structural linkage between ligand discrimination and receptor 
      activation by type I interferons.
    findings: []
  - id: PMID:30936491
    title: Decoding type I and III interferon signalling during viral infection.
    findings: []
  - id: PMID:8272872
    title: Association of transcription factor APRF and protein kinase Jak1 with
      the interleukin-6 signal transducer gp130.
    findings: []
  - id: Reactome:R-HSA-1059683
    title: Interleukin-6 signaling
    findings: []
  - id: Reactome:R-HSA-1067651
    title: IL6:IL6R-2 binds IL6ST:JAK1, JAK2, (TYK2)
    findings: []
  - id: Reactome:R-HSA-1067659
    title: Assembly of hexameric IL-6 receptor
    findings: []
  - id: Reactome:R-HSA-1067688
    title: IL6:IL6R binds IL6ST:JAK1,JAK2,(TYK2)
    findings: []
  - id: Reactome:R-HSA-1112510
    title: IL6ST is tyrosine phosphorylated
    findings: []
  - id: Reactome:R-HSA-1112514
    title: JAK activation
    findings: []
  - id: Reactome:R-HSA-1112565
    title: Tyrosine phosphorylated IL6ST binds STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-1112604
    title: Phosphorylated STATs are released
    findings: []
  - id: Reactome:R-HSA-1112690
    title: PTPN11 binds CBL
    findings: []
  - id: Reactome:R-HSA-1112708
    title: PTPN11 binds p-Y759-IL6ST
    findings: []
  - id: Reactome:R-HSA-1112727
    title: Serine phosphorylation of STATs
    findings: []
  - id: Reactome:R-HSA-1112755
    title: SOCS3 binds IL6ST
    findings: []
  - id: Reactome:R-HSA-1169406
    title: ISGylation of host proteins
    findings: []
  - id: Reactome:R-HSA-1295540
    title: IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3:STAT5A,STAT5B phosphorylates STAT5
    findings: []
  - id: Reactome:R-HSA-1678841
    title: Regulation of protein ISGylation by ISG15 deconjugating enzyme USP18
    findings: []
  - id: Reactome:R-HSA-448427
    title: Interleukin-27 binds Interleukin-27 receptor
    findings: []
  - id: Reactome:R-HSA-448480
    title: IL22 binds IL22RA1:JAK1 receptor complex
    findings: []
  - id: Reactome:R-HSA-448660
    title: IL31:IL31RA:JAK1 binds OSMR:JAK1
    findings: []
  - id: Reactome:R-HSA-448661
    title: IFNL1 binds IL10RB:TYK2 and IFNLR1:JAK1
    findings: []
  - id: Reactome:R-HSA-448708
    title: IL24 binds to IL22RA1:JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-448728
    title: IL19 binds IL20RA:JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-448744
    title: IL20RA binds IL20RB
    findings: []
  - id: Reactome:R-HSA-449115
    title: IL15:IL15RA binds IL2RB:JAK1 and IL2RG:JAK3
    findings: []
  - id: Reactome:R-HSA-449803
    title: IL10 dimer binds IL10RA:JAK1
    findings: []
  - id: Reactome:R-HSA-449811
    title: IL10 dimer:2xIL10RA1:JAK1 binds IL10RB:TYK2
    findings: []
  - id: Reactome:R-HSA-449958
    title: IL7:IL7R:JAK1 binds IL2RG:JAK3
    findings: []
  - id: Reactome:R-HSA-449976
    title: IL11:IL11RA binds IL6ST:JAK1,JAK2,(TYK2)
    findings: []
  - id: Reactome:R-HSA-449978
    title: IL7 binds IL7R:JAK1
    findings: []
  - id: Reactome:R-HSA-450027
    title: Interleukin-2 receptor alpha:IL2 binds Interleukin-2 receptor beta
    findings: []
  - id: Reactome:R-HSA-450063
    title: 'Interleukin-2: IL2 receptor alpha:beta binds IL2 receptor gamma subunit'
    findings: []
  - id: Reactome:R-HSA-451900
    title: IL2RB binds JAK1
    findings: []
  - id: Reactome:R-HSA-451942
    title: Within the IL-2R complex JAK3 phosphorylates JAK1
    findings: []
  - id: Reactome:R-HSA-452091
    title: Phosphorylation of IL2RB Y338 enables SHC recruitment
    findings: []
  - id: Reactome:R-HSA-452097
    title: Recruited STAT5 is phosphorylated
    findings: []
  - id: Reactome:R-HSA-452100
    title: SHC1 bound to IL2 receptor is phosphorylated
    findings: []
  - id: Reactome:R-HSA-452108
    title: Phosphorylation of IL2RB Y338, Y392 or Y510 enables STAT recruitment
    findings: []
  - id: Reactome:R-HSA-453104
    title: Phosphorylated SHC1 recruits GRB2:GAB2
    findings: []
  - id: Reactome:R-HSA-453111
    title: Phosphorylated SHC recruits GRB2:SOS1
    findings: []
  - id: Reactome:R-HSA-508247
    title: Gab2 binds the p85 subunit of Class 1A PI3 kinases
    findings: []
  - id: Reactome:R-HSA-508282
    title: SYK is a substrate for JAK1
    findings: []
  - id: Reactome:R-HSA-508292
    title: SYK binds IL2RB
    findings: []
  - id: Reactome:R-HSA-5672965
    title: RAS GEFs promote RAS nucleotide exchange
    findings: []
  - id: Reactome:R-HSA-5696482
    title: CTF1 binds LIFR:JAKs
    findings: []
  - id: Reactome:R-HSA-6783524
    title: OSM,LIF,CTF1 receptor complex binds gp130
    findings: []
  - id: Reactome:R-HSA-6783530
    title: gp130:JAKs bind CNTFR
    findings: []
  - id: Reactome:R-HSA-6783552
    title: OSM binds LIFR:JAKs,OSMR:JAKs
    findings: []
  - id: Reactome:R-HSA-6783556
    title: LIFR:JAKs bind gp130:JAKs:CNTFR
    findings: []
  - id: Reactome:R-HSA-6783681
    title: LIF binds LIFR
    findings: []
  - id: Reactome:R-HSA-6784006
    title: STAT3 is phosphorylated by p-Y-JAK1,P-Y-TYK2
    findings: []
  - id: Reactome:R-HSA-6784189
    title: JAKs bind LIFR
    findings: []
  - id: Reactome:R-HSA-6784204
    title: JAKs bind OSMR
    findings: []
  - id: Reactome:R-HSA-6784319
    title: JAK1,TYK2 phosphorylate JAK1,TYK2
    findings: []
  - id: Reactome:R-HSA-6784323
    title: IL10 dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2 binds STAT3
    findings: []
  - id: Reactome:R-HSA-6784324
    title: p-Y-JAK1,p-Y-TYK2 phosphorylate IL10RA
    findings: []
  - id: Reactome:R-HSA-6784791
    title: p-Y705-STAT3 dissociates from IL10 
      dimer:2xp-Y-IL10RA:p-Y-JAK1:2xIL10RB:p-Y-TYK2:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-6785165
    title: p-STAT5A, p-STAT5B dissociate from 
      IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3:p-STAT5A,p-STAT5B
    findings: []
  - id: Reactome:R-HSA-6786050
    title: IL4R, IL13RA, JAK2 and TYK2 are tyrosine phosphorylated
    findings: []
  - id: Reactome:R-HSA-6786058
    title: JAK1 binds IL4R in IL4-bound IL4R1
    findings: []
  - id: Reactome:R-HSA-6786072
    title: p-Y705-STAT3,p-Y641-STAT6 dissociate
    findings: []
  - id: Reactome:R-HSA-6786110
    title: JAK1 binds IL4R in IL13-bound IL13R type II
    findings: []
  - id: Reactome:R-HSA-6786124
    title: STAT3,STAT6 bind p-Y-IL4R
    findings: []
  - id: Reactome:R-HSA-6788571
    title: STAT1,STAT3,STAT6 bind IL13:IL13R type II
    findings: []
  - id: Reactome:R-HSA-6788582
    title: STAT1,STAT3,STAT6 phosphorylation
    findings: []
  - id: Reactome:R-HSA-6788628
    title: p-Y-STATs dissociate
    findings: []
  - id: Reactome:R-HSA-6809140
    title: IL35 binds IL-12RB2:IL6ST receptor
    findings: []
  - id: Reactome:R-HSA-873918
    title: Transphosphorylation of JAK1
    findings: []
  - id: Reactome:R-HSA-873919
    title: Phosphorylation of JAK2
    findings: []
  - id: Reactome:R-HSA-873921
    title: Binding of STAT1 to p-IFNGR1
    findings: []
  - id: Reactome:R-HSA-873922
    title: Phosphorylation of STAT1 by JAK kinases
    findings: []
  - id: Reactome:R-HSA-873926
    title: IFNG dimer binds IFNGR
    findings: []
  - id: Reactome:R-HSA-873927
    title: Release of STAT1 dimer from active receptor unit
    findings: []
  - id: Reactome:R-HSA-877269
    title: SOCS-1 and SOCS-3 binds to p-JAK2
    findings: []
  - id: Reactome:R-HSA-877300
    title: Interferon gamma signaling
    findings: []
  - id: Reactome:R-HSA-8854645
    title: IL22:IL22RA1:JAK1 binds IL10RB:TYK2
    findings: []
  - id: Reactome:R-HSA-8950210
    title: Interleukin-27 dissociates from Interleukin-27 receptor
    findings: []
  - id: Reactome:R-HSA-8950340
    title: IL27RA and IL6ST are phosphorylated after IL27:IL27 receptor 
      interaction and JAK's phosphorylation
    findings: []
  - id: Reactome:R-HSA-8950405
    title: JAK1/JAK2 bound to IL35:IL6ST:IL12RB2 receptor are phosphorylated
    findings: []
  - id: Reactome:R-HSA-8950441
    title: p-Y701-STAT1 and p-Y705-STAT3 dissociate from IL27:IL27 receptor
    findings: []
  - id: Reactome:R-HSA-8950448
    title: STAT4 binds to IL12RB2 in Interleukin-12 receptor complex
    findings: []
  - id: Reactome:R-HSA-8950453
    title: JAK1/JAK2 bound to IL12RB2:IL6ST receptor phosphorylates STAT1 and 
      STAT4
    findings: []
  - id: Reactome:R-HSA-8950485
    title: STAT3 and STAT1 are phosphorylated by JAKs after IL27:IL27R 
      interaction
    findings: []
  - id: Reactome:R-HSA-8950518
    title: STAT1, STAT3 bind p-Y611-IL27RA from Interleukin-27:Interleukin-27 
      receptor complex
    findings: []
  - id: Reactome:R-HSA-8950537
    title: JAK1, JAK2, TYK2 in IL27:EBI3:IL27RA:JAK1:IL6ST:(JAK1,JAK2,TYK2) are 
      phosphorylated
    findings: []
  - id: Reactome:R-HSA-8950757
    title: IL12RB2 in IL12A:IL12RB1:p-Y-TYK2:IL12B:IL12RB2:p-JAK2 is 
      phosphorylated
    findings: []
  - id: Reactome:R-HSA-8952807
    title: p-Y693-STAT4 dissociates after IL12:IL12R interaction
    findings: []
  - id: Reactome:R-HSA-8963734
    title: IL9 binds IL9R:JAK1 and IL2RG:JAK3
    findings: []
  - id: Reactome:R-HSA-8982162
    title: p‑Y705-STAT3 dissociates from IL19:IL20RA:p-JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-8982163
    title: IL19:IL20RA:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8982165
    title: IL19:IL20RA:p‑JAK1:IL20RB binds STAT3
    findings: []
  - id: Reactome:R-HSA-8983003
    title: IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3:PI3K-regulatory subunits binds 
      IRS1,IRS2
    findings: []
  - id: Reactome:R-HSA-8983063
    title: JAK3 in IL7:p-Y449-IL7R:JAK1:IL2RG:JAK3 is phosphorylated
    findings: []
  - id: Reactome:R-HSA-8983298
    title: IL15 binds IL2RB:JAK1 and IL2RG:JAK3
    findings: []
  - id: Reactome:R-HSA-8983300
    title: IL15RA:IL15:IL2RB:JAK1:IL2RG:JAK3 phosphorylates JAK3 and JAK1
    findings: []
  - id: Reactome:R-HSA-8983335
    title: IL15:IL15RA:IL2RB:JAK1:IL2RG:JAK3 translocates from the plasma 
      membrane to the endosome
    findings: []
  - id: Reactome:R-HSA-8983371
    title: IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 phosphorylates 
      STAT3 and STAT5
    findings: []
  - id: Reactome:R-HSA-8983374
    title: p-Y-STAT3 and p-STAT5 dissociates from 
      IL15:IL15RA:IL2RB:p-JAK1:IL2RG:p-JAK3:p-Y-STAT3:p-STAT5
    findings: []
  - id: Reactome:R-HSA-8983378
    title: IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3 binds STAT3 and 
      STAT5
    findings: []
  - id: Reactome:R-HSA-8983384
    title: IL15:IL15RA:p-Y-IL2RB:p-Y-JAK1:p-Y-IL2RG:p-Y-JAK3:p-Y-SHC1:GRB2 binds
      SOS1,SOS2
    findings: []
  - id: Reactome:R-HSA-8983518
    title: IL35 binds IL6ST:IL6ST receptor
    findings: []
  - id: Reactome:R-HSA-8983834
    title: JAK1/JAK2/TYK2 bound to IL6ST:IL6ST are phosphorylated
    findings: []
  - id: Reactome:R-HSA-8983835
    title: JAK1/JAK2/TYK2 bound to IL6ST:IL6ST phosphorylate STAT1
    findings: []
  - id: Reactome:R-HSA-8983841
    title: STAT1 associates with IL6ST:IL6ST
    findings: []
  - id: Reactome:R-HSA-8983845
    title: p-STAT1 dissociates from IL6ST:IL6ST
    findings: []
  - id: Reactome:R-HSA-8983983
    title: p-STAT1 and p-STAT4 dissociate from IL12RB2:IL6ST receptor
    findings: []
  - id: Reactome:R-HSA-8983996
    title: STAT1 and STAT4 associate with IL12RB2:IL6ST receptor
    findings: []
  - id: Reactome:R-HSA-8984001
    title: IL35 binds IL27RA:IL12RB2 receptor
    findings: []
  - id: Reactome:R-HSA-8984012
    title: JAK1,JAK2 bound to IL27RA:IL12RB2 receptor are phosphorylated
    findings: []
  - id: Reactome:R-HSA-8984014
    title: JAK1,JAK2 bound to IL27RA:IL12RB2 receptor phosphorylate STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8984021
    title: STAT1,STAT3 associate with IL27RA:IL12RB2 receptor
    findings: []
  - id: Reactome:R-HSA-8984023
    title: p-STAT1, p-STAT3 dissociate from IL27RA:IL12RB2 receptor
    findings: []
  - id: Reactome:R-HSA-8985900
    title: p-Y701-STAT1, p-Y705-STAT3, p-Y649-STAT5 dissociates from 
      IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-8985914
    title: IL9:IL9R:JAK1:IL2RG:JAK3 phosphorylates JAK3
    findings: []
  - id: Reactome:R-HSA-8985929
    title: IL9:p-Y407-IL9R:JAK1:IL2RG:p-904,939-JAK3 binds STAT1, STAT3, STAT5A 
      or STAT5B
    findings: []
  - id: Reactome:R-HSA-8985973
    title: IL9R is phosphorylated by IL9:IL9R:JAK1:IL2RG:p-Y904,939-JAK3
    findings: []
  - id: Reactome:R-HSA-8985988
    title: IL9:p-Y116-IL9R:JAK1:IL2RG:p-904,939-JAK3:STAT3 phosphorylates STAT1,
      STAT3 or STAT5
    findings: []
  - id: Reactome:R-HSA-8986446
    title: IL26 binds IL20RA:JAK1
    findings: []
  - id: Reactome:R-HSA-8986480
    title: IL26:IL20RA:JAK1 binds IL10RB:TYK2
    findings: []
  - id: Reactome:R-HSA-8986972
    title: IL24 binds IL20RA:JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-8986985
    title: IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:STAT1 phosphorylates 
      STAT1, STAT2, STAT3, STAT4 and STAT5
    findings: []
  - id: Reactome:R-HSA-8986994
    title: IL26:IL20RA:JAK1:IL10RB:TYK2 phosphorylates JAK1, TYK2
    findings: []
  - id: Reactome:R-HSA-8986995
    title: IL22:IL22RA1:p-JAK1:IL10RB:p-TYK2 phosphorylates IL22RA
    findings: []
  - id: Reactome:R-HSA-8987012
    title: IL24:IL22RA1:JAK1:IL20RB phosphorylates JAK1
    findings: []
  - id: Reactome:R-HSA-8987014
    title: IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:PTPN11:IL10RB:p-TYK2 binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987015
    title: IL20 binds IL20RA:JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-8987033
    title: p-STAT1, p-Y-STAT2, p-STAT3, p-STAT4, p-STAT5 dissociates from 
      IFNL1:p-Y343,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2:p-STAT1,p-STAT2,p-STAT3,p-STAT4,p-STAT5
    findings: []
  - id: Reactome:R-HSA-8987039
    title: JAK1 binds IL20RA
    findings: []
  - id: Reactome:R-HSA-8987040
    title: IFNL1:IFNLR1:p-JAK1:IL10RB:p-TYK2 phosphorylates IFNLR1
    findings: []
  - id: Reactome:R-HSA-8987042
    title: IL22:IL22RA1:JAK1:IL10RB:TYK2 phosphorylates JAK1,TYK2
    findings: []
  - id: Reactome:R-HSA-8987043
    title: IL22RA1 binds JAK1
    findings: []
  - id: Reactome:R-HSA-8987063
    title: IL24:IL22RA1:p-JAK1:IL20RB binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987070
    title: IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:STAT3 phosphorylates 
      STAT3
    findings: []
  - id: Reactome:R-HSA-8987080
    title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1 binds STAT1, STAT3
    findings: []
  - id: Reactome:R-HSA-8987084
    title: IL19:IL20RA:JAK1:IL20RB phosphorylates JAK1
    findings: []
  - id: Reactome:R-HSA-8987096
    title: IL24:IL22RA1:p-JAK1:IL20RB:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8987097
    title: IL24:p-IL20RA:p-JAK1:IL20RB binds STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8987104
    title: IL20:IL20RA:JAK1:IL20RB:p‑JAK2,p‑JAK3 binds STAT3
    findings: []
  - id: Reactome:R-HSA-8987105
    title: IFNL2,IFNL3 bind IL10RB:TYK2 and IFNLR1:JAK1
    findings: []
  - id: Reactome:R-HSA-8987120
    title: JAK1 binds IFNLR1
    findings: []
  - id: Reactome:R-HSA-8987129
    title: JAK1 in IL24:IL20RA:JAK1:IL20RB is phosphorylated
    findings: []
  - id: Reactome:R-HSA-8987132
    title: IL22:p‑Y251,p‑Y301‑IL22RA1:p‑JAK1:PTPN11:IL10RB:p‑TYK2 binds PTPN11
    findings: []
  - id: Reactome:R-HSA-8987141
    title: IL20:IL20RA:JAK1:IL20RB:p-JAK3,p-JAK2:STAT3 phosphorylates STAT3
    findings: []
  - id: Reactome:R-HSA-8987150
    title: IL24:IL20RA:p-JAK1:IL20RB:STAT1,STAT3 phosphorylates STAT1 or STAT3
    findings: []
  - id: Reactome:R-HSA-8987156
    title: p-STAT3 dissociates from 
      IL20:IL20RA:JAK1:IL20RB:p-Y1007,Y1008-JAK2,p-JAK3
    findings: []
  - id: Reactome:R-HSA-8987161
    title: p-STAT3 dissociates from IL24:IL22RA1:p‑JAK1:IL20RB:p‑STAT3
    findings: []
  - id: Reactome:R-HSA-8987179
    title: IL20:IL20RA:JAK1:IL20RB:JAK2,JAK3 phosphorylates JAK2,JAK3
    findings: []
  - id: Reactome:R-HSA-8987202
    title: IFNL1:IFNLR1:JAK1:IL10RB:TYK2 phosphorylates JAK1,TYK2
    findings: []
  - id: Reactome:R-HSA-8987220
    title: IL20:IL20RA:JAK1:IL20RB binds JAK2,JAK3
    findings: []
  - id: Reactome:R-HSA-8987230
    title: p-STAT1 and p-STAT3 dissociates from IL26:IL10RB:p-TYK2:IL20RA:p-JAK1
    findings: []
  - id: Reactome:R-HSA-8987236
    title: p-Y705-STAT3 dissociates from  
      IL22:p-Y251,p-Y301-IL22RA1:p-JAK1:IL10RB:p-TYK2:p-Y705-STAT3
    findings: []
  - id: Reactome:R-HSA-8987255
    title: IL26:IL10RB:p-TYK2:IL20RA:p-JAK1:STAT1,STAT3  phosphorylates 
      STAT1,STAT3
    findings: []
  - id: Reactome:R-HSA-8987266
    title: IFNL1:p-Y434,Y517-IFNLR1:p-JAK1:IL10RB:p-TYK2 binds STAT1, STAT2, 
      STAT3, STAT4, STAT5
    findings: []
  - id: Reactome:R-HSA-8987270
    title: p-STAT1,p-STAT3 dissociate from 
      IL24:IL20RA:p-Y1022,Y1023-JAK1:IL20RB:p-STAT1, p-STAT3
    findings: []
  - id: Reactome:R-HSA-9005980
    title: IL21 binds IL21R:JAK1
    findings: []
  - id: Reactome:R-HSA-9006844
    title: IL21:IL21R:JAK1 binds IL2RG:JAK3
    findings: []
  - id: Reactome:R-HSA-9006850
    title: IL21 receptor JAK phosphorylation
    findings: []
  - id: Reactome:R-HSA-9006870
    title: IL21 receptor STAT phosphorylation
    findings: []
  - id: Reactome:R-HSA-9006873
    title: IL21 receptor STAT binding
    findings: []
  - id: Reactome:R-HSA-9009227
    title: IL20 binds to IL22RA1:JAK1:IL20RB
    findings: []
  - id: Reactome:R-HSA-9011748
    title: IL9R binds JAK1
    findings: []
  - id: Reactome:R-HSA-9020558
    title: Interleukin-2 signaling
    findings: []
  - id: Reactome:R-HSA-9025969
    title: IL7:p-Y449-IL7R:JAK1:IL2RG:p-JAK3 binds STAT5
    findings: []
  - id: Reactome:R-HSA-909552
    title: Phosphorylation of STAT1 at Ser727
    findings: []
  - id: Reactome:R-HSA-909718
    title: Formation of p-STAT1 homodimer
    findings: []
  - id: Reactome:R-HSA-909719
    title: Recruitment of STAT2 to p-IFNAR1
    findings: []
  - id: Reactome:R-HSA-909720
    title: IFN alpha/beta binds to IFNAR2
    findings: []
  - id: Reactome:R-HSA-909722
    title: Release of p-STAT2:p-STAT1 dimer
    findings: []
  - id: Reactome:R-HSA-909724
    title: Recruitment of IFNAR1
    findings: []
  - id: Reactome:R-HSA-909726
    title: Phosphorylation of STAT1
    findings: []
  - id: Reactome:R-HSA-909729
    title: Activation of JAK kinases
    findings: []
  - id: Reactome:R-HSA-909730
    title: Phosphorylation of INFAR1 by TYK2
    findings: []
  - id: Reactome:R-HSA-909732
    title: Phosphorylation of STAT2
    findings: []
  - id: Reactome:R-HSA-909733
    title: Interferon alpha/beta signaling
    findings: []
  - id: Reactome:R-HSA-912527
    title: SHC1 mediates cytokine-induced phosphorylation of GAB2
    findings: []
  - id: Reactome:R-HSA-913374
    title: Phosphorylated SHC1 recruits SHIP
    findings: []
  - id: Reactome:R-HSA-913424
    title: The SHC1:SHIP1 complex is stabilized by GRB2
    findings: []
  - id: Reactome:R-HSA-919404
    title: Phosphorylated STAT5 is released
    findings: []
  - id: Reactome:R-HSA-9674816
    title: p-Y546,Y584-PTPN11 (in CSF3 
      dimer:2xp-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:SHC:GRB2:PTPN11)
      dephosphorylates KRAS
    findings: []
  - id: Reactome:R-HSA-9677579
    title: CSF3 dimer (GCSF dimer) binds CSF3R:JAK1:LYN
    findings: []
  - id: Reactome:R-HSA-9677585
    title: CSF3 dimer:CSFR:LYN:JAK1 binds CSFR:LYN:JAK1
    findings: []
  - id: Reactome:R-HSA-9678561
    title: IFNGR1:JAK1:INFGR2:JAK2 binds JAK1,2 inhibitors
    findings: []
  - id: Reactome:R-HSA-9678935
    title: IFNAR2:JAK1:STAT2 binds JAK1,2 inhibitors
    findings: []
  - id: Reactome:R-HSA-9696179
    title: IFNAR2:JAK1:STAT2 binds type 1 interferon analogs
    findings: []
  - id: Reactome:R-HSA-9705738
    title: SOCS1,3 ubiquitinates CSF3R in SOCS1,3:p-4Y-CSF3R:CSF3 
      dimer:LYN:p-Y-JAK1:p-JAK2:p-SYK:p-HCK:p-TYK2:CUL5:ELOB:ELOC:RNF7
    findings: []
  - id: Reactome:R-HSA-9707977
    title: CSF3 
      dimer:2xK48polyUb-K655,p-4Y-CSF3R:LYN:p-Y-JAK1:p-JAK2:p-Y-SYK:p-HCK:p-TYK2
      translocates from the endocytic vesicle membrane to the lysosomal membrane
    findings: []
  - id: Reactome:R-HSA-9732729
    title: Activated JAK1 binds RAF1
    findings: []
  - id: Reactome:R-HSA-9732738
    title: JAK1-mediated phosphorylation of RAF1
    findings: []
  - id: Reactome:R-HSA-9732753
    title: JAK1-activated RAF1 phosphorylates MAPKs
    findings: []
  - id: Reactome:R-HSA-997309
    title: Dephosphorylation of STAT1 by SHP2
    findings: []
  - id: Reactome:R-HSA-997311
    title: Dephosphorylation of TYK2 by PTP1B
    findings: []
  - id: Reactome:R-HSA-997314
    title: Dephosphorylation of JAK1 by SHP1
    findings: []
existing_annotations:
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Well-supported core molecular function - JAK1 is a non-receptor 
        tyrosine kinase
      action: ACCEPT
      reason: This is JAK1's primary molecular function, extensively validated 
        by biochemical and functional studies. The IBA evidence is supported by 
        direct experimental evidence.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core biological process - JAK1 is a central component of JAK-STAT
        signaling
      action: ACCEPT
      reason: This is the canonical pathway mediated by JAK1. Essential for 
        multiple cytokine receptor signaling cascades.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Core biological process - JAK1 mediates signaling for multiple 
        cytokine families
      action: ACCEPT
      reason: JAK1 is required for Type I/II interferons, IL-6 family, and 
        γc-dependent cytokines. This is a fundamental process for JAK1.
  - term:
      id: GO:0035556
      label: intracellular signal transduction
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Accurate but general biological process
      action: KEEP_AS_NON_CORE
      reason: While accurate, this is too general. More specific cytokine 
        signaling terms better describe JAK1's function.
  - term:
      id: GO:0030154
      label: cell differentiation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Valid downstream process mediated by JAK1-dependent cytokines
      action: KEEP_AS_NON_CORE
      reason: JAK1 regulates cell differentiation indirectly through cytokine 
        signaling (e.g., lymphocyte development via IL-7), but this is a 
        downstream consequence rather than core function.
  - term:
      id: GO:0005131
      label: growth hormone receptor binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Specific receptor interaction supported by experimental evidence
      action: KEEP_AS_NON_CORE
      reason: JAK1 does bind growth hormone receptor, but this is one of many 
        receptor interactions. Core function is broader tyrosine kinase 
        activity.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Valid but less specific than protein tyrosine kinase activity
      action: KEEP_AS_NON_CORE
      reason: Accurate but GO:0004715 (non-membrane spanning protein tyrosine 
        kinase activity) is more specific and preferred.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Core molecular function - accurate and specific
      action: ACCEPT
      reason: This is JAK1's primary catalytic activity. Well-supported by 
        extensive biochemical evidence.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Essential cofactor binding for kinase activity
      action: ACCEPT
      reason: ATP binding is required for JAK1's tyrosine kinase activity. This 
        is a core molecular function.
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Too general - ATP binding is more specific for kinase function
      action: REMOVE
      reason: While JAK1 does bind nucleotides, this term is overly general and 
        uninformative. The more specific GO:0005524 (ATP binding) already 
        captures JAK1's requirement for ATP as a cofactor for its tyrosine 
        kinase activity. Per GO curation guidelines, overly general terms should
        be removed in favor of more specific functional annotations.
      additional_reference_ids:
        - file:human/JAK1/JAK1-deep-research.md
      supported_by:
        - reference_id: file:human/JAK1/JAK1-deep-research.md
          supporting_text: The kinase domain binds ATP and catalyzes the 
            transfer of the γ-phosphate to tyrosine residues on substrates
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Valid but less specific than protein tyrosine kinase activity
      action: KEEP_AS_NON_CORE
      reason: Accurate but too general. More specific tyrosine kinase terms are 
        preferred.
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Too general - represents broad enzyme class
      action: REMOVE
      reason: This is overly general and doesn't provide useful functional 
        information about JAK1's specific role as a tyrosine kinase.
  - term:
      id: GO:0022407
      label: regulation of cell-cell adhesion
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Downstream effect of JAK1 signaling in specific contexts
      action: KEEP_AS_NON_CORE
      reason: While JAK1 can influence cell adhesion through downstream 
        signaling, this is context-specific and not a core function.
  - term:
      id: GO:0046872
      label: metal ion binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: General cofactor binding - not specific to JAK1 function
      action: REMOVE
      reason: Too general and not informative about JAK1's specific biological 
        role. Many proteins bind metal ions.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16273093
    review:
      summary: General protein binding - lacks specificity per GO curation 
        guidelines
      action: REMOVE
      reason: Generic protein binding annotations are removed per GO curation 
        guidelines in favor of more specific functional terms. PMID:16273093 is 
        a protein microarray study showing ErbB receptor interactions, but this 
        doesn't provide specific functional information about JAK1's role. 
        JAK1's specific receptor binding functions are better captured by terms 
        like cytokine receptor binding.
      additional_reference_ids:
        - file:human/JAK1/JAK1-deep-research.md
      supported_by:
        - reference_id: PMID:16273093
          supporting_text: A quantitative protein interaction network for the 
            ErbB receptors using protein microarrays.
  - term:
      id: GO:0031730
      label: CCR5 chemokine receptor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Specific receptor binding interaction
      action: KEEP_AS_NON_CORE
      reason: JAK1 can bind CCR5 chemokine receptor, but this is a specific 
        interaction among many. Core function is broader tyrosine kinase 
        activity.
  - term:
      id: GO:0035771
      label: interleukin-4-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:12574355
    review:
      summary: Specific cytokine pathway mediated by JAK1 supported by direct 
        experimental evidence
      action: ACCEPT
      reason: PMID:12574355 demonstrates that IL-4 induces AID expression via 
        "IL-4-activated JAK1, JAK3, and STAT6 phosphorylations" providing direct
        evidence for JAK1's essential role in IL-4 signaling.
      supported_by:
        - reference_id: PMID:12574355
          supporting_text: IL-4-dependent AID induction was inhibited by a 
            dominant-negative STAT6, indicating that IL-4 induced AID expression
            via the Janus kinase (JAK)/STAT6 signaling pathway. Moreover, 
            triggering of CD45 with anti-CD45 Abs can inhibit IL-4-induced AID 
            expression, and this CD45-mediated AID inhibition correlated with 
            the ability of anti-CD45 to suppress IL-4-activated JAK1, JAK3, and 
            STAT6 phosphorylations
  - term:
      id: GO:0038111
      label: interleukin-7-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:29202461
    retired: true
    review:
      summary: Critical cytokine pathway for lymphocyte development
      action: ACCEPT
      reason: JAK1 is essential for IL-7 signaling, which is crucial for T-cell 
        and B-cell development. Core pathway for JAK1.
      supported_by:
        - reference_id: PMID:29202461
          supporting_text: The phosphorylated active form of JAK3 then 
            phosphorylates tyrosine 449 on IL-7Rα, generating a docking site for
            the signal transducers and activators of transcription 5 (STAT5)
  - term:
      id: GO:0072540
      label: T-helper 17 cell lineage commitment
    evidence_type: TAS
    original_reference_id: PMID:27893700
    review:
      summary: Downstream differentiation process mediated by JAK1
      action: KEEP_AS_NON_CORE
      reason: JAK1 contributes to Th17 differentiation through cytokine 
        signaling, but this is a downstream consequence rather than core 
        function.
      supported_by:
        - reference_id: PMID:27893700
          supporting_text: Trans-presentation of IL-6 by dendritic cells is 
            required for the priming of pathogenic T(H)17 cells.
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:28753426
    retired: true
    review:
      summary: Downstream transcriptional effect of JAK1 signaling
      action: KEEP_AS_NON_CORE
      reason: JAK1 regulates transcription indirectly through STAT activation, 
        but the core function is tyrosine kinase activity.
      supported_by:
        - reference_id: PMID:28753426
          supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1
            Is Critical for Interferon Antiviral Activity.
  - term:
      id: GO:1900182
      label: positive regulation of protein localization to nucleus
    evidence_type: IDA
    original_reference_id: PMID:26479788
    review:
      summary: Nuclear translocation regulation through JAK1 signaling
      action: KEEP_AS_NON_CORE
      reason: JAK1 promotes STAT nuclear translocation, but this is a 
        consequence of its kinase activity.
      supported_by:
        - reference_id: PMID:26479788
          supporting_text: PARP9-DTX3L ubiquitin ligase targets host histone 
            H2BJ and viral 3C protease to enhance interferon signaling and 
            control viral infection.
  - term:
      id: GO:0060337
      label: type I interferon-mediated signaling pathway
    evidence_type: IMP
    original_reference_id: PMID:23391734
    retired: true
    review:
      summary: Core cytokine pathway - JAK1 essential for Type I IFN responses
      action: ACCEPT
      reason: Type I interferon signaling is absolutely dependent on JAK1. This 
        is a core biological process for JAK1.
      supported_by:
        - reference_id: PMID:23391734
          supporting_text: Patient fibroblasts were indeed abnormally permissive
            for viral replication in vitro, associated with profound failure of 
            type I IFN signaling and absence of STAT2 protein
  - term:
      id: GO:0035723
      label: interleukin-15-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7568001
    review:
      summary: Specific γc-dependent cytokine pathway mediated by JAK1
      action: ACCEPT
      reason: IL-15 signaling through γc receptor requires JAK1. Core cytokine 
        pathway function.
      supported_by:
        - reference_id: PMID:7568001
          supporting_text: IL-2 and IL-15 rapidly induced the tyrosine 
            phosphorylation of STAT3 and STAT5, and DNA-binding complexes 
            containing STAT3 and STAT5 were rapidly activated by these cytokines
            in T cells
  - term:
      id: GO:0038110
      label: interleukin-2-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7568005
    retired: true
    review:
      summary: Core γc-dependent cytokine pathway requiring JAK1
      action: ACCEPT
      reason: IL-2 is a prototypical γc cytokine requiring JAK1 for signaling. 
        Core function.
      supported_by:
        - reference_id: PMID:7568005
          supporting_text: Two Janus family protein tyrosine kinases (PTKs), 
            Jak1 and Jak3, were shown to associate with IL-2R beta c and IL-2R 
            gamma c, respectively, and their PTK activities are increased after 
            IL-2 stimulation
  - term:
      id: GO:0038154
      label: interleukin-11-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:28781374
    retired: true
    review:
      summary: gp130-dependent cytokine pathway mediated by JAK1
      action: ACCEPT
      reason: IL-11 signals through gp130 receptor and requires JAK1. Core IL-6 
        family cytokine function.
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0140105
      label: interleukin-10-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7543512
    review:
      summary: IL-10 cytokine signaling pathway requiring JAK1
      action: ACCEPT
      reason: IL-10 signaling requires JAK1 for STAT activation. Core 
        anti-inflammatory cytokine pathway.
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: IL-10 induces the tyrosine phosphorylation of tyk2 
            and Jak1 and the differential assembly of STAT1 alpha and STAT3 
            complexes in human T cells and monocytes.
  - term:
      id: GO:0038113
      label: interleukin-9-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:9535918
    retired: true
    review:
      summary: γc-dependent cytokine pathway mediated by JAK1
      action: ACCEPT
      reason: IL-9 signals through γc receptor and requires JAK1. Core cytokine 
        signaling function.
      supported_by:
        - reference_id: PMID:9535918
          supporting_text: Heteromerization of the gammac chain with the 
            interleukin-9 receptor alpha subunit leads to STAT activation and 
            prevention of apoptosis
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: IMP
    original_reference_id: PMID:28111307
    review:
      summary: Core catalytic activity of JAK1 as a tyrosine kinase
      action: ACCEPT
      reason: Protein phosphorylation is the fundamental enzymatic activity of 
        JAK1. Core molecular function.
      supported_by:
        - reference_id: PMID:28111307
          supporting_text: JAK1 gain-of-function causes an autosomal dominant 
            immune dysregulatory and hypereosinophilic syndrome.
  - term:
      id: GO:0031625
      label: ubiquitin protein ligase binding
    evidence_type: IPI
    original_reference_id: PMID:24882218
    review:
      summary: Regulatory interaction for JAK1 degradation control
      action: KEEP_AS_NON_CORE
      reason: JAK1 binds ubiquitin ligases for regulation, but this is 
        regulatory rather than core function.
      supported_by:
        - reference_id: PMID:24882218
          supporting_text: 2014 May 29. Unanchored K48-linked polyubiquitin 
            synthesized by the E3-ubiquitin ligase TRIM6 stimulates the 
            interferon-IKKε kinase-mediated antiviral response.
  - term:
      id: GO:0034112
      label: positive regulation of homotypic cell-cell adhesion
    evidence_type: IMP
    original_reference_id: PMID:21679692
    review:
      summary: Downstream cellular effect of JAK1 signaling
      action: KEEP_AS_NON_CORE
      reason: Cell adhesion regulation is a downstream consequence of JAK1 
        signaling in specific contexts.
      supported_by:
        - reference_id: PMID:21679692
          supporting_text: The tight junction protein ZO-2 and Janus kinase 1 
            mediate intercellular communications in vascular smooth muscle 
            cells.
  - term:
      id: GO:0019903
      label: protein phosphatase binding
    evidence_type: IPI
    original_reference_id: PMID:11909529
    review:
      summary: Regulatory interaction for JAK1 activity control
      action: KEEP_AS_NON_CORE
      reason: Phosphatase binding regulates JAK1 activity but is not the core 
        function.
      supported_by:
        - reference_id: PMID:11909529
          supporting_text: The T cell protein tyrosine phosphatase is a negative
            regulator of janus family kinases 1 and 3.
  - term:
      id: GO:0046677
      label: response to antibiotic
    evidence_type: IDA
    original_reference_id: PMID:16280321
    review:
      summary: Context-specific response mediated through JAK1 signaling
      action: KEEP_AS_NON_CORE
      reason: Antibiotic response is context-specific and not representative of 
        JAK1's core function.
      supported_by:
        - reference_id: PMID:16280321
          supporting_text: 2005 Nov 9. The heat shock protein 90-CDC37 chaperone
            complex is required for signaling by types I and II interferons.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: Duplicate annotation - cytokine-mediated signaling
      action: ACCEPT
      reason: Valid annotation for JAK1's role in cytokine signaling, even 
        though duplicated.
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Duplicate annotation - non-membrane spanning kinase
      action: ACCEPT
      reason: Valid annotation for JAK1's kinase activity, even though 
        duplicated.
  - term:
      id: GO:0035556
      label: intracellular signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: Accurate but general biological process
      action: KEEP_AS_NON_CORE
      reason: While accurate, this is too general. More specific terms like 
        JAK-STAT pathway and cytokine signaling better describe JAK1's core 
        function.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Duplicate annotation - JAK-STAT pathway
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling, even 
        though duplicated.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Duplicate annotation - cytokine signaling
      action: ACCEPT
      reason: Valid annotation for JAK1's cytokine signaling role, even though 
        duplicated.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16710296
    review:
      summary: UBP43 direct binding interaction confirmed by experimental 
        evidence
      action: REMOVE
      reason: PMID:16710296 demonstrates that "Ubp43 specifically binds to the 
        IFNAR2 receptor subunit and inhibits the activity of receptor-associated
        JAK1." While this shows direct binding, generic protein binding 
        annotations are removed per GO curation guidelines in favor of more 
        specific functional terms.
      supported_by:
        - reference_id: PMID:16710296
          supporting_text: May 18. UBP43 is a novel regulator of interferon 
            signaling independent of its ISG15 isopeptidase activity.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21220115
    review:
      summary: Structural study showing JAK1 binding to gp130/IL-6 receptor 
        complex
      action: MODIFY
      reason: PMID:21220115 provides structural snapshots of full-length JAK1 in
        complex with gp130/IL-6/IL-6Rα cytokine receptor complex. This 
        demonstrates specific receptor binding rather than generic protein 
        binding. The interaction should be captured as cytokine receptor 
        binding, which is more informative than generic protein binding.
      proposed_replacement_terms:
        - id: GO:0005126
          label: cytokine receptor binding
      additional_reference_ids:
        - file:human/JAK1/JAK1-deep-research.md
      supported_by:
        - reference_id: PMID:21220115
          supporting_text: Structural snapshots of full-length Jak1, a 
            transmembrane gp130/IL-6/IL-6Rα cytokine receptor complex, and the 
            receptor-Jak1 holocomplex
        - reference_id: file:human/JAK1/JAK1-deep-research.md
          supporting_text: Through its N-terminal domains, JAK1 is tightly but 
            non-covalently associated with membrane-proximal regions of type I 
            and II cytokine receptors
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:25065853
    review:
      summary: STAT3 binding in drug resistance context
      action: REMOVE
      reason: Drug resistance study showing feedback activation. Not informative
        for normal JAK1 function.
      supported_by:
        - reference_id: PMID:25065853
          supporting_text: 2014 Jul 24. Drug resistance via feedback activation 
            of Stat3 in oncogene-addicted cancer cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26175413
    review:
      summary: JAK2 interaction in JAK inhibitor study
      action: REMOVE
      reason: JAK inhibitor drug study, not informative for normal JAK1 
        function.
      supported_by:
        - reference_id: PMID:26175413
          supporting_text: CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK
            Inhibitor Persistence and Demonstrates Efficacy in 
            Myeloproliferative Neoplasms.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: Large-scale interactome study
      action: REMOVE
      reason: General proteome-wide interactome study, uninformative generic 
        protein binding.
      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein
            communities and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:32953130
    review:
      summary: SARS-CoV-2 N protein interaction - viral immune evasion mechanism
      action: REMOVE
      reason: While PMID:32953130 demonstrates that SARS-CoV-2 N protein 
        antagonizes JAK1 function by suppressing STAT1/STAT2 phosphorylation and
        nuclear translocation, this represents a pathological interaction during
        viral infection rather than normal JAK1 function. Generic protein 
        binding annotations are removed per GO curation guidelines, and this 
        specific viral interaction is not representative of JAK1's core cellular
        functions.
      additional_reference_ids:
        - file:human/JAK1/JAK1-deep-research.md
      supported_by:
        - reference_id: PMID:32953130
          supporting_text: SARS-CoV-2 N protein antagonizes type I interferon 
            signaling by suppressing phosphorylation and nuclear translocation 
            of STAT1 and STAT2
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: Dual proteome-scale network study
      action: REMOVE
      reason: Large-scale proteome study, uninformative generic protein binding.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34521819
    review:
      summary: Invalid PMID - cannot retrieve
      action: REMOVE
      reason: PMID appears to be invalid or retracted, cannot verify 
        interaction.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34950606
    review:
      summary: SARS-CoV-2 protein interactions
      action: REMOVE
      reason: Duplicate viral antagonism study, already covered by 
        PMID:32953130.
      supported_by:
        - reference_id: PMID:34950606
          supporting_text: Severe Acute Respiratory Syndrome Coronavirus 2 
            (SARS-CoV-2) Membrane (M) and Spike (S) Proteins Antagonize Host 
            Type I Interferon Response.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:35512704
    review:
      summary: Cancer mutation-directed interactions
      action: REMOVE
      reason: Mutation-specific interactions in cancer, not representative of 
        normal JAK1 function.
      supported_by:
        - reference_id: PMID:35512704
          supporting_text: 2022 May 4. Systematic discovery of mutation-directed
            neo-protein-protein interactions in cancer.
  - term:
      id: GO:0005131
      label: growth hormone receptor binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: Specific receptor interaction but not core function
      action: KEEP_AS_NON_CORE
      reason: JAK1 does bind growth hormone receptor, but this is one of many 
        receptor interactions. Core function is broader tyrosine kinase activity
        for multiple cytokine receptors.
  - term:
      id: GO:0019221
      label: cytokine-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6785807
    review:
      summary: Duplicate annotation from Reactome
      action: ACCEPT
      reason: Valid annotation from Reactome pathway analysis, even though 
        duplicated.
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112602
    review:
      summary: Duplicate Reactome annotation - IL6 receptor signaling
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's role in IL-6 signaling.
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112703
    review:
      summary: Duplicate Reactome annotation - PTPN11 phosphorylation
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's kinase activity.
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786095
    review:
      summary: Duplicate Reactome annotation - STAT3/STAT6 phosphorylation
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's role in STAT 
        phosphorylation.
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786096
    review:
      summary: Duplicate Reactome annotation - IL4R phosphorylation
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's role in IL-4 signaling.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: EXP
    original_reference_id: PMID:10825200
    review:
      summary: IL-2 signaling hierarchy study
      action: ACCEPT
      reason: Experimental evidence for JAK1's tyrosine kinase activity in IL-2 
        signaling. Core function.
      supported_by:
        - reference_id: PMID:10825200
          supporting_text: Interleukin-2 (IL-2) activates several different 
            families of tyrosine kinases, but precisely how these kinases 
            interact is not completely understood
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: EXP
    original_reference_id: PMID:1386289
    review:
      summary: Early characterization of JAK1 in interferon signaling
      action: ACCEPT
      reason: Foundational paper demonstrating JAK1's tyrosine kinase activity 
        in IFN signaling. Core function.
      supported_by:
        - reference_id: PMID:1386289
          supporting_text: A protein tyrosine kinase in the interferon 
            alpha/beta signaling pathway
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: EXP
    original_reference_id: PMID:9446616
    review:
      summary: IFN-gamma activation of Raf-1 via JAK1
      action: ACCEPT
      reason: Experimental evidence for JAK1 kinase activity in IFN-gamma 
        signaling. Core function.
      supported_by:
        - reference_id: PMID:9446616
          supporting_text: Interferon gamma activation of Raf-1 is 
            Jak1-dependent and p21ras-independent
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452122
    review:
      summary: Reactome annotation - IL2RB phosphorylation
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's kinase activity in IL-2 
        signaling.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873924
    review:
      summary: Reactome annotation - IFNGR1 phosphorylation
      action: ACCEPT
      reason: Valid annotation from Reactome for JAK1's role in IFN-gamma 
        signaling.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: NAS
    original_reference_id: PMID:12574355
    review:
      summary: Duplicate JAK-STAT pathway annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:12574355
          supporting_text: IL-4-dependent AID induction was inhibited by a 
            dominant-negative STAT6, indicating that IL-4 induced AID expression
            via the Janus kinase (JAK)/STAT6 signaling pathway
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:8272873
    review:
      summary: JAK-Tyk kinases in IL-6 family signaling
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity in IL-6 family cytokine 
        signaling. Core function.
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:8272873
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: PMID:34813358
    review:
      summary: IFNAR1/IFNAR2 distinct roles study
      action: ACCEPT
      reason: Valid annotation for JAK1's kinase activity in interferon 
        signaling.
      supported_by:
        - reference_id: PMID:34813358
          supporting_text: Ligand binding results in the cross-phosphorylation 
            of TYK2 and JAK1, which then phosphorylate tyrosine residues in the 
            ICDs of the receptor subunits and members of the STAT family of 
            transcription factors
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:7657660
    review:
      summary: STAT1 phosphorylation by JAK1
      action: ACCEPT
      reason: Valid annotation for JAK1's kinase activity.
      supported_by:
        - reference_id: PMID:7657660
          supporting_text: Co-expression of Stat1 with Tyk2, Jak1, or Jak2 
            resulted in the specific tyrosine phosphorylation of Stat1 at Tyr701
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: PMID:8232552
    review:
      summary: Core molecular function confirmed by foundational interferon 
        signaling study
      action: ACCEPT
      reason: PMID:8232552 established that JAK1 is "completely defective in 
        interferon response" when absent and "complementation of this mutant 
        with JAK1 restored the response," demonstrating JAK1's essential 
        tyrosine kinase activity in interferon signaling.
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction
  - term:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:8232552
    review:
      summary: Duplicate annotation from key interferon paper
      action: ACCEPT
      reason: Valid annotation from foundational JAK1 paper.
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction
  - term:
      id: GO:0006357
      label: regulation of transcription by RNA polymerase II
    evidence_type: IDA
    original_reference_id: PMID:9020188
    retired: true
    review:
      summary: STAT2 transcriptional activation
      action: KEEP_AS_NON_CORE
      reason: JAK1 regulates transcription indirectly through STAT activation. 
        Downstream effect.
      supported_by:
        - reference_id: PMID:9020188
          supporting_text: Stat2 is a transcriptional activator that requires 
            sequence-specific contacts provided by stat1 and p48 for stable 
            interaction with DNA.
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:23139419
    retired: true
    review:
      summary: STAT2 Ser287 phosphorylation in IFN signaling
      action: ACCEPT
      reason: Valid annotation for JAK1's role in interferon signaling.
      supported_by:
        - reference_id: PMID:23139419
          supporting_text: Identification of STAT2 serine 287 as a novel 
            regulatory phosphorylation site in type I interferon-induced 
            cellular responses
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:28753426
    retired: true
    review:
      summary: SETD2-mediated STAT1 methylation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in STAT signaling.
      supported_by:
        - reference_id: PMID:28753426
          supporting_text: Methyltransferase SETD2-Mediated Methylation of STAT1
            Is Critical for Interferon Antiviral Activity
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:7526154
    retired: true
    review:
      summary: TYK2 binding to IFN receptor
      action: ACCEPT
      reason: Valid annotation for JAK1's role in interferon signaling.
      supported_by:
        - reference_id: PMID:7526154
          supporting_text: Direct binding to and tyrosine phosphorylation of the
            alpha subunit of the type I interferon receptor by p135tyk2 tyrosine
            kinase
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:7657660
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:7657660
          supporting_text: Phosphorylation and activation of the DNA binding 
            activity of purified Stat1 by the Janus protein-tyrosine kinases and
            the epidermal growth factor receptor
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:7759950
    retired: true
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:7759950
          supporting_text: Soluble and membrane-anchored forms of the human 
            IFN-alpha/beta receptor
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:8605876
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:8605876
          supporting_text: Phosphorylated interferon-alpha receptor 1 subunit 
            (IFNaR1) acts as a docking site for the latent form of the 113 kDa 
            STAT2 protein
    retired: true
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: TAS
    original_reference_id: PMID:8232552
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IDA
    original_reference_id: PMID:8232552
    review:
      summary: Duplicate JAK-STAT annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction
  - term:
      id: GO:1900182
      label: positive regulation of protein localization to nucleus
    evidence_type: IDA
    original_reference_id: PMID:8605876
    review:
      summary: STAT2 nuclear localization
      action: KEEP_AS_NON_CORE
      reason: JAK1 promotes STAT nuclear translocation, but this is downstream 
        of kinase activity.
      supported_by:
        - reference_id: PMID:8605876
          supporting_text: Phosphorylated interferon-alpha receptor 1 subunit 
            (IFNaR1) acts as a docking site for the latent form of the 113 kDa 
            STAT2 protein.
    retired: true
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:7532278
    review:
      summary: STAT2 in IFN signaling pathway
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity. Core function.
      supported_by:
        - reference_id: PMID:7532278
          supporting_text: Role of STAT2 in the alpha interferon signaling 
            pathway
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:7973659
    review:
      summary: JAK1 and JAK3 with IL-2 receptor
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity in IL-2 signaling. Core 
        function.
      supported_by:
        - reference_id: PMID:7973659
          supporting_text: Functional activation of Jak1 and Jak3 by selective 
            association with IL-2 receptor subunits
  - term:
      id: GO:0030154
      label: cell differentiation
    evidence_type: IDA
    original_reference_id: PMID:28781374
    retired: true
    review:
      summary: IL-11-induced MDSC differentiation
      action: KEEP_AS_NON_CORE
      reason: JAK1 contributes to cell differentiation through IL-11 signaling, 
        but this is downstream.
      supported_by:
        - reference_id: PMID:28781374
          supporting_text: IL-11 induces differentiation of myeloid-derived 
            suppressor cells through activation of STAT3 signalling pathway.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IC
    original_reference_id: PMID:7543512
    review:
      summary: IL-10 induced JAK1 phosphorylation
      action: ACCEPT
      reason: Inferred from IL-10 signaling studies. Core kinase function.
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: '# IL-10 induces the tyrosine phosphorylation of tyk2 and
            Jak1 and the differential assembly of STAT1 alpha and STAT3 complexes
            in human T cells and monocytes...'
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:8756628
    review:
      summary: IL-9 receptor signaling
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity in IL-9 signaling. Core 
        function.
      supported_by:
        - reference_id: PMID:8756628
          supporting_text: A single tyrosine of the interleukin-9 (IL-9) 
            receptor is required for STAT activation, antiapoptotic activity, 
            and growth regulation by IL-9
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:10702271
    review:
      summary: IL-7 induced Pyk2 activation
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity in IL-7 signaling. Core 
        function.
      supported_by:
        - reference_id: PMID:10702271
          supporting_text: Interleukin (IL)-7 induces rapid activation of Pyk2, 
            which is bound to Janus kinase 1 and IL-7Ralpha
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:15226449
    review:
      summary: IL-7 receptor and Bcl2 regulation
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity. Core function.
      supported_by:
        - reference_id: PMID:15226449
          supporting_text: Distinct regions of the interleukin-7 receptor 
            regulate different Bcl2 family members
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:7929391
    review:
      summary: IL-4 and IL-9 receptor activation
      action: ACCEPT
      reason: Direct evidence for JAK1 kinase activity in IL-4/IL-9 signaling. 
        Core function.
      supported_by:
        - reference_id: PMID:7929391
          supporting_text: JAK1 kinase forms complexes with interleukin-4 
            receptor and 4PS/insulin receptor substrate-1-like protein and is 
            activated by interleukin-4 and interleukin-9 in T lymphocytes
  - term:
      id: GO:0035771
      label: interleukin-4-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7760829
    review:
      summary: Duplicate IL-4 pathway annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's role in IL-4 signaling.
      supported_by:
        - reference_id: PMID:7760829
          supporting_text: Cloning of murine Stat6 and human Stat6, Stat 
            proteins that are tyrosine phosphorylated in responses to IL-4 and 
            IL-3 but are not required for mitogenesis
    retired: true
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: EXP
    original_reference_id: PMID:31892268
    review:
      summary: JAK1 pseudokinase domain characterization
      action: ACCEPT
      reason: Experimental evidence for JAK1 kinase activity and regulation. 
        Core function.
      supported_by:
        - reference_id: PMID:31892268
          supporting_text: Characterization of JAK1 Pseudokinase Domain in 
            Cytokine Signaling
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IMP
    original_reference_id: PMID:28111307
    review:
      summary: JAK1 gain-of-function syndrome
      action: ACCEPT
      reason: Valid annotation demonstrating JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:28111307
          supporting_text: JAK1 gain-of-function causes an autosomal dominant 
            immune dysregulatory and hypereosinophilic syndrome
  - term:
      id: GO:0007259
      label: cell surface receptor signaling pathway via JAK-STAT
    evidence_type: IMP
    original_reference_id: PMID:32750333
    review:
      summary: Autoinflammatory syndrome study
      action: ACCEPT
      reason: Valid annotation demonstrating JAK1's role in JAK-STAT signaling.
      supported_by:
        - reference_id: PMID:32750333
          supporting_text: Complex Autoinflammatory Syndrome Unveils Fundamental
            Principles of JAK1 Kinase Transcriptional and Biochemical Function
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: IMP
    original_reference_id: PMID:32750333
    review:
      summary: Duplicate protein phosphorylation annotation
      action: ACCEPT
      reason: Valid annotation for JAK1's phosphorylation activity.
      supported_by:
        - reference_id: PMID:32750333
          supporting_text: Complex Autoinflammatory Syndrome Unveils Fundamental
            Principles of JAK1 Kinase Transcriptional and Biochemical Function
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21679692
    review:
      summary: ZO-2 binding in smooth muscle cells
      action: REMOVE
      reason: Context-specific protein interaction, not informative for JAK1 
        core function.
      supported_by:
        - reference_id: PMID:21679692
          supporting_text: The tight junction protein ZO-2 and Janus kinase 1 
            mediate intercellular communications in vascular smooth muscle 
            cells.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:7759950
    review:
      summary: Type I IFN receptor binding - demonstrates receptor-kinase 
        association
      action: MODIFY
      reason: PMID:7759950 describes soluble and membrane-anchored forms of the 
        human IFN-α/β receptor, establishing the foundation for understanding 
        JAK1's association with IFNAR receptor subunits. This represents 
        specific cytokine receptor binding rather than generic protein binding. 
        The interaction is better captured as cytokine receptor binding, which 
        is more functionally informative.
      proposed_replacement_terms:
        - id: GO:0005126
          label: cytokine receptor binding
      additional_reference_ids:
        - file:human/JAK1/JAK1-deep-research.md
      supported_by:
        - reference_id: PMID:7759950
          supporting_text: Soluble and membrane-anchored forms of the human 
            IFN-alpha/beta receptor
        - reference_id: file:human/JAK1/JAK1-deep-research.md
          supporting_text: JAK1 associates with the IFNAR2 receptor subunit, 
            while TYK2 associates with IFNAR1
  - term:
      id: GO:0005131
      label: growth hormone receptor binding
    evidence_type: ISS
    original_reference_id: PMID:10502458
    review:
      summary: Growth hormone receptor association
      action: KEEP_AS_NON_CORE
      reason: JAK1 does bind GH receptor, but this is one of many receptor 
        interactions.
      supported_by:
        - reference_id: PMID:10502458
          supporting_text: The growth hormone receptor associates with Jak1, 
            Jak2 and Tyk2 in human liver.
  - term:
      id: GO:0004713
      label: protein tyrosine kinase activity
    evidence_type: TAS
    original_reference_id: PMID:1848670
    review:
      summary: Early JAK1 characterization paper
      action: ACCEPT
      reason: Foundational paper identifying JAK1 as a tyrosine kinase. Core 
        function.
      supported_by:
        - reference_id: PMID:1848670
          supporting_text: Two novel protein-tyrosine kinases, each with a 
            second phosphotransferase-related catalytic domain, define a new 
            class of protein kinase
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: TAS
    original_reference_id: PMID:1848670
    review:
      summary: Core catalytic activity of JAK1 as a tyrosine kinase
      action: ACCEPT
      reason: Protein phosphorylation is the fundamental enzymatic activity of 
        JAK1. This foundational paper provides traceable author statement 
        supporting this core function.
      supported_by:
        - reference_id: PMID:1848670
          supporting_text: Two novel protein-tyrosine kinases, each with a 
            second phosphotransferase-related catalytic domain, define a new 
            class of protein kinase.
  - term:
      id: GO:0035556
      label: intracellular signal transduction
    evidence_type: TAS
    original_reference_id: PMID:8232552
    review:
      summary: Accurate but general biological process
      action: KEEP_AS_NON_CORE
      reason: While accurate, this is too general. More specific terms like 
        JAK-STAT pathway and cytokine signaling better describe JAK1's core 
        function.
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: file:human/JAK1/JAK1-deep-research.md
    review:
      summary: Core cytokine pathway - JAK1 is the primary kinase for IL-6 
        family signaling
      action: NEW
      reason: JAK1 is essential for IL-6 family cytokine signaling through gp130
        receptor complexes. The deep research document establishes JAK1 as the 
        principal kinase mediating IL-6, IL-11, IL-27, LIF, and oncostatin M 
        signaling. This is a core biological process that was missing from the 
        existing annotations but is well-supported by experimental evidence.
      additional_reference_ids:
        - PMID:7537214
        - Reactome:R-HSA-1112602
      supported_by:
        - reference_id: file:human/JAK1/JAK1-deep-research.md
          supporting_text: JAK1 serves as the principal kinase for IL-6 family 
            cytokines including IL-6, IL-11, IL-27, LIF (leukemia inhibitory 
            factor), and oncostatin M. In these pathways, JAK1 phosphorylates 
            the gp130 receptor subunit and activates STAT1/STAT3
        - reference_id: PMID:7537214
          supporting_text: A major role for the protein tyrosine kinase JAK1 in 
            the JAK/STAT signal transduction pathway in response to 
            interleukin-6
  - term:
      id: GO:0060333
      label: type II interferon-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: file:human/JAK1/JAK1-deep-research.md
    review:
      summary: Core interferon pathway - JAK1 essential for IFN-γ signaling
      action: NEW
      reason: JAK1 is absolutely required for type II interferon (IFN-γ) 
        signaling, where it pairs with JAK2 in the IFNGR1/IFNGR2 receptor 
        complex. The deep research document and foundational studies demonstrate
        that cells lacking JAK1 are completely unresponsive to IFN-γ. This core 
        biological process was missing from existing annotations despite strong 
        experimental evidence.
      additional_reference_ids:
        - PMID:8232552
        - PMID:9446616
      supported_by:
        - reference_id: file:human/JAK1/JAK1-deep-research.md
          supporting_text: JAK1 pairs with JAK2 in the IFNGR1/IFNGR2 receptor 
            complex. IFN-γ signaling leads to STAT1 homodimerization that binds 
            to gamma-activated sequences (GAS) in promoters of pro-inflammatory 
            genes
        - reference_id: PMID:8232552
          supporting_text: JAK1 complements defects in interferon-alpha/beta and
            -gamma signal transduction
        - reference_id: PMID:9446616
          supporting_text: Interferon gamma activation of Raf-1 is 
            Jak1-dependent and p21ras-independent.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: JAK1 is a cytoplasmic non-receptor tyrosine kinase that localizes
        to the cytosol when not associated with activated cytokine receptors. It
        translocates and associates with membrane receptors upon cytokine 
        stimulation.
      action: ACCEPT
      reason: Cytosol localization is essential for JAK1's function as a mobile 
        signaling kinase that can be recruited to activated cytokine receptors 
        and also phosphorylate cytoplasmic STAT transcription factors.
  - term:
      id: GO:0060397
      label: growth hormone receptor signaling pathway via JAK-STAT
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005768
      label: endosome
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0012505
      label: endomembrane system
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0016020
      label: membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0051239
      label: regulation of multicellular organismal process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0098761
      label: cellular response to interleukin-7
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060333
      label: type II interferon-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:15864272
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:15864272
          supporting_text: Mechanisms of type-I- and type-II-interferon-mediated
            signalling.
  - term:
      id: GO:0098586
      label: cellular response to virus
    evidence_type: NAS
    original_reference_id: PMID:15864272
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:15864272
          supporting_text: Mechanisms of type-I- and type-II-interferon-mediated
            signalling.
  - term:
      id: GO:0038110
      label: interleukin-2-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9020558
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060333
      label: type II interferon-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-877300
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0060337
      label: type I interferon-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909733
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1059683
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0038196
      label: type III interferon-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:30936491
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:30936491
          supporting_text: 2019 Apr 1. Decoding type I and III interferon 
            signalling during viral infection.
  - term:
      id: GO:0043235
      label: receptor complex
    evidence_type: IPI
    original_reference_id: PMID:21854986
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:21854986
          supporting_text: Structural linkage between ligand discrimination and 
            receptor activation by type I interferons.
  - term:
      id: GO:0060337
      label: type I interferon-mediated signaling pathway
    evidence_type: NAS
    original_reference_id: PMID:30936491
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:30936491
          supporting_text: 2019 Apr 1. Decoding type I and III interferon 
            signalling during viral infection.
  - term:
      id: GO:0098586
      label: cellular response to virus
    evidence_type: NAS
    original_reference_id: PMID:30936491
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:30936491
          supporting_text: 2019 Apr 1. Decoding type I and III interferon 
            signalling during viral infection.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986994
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987080
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987097
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987129
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987150
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987230
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987255
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987270
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: TAS
    original_reference_id: PMID:34813358
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:34813358
          supporting_text: 2021 Nov 23. IFNAR1 and IFNAR2 play distinct roles in
            initiating type I interferon-induced JAK-STAT signaling and 
            activating STATs.
  - term:
      id: GO:0060333
      label: type II interferon-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8232552
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction.
  - term:
      id: GO:0060337
      label: type I interferon-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8232552
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8232552
          supporting_text: The protein tyrosine kinase JAK1 complements defects 
            in interferon-alpha/beta and -gamma signal transduction.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IC
    original_reference_id: PMID:7532278
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7532278
          supporting_text: Role of STAT2 in the alpha interferon signaling 
            pathway.
  - term:
      id: GO:0060337
      label: type I interferon-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7532278
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7532278
          supporting_text: Role of STAT2 in the alpha interferon signaling 
            pathway.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:7973659
    review:
      summary: JAK1 associates with the cytoplasmic domains of activated 
        cytokine receptors at the plasma membrane, where it becomes 
        phosphorylated and activated to propagate downstream signaling cascades.
      action: ACCEPT
      reason: JAK1's association with the cytoplasmic side of plasma 
        membrane-bound receptors is crucial for cytokine signal transduction, 
        allowing it to be activated by receptor engagement and to phosphorylate 
        other signaling proteins in close proximity to the membrane.
      supported_by:
        - reference_id: PMID:7973659
          supporting_text: Functional activation of Jak1 and Jak3 by selective 
            association with IL-2 receptor subunits.
  - term:
      id: GO:0038154
      label: interleukin-11-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8272872
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8272872
          supporting_text: Association of transcription factor APRF and protein 
            kinase Jak1 with the interleukin-6 signal transducer gp130.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:8272873
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:7543512
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7543512
          supporting_text: IL-10 induces the tyrosine phosphorylation of tyk2 
            and Jak1 and the differential assembly of STAT1 alpha and STAT3 
            complexes in human T cells and monocytes.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:8756628
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8756628
          supporting_text: A single tyrosine of the interleukin-9 (IL-9) 
            receptor is required for STAT activation, antiapoptotic activity, 
            and growth regulation by IL-9.
  - term:
      id: GO:0038113
      label: interleukin-9-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8756628
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8756628
          supporting_text: A single tyrosine of the interleukin-9 (IL-9) 
            receptor is required for STAT activation, antiapoptotic activity, 
            and growth regulation by IL-9.
  - term:
      id: GO:0038110
      label: interleukin-2-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7973659
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7973659
          supporting_text: Functional activation of Jak1 and Jak3 by selective 
            association with IL-2 receptor subunits.
  - term:
      id: GO:0005886
      label: plasma membrane
    evidence_type: IC
    original_reference_id: PMID:10702271
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:10702271
          supporting_text: Interleukin (IL)-7 induces rapid activation of Pyk2, 
            which is bound to Janus kinase 1 and IL-7Ralpha.
  - term:
      id: GO:0009898
      label: cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:20974963
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:20974963
          supporting_text: Thymic stromal lymphopoietin-mediated STAT5 
            phosphorylation via kinases JAK1 and JAK2 reveals a key difference 
            from IL-7-induced signaling.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:7973659
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7973659
          supporting_text: Functional activation of Jak1 and Jak3 by selective 
            association with IL-2 receptor subunits.
  - term:
      id: GO:0038111
      label: interleukin-7-mediated signaling pathway
    evidence_type: IC
    original_reference_id: PMID:20974963
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:20974963
          supporting_text: Thymic stromal lymphopoietin-mediated STAT5 
            phosphorylation via kinases JAK1 and JAK2 reveals a key difference 
            from IL-7-induced signaling.
  - term:
      id: GO:0031234
      label: extrinsic component of cytoplasmic side of plasma membrane
    evidence_type: IC
    original_reference_id: PMID:7929391
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7929391
          supporting_text: JAK1 kinase forms complexes with interleukin-4 
            receptor and 4PS/insulin receptor substrate-1-like protein and is 
            activated by interleukin-4 and interleukin-9 in T lymphocytes.
  - term:
      id: GO:0035771
      label: interleukin-4-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:7929391
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:7929391
          supporting_text: JAK1 kinase forms complexes with interleukin-4 
            receptor and 4PS/insulin receptor substrate-1-like protein and is 
            activated by interleukin-4 and interleukin-9 in T lymphocytes.
  - term:
      id: GO:0009898
      label: cytoplasmic side of plasma membrane
    evidence_type: IDA
    original_reference_id: PMID:8272873
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components.
  - term:
      id: GO:0070102
      label: interleukin-6-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:8272873
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:8272873
          supporting_text: Association and activation of Jak-Tyk kinases by 
            CNTF-LIF-OSM-IL-6 beta receptor components.
  - term:
      id: GO:0150105
      label: protein localization to cell-cell junction
    evidence_type: IMP
    original_reference_id: PMID:21679692
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:21679692
          supporting_text: The tight junction protein ZO-2 and Janus kinase 1 
            mediate intercellular communications in vascular smooth muscle 
            cells.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950340
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950405
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950441
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950453
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950485
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950518
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950537
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982162
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982163
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8982165
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983300
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983834
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983835
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983841
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983845
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983983
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983996
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984012
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984014
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984021
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984023
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986985
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986995
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987012
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987014
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987033
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987040
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987042
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987063
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987070
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987084
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987096
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987132
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987161
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987202
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987236
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987266
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9009227
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1067651
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1067659
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1067688
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112514
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1169406
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1295540
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1678841
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448427
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448480
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448660
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448661
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448708
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448728
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-448744
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449115
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449803
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449811
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449958
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449976
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-449978
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-450027
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-450063
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-451900
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-451942
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5696482
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6783524
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6783530
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6783552
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6783556
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6783681
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784189
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784204
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784319
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6785165
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786050
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786058
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786096
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786110
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788571
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788582
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6788628
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6809140
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873918
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873919
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873926
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-877269
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8854645
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950210
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950448
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8950757
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8952807
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8963734
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983003
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983063
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983298
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983335
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983518
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8984001
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985900
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985914
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985929
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985973
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8985988
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986446
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986480
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8986972
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987015
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987039
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987043
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987104
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987105
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987120
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987141
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987156
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987179
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8987220
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9005980
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006844
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006850
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9011748
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9025969
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909720
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909724
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909729
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9677579
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9677585
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9678561
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9678935
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9696179
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-997314
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005768
      label: endosome
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983335
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:1903672
      label: positive regulation of sprouting angiogenesis
    evidence_type: IGI
    original_reference_id: PMID:20299512
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:20299512
          supporting_text: 2010 Mar 18. Members of the microRNA-17-92 cluster 
            exhibit a cell-intrinsic antiangiogenic function in endothelial 
            cells.
  - term:
      id: GO:0005925
      label: focal adhesion
    evidence_type: HDA
    original_reference_id: PMID:21423176
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:21423176
          supporting_text: Analysis of the myosin-II-responsive focal adhesion 
            proteome reveals a role for β-Pix in negative regulation of focal 
            adhesion maturation.
  - term:
      id: GO:0038110
      label: interleukin-2-mediated signaling pathway
    evidence_type: IDA
    original_reference_id: PMID:11909529
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:11909529
          supporting_text: The T cell protein tyrosine phosphatase is a negative
            regulator of janus family kinases 1 and 3.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112510
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112565
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112602
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112604
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112690
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112703
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112708
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112727
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-1112755
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452091
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452097
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452100
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452108
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-452122
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-453104
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-453111
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-508247
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-508282
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-508292
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5672965
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784006
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784323
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784324
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6784791
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786072
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786095
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6786124
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873921
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873922
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873924
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-873927
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983371
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983374
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983378
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-8983384
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006870
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9006873
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909552
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909718
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909719
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909722
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909726
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909730
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-909732
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-912527
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-913374
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-913424
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-919404
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9674816
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9705738
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9707977
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9732729
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9732738
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9732753
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-997309
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-997311
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:10502458
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:10502458
          supporting_text: The growth hormone receptor associates with Jak1, 
            Jak2 and Tyk2 in human liver.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:10502458
    review:
      summary: 'TODO: Review this GOA annotation'
      action: PENDING
      supported_by:
        - reference_id: PMID:10502458
          supporting_text: The growth hormone receptor associates with Jak1, 
            Jak2 and Tyk2 in human liver.
core_functions:
  - description: Non-receptor tyrosine kinase essential for multiple cytokine 
      signaling pathways via JAK-STAT cascade
    molecular_function:
      id: GO:0004715
      label: non-membrane spanning protein tyrosine kinase activity
    directly_involved_in:
      - id: GO:0007259
        label: cell surface receptor signaling pathway via JAK-STAT
      - id: GO:0019221
        label: cytokine-mediated signaling pathway
      - id: GO:0060337
        label: type I interferon-mediated signaling pathway
      - id: GO:0060333
        label: type II interferon-mediated signaling pathway
      - id: GO:0070102
        label: interleukin-6-mediated signaling pathway
      - id: GO:0038110
        label: interleukin-2-mediated signaling pathway
      - id: GO:0035771
        label: interleukin-4-mediated signaling pathway
      - id: GO:0038111
        label: interleukin-7-mediated signaling pathway
      - id: GO:0140105
        label: interleukin-10-mediated signaling pathway
      - id: GO:0006468
        label: protein phosphorylation
    locations:
      - id: GO:0005829
        label: cytosol
      - id: GO:0031234
        label: extrinsic component of cytoplasmic side of plasma membrane
    anatomical_locations:
      - id: UBERON:0002405
        label: immune system
      - id: UBERON:0002048
        label: lung
      - id: UBERON:0002107
        label: liver
      - id: UBERON:0001017
        label: central nervous system
    substrates:
      - id: TEMP:JAK1_IFNAR_complex
        label: JAK1-IFNAR complex
        description: JAK1 (with TYK2) at Type I interferon receptor for IFN-α/β 
          signaling
      - id: TEMP:JAK1_IFNGR_complex
        label: JAK1-IFNGR complex
        description: JAK1 (with JAK2) at IFN-γ receptor for Type II interferon 
          signaling
      - id: TEMP:JAK1_gp130_complex
        label: JAK1-gp130 complex
        description: JAK1 at gp130-containing IL-6 family cytokine receptor 
          complexes
      - id: TEMP:JAK1_gammac_complex
        label: JAK1-γc complex
        description: JAK1 (with JAK3) at common γ-chain cytokine receptors 
          (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21)
      - id: TEMP:STAT_phosphorylation_complex
        label: JAK1-STAT phosphorylation complex
        description: JAK1 phosphorylating STAT transcription factors (STAT1, 
          STAT2, STAT3, STAT5, STAT6)
    supported_by:
      - reference_id: PMID:8232552
        supporting_text: JAK1 complements defects in interferon-alpha/beta and 
          -gamma signal transduction
      - reference_id: PMID:9590172
        supporting_text: JAK1 demonstrates obligatory and nonredundant roles in 
          cytokine-induced biologic responses
      - reference_id: file:human/JAK1/JAK1-deep-research.md
        supporting_text: JAK1 is required for signaling by Type I/II 
          interferons, γc-dependent cytokines, and gp130-dependent cytokines
suggested_questions:
  - question: How does JAK1 achieve specificity in cytokine signaling despite 
      being used by multiple different cytokine receptors?
  - question: What are the molecular mechanisms of JAK1 activation and how do 
      negative regulatory mechanisms prevent inappropriate signaling?
  - question: How do JAK1 inhibitors achieve selectivity and what are the 
      structural determinants of drug binding and specificity?
  - question: What role does JAK1 play in immune cell development versus mature 
      immune cell function and how is this regulated?
suggested_experiments:
  - description: Cryo-EM structures of JAK1 in complex with different cytokine 
      receptors to understand receptor-specific activation mechanisms
  - description: Single-cell RNA sequencing of immune cells with JAK1 
      perturbations to map cell-type-specific transcriptional responses
  - description: Chemical proteomics to identify off-target effects and 
      selectivity profiles of JAK1 inhibitors in development
  - description: Real-time measurement of JAK1 kinase activity using FRET-based 
      biosensors in response to different cytokines
status: COMPLETE

JAK1

Gene Description