GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P14373	Q9Y2H1	1	ubiquitination	up-regulates activity	0.2	TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1	SIGNOR-270347
P27361	Q8TB45	1	phosphorylation	up-regulates quantity by stabilization	0.282	Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.	SIGNOR-277587
Q99856	P0DOX6	1	transcriptional regulation	up-regulates quantity by expression	0.2	In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.\| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene.	SIGNOR-268532
P35638	P49715	1	transcriptional regulation	down-regulates quantity	0.519	We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process.	SIGNOR-255913
Q86TM6	O15354	1	polyubiquitination	down-regulates quantity by destabilization	0.4	We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R.	SIGNOR-272631
P02818	P25774	0	cleavage	down-regulates quantity by destabilization	0.309	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256323
Q13177	P08670	1	phosphorylation	down-regulates activity	0.307	In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK.	SIGNOR-250243
Q05086	P20618	1	ubiquitination	down-regulates quantity by destabilization	0.355	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265131
P07101	O75582	0	phosphorylation	up-regulates	0.337	Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax. studies on th from several species suggest that ser40 is the main site involved in direct activation of th	SIGNOR-95491
Q9H334	Q9P283	1	transcriptional regulation	down-regulates quantity by repression	0.33	FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.	SIGNOR-269050
P09874	P00533	0	phosphorylation	up-regulates activity	0.394	EGFR and MET heterodimer interacts with and phosphorylates PARP1.	SIGNOR-279169
O60885	P27361	0	null	down-regulates activity	0.312	The MYC stabilizing kinase, ERK1, regulates MYC levels directly and indirectly by inhibiting BRD4 kinase activity.	SIGNOR-262048
P04637	P53355	0	phosphorylation	up-regulates	0.558	Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10).	SIGNOR-153491
Q92574	P06493	0	phosphorylation	down-regulates	0.489	Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin b.Cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70s6 kinase by the hamartin-tuberin complex	SIGNOR-118584
Q93009	P60484	1	deubiquitination	down-regulates activity	0.741	BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP\|hese data indicate that BCR-ABL phosphorylation of HAUSP modulates HAUSP’s deubiquitinase activity toward PTEN.	SIGNOR-276533
P17252	P32004	1	phosphorylation	down-regulates activity	0.2	CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.	SIGNOR-276283
Q06124	P01112	1	dephosphorylation	up-regulates activity	0.681	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-252094
P16949	P05771	0	phosphorylation	down-regulates	0.2	Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation.	SIGNOR-50598
Q9H0K1	Q09472	1	phosphorylation	down-regulates activity	0.278	Indeed, overexpression of SIK2 increased p300 phosphorylation at Ser89, while knockdown of SIK2 decreased it (Fig. 4B).	SIGNOR-278368
Q12933	Q13546	1	ubiquitination	up-regulates activity	0.895	Following binding to tradd, traf2 was thought to mediate non-degradative lys-63-linked polyubiquitination of rip1 via its ring e3 ligase domain. Rip1 is known to directly interact with traf2.	SIGNOR-59689
P49757	P41743	0	phosphorylation	down-regulates	0.771	Numb is regulated by phosphorylation since the protein is released from ccss and no longer binds integrins when phosphorylated by atypical protein kinase c (apkc).	SIGNOR-156765
Q15759	P04637	1	phosphorylation	up-regulates	0.611	We show that prak activates p53 by direct phosphorylation.	SIGNOR-152843
P49768	Q99590	0	cleavage	up-regulates activity	0.294	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261758
O94804	P15311	1	phosphorylation	up-regulates activity	0.473	Ezrin activation by LOK phosphorylation involves a PIP 2 -dependent wedge mechanism.\|The specificity of kinases depends on local peptide consensus sequences, which in the case of ezrin phosphorylation by LOK involves the hydrophobic residue Y565 positioned -2 residues from T567.	SIGNOR-278204
O60229	Q8IW41	0	phosphorylation	up-regulates activity	0.385	The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements. The fragment SR3-6, but not the mutated fragment SR3-6-S487A, is phosphorylated by MK5.	SIGNOR-263093
O15294	P98170	0	ubiquitination	down-regulates quantity	0.2	These results demonstrate that XIAP acts as an E3 ubiquitin ligase and ubiquitinates OGT in HCT116 colon cancer cells.\|XIAP promotes the ubiquitin-dependent proteasomal degradation of OGT.	SIGNOR-278800
Q53ET0	P57059	0	phosphorylation	down-regulates	0.644	These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.	SIGNOR-147707
O95997	O95155	0	polyubiquitination	down-regulates quantity by destabilization	0.2	We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells.	SIGNOR-271523
P06730	P05771	0	phosphorylation	up-regulates	0.348	Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .	SIGNOR-248946
P32004	Q15349	0	phosphorylation	up-regulates activity	0.515	Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. \| These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152.	SIGNOR-248949
P11388	P53350	0	phosphorylation	up-regulates	0.481	Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin	SIGNOR-182844
P00533	Q9UBN7	1	phosphorylation	down-regulates	0.44	A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.	SIGNOR-162431
O43251	O14920	0	phosphorylation	up-regulates activity	0.2	Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.	SIGNOR-279336
P68400	P10242	1	phosphorylation	down-regulates activity	0.34	For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants.	SIGNOR-250918
Q6IA17	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	Activation of GSK3beta promotes Sigirr degradation in the proteasome .\|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2.	SIGNOR-279053
Q5S007	P26038	1	phosphorylation	up-regulates activity	0.551	This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process.	SIGNOR-154498
P10242	P09488	1	transcriptional regulation	up-regulates quantity by expression	0.2	Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation	SIGNOR-253975
Q2TAL8	P54577	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269412
P48551	Q92793	0	acetylation	up-regulates activity	0.347	By binding to IFNalphaR2 within the region where two adjacent proline boxes bear phospho-Ser364 and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)RF9 interacts with the acetyl-Lys399 motif by means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2.	SIGNOR-217783
P61586	Q3KR16	0	guanine nucleotide exchange factor	up-regulates activity	0.583	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-260567
Q05655	P49841	1	phosphorylation	down-regulates activity	0.271	In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.\|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.	SIGNOR-280084
Q9UKY1	P63279	0	sumoylation	up-regulates quantity by stabilization	0.452	Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1. The sumoylation of zinc‐fingers and homeoboxes 1 (ZHX1) by ubc9 regulates its stability and transcriptional repression activity. However, in the current work, we demonstrated that ZHX1 was only SUMOylated by SUMO1.	SIGNOR-263901
O95466	Q05655	0	phosphorylation	up-regulates activity	0.27	PKC\u03b4 induces FMNL1 phosphorylation.	SIGNOR-279261
P06241	Q9C0B5	1	phosphorylation	up-regulates quantity by stabilization	0.388	Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).	SIGNOR-279738
P62714	P10415	1	dephosphorylation	up-regulates activity	0.385	The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.	SIGNOR-248589
P51665	Q05086	0	ubiquitination	down-regulates quantity by destabilization	0.271	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265134
Q9NRC8	Q13315	1	deacetylation	down-regulates activity	0.36	Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. \|Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016	SIGNOR-275890
P48507	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.439	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy	SIGNOR-279869
O00429	Q05655	0	phosphorylation	up-regulates	0.2	Drp1 was specifically phosphorylated in mitosis by cdk1/cyclin b on ser-585. Exogenous expression of unphosphorylated mutant drp1s585a led to reduced mitotic mitochondrial fragmentation.	SIGNOR-153148
Q06124	P01111	1	dephosphorylation	up-regulates activity	0.673	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-255754
P43250	O75581	1	phosphorylation	up-regulates activity	0.345	In contrast to the GRK5 and GRK6 stimulated activity of wild-type LRP6, the LRP6 M5 mutant failed to respond to the expression of GRK5 or GRK6 (XREF_FIG C) by increased TOPflash reporter activity, indicating that PPPSP motifs are indispensable for GRK5- and GRK6 mediated LRP6 activation.\|Our findings that GRK5 and GRK6 phosphorylate the single membrane-spanning receptor LRP6 on defined serine/threonine sites ( i.e. serine 1490) within proline-rich PPPSP motifs and thereby activate LRP6 are important and interesting in two respects.	SIGNOR-279412
Q13627	P13807	1	phosphorylation	down-regulates activity	0.267	DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.	SIGNOR-260632
Q9Y3V2	Q16665	1	sumoylation	up-regulates	0.457	Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia	SIGNOR-158590
P31749	Q15121	1	phosphorylation	up-regulates activity	0.517	Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.	SIGNOR-102092
P20701	P12931	0	phosphorylation	down-regulates activity	0.421	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254741
Q5T447	P55211	1	polyubiquitination	down-regulates activity	0.2	HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.	SIGNOR-272329
O75626	P01106	1	transcriptional regulation	down-regulates quantity by repression	0.436	The positive regulatory domain i binding factor 1 (prdi-bf1 or blimp-1) protein represses the transcription of specific target genes, including c-myc, the mhc class ii trans-activator, pax-5, and cd23b	SIGNOR-99119
P36956	Q7KZF4	1	transcriptional regulation	down-regulates quantity by repression	0.2	These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.	SIGNOR-259137
P04637	O15527	1	transcriptional regulation	up-regulates quantity by expression	0.429	Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1.	SIGNOR-255440
O15530	Q13464	0	phosphorylation	up-regulates activity	0.298	Additional phosphorylation of PDK1 by ROCK-I improves the stability of the ROCK-I and PDK1 complex.	SIGNOR-279758
P49841	Q9BPU6	1	phosphorylation	up-regulates activity	0.431	The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.	SIGNOR-264835
P00519	O75496	1	phosphorylation	up-regulates activity	0.355	Taken together, suggests that c-Abl binds and phosphorylates geminin on Y150 in G2/M/early G1 phases.	SIGNOR-278505
P16220	P35575	1	transcriptional regulation	up-regulates quantity	0.2	Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB	SIGNOR-256105
P11802	Q9NS23	1	phosphorylation	down-regulates	0.409	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.	SIGNOR-159849
P03372	O14965	0	phosphorylation	up-regulates activity	0.357	Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .\|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.	SIGNOR-278508
P28482	O43524	1	phosphorylation	down-regulates quantity by destabilization	0.717	Here, we show that erk downregulates forkhead box o 3a (foxo3a) by directly interacting with and phosphorylating foxo3a at ser 294, ser 344 and ser 425, which consequently promotes cell proliferation and tumorigenesisMDM2 is required for ERk-mediated FOXO3a degradation.	SIGNOR-160415
Q13501	Q14680	0	phosphorylation	up-regulates activity	0.2	Consistent with our SILAC experiments, MELK directly phosphorylated SQSTM1 (XREF_FIG).\|Furthermore, we show that MELK promotes melanoma growth by activating NF-kappaB pathway activity via Sequestosome 1 (SQSTM1 and p62).	SIGNOR-279544
P12931	Q14653	1	phosphorylation	up-regulates activity	0.314	Mechanistically, the progesterone-PGR axis activates SRC, which then mediates phosphorylation of IRF3 at Y107.\|Taken together, these results suggest that P4 induces PGR-dependent activation of SRC, which promotes virus-triggered activation of IRF3 as well as induction of downstream antiviral genes.In the above experiments, we noticed that SeV-induced phosphorylation of IRF3S386 but not phosphorylation of TBK1S172 (p-TBK1S172, a hallmark for TBK1 activation) was increased by P4 treatment (Fig. 4g) or decreased by knockout of PGR (Fig. 4h).	SIGNOR-279118
Q9Y463	P38936	1	phosphorylation	up-regulates activity	0.258	Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and rna interference experiments demonstrated that mirk phosphorylates p21 within its nuclear localization domain at ser-153 causing a portion of the typically nuclear p21 to localize in the cytoplasm.Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules.	SIGNOR-235635
P52565	P53350	0	phosphorylation	up-regulates activity	0.2	PLK1 phosphorylates RhoGDI1 at Thr7/91 residue in vitro and in vivo. Collectively, we demonstrate that the phosphorylation of RhoGDI1 by PLK1 promotes cancer cell migration and invasion through RhoA activation.	SIGNOR-277882
P09874	Q9P1Y6	0	ubiquitination	down-regulates quantity by destabilization	0.2	Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation.	SIGNOR-278774
P27361	P43364	1	phosphorylation	up-regulates	0.3	Mage-11 ser-174 appears to be a post-translational regulatory site phosphorylated by erk1, based on the inhibitory effect of the s174a mutation in the context of shorter ar nh2-terminal fragments (19), and the greater transcriptional activity of gal-mage-11 fusion proteins containing the s174d phosphomimetic.	SIGNOR-188466
P52630	P29597	0	phosphorylation	up-regulates activity	0.789	JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).	SIGNOR-279133
Q9NZA1	P06241	0	phosphorylation	up-regulates activity	0.296	In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59(fyn) in HeLa cells.	SIGNOR-274006
P46934	P37840	1	ubiquitination	down-regulates quantity by destabilization	0.372	Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates alpha-synuclein, unlike ligases previously implicated in its degradation.	SIGNOR-278611
P31749	Q05655	1	phosphorylation	up-regulates activity	0.26	Of note, the amino acid sequence adjacent to Ser204 phosphorylation site matches the minimal AKT substrate motif (RxxpS) suggesting that AKT1 could potentially directly regulate PRKCD through phosphorylation.\|This integrative analysis allowed us to confirm that the enrichment of PRKCD centered network is likely the result of elevated phosphorylation of PRKCD by AKT1.	SIGNOR-280175
P08648	Q9BTC0	0	transcriptional regulation	up-regulates quantity by expression	0.2	Dido1 upregulates the expression of Integrin αV, thereby influencing the attachment, apoptosis and migration of melanoma cells.	SIGNOR-261580
O43164	P31323	1	polyubiquitination	down-regulates quantity by destabilization	0.2	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271858
Q13485	O15198	0	phosphorylation	up-regulates	0.685	Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.	SIGNOR-168740
P12931	P78536	1	phosphorylation	up-regulates activity	0.458	These data suggests that Src mediates TACE activation in mechanically stressed cardiomyocytes and this mechanism could be exploited for specific blockade of TNFalpha secretion and its detrimental effects in congestive heart failure.\|We found that the non receptor tyrosine kinase Src mediates TACE activation in mechanically stretched rat cardiomyocytes by phosphorylating the Tyr 702 residue within the intracellular tail of TACE.	SIGNOR-279115
P06493	P62136	1	phosphorylation	down-regulates activity	0.575	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.	SIGNOR-151799
P59047	Q02156	0	phosphorylation	up-regulates activity	0.2	MATER protein as substrate of PKCepsilon in human cumulus cells. we performed coimmunoprecipitation experiments using HEK293T cells expressing human MATER; a similar approach was then followed in human cumulus/follicular cells. In MATER(+)HEK293T cells, we observed that this protein acts as a phosphorylation substrate of PKCepsilon. Since PKCepsilon is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of MATER in follicular maturation.	SIGNOR-263175
P15498	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.75	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-260580
Q13315	P12956	1	phosphorylation	up-regulates activity	0.713	Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.	SIGNOR-274020
P67775	Q96HP0	1	phosphorylation	down-regulates activity	0.2	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275669
Q15759	P10636	1	phosphorylation	down-regulates activity	0.341	Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.\|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.	SIGNOR-279637
Q9BXM7	P04637	1	phosphorylation	up-regulates activity	0.321	Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.\|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria.	SIGNOR-278418
Q07812	Q9NY61	0	transcriptional regulation	down-regulates quantity	0.2	We identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response. Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes.	SIGNOR-259916
O60890	P61586	1	gtpase-activating protein	up-regulates activity	0.636	OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro	SIGNOR-268397
P37231	O75376	0	transcriptional regulation	down-regulates quantity by repression	0.708	In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.	SIGNOR-253507
Q9Y2H9	P60484	1	phosphorylation	down-regulates	0.515	Mast1 was found to associate to pten.	SIGNOR-138003
P26927	P03952	0	cleavage	up-regulates activity	0.325	Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.	SIGNOR-256511
Q4VCS5	Q9GZV5	1	relocalization	down-regulates	0.678	Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.	SIGNOR-201132
Q13526	P35568	1	isomerization	up-regulates activity	0.2	In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells\|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation\|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events	SIGNOR-265757
P31749	Q96HP0	1	phosphorylation	up-regulates activity	0.372	Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons\|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). \| In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching	SIGNOR-275666
P18146	Q9Y222	0	transcriptional regulation	up-regulates quantity by expression	0.2	Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.	SIGNOR-261584
Q13207	P38936	1	transcriptional regulation	down-regulates quantity by repression	0.345	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249593
Q92830	Q16695	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-269604
Q96N67	P04626	0	phosphorylation	up-regulates	0.531	We show that the nrg1 receptor erbb2 directly binds and activates dock7 by phosphorylating tyr-1118. thus, dock7 functions as an intracellular substrate for erbb2 to promote schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of rho gtpase-gefs of the dock180 family.	SIGNOR-178348
Q13177	P55210	1	phosphorylation	down-regulates	0.351	Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.	SIGNOR-173655

P14373

Q9Y2H1

1

ubiquitination

up-regulates activity

0.2

TRIM27 catalyzes non-degradative K6- and K11-linked ubiquitination of the serine/threonine kinase 38-like (STK38L) kinase. In turn, STK38L ubiquitination promotes its activation and phosphorylation of ULK1 at Ser495, rendering ULK1 in a permissive state for TRIM27-mediated hyper-ubiquitination of ULK1

SIGNOR-270347

P27361

Q8TB45

1

phosphorylation

up-regulates quantity by stabilization

0.282

Screening the DEPTOR interactome identified that the association of USP-7 deubiquitinase with DEPTOR was dependent upon S235 phosphorylation. Inhibition of USP-7 activity resulted in DEPTOR polyubiquitination and degradation. A scansite search suggested that ERK1 may be responsible for S235 phosphorylation, which was confirmed through the use of inhibitors, ERK1 knockdown, and an in vitro kinase assay.

SIGNOR-277587

Q99856

P0DOX6

1

transcriptional regulation

up-regulates quantity by expression

0.2

In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene.

SIGNOR-268532

P35638

P49715

1

transcriptional regulation

down-regulates quantity

0.519

We find that expression of CHOP, a nuclear protein that dimerizes avidly with C/EBP isoforms alpha and beta and directs the resulting heterodimer away from classic C/EBP-binding sites, markedly inhibits this differentiation process.

SIGNOR-255913

Q86TM6

O15354

1

polyubiquitination

down-regulates quantity by destabilization

0.4

We demonstrated that endogenous HRD1 interacts with Pael-R, and that HRD1 promotes the degradation of Pael-R and protects cell death caused by the accumulation of Pael-R.

SIGNOR-272631

P02818

P25774

0

cleavage

down-regulates quantity by destabilization

0.309

This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.

SIGNOR-256323

Q13177

P08670

1

phosphorylation

down-regulates activity

0.307

In vitro analyses revealed that vimentin served as an excellent substrate for PAK. This phosphorylated vimentin lost the potential to form 10 nm filaments. We identified Ser25, Ser38, Ser50, Ser65 and Ser72 in the amino-terminal head domain as the major phosphorylation sites on vimentin for PAK.

SIGNOR-250243

Q05086

P20618

1

ubiquitination

down-regulates quantity by destabilization

0.355

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265131

P07101

O75582

0

phosphorylation

up-regulates

0.337

Recombinant human tyrosine hydroxylase (hth1) was found to be phosphorylated by mitogen and stress-activated protein kinase 1 (msk1) at ser40 and by p38 regulated/activated kinase (prak) on ser19. Phosphorylation by msk1 induced an increase in vmax. studies on th from several species suggest that ser40 is the main site involved in direct activation of th

SIGNOR-95491

Q9H334

Q9P283

1

transcriptional regulation

down-regulates quantity by repression

0.33

FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein semaphorin 5B in endothelial cells.

SIGNOR-269050

P09874

P00533

0

phosphorylation

up-regulates activity

0.394

EGFR and MET heterodimer interacts with and phosphorylates PARP1.

SIGNOR-279169

O60885

P27361

0

null

down-regulates activity

0.312

The MYC stabilizing kinase, ERK1, regulates MYC levels directly and indirectly by inhibiting BRD4 kinase activity.

SIGNOR-262048

P04637

P53355

0

phosphorylation

up-regulates

0.558

Dna damage-activated protein kinases like chk1/2 modify the box-i domain of p53 at thr18 and ser20 (46) by an allosteric mechanism (10).

SIGNOR-153491

Q92574

P06493

0

phosphorylation

down-regulates

0.489

Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin b.Cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70s6 kinase by the hamartin-tuberin complex

SIGNOR-118584

Q93009

P60484

1

deubiquitination

down-regulates activity

0.741

BCR-ABL disrupts PTEN nuclear-cytoplasmic shuttling through phosphorylation-dependent activation of HAUSP|hese data indicate that BCR-ABL phosphorylation of HAUSP modulates HAUSP’s deubiquitinase activity toward PTEN.

SIGNOR-276533

P17252

P32004

1

phosphorylation

down-regulates activity

0.2

CKII phosphorylates T1172 of the L1 CD and phosphorylation of T1172 is responsible for loss of 2C2 signal.

SIGNOR-276283

Q06124

P01112

1

dephosphorylation

up-regulates activity

0.681

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-252094

P16949

P05771

0

phosphorylation

down-regulates

0.2

Op18 is multisite phosphorylated on four ser residues during mitosis;two of these ser residues, ser-25 and ser-38, are targets for cyclin-dependent protein kinases. our findings suggest that stathmin phosphorylation in reh6 cells could be in part mediated by pkc activation.

SIGNOR-50598

Q9H0K1

Q09472

1

phosphorylation

down-regulates activity

0.278

Indeed, overexpression of SIK2 increased p300 phosphorylation at Ser89, while knockdown of SIK2 decreased it (Fig. 4B).

SIGNOR-278368

Q12933

Q13546

1

ubiquitination

up-regulates activity

0.895

Following binding to tradd, traf2 was thought to mediate non-degradative lys-63-linked polyubiquitination of rip1 via its ring e3 ligase domain. Rip1 is known to directly interact with traf2.

SIGNOR-59689

P49757

P41743

0

phosphorylation

down-regulates

0.771

Numb is regulated by phosphorylation since the protein is released from ccss and no longer binds integrins when phosphorylated by atypical protein kinase c (apkc).

SIGNOR-156765

Q15759

P04637

1

phosphorylation

up-regulates

0.611

We show that prak activates p53 by direct phosphorylation.

SIGNOR-152843

P49768

Q99590

0

cleavage

up-regulates activity

0.294

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261758

O94804

P15311

1

phosphorylation

up-regulates activity

0.473

Ezrin activation by LOK phosphorylation involves a PIP 2 -dependent wedge mechanism.|The specificity of kinases depends on local peptide consensus sequences, which in the case of ezrin phosphorylation by LOK involves the hydrophobic residue Y565 positioned -2 residues from T567.

SIGNOR-278204

O60229

Q8IW41

0

phosphorylation

up-regulates activity

0.385

The brain-specific nucleotide exchange factor kalirin-7 (Kal7) was identified as an MK5 interaction partner and substrate protein. The MK5 substrate Kal7, a Rho GEF and known activator of Rac GTPases, further contributes to PAK activation and actin filament reorganization. Thus, the coordinated phosphorylation of Borg proteins and Kal7 by ERK3 and MK5 constitute a novel signaling cascade involving feed-forward circuits, multiple GTPases, and cytoskeletal elements. The fragment SR3-6, but not the mutated fragment SR3-6-S487A, is phosphorylated by MK5.

SIGNOR-263093

O15294

P98170

0

ubiquitination

down-regulates quantity

0.2

These results demonstrate that XIAP acts as an E3 ubiquitin ligase and ubiquitinates OGT in HCT116 colon cancer cells.|XIAP promotes the ubiquitin-dependent proteasomal degradation of OGT.

SIGNOR-278800

Q53ET0

P57059

0

phosphorylation

down-regulates

0.644

These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities.

SIGNOR-147707

O95997

O95155

0

polyubiquitination

down-regulates quantity by destabilization

0.2

We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells.

SIGNOR-271523

P06730

P05771

0

phosphorylation

up-regulates

0.348

Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .

SIGNOR-248946

P32004

Q15349

0

phosphorylation

up-regulates activity

0.515

Western blot analysis demonstrated that the L1 kinase activity from PC12 cells that phosphorylated this site was co-eluted with the S6 kinase, p90(rsk). Moreover, S6 kinase activity and p90(rsk) immunoreactivity co-immunoprecipitate with L1 from brain, and metabolic labeling studies have demonstrated that Ser1152 is phosphorylated in vivo in the developing rat brain. | These data demonstrate that the membrane-proximal 15 amino acids of the cytoplasmic domain of L1 are important for neurite outgrowth on L1, and the interactions it mediates may be regulated by phosphorylation of Ser1152.

SIGNOR-248949

P11388

P53350

0

phosphorylation

up-regulates

0.481

Here we report that when phosphorylated, ser 1524 of topo iialpha acts as a binding site for the brct domain of mdc1 (mediator of dna damage checkpoint protein-1), thereby recruiting mdc1 to chromatin

SIGNOR-182844

P00533

Q9UBN7

1

phosphorylation

down-regulates

0.44

A negative feedback loop consisting of egfr-mediated phosphorylation of hdac6 tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin.

SIGNOR-162431

O43251

O14920

0

phosphorylation

up-regulates activity

0.2

Phosphorylation of RTA by IKKbeta increases RTA transcriptional activity and consequently viral mRNA production.

SIGNOR-279336

P68400

P10242

1

phosphorylation

down-regulates activity

0.34

For c-Myb mutational analysis of the CKII phosphorylation sites showed altered steady state DNA binding. Replacing Ser-11/12 by alanine residues resulted in increased DNA binding compared to wt c-Myb or Myb Asp-11/12 as demonstrated by up to 10-fold differences in the dissociation constants.

SIGNOR-250918

Q6IA17

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

Activation of GSK3beta promotes Sigirr degradation in the proteasome .|Taken together, IL-37-induced Sigirr internalization is dependent on phosphorylation of Sigirr in T372 residue by GSK3\u03b2.

SIGNOR-279053

Q5S007

P26038

1

phosphorylation

up-regulates activity

0.551

This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process.

SIGNOR-154498

P10242

P09488

1

transcriptional regulation

up-regulates quantity by expression

0.2

Functional analysis of the GSTM1 promoter using reporter assays indicated that both the DNA binding and transactivation domains of Myb were required for transcriptional activation

SIGNOR-253975

Q2TAL8

P54577

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269412

P48551

Q92793

0

acetylation

up-regulates activity

0.347

By binding to IFNalphaR2 within the region where two adjacent proline boxes bear phospho-Ser364 and phospho-Ser384, CBP acetylates IFNalphaR2 on Lys399, which in turn serves as the docking site for interferon regulatory factor 9 (IRF9)RF9 interacts with the acetyl-Lys399 motif by means of its IRF homology2 (IH2) domain, leading to formation of the ISGF3 complex that includes IRF9, STAT1, and STAT2.

SIGNOR-217783

P61586

Q3KR16

0

guanine nucleotide exchange factor

up-regulates activity

0.583

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-260567

Q05655

P49841

1

phosphorylation

down-regulates activity

0.271

In the TFEB activation pathway, activated PKC\u03b4 phosphorylates and inactivates GSK3\u03b2, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.|In the TFEB activation pathway, activated PKCdelta phosphorylates and inactivates GSK3beta, leading to the reduced phosphorylation of TFEB at Ser134 and Ser138 residues; this reduced phosphorylation is critical for the cytoplasmic sequestration of TFEB.

SIGNOR-280084

Q9UKY1

P63279

0

sumoylation

up-regulates quantity by stabilization

0.452

Here, we report that the SUMO-E2 conjugating enzyme Ubc9 was identified to interact with ZHX1 by an interaction screen using a yeast two-hybrid system. This interaction was confirmed by co-immunoprecipitation and co-localization assays. Further study showed that ZHX1 is SUMOylated by Ubc9 with SUMO1 at the sites K159, K454, and K626. Furthermore, we demonstrated that the SUMOylation of ZHX1 regulated the stability, ubiquitination and transcriptional activity of ZHX1. The sumoylation of zinc‐fingers and homeoboxes 1 (ZHX1) by ubc9 regulates its stability and transcriptional repression activity. However, in the current work, we demonstrated that ZHX1 was only SUMOylated by SUMO1.

SIGNOR-263901

O95466

Q05655

0

phosphorylation

up-regulates activity

0.27

PKC\u03b4 induces FMNL1 phosphorylation.

SIGNOR-279261

P06241

Q9C0B5

1

phosphorylation

up-regulates quantity by stabilization

0.388

Our study demonstrates that under basal conditions, PSD-95 and Fyn cooperatively stabilize DHHC5 at the synaptic membrane through Fyn-mediated phosphorylation of DHHC5 at tyrosine residue 533 and the subsequent inhibition of DHHC5 association with endocytic proteins (Fig. 10).

SIGNOR-279738

P62714

P10415

1

dephosphorylation

up-regulates activity

0.385

The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.

SIGNOR-248589

P51665

Q05086

0

ubiquitination

down-regulates quantity by destabilization

0.271

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265134

Q9NRC8

Q13315

1

deacetylation

down-regulates activity

0.36

Here, we report that sirtuin 7 (SIRT7)-mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. |Upon DNA damage, ATM is activated via a series of highly organized machineries, including acetylation by the histone acetyltransferase TIP60 at lysine 3016

SIGNOR-275890

P48507

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.439

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy

SIGNOR-279869

O00429

Q05655

0

phosphorylation

up-regulates

0.2

Drp1 was specifically phosphorylated in mitosis by cdk1/cyclin b on ser-585. Exogenous expression of unphosphorylated mutant drp1s585a led to reduced mitotic mitochondrial fragmentation.

SIGNOR-153148

Q06124

P01111

1

dephosphorylation

up-regulates activity

0.673

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-255754

P43250

O75581

1

phosphorylation

up-regulates activity

0.345

In contrast to the GRK5 and GRK6 stimulated activity of wild-type LRP6, the LRP6 M5 mutant failed to respond to the expression of GRK5 or GRK6 (XREF_FIG C) by increased TOPflash reporter activity, indicating that PPPSP motifs are indispensable for GRK5- and GRK6 mediated LRP6 activation.|Our findings that GRK5 and GRK6 phosphorylate the single membrane-spanning receptor LRP6 on defined serine/threonine sites ( i.e. serine 1490) within proline-rich PPPSP motifs and thereby activate LRP6 are important and interesting in two respects.

SIGNOR-279412

Q13627

P13807

1

phosphorylation

down-regulates activity

0.267

DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.

SIGNOR-260632

Q9Y3V2

Q16665

1

sumoylation

up-regulates

0.457

Rsume,_a small_rwd-containing protein, enhances sumo conjugation and stabilizes hif-1alpha during hypoxia

SIGNOR-158590

P31749

Q15121

1

phosphorylation

up-regulates activity

0.517

Protein kinase b/akt binds and phosphorylates ped/pea-15, stabilizing its antiapoptotic action.

SIGNOR-102092

P20701

P12931

0

phosphorylation

down-regulates activity

0.421

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254741

Q5T447

P55211

1

polyubiquitination

down-regulates activity

0.2

HECTD3 binds and ubiquitinates caspase-9.HECTD3 inhibits caspase-9 oligomerization and association with Apaf-1. HECTD3 suppressing caspase-9 activation is dependent on T157 phosphorylation by ERK.

SIGNOR-272329

O75626

P01106

1

transcriptional regulation

down-regulates quantity by repression

0.436

The positive regulatory domain i binding factor 1 (prdi-bf1 or blimp-1) protein represses the transcription of specific target genes, including c-myc, the mhc class ii trans-activator, pax-5, and cd23b

SIGNOR-99119

P36956

Q7KZF4

1

transcriptional regulation

down-regulates quantity by repression

0.2

These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.

SIGNOR-259137

P04637

O15527

1

transcriptional regulation

up-regulates quantity by expression

0.429

Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1.

SIGNOR-255440

O15530

Q13464

0

phosphorylation

up-regulates activity

0.298

Additional phosphorylation of PDK1 by ROCK-I improves the stability of the ROCK-I and PDK1 complex.

SIGNOR-279758

P49841

Q9BPU6

1

phosphorylation

up-regulates activity

0.431

The T516 phosphorylation was achieved by the glycogen synthase kinase-3beta (GSK-3beta), which can phosphorylate the wildtype protein but not the non-phosphorylatable mutant. Furthermore, we have shown that T516 phosphorylation is essential for the tubulin-binding property of CRMP5. Therefore, CRMP5-induced growth inhibition is dependent on T516 phosphorylation through the GSK-3beta pathway.

SIGNOR-264835

P00519

O75496

1

phosphorylation

up-regulates activity

0.355

Taken together, suggests that c-Abl binds and phosphorylates geminin on Y150 in G2/M/early G1 phases.

SIGNOR-278505

P16220

P35575

1

transcriptional regulation

up-regulates quantity

0.2

Further, CRTC2 is required for the glucocorticoid-associated cooperative mRNA expression of the glucose-6-phosphatase, a rate-limiting enzyme for hepatic gluconeogenesis, by facilitating the attraction of GR and itself to its promoter region already occupied by CREB

SIGNOR-256105

P11802

Q9NS23

1

phosphorylation

down-regulates

0.409

This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

SIGNOR-159849

P03372

O14965

0

phosphorylation

up-regulates activity

0.357

Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.

SIGNOR-278508

P28482

O43524

1

phosphorylation

down-regulates quantity by destabilization

0.717

Here, we show that erk downregulates forkhead box o 3a (foxo3a) by directly interacting with and phosphorylating foxo3a at ser 294, ser 344 and ser 425, which consequently promotes cell proliferation and tumorigenesisMDM2 is required for ERk-mediated FOXO3a degradation.

SIGNOR-160415

Q13501

Q14680

0

phosphorylation

up-regulates activity

0.2

Consistent with our SILAC experiments, MELK directly phosphorylated SQSTM1 (XREF_FIG).|Furthermore, we show that MELK promotes melanoma growth by activating NF-kappaB pathway activity via Sequestosome 1 (SQSTM1 and p62).

SIGNOR-279544

P12931

Q14653

1

phosphorylation

up-regulates activity

0.314

Mechanistically, the progesterone-PGR axis activates SRC, which then mediates phosphorylation of IRF3 at Y107.|Taken together, these results suggest that P4 induces PGR-dependent activation of SRC, which promotes virus-triggered activation of IRF3 as well as induction of downstream antiviral genes.In the above experiments, we noticed that SeV-induced phosphorylation of IRF3S386 but not phosphorylation of TBK1S172 (p-TBK1S172, a hallmark for TBK1 activation) was increased by P4 treatment (Fig. 4g) or decreased by knockout of PGR (Fig. 4h).

SIGNOR-279118

Q9Y463

P38936

1

phosphorylation

up-regulates activity

0.258

Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21cip1. Overexpression and rna interference experiments demonstrated that mirk phosphorylates p21 within its nuclear localization domain at ser-153 causing a portion of the typically nuclear p21 to localize in the cytoplasm.Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules.

SIGNOR-235635

P52565

P53350

0

phosphorylation

up-regulates activity

0.2

PLK1 phosphorylates RhoGDI1 at Thr7/91 residue in vitro and in vivo. Collectively, we demonstrate that the phosphorylation of RhoGDI1 by PLK1 promotes cancer cell migration and invasion through RhoA activation.

SIGNOR-277882

P09874

Q9P1Y6

0

ubiquitination

down-regulates quantity by destabilization

0.2

Furthermore, PHRF1 mediates PARP1 polyubiquitination for proteasomal degradation.

SIGNOR-278774

P27361

P43364

1

phosphorylation

up-regulates

0.3

Mage-11 ser-174 appears to be a post-translational regulatory site phosphorylated by erk1, based on the inhibitory effect of the s174a mutation in the context of shorter ar nh2-terminal fragments (19), and the greater transcriptional activity of gal-mage-11 fusion proteins containing the s174d phosphomimetic.

SIGNOR-188466

P52630

P29597

0

phosphorylation

up-regulates activity

0.789

JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).

SIGNOR-279133

Q9NZA1

P06241

0

phosphorylation

up-regulates activity

0.296

In this paper, we demonstrate that p64 becomes tyrosine phosphorylated when co-expressed with p59(fyn) in HeLa cells.

SIGNOR-274006

P46934

P37840

1

ubiquitination

down-regulates quantity by destabilization

0.372

Here we show that the ubiquitin ligase Nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates alpha-synuclein, unlike ligases previously implicated in its degradation.

SIGNOR-278611

P31749

Q05655

1

phosphorylation

up-regulates activity

0.26

Of note, the amino acid sequence adjacent to Ser204 phosphorylation site matches the minimal AKT substrate motif (RxxpS) suggesting that AKT1 could potentially directly regulate PRKCD through phosphorylation.|This integrative analysis allowed us to confirm that the enrichment of PRKCD centered network is likely the result of elevated phosphorylation of PRKCD by AKT1.

SIGNOR-280175

P08648

Q9BTC0

0

transcriptional regulation

up-regulates quantity by expression

0.2

Dido1 upregulates the expression of Integrin αV, thereby influencing the attachment, apoptosis and migration of melanoma cells.

SIGNOR-261580

O43164

P31323

1

polyubiquitination

down-regulates quantity by destabilization

0.2

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271858

Q13485

O15198

0

phosphorylation

up-regulates

0.685

Whereas alk5 signalling is mediated by phosphorylation of smad2 and smad3 proteins, alk1 signalling is mediated by smad1, smad5, and smad8. Activated smads form a complex with the common smad (co-smad; smad4 in mammals) and shuttle into the nucleus.

SIGNOR-168740

P12931

P78536

1

phosphorylation

up-regulates activity

0.458

These data suggests that Src mediates TACE activation in mechanically stressed cardiomyocytes and this mechanism could be exploited for specific blockade of TNFalpha secretion and its detrimental effects in congestive heart failure.|We found that the non receptor tyrosine kinase Src mediates TACE activation in mechanically stretched rat cardiomyocytes by phosphorylating the Tyr 702 residue within the intracellular tail of TACE.

SIGNOR-279115

P06493

P62136

1

phosphorylation

down-regulates activity

0.575

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.

SIGNOR-151799

P59047

Q02156

0

phosphorylation

up-regulates activity

0.2

MATER protein as substrate of PKCepsilon in human cumulus cells. we performed coimmunoprecipitation experiments using HEK293T cells expressing human MATER; a similar approach was then followed in human cumulus/follicular cells. In MATER(+)HEK293T cells, we observed that this protein acts as a phosphorylation substrate of PKCepsilon. Since PKCepsilon is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of MATER in follicular maturation.

SIGNOR-263175

P15498

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.75

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-260580

Q13315

P12956

1

phosphorylation

up-regulates activity

0.713

Ku70 phosphorylation occurs within minutes of genotoxic stress and involves DNA-PKcs and/or ATM kinase activities.By using specific vectors enabling the simultaneous shRNA-mediated inhibition of endogenous Ku70 and the expression of exogenous Ku70 resistant to shRNA (i.e. S27-S33-Ku70 and A27-A33-Ku70 expressing cells), we showed that phospho-Ku70 contributes to faster but error-prone DNA repair resulting in higher levels of chromosomal breaks.

SIGNOR-274020

P67775

Q96HP0

1

phosphorylation

down-regulates activity

0.2

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275669

Q15759

P10636

1

phosphorylation

down-regulates activity

0.341

Phosphorylation of tau by SAPK3 and SAPK4 resulted in a marked reduction in its ability to promote microtubule assembly.|Tau phosphorylated by SAPK2b and SAPK2a also reacted with AT8, whereas AT8 failed to recognise tau phosphorylated by SAPK1gamma.

SIGNOR-279637

Q9BXM7

P04637

1

phosphorylation

up-regulates activity

0.321

Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria.

SIGNOR-278418

Q07812

Q9NY61

0

transcriptional regulation

down-regulates quantity

0.2

We identify the transcriptional regulator apoptosis-antagonizing transcription factor (AATF)/Che-1 as a critical regulator of the cellular outcome of the p53 response. Upon genotoxic stress, AATF is phosphorylated by the checkpoint kinase MK2. Phosphorylation results in the release of AATF from cytoplasmic MRLC3 and subsequent nuclear translocation where AATF binds to the PUMA, BAX and BAK promoter regions to repress p53-driven expression of these pro-apoptotic genes.

SIGNOR-259916

O60890

P61586

1

gtpase-activating protein

up-regulates activity

0.636

OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro

SIGNOR-268397

P37231

O75376

0

transcriptional regulation

down-regulates quantity by repression

0.708

In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.

SIGNOR-253507

Q9Y2H9

P60484

1

phosphorylation

down-regulates

0.515

Mast1 was found to associate to pten.

SIGNOR-138003

P26927

P03952

0

cleavage

up-regulates activity

0.325

Proteolytic cleavage of pro-MSP at a single site yields active MSP, a disulfide-linked alphabeta-chain heterodimer. human kallikrein cleaved only at Arg483–Val484, the cleavage site for formation of a- and b-chains.

SIGNOR-256511

Q4VCS5

Q9GZV5

1

relocalization

down-regulates

0.678

Yap/taz and angiomotin (amot) family proteins were shown to interact, resulting in yap/taz localization to tight junctions and inhibition through phosphorylation-dependent and -independent mechanisms.

SIGNOR-201132

Q13526

P35568

1

isomerization

up-regulates activity

0.2

In this study, the association of Par14 with insulin receptor substrate 1 (IRS-1) was demonstrated in HepG2 cells|Therefore, although Pin1 and Par14 associate with different portions of IRS-1, the prolyl cis/trans isomerization in multiple sites of IRS-1 by these isomerases appears to be critical for efficient insulin receptor-induced IRS-1 phosphorylation|Par14 overexpression in HepG2 markedly enhanced insulin-induced IRS-1 phosphorylation and its downstream events

SIGNOR-265757

P31749

Q96HP0

1

phosphorylation

up-regulates activity

0.372

Akt and PP2A reciprocally regulate the guanine nucleotide exchange factor Dock6 to control axon growth of sensory neurons|At later developmental stages, the abundance of the kinase Akt increased, resulting in the binding of Akt to Dock6 and the phosphorylation of Dock6 at Ser(1194). | In dorsal root ganglion neurons from mice lacking Dock6, reintroduction of Dock6 with a nonphosphorylatable S1194A mutation rescued axon extension but not branch number, whereas reintroduction of Dock6 with a phosphomimetic S1194E mutation resulted in premature branching

SIGNOR-275666

P18146

Q9Y222

0

transcriptional regulation

up-regulates quantity by expression

0.2

Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.

SIGNOR-261584

Q13207

P38936

1

transcriptional regulation

down-regulates quantity by repression

0.345

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249593

Q92830

Q16695

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-269604

Q96N67

P04626

0

phosphorylation

up-regulates

0.531

We show that the nrg1 receptor erbb2 directly binds and activates dock7 by phosphorylating tyr-1118. thus, dock7 functions as an intracellular substrate for erbb2 to promote schwann cell migration. This provides an unanticipated mechanism through which ligand-dependent tyrosine phosphorylation can trigger the activation of rho gtpase-gefs of the dock180 family.

SIGNOR-178348

Q13177

P55210

1

phosphorylation

down-regulates

0.351

Pak2 can bind with caspase-7 and phosphorylate caspase-7 at the ser-30, thr-173, and ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis.

SIGNOR-173655