GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P38936	Q13207	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
O14867	Q9BYM8	ubiquitination	down-regulates quantity by destabilization	0.345	HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.	SIGNOR-236971
O00429	P42345	phosphorylation	up-regulates activity	0.345	Furthermore, we confirmed also in Jurkat cells that the specific silencing of both ERK1/2 and mTOR by siRNA downregulates Drp1 phosphorylation on Ser616	SIGNOR-275430
P53779	Q00535	phosphorylation	down-regulates activity	0.345	Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3) on Thr131 and inhibits its kinase activity, leading to reduced c-Jun phosphorylation.	SIGNOR-250668
P61978	P27361	phosphorylation	down-regulates	0.345	Erk phosphorylation drives cytoplasmic accumulation of hnrnp-k and inhibition of mrna translation mitogen-activated protein kinase/extracellular-signal-regulated kinase (mapk/erk) efficiently phosphorylates hnrnp-k both in vitro and in vivo at serines 284 and 353.	SIGNOR-145375
P23246	P49841	phosphorylation	down-regulates	0.345	Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687	SIGNOR-168392
P10415	P06493	phosphorylation	up-regulates activity	0.345	Using synthetic peptides and mutant cell lines, we identified threonine 56, one of two consensus sites for cdc2 within the bcl-2 sequence, as a residue phosphorylated by cdc2. Mutation at threonine 56 abrogated the cell cycle inhibitory effect of bcl-2 without affecting anti-apoptotic function.Taken together, our present findings indicate that phosphorylation of bcl-2 at threonine 56 by cdc2 is required for bcl-2-mediated cell cycle inhibition, which may have some roles during mitosis in the normal cell cycle.	SIGNOR-76837
Q86UR5	A6NNM3	binding	down-regulates activity	0.345	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264364
O43474	P42226	transcriptional regulation	up-regulates quantity by expression	0.345	STAT6 coordinates and synergizes with both PPAR? and Krppel-like factor 4 (KLF4), a member of a family of proteins that contribute to macrophage function.	SIGNOR-249568
P0DP24	P00533	phosphorylation	down-regulates	0.345	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266319
P42566	Q16539	phosphorylation	up-regulates	0.345	Tnf-_ induces phosphorylation of eps15 at ser-796eps15 is a substrate for p38_these results suggest an attractive model in which p38 phosphorylates both eps15 and egfr to trigger efficient endocytosis	SIGNOR-203315
P15514	P12931	cleavage	up-regulates	0.345	Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.	SIGNOR-236537
P49840	P17252	phosphorylation	down-regulates	0.345	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115714
O43561	Q9Y4K3	ubiquitination	up-regulates activity	0.345	Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.\|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.	SIGNOR-278675
Q13586	P06493	phosphorylation	down-regulates	0.345	Stim1 is phosphorylated during mitosis. Removal of ten mpm-2 recognition sites by truncation at amino acid 482 abolished mpm-2 recognition of mitotic stim1, and significantly rescued stim1 rearrangement and soce response in mitosis. We identified ser 486 and ser 668 as mitosis-specific phosphorylation sites, and stim1 containing mutations of these sites to alanine also significantly rescued mitotic soce.	SIGNOR-189017
P13569	Q9UEW8	phosphorylation	down-regulates activity	0.345	SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.	SIGNOR-263134
P29590	P06493	phosphorylation	down-regulates	0.345	Here, we show that klhl20, a cullin3 (cul3) substrate adaptor induced by hif-1, coordinates with the actions of cdk1/2 and pin1 to mediate hypoxia-induced pml proteasomal degradation.	SIGNOR-176033
Q9HAW4	Q9UKB1	ubiquitination	down-regulates	0.345	Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbetatrcp ubiquitin ligase.	SIGNOR-148438
O75469	Q00535	phosphorylation	down-regulates activity	0.345	In vitro kinase assays showed that Cdk5 directly phosphorylates PXR.\|Taken together, these data indicate that Cdk5 negatively regulates PXR activity, and that inhibition of Cdk5 is at least partially responsible for flavonoids induced activation of PXR.	SIGNOR-279402
P35580	Q06413	transcriptional regulation	up-regulates quantity by expression	0.345	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238769
P50552	Q9C026	ubiquitination	down-regulates quantity	0.345	TRIM9 ubiquitinates VASP but not Mena or EVL.\|Thus TRIM9 negatively regulates VASP localization to filopodia tips, whereas netrin promotes VASP tip localization.	SIGNOR-278580
O95166	Q96A56	binding	up-regulates	0.345	Tp53inp1 is also able to interact with atg8-family proteins	SIGNOR-196664
O75581	P43250	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
Q96BY2	O95071	ubiquitination	down-regulates quantity by destabilization	0.345	We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.	SIGNOR-278581
Q38SD2	P53350	phosphorylation	up-regulates activity	0.345	Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes	SIGNOR-275467
P29353	P40189	binding	up-regulates	0.345	Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase.	SIGNOR-250574
O00213	O00141	phosphorylation	down-regulates activity	0.345	In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).\|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG).	SIGNOR-278220
Q5JR12	P45983	phosphorylation	down-regulates	0.344	Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.	SIGNOR-178930
O43663	Q00536	phosphorylation	up-regulates activity	0.344	Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.\|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process	SIGNOR-273017
Q96FI4	Q03468	binding	up-regulates activity	0.344	CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells.	SIGNOR-251931
P61978	Q05655	phosphorylation	down-regulates	0.344	Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment	SIGNOR-67515
Q9BQ15	Q9UKA1	binding	down-regulates quantity by destabilization	0.344	Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation.	SIGNOR-271655
Q9Y5T5	P53350	phosphorylation	up-regulates activity	0.344	Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D).	SIGNOR-274015
Q92934	O75582	phosphorylation	down-regulates activity	0.344	Phosphorylation of Bad at Ser112 in response to growth factors or cytokines is generally linked to cell survival. Knockdown of MSK1 suppressed Bad phosphorylation after calcium ionophore A23187 treatment in neuronal cells	SIGNOR-262990
P60709	Q9Y613	binding	up-regulates quantity by stabilization	0.344	Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation	SIGNOR-276613
Q13330	P78368	phosphorylation	up-regulates activity	0.344	CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.\|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells.	SIGNOR-280236
Q13351	P68400	phosphorylation	up-regulates activity	0.344	Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41	SIGNOR-241361
P04626	O14672	cleavage	up-regulates activity	0.344	The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.	SIGNOR-259845
P50148	P50406	binding	up-regulates activity	0.344	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-257340
P61586	Q9NPG1	binding	up-regulates activity	0.344	Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades.	SIGNOR-167865
Q13105	P51610	binding	down-regulates activity	0.344	We show here that HCF-1 directly binds to the Myc-interacting protein Miz-1. HCF-1 Represses Gal4-Miz-1-mediated Transcriptional Activation	SIGNOR-223590
P06213	P23467	dephosphorylation	down-regulates	0.344	Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.	SIGNOR-75997
P09629	P68400	phosphorylation	down-regulates activity	0.344	Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. \| Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation.	SIGNOR-250896
Q14161	Q05209	dephosphorylation	down-regulates	0.344	Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.	SIGNOR-142719
P40692	P00519	phosphorylation	up-regulates quantity by stabilization	0.344	We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.\|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp70 and that in the absence of ABL1 activity at least a portion of MLH1 is degraded.	SIGNOR-279581
P15056	O00141	phosphorylation	down-regulates activity	0.344	Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.\|We observed that SGK inhibits B-Raf activity.	SIGNOR-279110
Q14807	P06493	phosphorylation	up-regulates activity	0.344	Cdc2-mediated phosphorylation of kid controls its distribution to spindle and chromosomes. We identify ser427 and thr463 as m phase-specific phosphorylation sites and cdc2-cyclin b as a thr463 kinase. Kid with a thr463 to alanine mutation fails to be localized on chromosomes and is only detected along spindles, although it retains the ability to bind dna or chromosomes	SIGNOR-100964
P33151	O00192	binding	up-regulates quantity by stabilization	0.344	To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.	SIGNOR-252129
Q8WUI4	Q7KZI7	phosphorylation	down-regulates	0.344	We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function	SIGNOR-149583
P35638	P68400	phosphorylation	down-regulates activity	0.344	CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. \| The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites	SIGNOR-250850
Q99459	O00311	phosphorylation	down-regulates activity	0.344	During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway .	SIGNOR-280203
P53396	Q9H0H3	binding	down-regulates quantity by destabilization	0.344	Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells.	SIGNOR-272333
P48729	Q5T0W9	binding	up-regulates quantity	0.344	We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.	SIGNOR-273746
O94763	P23443	phosphorylation	down-regulates activity	0.344	Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.	SIGNOR-262943
P63092	Q14833	binding	up-regulates activity	0.344	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264082
P46934	P27216	relocalization	up-regulates quantity	0.344	Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb.	SIGNOR-272571
Q96EB6	Q13043	phosphorylation	down-regulates activity	0.344	We found that MST1 increases p53 acetylation and transactivation by inhibiting the deacetylation of Sirtuin 1 (Sirt1) and its interaction with p53 and that Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity.	SIGNOR-279574
P01106	Q9Y4K3	ubiquitination	down-regulates activity	0.344	We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).	SIGNOR-278563
P03372	P62877	ubiquitination	down-regulates quantity by destabilization	0.344	I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERalpha protein.	SIGNOR-271434
Q13976	P17252	phosphorylation	up-regulates	0.344	Antibodies generated against phosphorylated threonine 58 were used to demonstrate phosphorylation in response to pma treatment of the cells with kinetics similar to vasodilator-stimulated phosphoprotein phosphorylation. A phospho-mimetic mutation at this site (t58e) generated a partially activated pkg that was more sensitive to cgmp levels. A phospho- mutation (t58a) revealed that this residue is important but not sufficient for pkg activation by pkc.	SIGNOR-98803
Q9BQS8	Q9H0B6	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
Q04759	P06241	phosphorylation	up-regulates	0.344	Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.	SIGNOR-68798
Q9C035	P19474	monoubiquitination	up-regulates quantity	0.344	Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.	SIGNOR-271672
P21860	Q01973	phosphorylation	up-regulates activity	0.343	Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.\|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells.	SIGNOR-279279
Q13501	P06493	phosphorylation	up-regulates	0.343	Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.	SIGNOR-169012
O14920	P53350	phosphorylation	down-regulates	0.343	Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma	SIGNOR-181802
P42224	P00519	phosphorylation	up-regulates activity	0.343	Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).\|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.	SIGNOR-279491
Q99717	Q9UNE7	ubiquitination	down-regulates	0.343	In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne	SIGNOR-195690
Q9UGK3	O60674	phosphorylation	up-regulates activity	0.343	To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase \|On the other hand, the phosphorylation levels of Y22F, Y310F, and Y322F by GST-JH1 were reduced to 8060% of the levels of wild-type STAP-2, which suggests that these three are potential phosphorylation sites by activated JAK2.	SIGNOR-249372
P08754	P11229	binding	up-regulates activity	0.343	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-256878
O43318	Q9BZR9	polyubiquitination	up-regulates activity	0.343	These results suggest that TRIM8 could mediate K63-linked polyubiquitination of TAK1 at residue K158.These results suggest that TRIM8 is involved in TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked TAK1 polyubiquitination and subsequent activation.	SIGNOR-271890
P50613	P41743	phosphorylation	up-regulates activity	0.343	PKC\u03b9 activates CDK7 to promote glucose consumption.\|PKC\u03b9 phosphorylates Thr170 on CDK7 in vitro, can associate with CDK7 in cells, and is activated downstream of PI3K signaling xref , xref \u2013 xref .	SIGNOR-280088
Q15256	P17612	phosphorylation	down-regulates activity	0.343	The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue. treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant.‚	SIGNOR-250038
Q13351	P19784	phosphorylation	up-regulates activity	0.343	Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41	SIGNOR-241365
Q13158	O14965	phosphorylation	up-regulates	0.343	Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194	SIGNOR-176739
P12830	P54253	transcriptional regulation	up-regulates quantity by expression	0.343	Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner	SIGNOR-261577
O00459	P36897	binding	up-regulates	0.343	These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.	SIGNOR-227531
Q92945	P31751	phosphorylation	down-regulates	0.343	AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRPs ability to promote rapid mRNA decay.	SIGNOR-151220
P46109	Q18PE1	binding	up-regulates activity	0.343	Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7.	SIGNOR-273848
P36871	Q13153	phosphorylation	up-regulates	0.343	The signaling kinase p21-activated kinase 1 (pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (pgm),	SIGNOR-127135
P15172	Q7Z6Z7	ubiquitination	down-regulates quantity	0.343	Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.\|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein.	SIGNOR-278694
P54868	Q9NXA8	post translational modification	up-regulates activity	0.343	We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.\|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity\|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5	SIGNOR-267641
P19429	P17252	phosphorylation	up-regulates activity	0.343	In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. \| Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.	SIGNOR-249066
P68104	P36897	phosphorylation	down-regulates	0.343	Phosphorylation of eEF1A1 at Ser300 by T_R-I results in inhibition of mRNA translation	SIGNOR-167943
Q9Y6W5	Q96EV8	binding	up-regulates activity	0.343	Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1.	SIGNOR-265659
P49841	Q02750	phosphorylation	up-regulates activity	0.343	In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.	SIGNOR-236622
Q14847	P00519	phosphorylation	up-regulates	0.343	C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins.	SIGNOR-124719
O94916	P29350	dephosphorylation	down-regulates activity	0.343	We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity	SIGNOR-248467
Q38SD2	P00533	phosphorylation	down-regulates activity	0.343	In this study, we demonstrate that EGFR regulates the kinase activity of LRRK1 via tyrosine phosphorylation and that this is required for proper endosomal trafficking of EGFR. Phosphorylation of LRRK1 at Tyr-944 results in reduced LRRK1 kinase activity.	SIGNOR-262856
P10644	P24941	phosphorylation	up-regulates	0.343	In this context, we have identified rialpha as a novel substrate for the g(1)/s-cyclin-dependent kinase, cdk2/cyclin e, and found that rialpha is specifically phosphorylated at the serine residue.	SIGNOR-145577
O14818	P51149	binding	up-regulates activity	0.343	Rab7 Forms a Complex with the Proteasome -Subunit XAPC. In this study the proteasome alpha-subunit XAPC7 (also known as PSMA7, RC6-1, and HSPC in mammals) was identified to interact specifically with Rab7 and was recruited to multivesicular late endosomes through this interaction.	SIGNOR-261303
Q02790	P68400	phosphorylation	down-regulates activity	0.343	Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. \| Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90	SIGNOR-250865
Q01860	P27361	phosphorylation	down-regulates	0.343	Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.	SIGNOR-192101
P16662	P12931	phosphorylation	up-regulates	0.343	Overexpression of regular or active src, but not dominant-negative src, in 2b7-transfected cos-1 cells increased 2b7 activity and phospho-y438-2b7 by 50%	SIGNOR-184613
Q8TDQ1	P06241	phosphorylation	up-regulates activity	0.343	Y236 (YVTM) and Y263 (YCNM) fit with the consensus motif reported to bind the p85α regulatory subunit of PI3K (16). \|The association between IREM-1 and p85α was only perceived in the presence of c-Fyn, suggesting that tyrosine phosphorylation of IREM-1 cytoplasmic tail of IREM-1 was required for the interaction.	SIGNOR-275620
P07333	Q00341	transcriptional regulation	down-regulates quantity by repression	0.342	Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer.	SIGNOR-266696
P29590	P68400	phosphorylation	down-regulates	0.342	Here we show that ck2 regulates pml protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at ser517.	SIGNOR-148306
P04049	Q13131	phosphorylation	down-regulates	0.342	Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo.	SIGNOR-47148
Q9Y4H2	P16220	transcriptional regulation	up-regulates quantity by expression	0.342	Taken together, these results indicate that the IRS2 gene is a direct target for CREB action in vivo	SIGNOR-278145
P06127	P68400	phosphorylation	up-regulates	0.342	In this study, we use jurkat t cell transfectants of cd5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase ii (ckii) is responsible for the constitutive phosphorylation of cd5 molecules at a cluster of three serine residues located at the extreme c terminus (s458, s459, and s461)	SIGNOR-62311

P38936

Q13207

0

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

O14867

Q9BYM8

0

ubiquitination

down-regulates quantity by destabilization

0.345

HOIL-1 bound Bach1 in vivo and thus stimulated its polyubiquitination in vitro. These results suggest that heme regulates the polyubiquitination of Bach1 and subsequent degradation and that HOIL-1 may function as an E3 ligase in this process.

SIGNOR-236971

O00429

P42345

0

phosphorylation

up-regulates activity

0.345

Furthermore, we confirmed also in Jurkat cells that the specific silencing of both ERK1/2 and mTOR by siRNA downregulates Drp1 phosphorylation on Ser616

SIGNOR-275430

P53779

Q00535

0

phosphorylation

down-regulates activity

0.345

Here, we show that cdk5 directly phosphorylates c-Jun N-terminal kinase 3 (JNK3) on Thr131 and inhibits its kinase activity, leading to reduced c-Jun phosphorylation.

SIGNOR-250668

P61978

P27361

0

phosphorylation

down-regulates

0.345

Erk phosphorylation drives cytoplasmic accumulation of hnrnp-k and inhibition of mrna translation mitogen-activated protein kinase/extracellular-signal-regulated kinase (mapk/erk) efficiently phosphorylates hnrnp-k both in vitro and in vivo at serines 284 and 353.

SIGNOR-145375

P23246

P49841

0

phosphorylation

down-regulates

0.345

Psf is directly phosphorylated by gsk3, thus promoting interaction of psf with trap150, which prevents psf from binding cd45 pre-mrna. / threonine phosphorylation of psf by gsk3 primarily occurs on residue t687

SIGNOR-168392

P10415

P06493

0

phosphorylation

up-regulates activity

0.345

Using synthetic peptides and mutant cell lines, we identified threonine 56, one of two consensus sites for cdc2 within the bcl-2 sequence, as a residue phosphorylated by cdc2. Mutation at threonine 56 abrogated the cell cycle inhibitory effect of bcl-2 without affecting anti-apoptotic function.Taken together, our present findings indicate that phosphorylation of bcl-2 at threonine 56 by cdc2 is required for bcl-2-mediated cell cycle inhibition, which may have some roles during mitosis in the normal cell cycle.

SIGNOR-76837

Q86UR5

A6NNM3

0

binding

down-regulates activity

0.345

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264364

O43474

P42226

0

transcriptional regulation

up-regulates quantity by expression

0.345

STAT6 coordinates and synergizes with both PPAR? and Krppel-like factor 4 (KLF4), a member of a family of proteins that contribute to macrophage function.

SIGNOR-249568

P0DP24

P00533

0

phosphorylation

down-regulates

0.345

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266319

P42566

Q16539

0

phosphorylation

up-regulates

0.345

Tnf-_ induces phosphorylation of eps15 at ser-796eps15 is a substrate for p38_these results suggest an attractive model in which p38 phosphorylates both eps15 and egfr to trigger efficient endocytosis

SIGNOR-203315

P15514

P12931

0

cleavage

up-regulates

0.345

Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.

SIGNOR-236537

P49840

P17252

0

phosphorylation

down-regulates

0.345

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115714

O43561

Q9Y4K3

0

ubiquitination

up-regulates activity

0.345

Interestingly, this study has demonstrated that the membrane-proximal region of linker for activation of T cells preceding tyrosine-132 mediates its association with TRAF6, which promotes the ubiquitination of linker for activation of T cells and, in turn, the phosphorylation of tyrosine residues on linker for activation of T cells.|Moreover, LAT was ubiquitinated at Lysine 88 by TRAF6 via K63 linked chain.

SIGNOR-278675

Q13586

P06493

0

phosphorylation

down-regulates

0.345

Stim1 is phosphorylated during mitosis. Removal of ten mpm-2 recognition sites by truncation at amino acid 482 abolished mpm-2 recognition of mitotic stim1, and significantly rescued stim1 rearrangement and soce response in mitosis. We identified ser 486 and ser 668 as mitosis-specific phosphorylation sites, and stim1 containing mutations of these sites to alanine also significantly rescued mitotic soce.

SIGNOR-189017

P13569

Q9UEW8

0

phosphorylation

down-regulates activity

0.345

SPAK phosphorylates the transporters to reduce their surface expression and thus their activity and consequently inhibits ductal secretion to stabilize the resting state. PP1 reverses the effect of SPAK. Molecular analysis revealed that the WNK kinases acted as scaffolds to recruit SPAK, which phosphorylated CFTR and NBCe1-B, reducing their cell surface expression.

SIGNOR-263134

P29590

P06493

0

phosphorylation

down-regulates

0.345

Here, we show that klhl20, a cullin3 (cul3) substrate adaptor induced by hif-1, coordinates with the actions of cdk1/2 and pin1 to mediate hypoxia-induced pml proteasomal degradation.

SIGNOR-176033

Q9HAW4

Q9UKB1

0

ubiquitination

down-regulates

0.345

Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbetatrcp ubiquitin ligase.

SIGNOR-148438

O75469

Q00535

0

phosphorylation

down-regulates activity

0.345

In vitro kinase assays showed that Cdk5 directly phosphorylates PXR.|Taken together, these data indicate that Cdk5 negatively regulates PXR activity, and that inhibition of Cdk5 is at least partially responsible for flavonoids induced activation of PXR.

SIGNOR-279402

P35580

Q06413

0

transcriptional regulation

up-regulates quantity by expression

0.345

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238769

P50552

Q9C026

0

ubiquitination

down-regulates quantity

0.345

TRIM9 ubiquitinates VASP but not Mena or EVL.|Thus TRIM9 negatively regulates VASP localization to filopodia tips, whereas netrin promotes VASP tip localization.

SIGNOR-278580

O95166

Q96A56

0

binding

up-regulates

0.345

Tp53inp1 is also able to interact with atg8-family proteins

SIGNOR-196664

O75581

P43250

0

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

Q96BY2

O95071

0

ubiquitination

down-regulates quantity by destabilization

0.345

We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells.

SIGNOR-278581

Q38SD2

P53350

0

phosphorylation

up-regulates activity

0.345

Here we show that LRRK1 is a PLK1 substrate that is phosphorylated on Ser 1790. PLK1 phosphorylation is required for CDK1-mediated activation of LRRK1 at the centrosomes

SIGNOR-275467

P29353

P40189

0

binding

up-regulates

0.345

Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase.

SIGNOR-250574

O00213

O00141

0

phosphorylation

down-regulates activity

0.345

In the present study, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 attenuates the interaction between FE65 and APP (XREF_FIG).|In this regard, we demonstrated that phosphorylation of FE65 Ser 610 by SGK1 abolishes the effect of FE65 on APP processing and the amount of secreted Abeta is comparable to APP + Mock control (XREF_FIG).

SIGNOR-278220

Q5JR12

P45983

0

phosphorylation

down-regulates

0.344

Specific phosphorylation of pp2czeta at ser (92) by stress-activated jnk attenuates its phosphatase activity in cells.

SIGNOR-178930

O43663

Q00536

0

phosphorylation

up-regulates activity

0.344

Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process

SIGNOR-273017

Q96FI4

Q03468

0

binding

up-regulates activity

0.344

CSB stimulates NEIL1 incision activity in vitro, and CSB and NEIL1 co-immunoprecipitate and co-localize in HeLa cells.

SIGNOR-251931

P61978

Q05655

0

phosphorylation

down-regulates

0.344

Ser302 is a major k protein site phosphorylated by pkcdelta in vitrothe ability of pkc_ to inducibly bind and phosphorylate k protein may serve not only to alter the activity of k protein itself, but k protein may also provide an avenue for pkc_ to engage in a cross-talk with other k protein molecular partners in response to specific changes in the extracellular environment

SIGNOR-67515

Q9BQ15

Q9UKA1

0

binding

down-regulates quantity by destabilization

0.344

Here, we report that hSSB1 is the bona fide substrate for an Fbxl5-containing SCF (Skp1-Cul1-F box) E3 ligase. Fbxl5 interacts with and targets hSSB1 for ubiquitination and degradation, which could be prevented by ATM-mediated hSSB1 T117 phosphorylation.

SIGNOR-271655

Q9Y5T5

P53350

0

phosphorylation

up-regulates activity

0.344

Plk1 phosphorylates and activates Usp16. In vitro phosphorylation of Usp16 with single (S330A, S386A, or S486A) or collective 3A (S330A/S386A/S486A) mutation showed that Plk1 phosphorylated Usp16 at all three sites (Fig. S2 D).

SIGNOR-274015

Q92934

O75582

0

phosphorylation

down-regulates activity

0.344

Phosphorylation of Bad at Ser112 in response to growth factors or cytokines is generally linked to cell survival. Knockdown of MSK1 suppressed Bad phosphorylation after calcium ionophore A23187 treatment in neuronal cells

SIGNOR-262990

P60709

Q9Y613

0

binding

up-regulates quantity by stabilization

0.344

Fhos, a mammalian formin, directly binds to F-actin via a region N-terminal to the FH1 domain and forms a homotypic complex via the FH2 domain to promote actin fiber formation

SIGNOR-276613

Q13330

P78368

0

phosphorylation

up-regulates activity

0.344

CKI-gamma2 could further potentiate the ER corepressive function of metastasis-associated protein-1 short form.|These findings identified metastasis-associated protein-1 short form as a target of CKI-gamma2, and provided new evidence to suggest that CKI-gamma2 phosphorylates and modulates the functions of metastasis-associated protein-1 short form, and that these extranuclear effects of estrogen might have important implications in regulating the functions of metastasis-associated protein-1 short form in human mammary epithelial and cancer cells.

SIGNOR-280236

Q13351

P68400

0

phosphorylation

up-regulates activity

0.344

Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41

SIGNOR-241361

P04626

O14672

0

cleavage

up-regulates activity

0.344

The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.

SIGNOR-259845

P50148

P50406

0

binding

up-regulates activity

0.344

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-257340

P61586

Q9NPG1

0

binding

up-regulates activity

0.344

Upon ligand binding, non-canonical wnt signaling controls tissue polarity and cell movement through the activation of rhoa, c-jun n-terminal kinase (jnk), and nemo-like kinase (nlk) signaling cascades.

SIGNOR-167865

Q13105

P51610

0

binding

down-regulates activity

0.344

We show here that HCF-1 directly binds to the Myc-interacting protein Miz-1. HCF-1 Represses Gal4-Miz-1-mediated Transcriptional Activation

SIGNOR-223590

P06213

P23467

0

dephosphorylation

down-regulates

0.344

Identification of tyrosine phosphatases that dephosphorylate the insulin receptor.

SIGNOR-75997

P09629

P68400

0

phosphorylation

down-regulates activity

0.344

Thus, we concluded that CKII can phosphorylate HOXB7 in vitro and that this phosphorylation occurs at both of the CKII target sites, S133 and T204. | Wild-type HOXB7 inhibited the differentiation of 32D cells, whereas mutations in the Pbx-binding pentapeptide motif or the DNA-binding homeodomain, as well as internal deletions of the N-terminal unique region, blocked this effect. Interestingly, mutations eliminating two target sites for casein kinase II, the glutamate-rich C terminus, or the first 14 amino acids of HOXB7, led to enhanced 32D differentiation.

SIGNOR-250896

Q14161

Q05209

0

dephosphorylation

down-regulates

0.344

Conversely, a gfp-pkl phosphorylation mutant, y286/392/592f (gfp-pkl triple yf) (brown et al., 2005), was not phosphorylated during adhesion and the addition of ptp-pest had no effect, suggesting one or more of these tyrosine residues are dephosphorylated by ptppest. Taken together, these data strongly suggest pkl as a direct substrate for ptp-pest.

SIGNOR-142719

P40692

P00519

0

phosphorylation

up-regulates quantity by stabilization

0.344

We also observed phosphorylation of MLH1 by ABL1 in an in vitro kinase assay with purified recombinant ABL1 and MLH1, confirming there is a direct phosphorylation between ABL1 and the MLH1 component of the MLH1-PMS2 heterodimer.|we propose that ABL1 prevents MLH1 from being targeted for degradation by the chaperone Hsp70 and that in the absence of ABL1 activity at least a portion of MLH1 is degraded.

SIGNOR-279581

P15056

O00141

0

phosphorylation

down-regulates activity

0.344

Serum- and glucocorticoid-inducible kinase SGK phosphorylates and negatively regulates B-Raf.|We observed that SGK inhibits B-Raf activity.

SIGNOR-279110

Q14807

P06493

0

phosphorylation

up-regulates activity

0.344

Cdc2-mediated phosphorylation of kid controls its distribution to spindle and chromosomes. We identify ser427 and thr463 as m phase-specific phosphorylation sites and cdc2-cyclin b as a thr463 kinase. Kid with a thr463 to alanine mutation fails to be localized on chromosomes and is only detected along spindles, although it retains the ability to bind dna or chromosomes

SIGNOR-100964

P33151

O00192

0

binding

up-regulates quantity by stabilization

0.344

To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.

SIGNOR-252129

Q8WUI4

Q7KZI7

0

phosphorylation

down-regulates

0.344

We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function

SIGNOR-149583

P35638

P68400

0

phosphorylation

down-regulates activity

0.344

CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation. | The serine to alanine substituted site CHOP mutant was not phosphorylated by CK2, indicating that serines 14–15 and 30–31 of CHOP are the CK2 phosphoacceptor sites

SIGNOR-250850

Q99459

O00311

0

phosphorylation

down-regulates activity

0.344

During SPOC, Dbf4 binds to Cdc5 and promotes Cdc7-mediated phosphorylation of Cdc5, which then presumably prevents Cdc5 from recognizing its substrates in the MEN pathway .

SIGNOR-280203

P53396

Q9H0H3

0

binding

down-regulates quantity by destabilization

0.344

Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells.

SIGNOR-272333

P48729

Q5T0W9

0

binding

up-regulates quantity

0.344

We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.

SIGNOR-273746

O94763

P23443

0

phosphorylation

down-regulates activity

0.344

Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.

SIGNOR-262943

P63092

Q14833

0

binding

up-regulates activity

0.344

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264082

P46934

P27216

0

relocalization

up-regulates quantity

0.344

Annexin XIII has two known isoforms, a and b, that are apically localized, although XIIIa is also found in the basolateral compartment. In vitro binding and coprecipitation experiments showed that the Nedd4-C2 domain interacts with both annexin XIIIa and b in the presence of Ca2+, and the interaction is direct and optimal at 1 μM Ca2+.These results suggest that the apical membrane localization of Nedd4 is mediated by an association of its C2 domain with the apically targeted annexin XIIIb.

SIGNOR-272571

Q96EB6

Q13043

0

phosphorylation

down-regulates activity

0.344

We found that MST1 increases p53 acetylation and transactivation by inhibiting the deacetylation of Sirtuin 1 (Sirt1) and its interaction with p53 and that Sirt1 can be phosphorylated by MST1 leading to the inhibition of Sirt1 activity.

SIGNOR-279574

P01106

Q9Y4K3

0

ubiquitination

down-regulates activity

0.344

We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).

SIGNOR-278563

P03372

P62877

0

ubiquitination

down-regulates quantity by destabilization

0.344

I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERalpha protein.

SIGNOR-271434

Q13976

P17252

0

phosphorylation

up-regulates

0.344

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

SIGNOR-98803

Q9BQS8

Q9H0B6

0

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

Q04759

P06241

0

phosphorylation

up-regulates

0.344

Further indications of direct interaction are that p59fyn potentiates ?PKC Catalytic activity and that ?PKC Is a substrate for tyrosine phosphorylation by p59fyn.

SIGNOR-68798

Q9C035

P19474

0

monoubiquitination

up-regulates quantity

0.344

Here, we show that TRIM5alpha functions as a RING-finger-type E3 ubiquitin ligase both in vitro and in vivo and ubiquitinates itself in cooperation with the E2 ubiquitin-conjugating enzyme UbcH5B. Thus, the ubiquitination of TRIM5alpha is catalyzed by itself and Ro52. Unexpectedly, although TRIM5alpha is ubiquitinated, our results have revealed that the proteasome inhibitors MG115 and MG132 do not stabilize it in HeLa cells, suggesting that the ubiquitination of TRIM5alpha does not lead to proteasomal degradation. Importantly, TRIM5alpha is clearly conjugated by a single ubiquitin molecule (monoubiquitination). Our monoubiquitin-fusion assay suggests that monoubiquitination is a signal for TRIM5alpha to translocate from cytoplasmic bodies to the cytoplasm.

SIGNOR-271672

P21860

Q01973

0

phosphorylation

up-regulates activity

0.343

Here we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and pro-apoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation, as well as kinase activity-independent sustainment of the EGFR-ERBB3 association, ERBB3 phosphorylation, and consequential PI3K activation.|ROR1 knockdown decreased phosphorylations of ERBB3, c-Src, and AKT in NKX2-1 + / ROR1 + NCI-H1975, SK-LC-5, and NCI-H358 cells.

SIGNOR-279279

Q13501

P06493

0

phosphorylation

up-regulates

0.343

Here we show that cdk1 phosphorylates p62 in vitro and in vivo at t269 and s272, which is necessary for the maintenance of appropriate cyclin b1 levels and the levels of cdk1 activity necessary to allow cells to properly enter and exit mitosis.

SIGNOR-169012

O14920

P53350

0

phosphorylation

down-regulates

0.343

Plk1 phosphorylates serines 733, 740, and 750 in the gammabd of ikkbeta in vitro. Phosphorylating gammabd with plk1 decreased its affinity for ikkgamma

SIGNOR-181802

P42224

P00519

0

phosphorylation

up-regulates activity

0.343

Our study unexpectedly found that c-Abl, another kinase other than JAKs, also contributes to STAT1 Y701 phosphorylation independently (XREF_FIG).|reported that c-Abl, but not Arg, could induce neuronal loss by prompting STAT1 activation and interferon production.

SIGNOR-279491

Q99717

Q9UNE7

0

ubiquitination

down-regulates

0.343

In ad-dition, some proteins (e.g. Chip, carboxyl terminus of hsc70-interacting protein) inhibit the signaling activi-ties of smad1/5 by recruiting smad1/5 from the functional r-/co-smad complex and further pro-moting the ubiquitination and degradation of smad1/5 in a chaperone-independent manne

SIGNOR-195690

Q9UGK3

O60674

0

phosphorylation

up-regulates activity

0.343

To examine this possibility, STAP-2 was co-transfected with constitutively active tyrosine kinases in HEK-293 cells. STAP-2 was strongly phosphorylated by various tyrosine kinases, including v-Src (Fig.2 A-a), a JAK2 tyrosine kinase |On the other hand, the phosphorylation levels of Y22F, Y310F, and Y322F by GST-JH1 were reduced to 8060% of the levels of wild-type STAP-2, which suggests that these three are potential phosphorylation sites by activated JAK2.

SIGNOR-249372

P08754

P11229

0

binding

up-regulates activity

0.343

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-256878

O43318

Q9BZR9

0

polyubiquitination

up-regulates activity

0.343

These results suggest that TRIM8 could mediate K63-linked polyubiquitination of TAK1 at residue K158.These results suggest that TRIM8 is involved in TNFα- and IL-1β–induced NF-κB activation by mediating K63-linked TAK1 polyubiquitination and subsequent activation.

SIGNOR-271890

P50613

P41743

0

phosphorylation

up-regulates activity

0.343

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

SIGNOR-280088

Q15256

P17612

0

phosphorylation

down-regulates activity

0.343

The PKA phosphorylation site on PTP-SL was identified as the Ser(231) residue. treatment of COS-7 cells with PKA activators, or overexpression of the Calpha catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38alpha by wild-type PTP-SL, but not by a PTP-SL S231A mutant.‚

SIGNOR-250038

Q13351

P19784

0

phosphorylation

up-regulates activity

0.343

Regulation of erythroid Krppel-like factor (EKLF) transcriptional activity by phosphorylation of a protein kinase casein kinase II site within its interaction domain. the transactivation capability of EKLF is augmented by co-transfection of CKIIalpha. in vitro assays demonstrate that CKIIalpha interacts with EKLF, and that the EKLF interaction domain is phosphorylated by CKII only at Thr-41

SIGNOR-241365

Q13158

O14965

0

phosphorylation

up-regulates

0.343

Here, we report that aur-a phosphorylates s203 of the fas associated with death domain protein (fadd)phosphorylation of s203 by aur-a serves to prime fadd for plk1-mediated phosphorylation at s194

SIGNOR-176739

P12830

P54253

0

transcriptional regulation

up-regulates quantity by expression

0.343

Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner

SIGNOR-261577

O00459

P36897

0

binding

up-regulates

0.343

These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.

SIGNOR-227531

Q92945

P31751

0

phosphorylation

down-regulates

0.343

AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRPs ability to promote rapid mRNA decay.

SIGNOR-151220

P46109

Q18PE1

0

binding

up-regulates activity

0.343

Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7.

SIGNOR-273848

P36871

Q13153

0

phosphorylation

up-regulates

0.343

The signaling kinase p21-activated kinase 1 (pak1) binds to, phosphorylates and enhances the enzymatic activity of phosphoglucomutase 1 (pgm),

SIGNOR-127135

P15172

Q7Z6Z7

0

ubiquitination

down-regulates quantity

0.343

Importantly, addition of WT HUWE1 to a proteolytic reaction mixture enhanced the degradation of MyoD.|Mass-spectrometry analyses show that HUWE1 can ubiquitinate MyoD at its N-terminal residue, though the preferred sites are - at least in a cell free system - the internal lysines of the protein.

SIGNOR-278694

P54868

Q9NXA8

0

post translational modification

up-regulates activity

0.343

We demonstrate that SIRT5 regu-lates succinylation of the rate-limiting ketogenicenzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(HMGCS2) both in vivo and in vitro.|Succinylation of Lysine Residues within the SubstrateBinding Pocket Inhibits HMGCS2 Activity|Here, we use a label-freequantitative proteomic approach to characterizethe lysine succinylome in liver mitochondria and itsregulation by the desuccinylase SIRT5

SIGNOR-267641

P19429

P17252

0

phosphorylation

up-regulates activity

0.343

In addition to the established phosphorylation sites (S22 and S23) we found that S38 and S165 were the other two main sites of phosphorylation. | Phosphorylation of S22/23A also decreased its affinity for troponin C indicating that phosphorylation of S38 and/or S165 impedes binding of troponin I to troponin C. Formation of a troponin I/troponin C complex prior to cAMP-dependent protein kinase treatment did not prevent overphosphorylation.

SIGNOR-249066

P68104

P36897

0

phosphorylation

down-regulates

0.343

Phosphorylation of eEF1A1 at Ser300 by T_R-I results in inhibition of mRNA translation

SIGNOR-167943

Q9Y6W5

Q96EV8

0

binding

up-regulates activity

0.343

Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Although dysbindin-1, WAVE2 and Abi-1 form a ternary complex, dysbindin-1 promoted the binding of WAVE2 to Abi-1.

SIGNOR-265659

P49841

Q02750

0

phosphorylation

up-regulates activity

0.343

In vitro kinase assay was carried out using a recombinant human active mek1 and we found that gsk-3beta was phosphorylated on tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with u0126 inhibited serum-induced nuclear translocation of gsk-3beta. These results suggested that mek1/2 induces tyrosine phosphorylation of gsk-3beta and this cellular event might induce nuclear translocation of gsk-3beta.

SIGNOR-236622

Q14847

P00519

0

phosphorylation

up-regulates

0.343

C-abl activation by apoptotic agents specifically promotes phosphorylation of lasp-1 at tyrosine 171, which is associated with the loss of lasp-1 localization to focal adhesions and induction of cell death. Thus, lasp-1 is a dynamic focal adhesion protein necessary for cell migration and survival in response to growth factors and ecm proteins.

SIGNOR-124719

O94916

P29350

0

dephosphorylation

down-regulates activity

0.343

We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity

SIGNOR-248467

Q38SD2

P00533

0

phosphorylation

down-regulates activity

0.343

In this study, we demonstrate that EGFR regulates the kinase activity of LRRK1 via tyrosine phosphorylation and that this is required for proper endosomal trafficking of EGFR. Phosphorylation of LRRK1 at Tyr-944 results in reduced LRRK1 kinase activity.

SIGNOR-262856

P10644

P24941

0

phosphorylation

up-regulates

0.343

In this context, we have identified rialpha as a novel substrate for the g(1)/s-cyclin-dependent kinase, cdk2/cyclin e, and found that rialpha is specifically phosphorylated at the serine residue.

SIGNOR-145577

O14818

P51149

0

binding

up-regulates activity

0.343

Rab7 Forms a Complex with the Proteasome -Subunit XAPC. In this study the proteasome alpha-subunit XAPC7 (also known as PSMA7, RC6-1, and HSPC in mammals) was identified to interact specifically with Rab7 and was recruited to multivesicular late endosomes through this interaction.

SIGNOR-261303

Q02790

P68400

0

phosphorylation

down-regulates activity

0.343

Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. | Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90

SIGNOR-250865

Q01860

P27361

0

phosphorylation

down-regulates

0.343

Phosphorylation of this site downregulates nanog, sox2, rex1 and upregulates bmp4, gata6, ddlx5.

SIGNOR-192101

P16662

P12931

0

phosphorylation

up-regulates

0.343

Overexpression of regular or active src, but not dominant-negative src, in 2b7-transfected cos-1 cells increased 2b7 activity and phospho-y438-2b7 by 50%

SIGNOR-184613

Q8TDQ1

P06241

0

phosphorylation

up-regulates activity

0.343

Y236 (YVTM) and Y263 (YCNM) fit with the consensus motif reported to bind the p85α regulatory subunit of PI3K (16). |The association between IREM-1 and p85α was only perceived in the presence of c-Fyn, suggesting that tyrosine phosphorylation of IREM-1 cytoplasmic tail of IREM-1 was required for the interaction.

SIGNOR-275620

P07333

Q00341

0

transcriptional regulation

down-regulates quantity by repression

0.342

Vigilin (Vgl1) is essential for heterochromatin formation, chromosome segregation, and mRNA stability and is associated with autism spectrum disorders and cancer: vigilin, for example, can suppress proto-oncogene c-fms expression in breast cancer.

SIGNOR-266696

P29590

P68400

0

phosphorylation

down-regulates

0.342

Here we show that ck2 regulates pml protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at ser517.

SIGNOR-148306

P04049

Q13131

0

phosphorylation

down-regulates

0.342

Ampk also phosphorylated full-length, kinase-defective raf-1 (k375m) to generate two [32p]phosphopeptides, one co-migrating with synthetic tryptic peptide containing phospho-ser621 and the other with phospho-ser259. The catalytic subunit of PKA also phosphorylated Ser621 in vitro, while its overexpression in intact cells resulted in increased phosphorylation of Ser621 and decreased activity of Raf-1. These results suggest that phosphorylation of Ser621 inactivates Raf-1, but do not prove that PKA is responsible for this in vivo.

SIGNOR-47148

Q9Y4H2

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.342

Taken together, these results indicate that the IRS2 gene is a direct target for CREB action in vivo

SIGNOR-278145

P06127

P68400

0

phosphorylation

up-regulates

0.342

In this study, we use jurkat t cell transfectants of cd5 cytoplasmic tail mutants to reveal phosphorylation sites relevant to signal transduction. Our results show that casein kinase ii (ckii) is responsible for the constitutive phosphorylation of cd5 molecules at a cluster of three serine residues located at the extreme c terminus (s458, s459, and s461)

SIGNOR-62311