Motif 991 (n=50)
Position-wise Probabilities
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| uniprot | genes | site | source | protein | function |
|---|---|---|---|---|---|
| A6NKT7 | RGPD3 | T1185 | ochoa | RanBP2-like and GRIP domain-containing protein 3 | None |
| O14715 | RGPD8 | T1184 | ochoa | RANBP2-like and GRIP domain-containing protein 8 (Ran-binding protein 2-like 3) (RanBP2-like 3) (RanBP2L3) | None |
| O14733 | MAP2K7 | T275 | psp | Dual specificity mitogen-activated protein kinase kinase 7 (MAP kinase kinase 7) (MAPKK 7) (EC 2.7.12.2) (JNK-activating kinase 2) (MAPK/ERK kinase 7) (MEK 7) (Stress-activated protein kinase kinase 4) (SAPK kinase 4) (SAPKK-4) (SAPKK4) (c-Jun N-terminal kinase kinase 2) (JNK kinase 2) (JNKK 2) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by pro-inflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074). {ECO:0000269|PubMed:28111074, ECO:0000269|PubMed:9312068, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, ECO:0000269|Ref.5}. |
| O15264 | MAPK13 | T180 | ochoa|psp | Mitogen-activated protein kinase 13 (MAP kinase 13) (MAPK 13) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 delta) (MAP kinase p38 delta) (Stress-activated protein kinase 4) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212, ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148, ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666, ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}. |
| O43318 | MAP3K7 | T187 | psp | Mitogen-activated protein kinase kinase kinase 7 (EC 2.7.11.25) (Transforming growth factor-beta-activated kinase 1) (TGF-beta-activated kinase 1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:16893890, PubMed:9079627). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:11460167, PubMed:8663074). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:11460167, PubMed:12589052, PubMed:8663074). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:12589052, PubMed:8663074). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity). Phosphorylates STING1 in response to cGAMP-activation, promoting association between STEEP1 and STING1 and STING1 translocation to COPII vesicles (PubMed:37832545). {ECO:0000250|UniProtKB:Q62073, ECO:0000269|PubMed:10094049, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:12589052, ECO:0000269|PubMed:16845370, ECO:0000269|PubMed:16893890, ECO:0000269|PubMed:21512573, ECO:0000269|PubMed:37832545, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9079627}. |
| O76039 | CDKL5 | T169 | psp | Cyclin-dependent kinase-like 5 (EC 2.7.11.22) (Serine/threonine-protein kinase 9) | Mediates phosphorylation of MECP2 (PubMed:15917271, PubMed:16935860). May regulate ciliogenesis (PubMed:29420175). {ECO:0000269|PubMed:15917271, ECO:0000269|PubMed:16935860, ECO:0000269|PubMed:29420175}. |
| P0DJD0 | RGPD1 | T1169 | ochoa | RANBP2-like and GRIP domain-containing protein 1 (Ran-binding protein 2-like 6) (RanBP2-like 6) (RanBP2L6) | None |
| P0DJD1 | RGPD2 | T1177 | ochoa | RANBP2-like and GRIP domain-containing protein 2 (Ran-binding protein 2-like 2) (RanBP2-like 2) (RanBP2L2) | None |
| P11802 | CDK4 | T172 | psp | Cyclin-dependent kinase 4 (EC 2.7.11.22) (Cell division protein kinase 4) (PSK-J3) | Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex. {ECO:0000269|PubMed:15241418, ECO:0000269|PubMed:18827403, ECO:0000269|PubMed:9003781}. |
| P19525 | EIF2AK2 | T446 | psp | Interferon-induced, double-stranded RNA-activated protein kinase (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 2) (eIF-2A protein kinase 2) (Interferon-inducible RNA-dependent protein kinase) (P1/eIF-2A protein kinase) (Protein kinase RNA-activated) (PKR) (Protein kinase R) (Tyrosine-protein kinase EIF2AK2) (EC 2.7.10.2) (p68 kinase) | IFN-induced dsRNA-dependent serine/threonine-protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) and plays a key role in the innate immune response to viral infection (PubMed:18835251, PubMed:19189853, PubMed:19507191, PubMed:21072047, PubMed:21123651, PubMed:22381929, PubMed:22948139, PubMed:23229543). Inhibits viral replication via the integrated stress response (ISR): EIF2S1/eIF-2-alpha phosphorylation in response to viral infection converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, resulting to a shutdown of cellular and viral protein synthesis, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4 (PubMed:19189853, PubMed:21123651, PubMed:22948139, PubMed:23229543). Exerts its antiviral activity on a wide range of DNA and RNA viruses including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV) and herpes simplex virus 1 (HHV-1) (PubMed:11836380, PubMed:19189853, PubMed:19840259, PubMed:20171114, PubMed:21710204, PubMed:23115276, PubMed:23399035). Also involved in the regulation of signal transduction, apoptosis, cell proliferation and differentiation: phosphorylates other substrates including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1 and the HHV-1 viral protein US11 (PubMed:11836380, PubMed:19229320, PubMed:22214662). In addition to serine/threonine-protein kinase activity, also has tyrosine-protein kinase activity and phosphorylates CDK1 at 'Tyr-4' upon DNA damage, facilitating its ubiquitination and proteasomal degradation (PubMed:20395957). Either as an adapter protein and/or via its kinase activity, can regulate various signaling pathways (p38 MAP kinase, NF-kappa-B and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding pro-inflammatory cytokines and IFNs (PubMed:22948139, PubMed:23084476, PubMed:23372823). Activates the NF-kappa-B pathway via interaction with IKBKB and TRAF family of proteins and activates the p38 MAP kinase pathway via interaction with MAP2K6 (PubMed:10848580, PubMed:15121867, PubMed:15229216). Can act as both a positive and negative regulator of the insulin signaling pathway (ISP) (PubMed:20685959). Negatively regulates ISP by inducing the inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312' and positively regulates ISP via phosphorylation of PPP2R5A which activates FOXO1, which in turn up-regulates the expression of insulin receptor substrate 2 (IRS2) (PubMed:20685959). Can regulate NLRP3 inflammasome assembly and the activation of NLRP3, NLRP1, AIM2 and NLRC4 inflammasomes (PubMed:22801494). Plays a role in the regulation of the cytoskeleton by binding to gelsolin (GSN), sequestering the protein in an inactive conformation away from actin (By similarity). {ECO:0000250|UniProtKB:Q03963, ECO:0000269|PubMed:10848580, ECO:0000269|PubMed:11836380, ECO:0000269|PubMed:15121867, ECO:0000269|PubMed:15229216, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:19189853, ECO:0000269|PubMed:19229320, ECO:0000269|PubMed:19507191, ECO:0000269|PubMed:19840259, ECO:0000269|PubMed:20171114, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20685959, ECO:0000269|PubMed:21072047, ECO:0000269|PubMed:21123651, ECO:0000269|PubMed:21710204, ECO:0000269|PubMed:22214662, ECO:0000269|PubMed:22381929, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:22948139, ECO:0000269|PubMed:23084476, ECO:0000269|PubMed:23115276, ECO:0000269|PubMed:23229543, ECO:0000269|PubMed:23372823, ECO:0000269|PubMed:23399035, ECO:0000269|PubMed:32197074}. |
| P20794 | MAK | T157 | psp | Serine/threonine-protein kinase MAK (EC 2.7.11.1) (Male germ cell-associated kinase) | Essential for the regulation of ciliary length and required for the long-term survival of photoreceptors (By similarity). Phosphorylates FZR1 in a cell cycle-dependent manner. Plays a role in the transcriptional coactivation of AR. Could play an important function in spermatogenesis. May play a role in chromosomal stability in prostate cancer cells. {ECO:0000250, ECO:0000269|PubMed:12084720, ECO:0000269|PubMed:16951154, ECO:0000269|PubMed:21986944}. |
| P27361 | MAPK3 | T202 | ochoa|psp | Mitogen-activated protein kinase 3 (MAP kinase 3) (MAPK 3) (EC 2.7.11.24) (ERT2) (Extracellular signal-regulated kinase 1) (ERK-1) (Insulin-stimulated MAP2 kinase) (MAP kinase isoform p44) (p44-MAPK) (Microtubule-associated protein 2 kinase) (p44-ERK1) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:34497368). MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DEPTOR, FRS2 or GRB10) (PubMed:35216969). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. {ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:34497368, ECO:0000269|PubMed:35216969, ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9480836}. |
| P28482 | MAPK1 | T185 | ochoa|psp | Mitogen-activated protein kinase 1 (MAP kinase 1) (MAPK 1) (EC 2.7.11.24) (ERT1) (Extracellular signal-regulated kinase 2) (ERK-2) (MAP kinase isoform p42) (p42-MAPK) (Mitogen-activated protein kinase 2) (MAP kinase 2) (MAPK 2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade also plays a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1 and FXR1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity). Phosphorylates phosphoglycerate kinase PGK1 under hypoxic conditions to promote its targeting to the mitochondrion and suppress the formation of acetyl-coenzyme A from pyruvate (PubMed:26942675). {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087, ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391, ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:26942675, ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608, ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836, ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160, ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474, ECO:0000303|PubMed:21779493}.; FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity. {ECO:0000269|PubMed:19879846}. |
| P37173 | TGFBR2 | S416 | psp | TGF-beta receptor type-2 (TGFR-2) (EC 2.7.11.30) (TGF-beta type II receptor) (Transforming growth factor-beta receptor type II) (TGF-beta receptor type II) (TbetaR-II) | Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways. {ECO:0000269|PubMed:7774578}.; FUNCTION: [Isoform 1]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 2]: Has transforming growth factor beta-activated receptor activity. {ECO:0000269|PubMed:8635485}.; FUNCTION: [Isoform 3]: Binds TGFB1, TGFB2 and TGFB3 in the picomolar affinity range without the participation of additional receptors. Blocks activation of SMAD2 and SMAD3 by TGFB1. {ECO:0000269|PubMed:34568316}. |
| P45983 | MAPK8 | T183 | ochoa|psp | Mitogen-activated protein kinase 8 (MAP kinase 8) (MAPK 8) (EC 2.7.11.24) (JNK-46) (Stress-activated protein kinase 1c) (SAPK1c) (Stress-activated protein kinase JNK1) (c-Jun N-terminal kinase 1) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway (PubMed:28943315). In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:18307971). Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins (PubMed:21856198). Loss of this interaction abrogates the acetylation required for replication initiation (PubMed:21856198). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 (PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells. Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation (PubMed:21095239). Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy (PubMed:18570871). Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH (PubMed:16581800, PubMed:17296730, PubMed:20027304). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity (PubMed:10747973). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly (PubMed:22966201). Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity (PubMed:27568560). Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome (PubMed:28943315). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:P49185, ECO:0000250|UniProtKB:Q91Y86, ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:17296730, ECO:0000269|PubMed:18307971, ECO:0000269|PubMed:18570871, ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21095239, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:21856198, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:22966201, ECO:0000269|PubMed:27568560, ECO:0000269|PubMed:28943315, ECO:0000269|PubMed:34048572}.; FUNCTION: JNK1 isoforms display different binding patterns: beta-1 preferentially binds to c-Jun, whereas alpha-1, alpha-2, and beta-2 have a similar low level of binding to both c-Jun or ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. |
| P45984 | MAPK9 | T183 | ochoa|psp | Mitogen-activated protein kinase 9 (MAP kinase 9) (MAPK 9) (EC 2.7.11.24) (JNK-55) (Stress-activated protein kinase 1a) (SAPK1a) (Stress-activated protein kinase JNK2) (c-Jun N-terminal kinase 2) | Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 (PubMed:10376527, PubMed:15805466, PubMed:17525747, PubMed:19675674, PubMed:20595622, PubMed:21364637, PubMed:22441692, PubMed:34048572). In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (PubMed:10376527). In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 (PubMed:15805466). Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 (PubMed:17525747, PubMed:21364637). In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells (PubMed:19290929). Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels (PubMed:19290929). Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption (PubMed:20595622). When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway (PubMed:19675674). Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock (PubMed:22441692). Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity). Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation (PubMed:34048572). {ECO:0000250|UniProtKB:Q9WTU6, ECO:0000269|PubMed:10376527, ECO:0000269|PubMed:15805466, ECO:0000269|PubMed:17525747, ECO:0000269|PubMed:19675674, ECO:0000269|PubMed:20595622, ECO:0000269|PubMed:21364637, ECO:0000269|PubMed:22441692, ECO:0000269|PubMed:34048572, ECO:0000303|PubMed:19290929}.; FUNCTION: MAPK9 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it. |
| P45985 | MAP2K4 | T261 | psp | Dual specificity mitogen-activated protein kinase kinase 4 (MAP kinase kinase 4) (MAPKK 4) (EC 2.7.12.2) (JNK-activating kinase 1) (MAPK/ERK kinase 4) (MEK 4) (SAPK/ERK kinase 1) (SEK1) (Stress-activated protein kinase kinase 1) (SAPK kinase 1) (SAPKK-1) (SAPKK1) (c-Jun N-terminal kinase kinase 1) (JNKK) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to pro-inflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14. {ECO:0000269|PubMed:7716521}. |
| P46734 | MAP2K3 | T222 | psp | Dual specificity mitogen-activated protein kinase kinase 3 (MAP kinase kinase 3) (MAPKK 3) (EC 2.7.12.2) (MAPK/ERK kinase 3) (MEK 3) (Stress-activated protein kinase kinase 2) (SAPK kinase 2) (SAPKK-2) (SAPKK2) | Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}. |
| P49137 | MAPKAPK2 | T221 | ochoa | MAP kinase-activated protein kinase 2 (MAPK-activated protein kinase 2) (MAPKAP kinase 2) (MAPKAP-K2) (MAPKAPK-2) (MK-2) (MK2) (EC 2.7.11.1) | Stress-activated serine/threonine-protein kinase involved in cytokine production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, CEP131, ELAVL1, HNRNPA0, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Phosphorylates HSF1; leading to the interaction with HSP90 proteins and inhibiting HSF1 homotrimerization, DNA-binding and transactivation activities (PubMed:16278218). Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to the dissociation of HSP27/HSPB1 from large small heat-shock protein (sHsps) oligomers and impairment of their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to the regulation of the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity, leading to inhibition of dependent degradation of ARE-containing transcripts. Phosphorylates CEP131 in response to cellular stress induced by ultraviolet irradiation which promotes binding of CEP131 to 14-3-3 proteins and inhibits formation of novel centriolar satellites (PubMed:26616734). Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilization of GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:12456657, ECO:0000269|PubMed:12565831, ECO:0000269|PubMed:14499342, ECO:0000269|PubMed:14517288, ECO:0000269|PubMed:15014438, ECO:0000269|PubMed:15629715, ECO:0000269|PubMed:16278218, ECO:0000269|PubMed:16456544, ECO:0000269|PubMed:17481585, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:26616734, ECO:0000269|PubMed:8093612, ECO:0000269|PubMed:8280084, ECO:0000269|PubMed:8774846}. |
| P49759 | CLK1 | S337 | ochoa | Dual specificity protein kinase CLK1 (EC 2.7.12.1) (CDC-like kinase 1) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates: SRSF1, SRSF3 and PTPN1 (PubMed:10480872, PubMed:19168442). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (PubMed:19168442). {ECO:0000269|PubMed:10480872, ECO:0000269|PubMed:19168442}. |
| P49792 | RANBP2 | T2160 | ochoa | E3 SUMO-protein ligase RanBP2 (EC 2.3.2.-) (358 kDa nucleoporin) (Nuclear pore complex protein Nup358) (Nucleoporin Nup358) (Ran-binding protein 2) (RanBP2) (p270) | E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:15931224, PubMed:22194619). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830). {ECO:0000269|PubMed:11792325, ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15931224, ECO:0000269|PubMed:20386726, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:22155184, ECO:0000269|PubMed:22194619, ECO:0000269|PubMed:22902403, ECO:0000269|PubMed:23353830, ECO:0000269|PubMed:7775481, ECO:0000303|PubMed:10078529}. |
| P50750 | CDK9 | T186 | ochoa|psp | Cyclin-dependent kinase 9 (EC 2.7.11.22) (EC 2.7.11.23) (C-2K) (Cell division cycle 2-like protein kinase 4) (Cell division protein kinase 9) (Serine/threonine-protein kinase PITALRE) (Tat-associated kinase complex catalytic subunit) | Protein kinase involved in the regulation of transcription (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245). Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:16427012, PubMed:20930849, PubMed:28426094, PubMed:30134174). This complex is inactive when in the 7SK snRNP complex form (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849, PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELFE (PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:16427012, PubMed:20081228, PubMed:20980437, PubMed:21127351, PubMed:9857195). Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166). Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351). Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single-stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage (PubMed:20493174). In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription (PubMed:21127351). AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect (PubMed:10912001, PubMed:11112772, PubMed:9857195). The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5 recruitment to chromatin and histone acetyltransferase activity (PubMed:29335245). {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:16427012, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:29335245, ECO:0000269|PubMed:30134174, ECO:0000269|PubMed:9857195}. |
| P52564 | MAP2K6 | T211 | psp | Dual specificity mitogen-activated protein kinase kinase 6 (MAP kinase kinase 6) (MAPKK 6) (EC 2.7.12.2) (MAPK/ERK kinase 6) (MEK 6) (Stress-activated protein kinase kinase 3) (SAPK kinase 3) (SAPKK-3) (SAPKK3) | Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. {ECO:0000269|PubMed:10961885, ECO:0000269|PubMed:11727828, ECO:0000269|PubMed:15550393, ECO:0000269|PubMed:20869211, ECO:0000269|PubMed:8622669, ECO:0000269|PubMed:8626699, ECO:0000269|PubMed:8663074, ECO:0000269|PubMed:9218798}. |
| P53778 | MAPK12 | T183 | ochoa | Mitogen-activated protein kinase 12 (MAP kinase 12) (MAPK 12) (EC 2.7.11.24) (Extracellular signal-regulated kinase 6) (ERK-6) (Mitogen-activated protein kinase p38 gamma) (MAP kinase p38 gamma) (Stress-activated protein kinase 3) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration. {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917, ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070, ECO:0000269|PubMed:9430721}. |
| P53779 | MAPK10 | T221 | ochoa|psp | Mitogen-activated protein kinase 10 (MAP kinase 10) (MAPK 10) (EC 2.7.11.24) (MAP kinase p49 3F12) (Stress-activated protein kinase 1b) (SAPK1b) (Stress-activated protein kinase JNK3) (c-Jun N-terminal kinase 3) | Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296). {ECO:0000269|PubMed:11718727, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22441692}. |
| Q00534 | CDK6 | T177 | psp | Cyclin-dependent kinase 6 (EC 2.7.11.22) (Cell division protein kinase 6) (Serine/threonine-protein kinase PLSTIRE) | Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}. |
| Q13164 | MAPK7 | T219 | ochoa|psp | Mitogen-activated protein kinase 7 (MAP kinase 7) (MAPK 7) (EC 2.7.11.24) (Big MAP kinase 1) (BMK-1) (Extracellular signal-regulated kinase 5) (ERK-5) | Plays a role in various cellular processes such as proliferation, differentiation and cell survival. The upstream activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it translocates to the nucleus and phosphorylates various downstream targets including MEF2C. EGF activates MAPK7 through a Ras-independent and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via interaction with STUB1/CHIP and promotion of STUB1-mediated ubiquitination and degradation of ICER-type isoforms of CREM (By similarity). May have a role in muscle cell differentiation. May be important for endothelial function and maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact specifically with one another and not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth factor-induced cell cycle progression. Involved in the regulation of p53/TP53 by disrupting the PML-MDM2 interaction. {ECO:0000250|UniProtKB:P0C865, ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431, ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}. |
| Q13523 | PRP4K | T847 | ochoa | Serine/threonine-protein kinase PRP4 homolog (EC 2.7.11.1) (PRP4 kinase) (PRP4 pre-mRNA-processing factor 4 homolog) | Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation (PubMed:10799319, PubMed:12077342, PubMed:17513757, PubMed:17998396). Connects chromatin mediated regulation of transcription and pre-mRNA splicing (PubMed:12077342). During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC) (PubMed:20118938). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation (PubMed:12077342). Associates and probably phosphorylates SMARCA4 and NCOR1 (PubMed:12077342). Phosphorylates SRSF1 (PubMed:11418604). Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores (PubMed:17998396). Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13 (PubMed:10799319, PubMed:17513757). Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control (PubMed:29695716). {ECO:0000269|PubMed:10799319, ECO:0000269|PubMed:11418604, ECO:0000269|PubMed:12077342, ECO:0000269|PubMed:17513757, ECO:0000269|PubMed:17998396, ECO:0000269|PubMed:20118938, ECO:0000269|PubMed:29695716}. |
| Q13627 | DYRK1A | Y319 | ochoa | Dual specificity tyrosine-phosphorylation-regulated kinase 1A (EC 2.7.11.23) (EC 2.7.12.1) (Dual specificity YAK1-related kinase) (HP86) (Protein kinase minibrain homolog) (MNBH) (hMNB) | Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:20981014, PubMed:21127067, PubMed:23665168, PubMed:30773093, PubMed:8769099). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (PubMed:23665168). Plays an important role in double-strand breaks (DSBs) repair following DNA damage (PubMed:31024071). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (PubMed:30773093). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:25620562, PubMed:29849146). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (PubMed:14500717). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (By similarity). This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity). {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q63470, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:21127067, ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:25620562, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30773093, ECO:0000269|PubMed:31024071, ECO:0000269|PubMed:8769099}. |
| Q14004 | CDK13 | T871 | ochoa | Cyclin-dependent kinase 13 (EC 2.7.11.22) (EC 2.7.11.23) (CDC2-related protein kinase 5) (Cell division cycle 2-like protein kinase 5) (Cell division protein kinase 13) (hCDK13) (Cholinesterase-related cell division controller) | Cyclin-dependent kinase which displays CTD kinase activity and is required for RNA splicing. Has CTD kinase activity by hyperphosphorylating the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit RPB1, thereby acting as a key regulator of transcription elongation. Required for RNA splicing, probably by phosphorylating SRSF1/SF2. Required during hematopoiesis. In case of infection by HIV-1 virus, interacts with HIV-1 Tat protein acetylated at 'Lys-50' and 'Lys-51', thereby increasing HIV-1 mRNA splicing and promoting the production of the doubly spliced HIV-1 protein Nef. {ECO:0000269|PubMed:16721827, ECO:0000269|PubMed:1731328, ECO:0000269|PubMed:18480452, ECO:0000269|PubMed:20952539}. |
| Q14012 | CAMK1 | S176 | ochoa | Calcium/calmodulin-dependent protein kinase type 1 (EC 2.7.11.17) (CaM kinase I) (CaM-KI) (CaM kinase I alpha) (CaMKI-alpha) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I. {ECO:0000250, ECO:0000269|PubMed:11114197, ECO:0000269|PubMed:12193581, ECO:0000269|PubMed:14507913, ECO:0000269|PubMed:14754892, ECO:0000269|PubMed:17056143, ECO:0000269|PubMed:17442826, ECO:0000269|PubMed:18184567, ECO:0000269|PubMed:20181577}. |
| Q15759 | MAPK11 | T180 | psp | Mitogen-activated protein kinase 11 (MAP kinase 11) (MAPK 11) (EC 2.7.11.24) (Mitogen-activated protein kinase p38 beta) (MAP kinase p38 beta) (p38b) (Stress-activated protein kinase 2b) (SAPK2b) (p38-2) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors (PubMed:12452429, PubMed:20626350, PubMed:35857590). Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each (PubMed:12452429, PubMed:20626350, PubMed:35857590). MAPK11 functions are mostly redundant with those of MAPK14 (PubMed:12452429, PubMed:20626350, PubMed:35857590). Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets (PubMed:12452429, PubMed:20626350). RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery. On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17. Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Additional examples of p38 MAPK substrates are the FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:15356147, PubMed:9430721). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers (PubMed:10330143, PubMed:15356147, PubMed:9430721). The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). Phosphorylates methyltransferase DOT1L on 'Ser-834', 'Thr-900', 'Ser-902', 'Thr-984', 'Ser-1001', 'Ser-1009' and 'Ser-1104' (PubMed:38270553). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:15356147, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:38270553, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:12452429, ECO:0000303|PubMed:20626350}. |
| Q16539 | MAPK14 | T180 | ochoa|psp | Mitogen-activated protein kinase 14 (MAP kinase 14) (MAPK 14) (EC 2.7.11.24) (Cytokine suppressive anti-inflammatory drug-binding protein) (CSAID-binding protein) (CSBP) (MAP kinase MXI2) (MAX-interacting protein 2) (Mitogen-activated protein kinase p38 alpha) (MAP kinase p38 alpha) (Stress-activated protein kinase 2a) (SAPK2a) | Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases which are activated through phosphorylation and further phosphorylate additional targets. RPS6KA5/MSK1 and RPS6KA4/MSK2 can directly phosphorylate and activate transcription factors such as CREB1, ATF1, the NF-kappa-B isoform RELA/NFKB3, STAT1 and STAT3, but can also phosphorylate histone H3 and the nucleosomal protein HMGN1 (PubMed:9687510, PubMed:9792677). RPS6KA5/MSK1 and RPS6KA4/MSK2 play important roles in the rapid induction of immediate-early genes in response to stress or mitogenic stimuli, either by inducing chromatin remodeling or by recruiting the transcription machinery (PubMed:9687510, PubMed:9792677). On the other hand, two other kinase targets, MAPKAPK2/MK2 and MAPKAPK3/MK3, participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating ZFP36 (tristetraprolin) and ELAVL1, and by regulating EEF2K, which is important for the elongation of mRNA during translation. MKNK1/MNK1 and MKNK2/MNK2, two other kinases activated by p38 MAPKs, regulate protein synthesis by phosphorylating the initiation factor EIF4E2 (PubMed:11154262). MAPK14 also interacts with casein kinase II, leading to its activation through autophosphorylation and further phosphorylation of TP53/p53 (PubMed:10747897). In the cytoplasm, the p38 MAPK pathway is an important regulator of protein turnover. For example, CFLAR is an inhibitor of TNF-induced apoptosis whose proteasome-mediated degradation is regulated by p38 MAPK phosphorylation. In a similar way, MAPK14 phosphorylates the ubiquitin ligase SIAH2, regulating its activity towards EGLN3 (PubMed:17003045). MAPK14 may also inhibit the lysosomal degradation pathway of autophagy by interfering with the intracellular trafficking of the transmembrane protein ATG9 (PubMed:19893488). Another function of MAPK14 is to regulate the endocytosis of membrane receptors by different mechanisms that impinge on the small GTPase RAB5A. In addition, clathrin-mediated EGFR internalization induced by inflammatory cytokines and UV irradiation depends on MAPK14-mediated phosphorylation of EGFR itself as well as of RAB5A effectors (PubMed:16932740). Ectodomain shedding of transmembrane proteins is regulated by p38 MAPKs as well. In response to inflammatory stimuli, p38 MAPKs phosphorylate the membrane-associated metalloprotease ADAM17 (PubMed:20188673). Such phosphorylation is required for ADAM17-mediated ectodomain shedding of TGF-alpha family ligands, which results in the activation of EGFR signaling and cell proliferation. Another p38 MAPK substrate is FGFR1. FGFR1 can be translocated from the extracellular space into the cytosol and nucleus of target cells, and regulates processes such as rRNA synthesis and cell growth. FGFR1 translocation requires p38 MAPK activation. In the nucleus, many transcription factors are phosphorylated and activated by p38 MAPKs in response to different stimuli. Classical examples include ATF1, ATF2, ATF6, ELK1, PTPRH, DDIT3, TP53/p53 and MEF2C and MEF2A (PubMed:10330143, PubMed:9430721, PubMed:9858528). The p38 MAPKs are emerging as important modulators of gene expression by regulating chromatin modifiers and remodelers. The promoters of several genes involved in the inflammatory response, such as IL6, IL8 and IL12B, display a p38 MAPK-dependent enrichment of histone H3 phosphorylation on 'Ser-10' (H3S10ph) in LPS-stimulated myeloid cells. This phosphorylation enhances the accessibility of the cryptic NF-kappa-B-binding sites marking promoters for increased NF-kappa-B recruitment. Phosphorylates CDC25B and CDC25C which is required for binding to 14-3-3 proteins and leads to initiation of a G2 delay after ultraviolet radiation (PubMed:11333986). Phosphorylates TIAR following DNA damage, releasing TIAR from GADD45A mRNA and preventing mRNA degradation (PubMed:20932473). The p38 MAPKs may also have kinase-independent roles, which are thought to be due to the binding to targets in the absence of phosphorylation. Protein O-Glc-N-acylation catalyzed by the OGT is regulated by MAPK14, and, although OGT does not seem to be phosphorylated by MAPK14, their interaction increases upon MAPK14 activation induced by glucose deprivation. This interaction may regulate OGT activity by recruiting it to specific targets such as neurofilament H, stimulating its O-Glc-N-acylation. Required in mid-fetal development for the growth of embryo-derived blood vessels in the labyrinth layer of the placenta. Also plays an essential role in developmental and stress-induced erythropoiesis, through regulation of EPO gene expression (PubMed:10943842). Isoform MXI2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2. Isoform EXIP may play a role in the early onset of apoptosis. Phosphorylates S100A9 at 'Thr-113' (PubMed:15905572). Phosphorylates NLRP1 downstream of MAP3K20/ZAK in response to UV-B irradiation and ribosome collisions, promoting activation of the NLRP1 inflammasome and pyroptosis (PubMed:35857590). {ECO:0000269|PubMed:10330143, ECO:0000269|PubMed:10747897, ECO:0000269|PubMed:10943842, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11333986, ECO:0000269|PubMed:15905572, ECO:0000269|PubMed:16932740, ECO:0000269|PubMed:17003045, ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:19893488, ECO:0000269|PubMed:20188673, ECO:0000269|PubMed:20932473, ECO:0000269|PubMed:35857590, ECO:0000269|PubMed:9430721, ECO:0000269|PubMed:9687510, ECO:0000269|PubMed:9792677, ECO:0000269|PubMed:9858528}.; FUNCTION: (Microbial infection) Activated by phosphorylation by M.tuberculosis EsxA in T-cells leading to inhibition of IFN-gamma production; phosphorylation is apparent within 15 minutes and is inhibited by kinase-specific inhibitors SB203580 and siRNA (PubMed:21586573). {ECO:0000269|PubMed:21586573}. |
| Q86Z02 | HIPK1 | S350 | ochoa | Homeodomain-interacting protein kinase 1 (EC 2.7.11.1) (Nuclear body-associated kinase 2) | Serine/threonine-protein kinase involved in transcription regulation and TNF-mediated cellular apoptosis. Plays a role as a corepressor for homeodomain transcription factors. Phosphorylates DAXX and MYB. Phosphorylates DAXX in response to stress, and mediates its translocation from the nucleus to the cytoplasm. Inactivates MYB transcription factor activity by phosphorylation. Prevents MAP3K5-JNK activation in the absence of TNF. TNF triggers its translocation to the cytoplasm in response to stress stimuli, thus activating nuclear MAP3K5-JNK by derepression and promoting apoptosis. May be involved in anti-oxidative stress responses. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. Promotes angiogenesis and to be involved in erythroid differentiation. May be involved in malignant squamous cell tumor formation. Phosphorylates PAGE4 at 'Thr-51' which is critical for the ability of PAGE4 to potentiate the transcriptional activator activity of JUN (PubMed:24559171). {ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:12968034, ECO:0000269|PubMed:15701637, ECO:0000269|PubMed:16390825, ECO:0000269|PubMed:19646965, ECO:0000269|PubMed:24559171}. |
| Q8IU85 | CAMK1D | S179 | ochoa | Calcium/calmodulin-dependent protein kinase type 1D (EC 2.7.11.17) (CaM kinase I delta) (CaM kinase ID) (CaM-KI delta) (CaMKI delta) (CaMKID) (CaMKI-like protein kinase) (CKLiK) | Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, activates CREB-dependent gene transcription, regulates calcium-mediated granulocyte function and respiratory burst and promotes basal dendritic growth of hippocampal neurons. In neutrophil cells, required for cytokine-induced proliferative responses and activation of the respiratory burst. Activates the transcription factor CREB1 in hippocampal neuron nuclei. May play a role in apoptosis of erythroleukemia cells. In vitro, phosphorylates transcription factor CREM isoform Beta. {ECO:0000269|PubMed:11050006, ECO:0000269|PubMed:15840691, ECO:0000269|PubMed:16324104, ECO:0000269|PubMed:17056143}. |
| Q8TD08 | MAPK15 | T175 | psp | Mitogen-activated protein kinase 15 (MAP kinase 15) (MAPK 15) (EC 2.7.11.24) (Extracellular signal-regulated kinase 7) (ERK-7) (Extracellular signal-regulated kinase 8) (ERK-8) | Atypical MAPK protein that regulates several process such as autophagy, ciliogenesis, protein trafficking/secretion and genome integrity, in a kinase activity-dependent manner (PubMed:20733054, PubMed:21847093, PubMed:22948227, PubMed:24618899, PubMed:29021280). Controls both, basal and starvation-induced autophagy throught its interaction with GABARAP, MAP1LC3B and GABARAPL1 leading to autophagosome formation, SQSTM1 degradation and reduced MAP1LC3B inhibitory phosphorylation (PubMed:22948227). Regulates primary cilium formation and the localization of ciliary proteins involved in cilium structure, transport, and signaling (PubMed:29021280). Prevents the relocation of the sugar-adding enzymes from the Golgi to the endoplasmic reticulum, thereby restricting the production of sugar-coated proteins (PubMed:24618899). Upon amino-acid starvation, mediates transitional endoplasmic reticulum site disassembly and inhibition of secretion (PubMed:21847093). Binds to chromatin leading to MAPK15 activation and interaction with PCNA, that which protects genomic integrity by inhibiting MDM2-mediated degradation of PCNA (PubMed:20733054). Regulates DA transporter (DAT) activity and protein expression via activation of RhoA (PubMed:28842414). In response to H(2)O(2) treatment phosphorylates ELAVL1, thus preventing it from binding to the PDCD4 3'UTR and rendering the PDCD4 mRNA accessible to miR-21 and leading to its degradation and loss of protein expression (PubMed:26595526). Also functions in a kinase activity-independent manner as a negative regulator of growth (By similarity). Phosphorylates in vitro FOS and MBP (PubMed:11875070, PubMed:16484222, PubMed:19166846, PubMed:20638370). During oocyte maturation, plays a key role in the microtubule organization and meiotic cell cycle progression in oocytes, fertilized eggs, and early embryos (By similarity). Interacts with ESRRA promoting its re-localization from the nucleus to the cytoplasm and then prevents its transcriptional activity (PubMed:21190936). {ECO:0000250|UniProtKB:Q80Y86, ECO:0000250|UniProtKB:Q9Z2A6, ECO:0000269|PubMed:11875070, ECO:0000269|PubMed:16484222, ECO:0000269|PubMed:19166846, ECO:0000269|PubMed:20638370, ECO:0000269|PubMed:20733054, ECO:0000269|PubMed:21190936, ECO:0000269|PubMed:21847093, ECO:0000269|PubMed:22948227, ECO:0000269|PubMed:24618899, ECO:0000269|PubMed:26595526, ECO:0000269|PubMed:28842414, ECO:0000269|PubMed:29021280}. |
| Q8WWW8 | GAB3 | T163 | ochoa | GRB2-associated-binding protein 3 (GRB2-associated binder 3) (Growth factor receptor bound protein 2-associated protein 3) | None |
| Q99666 | RGPD5 | T1184 | ochoa | RANBP2-like and GRIP domain-containing protein 5/6 (Ran-binding protein 2-like 1/2) (RanBP2-like 1/2) (RanBP2L1) (RanBP2L2) (Sperm membrane protein BS-63) | None |
| Q9H2X6 | HIPK2 | S359 | ochoa|psp | Homeodomain-interacting protein kinase 2 (hHIPk2) (EC 2.7.11.1) | Serine/threonine-protein kinase involved in transcription regulation, p53/TP53-mediated cellular apoptosis and regulation of the cell cycle. Acts as a corepressor of several transcription factors, including SMAD1 and POU4F1/Brn3a and probably NK homeodomain transcription factors. Phosphorylates PDX1, ATF1, PML, p53/TP53, CREB1, CTBP1, CBX4, RUNX1, EP300, CTNNB1, HMGA1, ZBTB4 and DAZAP2. Inhibits cell growth and promotes apoptosis through the activation of p53/TP53 both at the transcription level and at the protein level (by phosphorylation and indirect acetylation). The phosphorylation of p53/TP53 may be mediated by a p53/TP53-HIPK2-AXIN1 complex. Involved in the response to hypoxia by acting as a transcriptional co-suppressor of HIF1A. Mediates transcriptional activation of TP73. In response to TGFB, cooperates with DAXX to activate JNK. Negative regulator through phosphorylation and subsequent proteasomal degradation of CTNNB1 and the antiapoptotic factor CTBP1. In the Wnt/beta-catenin signaling pathway acts as an intermediate kinase between MAP3K7/TAK1 and NLK to promote the proteasomal degradation of MYB. Phosphorylates CBX4 upon DNA damage and promotes its E3 SUMO-protein ligase activity. Activates CREB1 and ATF1 transcription factors by phosphorylation in response to genotoxic stress. In response to DNA damage, stabilizes PML by phosphorylation. PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation. Promotes angiogenesis, and is involved in erythroid differentiation, especially during fetal liver erythropoiesis. Phosphorylation of RUNX1 and EP300 stimulates EP300 transcription regulation activity. Triggers ZBTB4 protein degradation in response to DNA damage. In response to DNA damage, phosphorylates DAZAP2 which localizes DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent proteasomal degradation (PubMed:33591310). Modulates HMGA1 DNA-binding affinity. In response to high glucose, triggers phosphorylation-mediated subnuclear localization shifting of PDX1. Involved in the regulation of eye size, lens formation and retinal lamination during late embryogenesis. {ECO:0000269|PubMed:11740489, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12851404, ECO:0000269|PubMed:12874272, ECO:0000269|PubMed:14678985, ECO:0000269|PubMed:17018294, ECO:0000269|PubMed:17960875, ECO:0000269|PubMed:18695000, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19046997, ECO:0000269|PubMed:19448668, ECO:0000269|PubMed:20307497, ECO:0000269|PubMed:20573984, ECO:0000269|PubMed:20637728, ECO:0000269|PubMed:20980392, ECO:0000269|PubMed:21192925, ECO:0000269|PubMed:22825850, ECO:0000269|PubMed:33591310}. |
| Q9H422 | HIPK3 | S357 | ochoa | Homeodomain-interacting protein kinase 3 (EC 2.7.11.1) (Androgen receptor-interacting nuclear protein kinase) (ANPK) (Fas-interacting serine/threonine-protein kinase) (FIST) (Homolog of protein kinase YAK1) | Serine/threonine-protein kinase involved in transcription regulation, apoptosis and steroidogenic gene expression. Phosphorylates JUN and RUNX2. Seems to negatively regulate apoptosis by promoting FADD phosphorylation. Enhances androgen receptor-mediated transcription. May act as a transcriptional corepressor for NK homeodomain transcription factors. The phosphorylation of NR5A1 activates SF1 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. In osteoblasts, supports transcription activation: phosphorylates RUNX2 that synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). {ECO:0000269|PubMed:14766760, ECO:0000269|PubMed:17210646}. |
| Q9HAZ1 | CLK4 | S335 | ochoa | Dual specificity protein kinase CLK4 (EC 2.7.12.1) (CDC-like kinase 4) | Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:11170754, ECO:0000269|PubMed:19168442}. |
| Q9NYV4 | CDK12 | T893 | ochoa | Cyclin-dependent kinase 12 (EC 2.7.11.22) (EC 2.7.11.23) (Cdc2-related kinase, arginine/serine-rich) (CrkRS) (Cell division cycle 2-related protein kinase 7) (CDC2-related protein kinase 7) (Cell division protein kinase 12) (hCDK12) | Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| Q9NZJ5 | EIF2AK3 | T982 | psp | Eukaryotic translation initiation factor 2-alpha kinase 3 (EC 2.7.11.1) (PRKR-like endoplasmic reticulum kinase) (Pancreatic eIF2-alpha kinase) (HsPEK) (Protein tyrosine kinase EIF2AK3) (EC 2.7.10.2) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to various stress, such as unfolded protein response (UPR) (PubMed:10026192, PubMed:10677345, PubMed:11907036, PubMed:12086964, PubMed:25925385, PubMed:31023583). Key effector of the integrated stress response (ISR) to unfolded proteins: EIF2AK3/PERK specifically recognizes and binds misfolded proteins, leading to its activation and EIF2S1/eIF-2-alpha phosphorylation (PubMed:10677345, PubMed:27917829, PubMed:31023583). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1, and hence allowing ATF4- and QRICH1-mediated reprogramming (PubMed:10026192, PubMed:10677345, PubMed:31023583, PubMed:33384352). The EIF2AK3/PERK-mediated unfolded protein response increases mitochondrial oxidative phosphorylation by promoting ATF4-mediated expression of COX7A2L/SCAF1, thereby increasing formation of respiratory chain supercomplexes (PubMed:31023583). In contrast to most subcellular compartments, mitochondria are protected from the EIF2AK3/PERK-mediated unfolded protein response due to EIF2AK3/PERK inhibition by ATAD3A at mitochondria-endoplasmic reticulum contact sites (PubMed:39116259). In addition to EIF2S1/eIF-2-alpha, also phosphorylates NFE2L2/NRF2 in response to stress, promoting release of NFE2L2/NRF2 from the BCR(KEAP1) complex, leading to nuclear accumulation and activation of NFE2L2/NRF2 (By similarity). Serves as a critical effector of unfolded protein response (UPR)-induced G1 growth arrest due to the loss of cyclin-D1 (CCND1) (By similarity). Involved in control of mitochondrial morphology and function (By similarity). {ECO:0000250|UniProtKB:Q9Z2B5, ECO:0000269|PubMed:10026192, ECO:0000269|PubMed:10677345, ECO:0000269|PubMed:11907036, ECO:0000269|PubMed:12086964, ECO:0000269|PubMed:25925385, ECO:0000269|PubMed:27917829, ECO:0000269|PubMed:31023583, ECO:0000269|PubMed:33384352, ECO:0000269|PubMed:39116259}. |
| Q9P2K8 | EIF2AK4 | T899 | psp | eIF-2-alpha kinase GCN2 (EC 2.7.11.1) (Eukaryotic translation initiation factor 2-alpha kinase 4) (GCN2-like protein) | Metabolic-stress sensing protein kinase that phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha) in response to low amino acid availability (PubMed:25329545, PubMed:32610081). Plays a role as an activator of the integrated stress response (ISR) required for adaptation to amino acid starvation (By similarity). EIF2S1/eIF-2-alpha phosphorylation in response to stress converts EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, leading to a global attenuation of cap-dependent translation, and thus to a reduced overall utilization of amino acids, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4, and hence allowing ATF4-mediated reprogramming of amino acid biosynthetic gene expression to alleviate nutrient depletion (PubMed:32610081). Binds uncharged tRNAs (By similarity). Required for the translational induction of protein kinase PRKCH following amino acid starvation (By similarity). Involved in cell cycle arrest by promoting cyclin D1 mRNA translation repression after the unfolded protein response pathway (UPR) activation or cell cycle inhibitor CDKN1A/p21 mRNA translation activation in response to amino acid deprivation (PubMed:26102367). Plays a role in the consolidation of synaptic plasticity, learning as well as formation of long-term memory (By similarity). Plays a role in neurite outgrowth inhibition (By similarity). Plays a proapoptotic role in response to glucose deprivation (By similarity). Promotes global cellular protein synthesis repression in response to UV irradiation independently of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 MAPK signaling pathways (By similarity). Plays a role in the antiviral response against alphavirus infection; impairs early viral mRNA translation of the incoming genomic virus RNA, thus preventing alphavirus replication (By similarity). {ECO:0000250|UniProtKB:P15442, ECO:0000250|UniProtKB:Q9QZ05, ECO:0000269|PubMed:25329545, ECO:0000269|PubMed:26102367, ECO:0000269|PubMed:32610081}.; FUNCTION: (Microbial infection) Plays a role in modulating the adaptive immune response to yellow fever virus infection; promotes dendritic cells to initiate autophagy and antigene presentation to both CD4(+) and CD8(+) T-cells under amino acid starvation (PubMed:24310610). {ECO:0000269|PubMed:24310610}. |
| Q9UBE8 | NLK | T298 | ochoa | Serine/threonine-protein kinase NLK (EC 2.7.11.24) (Nemo-like kinase) (Protein LAK1) | Serine/threonine-protein kinase that regulates a number of transcription factors with key roles in cell fate determination (PubMed:12482967, PubMed:14960582, PubMed:15004007, PubMed:15764709, PubMed:20061393, PubMed:20874444, PubMed:21454679). Positive effector of the non-canonical Wnt signaling pathway, acting downstream of WNT5A, MAP3K7/TAK1 and HIPK2 (PubMed:15004007, PubMed:15764709). Negative regulator of the canonical Wnt/beta-catenin signaling pathway (PubMed:12482967). Binds to and phosphorylates TCF7L2/TCF4 and LEF1, promoting the dissociation of the TCF7L2/LEF1/beta-catenin complex from DNA, as well as the ubiquitination and subsequent proteolysis of LEF1 (PubMed:21454679). Together these effects inhibit the transcriptional activation of canonical Wnt/beta-catenin target genes (PubMed:12482967, PubMed:21454679). Negative regulator of the Notch signaling pathway (PubMed:20118921). Binds to and phosphorylates NOTCH1, thereby preventing the formation of a transcriptionally active ternary complex of NOTCH1, RBPJ/RBPSUH and MAML1 (PubMed:20118921). Negative regulator of the MYB family of transcription factors (PubMed:15082531). Phosphorylation of MYB leads to its subsequent proteolysis while phosphorylation of MYBL1 and MYBL2 inhibits their interaction with the coactivator CREBBP (PubMed:15082531). Other transcription factors may also be inhibited by direct phosphorylation of CREBBP itself (PubMed:15082531). Acts downstream of IL6 and MAP3K7/TAK1 to phosphorylate STAT3, which is in turn required for activation of NLK by MAP3K7/TAK1 (PubMed:15004007, PubMed:15764709). Upon IL1B stimulus, cooperates with ATF5 to activate the transactivation activity of C/EBP subfamily members (PubMed:25512613). Phosphorylates ATF5 but also stabilizes ATF5 protein levels in a kinase-independent manner (PubMed:25512613). Acts as an inhibitor of the mTORC1 complex in response to osmotic stress by mediating phosphorylation of RPTOR, thereby preventing recruitment of the mTORC1 complex to lysosomes (PubMed:26588989). {ECO:0000269|PubMed:12482967, ECO:0000269|PubMed:14960582, ECO:0000269|PubMed:15004007, ECO:0000269|PubMed:15082531, ECO:0000269|PubMed:15764709, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20118921, ECO:0000269|PubMed:20874444, ECO:0000269|PubMed:21454679, ECO:0000269|PubMed:25512613, ECO:0000269|PubMed:26588989}. |
| Q9UPZ9 | CILK1 | T157 | ochoa|psp | Serine/threonine-protein kinase ICK (EC 2.7.11.1) (Ciliogenesis associated kinase 1) (Intestinal cell kinase) (hICK) (Laryngeal cancer kinase 2) (LCK2) (MAK-related kinase) (MRK) | Required for ciliogenesis (PubMed:24797473). Phosphorylates KIF3A (By similarity). Involved in the control of ciliary length (PubMed:24853502). Regulates the ciliary localization of SHH pathway components as well as the localization of IFT components at ciliary tips (By similarity). May play a key role in the development of multiple organ systems and particularly in cardiac development (By similarity). Regulates intraflagellar transport (IFT) speed and negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner and this regulation requires its kinase activity (By similarity). {ECO:0000250|UniProtKB:Q62726, ECO:0000250|UniProtKB:Q9JKV2, ECO:0000269|PubMed:24797473, ECO:0000269|PubMed:24853502}. |
| Q9UQ07 | MOK | T159 | psp | MAPK/MAK/MRK overlapping kinase (EC 2.7.11.22) (MOK protein kinase) (Renal tumor antigen 1) (RAGE-1) | Able to phosphorylate several exogenous substrates and to undergo autophosphorylation. Negatively regulates cilium length in a cAMP and mTORC1 signaling-dependent manner. {ECO:0000250|UniProtKB:Q9WVS4}. |
| Q9Y463 | DYRK1B | Y271 | ochoa|psp | Dual specificity tyrosine-phosphorylation-regulated kinase 1B (EC 2.7.12.1) (Minibrain-related kinase) (Mirk protein kinase) | Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenance (PubMed:33469661). During DNA damage, mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2 (PubMed:32611815). Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1). {ECO:0000269|PubMed:10910078, ECO:0000269|PubMed:11980910, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:24827035, ECO:0000269|PubMed:33469661}. |
| Q59H18 | TNNI3K | T622 | Sugiyama | Serine/threonine-protein kinase TNNI3K (EC 2.7.11.1) (Cardiac ankyrin repeat kinase) (Cardiac troponin I-interacting kinase) (TNNI3-interacting kinase) | May play a role in cardiac physiology. {ECO:0000303|PubMed:12721663}. |
| Q86V86 | PIM3 | T202 | Sugiyama | Serine/threonine-protein kinase pim-3 (EC 2.7.11.1) | Proto-oncogene with serine/threonine kinase activity that can prevent apoptosis, promote cell survival and protein translation. May contribute to tumorigenesis through: the delivery of survival signaling through phosphorylation of BAD which induces release of the anti-apoptotic protein Bcl-X(L), the regulation of cell cycle progression, protein synthesis and by regulation of MYC transcriptional activity. Additionally to this role on tumorigenesis, can also negatively regulate insulin secretion by inhibiting the activation of MAPK1/3 (ERK1/2), through SOCS6. Involved also in the control of energy metabolism and regulation of AMPK activity in modulating MYC and PPARGC1A protein levels and cell growth. {ECO:0000269|PubMed:15540201, ECO:0000269|PubMed:16818649, ECO:0000269|PubMed:17270021, ECO:0000269|PubMed:17876606, ECO:0000269|PubMed:18593906}. |
Download
| reactome_id | name | p | -log10_p |
|---|---|---|---|
| R-HSA-450294 | MAP kinase activation | 1.110223e-16 | 15.955 |
| R-HSA-448424 | Interleukin-17 signaling | 1.110223e-16 | 15.955 |
| R-HSA-2559580 | Oxidative Stress Induced Senescence | 1.110223e-16 | 15.955 |
| R-HSA-975138 | TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation | 1.110223e-16 | 15.955 |
| R-HSA-975871 | MyD88 cascade initiated on plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-168176 | Toll Like Receptor 5 (TLR5) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-168142 | Toll Like Receptor 10 (TLR10) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-937061 | TRIF (TICAM1)-mediated TLR4 signaling | 1.110223e-16 | 15.955 |
| R-HSA-166166 | MyD88-independent TLR4 cascade | 1.110223e-16 | 15.955 |
| R-HSA-975155 | MyD88 dependent cascade initiated on endosome | 1.110223e-16 | 15.955 |
| R-HSA-168164 | Toll Like Receptor 3 (TLR3) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-166058 | MyD88:MAL(TIRAP) cascade initiated on plasma membrane | 1.110223e-16 | 15.955 |
| R-HSA-168188 | Toll Like Receptor TLR6:TLR2 Cascade | 1.110223e-16 | 15.955 |
| R-HSA-168179 | Toll Like Receptor TLR1:TLR2 Cascade | 1.110223e-16 | 15.955 |
| R-HSA-181438 | Toll Like Receptor 2 (TLR2) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-168181 | Toll Like Receptor 7/8 (TLR7/8) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-168138 | Toll Like Receptor 9 (TLR9) Cascade | 1.110223e-16 | 15.955 |
| R-HSA-2559583 | Cellular Senescence | 2.220446e-16 | 15.654 |
| R-HSA-166016 | Toll Like Receptor 4 (TLR4) Cascade | 4.440892e-16 | 15.353 |
| R-HSA-450282 | MAPK targets/ Nuclear events mediated by MAP kinases | 6.328271e-15 | 14.199 |
| R-HSA-168898 | Toll-like Receptor Cascades | 1.088019e-14 | 13.963 |
| R-HSA-450341 | Activation of the AP-1 family of transcription factors | 2.509104e-14 | 13.600 |
| R-HSA-187687 | Signalling to ERKs | 1.493312e-10 | 9.826 |
| R-HSA-450321 | JNK (c-Jun kinases) phosphorylation and activation mediated by activated human ... | 4.799453e-10 | 9.319 |
| R-HSA-450302 | activated TAK1 mediates p38 MAPK activation | 6.003459e-10 | 9.222 |
| R-HSA-1280215 | Cytokine Signaling in Immune system | 1.679206e-09 | 8.775 |
| R-HSA-2262752 | Cellular responses to stress | 5.290296e-09 | 8.277 |
| R-HSA-168638 | NOD1/2 Signaling Pathway | 7.096827e-09 | 8.149 |
| R-HSA-171007 | p38MAPK events | 7.573765e-09 | 8.121 |
| R-HSA-449147 | Signaling by Interleukins | 2.561216e-08 | 7.592 |
| R-HSA-198753 | ERK/MAPK targets | 3.569013e-08 | 7.447 |
| R-HSA-167044 | Signalling to RAS | 3.569013e-08 | 7.447 |
| R-HSA-187037 | Signaling by NTRK1 (TRKA) | 3.247450e-08 | 7.488 |
| R-HSA-8953897 | Cellular responses to stimuli | 3.145220e-08 | 7.502 |
| R-HSA-166520 | Signaling by NTRKs | 1.008592e-07 | 6.996 |
| R-HSA-168643 | Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signali... | 1.919745e-07 | 6.717 |
| R-HSA-2871796 | FCERI mediated MAPK activation | 2.357089e-07 | 6.628 |
| R-HSA-198725 | Nuclear Events (kinase and transcription factor activation) | 3.537753e-07 | 6.451 |
| R-HSA-2454202 | Fc epsilon receptor (FCERI) signaling | 8.918907e-07 | 6.050 |
| R-HSA-5210891 | Uptake and function of anthrax toxins | 1.123814e-06 | 5.949 |
| R-HSA-168249 | Innate Immune System | 1.509243e-06 | 5.821 |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants | 3.461793e-06 | 5.461 |
| R-HSA-9700206 | Signaling by ALK in cancer | 3.461793e-06 | 5.461 |
| R-HSA-525793 | Myogenesis | 4.904743e-06 | 5.309 |
| R-HSA-2151209 | Activation of PPARGC1A (PGC-1alpha) by phosphorylation | 1.337602e-05 | 4.874 |
| R-HSA-2559585 | Oncogene Induced Senescence | 1.419163e-05 | 4.848 |
| R-HSA-2559582 | Senescence-Associated Secretory Phenotype (SASP) | 1.503378e-05 | 4.823 |
| R-HSA-202670 | ERKs are inactivated | 2.044892e-05 | 4.689 |
| R-HSA-168256 | Immune System | 1.831656e-05 | 4.737 |
| R-HSA-9632693 | Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects | 5.120325e-05 | 4.291 |
| R-HSA-9630750 | Evasion of Oncogene Induced Senescence Due to p16INK4A Defects | 5.120325e-05 | 4.291 |
| R-HSA-9630794 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4... | 5.120325e-05 | 4.291 |
| R-HSA-9632700 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 5.120325e-05 | 4.291 |
| R-HSA-5339562 | Uptake and actions of bacterial toxins | 5.647939e-05 | 4.248 |
| R-HSA-881907 | Gastrin-CREB signalling pathway via PKC and MAPK | 8.195677e-05 | 4.086 |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway | 8.224169e-05 | 4.085 |
| R-HSA-9630747 | Diseases of Cellular Senescence | 9.082865e-05 | 4.042 |
| R-HSA-9675132 | Diseases of cellular response to stress | 9.082865e-05 | 4.042 |
| R-HSA-194138 | Signaling by VEGF | 1.203547e-04 | 3.920 |
| R-HSA-9754119 | Drug-mediated inhibition of CDK4/CDK6 activity | 2.034706e-04 | 3.691 |
| R-HSA-9652169 | Signaling by MAP2K mutants | 2.034706e-04 | 3.691 |
| R-HSA-3700989 | Transcriptional Regulation by TP53 | 2.360596e-04 | 3.627 |
| R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation | 3.249651e-04 | 3.488 |
| R-HSA-5674499 | Negative feedback regulation of MAPK pathway | 3.601441e-04 | 3.444 |
| R-HSA-913531 | Interferon Signaling | 4.416722e-04 | 3.355 |
| R-HSA-9842640 | Signaling by LTK in cancer | 4.548103e-04 | 3.342 |
| R-HSA-2173796 | SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 4.812317e-04 | 3.318 |
| R-HSA-5633007 | Regulation of TP53 Activity | 3.625695e-04 | 3.441 |
| R-HSA-170834 | Signaling by TGF-beta Receptor Complex | 5.253113e-04 | 3.280 |
| R-HSA-9732724 | IFNG signaling activates MAPKs | 5.602662e-04 | 3.252 |
| R-HSA-3371453 | Regulation of HSF1-mediated heat shock response | 6.216832e-04 | 3.206 |
| R-HSA-5675221 | Negative regulation of MAPK pathway | 6.566793e-04 | 3.183 |
| R-HSA-444257 | RSK activation | 6.764398e-04 | 3.170 |
| R-HSA-74749 | Signal attenuation | 9.406539e-04 | 3.027 |
| R-HSA-9627069 | Regulation of the apoptosome activity | 9.406539e-04 | 3.027 |
| R-HSA-111458 | Formation of apoptosome | 9.406539e-04 | 3.027 |
| R-HSA-9635465 | Suppression of apoptosis | 1.088552e-03 | 2.963 |
| R-HSA-3371556 | Cellular response to heat stress | 1.198283e-03 | 2.921 |
| R-HSA-111461 | Cytochrome c-mediated apoptotic response | 1.246884e-03 | 2.904 |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | 1.343475e-03 | 2.872 |
| R-HSA-2173793 | Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1.411336e-03 | 2.850 |
| R-HSA-109606 | Intrinsic Pathway for Apoptosis | 1.411336e-03 | 2.850 |
| R-HSA-879415 | Advanced glycosylation endproduct receptor signaling | 1.415578e-03 | 2.849 |
| R-HSA-9661069 | Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) | 1.594565e-03 | 2.797 |
| R-HSA-9659787 | Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects | 1.594565e-03 | 2.797 |
| R-HSA-170968 | Frs2-mediated activation | 1.594565e-03 | 2.797 |
| R-HSA-162658 | Golgi Cisternae Pericentriolar Stack Reorganization | 1.594565e-03 | 2.797 |
| R-HSA-5578768 | Physiological factors | 1.783776e-03 | 2.749 |
| R-HSA-2032785 | YAP1- and WWTR1 (TAZ)-stimulated gene expression | 1.783776e-03 | 2.749 |
| R-HSA-1502540 | Signaling by Activin | 1.983142e-03 | 2.703 |
| R-HSA-1295596 | Spry regulation of FGF signaling | 1.983142e-03 | 2.703 |
| R-HSA-169893 | Prolonged ERK activation events | 2.192592e-03 | 2.659 |
| R-HSA-450604 | KSRP (KHSRP) binds and destabilizes mRNA | 2.192592e-03 | 2.659 |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers | 2.262378e-03 | 2.645 |
| R-HSA-450531 | Regulation of mRNA stability by proteins that bind AU-rich elements | 2.652602e-03 | 2.576 |
| R-HSA-9824439 | Bacterial Infection Pathways | 2.746720e-03 | 2.561 |
| R-HSA-4086398 | Ca2+ pathway | 2.746726e-03 | 2.561 |
| R-HSA-446652 | Interleukin-1 family signaling | 2.759689e-03 | 2.559 |
| R-HSA-1169410 | Antiviral mechanism by IFN-stimulated genes | 2.877402e-03 | 2.541 |
| R-HSA-111471 | Apoptotic factor-mediated response | 2.880772e-03 | 2.540 |
| R-HSA-1169408 | ISG15 antiviral mechanism | 2.941109e-03 | 2.531 |
| R-HSA-112409 | RAF-independent MAPK1/3 activation | 4.223111e-03 | 2.374 |
| R-HSA-6796648 | TP53 Regulates Transcription of DNA Repair Genes | 3.248238e-03 | 2.488 |
| R-HSA-9006936 | Signaling by TGFB family members | 3.251136e-03 | 2.488 |
| R-HSA-445144 | Signal transduction by L1 | 3.388737e-03 | 2.470 |
| R-HSA-9634638 | Estrogen-dependent nuclear events downstream of ESR-membrane signaling | 4.520284e-03 | 2.345 |
| R-HSA-438064 | Post NMDA receptor activation events | 4.411237e-03 | 2.355 |
| R-HSA-1181150 | Signaling by NODAL | 3.388737e-03 | 2.470 |
| R-HSA-1640170 | Cell Cycle | 3.199683e-03 | 2.495 |
| R-HSA-982772 | Growth hormone receptor signaling | 4.520284e-03 | 2.345 |
| R-HSA-212436 | Generic Transcription Pathway | 6.062406e-03 | 2.217 |
| R-HSA-5654732 | Negative regulation of FGFR3 signaling | 6.146070e-03 | 2.211 |
| R-HSA-8940973 | RUNX2 regulates osteoblast differentiation | 6.146070e-03 | 2.211 |
| R-HSA-5654733 | Negative regulation of FGFR4 signaling | 6.498759e-03 | 2.187 |
| R-HSA-9020702 | Interleukin-1 signaling | 6.741841e-03 | 2.171 |
| R-HSA-9630791 | Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 | 6.808168e-03 | 2.167 |
| R-HSA-9632697 | Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding... | 6.808168e-03 | 2.167 |
| R-HSA-3642279 | TGFBR2 MSI Frameshift Mutants in Cancer | 6.808168e-03 | 2.167 |
| R-HSA-169131 | Inhibition of PKR | 6.808168e-03 | 2.167 |
| R-HSA-9687139 | Aberrant regulation of mitotic cell cycle due to RB1 defects | 6.860475e-03 | 2.164 |
| R-HSA-456926 | Thrombin signalling through proteinase activated receptors (PARs) | 6.860475e-03 | 2.164 |
| R-HSA-442755 | Activation of NMDA receptors and postsynaptic events | 6.907517e-03 | 2.161 |
| R-HSA-9675126 | Diseases of mitotic cell cycle | 7.610739e-03 | 2.119 |
| R-HSA-2173795 | Downregulation of SMAD2/3:SMAD4 transcriptional activity | 7.610739e-03 | 2.119 |
| R-HSA-442742 | CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling | 7.999160e-03 | 2.097 |
| R-HSA-5654726 | Negative regulation of FGFR1 signaling | 7.999160e-03 | 2.097 |
| R-HSA-5654727 | Negative regulation of FGFR2 signaling | 8.802269e-03 | 2.055 |
| R-HSA-9768919 | NPAS4 regulates expression of target genes | 8.802269e-03 | 2.055 |
| R-HSA-8941326 | RUNX2 regulates bone development | 9.639988e-03 | 2.016 |
| R-HSA-6802948 | Signaling by high-kinase activity BRAF mutants | 1.007167e-02 | 1.997 |
| R-HSA-176034 | Interactions of Tat with host cellular proteins | 1.019517e-02 | 1.992 |
| R-HSA-1592230 | Mitochondrial biogenesis | 1.030964e-02 | 1.987 |
| R-HSA-8878166 | Transcriptional regulation by RUNX2 | 1.073777e-02 | 1.969 |
| R-HSA-68875 | Mitotic Prophase | 1.095566e-02 | 1.960 |
| R-HSA-168276 | NS1 Mediated Effects on Host Pathways | 1.096039e-02 | 1.960 |
| R-HSA-5663205 | Infectious disease | 1.163804e-02 | 1.934 |
| R-HSA-73857 | RNA Polymerase II Transcription | 1.179197e-02 | 1.928 |
| R-HSA-1643685 | Disease | 1.216414e-02 | 1.915 |
| R-HSA-5674135 | MAP2K and MAPK activation | 1.235592e-02 | 1.908 |
| R-HSA-9656223 | Signaling by RAF1 mutants | 1.235592e-02 | 1.908 |
| R-HSA-9637690 | Response of Mtb to phagocytosis | 1.332722e-02 | 1.875 |
| R-HSA-5654743 | Signaling by FGFR4 | 1.332722e-02 | 1.875 |
| R-HSA-198765 | Signalling to ERK5 | 1.357082e-02 | 1.867 |
| R-HSA-3642278 | Loss of Function of TGFBR2 in Cancer | 1.357082e-02 | 1.867 |
| R-HSA-3656535 | TGFBR1 LBD Mutants in Cancer | 1.357082e-02 | 1.867 |
| R-HSA-3645790 | TGFBR2 Kinase Domain Mutants in Cancer | 1.357082e-02 | 1.867 |
| R-HSA-69236 | G1 Phase | 1.382498e-02 | 1.859 |
| R-HSA-69231 | Cyclin D associated events in G1 | 1.382498e-02 | 1.859 |
| R-HSA-69601 | Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A | 1.433072e-02 | 1.844 |
| R-HSA-69613 | p53-Independent G1/S DNA Damage Checkpoint | 1.433072e-02 | 1.844 |
| R-HSA-5654741 | Signaling by FGFR3 | 1.433072e-02 | 1.844 |
| R-HSA-69278 | Cell Cycle, Mitotic | 1.476620e-02 | 1.831 |
| R-HSA-6802955 | Paradoxical activation of RAF signaling by kinase inactive BRAF | 1.484441e-02 | 1.828 |
| R-HSA-6802946 | Signaling by moderate kinase activity BRAF mutants | 1.484441e-02 | 1.828 |
| R-HSA-9649948 | Signaling downstream of RAS mutants | 1.484441e-02 | 1.828 |
| R-HSA-6802949 | Signaling by RAS mutants | 1.484441e-02 | 1.828 |
| R-HSA-74160 | Gene expression (Transcription) | 1.491354e-02 | 1.826 |
| R-HSA-3858494 | Beta-catenin independent WNT signaling | 1.558691e-02 | 1.807 |
| R-HSA-9725371 | Nuclear events stimulated by ALK signaling in cancer | 1.589534e-02 | 1.799 |
| R-HSA-111446 | Activation of BIM and translocation to mitochondria | 1.693518e-02 | 1.771 |
| R-HSA-139910 | Activation of BMF and translocation to mitochondria | 1.693518e-02 | 1.771 |
| R-HSA-9634815 | Transcriptional Regulation by NPAS4 | 1.808989e-02 | 1.743 |
| R-HSA-3656532 | TGFBR1 KD Mutants in Cancer | 2.028826e-02 | 1.693 |
| R-HSA-3656534 | Loss of Function of TGFBR1 in Cancer | 2.363012e-02 | 1.627 |
| R-HSA-3304356 | SMAD2/3 Phosphorylation Motif Mutants in Cancer | 2.363012e-02 | 1.627 |
| R-HSA-8849470 | PTK6 Regulates Cell Cycle | 2.696078e-02 | 1.569 |
| R-HSA-9652817 | Signaling by MAPK mutants | 2.696078e-02 | 1.569 |
| R-HSA-9833482 | PKR-mediated signaling | 3.663358e-02 | 1.436 |
| R-HSA-6802952 | Signaling by BRAF and RAF1 fusions | 2.603656e-02 | 1.584 |
| R-HSA-3304351 | Signaling by TGF-beta Receptor Complex in Cancer | 3.028029e-02 | 1.519 |
| R-HSA-3304349 | Loss of Function of SMAD2/3 in Cancer | 2.696078e-02 | 1.569 |
| R-HSA-9839389 | TGFBR3 regulates TGF-beta signaling | 3.358868e-02 | 1.474 |
| R-HSA-199920 | CREB phosphorylation | 3.028029e-02 | 1.519 |
| R-HSA-9007892 | Interleukin-38 signaling | 2.028826e-02 | 1.693 |
| R-HSA-453279 | Mitotic G1 phase and G1/S transition | 1.870123e-02 | 1.728 |
| R-HSA-9856649 | Transcriptional and post-translational regulation of MITF-M expression and activ... | 3.010068e-02 | 1.521 |
| R-HSA-74751 | Insulin receptor signalling cascade | 2.538280e-02 | 1.595 |
| R-HSA-8943724 | Regulation of PTEN gene transcription | 2.283714e-02 | 1.641 |
| R-HSA-73887 | Death Receptor Signaling | 2.116812e-02 | 1.674 |
| R-HSA-9658195 | Leishmania infection | 1.955934e-02 | 1.709 |
| R-HSA-9824443 | Parasitic Infection Pathways | 1.955934e-02 | 1.709 |
| R-HSA-9764725 | Negative Regulation of CDH1 Gene Transcription | 2.283714e-02 | 1.641 |
| R-HSA-375165 | NCAM signaling for neurite out-growth | 2.409600e-02 | 1.618 |
| R-HSA-5654738 | Signaling by FGFR2 | 3.663358e-02 | 1.436 |
| R-HSA-5654736 | Signaling by FGFR1 | 2.040501e-02 | 1.690 |
| R-HSA-9764560 | Regulation of CDH1 Gene Transcription | 2.940673e-02 | 1.532 |
| R-HSA-75893 | TNF signaling | 2.040501e-02 | 1.690 |
| R-HSA-69615 | G1/S DNA Damage Checkpoints | 2.473593e-02 | 1.607 |
| R-HSA-109581 | Apoptosis | 2.380574e-02 | 1.623 |
| R-HSA-111995 | phospho-PLA2 pathway | 3.688598e-02 | 1.433 |
| R-HSA-112411 | MAPK1 (ERK2) activation | 4.017224e-02 | 1.396 |
| R-HSA-9700645 | ALK mutants bind TKIs | 4.017224e-02 | 1.396 |
| R-HSA-9619229 | Activation of RAC1 downstream of NMDARs | 4.017224e-02 | 1.396 |
| R-HSA-937042 | IRAK2 mediated activation of TAK1 complex | 4.017224e-02 | 1.396 |
| R-HSA-9634635 | Estrogen-stimulated signaling through PRKCZ | 4.017224e-02 | 1.396 |
| R-HSA-6802957 | Oncogenic MAPK signaling | 4.047779e-02 | 1.393 |
| R-HSA-5357801 | Programmed Cell Death | 4.180928e-02 | 1.379 |
| R-HSA-110056 | MAPK3 (ERK1) activation | 4.344749e-02 | 1.362 |
| R-HSA-9014325 | TICAM1,TRAF6-dependent induction of TAK1 complex | 4.344749e-02 | 1.362 |
| R-HSA-112314 | Neurotransmitter receptors and postsynaptic signal transmission | 4.508566e-02 | 1.346 |
| R-HSA-162582 | Signal Transduction | 4.522233e-02 | 1.345 |
| R-HSA-9730414 | MITF-M-regulated melanocyte development | 4.556395e-02 | 1.341 |
| R-HSA-9645460 | Alpha-protein kinase 1 signaling pathway | 4.671177e-02 | 1.331 |
| R-HSA-9662834 | CD163 mediating an anti-inflammatory response | 4.671177e-02 | 1.331 |
| R-HSA-74752 | Signaling by Insulin receptor | 4.776089e-02 | 1.321 |
| R-HSA-190236 | Signaling by FGFR | 5.373055e-02 | 1.270 |
| R-HSA-9009391 | Extra-nuclear estrogen signaling | 5.636643e-02 | 1.249 |
| R-HSA-6811555 | PI5P Regulates TP53 Acetylation | 5.643912e-02 | 1.248 |
| R-HSA-8939211 | ESR-mediated signaling | 5.779571e-02 | 1.238 |
| R-HSA-975163 | IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation | 5.965986e-02 | 1.224 |
| R-HSA-205043 | NRIF signals cell death from the nucleus | 5.965986e-02 | 1.224 |
| R-HSA-5684264 | MAP3K8 (TPL2)-dependent MAPK1/3 activation | 5.965986e-02 | 1.224 |
| R-HSA-2173791 | TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) | 6.286980e-02 | 1.202 |
| R-HSA-937072 | TRAF6-mediated induction of TAK1 complex within TLR4 complex | 6.286980e-02 | 1.202 |
| R-HSA-450513 | Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA | 6.286980e-02 | 1.202 |
| R-HSA-450385 | Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA | 6.286980e-02 | 1.202 |
| R-HSA-9664420 | Killing mechanisms | 6.606899e-02 | 1.180 |
| R-HSA-9673324 | WNT5:FZD7-mediated leishmania damping | 6.606899e-02 | 1.180 |
| R-HSA-69620 | Cell Cycle Checkpoints | 6.964695e-02 | 1.157 |
| R-HSA-909733 | Interferon alpha/beta signaling | 7.211558e-02 | 1.142 |
| R-HSA-9909505 | Modulation of host responses by IFN-stimulated genes | 7.243523e-02 | 1.140 |
| R-HSA-373760 | L1CAM interactions | 7.308242e-02 | 1.136 |
| R-HSA-416476 | G alpha (q) signalling events | 7.322196e-02 | 1.135 |
| R-HSA-432142 | Platelet sensitization by LDL | 7.560235e-02 | 1.121 |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis | 7.797945e-02 | 1.108 |
| R-HSA-76002 | Platelet activation, signaling and aggregation | 7.936063e-02 | 1.100 |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 7.996685e-02 | 1.097 |
| R-HSA-162909 | Host Interactions of HIV factors | 8.096652e-02 | 1.092 |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | 8.807230e-02 | 1.055 |
| R-HSA-9617324 | Negative regulation of NMDA receptor-mediated neuronal transmission | 8.816501e-02 | 1.055 |
| R-HSA-5673001 | RAF/MAP kinase cascade | 8.897813e-02 | 1.051 |
| R-HSA-5576891 | Cardiac conduction | 9.013615e-02 | 1.045 |
| R-HSA-2173788 | Downregulation of TGF-beta receptor signaling | 9.127939e-02 | 1.040 |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | 9.362867e-02 | 1.029 |
| R-HSA-195721 | Signaling by WNT | 9.497585e-02 | 1.022 |
| R-HSA-418592 | ADP signalling through P2Y purinoceptor 1 | 9.747686e-02 | 1.011 |
| R-HSA-6807070 | PTEN Regulation | 9.959788e-02 | 1.002 |
| R-HSA-9664407 | Parasite infection | 1.006661e-01 | 0.997 |
| R-HSA-9664417 | Leishmania phagocytosis | 1.006661e-01 | 0.997 |
| R-HSA-9664422 | FCGR3A-mediated phagocytosis | 1.006661e-01 | 0.997 |
| R-HSA-2029482 | Regulation of actin dynamics for phagocytic cup formation | 1.017376e-01 | 0.993 |
| R-HSA-8934593 | Regulation of RUNX1 Expression and Activity | 1.036328e-01 | 0.985 |
| R-HSA-162599 | Late Phase of HIV Life Cycle | 1.038902e-01 | 0.983 |
| R-HSA-9705671 | SARS-CoV-2 activates/modulates innate and adaptive immune responses | 1.038902e-01 | 0.983 |
| R-HSA-167243 | Tat-mediated HIV elongation arrest and recovery | 1.066953e-01 | 0.972 |
| R-HSA-167238 | Pausing and recovery of Tat-mediated HIV elongation | 1.066953e-01 | 0.972 |
| R-HSA-73728 | RNA Polymerase I Promoter Opening | 1.066953e-01 | 0.972 |
| R-HSA-5357956 | TNFR1-induced NF-kappa-B signaling pathway | 1.066953e-01 | 0.972 |
| R-HSA-167287 | HIV elongation arrest and recovery | 1.097475e-01 | 0.960 |
| R-HSA-167290 | Pausing and recovery of HIV elongation | 1.097475e-01 | 0.960 |
| R-HSA-1852241 | Organelle biogenesis and maintenance | 1.103158e-01 | 0.957 |
| R-HSA-112315 | Transmission across Chemical Synapses | 1.124790e-01 | 0.949 |
| R-HSA-5619107 | Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC... | 1.158213e-01 | 0.936 |
| R-HSA-114452 | Activation of BH3-only proteins | 1.158213e-01 | 0.936 |
| R-HSA-1855196 | IP3 and IP4 transport between cytosol and nucleus | 1.188429e-01 | 0.925 |
| R-HSA-1855229 | IP6 and IP7 transport between cytosol and nucleus | 1.188429e-01 | 0.925 |
| R-HSA-9833109 | Evasion by RSV of host interferon responses | 1.188429e-01 | 0.925 |
| R-HSA-162587 | HIV Life Cycle | 1.204194e-01 | 0.919 |
| R-HSA-1538133 | G0 and Early G1 | 1.218544e-01 | 0.914 |
| R-HSA-877300 | Interferon gamma signaling | 1.226712e-01 | 0.911 |
| R-HSA-1855170 | IPs transport between nucleus and cytosol | 1.248558e-01 | 0.904 |
| R-HSA-159227 | Transport of the SLBP independent Mature mRNA | 1.248558e-01 | 0.904 |
| R-HSA-8939243 | RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not kno... | 1.248558e-01 | 0.904 |
| R-HSA-9022692 | Regulation of MECP2 expression and activity | 1.248558e-01 | 0.904 |
| R-HSA-6804758 | Regulation of TP53 Activity through Acetylation | 1.248558e-01 | 0.904 |
| R-HSA-159230 | Transport of the SLBP Dependant Mature mRNA | 1.278471e-01 | 0.893 |
| R-HSA-170822 | Regulation of Glucokinase by Glucokinase Regulatory Protein | 1.278471e-01 | 0.893 |
| R-HSA-5683057 | MAPK family signaling cascades | 1.303606e-01 | 0.885 |
| R-HSA-75815 | Ubiquitin-dependent degradation of Cyclin D | 1.308283e-01 | 0.883 |
| R-HSA-180746 | Nuclear import of Rev protein | 1.308283e-01 | 0.883 |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells | 1.308283e-01 | 0.883 |
| R-HSA-392518 | Signal amplification | 1.308283e-01 | 0.883 |
| R-HSA-3301854 | Nuclear Pore Complex (NPC) Disassembly | 1.337996e-01 | 0.874 |
| R-HSA-381042 | PERK regulates gene expression | 1.337996e-01 | 0.874 |
| R-HSA-8853659 | RET signaling | 1.367608e-01 | 0.864 |
| R-HSA-180910 | Vpr-mediated nuclear import of PICs | 1.397122e-01 | 0.855 |
| R-HSA-9764274 | Regulation of Expression and Function of Type I Classical Cadherins | 1.398773e-01 | 0.854 |
| R-HSA-9764265 | Regulation of CDH1 Expression and Function | 1.398773e-01 | 0.854 |
| R-HSA-2029480 | Fcgamma receptor (FCGR) dependent phagocytosis | 1.410429e-01 | 0.851 |
| R-HSA-165054 | Rev-mediated nuclear export of HIV RNA | 1.426536e-01 | 0.846 |
| R-HSA-9006931 | Signaling by Nuclear Receptors | 1.428139e-01 | 0.845 |
| R-HSA-167200 | Formation of HIV-1 elongation complex containing HIV-1 Tat | 1.455851e-01 | 0.837 |
| R-HSA-159231 | Transport of Mature mRNA Derived from an Intronless Transcript | 1.455851e-01 | 0.837 |
| R-HSA-168255 | Influenza Infection | 1.469028e-01 | 0.833 |
| R-HSA-159234 | Transport of Mature mRNAs Derived from Intronless Transcripts | 1.485068e-01 | 0.828 |
| R-HSA-167246 | Tat-mediated elongation of the HIV-1 transcript | 1.485068e-01 | 0.828 |
| R-HSA-167152 | Formation of HIV elongation complex in the absence of HIV Tat | 1.485068e-01 | 0.828 |
| R-HSA-167169 | HIV Transcription Elongation | 1.485068e-01 | 0.828 |
| R-HSA-177243 | Interactions of Rev with host cellular proteins | 1.485068e-01 | 0.828 |
| R-HSA-176033 | Interactions of Vpr with host cellular proteins | 1.485068e-01 | 0.828 |
| R-HSA-168271 | Transport of Ribonucleoproteins into the Host Nucleus | 1.514187e-01 | 0.820 |
| R-HSA-9929491 | SPOP-mediated proteasomal degradation of PD-L1(CD274) | 1.514187e-01 | 0.820 |
| R-HSA-111996 | Ca-dependent events | 1.572132e-01 | 0.804 |
| R-HSA-68886 | M Phase | 1.589216e-01 | 0.799 |
| R-HSA-2173789 | TGF-beta receptor signaling activates SMADs | 1.600959e-01 | 0.796 |
| R-HSA-187577 | SCF(Skp2)-mediated degradation of p27/p21 | 1.629689e-01 | 0.788 |
| R-HSA-3214858 | RMTs methylate histone arginines | 1.629689e-01 | 0.788 |
| R-HSA-2142691 | Synthesis of Leukotrienes (LT) and Eoxins (EX) | 1.629689e-01 | 0.788 |
| R-HSA-168333 | NEP/NS2 Interacts with the Cellular Export Machinery | 1.658322e-01 | 0.780 |
| R-HSA-9824585 | Regulation of MITF-M-dependent genes involved in pigmentation | 1.658322e-01 | 0.780 |
| R-HSA-8953854 | Metabolism of RNA | 1.671672e-01 | 0.777 |
| R-HSA-9759476 | Regulation of Homotypic Cell-Cell Adhesion | 1.671852e-01 | 0.777 |
| R-HSA-168274 | Export of Viral Ribonucleoproteins from Nucleus | 1.686859e-01 | 0.773 |
| R-HSA-9839373 | Signaling by TGFBR3 | 1.686859e-01 | 0.773 |
| R-HSA-5357905 | Regulation of TNFR1 signaling | 1.686859e-01 | 0.773 |
| R-HSA-445989 | TAK1-dependent IKK and NF-kappa-B activation | 1.715301e-01 | 0.766 |
| R-HSA-437239 | Recycling pathway of L1 | 1.715301e-01 | 0.766 |
| R-HSA-912446 | Meiotic recombination | 1.828114e-01 | 0.738 |
| R-HSA-1169091 | Activation of NF-kappaB in B cells | 1.828114e-01 | 0.738 |
| R-HSA-112382 | Formation of RNA Pol II elongation complex | 1.856080e-01 | 0.731 |
| R-HSA-397014 | Muscle contraction | 1.879278e-01 | 0.726 |
| R-HSA-75955 | RNA Polymerase II Transcription Elongation | 1.883953e-01 | 0.725 |
| R-HSA-418990 | Adherens junctions interactions | 1.953369e-01 | 0.709 |
| R-HSA-193648 | NRAGE signals death through JNK | 1.967011e-01 | 0.706 |
| R-HSA-2980766 | Nuclear Envelope Breakdown | 1.994511e-01 | 0.700 |
| R-HSA-194441 | Metabolism of non-coding RNA | 2.049233e-01 | 0.688 |
| R-HSA-191859 | snRNP Assembly | 2.049233e-01 | 0.688 |
| R-HSA-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at... | 2.049233e-01 | 0.688 |
| R-HSA-8878171 | Transcriptional regulation by RUNX1 | 2.052747e-01 | 0.688 |
| R-HSA-162906 | HIV Infection | 2.065212e-01 | 0.685 |
| R-HSA-9705683 | SARS-CoV-2-host interactions | 2.077685e-01 | 0.682 |
| R-HSA-168325 | Viral Messenger RNA Synthesis | 2.103589e-01 | 0.677 |
| R-HSA-112043 | PLC beta mediated events | 2.103589e-01 | 0.677 |
| R-HSA-6784531 | tRNA processing in the nucleus | 2.130630e-01 | 0.671 |
| R-HSA-9616222 | Transcriptional regulation of granulopoiesis | 2.130630e-01 | 0.671 |
| R-HSA-8848021 | Signaling by PTK6 | 2.157580e-01 | 0.666 |
| R-HSA-9006927 | Signaling by Non-Receptor Tyrosine Kinases | 2.157580e-01 | 0.666 |
| R-HSA-6798695 | Neutrophil degranulation | 2.236268e-01 | 0.650 |
| R-HSA-112040 | G-protein mediated events | 2.264476e-01 | 0.645 |
| R-HSA-5693606 | DNA Double Strand Break Response | 2.264476e-01 | 0.645 |
| R-HSA-167172 | Transcription of the HIV genome | 2.290976e-01 | 0.640 |
| R-HSA-112316 | Neuronal System | 2.335577e-01 | 0.632 |
| R-HSA-1168372 | Downstream signaling events of B Cell Receptor (BCR) | 2.343708e-01 | 0.630 |
| R-HSA-69202 | Cyclin E associated events during G1/S transition | 2.343708e-01 | 0.630 |
| R-HSA-421270 | Cell-cell junction organization | 2.366564e-01 | 0.626 |
| R-HSA-5578749 | Transcriptional regulation by small RNAs | 2.396086e-01 | 0.620 |
| R-HSA-69656 | Cyclin A:Cdk2-associated events at S phase entry | 2.396086e-01 | 0.620 |
| R-HSA-5688426 | Deubiquitination | 2.417099e-01 | 0.617 |
| R-HSA-159236 | Transport of Mature mRNA derived from an Intron-Containing Transcript | 2.422143e-01 | 0.616 |
| R-HSA-204998 | Cell death signalling via NRAGE, NRIF and NADE | 2.422143e-01 | 0.616 |
| R-HSA-674695 | RNA Polymerase II Pre-transcription Events | 2.448112e-01 | 0.611 |
| R-HSA-73854 | RNA Polymerase I Promoter Clearance | 2.499789e-01 | 0.602 |
| R-HSA-5689603 | UCH proteinases | 2.499789e-01 | 0.602 |
| R-HSA-73864 | RNA Polymerase I Transcription | 2.551119e-01 | 0.593 |
| R-HSA-72202 | Transport of Mature Transcript to Cytoplasm | 2.652745e-01 | 0.576 |
| R-HSA-446728 | Cell junction organization | 2.708484e-01 | 0.567 |
| R-HSA-72203 | Processing of Capped Intron-Containing Pre-mRNA | 2.721167e-01 | 0.565 |
| R-HSA-1500620 | Meiosis | 2.728071e-01 | 0.564 |
| R-HSA-141444 | Amplification of signal from unattached kinetochores via a MAD2 inhibitory si... | 2.753010e-01 | 0.560 |
| R-HSA-141424 | Amplification of signal from the kinetochores | 2.753010e-01 | 0.560 |
| R-HSA-9909615 | Regulation of PD-L1(CD274) Post-translational modification | 2.753010e-01 | 0.560 |
| R-HSA-6807505 | RNA polymerase II transcribes snRNA genes | 2.777866e-01 | 0.556 |
| R-HSA-202424 | Downstream TCR signaling | 2.876454e-01 | 0.541 |
| R-HSA-8986944 | Transcriptional Regulation by MECP2 | 2.900894e-01 | 0.537 |
| R-HSA-1257604 | PIP3 activates AKT signaling | 2.923976e-01 | 0.534 |
| R-HSA-422475 | Axon guidance | 3.048883e-01 | 0.516 |
| R-HSA-5607764 | CLEC7A (Dectin-1) signaling | 3.069682e-01 | 0.513 |
| R-HSA-381340 | Transcriptional regulation of white adipocyte differentiation | 3.069682e-01 | 0.513 |
| R-HSA-193704 | p75 NTR receptor-mediated signalling | 3.140808e-01 | 0.503 |
| R-HSA-69618 | Mitotic Spindle Checkpoint | 3.164357e-01 | 0.500 |
| R-HSA-70171 | Glycolysis | 3.164357e-01 | 0.500 |
| R-HSA-1500931 | Cell-Cell communication | 3.189193e-01 | 0.496 |
| R-HSA-9633012 | Response of EIF2AK4 (GCN2) to amino acid deficiency | 3.257762e-01 | 0.487 |
| R-HSA-111885 | Opioid Signalling | 3.257762e-01 | 0.487 |
| R-HSA-9833110 | RSV-host interactions | 3.280917e-01 | 0.484 |
| R-HSA-418346 | Platelet homeostasis | 3.326992e-01 | 0.478 |
| R-HSA-211000 | Gene Silencing by RNA | 3.349914e-01 | 0.475 |
| R-HSA-9648025 | EML4 and NUDC in mitotic spindle formation | 3.395524e-01 | 0.469 |
| R-HSA-9675108 | Nervous system development | 3.397168e-01 | 0.469 |
| R-HSA-202403 | TCR signaling | 3.418215e-01 | 0.466 |
| R-HSA-1483249 | Inositol phosphate metabolism | 3.463365e-01 | 0.461 |
| R-HSA-9006925 | Intracellular signaling by second messengers | 3.514502e-01 | 0.454 |
| R-HSA-1266738 | Developmental Biology | 3.569050e-01 | 0.447 |
| R-HSA-9694516 | SARS-CoV-2 Infection | 3.601289e-01 | 0.444 |
| R-HSA-70326 | Glucose metabolism | 3.619011e-01 | 0.441 |
| R-HSA-2500257 | Resolution of Sister Chromatid Cohesion | 3.706312e-01 | 0.431 |
| R-HSA-69206 | G1/S Transition | 3.813790e-01 | 0.419 |
| R-HSA-1474165 | Reproduction | 3.940387e-01 | 0.404 |
| R-HSA-9843745 | Adipogenesis | 3.961238e-01 | 0.402 |
| R-HSA-9018519 | Estrogen-dependent gene expression | 4.084871e-01 | 0.389 |
| R-HSA-9820952 | Respiratory Syncytial Virus Infection Pathway | 4.105234e-01 | 0.387 |
| R-HSA-381119 | Unfolded Protein Response (UPR) | 4.145753e-01 | 0.382 |
| R-HSA-2871837 | FCERI mediated NF-kB activation | 4.265675e-01 | 0.370 |
| R-HSA-69242 | S Phase | 4.344280e-01 | 0.362 |
| R-HSA-9856651 | MITF-M-dependent gene expression | 4.383185e-01 | 0.358 |
| R-HSA-9755511 | KEAP1-NFE2L2 pathway | 4.402539e-01 | 0.356 |
| R-HSA-2142753 | Arachidonate metabolism | 4.421827e-01 | 0.354 |
| R-HSA-5693532 | DNA Double-Strand Break Repair | 4.441050e-01 | 0.353 |
| R-HSA-168273 | Influenza Viral RNA Transcription and Replication | 4.479301e-01 | 0.349 |
| R-HSA-9610379 | HCMV Late Events | 4.517294e-01 | 0.345 |
| R-HSA-9711097 | Cellular response to starvation | 4.536194e-01 | 0.343 |
| R-HSA-983705 | Signaling by the B Cell Receptor (BCR) | 4.536194e-01 | 0.343 |
| R-HSA-2467813 | Separation of Sister Chromatids | 4.648257e-01 | 0.333 |
| R-HSA-5619102 | SLC transporter disorders | 4.703440e-01 | 0.328 |
| R-HSA-72306 | tRNA processing | 4.776148e-01 | 0.321 |
| R-HSA-5621481 | C-type lectin receptors (CLRs) | 4.794172e-01 | 0.319 |
| R-HSA-9909648 | Regulation of PD-L1(CD274) expression | 4.812134e-01 | 0.318 |
| R-HSA-9664433 | Leishmania parasite growth and survival | 4.830036e-01 | 0.316 |
| R-HSA-9662851 | Anti-inflammatory response favouring Leishmania parasite infection | 4.830036e-01 | 0.316 |
| R-HSA-5689880 | Ub-specific processing proteases | 4.830036e-01 | 0.316 |
| R-HSA-388396 | GPCR downstream signalling | 5.145447e-01 | 0.289 |
| R-HSA-68877 | Mitotic Prometaphase | 5.175593e-01 | 0.286 |
| R-HSA-72163 | mRNA Splicing - Major Pathway | 5.192263e-01 | 0.285 |
| R-HSA-9609690 | HCMV Early Events | 5.225432e-01 | 0.282 |
| R-HSA-109582 | Hemostasis | 5.230695e-01 | 0.281 |
| R-HSA-389948 | Co-inhibition by PD-1 | 5.291097e-01 | 0.276 |
| R-HSA-72172 | mRNA Splicing | 5.371934e-01 | 0.270 |
| R-HSA-68882 | Mitotic Anaphase | 5.560423e-01 | 0.255 |
| R-HSA-2555396 | Mitotic Metaphase and Anaphase | 5.575786e-01 | 0.254 |
| R-HSA-9824446 | Viral Infection Pathways | 5.577499e-01 | 0.254 |
| R-HSA-372790 | Signaling by GPCR | 5.828313e-01 | 0.234 |
| R-HSA-3247509 | Chromatin modifying enzymes | 5.829108e-01 | 0.234 |
| R-HSA-9679506 | SARS-CoV Infections | 5.899275e-01 | 0.229 |
| R-HSA-5619115 | Disorders of transmembrane transporters | 6.013163e-01 | 0.221 |
| R-HSA-4839726 | Chromatin organization | 6.040762e-01 | 0.219 |
| R-HSA-9609646 | HCMV Infection | 6.054491e-01 | 0.218 |
| R-HSA-388841 | Regulation of T cell activation by CD28 family | 6.135890e-01 | 0.212 |
| R-HSA-9711123 | Cellular response to chemical stress | 6.293772e-01 | 0.201 |
| R-HSA-597592 | Post-translational protein modification | 6.923234e-01 | 0.160 |
| R-HSA-73894 | DNA Repair | 7.311103e-01 | 0.136 |
| R-HSA-418594 | G alpha (i) signalling events | 7.727303e-01 | 0.112 |
| R-HSA-8978868 | Fatty acid metabolism | 7.727303e-01 | 0.112 |
| R-HSA-71387 | Metabolism of carbohydrates and carbohydrate derivatives | 8.080071e-01 | 0.093 |
| R-HSA-1280218 | Adaptive Immune System | 8.870561e-01 | 0.052 |
| R-HSA-392499 | Metabolism of proteins | 9.325181e-01 | 0.030 |
| R-HSA-556833 | Metabolism of lipids | 9.955361e-01 | 0.002 |
| R-HSA-1430728 | Metabolism | 9.999922e-01 | 0.000 |
Download
| kinase | JSD_mean | pearson_surrounding | kinase_max_IC_position | max_position_JSD |
|---|---|---|---|---|
PKR |
0.670 | 0.061 | 1 | 0.605 |
GAK |
0.670 | 0.143 | 1 | 0.732 |
BIKE |
0.667 | 0.183 | 1 | 0.728 |
P38D |
0.664 | 0.134 | 1 | 0.524 |
MPSK1 |
0.663 | 0.124 | 1 | 0.705 |
DAPK2 |
0.663 | 0.057 | -3 | 0.814 |
VRK2 |
0.663 | -0.043 | 1 | 0.612 |
NLK |
0.663 | 0.101 | 1 | 0.627 |
ALK4 |
0.662 | 0.086 | -2 | 0.591 |
TAK1 |
0.662 | 0.025 | 1 | 0.556 |
BRAF |
0.662 | 0.019 | -4 | 0.594 |
TTK |
0.661 | 0.028 | -2 | 0.559 |
P38B |
0.661 | 0.118 | 1 | 0.502 |
DAPK3 |
0.660 | 0.074 | -3 | 0.724 |
NEK5 |
0.660 | 0.014 | 1 | 0.570 |
P38A |
0.660 | 0.114 | 1 | 0.565 |
ANKRD3 |
0.659 | 0.023 | 1 | 0.562 |
PBK |
0.659 | 0.150 | 1 | 0.706 |
JNK2 |
0.658 | 0.096 | 1 | 0.511 |
BMPR2 |
0.658 | -0.018 | -2 | 0.627 |
PINK1 |
0.658 | 0.100 | 1 | 0.710 |
CAMLCK |
0.658 | 0.032 | -2 | 0.653 |
MOS |
0.656 | 0.043 | 1 | 0.707 |
AAK1 |
0.656 | 0.188 | 1 | 0.688 |
BMPR1B |
0.656 | 0.103 | 1 | 0.635 |
MLK2 |
0.655 | 0.033 | 2 | 0.612 |
LRRK2 |
0.655 | -0.057 | 2 | 0.663 |
PRP4 |
0.655 | 0.078 | -3 | 0.738 |
NIK |
0.655 | -0.032 | -3 | 0.818 |
MEK1 |
0.654 | -0.067 | 2 | 0.604 |
JNK3 |
0.654 | 0.083 | 1 | 0.540 |
ERK5 |
0.654 | 0.087 | 1 | 0.588 |
BMPR1A |
0.654 | 0.108 | 1 | 0.626 |
CAMK1B |
0.654 | 0.096 | -3 | 0.804 |
NEK1 |
0.653 | -0.018 | 1 | 0.511 |
ALK2 |
0.653 | 0.054 | -2 | 0.563 |
VRK1 |
0.653 | -0.094 | 2 | 0.624 |
TAO2 |
0.652 | -0.052 | 2 | 0.665 |
ERK7 |
0.652 | 0.119 | 2 | 0.562 |
MST2 |
0.652 | -0.029 | 1 | 0.501 |
PRPK |
0.652 | -0.022 | -1 | 0.626 |
MEKK2 |
0.652 | -0.052 | 2 | 0.606 |
ICK |
0.652 | 0.067 | -3 | 0.791 |
ATR |
0.652 | 0.015 | 1 | 0.605 |
TNIK |
0.651 | -0.052 | 3 | 0.404 |
NEK8 |
0.651 | -0.049 | 2 | 0.640 |
SKMLCK |
0.651 | 0.060 | -2 | 0.653 |
CDK5 |
0.651 | 0.076 | 1 | 0.618 |
TGFBR1 |
0.650 | 0.062 | -2 | 0.567 |
TLK2 |
0.650 | 0.038 | 1 | 0.559 |
P38G |
0.650 | 0.093 | 1 | 0.479 |
MYO3B |
0.650 | -0.013 | 2 | 0.631 |
TAO3 |
0.650 | -0.048 | 1 | 0.489 |
CDKL1 |
0.649 | 0.044 | -3 | 0.761 |
MLK3 |
0.649 | 0.061 | 2 | 0.630 |
DAPK1 |
0.649 | 0.055 | -3 | 0.707 |
MINK |
0.649 | -0.060 | 1 | 0.467 |
MYO3A |
0.649 | -0.030 | 1 | 0.496 |
ACVR2B |
0.649 | 0.053 | -2 | 0.566 |
CAMK2G |
0.649 | 0.146 | 2 | 0.767 |
CAMKK1 |
0.648 | -0.066 | -2 | 0.537 |
ERK2 |
0.648 | 0.063 | 1 | 0.526 |
HGK |
0.648 | -0.058 | 3 | 0.407 |
MEK5 |
0.648 | -0.149 | 2 | 0.597 |
LKB1 |
0.648 | -0.053 | -3 | 0.815 |
MEKK1 |
0.648 | -0.076 | 1 | 0.509 |
SMMLCK |
0.647 | 0.015 | -3 | 0.762 |
PIM1 |
0.647 | 0.093 | -3 | 0.706 |
JNK1 |
0.647 | 0.080 | 1 | 0.526 |
NEK9 |
0.647 | 0.015 | 2 | 0.634 |
ERK1 |
0.647 | 0.092 | 1 | 0.501 |
LATS1 |
0.646 | 0.023 | -3 | 0.779 |
NEK4 |
0.646 | -0.057 | 1 | 0.489 |
MEK2 |
0.646 | -0.080 | 2 | 0.557 |
RAF1 |
0.646 | -0.018 | 1 | 0.547 |
CDK18 |
0.646 | 0.119 | 1 | 0.548 |
COT |
0.646 | 0.120 | 2 | 0.709 |
PDK1 |
0.646 | -0.065 | 1 | 0.502 |
PASK |
0.646 | 0.017 | -3 | 0.778 |
MLK4 |
0.646 | 0.034 | 2 | 0.597 |
ACVR2A |
0.645 | 0.029 | -2 | 0.547 |
CAMKK2 |
0.644 | -0.108 | -2 | 0.546 |
ALPHAK3 |
0.644 | -0.002 | -1 | 0.584 |
YSK4 |
0.644 | -0.049 | 1 | 0.447 |
MEKK6 |
0.644 | -0.055 | 1 | 0.471 |
MLK1 |
0.643 | -0.000 | 2 | 0.629 |
PERK |
0.643 | -0.063 | -2 | 0.582 |
CDK17 |
0.643 | 0.094 | 1 | 0.505 |
CDK8 |
0.643 | 0.114 | 1 | 0.558 |
OSR1 |
0.643 | -0.057 | 2 | 0.584 |
GCK |
0.643 | -0.098 | 1 | 0.509 |
CDK16 |
0.643 | 0.098 | 1 | 0.529 |
PAK1 |
0.643 | 0.138 | -2 | 0.639 |
DLK |
0.643 | -0.127 | 1 | 0.521 |
EEF2K |
0.642 | -0.081 | 3 | 0.373 |
ROCK2 |
0.642 | 0.020 | -3 | 0.700 |
MST1 |
0.642 | -0.099 | 1 | 0.467 |
CDK14 |
0.641 | 0.078 | 1 | 0.572 |
IRAK4 |
0.641 | -0.019 | 1 | 0.538 |
HIPK1 |
0.641 | 0.063 | 1 | 0.593 |
PLK1 |
0.641 | -0.006 | -2 | 0.560 |
CDK6 |
0.641 | 0.062 | 1 | 0.559 |
WNK4 |
0.641 | -0.023 | -2 | 0.664 |
DRAK1 |
0.641 | 0.025 | 1 | 0.541 |
CHAK2 |
0.641 | -0.006 | -1 | 0.638 |
MAP3K15 |
0.641 | -0.087 | 1 | 0.419 |
STK33 |
0.641 | 0.204 | 2 | 0.758 |
PIM3 |
0.641 | 0.077 | -3 | 0.762 |
ZAK |
0.641 | -0.078 | 1 | 0.431 |
HRI |
0.640 | -0.088 | -2 | 0.611 |
MAK |
0.640 | 0.105 | -2 | 0.623 |
RIPK3 |
0.640 | -0.005 | 3 | 0.412 |
MST3 |
0.640 | -0.053 | 2 | 0.637 |
LOK |
0.640 | -0.051 | -2 | 0.590 |
ATM |
0.640 | 0.032 | 1 | 0.569 |
CDK7 |
0.640 | 0.090 | 1 | 0.588 |
YSK1 |
0.640 | -0.058 | 2 | 0.619 |
NEK2 |
0.639 | -0.003 | 2 | 0.627 |
DMPK1 |
0.639 | 0.042 | -3 | 0.678 |
HPK1 |
0.639 | -0.074 | 1 | 0.472 |
DYRK2 |
0.638 | 0.062 | 1 | 0.579 |
CDKL5 |
0.638 | 0.063 | -3 | 0.755 |
DSTYK |
0.638 | 0.056 | 2 | 0.684 |
CDC7 |
0.638 | 0.029 | 1 | 0.680 |
KHS1 |
0.638 | -0.085 | 1 | 0.456 |
KHS2 |
0.637 | -0.066 | 1 | 0.480 |
PIM2 |
0.637 | 0.052 | -3 | 0.686 |
NEK11 |
0.637 | -0.125 | 1 | 0.475 |
IRE2 |
0.637 | -0.019 | 2 | 0.588 |
PLK3 |
0.637 | 0.097 | 2 | 0.740 |
HIPK3 |
0.637 | 0.066 | 1 | 0.549 |
PAK2 |
0.637 | 0.056 | -2 | 0.623 |
NEK7 |
0.636 | 0.021 | -3 | 0.839 |
GRK6 |
0.636 | -0.033 | 1 | 0.590 |
MASTL |
0.636 | -0.084 | -2 | 0.605 |
MEKK3 |
0.636 | -0.118 | 1 | 0.483 |
BUB1 |
0.635 | 0.017 | -5 | 0.607 |
PKCD |
0.635 | 0.013 | 2 | 0.659 |
TTBK2 |
0.635 | 0.181 | 2 | 0.762 |
NEK3 |
0.635 | -0.036 | 1 | 0.431 |
DYRK1A |
0.635 | 0.054 | 1 | 0.587 |
TLK1 |
0.635 | -0.050 | -2 | 0.580 |
CDK1 |
0.635 | 0.050 | 1 | 0.558 |
CDK3 |
0.634 | 0.063 | 1 | 0.529 |
CLK3 |
0.634 | 0.043 | 1 | 0.676 |
IRE1 |
0.634 | -0.006 | 1 | 0.572 |
CDK4 |
0.634 | 0.044 | 1 | 0.529 |
ASK1 |
0.634 | -0.124 | 1 | 0.410 |
YANK3 |
0.634 | 0.279 | 2 | 0.767 |
GRK5 |
0.634 | -0.086 | -3 | 0.782 |
PDHK4 |
0.634 | -0.131 | 1 | 0.564 |
HIPK4 |
0.634 | 0.057 | 1 | 0.639 |
CDK2 |
0.633 | 0.024 | 1 | 0.592 |
MOK |
0.633 | 0.058 | 1 | 0.607 |
PAK3 |
0.633 | 0.078 | -2 | 0.645 |
WNK1 |
0.633 | -0.000 | -2 | 0.656 |
RIPK1 |
0.633 | -0.074 | 1 | 0.535 |
SMG1 |
0.633 | 0.019 | 1 | 0.569 |
DCAMKL2 |
0.633 | 0.120 | -3 | 0.736 |
DYRK1B |
0.632 | 0.058 | 1 | 0.577 |
WNK3 |
0.632 | -0.041 | 1 | 0.524 |
ULK2 |
0.631 | -0.012 | 2 | 0.609 |
PKN3 |
0.631 | -0.009 | -3 | 0.774 |
GSK3A |
0.631 | -0.006 | 4 | 0.250 |
PLK2 |
0.630 | 0.142 | -3 | 0.756 |
CDK13 |
0.630 | 0.050 | 1 | 0.560 |
TSSK2 |
0.630 | -0.038 | -5 | 0.644 |
SLK |
0.630 | -0.069 | -2 | 0.533 |
DCAMKL1 |
0.630 | 0.030 | -3 | 0.705 |
NEK6 |
0.630 | -0.002 | -2 | 0.604 |
TAO1 |
0.630 | -0.088 | 1 | 0.394 |
P70S6KB |
0.629 | 0.005 | -3 | 0.734 |
ROCK1 |
0.629 | 0.005 | -3 | 0.673 |
CDK19 |
0.629 | 0.101 | 1 | 0.537 |
TGFBR2 |
0.629 | -0.020 | -2 | 0.557 |
MYLK4 |
0.628 | 0.027 | -2 | 0.598 |
PKCZ |
0.628 | -0.007 | 2 | 0.636 |
GSK3B |
0.628 | -0.034 | 4 | 0.247 |
PDHK1 |
0.627 | -0.141 | 1 | 0.523 |
CHAK1 |
0.627 | -0.093 | 2 | 0.591 |
CHK1 |
0.627 | -0.028 | -3 | 0.756 |
DYRK4 |
0.627 | 0.075 | 1 | 0.540 |
MRCKB |
0.626 | 0.016 | -3 | 0.663 |
HIPK2 |
0.626 | 0.068 | 1 | 0.541 |
DYRK3 |
0.626 | 0.045 | 1 | 0.586 |
CDK12 |
0.626 | 0.045 | 1 | 0.526 |
GRK7 |
0.625 | -0.038 | 1 | 0.538 |
YANK2 |
0.625 | 0.247 | 2 | 0.780 |
PKN2 |
0.624 | -0.013 | -3 | 0.760 |
IRAK1 |
0.624 | -0.097 | -1 | 0.651 |
DNAPK |
0.623 | -0.041 | 1 | 0.453 |
CDK9 |
0.623 | 0.040 | 1 | 0.551 |
GRK2 |
0.623 | -0.029 | -2 | 0.470 |
TBK1 |
0.623 | -0.061 | 1 | 0.404 |
STLK3 |
0.622 | -0.157 | 1 | 0.407 |
MARK4 |
0.622 | -0.083 | 4 | 0.460 |
HASPIN |
0.622 | -0.050 | -1 | 0.493 |
CLK4 |
0.622 | 0.019 | -3 | 0.698 |
CAMK2D |
0.622 | 0.023 | -3 | 0.792 |
NUAK2 |
0.621 | -0.043 | -3 | 0.765 |
TTBK1 |
0.621 | 0.215 | 2 | 0.796 |
PKCB |
0.621 | 0.004 | 2 | 0.614 |
AMPKA1 |
0.620 | -0.084 | -3 | 0.779 |
CDK10 |
0.620 | 0.055 | 1 | 0.576 |
MRCKA |
0.620 | -0.019 | -3 | 0.678 |
TSSK1 |
0.620 | -0.054 | -3 | 0.802 |
PLK4 |
0.620 | 0.004 | 2 | 0.496 |
NDR1 |
0.619 | 0.013 | -3 | 0.758 |
CAMK2B |
0.619 | 0.048 | 2 | 0.719 |
MELK |
0.619 | -0.035 | -3 | 0.737 |
SGK3 |
0.618 | 0.003 | -3 | 0.683 |
MTOR |
0.618 | -0.106 | 1 | 0.507 |
MST4 |
0.618 | -0.065 | 2 | 0.616 |
HUNK |
0.617 | -0.102 | 2 | 0.624 |
IKKE |
0.617 | -0.075 | 1 | 0.391 |
GCN2 |
0.617 | -0.040 | 2 | 0.622 |
AKT2 |
0.617 | 0.015 | -3 | 0.628 |
PKCH |
0.617 | -0.037 | 2 | 0.595 |
PKCA |
0.617 | -0.022 | 2 | 0.613 |
CAMK1G |
0.616 | 0.052 | -3 | 0.712 |
AURB |
0.616 | 0.008 | -2 | 0.501 |
MARK2 |
0.616 | -0.069 | 4 | 0.406 |
FAM20C |
0.616 | 0.041 | 2 | 0.457 |
PKCI |
0.616 | -0.005 | 2 | 0.617 |
GRK1 |
0.616 | -0.017 | -2 | 0.524 |
SRPK1 |
0.615 | 0.010 | -3 | 0.702 |
GRK4 |
0.615 | -0.065 | -2 | 0.545 |
IKKB |
0.615 | -0.038 | -2 | 0.543 |
CAMK2A |
0.615 | 0.039 | 2 | 0.734 |
ULK1 |
0.614 | -0.062 | -3 | 0.829 |
PKCG |
0.614 | -0.013 | 2 | 0.661 |
SSTK |
0.614 | -0.046 | 4 | 0.436 |
CRIK |
0.613 | -0.011 | -3 | 0.642 |
NIM1 |
0.613 | -0.079 | 3 | 0.403 |
RSK2 |
0.613 | 0.003 | -3 | 0.716 |
CAMK1D |
0.613 | 0.013 | -3 | 0.619 |
CK2A2 |
0.612 | 0.014 | 1 | 0.619 |
PKCE |
0.612 | -0.002 | 2 | 0.626 |
IKKA |
0.612 | -0.007 | -2 | 0.520 |
QIK |
0.611 | -0.102 | -3 | 0.768 |
AURA |
0.611 | 0.026 | -2 | 0.474 |
PKACG |
0.611 | -0.004 | -2 | 0.561 |
NDR2 |
0.610 | 0.038 | -3 | 0.759 |
PRKD1 |
0.610 | -0.005 | -3 | 0.779 |
PRKD3 |
0.610 | -0.016 | -3 | 0.690 |
SRPK3 |
0.610 | -0.027 | -3 | 0.679 |
SGK1 |
0.610 | 0.009 | -3 | 0.546 |
PKCT |
0.609 | -0.033 | 2 | 0.596 |
AMPKA2 |
0.609 | -0.082 | -3 | 0.743 |
AKT1 |
0.609 | 0.003 | -3 | 0.635 |
RIPK2 |
0.609 | -0.158 | 1 | 0.401 |
CLK1 |
0.608 | 0.011 | -3 | 0.679 |
CAMK4 |
0.608 | -0.095 | -3 | 0.739 |
RSK3 |
0.607 | 0.006 | -3 | 0.716 |
MAPKAPK3 |
0.607 | -0.035 | -3 | 0.717 |
TNK2 |
0.607 | 0.314 | 3 | 0.576 |
LATS2 |
0.607 | 0.022 | -5 | 0.764 |
PKG2 |
0.606 | -0.007 | -2 | 0.510 |
P90RSK |
0.606 | -0.035 | -3 | 0.728 |
AURC |
0.606 | 0.020 | -2 | 0.497 |
PRKD2 |
0.606 | -0.003 | -3 | 0.715 |
CK2A1 |
0.605 | 0.008 | 1 | 0.590 |
KIS |
0.604 | 0.065 | 1 | 0.565 |
MARK1 |
0.604 | -0.106 | 4 | 0.411 |
MARK3 |
0.604 | -0.084 | 4 | 0.403 |
QSK |
0.603 | -0.096 | 4 | 0.428 |
MSK2 |
0.603 | -0.021 | -3 | 0.691 |
GRK3 |
0.602 | -0.024 | -2 | 0.431 |
CHK2 |
0.601 | -0.033 | -3 | 0.571 |
P70S6K |
0.601 | -0.023 | -3 | 0.657 |
SIK |
0.601 | -0.065 | -3 | 0.692 |
MNK2 |
0.601 | -0.037 | -2 | 0.606 |
MSK1 |
0.601 | -0.016 | -3 | 0.688 |
SRPK2 |
0.601 | 0.001 | -3 | 0.630 |
SBK |
0.601 | 0.012 | -3 | 0.523 |
CAMK1A |
0.600 | 0.001 | -3 | 0.589 |
CLK2 |
0.600 | 0.017 | -3 | 0.681 |
BCKDK |
0.600 | -0.147 | -1 | 0.650 |
PHKG1 |
0.600 | -0.060 | -3 | 0.750 |
MNK1 |
0.599 | -0.042 | -2 | 0.598 |
RSK4 |
0.599 | -0.008 | -3 | 0.675 |
PKACB |
0.598 | 0.006 | -2 | 0.520 |
EPHB4 |
0.598 | 0.282 | -1 | 0.665 |
EPHA6 |
0.597 | 0.255 | -1 | 0.630 |
EPHA4 |
0.596 | 0.303 | 2 | 0.756 |
MAPKAPK5 |
0.596 | -0.018 | -3 | 0.692 |
SNRK |
0.596 | -0.122 | 2 | 0.521 |
PTK2B |
0.595 | 0.285 | -1 | 0.658 |
PAK6 |
0.594 | -0.001 | -2 | 0.574 |
PKN1 |
0.594 | -0.015 | -3 | 0.669 |
EPHB2 |
0.594 | 0.277 | -1 | 0.651 |
AKT3 |
0.594 | 0.008 | -3 | 0.566 |
NUAK1 |
0.594 | -0.081 | -3 | 0.724 |
CK1D |
0.594 | -0.007 | -3 | 0.390 |
CK1A2 |
0.593 | 0.001 | -3 | 0.389 |
EPHB1 |
0.593 | 0.254 | 1 | 0.548 |
MAPKAPK2 |
0.593 | -0.014 | -3 | 0.664 |
EPHA7 |
0.592 | 0.291 | 2 | 0.753 |
BRSK1 |
0.592 | -0.057 | -3 | 0.725 |
EPHB3 |
0.590 | 0.245 | -1 | 0.666 |
SRMS |
0.590 | 0.208 | 1 | 0.590 |
ABL2 |
0.589 | 0.115 | -1 | 0.665 |
LTK |
0.589 | 0.163 | 3 | 0.534 |
EPHA3 |
0.589 | 0.273 | 2 | 0.746 |
PKACA |
0.589 | 0.003 | -2 | 0.478 |
MERTK |
0.588 | 0.180 | 3 | 0.493 |
TXK |
0.588 | 0.136 | 1 | 0.615 |
BLK |
0.588 | 0.171 | -1 | 0.583 |
EPHA5 |
0.588 | 0.252 | 2 | 0.712 |
PAK5 |
0.588 | -0.011 | -2 | 0.540 |
CK1E |
0.587 | -0.015 | -3 | 0.442 |
BRSK2 |
0.587 | -0.107 | -3 | 0.749 |
ABL1 |
0.586 | 0.112 | -1 | 0.671 |
PDHK3_TYR |
0.586 | 0.024 | 4 | 0.485 |
ITK |
0.585 | 0.175 | -1 | 0.660 |
TYRO3 |
0.585 | 0.090 | 3 | 0.477 |
PAK4 |
0.585 | 0.003 | -2 | 0.531 |
YES1 |
0.584 | 0.114 | -1 | 0.630 |
TEC |
0.584 | 0.095 | -1 | 0.692 |
EPHA8 |
0.584 | 0.244 | -1 | 0.603 |
MST1R |
0.583 | 0.107 | 3 | 0.513 |
AXL |
0.583 | 0.137 | 3 | 0.497 |
ALK |
0.583 | 0.113 | 3 | 0.541 |
FER |
0.582 | 0.082 | 1 | 0.630 |
PHKG2 |
0.582 | -0.077 | -3 | 0.718 |
LCK |
0.582 | 0.122 | -1 | 0.590 |
EPHA1 |
0.581 | 0.165 | 3 | 0.558 |
CSF1R |
0.580 | 0.068 | 3 | 0.506 |
PRKX |
0.580 | 0.012 | -3 | 0.576 |
BMX |
0.580 | 0.097 | -1 | 0.615 |
LIMK2_TYR |
0.579 | 0.013 | -3 | 0.841 |
PKMYT1_TYR |
0.579 | -0.008 | 3 | 0.441 |
PDGFRB |
0.579 | 0.093 | 3 | 0.512 |
TEK |
0.579 | 0.096 | 3 | 0.493 |
HCK |
0.579 | 0.108 | -1 | 0.620 |
INSRR |
0.578 | 0.068 | 3 | 0.473 |
ROS1 |
0.578 | 0.015 | 3 | 0.480 |
MAP2K4_TYR |
0.578 | -0.045 | -1 | 0.640 |
BTK |
0.577 | 0.092 | -1 | 0.709 |
EPHA2 |
0.577 | 0.215 | -1 | 0.613 |
MAP2K6_TYR |
0.577 | -0.038 | -1 | 0.607 |
PTK2 |
0.577 | 0.225 | -1 | 0.511 |
MET |
0.576 | 0.103 | 3 | 0.531 |
LIMK1_TYR |
0.576 | -0.052 | 2 | 0.645 |
DDR1 |
0.576 | 0.036 | 4 | 0.432 |
FGFR1 |
0.576 | 0.102 | 3 | 0.516 |
FLT3 |
0.575 | 0.060 | 3 | 0.503 |
PDHK1_TYR |
0.575 | -0.038 | -1 | 0.608 |
CSK |
0.575 | 0.200 | 2 | 0.767 |
FGFR2 |
0.574 | 0.085 | 3 | 0.492 |
KDR |
0.574 | 0.051 | 3 | 0.514 |
PKG1 |
0.574 | -0.017 | -2 | 0.480 |
KIT |
0.574 | 0.058 | 3 | 0.506 |
BMPR2_TYR |
0.574 | 0.004 | -1 | 0.577 |
FRK |
0.573 | 0.106 | -1 | 0.640 |
RET |
0.573 | -0.013 | 1 | 0.474 |
TESK1_TYR |
0.573 | -0.138 | 3 | 0.416 |
MAP2K7_TYR |
0.573 | -0.163 | 2 | 0.647 |
LYN |
0.572 | 0.083 | 3 | 0.456 |
PDHK4_TYR |
0.571 | -0.116 | 2 | 0.648 |
JAK2 |
0.571 | -0.022 | 1 | 0.448 |
PINK1_TYR |
0.571 | -0.136 | 1 | 0.581 |
FGFR4 |
0.571 | 0.172 | -1 | 0.618 |
NTRK1 |
0.570 | 0.049 | -1 | 0.665 |
PDGFRA |
0.570 | 0.024 | 3 | 0.514 |
FGFR3 |
0.569 | 0.073 | 3 | 0.490 |
NTRK2 |
0.569 | 0.038 | 3 | 0.475 |
CK1G3 |
0.569 | 0.026 | -3 | 0.253 |
TYK2 |
0.569 | -0.075 | 1 | 0.472 |
MATK |
0.569 | 0.068 | -1 | 0.603 |
FYN |
0.568 | 0.078 | -1 | 0.540 |
PTK6 |
0.568 | -0.034 | -1 | 0.656 |
CK1G1 |
0.567 | 0.002 | -3 | 0.438 |
WEE1_TYR |
0.567 | -0.017 | -1 | 0.662 |
NTRK3 |
0.567 | 0.049 | -1 | 0.620 |
INSR |
0.566 | 0.041 | 3 | 0.450 |
DDR2 |
0.566 | 0.046 | 3 | 0.526 |
SRC |
0.565 | 0.079 | -1 | 0.568 |
FGR |
0.565 | -0.007 | 1 | 0.616 |
JAK1 |
0.565 | 0.005 | 1 | 0.384 |
TNK1 |
0.565 | -0.049 | 3 | 0.463 |
FLT4 |
0.563 | 0.025 | 3 | 0.454 |
ERBB2 |
0.562 | 0.025 | 1 | 0.445 |
EGFR |
0.561 | 0.095 | 1 | 0.357 |
JAK3 |
0.561 | -0.078 | 1 | 0.455 |
FES |
0.560 | 0.069 | -1 | 0.616 |
ERBB4 |
0.558 | 0.074 | 1 | 0.423 |
FLT1 |
0.557 | -0.009 | -1 | 0.600 |
IGF1R |
0.556 | 0.022 | 3 | 0.422 |
CK1A |
0.552 | 0.047 | -3 | 0.301 |
TNNI3K_TYR |
0.551 | -0.095 | 1 | 0.494 |
SYK |
0.551 | 0.048 | -1 | 0.515 |
MUSK |
0.550 | -0.034 | 1 | 0.369 |
NEK10_TYR |
0.547 | -0.156 | 1 | 0.377 |
CK1G2 |
0.543 | -0.015 | -3 | 0.349 |
ZAP70 |
0.530 | -0.003 | -1 | 0.468 |