GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
O95271	O15234	1	ADP-ribosylation	down-regulates quantity by destabilization	0.2	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263383
Q13976	P17252	0	phosphorylation	up-regulates	0.344	Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.	SIGNOR-98803
Q13185	O14965	0	phosphorylation	up-regulates activity	0.363	We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.	SIGNOR-280185
P46527	Q9UBF6	0	ubiquitination	down-regulates activity	0.348	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271447
P49841	Q05397	0	phosphorylation	up-regulates activity	0.365	Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).\|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling.	SIGNOR-278986
Q93045	P17612	0	phosphorylation	down-regulates activity	0.309	Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation	SIGNOR-250056
P31749	P35226	1	phosphorylation	up-regulates activity	0.437	The polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate	SIGNOR-252559
P10721	Q13191	0	ubiquitination	down-regulates activity	0.328	KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT.	SIGNOR-260105
P22694	Q6PIY7	1	phosphorylation	down-regulates activity	0.2	We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.	SIGNOR-259403
Q00535	Q9NQT8	1	phosphorylation	down-regulates activity	0.365	Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport.	SIGNOR-262737
Q13188	P25098	0	phosphorylation	up-regulates activity	0.2	Taken together, these studies support a role for GRK2 phosphorylation of Mst2 residues Ser-18 and Ser-316 in EGF-promoted centrosome separation.\|Thus GRK2 appears to mediate EGF promoted cleavage and activation of Mst2.	SIGNOR-278206
P12931	P78357	1	phosphorylation	down-regulates activity	0.336	If that is the case, then our genetic results support the notion that p190 is negatively regulated by both Src and integrin.\|The Src family of tyrosine kinases phosphorylate mammalian p190.	SIGNOR-279572
P50613	P50750	1	phosphorylation	up-regulates activity	0.551	Cdk7 activates Cdk9 in vitro .\|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.	SIGNOR-279455
P29474	P17612	0	phosphorylation	up-regulates	0.399	Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.	SIGNOR-112371
Q9UQM7	Q9Y618	1	phosphorylation	down-regulates	0.2	We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.	SIGNOR-191773
O00712	Q14938	1	transcriptional regulation	up-regulates quantity	0.42	We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.	SIGNOR-268870
Q96KB5	P05412	1	phosphorylation	up-regulates activity	0.43	TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun.\|These data confirm the phosphorylation of c-Jun by TOPK at serine 63 and 73 during the development of resistance to EGFR-targeted TKIs.	SIGNOR-278156
O14965	P16949	1	phosphorylation	down-regulates activity	0.388	Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.\|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .	SIGNOR-278913
Q13562	Q12857	0	transcriptional regulation	up-regulates quantity	0.284	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268890
O15151	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.948	Here we demonstrate that MdmX acts as a ubiquitin ligase in vitro, being capable of autoubiquitination, as well as mediating the ubiquitination of p53.	SIGNOR-271389
P10275	P50750	0	phosphorylation	up-regulates activity	0.537	AR S81 phosphorylation by CDK9 is tightly linked to chromatin binding and transcriptional activation.	SIGNOR-279456
Q00535	Q9UKV5	1	phosphorylation	down-regulates quantity by destabilization	0.248	We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78.	SIGNOR-277356
P10747	P06239	0	phosphorylation	up-regulates	0.754	We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor	SIGNOR-45524
Q06124	P12931	1	dephosphorylation	up-regulates activity	0.653	Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B	SIGNOR-248671
P28482	P51812	1	phosphorylation	up-regulates	0.728	Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.	SIGNOR-161518
P50613	P41743	0	phosphorylation	up-regulates activity	0.343	PKC\u03b9 activates CDK7 to promote glucose consumption.\|PKC\u03b9 phosphorylates Thr170 on CDK7 in vitro, can associate with CDK7 in cells, and is activated downstream of PI3K signaling xref , xref \u2013 xref .	SIGNOR-280088
Q8IVP5	O75385	0	phosphorylation	up-regulates activity	0.595	Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3.	SIGNOR-273606
O76054	P17612	0	phosphorylation	up-regulates activity	0.2	These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.	SIGNOR-276027
Q13200	Q9P1W9	0	phosphorylation	up-regulates activity	0.2	Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).	SIGNOR-273896
Q13315	Q9BUR4	1	phosphorylation	up-regulates activity	0.337	Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.	SIGNOR-273511
O43561	Q12913	0	dephosphorylation	down-regulates activity	0.353	Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation	SIGNOR-248696
P51955	Q8NG66	1	phosphorylation	up-regulates	0.393	Nek2 directly phosphorylated nek11 in the c-terminal non-catalytic region and elevated nek11 kinase activity.	SIGNOR-124944
P07101	P23246	0	transcriptional regulation	down-regulates quantity by repression	0.2	It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter.	SIGNOR-271697
Q9UQ26	O14795	1	relocalization	up-regulates activity	0.358	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264383
P04637	P51959	1	transcriptional regulation	up-regulates quantity by expression	0.791	Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation.	SIGNOR-268961
Q86WV6	Q9UK80	0	deubiquitination	down-regulates activity	0.2	In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I	SIGNOR-273671
P35968	Q12913	0	dephosphorylation	down-regulates	0.699	The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.	SIGNOR-181672
P05067	P56817	0	cleavage	up-regulates activity	0.794	Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ.	SIGNOR-255480
Q6N021	O60674	0	phosphorylation	up-regulates activity	0.418	Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin.	SIGNOR-277289
P52564	Q16539	1	phosphorylation	up-regulates activity	0.744	These data indicate that mkk6 phosphorylates p38 map kinase on thr-180 and tyr-182, the sites of phosphorylation that activate p38 map kinase	SIGNOR-40427
Q8NHL6	Q86YJ5	0	ubiquitination	down-regulates quantity by destabilization	0.2	MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.	SIGNOR-271534
O15519	P05771	0	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins	SIGNOR-276146
P10636-5	Q96L34	0	phosphorylation	down-regulates activity	0.419	AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).	SIGNOR-273932
O00327	P04275	1	transcriptional regulation	down-regulates quantity by repression	0.324	We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype.	SIGNOR-253704
P27361	P15923	1	phosphorylation	down-regulates quantity by destabilization	0.372	Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. \|Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)\|anti_phospho_M2 peptide (SSPSpTPVGSPQG)	SIGNOR-249117
P38936	Q9UHC7	0	polyubiquitination	down-regulates quantity by destabilization	0.313	Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21.	SIGNOR-271845
P08559	Q9P2J9	0	dephosphorylation	up-regulates activity	0.658	Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial serine phosphatase that activates phosphorylated pyruvate dehydrogenase complex by dephosphorylation	SIGNOR-251665
P24941	Q05516	1	phosphorylation	down-regulates	0.282	Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.	SIGNOR-160630
P12931	P42224	1	phosphorylation	up-regulates activity	0.559	The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation.	SIGNOR-235696
Q99986	P16104	1	phosphorylation	up-regulates activity	0.2	In response to DNA damage induced by ionizing radiation, histone H2AX is phosphorylated in Ser139 by VRK1.	SIGNOR-278370
Q13043	P17252	1	phosphorylation	up-regulates activity	0.2	Mst1 and Mst2 activate PKC\u03b1 to disrupt the LyGDI-Rac complex.\|Thus, the phosphorylation of PKC\u03b1 at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKC\u03b1.	SIGNOR-280146
Q99835	Q5GLZ8	0	ubiquitination	down-regulates quantity by destabilization	0.2	Our data showed that Herc4 mediated Smo degradation by proteasome and lysosome, but mainly by proteasome.\|Using the cell based ubiquitination assay, we found that both Myc-SmoK13R and Myc-SmoK49R exhibited reduced ubiquitination compared with Myc-Smo by Herc4, but Myc-SmoK49R resulted in a more dramatic reduction in Smo ubiquitination (XREF_FIG), suggesting that Smo is ubiquitinated by Herc4 at multiple Lys residues.	SIGNOR-278521
P01178-PRO_0000020495	Q9UIQ6	0	cleavage	down-regulates quantity by destabilization	0.2	It has been shown that the steady state of the mature OT form can be controlled by an oxytocinase (P-LAP) that is produced in periphery and centrally by the OT-magnocellular neurons. Noticeably, P-LAP is also expressed in parvocellular OT neurons and in other brain structures\| The OT intermediate forms are produced from E16.5 (see above) but the mature amidated OT form is detected only from birth. The released mature form is then degraded by an oxytocinase (PLAP)	SIGNOR-268552
Q9ULZ3	Q07812	1	relocalization	up-regulates	0.353	Asc directly induces bax-mediated apoptosis. Asc induces the translocation of bax to the mitochondria, bax-dependent cycs release from the mitochondria and casp9 activation.	SIGNOR-149522
P04637	O15111	0	phosphorylation	up-regulates activity	0.429	In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.\|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].	SIGNOR-280231
P05787	P06493	0	phosphorylation	up-regulates	0.248	With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.	SIGNOR-56054
P23276	P14138	1	cleavage	up-regulates activity	0.676	These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.	SIGNOR-256354
Q5TG30	P61586	1	gtpase-activating protein	down-regulates activity	0.432	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260496
Q5S007	Q05397	1	phosphorylation	down-regulates activity	0.2	LRRK2 inhibits FAK activation in a kinase dependent manner, meaning that the G2019S gain-of-function mutation results in the excessive inhibition of FAK activation and microglial motility.\|Taken together, these results suggest that LRRK2 directly phosphorylate FAK at T474.	SIGNOR-278281
O15264	P04637	1	phosphorylation	up-regulates	0.462	In mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.	SIGNOR-72691
O43561	P06239	0	phosphorylation	up-regulates	0.758	Evidence of lat as a dual substrate for lck and syk in t lymphocytes.Lat is a linker protein essential for activation of t lymphocytes. Its rapid tyrosine-phosphorylation upon t cell receptor (tcr) stimulation recruits downstream signaling molecules for membrane targeting and activation.	SIGNOR-149182
P06241	P08575	0	dephosphorylation	up-regulates activity	0.73	On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.	SIGNOR-248352
P84022	P50750	0	phosphorylation	down-regulates activity	0.622	Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161589
P40337	Q96PY6	0	phosphorylation	down-regulates quantity by destabilization	0.257	Nek1 phosphorylates Von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization. Mutation of pVHL at S-168 increases protein stability.	SIGNOR-276434
P06493	O43683	1	phosphorylation	up-regulates	0.861	The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609	SIGNOR-147065
P61586	Q14CB8	0	gtpase-activating protein	down-regulates activity	0.568	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260471
P68400	Q99808	1	phosphorylation	up-regulates activity	0.2	These data suggest that inhibition of CK2-mediated phosphorylation at Ser254 had the same effect on transporter function as the actual loss of Ser254 in mENT1a, implying that this site is constitutively phosphorylated by CK2.	SIGNOR-276063
P08151	Q15915	0	relocalization	up-regulates	0.377	Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels	SIGNOR-105491
P05771	Q9Y5S8	1	phosphorylation	up-regulates activity	0.2	Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly	SIGNOR-264729
Q99075	P78536	0	cleavage	up-regulates activity	0.591	ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF	SIGNOR-259844
P00533	Q05397	1	phosphorylation	up-regulates	0.595	In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases.	SIGNOR-167646
P38936	P15173	0	transcriptional regulation	down-regulates quantity by repression	0.331	P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells	SIGNOR-251575
Q14164	Q92985	1	phosphorylation	up-regulates	0.687	In response to a viral infection, phosphorylated on ser-477 and ser-479 by tbk1 and ikbke1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein e3.	SIGNOR-79139
P55210	Q14790	0	cleavage	up-regulates	0.742	Casp8 can activate downstream caspases like caspase-6, and caspase-7 by directly cleaving them.	SIGNOR-58118
P11309	Q00987	1	phosphorylation	up-regulates	0.388	Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt.	SIGNOR-178619
Q5VWQ8	P35222	1	relocalization	down-regulates quantity	0.299	DAB2IP prevents β-catenin nuclear translocation.	SIGNOR-254755
P05546	P08246	0	cleavage	down-regulates activity	0.451	Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.	SIGNOR-256510
O00141	P42224	1	phosphorylation	up-regulates activity	0.252	Notably, A\u03b2-activated SGK1 or JAK2 kinase phosphorylates STAT1 and induces its association with Tau(1\u2013368).	SIGNOR-279281
P68400	Q9UJU2	1	phosphorylation	up-regulates	0.303	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-23958
Q13224	P29323	0	phosphorylation	up-regulates quantity	0.443	In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs.	SIGNOR-279710
P67775	Q9Y314	0	ubiquitination	down-regulates quantity by destabilization	0.338	NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.	SIGNOR-271498
Q15208	Q9Y6E0	0	phosphorylation	up-regulates	0.381	Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.	SIGNOR-142467
O15067	P28482	0	phosphorylation	up-regulates	0.2	T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation.	SIGNOR-267306
P68431	P41229	0	demethylation	up-regulates activity	0.2	KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.	SIGNOR-264305
Q01196	Q86X55	0	methylation	down-regulates activity	0.282	We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus.	SIGNOR-261967
Q96EB6	Q13627	0	phosphorylation	up-regulates activity	0.54	DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.\|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.	SIGNOR-278473
P0C0S8	Q86Y13	0	monoubiquitination	up-regulates activity	0.2	2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.	SIGNOR-271749
Q9UNH5	P30305	1	dephosphorylation	down-regulates activity	0.56	Cdc14A inhibits Cdc25A and Cdc25B activity, the latter through direct binding and dephosphorylation ( ).\|Together, these data indicate that Cdc14A dephosphorylates Cdc25B, inhibiting its catalytic activity.	SIGNOR-276968
P42261	Q13555	0	phosphorylation	up-regulates activity	0.63	In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. \| This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.	SIGNOR-250697
Q00987	P48730	0	phosphorylation	down-regulates	0.345	Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase.	SIGNOR-167497
O00418	Q9UKB1	0	ubiquitination	down-regulates	0.436	Eef2k was degraded by the ubiquitin-proteasome system through the ubiquitin ligase scf(__trcp) (skp1-cul1-f-box protein, __-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eef2k on a canonical __trcp-binding domain	SIGNOR-197730
Q2M1P5	Q99835	0	relocalization	up-regulates activity	0.632	Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli proteins.	SIGNOR-209605
Q14289	Q06124	0	dephosphorylation	down-regulates activity	0.725	We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. \|We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity.	SIGNOR-277084
Q9ULU4	P25440	0	relocalization	up-regulates activity	0.287	ZMYND8 and BRD2 therefore work together to protect H4Ac domains from HDAC activity.\|Further, when BRD2 was depleted, ZMYND8 accumulation was lost (Fig. 2e), indicating that either BRD2, or the underlying H4Ac, is required for ZMYND8 loading.	SIGNOR-262036
Q9UBS5	P27361	0	phosphorylation	down-regulates quantity by destabilization	0.276	We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1.	SIGNOR-277854
P19174	P00519	0	phosphorylation	down-regulates activity	0.59	C-Abl induces Tyr phosphorylation of PLC-γ1 in vivo. These findings demonstrate that c-Abl phosphorylates PLC-γ1 in vivo predominantly at Tyr 771 and Tyr 1003.c-Abl phosphorylation of PLC-γ1 causes downregulation of PLC activity.	SIGNOR-276001
Q92830	P84243	1	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269603
Q7KZI7	Q9NQT8	1	phosphorylation	down-regulates activity	0.415	We report here the identification of GAKIN/KIF13B as a novel in vivo substrate for Par1b and present evidence that GAKIN/KIF13B plays a critical role in axon formation in neurons, which is negatively regulated by Par1b-mediated phosphorylation. Par1b phosphorylates GAKIN/KIF13B at both Ser1381 and Ser1410.	SIGNOR-262956
Q15208	O14980	1	phosphorylation	up-regulates activity	0.2	We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit.	SIGNOR-277483
Q9NRA0	P28482	0	phosphorylation	up-regulates	0.451	Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1	SIGNOR-153383

O95271

O15234

1

ADP-ribosylation

down-regulates quantity by destabilization

0.2

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263383

Q13976

P17252

0

phosphorylation

up-regulates

0.344

Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.

SIGNOR-98803

Q13185

O14965

0

phosphorylation

up-regulates activity

0.363

We report for the first time that during mitotic cell division, heterochromatin protein 1\u03b3 colocalizes and is phosphorylated at serine 83 in G2/M phase by Aurora A.

SIGNOR-280185

P46527

Q9UBF6

0

ubiquitination

down-regulates activity

0.348

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271447

P49841

Q05397

0

phosphorylation

up-regulates activity

0.365

Inhibition of FAK by its small molecule inhibitor attenuated IL-33-induced tyrosine 216 phosphorylation of GSK3beta in a both time- and dose dependent manner (XREF_FIG).|The current study indicates that FAK activated GSK3beta modulates ST2L internalization and signaling.

SIGNOR-278986

Q93045

P17612

0

phosphorylation

down-regulates activity

0.309

Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation

SIGNOR-250056

P31749

P35226

1

phosphorylation

up-regulates activity

0.437

The polycomb group silencing protein Bmi1 can be phosphorylated by AKT, which enhances its oncogenic potential in PCa. Overexpression of Bmi1 can act in combination with PTEN haploinsufficiency to induce invasive carcinogenic formation in the prostate

SIGNOR-252559

P10721

Q13191

0

ubiquitination

down-regulates activity

0.328

KIT binds to and induces the phosphorylation of Cbl proteins, which in turn act as E3 ligases, mediating the ubiquitination and degradation of KIT and themselves. Tyrosine kinase binding and RING finger domains of Cbl are essential for Cbl-mediated ubiquitination and degradation of KIT.

SIGNOR-260105

P22694

Q6PIY7

1

phosphorylation

down-regulates activity

0.2

We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.

SIGNOR-259403

Q00535

Q9NQT8

1

phosphorylation

down-regulates activity

0.365

Overexpression of Cdk5 or its activator p35 promoted and inhibition of Cdk5 activity prevented the KIF13B-TRPV1 association, indicating that Cdk5 promotes TRPV1 anterograde transport by mediating the motor-cargo association. Cdk5 phosphorylates KIF13B at Thr-506, a residue located in the FHA domain. T506A mutation reduced the motor-cargo interaction and the cell-permeable TAT-T506 peptide, targeting to the Thr-506, decreased TRPV1 surface localization, demonstrating the essential role of Thr-506 phosphorylation in TRPV1 transport.

SIGNOR-262737

Q13188

P25098

0

phosphorylation

up-regulates activity

0.2

Taken together, these studies support a role for GRK2 phosphorylation of Mst2 residues Ser-18 and Ser-316 in EGF-promoted centrosome separation.|Thus GRK2 appears to mediate EGF promoted cleavage and activation of Mst2.

SIGNOR-278206

P12931

P78357

1

phosphorylation

down-regulates activity

0.336

If that is the case, then our genetic results support the notion that p190 is negatively regulated by both Src and integrin.|The Src family of tyrosine kinases phosphorylate mammalian p190.

SIGNOR-279572

P50613

P50750

1

phosphorylation

up-regulates activity

0.551

Cdk7 activates Cdk9 in vitro .|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate.

SIGNOR-279455

P29474

P17612

0

phosphorylation

up-regulates

0.399

Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase aon serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.

SIGNOR-112371

Q9UQM7

Q9Y618

1

phosphorylation

down-regulates

0.2

We demonstrated that camkii directly bound and phosphorylated smrt at ser-1407, thereby facilitating smrt translocation from the nucleus to the cytoplasm and proteasome-dependent degradation.

SIGNOR-191773

O00712

Q14938

1

transcriptional regulation

up-regulates quantity

0.42

We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.

SIGNOR-268870

Q96KB5

P05412

1

phosphorylation

up-regulates activity

0.43

TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun.|These data confirm the phosphorylation of c-Jun by TOPK at serine 63 and 73 during the development of resistance to EGFR-targeted TKIs.

SIGNOR-278156

O14965

P16949

1

phosphorylation

down-regulates activity

0.388

Inhibition of AURKA activity activates stathmin function via reduced phosphorylation and facilitates microtubule destabilization in RB1 -/- cells, heavily impacting the bipolar spindle formation and inducing mitotic cell death selectively in RB1 -/- cells.|Two serine phosphorylation sites, Ser16 and Ser63, in stathmin contain a consensus sequence for AURKA phosphorylation and the mutations in these two serine sites abolished stathmin phosphorylation by AURKA, suggesting that stathmin is a substrate of AURKA for phosphorylation xref , xref .

SIGNOR-278913

Q13562

Q12857

0

transcriptional regulation

up-regulates quantity

0.284

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268890

O15151

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.948

Here we demonstrate that MdmX acts as a ubiquitin ligase in vitro, being capable of autoubiquitination, as well as mediating the ubiquitination of p53.

SIGNOR-271389

P10275

P50750

0

phosphorylation

up-regulates activity

0.537

AR S81 phosphorylation by CDK9 is tightly linked to chromatin binding and transcriptional activation.

SIGNOR-279456

Q00535

Q9UKV5

1

phosphorylation

down-regulates quantity by destabilization

0.248

We found that GP78 expression is decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78.

SIGNOR-277356

P10747

P06239

0

phosphorylation

up-regulates

0.754

We demonstrate that emt can phosphorylate all four tyrosines of the cd28 tail, in contrast to lck, which phosphorylates only tyrosine 173. Together with evidence that in vivo, tyrosines other than tyrosine 173 become phosphorylated following cd28 stimulation, this finding suggests that, like lck, one function of emt during cd28 signaling is phosphorylation of the receptor

SIGNOR-45524

Q06124

P12931

1

dephosphorylation

up-regulates activity

0.653

Several protein tyrosine phosphatases are capable of activating Src by dephosphorylating Y530 (reviewed in ref. 9). These include PTP-α, PTP-λ, SHP-1, SHP-2, and PTP1B

SIGNOR-248671

P28482

P51812

1

phosphorylation

up-regulates

0.728

Erk-activates the rsk family of serine/threonine kinases,rsk1, rsk2, and rsk3.

SIGNOR-161518

P50613

P41743

0

phosphorylation

up-regulates activity

0.343

PKC\u03b9 activates CDK7 to promote glucose consumption.|PKC\u03b9 phosphorylates Thr170 on CDK7 in vitro, can associate with CDK7 in cells, and is activated downstream of PI3K signaling xref , xref \u2013 xref .

SIGNOR-280088

Q8IVP5

O75385

0

phosphorylation

up-regulates activity

0.595

Here, we show that ULK1 is upregulated and translocates to fragmented mitochondria upon mitophagy induction by either hypoxia or mitochondrial uncouplers. At mitochondria, ULK1 interacts with FUNDC1, phosphorylating it at serine 17, which enhances FUNDC1 binding to LC3.

SIGNOR-273606

O76054

P17612

0

phosphorylation

up-regulates activity

0.2

These results suggest that phosphorylation of SPF by PKA is a dynamic process and that, in the absence of PKA activity, SPF is rapidly inactivated.Thus, phosphorylation of SPF at Ser-289 appears necessary for maximal stimulation of squalene monooxygenase activity in vitro and absolutely required for the stimulation of cholesterol synthesis in cell culture.

SIGNOR-276027

Q13200

Q9P1W9

0

phosphorylation

up-regulates activity

0.2

Seven of these kinases (PIM1/2/3, MAP4K1/2, PKA, and NEK6) directly and robustly phosphorylated recombinant GST-Rpn1 at S361 in vitro (Fig. 3D and SI Appendix, Fig. S3 A and B).

SIGNOR-273896

Q13315

Q9BUR4

1

phosphorylation

up-regulates activity

0.337

Here, we show that in response to various types of DNA damage, including IR and UV, WRAP53β is phosphorylated on serine residue 64 by ATM with a time-course that parallels its accumulation at DNA lesions. Interestingly, recruitment of phosphorylated WRAP53β (pWRAP53βS64) to sites of such DNA damage promotes its interaction with γH2AX at these locations.

SIGNOR-273511

O43561

Q12913

0

dephosphorylation

down-regulates activity

0.353

Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation

SIGNOR-248696

P51955

Q8NG66

1

phosphorylation

up-regulates

0.393

Nek2 directly phosphorylated nek11 in the c-terminal non-catalytic region and elevated nek11 kinase activity.

SIGNOR-124944

P07101

P23246

0

transcriptional regulation

down-regulates quantity by repression

0.2

It has been reported that DJ-1 is a neuroprotective transcriptional co-activator that sequesters a transcriptional co-repressor polypyrimidine tract-binding protein-associated splicing factor (PSF) from the TH gene promoter.

SIGNOR-271697

Q9UQ26

O14795

1

relocalization

up-regulates activity

0.358

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264383

P04637

P51959

1

transcriptional regulation

up-regulates quantity by expression

0.791

Individual promoter and intron p53-binding motifs from the rat Cyclin G1 promoter region support transcriptional activation by p53 but do not show co-operative activation.

SIGNOR-268961

Q86WV6

Q9UK80

0

deubiquitination

down-regulates activity

0.2

In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. I

SIGNOR-273671

P35968

Q12913

0

dephosphorylation

down-regulates

0.699

The autoactivation residues y1054 and y1059 are targeted by dep-1 and this results in the inhibition of kinase activity and the consequent general dephosphorylation of vegfr2.

SIGNOR-181672

P05067

P56817

0

cleavage

up-regulates activity

0.794

Beta-secretase 1 (BACE1) cleaves the type-I transmembrane protein APP to form the N-terminus of Aβ.

SIGNOR-255480

Q6N021

O60674

0

phosphorylation

up-regulates activity

0.418

Specifically, cytokine receptor-associated JAK2 phosphorylates TET2 at tyrosines 1939 and 1964. Phosphorylated TET2 interacts with the erythroid transcription factor KLF1, and this interaction with TET2 is increased upon exposure to erythropoietin.

SIGNOR-277289

P52564

Q16539

1

phosphorylation

up-regulates activity

0.744

These data indicate that mkk6 phosphorylates p38 map kinase on thr-180 and tyr-182, the sites of phosphorylation that activate p38 map kinase

SIGNOR-40427

Q8NHL6

Q86YJ5

0

ubiquitination

down-regulates quantity by destabilization

0.2

MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets.

SIGNOR-271534

O15519

P05771

0

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we identify serine 193 as a novel in vivo phosphorylation site of all c-FLIP proteins. c-FLIP S193 phosphorylation is mediated by PKCa and PKCb.S193 phosphorylation increases the stability of the short c-FLIP proteins

SIGNOR-276146

P10636-5

Q96L34

0

phosphorylation

down-regulates activity

0.419

AMPK phosphorylation inhibits tau binding of microtubules. In order to study further the phosphorylation of tau by AMPK, we compared phosphorylation of tau by MARK4 or AMPK using a panel of phospho-tau antibodies (Figure 2A). Five phosphorylation sites common to both kinases were identified (Thr231, Ser262, Ser356, Ser396 and Ser422). In addition, AMPK, but not MARK4, was capable of phosphorylating Ser214 (Figure 2A).

SIGNOR-273932

O00327

P04275

1

transcriptional regulation

down-regulates quantity by repression

0.324

We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype.

SIGNOR-253704

P27361

P15923

1

phosphorylation

down-regulates quantity by destabilization

0.372

Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. |Wild_type E47 but not the Mm mutant reacted to the antibodies, suggesting that E47 is at least phosphorylated at the M2 site (Figure 3A)|anti_phospho_M2 peptide (SSPSpTPVGSPQG)

SIGNOR-249117

P38936

Q9UHC7

0

polyubiquitination

down-regulates quantity by destabilization

0.313

Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21.

SIGNOR-271845

P08559

Q9P2J9

0

dephosphorylation

up-regulates activity

0.658

Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial serine phosphatase that activates phosphorylated pyruvate dehydrogenase complex by dephosphorylation

SIGNOR-251665

P24941

Q05516

1

phosphorylation

down-regulates

0.282

Here we show that the main cyclin-dependent kinase involved at the g(1) to s transition (cdk2) phosphorylates plzf at two consensus sites found within pest domains present in the hinge region of the protein. This phosphorylation triggers the ubiquitination and subsequent degradation of plzf, which impairs plzf transcriptional repression ability and antagonizes its growth inhibitory effects.

SIGNOR-160630

P12931

P42224

1

phosphorylation

up-regulates activity

0.559

The tyr701 phosphorylation of signal transducer and activator of transcription 1 (stat1) induced by interferon-gamma (ifn-gamma) and 12-o-tetradecanoylphorbol 13-acetate (tpa) was inhibited by the protein kinase c (pkc) inhibitor staurosporine, the tyrosine kinase inhibitor herbimycin, or the src kinase inhibitor pp2. An association between c-src and stat1 was increased by ifn-gamma and tpa, indicating the direct phosphorylation of stat1 by pkc-dependent c-src activation.

SIGNOR-235696

Q99986

P16104

1

phosphorylation

up-regulates activity

0.2

In response to DNA damage induced by ionizing radiation, histone H2AX is phosphorylated in Ser139 by VRK1.

SIGNOR-278370

Q13043

P17252

1

phosphorylation

up-regulates activity

0.2

Mst1 and Mst2 activate PKC\u03b1 to disrupt the LyGDI-Rac complex.|Thus, the phosphorylation of PKC\u03b1 at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKC\u03b1.

SIGNOR-280146

Q99835

Q5GLZ8

0

ubiquitination

down-regulates quantity by destabilization

0.2

Our data showed that Herc4 mediated Smo degradation by proteasome and lysosome, but mainly by proteasome.|Using the cell based ubiquitination assay, we found that both Myc-SmoK13R and Myc-SmoK49R exhibited reduced ubiquitination compared with Myc-Smo by Herc4, but Myc-SmoK49R resulted in a more dramatic reduction in Smo ubiquitination (XREF_FIG), suggesting that Smo is ubiquitinated by Herc4 at multiple Lys residues.

SIGNOR-278521

P01178-PRO_0000020495

Q9UIQ6

0

cleavage

down-regulates quantity by destabilization

0.2

It has been shown that the steady state of the mature OT form can be controlled by an oxytocinase (P-LAP) that is produced in periphery and centrally by the OT-magnocellular neurons. Noticeably, P-LAP is also expressed in parvocellular OT neurons and in other brain structures| The OT intermediate forms are produced from E16.5 (see above) but the mature amidated OT form is detected only from birth. The released mature form is then degraded by an oxytocinase (PLAP)

SIGNOR-268552

Q9ULZ3

Q07812

1

relocalization

up-regulates

0.353

Asc directly induces bax-mediated apoptosis. Asc induces the translocation of bax to the mitochondria, bax-dependent cycs release from the mitochondria and casp9 activation.

SIGNOR-149522

P04637

O15111

0

phosphorylation

up-regulates activity

0.429

In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].

SIGNOR-280231

P05787

P06493

0

phosphorylation

up-regulates

0.248

With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.

SIGNOR-56054

P23276

P14138

1

cleavage

up-regulates activity

0.676

These data demonstrate that the Kell blood group protein is a proteolytic enzyme that processes big ET-3, generating ET-3, a potent bioactive peptide with multiple biological roles.

SIGNOR-256354

Q5TG30

P61586

1

gtpase-activating protein

down-regulates activity

0.432

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260496

Q5S007

Q05397

1

phosphorylation

down-regulates activity

0.2

LRRK2 inhibits FAK activation in a kinase dependent manner, meaning that the G2019S gain-of-function mutation results in the excessive inhibition of FAK activation and microglial motility.|Taken together, these results suggest that LRRK2 directly phosphorylate FAK at T474.

SIGNOR-278281

O15264

P04637

1

phosphorylation

up-regulates

0.462

In mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.

SIGNOR-72691

O43561

P06239

0

phosphorylation

up-regulates

0.758

Evidence of lat as a dual substrate for lck and syk in t lymphocytes.Lat is a linker protein essential for activation of t lymphocytes. Its rapid tyrosine-phosphorylation upon t cell receptor (tcr) stimulation recruits downstream signaling molecules for membrane targeting and activation.

SIGNOR-149182

P06241

P08575

0

dephosphorylation

up-regulates activity

0.73

On the membrane SKAP55, via its phosphorylated Tyr-271, further binds the SH2 domain of Fyn to replace the low-affinity bound inhibitory site of the kinase. Consequently, CD45 may have transiently disassociated with the Tyr-232 residue of SKAP55 through dephosphorylation and simultaneously interacted with the released the phosphorylated inhibitory tyrosine residue of Fyn for dephosphorylation, resulting in activation of the Src family kinase Fyn and initiation of TCR-engaged signal transduction.

SIGNOR-248352

P84022

P50750

0

phosphorylation

down-regulates activity

0.622

Similarly, tgf-?-Induced and cdk8/9-mediated phosphorylation of smad3 at threonine 179 (t179) is important for binding of the nedd4l e3 ubiquitin ligase, which accelerates smad3 turnover;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161589

P40337

Q96PY6

0

phosphorylation

down-regulates quantity by destabilization

0.257

Nek1 phosphorylates Von Hippel-Lindau tumor suppressor to promote its proteasomal degradation and ciliary destabilization. Mutation of pVHL at S-168 increases protein stability.

SIGNOR-276434

P06493

O43683

1

phosphorylation

up-regulates

0.861

The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609

SIGNOR-147065

P61586

Q14CB8

0

gtpase-activating protein

down-regulates activity

0.568

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260471

P68400

Q99808

1

phosphorylation

up-regulates activity

0.2

These data suggest that inhibition of CK2-mediated phosphorylation at Ser254 had the same effect on transporter function as the actual loss of Ser254 in mENT1a, implying that this site is constitutively phosphorylated by CK2.

SIGNOR-276063

P08151

Q15915

0

relocalization

up-regulates

0.377

Co-expression of zic1 resulted in gli1 and gli3 proteins being translocated to the nucleus in varying levels

SIGNOR-105491

P05771

Q9Y5S8

1

phosphorylation

up-regulates activity

0.2

Site-directed mutagenesis and isothermal titration calorimetry indicated that protein kinase C-beta1 phosphorylates Nox1 at threonine 429. Moreover, Nox1 threonine 429 phosphorylation facilitated the association of Nox1 with the NoxA1 activation domain and was necessary for NADPH oxidase complex assembly

SIGNOR-264729

Q99075

P78536

0

cleavage

up-regulates activity

0.591

ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF

SIGNOR-259844

P00533

Q05397

1

phosphorylation

up-regulates

0.595

In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases.

SIGNOR-167646

P38936

P15173

0

transcriptional regulation

down-regulates quantity by repression

0.331

P21 is regulated by MyoD and myogenin in normal muscle cells and the inactivation of these factors in RMS cells contributes to the silencing of p21 in RMS cells

SIGNOR-251575

Q14164

Q92985

1

phosphorylation

up-regulates

0.687

In response to a viral infection, phosphorylated on ser-477 and ser-479 by tbk1 and ikbke1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein e3.

SIGNOR-79139

P55210

Q14790

0

cleavage

up-regulates

0.742

Casp8 can activate downstream caspases like caspase-6, and caspase-7 by directly cleaving them.

SIGNOR-58118

P11309

Q00987

1

phosphorylation

up-regulates

0.388

Additionally, the pim kinases phosphorylate mdm2 in vitro and in cultured cells at ser166 and ser186, two previously identified targets of other signaling pathways, including akt.

SIGNOR-178619

Q5VWQ8

P35222

1

relocalization

down-regulates quantity

0.299

DAB2IP prevents β-catenin nuclear translocation.

SIGNOR-254755

P05546

P08246

0

cleavage

down-regulates activity

0.451

Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.

SIGNOR-256510

O00141

P42224

1

phosphorylation

up-regulates activity

0.252

Notably, A\u03b2-activated SGK1 or JAK2 kinase phosphorylates STAT1 and induces its association with Tau(1\u2013368).

SIGNOR-279281

P68400

Q9UJU2

1

phosphorylation

up-regulates

0.303

Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.

SIGNOR-23958

Q13224

P29323

0

phosphorylation

up-regulates quantity

0.443

In addition, EPHB2 signaling leads to phosphorylation of GluN2B at tyrosine residue 1472 preventing clathrin dependent endocytosis, and increasing the surface retention of GluN2B containing NMDARs.

SIGNOR-279710

P67775

Q9Y314

0

ubiquitination

down-regulates quantity by destabilization

0.338

NOSIP mediates the monoubiquitination of the PP2A catalytic subunit and the loss of NOSIP results in an increase in PP2A activity in craniofacial tissue in NOSIP knockout mice.

SIGNOR-271498

Q15208

Q9Y6E0

0

phosphorylation

up-regulates

0.381

Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.

SIGNOR-142467

O15067

P28482

0

phosphorylation

up-regulates

0.2

T619 in PFAS is required to mediate ERK2-dependent purine synthesis stimulation. We demonstrate that ERK2, but not ERK1, phosphorylates the purine synthesis enzyme PFAS (phosphoribosylformylglycinamidine synthase) at T619 in cells to stimulate de novo purine synthesis. The expression of nonphosphorylatable PFAS (T619A) decreases purine synthesis, RAS-dependent cancer cell-colony formation, and tumor growth. Thus, ERK2-mediated PFAS phosphorylation facilitates the increase in nucleic acid synthesis required for anabolic cell growth and proliferation.

SIGNOR-267306

P68431

P41229

0

demethylation

up-regulates activity

0.2

KDM5 subfamily is capable of removing tri‐ and di‐ methyl marks from lysine 4 on histone H3 (H3K4). Depending on the methylation site, its effect on transcription can be either activating or repressing.

SIGNOR-264305

Q01196

Q86X55

0

methylation

down-regulates activity

0.282

We have found that PRMT4 is highly expressed in HSPCs, where it functions as an inhibitor of myeloid differentiation (Figure 7G). In these cells, PRMT4 methylates RUNX1 at R223, promoting the assembly of a DPF2-containing transcriptional co-repressive complex, and repressing transcription at the miR-223 locus.

SIGNOR-261967

Q96EB6

Q13627

0

phosphorylation

up-regulates activity

0.54

DYRK1A and DYRK3 directly phosphorylate SIRT1 at Thr(522), promoting deacetylation of p53.|DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.

SIGNOR-278473

P0C0S8

Q86Y13

0

monoubiquitination

up-regulates activity

0.2

2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase II release at the early stage of elongation.

SIGNOR-271749

Q9UNH5

P30305

1

dephosphorylation

down-regulates activity

0.56

Cdc14A inhibits Cdc25A and Cdc25B activity, the latter through direct binding and dephosphorylation ( ).|Together, these data indicate that Cdc14A dephosphorylates Cdc25B, inhibiting its catalytic activity.

SIGNOR-276968

P42261

Q13555

0

phosphorylation

up-regulates activity

0.63

In this study, CaM-kinase II enhanced kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. | This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-type glutamate receptors, and its phosphorylation may be important in enhancing postsynaptic responsiveness as occurs during synaptic plasticity.

SIGNOR-250697

Q00987

P48730

0

phosphorylation

down-regulates

0.345

Phosphorylation by casein kinase i promotes the turnover of the mdm2 oncoprotein via the scf(beta-trcp) ubiquitin ligase.

SIGNOR-167497

O00418

Q9UKB1

0

ubiquitination

down-regulates

0.436

Eef2k was degraded by the ubiquitin-proteasome system through the ubiquitin ligase scf(__trcp) (skp1-cul1-f-box protein, __-transducin repeat-containing protein) to enable rapid resumption of translation elongation. This event required autophosphorylation of eef2k on a canonical __trcp-binding domain

SIGNOR-197730

Q2M1P5

Q99835

0

relocalization

up-regulates activity

0.632

Here, we demonstrate that Kif7, a mammalian homologue of Drosophila Costal2 (Cos2), is a cilia-associated protein that regulates signaling from the membrane protein Smoothened (Smo) to Gli transcription factorsIn response to activation of Smo Kif7 at the cilia tip may antagonize Sufu to promote activation of Gli proteins.

SIGNOR-209605

Q14289

Q06124

0

dephosphorylation

down-regulates activity

0.725

We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. |We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM..... 1) RAFTK is a substrate of SHP2 in vitro and 2) dephosphorylation of RAFTK by SHP2 inhibits its kinase activity.

SIGNOR-277084

Q9ULU4

P25440

0

relocalization

up-regulates activity

0.287

ZMYND8 and BRD2 therefore work together to protect H4Ac domains from HDAC activity.|Further, when BRD2 was depleted, ZMYND8 accumulation was lost (Fig. 2e), indicating that either BRD2, or the underlying H4Ac, is required for ZMYND8 loading.

SIGNOR-262036

Q9UBS5

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.276

We found that, in addition to CaMKIIβ, also ERK1/2 is involved in the degradation pathway of GABAB receptors under physiological and ischemic conditions. In contrast to our previous view, CaMKIIβ does not appear to directly phosphorylate S867. Instead, the data support a mechanism in which CaMKIIβ activates ERK1/2, which then phosphorylates S867 and T872 in GABAB1.

SIGNOR-277854

P19174

P00519

0

phosphorylation

down-regulates activity

0.59

C-Abl induces Tyr phosphorylation of PLC-γ1 in vivo. These findings demonstrate that c-Abl phosphorylates PLC-γ1 in vivo predominantly at Tyr 771 and Tyr 1003.c-Abl phosphorylation of PLC-γ1 causes downregulation of PLC activity.

SIGNOR-276001

Q92830

P84243

1

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269603

Q7KZI7

Q9NQT8

1

phosphorylation

down-regulates activity

0.415

We report here the identification of GAKIN/KIF13B as a novel in vivo substrate for Par1b and present evidence that GAKIN/KIF13B plays a critical role in axon formation in neurons, which is negatively regulated by Par1b-mediated phosphorylation. Par1b phosphorylates GAKIN/KIF13B at both Ser1381 and Ser1410.

SIGNOR-262956

Q15208

O14980

1

phosphorylation

up-regulates activity

0.2

We further uncover that STK38 modulates XPO1 export activity by phosphorylating XPO1 on serine 1055, thus regulating its own nuclear exit.

SIGNOR-277483

Q9NRA0

P28482

0

phosphorylation

up-regulates

0.451

Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1

SIGNOR-153383