GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P04637	Q8NEZ5	0	ubiquitination	down-regulates quantity by destabilization	0.338	We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. \|SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.	SIGNOR-273448
P19793	O75469	2	binding	up-regulates	0.533	The constitutive androstane receptor (car, nr1i4), like fxr and pxr, binds dna as a heterodimer with rxr?	SIGNOR-111624
P04637	P49841	0	phosphorylation	up-regulates activity	0.728	Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity.	SIGNOR-251258
Q13501	Q9H492	2	binding	up-regulates	0.791	Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.	SIGNOR-156353
Q9BXM7	O95140	1	phosphorylation	down-regulates quantity	0.81	If PINK1 is responsible for the degradation of Mfn2, then silencing PINK1 should induce mitochondrial fusion by upregulating Mfn2 expression.\|We show that downregulation of Mfn2 is induced by proteasomal degradation triggered by PINK1, which phosphorylates Mfn2 at S442.	SIGNOR-278208
P17252	Q96QS3	1	phosphorylation	up-regulates activity	0.2	We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.	SIGNOR-277418
Q9Y2J4	Q9NRM7	2	relocalization	up-regulates activity	0.728	Ubiquitinated AMOTL2 then serves as a physical docking site for LATS2, which phosphorylates YAP to promote its cytoplasmic retention and degradation.	SIGNOR-271875
P04637	P06493	0	phosphorylation	up-regulates activity	0.579	The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A	SIGNOR-167779
P54646	O60825	1	phosphorylation	up-regulates activity	0.443	AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466	SIGNOR-250323
Q13148	P00519	0	phosphorylation	up-regulates quantity	0.2	The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.	SIGNOR-279135
O00635	Q9Y4K3	1	polyubiquitination	down-regulates quantity by destabilization	0.43	As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6.	SIGNOR-272009
P51812	P27361	0	phosphorylation	up-regulates	0.73	We have generated two monoclonal antibodies that recognize two phosphorylated sites, p-ser227 and p-thr577, in the n- and c-terminal kinase domains of rsk2, respectively. phosphorylation and activation of rsk2 by uv light involves the erk pathway	SIGNOR-81460
P36897	Q04771	1	phosphorylation	up-regulates activity	0.364	This directly demonstrates that TGFBR1 can activate ACVR1 in vivo.\|We show that in response to TGF-\u03b2, TGFBRI phosphorylates and activates ACVR1, which phosphorylates SMAD1/5.	SIGNOR-279490
P46020	P22612	0	phosphorylation	down-regulates activity	0.325	Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.	SIGNOR-267415
Q12879	P06241	0	phosphorylation	up-regulates activity	0.734	To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.	SIGNOR-247151
Q8IVH8	P19484	1	phosphorylation	down-regulates activity	0.25	However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.\|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.	SIGNOR-278282
Q05655	O15350	1	phosphorylation	up-regulates	0.307	The results show that pkcdeltacf phosphorylates the p73beta transactivation and dna-binding domains. pkcdeltacf-mediated phosphorylation of p73beta is associated with accumulation of p73beta and induction of p73beta-mediated transactivation.	SIGNOR-90279
P56704	Q9H461	2	binding	up-regulates	0.797	Structural basis of wnt recognition by frizzled.	SIGNOR-197638
Q9UNW8	P38405	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256945
Q9UPU5	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.2	Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604.	SIGNOR-275605
Q13315	Q9NPI1	1	phosphorylation	down-regulates activity	0.2	ATM Directly Phosphorylates BRD7 at Ser 263 Site.	SIGNOR-279780
Q8TEW6	P12931	2	binding	up-regulates	0.419	Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.	SIGNOR-101002
Q8NBL1	Q04721	2	binding	up-regulates	0.575	O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. O-glucose can be elongated by xylose to the trisaccharide, xylalfa1-3xylalfa1-3glcbeta1-o-ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus.	SIGNOR-198716
Q8NG27	Q01082	1	ubiquitination	down-regulates	0.403	The present study indicates that praja, a ring finger e3 ubiquitin ligase, interacts with elf and ubiquitinates it.	SIGNOR-141216
Q13418	Q13418	2	phosphorylation	up-regulates activity	0.2	Although ilk has been shown to autophosphorylate serine 343 (s343) is in the hydrophobic motif fsf within the activation loop of the kinase domain and has previously been suggested to be the target of autophosphorylation (9). Mutation of serine 343 to alanine (s343a) resulted in the inability of ilk to stimulate phosphorylation of pkb/akt in cos cells (9).	SIGNOR-106838
Q99558	O43318	0	phosphorylation	up-regulates activity	0.564	The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway\|Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.	SIGNOR-262833
O96006	P62753	1	transcriptional regulation	up-regulates quantity by expression	0.2	HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. \| Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid.	SIGNOR-266082
P67775	P13639	1	dephosphorylation	up-regulates	0.404	Protein phosphatases-2a and -2c (pp-2a and pp-2c) can each efficiently dephosphorylate phosphorylated eef-2	SIGNOR-38566
O96017	P62714	0	dephosphorylation	up-regulates activity	0.309	Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells\|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.	SIGNOR-248582
P17252	O60479	1	phosphorylation	down-regulates activity	0.307	Dlx3 is primarily phosphorylated by PKC alpha. By deletion and mutational analysis, we show that the serine residue S(138), located in the homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein can be directly phosphorylated by PKC and this affects the DNA binding activity of Dlx3.	SIGNOR-249096
P10275	Q15596	2	binding	up-regulates activity	0.901	The NCOA2 gene encodes a transcriptional coactivator (SRC-2) that modulates gene expression by hormone receptors, including AR. NCOA2 is both amplified and rarely mutated in prostate cancers, with higher NCOA2 levels resulting in increased androgen signaling readout. Furthermore, as mentioned previously, SRC-3, a close homolog encoded by NCOA3, is a substrate of SPOP whose protein levels are increased by SPOP mutation, potentially linking these common point mutations to the androgen axis	SIGNOR-251531
P84022	Q8N6I1	2	binding	down-regulates	0.397	In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.	SIGNOR-119171
P24158	P01019	1	cleavage	up-regulates activity	0.259	Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.	SIGNOR-256314
Q14767	P35555	2	binding	up-regulates activity	0.301	LTBP-2 interacts with fibrillin-1. The association of LTBP-2 with the ECM always coincided with that of fibrillin-1, and in fibroblast cultures the appearance of fibrillar fibrillin-1 structures preceded the assembly of LTBP-2 network.	SIGNOR-251891
P45452	P02675	1	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.\|MMP-13 27YVATRDN g-chain\| 20ADSGEGD a-chain\| 124RNSVDXLNXN b-chain\| 442LRTGKEKV a-chain	SIGNOR-263615
P21731	Q14344	2	binding	up-regulates activity	0.574	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257139
P17612	Q2Q1W2	1	phosphorylation	up-regulates quantity by stabilization	0.2	These observations suggested that LINK-A expression potentially inhibits PKA phosphorylation/activity and PKA-mediated phosphorylation of TRIM71 at Ser3.	SIGNOR-277454
Q00613	Q9UQM7	0	phosphorylation	up-regulates activity	0.513	Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells.	SIGNOR-250631
Q9UER7	P68400	0	phosphorylation	up-regulates	0.327	Daxx-sim is phosphorylated by ck2 kinase at residues s737 and s739. Phosphorylation promotes daxx-sim binding affinity toward sumo-1 over sumo-2/3, causing daxx preference for sumo-1 conjugation and interaction with sumo-1-modified factors.	SIGNOR-173105
P09471	P41146	2	binding	up-regulates activity	0.347	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257001
Q9H2X6	Q9P1Z0	1	phosphorylation	down-regulates activity	0.379	The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.	SIGNOR-262882
P46527	P31751	0	phosphorylation	down-regulates	0.53	Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.	SIGNOR-93122
P48551	P01562	2	binding	up-regulates activity	0.614	Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.	SIGNOR-219298
P12931	P31040	1	phosphorylation	up-regulates activity	0.267	Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.	SIGNOR-276420
P84022	Q14974	0	relocalization	up-regulates	0.524	Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation.	SIGNOR-78191
Q13153	P67775	0	dephosphorylation	down-regulates activity	0.357	Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.	SIGNOR-248641
P16104	Q99986	0	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
P00748	P01008	0	cleavage	down-regulates activity	0.6	Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1	SIGNOR-264139
O75367	P38398	0	ubiquitination	up-regulates activity	0.2	BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.	SIGNOR-278752
P19419	Q9UL54	0	phosphorylation	up-regulates activity	0.31	Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.	SIGNOR-246638
Q7Z553	Q9NPF5	2	binding	up-regulates quantity by stabilization	0.348	The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.	SIGNOR-264240
P12931	P31749	1	phosphorylation	up-regulates activity	0.677	Regulation of Akt/PKB Activation by Tyrosine PhosphorylationAs shown in Fig. 2 d, while mutation of Tyr340 has little effect on either tyrosine phosphorylation or kinase activity of Akt induced by Src527F, substitution of Tyr315 or Tyr326 with a phenylalanine, respectively, dramatically reduces both the tyrosine phosphorylation and kinase activity of Akt. The combination of these two mutations abolishes Src-induced tyrosine phosphorylation of Akt as well as its kinase activity.	SIGNOR-252623
O75116	P05067	1	phosphorylation	up-regulates quantity	0.386	Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.\|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.	SIGNOR-280109
Q9UKV5	P04234	1	polyubiquitination	down-regulates quantity by destabilization	0.474	Gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate.	SIGNOR-272670
P49715	P28845	1	transcriptional regulation	up-regulates quantity by expression	0.274	Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region.	SIGNOR-268971
P06400	O96017	0	phosphorylation	up-regulates activity	0.423	Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1	SIGNOR-153908
Q06413	Q15759	0	phosphorylation	up-regulates activity	0.538	In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2.	SIGNOR-280025
Q99717	O43541	1	transcriptional regulation	up-regulates quantity	0.599	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268940
O43424	A4D2P6	2	binding	up-regulates quantity	0.609	We identified a novel GluRdelta2-interacting protein, named Delphilin, that contains a single PDZ domain and formin homology (FH) domains FH1 and FH2 plus coiled-coil structure. Delphilin is selectively localized at the postsynaptic junction site of the parallel fiber-Purkinje cell synapse and colocalized with GluRdelta2. Thus, Delphilin is a postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GluRdelta2 with actin cytoskeleton and various signaling molecules.	SIGNOR-264475
Q9NYY3	Q9HC77	1	phosphorylation	up-regulates	0.579	Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.	SIGNOR-165999
P51843	Q13285	2	binding	down-regulates activity	0.702	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271784
P49674	P46937	1	phosphorylation	down-regulates	0.422	Phosphorylation of YAP (S381) and TAZ (S311) by Lats1/2 primes subsequent phosphorylation events by Casein Kinase 1 (CK1d/e); this sequential phosphorylation results in recruitment of b-transducin repeat-containing proteins (b-TRCP; a subunit of the SCF ubiquitin E3 ligase) and consequently leads to degradation of YAP/TAZ	SIGNOR-201170
Q00987	P31749	0	phosphorylation	up-regulates quantity by stabilization	0.811	Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186.	SIGNOR-116270
Q9UQK1	P54840	2	binding	up-regulates	0.753	In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)	SIGNOR-271731
O43521	Q07812	2	binding	up-regulates activity	0.832	We have shown that the interaction of the bims and bimad isoforms with bax leads to a conformational change in this protein analogous to that triggered by the bh3-only protein bid.We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome.	SIGNOR-87280
Q03052	P26583	2	binding	up-regulates activity	0.307	HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins	SIGNOR-240148
P43250	P14416	1	phosphorylation	down-regulates activity	0.447	GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.	SIGNOR-279046
Q9Y572	O43318	0	phosphorylation	up-regulates activity	0.2	Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.\|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.	SIGNOR-279634
P51813	P56945	1	phosphorylation	up-regulates quantity	0.506	Recombinant Bmx kinase was found to effectively phosphorylate the wt CAS SH3 domain on Tyr-12 (Figure 2B). A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells.	SIGNOR-276384
Q93009	P04637	1	deubiquitination	up-regulates	0.741	Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.	SIGNOR-139456
P11309	Q99683	1	phosphorylation	down-regulates	0.28	Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation	SIGNOR-187905
Q09472	Q96EB6	0	deacetylation	down-regulates	0.835	Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024	SIGNOR-182511
Q9BQS8	Q9H0B6	2	binding	up-regulates activity	0.344	Interestingly, bead capture assays indicated that the middle part of FYCO1 (residues 585–1233) interacts directly with the KLC2 light chain of kinesin 1 (Fig. 3a and Extended Data Fig. 7a, b). Residues 735–773 of FYCO1 were found to be necessary for its kinesin-1 binding (Fig. 3c and Extended Data Fig. 7b, c), and FYCO1(Δ735–773)-positive LEs failed to translocate to the cell periphery (Extended Data Fig. 7e).	SIGNOR-260599
P46531	P49840	0	phosphorylation	down-regulates	0.319	Taken together, our results indicate that gsk-3alfa is a negative regulator of notch1/nicd.	SIGNOR-183969
P28482	P19438	1	phosphorylation	down-regulates activity	0.5	Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation.\|Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a	SIGNOR-249453
P30301	P17612	0	phosphorylation	down-regulates activity	0.312	Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed.	SIGNOR-250018
P84103	O15355	0	dephosphorylation	down-regulates activity	0.2	Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.\|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.	SIGNOR-277048
P54792	P17252	2	binding	up-regulates	0.2	Our findings suggest a molecular interaction between pka, hdpr1, and dvl and a possible contribution of this interaction to tumorigenesis.	SIGNOR-199454
P05556	Q9Y490	2	binding	up-regulates activity	0.798	Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.	SIGNOR-257607
Q8WYL5	Q9BR76	1	dephosphorylation	up-regulates	0.446	Coronin 1b inhibits filament nucleation by arp2/3 complex and this inhibition is attenuated by phosphorylation of coronin 1b at serine 2, a site targeted by ssh1l.	SIGNOR-153604
P78527	P53350	2	phosphorylation	up-regulates activity	0.425	DNA-PKcs Promotes Plk1 Activation.\|Further analysis revealed that DNA-PKcs could directly phosphorylate the C-terminal PBD domain of Plk1 (lane 8).	SIGNOR-279562
O94921	O75581	1	phosphorylation	up-regulates	0.333	Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.	SIGNOR-162924
P36897	Q96JC1	2	binding	up-regulates activity	0.2	TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling.	SIGNOR-261375
P24941	Q15796	1	phosphorylation	down-regulates activity	0.488	Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.\|Moreover, CDK2 is the predominant cyclin-dependent kinase that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.	SIGNOR-279678
O15164	P04637	1	ubiquitination	down-regulates	0.532	New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation	SIGNOR-188726
Q8IUC6	Q9Y4K3	0	polyubiquitination	up-regulates	0.83	Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1	SIGNOR-271428
Q92879	P11802	0	phosphorylation	up-regulates activity	0.398	These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.	SIGNOR-262735
P62805	Q92993	0	acetylation	down-regulates activity	0.2	Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.	SIGNOR-262061
Q86Y07	Q13469	1	phosphorylation	up-regulates	0.369	We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.	SIGNOR-199263
P53602	P63000	1	lipidation	up-regulates activity	0.2	Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation.	SIGNOR-265892
Q9Y4K3	Q99558	2	binding	up-regulates activity	0.631	RANK activates NF-κB by interacting with TRAF6 via a novel TRAF6 interaction motif and TRAF6 potentially activates NIK, leading to NF-κB activation. TRAF6 has been demonstrated to interact with NIK.	SIGNOR-253048
Q9BYB0	Q8WZ74	2	binding	up-regulates activity	0.2	Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines.	SIGNOR-269702
Q9H6R7	P53350	0	phosphorylation	up-regulates activity	0.2	PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. we performed in vitro kinase assays followed by mass spectrometry and found that two sites (S686 and S695) in this cluster were phosphorylated. Thus, all of these results are in agreement that this cluster is phosphorylated by PLK1.	SIGNOR-273730
Q13315	P16104	1	phosphorylation	up-regulates	0.2	H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.	SIGNOR-160206
O75665	Q13099	2	binding	up-regulates activity	0.412	Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.	SIGNOR-251973
O14757	Q99638	1	phosphorylation	up-regulates activity	0.669	Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.\|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation.	SIGNOR-279503
Q9UP38	P56706	2	binding	up-regulates	0.67	Wnt7b can bind to fzd1 and -10 on the cell surface and cooperatively activate canonical wnt signaling.	SIGNOR-137931
P11137	Q76NI1	0	phosphorylation	up-regulates activity	0.369	V-KIND enhances Thr phosphorylation of MAP2.	SIGNOR-278950
P36873	Q69YH5	2	binding	up-regulates activity	0.371	This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.	SIGNOR-274003
P28482	Q15366	1	phosphorylation	up-regulates quantity by stabilization	0.318	We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).	SIGNOR-262912

P04637

Q8NEZ5

0

ubiquitination

down-regulates quantity by destabilization

0.338

We demonstrate here that SCFFbxo22-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCFFbxo22 ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. |SCFFbxo22 forms a ternary complex with p53 and KDM4A that targets methylated p53 for degradation.

SIGNOR-273448

P19793

O75469

2

binding

up-regulates

0.533

The constitutive androstane receptor (car, nr1i4), like fxr and pxr, binds dna as a heterodimer with rxr?

SIGNOR-111624

P04637

P49841

0

phosphorylation

up-regulates activity

0.728

Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity.

SIGNOR-251258

Q13501

Q9H492

2

binding

up-regulates

0.791

Sqstm1/p62 (named a170 in the mouse;hereafter p62) is the first proposed example of such proteins (bj_?_?Rk_?_?Y et al.,2005). It binds polyubiquitinated protein aggregates via its uba domain and interacts with lc3 on the autophagosome/ this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguishable from p62 inclusion bodies and that p62 is required for their formation.

SIGNOR-156353

Q9BXM7

O95140

1

phosphorylation

down-regulates quantity

0.81

If PINK1 is responsible for the degradation of Mfn2, then silencing PINK1 should induce mitochondrial fusion by upregulating Mfn2 expression.|We show that downregulation of Mfn2 is induced by proteasomal degradation triggered by PINK1, which phosphorylates Mfn2 at S442.

SIGNOR-278208

P17252

Q96QS3

1

phosphorylation

up-regulates activity

0.2

We confirm that ARX is phosphorylated by PRKCA and demonstrate phosphorylation at serine 174. We demonstrate that phosphorylation is required for correct transcriptional activity of the ARX protein using transcriptome-wide analysis of gene expression of phospho-null mutants (alanines replacing serines) compared to ARX wild-type (ARX-WT) overexpressed in pancreatic alpha TC cells.

SIGNOR-277418

Q9Y2J4

Q9NRM7

2

relocalization

up-regulates activity

0.728

Ubiquitinated AMOTL2 then serves as a physical docking site for LATS2, which phosphorylates YAP to promote its cytoplasmic retention and degradation.

SIGNOR-271875

P04637

P06493

0

phosphorylation

up-regulates activity

0.579

The N-terminus of E2F1 can interact directly with a region towards the C-terminus of p53, resulting in increased nuclear retention of p53 and p53-mediated transcription and apoptosis. This is inhibited by competition between p53 and cyclin A at the binding site within E2F19,10. The interaction between p53 and E2F1 is enhanced by phosphorylation of p53 on Ser315, a residue within the E2F1 binding region that is phosphorylated by cell cycle kinases such as cdk1, cdk2, cdk9 and Aurora kinase A

SIGNOR-167779

P54646

O60825

1

phosphorylation

up-regulates activity

0.443

AMPK phosphorylates and activates heart PFK-2 in vitro and in intact cells. activation of PFK-2 was due to the phosphorylation of Ser466

SIGNOR-250323

Q13148

P00519

0

phosphorylation

up-regulates quantity

0.2

The phosphorylation of tyrosine 43 of TDP-43 by c-Abl led to increased TDP-43 levels in the cytoplasm and increased the formation of G3BP1-positive stress granules in SH-SY5Y cells.

SIGNOR-279135

O00635

Q9Y4K3

1

polyubiquitination

down-regulates quantity by destabilization

0.43

As an E3 ligase, TRIM38 bound to TRAF6 and promoted K48-linked polyubiquitination, which led to the proteasomal degradation of TRAF6.

SIGNOR-272009

P51812

P27361

0

phosphorylation

up-regulates

0.73

We have generated two monoclonal antibodies that recognize two phosphorylated sites, p-ser227 and p-thr577, in the n- and c-terminal kinase domains of rsk2, respectively. phosphorylation and activation of rsk2 by uv light involves the erk pathway

SIGNOR-81460

P36897

Q04771

1

phosphorylation

up-regulates activity

0.364

This directly demonstrates that TGFBR1 can activate ACVR1 in vivo.|We show that in response to TGF-\u03b2, TGFBRI phosphorylates and activates ACVR1, which phosphorylates SMAD1/5.

SIGNOR-279490

P46020

P22612

0

phosphorylation

down-regulates activity

0.325

Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.

SIGNOR-267415

Q12879

P06241

0

phosphorylation

up-regulates activity

0.734

To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.

SIGNOR-247151

Q8IVH8

P19484

1

phosphorylation

down-regulates activity

0.25

However, although our results indicate that MAP4K3 initiates TFEB repression, MAP4K3 also promotes robust mTORC1 activation upon amino acid stimulation - ; hence, MAP4K3 and mTORC1 must ultimately work together to achieve robust suppression of autophagy.|Moreover, MAP4K3 serine 3 phosphorylation of TFEB is required for TFEB interaction with mTORC1-Rag GTPase-Ragulator complex and TFEB cytosolic sequestration.

SIGNOR-278282

Q05655

O15350

1

phosphorylation

up-regulates

0.307

The results show that pkcdeltacf phosphorylates the p73beta transactivation and dna-binding domains. pkcdeltacf-mediated phosphorylation of p73beta is associated with accumulation of p73beta and induction of p73beta-mediated transactivation.

SIGNOR-90279

P56704

Q9H461

2

binding

up-regulates

0.797

Structural basis of wnt recognition by frizzled.

SIGNOR-197638

Q9UNW8

P38405

2

binding

up-regulates activity

0.2

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256945

Q9UPU5

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.2

Epidermal growth factor (EGF) treatment, and the KrasG12D and EGFRL858R mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604.

SIGNOR-275605

Q13315

Q9NPI1

1

phosphorylation

down-regulates activity

0.2

ATM Directly Phosphorylates BRD7 at Ser 263 Site.

SIGNOR-279780

Q8TEW6

P12931

2

binding

up-regulates

0.419

Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.

SIGNOR-101002

Q8NBL1

Q04721

2

binding

up-regulates

0.575

O-glucosylation of epidermal growth factor-like (egf) repeats in the extracellular domain of notch is essential for notch function. O-glucose can be elongated by xylose to the trisaccharide, xylalfa1-3xylalfa1-3glcbeta1-o-ser, whose synthesis is catalyzed by the consecutive action of three glycosyltransferases. A udp-glucose:protein o-glucosyltransferase (poglut/rumi) transfers o-glucose to serine within the o-glucose consensus.

SIGNOR-198716

Q8NG27

Q01082

1

ubiquitination

down-regulates

0.403

The present study indicates that praja, a ring finger e3 ubiquitin ligase, interacts with elf and ubiquitinates it.

SIGNOR-141216

Q13418

2

phosphorylation

up-regulates activity

0.2

Although ilk has been shown to autophosphorylate serine 343 (s343) is in the hydrophobic motif fsf within the activation loop of the kinase domain and has previously been suggested to be the target of autophosphorylation (9). Mutation of serine 343 to alanine (s343a) resulted in the inability of ilk to stimulate phosphorylation of pkb/akt in cos cells (9).

SIGNOR-106838

Q99558

O43318

0

phosphorylation

up-regulates activity

0.564

The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway|Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.

SIGNOR-262833

O96006

P62753

1

transcriptional regulation

up-regulates quantity by expression

0.2

HDRE-like sequences act as positive regulatory elements for RP gene promoter activities in vivo. | Cotransfection of a plasmid expressing hDREF increased luciferase expression directed by each RP gene promoter more than 30% compared with the values obtained without the hDREF-expressing plasmid.

SIGNOR-266082

P67775

P13639

1

dephosphorylation

up-regulates

0.404

Protein phosphatases-2a and -2c (pp-2a and pp-2c) can each efficiently dephosphorylate phosphorylated eef-2

SIGNOR-38566

O96017

P62714

0

dephosphorylation

up-regulates activity

0.309

Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.

SIGNOR-248582

P17252

O60479

1

phosphorylation

down-regulates activity

0.307

Dlx3 is primarily phosphorylated by PKC alpha. By deletion and mutational analysis, we show that the serine residue S(138), located in the homeodomain of Dlx3 protein, was specifically phosphorylated by PKC. The phosphorylation of purified Dlx3 proteins by PKC partially inhibited formation of complexes between Dlx3 protein and DNA. These results suggest that Dlx3 protein can be directly phosphorylated by PKC and this affects the DNA binding activity of Dlx3.

SIGNOR-249096

P10275

Q15596

2

binding

up-regulates activity

0.901

The NCOA2 gene encodes a transcriptional coactivator (SRC-2) that modulates gene expression by hormone receptors, including AR. NCOA2 is both amplified and rarely mutated in prostate cancers, with higher NCOA2 levels resulting in increased androgen signaling readout. Furthermore, as mentioned previously, SRC-3, a close homolog encoded by NCOA3, is a substrate of SPOP whose protein levels are increased by SPOP mutation, potentially linking these common point mutations to the androgen axis

SIGNOR-251531

P84022

Q8N6I1

2

binding

down-regulates

0.397

In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.

SIGNOR-119171

P24158

P01019

1

cleavage

up-regulates activity

0.259

Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen.

SIGNOR-256314

Q14767

P35555

2

binding

up-regulates activity

0.301

LTBP-2 interacts with fibrillin-1. The association of LTBP-2 with the ECM always coincided with that of fibrillin-1, and in fibroblast cultures the appearance of fibrillar fibrillin-1 structures preceded the assembly of LTBP-2 network.

SIGNOR-251891

P45452

P02675

1

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain

SIGNOR-263615

P21731

Q14344

2

binding

up-regulates activity

0.574

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257139

P17612

Q2Q1W2

1

phosphorylation

up-regulates quantity by stabilization

0.2

These observations suggested that LINK-A expression potentially inhibits PKA phosphorylation/activity and PKA-mediated phosphorylation of TRIM71 at Ser3.

SIGNOR-277454

Q00613

Q9UQM7

0

phosphorylation

up-regulates activity

0.513

Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells.

SIGNOR-250631

Q9UER7

P68400

0

phosphorylation

up-regulates

0.327

Daxx-sim is phosphorylated by ck2 kinase at residues s737 and s739. Phosphorylation promotes daxx-sim binding affinity toward sumo-1 over sumo-2/3, causing daxx preference for sumo-1 conjugation and interaction with sumo-1-modified factors.

SIGNOR-173105

P09471

P41146

2

binding

up-regulates activity

0.347

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257001

Q9H2X6

Q9P1Z0

1

phosphorylation

down-regulates activity

0.379

The human protein kinase HIPK2 phosphorylates and downregulates the methyl-binding transcription factor ZBTB4.

SIGNOR-262882

P46527

P31751

0

phosphorylation

down-regulates

0.53

Akt-induced t157 phosphorylation causes retention of p27(kip1) in the cytoplasm, precluding p27(kip1)-induced g1 arrest.[__]Thus, cytoplasmic relocalization of p27(kip1), secondary to akt-mediated phosphorylation, is a novel mechanism whereby the growth inhibitory properties of p27(kip1) are functionally inactivated and the proliferation of breast cancer cells is sustained.

SIGNOR-93122

P48551

P01562

2

binding

up-regulates activity

0.614

Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.

SIGNOR-219298

P12931

P31040

1

phosphorylation

up-regulates activity

0.267

Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.

SIGNOR-276420

P84022

Q14974

0

relocalization

up-regulates

0.524

Here we show that the isolated smad 3 mh1 domain displays significant specific binding to importin beta. we propose that activation of all of the pathway-specific smad proteins (smads 1, 2, 3, 5, 8, and 9) exposes the conserved nls motif, which then binds directly to importin beta and triggers nuclear translocation.

SIGNOR-78191

Q13153

P67775

0

dephosphorylation

down-regulates activity

0.357

Both sites were dephosphorylated with the same kinetics; the anti-Ser(P)198 antibody was subsequently used as it exhibited lower background staining. Direct comparison of PP2Cα with purified PP1 and PP2A lead us to conclude that at the same molar ratio PP2Cα was the most efficient in dephosphorylating PAK1 (Fig. 1D). In this case we monitored two autophosphorylation sites in the Pak1 N-terminal regulatory region (Ser57 and Ser198/203) using phosphospecific antibodies: both sites showed the same kinetics of inactivation.

SIGNOR-248641

P16104

Q99986

0

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

P00748

P01008

0

cleavage

down-regulates activity

0.6

Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1

SIGNOR-264139

O75367

P38398

0

ubiquitination

up-regulates activity

0.2

BRCA1 Ubiquitinates K123 of mH2A1 in a Ligase-Activity-Dependent Manner.

SIGNOR-278752

P19419

Q9UL54

0

phosphorylation

up-regulates activity

0.31

Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.

SIGNOR-246638

Q7Z553

Q9NPF5

2

binding

up-regulates quantity by stabilization

0.348

The anti-tumorigenic effect of MDGA2 was mediated through direct stabilising of DNA methyltransferase 1 associated protein 1 (DMAP1), which played a tumour suppressive role in gastric cancer. MDGA2 expression and MG132 treatment increased the level of DMAP1, suggesting that the MDGA2–DMAP1 interaction stabilises DMAP1 by inhibiting its ubiquitin-mediated degradation.

SIGNOR-264240

P12931

P31749

1

phosphorylation

up-regulates activity

0.677

Regulation of Akt/PKB Activation by Tyrosine PhosphorylationAs shown in Fig. 2 d, while mutation of Tyr340 has little effect on either tyrosine phosphorylation or kinase activity of Akt induced by Src527F, substitution of Tyr315 or Tyr326 with a phenylalanine, respectively, dramatically reduces both the tyrosine phosphorylation and kinase activity of Akt. The combination of these two mutations abolishes Src-induced tyrosine phosphorylation of Akt as well as its kinase activity.

SIGNOR-252623

O75116

P05067

1

phosphorylation

up-regulates quantity

0.386

Moreover, SR3677 blocked ROCK2 phosphorylation of APP at threonine 654 (T654); in neurons, T654 was critical for APP processing to Abeta.|These observations suggest that ROCK2 inhibition reduces Abeta levels through independent mechanisms.

SIGNOR-280109

Q9UKV5

P04234

1

polyubiquitination

down-regulates quantity by destabilization

0.474

Gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate.

SIGNOR-272670

P49715

P28845

1

transcriptional regulation

up-regulates quantity by expression

0.274

Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region.

SIGNOR-268971

P06400

O96017

0

phosphorylation

up-regulates activity

0.423

Phosphorylation of prb at ser612 by chk1/2 leads to a complex between prb and e2f-1 after dna damageprb inhibits cell cycle progression through interactions with the e2f family of transcription factors. Here, we report that dna damage induced not only the dephosphorylation of prb at cdk phosphorylation sites and the binding of prb to e2f-1, but also the phosphorylation of prb at ser612. Phosphorylation of prb at ser612 enhanced the formation of a complex between prb and e2f-1

SIGNOR-153908

Q06413

Q15759

0

phosphorylation

up-regulates activity

0.538

In this study, we demonstrate that among the different Mitogen-activated protein kinases, the MADS-box transcription factors MEF2A and MEF2C are preferentially phosphorylated and activated by the p38 subfamily members p38alpha and p38beta2.

SIGNOR-280025

Q99717

O43541

1

transcriptional regulation

up-regulates quantity

0.599

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268940

O43424

A4D2P6

2

binding

up-regulates quantity

0.609

We identified a novel GluRdelta2-interacting protein, named Delphilin, that contains a single PDZ domain and formin homology (FH) domains FH1 and FH2 plus coiled-coil structure. Delphilin is selectively localized at the postsynaptic junction site of the parallel fiber-Purkinje cell synapse and colocalized with GluRdelta2. Thus, Delphilin is a postsynaptic scaffolding protein at the parallel fiber-Purkinje cell synapse, where it may serve to link GluRdelta2 with actin cytoskeleton and various signaling molecules.

SIGNOR-264475

Q9NYY3

Q9HC77

1

phosphorylation

up-regulates

0.579

Plk2 phosphorylates the s589 and s595 residues of cpap in vitro and in vivo. This phosphorylation is critical for procentriole formation during the centrosome cycle.

SIGNOR-165999

P51843

Q13285

2

binding

down-regulates activity

0.702

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271784

P49674

P46937

1

phosphorylation

down-regulates

0.422

Phosphorylation of YAP (S381) and TAZ (S311) by Lats1/2 primes subsequent phosphorylation events by Casein Kinase 1 (CK1d/e); this sequential phosphorylation results in recruitment of b-transducin repeat-containing proteins (b-TRCP; a subunit of the SCF ubiquitin E3 ligase) and consequently leads to degradation of YAP/TAZ

SIGNOR-201170

Q00987

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.811

Mitogen-induced activation of phosphatidylinositol 3-kinase (pi3-kinase) and its downstream target, the akt/pkb serine-threonine kinase, results in phosphorylation of mdm2 on serine 166 and serine 186. Phosphorylation on these sites is necessary for translocation of mdm2 from the cytoplasm into the nucleus.Both akt expression and serum treatment induced phosphorylation of mdm2 at ser186.

SIGNOR-116270

Q9UQK1

P54840

2

binding

up-regulates

0.753

In the liver, PTG and PPP1R3B(GL)are expressed at roughly equivalent levels [55], and they jointly promote hepatic glycogen mobilization and storage. PTG overexpression significantly increased glycogen content, mainly due to its ability to promote the redistribution of PP1 and glycogen synthase to glycogen granules, significantly increasing GS activity and glycogen synthesis (Figure 2)

SIGNOR-271731

O43521

Q07812

2

binding

up-regulates activity

0.832

We have shown that the interaction of the bims and bimad isoforms with bax leads to a conformational change in this protein analogous to that triggered by the bh3-only protein bid.We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome.

SIGNOR-87280

Q03052

P26583

2

binding

up-regulates activity

0.307

HMG2 and Oct2 interact via their HMG domains and POU homeodomains, respectively. This interaction is not restricted to Oct2, as other members of the octamer transcription factor family like Oct1 and Oct6 also interact with HMG2. The interaction with HMG2 results in a marked increase in the sequence-specific DNA binding activity of the Oct proteins

SIGNOR-240148

P43250

P14416

1

phosphorylation

down-regulates activity

0.447

GRK6 is located predominantly in dopaminergic neurons [ xref ] and functionally phosphorylates DRD2.

SIGNOR-279046

Q9Y572

O43318

0

phosphorylation

up-regulates activity

0.2

Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.

SIGNOR-279634

P51813

P56945

1

phosphorylation

up-regulates quantity

0.506

Recombinant Bmx kinase was found to effectively phosphorylate the wt CAS SH3 domain on Tyr-12 (Figure 2B). A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells.

SIGNOR-276384

Q93009

P04637

1

deubiquitination

up-regulates

0.741

Hausp counteracts the destabilizing effect of mdm2 by direct deubiquitination of p53.

SIGNOR-139456

P11309

Q99683

1

phosphorylation

down-regulates

0.28

Pim1 phosphorylates and negatively regulates ask1-mediated apoptosispim1 phosphorylation of ask1 on ser83 inhibited ask1-mediated c-jun n-terminal kinase phosphorylation

SIGNOR-187905

Q09472

Q96EB6

0

deacetylation

down-regulates

0.835

Sirt1 induces deacetylation and repression of p300 itself (81). Mutational analysis demonstrated that sirt1 repression of p300 involves both lysine 1020 and lysine 1024

SIGNOR-182511

Q9BQS8

Q9H0B6

2

binding

up-regulates activity

0.344

Interestingly, bead capture assays indicated that the middle part of FYCO1 (residues 585–1233) interacts directly with the KLC2 light chain of kinesin 1 (Fig. 3a and Extended Data Fig. 7a, b). Residues 735–773 of FYCO1 were found to be necessary for its kinesin-1 binding (Fig. 3c and Extended Data Fig. 7b, c), and FYCO1(Δ735–773)-positive LEs failed to translocate to the cell periphery (Extended Data Fig. 7e).

SIGNOR-260599

P46531

P49840

0

phosphorylation

down-regulates

0.319

Taken together, our results indicate that gsk-3alfa is a negative regulator of notch1/nicd.

SIGNOR-183969

P28482

P19438

1

phosphorylation

down-regulates activity

0.5

Phosphorylation of murine CD120a by p42(mapk/erk2) has been shown to inhibit its ability to initiate apoptosis while preserving signaling events such as NF-kappaB activation.|Additionally, we demonstrated that (i) the p42(mapk/erk2)-dependent phosphorylation of CD120a and DR3 occurred on Ser and Thr residues, (ii) p42(mapk/erk2) phosphorylated residues located in the membrane proximal regions but not the death domains of CD120a and DR3, (iii) Ser 253 is a preferred site of phosphorylation on CD120a

SIGNOR-249453

P30301

P17612

0

phosphorylation

down-regulates activity

0.312

Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed.

SIGNOR-250018

P84103

O15355

0

dephosphorylation

down-regulates activity

0.2

Here, we found that the PPM1G regulated SRSF3, and high levels of PPM1G decreased SRSF3 activity in HCC cells.|PPM1G interacted with SRSF3 and dephosphorylated SRSF3.

SIGNOR-277048

P54792

P17252

2

binding

up-regulates

0.2

Our findings suggest a molecular interaction between pka, hdpr1, and dvl and a possible contribution of this interaction to tumorigenesis.

SIGNOR-199454

P05556

Q9Y490

2

binding

up-regulates activity

0.798

Over the past 10 years, the binding of talin to the cytoplasmic tail of integrin-β subunits has been established to have a key role in integrin activation. Binding of the phosphotyrosinebinding (PTB)-domain-like subdomain of the protein 4.1, ezrin, radixin, moesin (FERM) domain of talin to the conserved WxxxNP(I/L)Y motif of the β-integrin tail permits additional weaker interactions between talin and the membrane-proximal region of the tail that trigger integrin activation, probably through the disruption of inhibitory interactions between α- and β-subunit cytoplasmic tails.

SIGNOR-257607

Q8WYL5

Q9BR76

1

dephosphorylation

up-regulates

0.446

Coronin 1b inhibits filament nucleation by arp2/3 complex and this inhibition is attenuated by phosphorylation of coronin 1b at serine 2, a site targeted by ssh1l.

SIGNOR-153604

P78527

P53350

2

phosphorylation

up-regulates activity

0.425

DNA-PKcs Promotes Plk1 Activation.|Further analysis revealed that DNA-PKcs could directly phosphorylate the C-terminal PBD domain of Plk1 (lane 8).

SIGNOR-279562

O94921

O75581

1

phosphorylation

up-regulates

0.333

Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.

SIGNOR-162924

P36897

Q96JC1

2

binding

up-regulates activity

0.2

TLP interacts with TGF-β and activin receptors in vivo. Endogenous TLP associates with both active and kinase-deficient TGF-beta and activin type II receptors, but interacts with the common-mediator Smad4 only in the presence of TGF-beta/activin signaling.

SIGNOR-261375

P24941

Q15796

1

phosphorylation

down-regulates activity

0.488

Moreover, CDK2 is the predominant CDK that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.|Moreover, CDK2 is the predominant cyclin-dependent kinase that phosphorylates Smad2 on T8 in myeloma cells, leading to inhibition of Smad2-Smad4 association that precludes transcriptional regulation by Smad2.

SIGNOR-279678

O15164

P04637

1

ubiquitination

down-regulates

0.532

New ring-domain e3-ubiquitin ligase trim24 that targets p53 for degradation

SIGNOR-188726

Q8IUC6

Q9Y4K3

0

polyubiquitination

up-regulates

0.83

Here, we show that the TRAF family proteins directly bind TICAM-1 and demonstrate that TRAF2 and TRAF6 bind different sites of the N-terminal TICAM-1 and accelerate its polyubiquitination. we speculate that polyubiquitination of TICAM-1 by TRAF2 and TRAF6 is required for TICAM-1 to induce IRF-3 and NF-κB activation. This is supported by the observation that polyubiquitination of TICAM-1 was required for TRAF3-binding to TICAM-1

SIGNOR-271428

Q92879

P11802

0

phosphorylation

up-regulates activity

0.398

These studies showed that both the increased levels of CUGBP1 and cdk4-mediated hyper-phosphorylation of CUGBP1 are involved in the age-associated induction of the CUGBP1-eIF2 complex. The CUGBP1-eIF2 complex is bound to C/EBPbeta mRNA in the liver of old animals, and this binding correlates with the increased amounts of liver-enriched activator protein and liver-enriched inhibitory protein.

SIGNOR-262735

P62805

Q92993

0

acetylation

down-regulates activity

0.2

Thus, the TIP60 HAT complex is recruited to MYC-target genes and, probably with other other HATs, contributes to histone acetylation in response to mitogenic signals.

SIGNOR-262061

Q86Y07

Q13469

1

phosphorylation

up-regulates

0.369

We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.

SIGNOR-199263

P53602

P63000

1

lipidation

up-regulates activity

0.2

Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation.

SIGNOR-265892

Q9Y4K3

Q99558

2

binding

up-regulates activity

0.631

RANK activates NF-κB by interacting with TRAF6 via a novel TRAF6 interaction motif and TRAF6 potentially activates NIK, leading to NF-κB activation. TRAF6 has been demonstrated to interact with NIK.

SIGNOR-253048

Q9BYB0

Q8WZ74

2

binding

up-regulates activity

0.2

Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines.

SIGNOR-269702

Q9H6R7

P53350

0

phosphorylation

up-regulates activity

0.2

PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. we performed in vitro kinase assays followed by mass spectrometry and found that two sites (S686 and S695) in this cluster were phosphorylated. Thus, all of these results are in agreement that this cluster is phosphorylated by PLK1.

SIGNOR-273730

Q13315

P16104

1

phosphorylation

up-regulates

0.2

H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.

SIGNOR-160206

O75665

Q13099

2

binding

up-regulates activity

0.412

Ofd1 acts at the distal centriole to build distal appendages, recruit Ift88, and stabilize centriolar microtubules at a defined length.

SIGNOR-251973

O14757

Q99638

1

phosphorylation

up-regulates activity

0.669

Chk1 inhibition with small interfering RNA (siRNA) reduces Rad9A stabilization and accumulation.|In the case of DNA damage, an activated Chk1 phosphorylates Rad9A or other proteins (TLK1) as a feedback mechanism to prevent Rad9A (poly) ubiquitination and degradation.

SIGNOR-279503

Q9UP38

P56706

2

binding

up-regulates

0.67

Wnt7b can bind to fzd1 and -10 on the cell surface and cooperatively activate canonical wnt signaling.

SIGNOR-137931

P11137

Q76NI1

0

phosphorylation

up-regulates activity

0.369

V-KIND enhances Thr phosphorylation of MAP2.

SIGNOR-278950

P36873

Q69YH5

2

binding

up-regulates activity

0.371

This result demonstrates that the three sites of Repo-Man (Ser-543, Ser-977, and Ser-981) are phosphorylated by Aurora B in early mitosis. We uncover that PP1γ is recruited to mitotic chromosomes by its regulatory subunit Repo-Man in the absence of Aurora B activity and that Aurora B regulates dissociation of PP1γ by phosphorylating and disrupting PP1γ-Repo-Man interactions on chromatin.

SIGNOR-274003

P28482

Q15366

1

phosphorylation

up-regulates quantity by stabilization

0.318

We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).

SIGNOR-262912