| Topic | Key points | Best sources | URLs + publication dates |
|---|---|---|---|
| Identity / domains | Human JAK1 is UniProt **P23458**, EC **2.7.10.2**. It contains a receptor-binding **FERM-SH2** N-terminus plus a **JH2 pseudokinase** and **JH1 catalytic kinase** C-terminus; KinFams separates residues **583–855** (pseudokinase) and **875–1153** (active kinase). (pqac-00000023, pqac-00000008) | Adeyelu et al. 2023; Lv et al. 2024 (pqac-00000023, pqac-00000008) | https://doi.org/10.3390/biom13020277 (Feb 2023); https://doi.org/10.1038/s41392-024-01934-w (Aug 2024) |
| Catalytic activity | JAK1 is the catalytic tyrosine kinase in JAK-STAT signaling; JH1 is the active TK domain, whereas JH2 is regulatory/pseudokinase. Reported catalytic-site/motif residues include **K908**, **D1003** (HRD), and **D1022** (DFG), and JAKs phosphorylate themselves, cytokine receptors, and STAT proteins. (pqac-00000023, pqac-00000005, pqac-00000006) | Adeyelu et al. 2023; Kwon 2026; Jarneborn et al. 2025 (pqac-00000023, pqac-00000005, pqac-00000006) | https://doi.org/10.3390/biom13020277 (Feb 2023); https://doi.org/10.3389/fmed.2026.1716179 (Jan 2026); https://doi.org/10.3390/pathogens14040324 (Mar 2025) |
| Activation / regulated residues | The JH2 domain exerts autoinhibitory control: deletion increases basal activity, and activation requires release/repositioning of TK from the inhibited state. JAK1 activation-loop tyrosines **Y1022/Y1023** are regulated phosphosites, with **Y1023** reported as more strongly phosphorylated. (pqac-00000007, pqac-00000002, pqac-00000009) | Lv et al. 2024; Sun et al. 2024; Djidjik et al. 2025 (pqac-00000007, pqac-00000002, pqac-00000009) | https://doi.org/10.1038/s41392-024-01934-w (Aug 2024); https://doi.org/10.1093/bib/bbae079 (Jan 2024); https://doi.org/10.3389/fimmu.2025.1669688 (Dec 2025) |
| Receptor / cytokine pairings | JAK1 binds receptor **box 1/box 2** motifs through FERM/SH2; a solved structure shows human JAK1 FERM-SH2 bound to **IFNλR1**. Reported JAK1 pairings include **IFN-γ (JAK1/JAK2)**, **IFN-α/β (JAK1/TYK2)**, **IL-10 (JAK1/TYK2)**, **IL-2/IL-4/IL-7/IL-21 (JAK1/JAK3)**, and **IL-6/gp130 signaling**. (pqac-00000007, pqac-00000010, pqac-00000009) | Lv et al. 2024; Jarneborn et al. 2025; Djidjik et al. 2025 (pqac-00000007, pqac-00000010, pqac-00000009) | https://doi.org/10.1038/s41392-024-01934-w (Aug 2024); https://doi.org/10.3390/pathogens14040324 (Mar 2025); https://doi.org/10.3389/fimmu.2025.1669688 (Dec 2025) |
| Inhibitor applications with quantitative efficacy | JAK1-selective inhibitors are in real-world/clinical use. In ulcerative colitis, reported remission data were **up to 80% at 8 weeks and 38% at 52 weeks for upadacitinib**, and **71.9% at week 12 / 76.4% at week 24 for filgotinib**; onset may occur within **days 1–3**. In atopic dermatitis meta-analyses, JKIs improved **IGA response RR 2.83**, **EASI75 RR 2.84**, and **PP-NRS SMD -0.49**; upadacitinib had rapid IGA effect **RR 5.3**, and abrocitinib **200 mg vs 100 mg RR 2.52** for IGA response. (pqac-00000001, pqac-00000011, pqac-00000012) | Caballero-Mateos & Cañadas-de la Fuente 2024; He et al. 2024 (pqac-00000001, pqac-00000011, pqac-00000012) | https://doi.org/10.3748/wjg.v30.i35.3942 (Sep 2024); https://doi.org/10.3389/fimmu.2024.1342810 (Feb 2024) |
| Safety signals with quantitative RRs | In AD meta-analyses, serious AEs/discontinuations were not increased overall, but drug-specific risks were noted: **abrocitinib 200 mg** acne **RR 4.34**, headache **RR 1.76**, nausea **RR 7.81**; **upadacitinib** acne **RR 6.23**, nasopharyngitis **RR 1.36**, blood CPK increase **RR 2.41**; TEAEs for systemic JKIs **RR 1.23**. Upadacitinib safety review found **16/25 (64%)** studies with no significant safety differences, while **8/25 (32%)** reported higher rates and **1/25 (4%)** lower rates. (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000016, pqac-00000019) | He et al. 2024; Mysler et al. 2024 (pqac-00000011, pqac-00000012, pqac-00000013, pqac-00000016, pqac-00000019) | https://doi.org/10.3389/fimmu.2024.1342810 (Feb 2024); https://doi.org/10.1007/s12325-023-02732-6 (Jan 2024) |
| Key clinical trials metadata | **NCT05507580**: Phase 4, completed, **461** adults with moderate-to-severe AD; evaluates **treat-to-target and dosing flexibility** of upadacitinib 15/30 mg, primary endpoint **EASI90 at week 24**. **NCT05602207**: Phase 4, completed, **24** adults with AD after inadequate dupilumab response; abrocitinib **100 mg QD** for 12 weeks, primary endpoint change in **EASI**. **NCT02914522 (SELECTION)**: Phase **2b/3**, completed, **1,351** participants with UC; filgotinib **100/200 mg** for induction and maintenance remission. **NCT05391061**: recruiting observational post-marketing Korean abrocitinib study, estimated **1100** participants, assessing safety/effectiveness to **52 weeks**. (pqac-00000029, pqac-00000027, pqac-00000028, pqac-00000030) | ClinicalTrials.gov registry entries (pqac-00000029, pqac-00000027, pqac-00000028, pqac-00000030) | https://clinicaltrials.gov/study/NCT05507580 (2023 registry entry); https://clinicaltrials.gov/study/NCT05602207 (2022 registry entry); https://clinicaltrials.gov/study/NCT02914522 (2016 registry entry); https://clinicaltrials.gov/study/NCT05391061 (2023 registry entry) |


*Table: This table compacts the most actionable functional-annotation facts for human JAK1 (UniProt P23458), including identity, mechanism, pathway pairings, therapeutic applications, safety signals, and trial metadata. It is useful as a citation-ready summary for downstream narrative reporting.*