GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q13950	P27361	0	phosphorylation	up-regulates	0.565	In this study, we identified two phosphorylation sites in runx2 at ser301 and ser319 that are required for mapk-dependent activation of runx2 transcriptional activity and osteoblast differentiation.	SIGNOR-188347
Q13153	P35240	1	phosphorylation	down-regulates	0.645	Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,	SIGNOR-159764
Q969R2	P48729	0	phosphorylation	up-regulates activity	0.2	CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.\|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.	SIGNOR-264877
P06239	Q96LC7	1	phosphorylation	up-regulates	0.26	These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling	SIGNOR-112491
P10398	P12931	0	phosphorylation	up-regulates activity	0.489	A-raf behaves like raf-1, being weakly activated by oncogenic ras more strongly activated by oncogenic src, and these signals synergize to give maximal activation	SIGNOR-236459
P63000	O60890	0	gtpase-activating protein	up-regulates activity	0.591	OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro	SIGNOR-268399
P19784	Q99801	1	phosphorylation	up-regulates	0.315	In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation.	SIGNOR-145501
P78527	P67809	1	phosphorylation	up-regulates activity	0.338	The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.	SIGNOR-277611
O14757	O15350	1	phosphorylation	up-regulates	0.536	We found that endogenous p73alpha is serine phosphorylated by endogenous chk1 upon dna damage, which is a mechanism required for the apoptotic-inducing function of p73alpha.	SIGNOR-118913
P27361	P27708	1	phosphorylation	up-regulates	0.2	Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol	SIGNOR-137179
Q96EB6	P23025	1	deacetylation	up-regulates activity	0.511	SIRT1 deacetylates XPA at residues K63, K67, and K215 to promote interactions with ATR	SIGNOR-262294
Q9NZJ5	O15294	1	phosphorylation	up-regulates activity	0.2	Collectively, these results indicate that upon cold and \u03b2-adrenergic stimulation PERK-activated OGT catalyzes the O-GlcNAcylation of CK2\u03b1 and TOM70 which enhances MIC19 import into the mitochondria increasing cristae formation and cell respiration (Figure 7I).\|Here, we report that the ER-resident kinase PERK is activated upon cold or \u03b2-adrenergic stimulation and directly phosphorylates OGT.	SIGNOR-279736
Q9UQM7	P51790	1	phosphorylation	up-regulates activity	0.337	Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current\|The N-terminus of CLC-3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII-dependent Cl(-) conductance, indicating that this residue is important in the gating of CLC-3 at the plasma membrane.	SIGNOR-275863
Q8WWN8	P60953	1	gtpase-activating protein	down-regulates activity	0.521	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260457
P04150	P45983	0	phosphorylation	down-regulates	0.638	Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.	SIGNOR-93558
Q01954	Q9NRD5	0	relocalization	up-regulates activity	0.307	we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction	SIGNOR-223414
P03372	P51812	0	phosphorylation	up-regulates	0.403	S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.	SIGNOR-182958
P27361	O60716	1	phosphorylation	down-regulates activity	0.293	Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation.	SIGNOR-277506
P54646	P08559	1	phosphorylation	up-regulates activity	0.2	AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex	SIGNOR-276838
P53350	O15530	0	phosphorylation	up-regulates activity	0.2	Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency	SIGNOR-243519
P49841	Q13887	1	phosphorylation	down-regulates	0.368	Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5	SIGNOR-203627
P22460	Q13131	0	phosphorylation	down-regulates activity	0.2	Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560	SIGNOR-277814
Q15120	P29803	1	phosphorylation	down-regulates	0.563	Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3)	SIGNOR-143974
P43694	P48775	1	transcriptional regulation	down-regulates quantity by repression	0.252	GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes.	SIGNOR-268994
Q8NBJ5	Q15848	1	palmitoylation	up-regulates activity	0.2	We conclude that GLT25D1 regulates HMW adiponectin secretion and lipid accumulation, consistent with changes in mice after high-fat feeding. These results suggest a novel function of GLT25D1 leading to decreased HMW adiponectin secretion in early obesity.	SIGNOR-261149
P53355	Q96FA3	1	phosphorylation	down-regulates quantity by destabilization	0.2	DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover.	SIGNOR-277531
Q96PU5	Q13114	1	ubiquitination	up-regulates activity	0.27	Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.\|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1.	SIGNOR-278587
Q14653	P12931	0	phosphorylation	up-regulates activity	0.314	Mechanistically, the progesterone-PGR axis activates SRC, which then mediates phosphorylation of IRF3 at Y107.\|Taken together, these results suggest that P4 induces PGR-dependent activation of SRC, which promotes virus-triggered activation of IRF3 as well as induction of downstream antiviral genes.In the above experiments, we noticed that SeV-induced phosphorylation of IRF3S386 but not phosphorylation of TBK1S172 (p-TBK1S172, a hallmark for TBK1 activation) was increased by P4 treatment (Fig. 4g) or decreased by knockout of PGR (Fig. 4h).	SIGNOR-279118
O00141	P19634	1	phosphorylation	up-regulates activity	0.304	Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].\|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.	SIGNOR-280123
Q96CX2	O14965	0	phosphorylation	up-regulates activity	0.272	In addition, Aurora A phosphorylated KCTD12 at serine 243, thereby initiating a positive feedback loop necessary for KCTD12 to exert its cancer-promoting effects.	SIGNOR-273544
Q03135	Q8ND25	0	polyubiquitination	down-regulates quantity by destabilization	0.364	The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. ZNRF1 mediates CAV1 polyubiquitination at lysine 39 and promote CAV1 degradation to modulate TLR4-mediated immune response.	SIGNOR-272327
P30304	P14635	1	dephosphorylation	up-regulates activity	0.855	Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .	SIGNOR-277137
P35125	P60953	0	relocalization	up-regulates	0.359	In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.	SIGNOR-98935
Q08209	Q12968	1	dephosphorylation	up-regulates	0.538	Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.	SIGNOR-176376
P56962	Q9UHD2	0	phosphorylation	up-regulates activity	0.291	Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202.	SIGNOR-273812
Q07955	Q96SB4	0	phosphorylation	up-regulates	0.799	These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.	SIGNOR-66465
Q8IZQ8	P49841	0	phosphorylation	down-regulates activity	0.397	In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity	SIGNOR-251247
P55957	P45983	0	phosphorylation	up-regulates activity	0.594	(b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay).	SIGNOR-279076
P60891	O95835	0	phosphorylation	down-regulates quantity by destabilization	0.2	Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.	SIGNOR-276505
Q16584	P49841	0	phosphorylation	up-regulates activity	0.336	Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).\|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).	SIGNOR-279615
Q6FI13	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265396
O60260	Q00535	0	phosphorylation	down-regulates	0.2	Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo.	SIGNOR-153445
P05129	P25098	1	phosphorylation	up-regulates	0.2	Phosphorylation of grk2 by protein kinase c abolishes its inhibition by calmodulinin vitro, grk2 was preferentially phosphorylated by pkc isoforms alpha, gamma, and delta	SIGNOR-83231
P34947	P30411	1	phosphorylation	down-regulates activity	0.489	Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.	SIGNOR-251208
Q92466	Q9UPU5	0	deubiquitination	up-regulates	0.703	Usp24-mediated ddb2 deubiquitination prevents ddb2 degradation	SIGNOR-199731
P24666	P31749	1	dephosphorylation	down-regulates activity	0.321	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248455
P01008	P00742	1	cleavage	down-regulates activity	0.877	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-264138
O43318	P49593	0	dephosphorylation	down-regulates activity	0.395	However, our current work shows that POPX2 can downregulate TAK1 and affect the anti-apoptotic activities of TAK1, implying that silencing POPX2 could facilitate TAK1 activation and will lead to increased cell survival.\|We have also demonstrated that POPX2 can directly dephosphorylate TAK1 (XREF_FIG).	SIGNOR-277047
P13500	Q16665	0	transcriptional regulation	up-regulates quantity by expression	0.403	These findings suggest that both MCP-1 and MCP-5 are HIF-1 target genes and that HIF-1α is involved in transcriptional induction of these two chemokines in astrocytes by hypoxia.	SIGNOR-251719
P49841	E9PAV3	1	phosphorylation	down-regulates	0.2	Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation.	SIGNOR-123262
P28482	P24928	1	phosphorylation	down-regulates	0.311	Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.	SIGNOR-120160
P46020	P22694	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-267413
P06493	P52732	1	phosphorylation	up-regulates activity	0.638	Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles.	SIGNOR-273887
Q5VWQ8	Q13546	0	phosphorylation	up-regulates activity	0.426	We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC.	SIGNOR-259976
P45984	P04637	1	phosphorylation	up-regulates	0.747	These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells.	SIGNOR-115835
O95886	Q9UPX8	1	relocalization	up-regulates activity	0.788	SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).	SIGNOR-264593
P55210	P09874	1	cleavage	down-regulates	0.719	Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis.	SIGNOR-83703
Q8NEZ5	P35613	1	ubiquitination	down-regulates quantity by destabilization	0.427	F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells	SIGNOR-273452
P19484	P05771	0	phosphorylation	up-regulates activity	0.33	This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor.	SIGNOR-255315
Q00987	P46934	0	ubiquitination	up-regulates quantity by stabilization	0.466	NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ].	SIGNOR-278769
P48730	P27707	1	phosphorylation	up-regulates activity	0.339	Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.\|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.	SIGNOR-280233
Q16659	Q9Y6Q9	1	phosphorylation	up-regulates	0.481	Here, we report that erk3 interacted with and phosphorylated steroid receptor coactivator 3 (src-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (s857)	SIGNOR-196957
Q92502	P60953	1	gtpase-activating protein	down-regulates activity	0.511	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260520
Q5VTY9	Q15465	1	palmitoylation	up-regulates	0.683	Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos	SIGNOR-124118
P62987	Q93009	0	cleavage	up-regulates quantity	0.735	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270823
P01137	P02452	1	transcriptional regulation	up-regulates quantity by expression	0.485	COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity	SIGNOR-277678
O75398	Q05925	1	transcriptional regulation	up-regulates quantity by expression	0.2	Deaf1 is the first transcription factor implicated in the regulation of En1, a critical determinant of eccrine fate, within keratinocytes.	SIGNOR-269062
P01112	Q07890	0	guanine nucleotide exchange factor	up-regulates	0.79	Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.	SIGNOR-175262
P68400	Q13133	1	phosphorylation	down-regulates	0.2	Ck2? Also phosphorylated lxr? At s198 in vitro, suggesting that ck2 may be a bona fide s198 kinase. our results show that macrophage lxr? Phosphorylation at s198 affects the transcriptional activity of the receptor in a gene-specific manner (fig. ?(Fig.3a)3a) and restricts the repertoire of genes regulated by lxr?	SIGNOR-160640
Q9BX66	P00519	0	phosphorylation	up-regulates activity	0.424	We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.	SIGNOR-278153
P23396	P31749	0	phosphorylation	up-regulates activity	0.368	Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.	SIGNOR-259815
P06213	Q9Y4H2	1	phosphorylation	down-regulates activity	0.757	Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor.	SIGNOR-251319
Q9NR19	Q14457	1	transcriptional regulation	up-regulates quantity by expression	0.2	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276561
Q9Y365	P68400	0	phosphorylation	down-regulates	0.409	Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity	SIGNOR-155740
Q14703	Q96BA8	1	cleavage	up-regulates	0.571	Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes	SIGNOR-143785
O96028	P38398	0	ubiquitination	down-regulates quantity by destabilization	0.2	Proteomic data analysis revealed interaction between NSD2 and BRCA1 and further study revealed that BRCA1 ubiquitinates NSD2 at K292 residue.\|These results suggested that BRCA1 interacts with and promotes degradation of NSD2 via polyubiquitination .	SIGNOR-278745
O15530	P17252	1	phosphorylation	up-regulates	0.417	One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.	SIGNOR-126066
O75385	P06733	1	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274029
Q9UQB3	P49841	0	phosphorylation	down-regulates quantity	0.347	Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.\|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin.	SIGNOR-279719
Q12879	Q13627	0	phosphorylation	up-regulates quantity	0.397	DYRK1A enhances the surface expression of GluN1 and GluN2A receptors.\|Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser 1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons.	SIGNOR-279327
O00141	P42858	1	phosphorylation	down-regulates	0.372	The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.	SIGNOR-121349
P42684	P00519	0	phosphorylation	up-regulates	0.517	The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization	SIGNOR-134396
P19784	P13349	1	phosphorylation	up-regulates activity	0.307	Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.	SIGNOR-251016
Q02156	P17302	1	phosphorylation	down-regulates activity	0.44	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-144465
P45983	Q96LC9	1	phosphorylation	up-regulates activity	0.689	Activated JNK causes BimL and Bmf phosphorylation in vivo. It is known that UV radiation causes the release of Bim and Bmf from dynein and myosin V motor complexes and that these proteins cause Bax/Bak-dependent apoptosis . The results of this study demonstrate that JNK can engage this apoptotic pathway by phosphorylation of BH3-only proteins, including Bim and Bmf.	SIGNOR-250116
Q96T68	P84243	1	methylation	up-regulates activity	0.2	Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.	SIGNOR-263894
P78362	P23443	0	phosphorylation	up-regulates activity	0.355	Altogether, these results identify S6K1-phosphorylated SRPK2 as an essential mediator of IGF1-stimulated SG formation in hPDAC cells.\|The nodes of the core SG network are known to contribute to SG formation to varying degrees and it is possible that S6K1-stimulated SRPK2 may impact their contribution; this is consistent with the predicted model whereby SG assembly is subject to regulation by positive and negative cooperativity of extrinsic factors with the core network interactions (14).	SIGNOR-280121
Q7Z6J0	O14964	1	ubiquitination	down-regulates quantity	0.246	Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.	SIGNOR-278575
P78352	P00519	0	phosphorylation	up-regulates activity	0.441	Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.\|c-Abl modulates the synaptic contact number and PSD-95 clustering.	SIGNOR-278391
P22612	Q14896	1	phosphorylation	up-regulates	0.275	Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).	SIGNOR-163788
P11309	P68431	1	phosphorylation	down-regulates activity	0.2	Pim1-dependent phosphorylation of histone h3 at serine 10 is required for myc-dependent transcriptional activation and oncogenic transformation.	SIGNOR-156946
P35232	P10721	0	phosphorylation	up-regulates activity	0.2	In this study, we showed that c-Kit associates with PHB to upregulate phospho-PHB in the lipid raft of the plasma membrane.\|c-Kit phosphorylates PHB at the Tyr259 residue.	SIGNOR-278362
Q6U7Q0	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.2	CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction.	SIGNOR-264891
P31749	P23588	1	phosphorylation	up-regulates	0.393	Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.	SIGNOR-252520
P17302	Q02156	0	phosphorylation	down-regulates activity	0.44	Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.\|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.	SIGNOR-144465
O95628	Q96T37	1	ubiquitination	down-regulates quantity by destabilization	0.359	We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4).	SIGNOR-271466
Q9H4B6	O00506	0	phosphorylation	down-regulates activity	0.28	STK25 inhibits the ability of SAV1 to counteract STRIPAK.\|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG).	SIGNOR-278369
Q9HAU4	P25490	1	ubiquitination	down-regulates quantity by destabilization	0.364	In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.\|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1.	SIGNOR-278544
P05067	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.267	These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ).	SIGNOR-280210
O75182	Q5VTB9	0	polyubiquitination	down-regulates quantity by destabilization	0.429	Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B.	SIGNOR-271943

Q13950

P27361

0

phosphorylation

up-regulates

0.565

In this study, we identified two phosphorylation sites in runx2 at ser301 and ser319 that are required for mapk-dependent activation of runx2 transcriptional activity and osteoblast differentiation.

SIGNOR-188347

Q13153

P35240

1

phosphorylation

down-regulates

0.645

Merlin contains a c-terminal serine 518, which is phosphorylated both by p21-activated kinase (pak) and protein kinase a (pka) (shaw et al., 2001;kissil et al., 2002;xiao et al., 2002;alfthan et al., 2004). Phosphorylation at this site is predicted to result in a more open conformation incapable of inhibiting cell growth,

SIGNOR-159764

Q969R2

P48729

0

phosphorylation

up-regulates activity

0.2

CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.

SIGNOR-264877

P06239

Q96LC7

1

phosphorylation

up-regulates

0.26

These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling

SIGNOR-112491

P10398

P12931

0

phosphorylation

up-regulates activity

0.489

A-raf behaves like raf-1, being weakly activated by oncogenic ras more strongly activated by oncogenic src, and these signals synergize to give maximal activation

SIGNOR-236459

P63000

O60890

0

gtpase-activating protein

up-regulates activity

0.591

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

SIGNOR-268399

P19784

Q99801

1

phosphorylation

up-regulates

0.315

In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation.

SIGNOR-145501

P78527

P67809

1

phosphorylation

up-regulates activity

0.338

The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction.DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus.

SIGNOR-277611

O14757

O15350

1

phosphorylation

up-regulates

0.536

We found that endogenous p73alpha is serine phosphorylated by endogenous chk1 upon dna damage, which is a mechanism required for the apoptotic-inducing function of p73alpha.

SIGNOR-118913

P27361

P27708

1

phosphorylation

up-regulates

0.2

Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol

SIGNOR-137179

Q96EB6

P23025

1

deacetylation

up-regulates activity

0.511

SIRT1 deacetylates XPA at residues K63, K67, and K215 to promote interactions with ATR

SIGNOR-262294

Q9NZJ5

O15294

1

phosphorylation

up-regulates activity

0.2

Collectively, these results indicate that upon cold and \u03b2-adrenergic stimulation PERK-activated OGT catalyzes the O-GlcNAcylation of CK2\u03b1 and TOM70 which enhances MIC19 import into the mitochondria increasing cristae formation and cell respiration (Figure 7I).|Here, we report that the ER-resident kinase PERK is activated upon cold or \u03b2-adrenergic stimulation and directly phosphorylates OGT.

SIGNOR-279736

Q9UQM7

P51790

1

phosphorylation

up-regulates activity

0.337

Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current|The N-terminus of CLC-3, which contains a CaMKII consensus sequence, was phosphorylated by CaMKII in vitro, and mutation of the serine at position 109 (S109A) abolished the CaMKII-dependent Cl(-) conductance, indicating that this residue is important in the gating of CLC-3 at the plasma membrane.

SIGNOR-275863

Q8WWN8

P60953

1

gtpase-activating protein

down-regulates activity

0.521

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

SIGNOR-260457

P04150

P45983

0

phosphorylation

down-regulates

0.638

Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription.

SIGNOR-93558

Q01954

Q9NRD5

0

relocalization

up-regulates activity

0.307

we found that the PDZ domain-containing protein PICK1 (protein interacting with C kinase) interacts specifically with the C-termini of BNC1 and ASIC. Our studies showing association of recombinant PICK1 with ASIC and BNC1, and the presence of both PICK1 and ASIC in the synaptosomal fraction

SIGNOR-223414

P03372

P51812

0

phosphorylation

up-regulates

0.403

S6k1 regulates estrogen receptor alpha (eralpha) by phosphorylating it on serine 167, leading to transcriptional activation of eralpha.

SIGNOR-182958

P27361

O60716

1

phosphorylation

down-regulates activity

0.293

Upon TGFβ treatment, activated extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylates T900 of p120-catenin to promote its interaction with Smurf1 and subsequent monoubiquitination. TGFβ promotes monoubiquitination of p120-catenin through Smurf1 to induce junction dissociation.

SIGNOR-277506

P54646

P08559

1

phosphorylation

up-regulates activity

0.2

AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex

SIGNOR-276838

P53350

O15530

0

phosphorylation

up-regulates activity

0.2

Here, we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces MYC phosphorylation and protein accumulation. We show that PDK1-PLK1-MYC signaling is critical for cancer cell growth and survival, and small-molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting of MYC dependency

SIGNOR-243519

P49841

Q13887

1

phosphorylation

down-regulates

0.368

Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5

SIGNOR-203627

P22460

Q13131

0

phosphorylation

down-regulates activity

0.2

Thus, AMPK directly phosphorylates the  subunit of KV1.5 at Ser592 and, to a lesser extent, at Ser560

SIGNOR-277814

Q15120

P29803

1

phosphorylation

down-regulates

0.563

Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3)

SIGNOR-143974

P43694

P48775

1

transcriptional regulation

down-regulates quantity by repression

0.252

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes.

SIGNOR-268994

Q8NBJ5

Q15848

1

palmitoylation

up-regulates activity

0.2

We conclude that GLT25D1 regulates HMW adiponectin secretion and lipid accumulation, consistent with changes in mice after high-fat feeding. These results suggest a novel function of GLT25D1 leading to decreased HMW adiponectin secretion in early obesity.

SIGNOR-261149

P53355

Q96FA3

1

phosphorylation

down-regulates quantity by destabilization

0.2

DAPK1, which directly binds to and phosphorylates Pellino1 at Ser39, leading to Pellino1 poly-ubiquitination and turnover.

SIGNOR-277531

Q96PU5

Q13114

1

ubiquitination

up-regulates activity

0.27

Nedd4l promotes TRAF3 to interact with cIAP1/2 and HECTD3.|Ubiquitination of TRAF3 by Nedd4l promotes interaction of TRAF3 with proteins such as cIAP1/2, HECTD3, and TBK1.

SIGNOR-278587

Q14653

P12931

0

phosphorylation

up-regulates activity

0.314

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

SIGNOR-279118

O00141

P19634

1

phosphorylation

up-regulates activity

0.304

Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.

SIGNOR-280123

Q96CX2

O14965

0

phosphorylation

up-regulates activity

0.272

In addition, Aurora A phosphorylated KCTD12 at serine 243, thereby initiating a positive feedback loop necessary for KCTD12 to exert its cancer-promoting effects.

SIGNOR-273544

Q03135

Q8ND25

0

polyubiquitination

down-regulates quantity by destabilization

0.364

The ubiquitin ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. ZNRF1 mediates CAV1 polyubiquitination at lysine 39 and promote CAV1 degradation to modulate TLR4-mediated immune response.

SIGNOR-272327

P30304

P14635

1

dephosphorylation

up-regulates activity

0.855

Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .

SIGNOR-277137

P35125

P60953

0

relocalization

up-regulates

0.359

In quiescent cells, tre17 is localized to intracellular filamentous and punctate structures in the cytoplasm, folded in an inactive conformation. Upon growth factor addition, cdc42 and rac1 become activated and recruit tre17 to the plasma membrane. Stable membrane localization of tre17 also requires polymerized actin. This recruitment process leads to a conformational change in tre17, such that the n-terminal portion of the molecule further stimulates the accumulation of cortical actin.

SIGNOR-98935

Q08209

Q12968

1

dephosphorylation

up-regulates

0.538

Calcineurin directly dephosphorylates nfat resulting in the nuclear import of nfat.

SIGNOR-176376

P56962

Q9UHD2

0

phosphorylation

up-regulates activity

0.291

Stx17 is phosphorylated by TBK1 whereby phospho-Stx17 controls the formation of the ATG13+FIP200+ mammalian pre-autophagosomal structure (mPAS) in response to induction of autophagy. TBK1 phosphorylates Stx17 at S202.

SIGNOR-273812

Q07955

Q96SB4

0

phosphorylation

up-regulates

0.799

These results suggest that the formation of complexes between sf2/asf and srpks, which is influenced by the phosphorylation state of sf2/asf, may have regulatory roles in the assembly and localization of this splicing factor.

SIGNOR-66465

Q8IZQ8

P49841

0

phosphorylation

down-regulates activity

0.397

In vitro and in vivo (HEK 293 cells) kinase assays with synthetic peptides and full-length myocardin demonstrated that myocardin was a primed GSK3beta substrate, with serines 455 to 467 and 624 to 636 being the major GSK3beta phosphorylation sites. GSK3β phosphorylation at the sites identified inhibits myocardin intrinsic transcriptional activity

SIGNOR-251247

P55957

P45983

0

phosphorylation

up-regulates activity

0.594

(b) Phosphorylation of Bid at Thr59 by JNK1 and JNK2 (in vitro kinase assay).

SIGNOR-279076

P60891

O95835

0

phosphorylation

down-regulates quantity by destabilization

0.2

Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.

SIGNOR-276505

Q16584

P49841

0

phosphorylation

up-regulates activity

0.336

Further, investigation revealed that MLK3 was phosphorylated at two residues Ser789 and Ser793 by GSK3\u03b2 ( xref ).|When, these two sites on MLK3 were mutated to non-phosphorable Ala, the activation of MLK3 by GSK3\u03b2 was blocked, and neuronal cell death upon NGF withdrawal also prevented ( xref ).

SIGNOR-279615

Q6FI13

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265396

O60260

Q00535

0

phosphorylation

down-regulates

0.2

Phosphorylation by cdk5 decreased the auto-ubiquitylation of parkin both in vitro and in vivo.

SIGNOR-153445

P05129

P25098

1

phosphorylation

up-regulates

0.2

Phosphorylation of grk2 by protein kinase c abolishes its inhibition by calmodulinin vitro, grk2 was preferentially phosphorylated by pkc isoforms alpha, gamma, and delta

SIGNOR-83231

P34947

P30411

1

phosphorylation

down-regulates activity

0.489

Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.

SIGNOR-251208

Q92466

Q9UPU5

0

deubiquitination

up-regulates

0.703

Usp24-mediated ddb2 deubiquitination prevents ddb2 degradation

SIGNOR-199731

P24666

P31749

1

dephosphorylation

down-regulates activity

0.321

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248455

P01008

P00742

1

cleavage

down-regulates activity

0.877

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-264138

O43318

P49593

0

dephosphorylation

down-regulates activity

0.395

However, our current work shows that POPX2 can downregulate TAK1 and affect the anti-apoptotic activities of TAK1, implying that silencing POPX2 could facilitate TAK1 activation and will lead to increased cell survival.|We have also demonstrated that POPX2 can directly dephosphorylate TAK1 (XREF_FIG).

SIGNOR-277047

P13500

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.403

These findings suggest that both MCP-1 and MCP-5 are HIF-1 target genes and that HIF-1α is involved in transcriptional induction of these two chemokines in astrocytes by hypoxia.

SIGNOR-251719

P49841

E9PAV3

1

phosphorylation

down-regulates

0.2

Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation.

SIGNOR-123262

P28482

P24928

1

phosphorylation

down-regulates

0.311

Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.

SIGNOR-120160

P46020

P22694

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-267413

P06493

P52732

1

phosphorylation

up-regulates activity

0.638

Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles.

SIGNOR-273887

Q5VWQ8

Q13546

0

phosphorylation

up-regulates activity

0.426

We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC.

SIGNOR-259976

P45984

P04637

1

phosphorylation

up-regulates

0.747

These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells.

SIGNOR-115835

O95886

Q9UPX8

1

relocalization

up-regulates activity

0.788

SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).

SIGNOR-264593

P55210

P09874

1

cleavage

down-regulates

0.719

Caspase-7 cleaves parp;redundancy exists between the caspase-3 and -7 at the level of parp proteolysis.

SIGNOR-83703

Q8NEZ5

P35613

1

ubiquitination

down-regulates quantity by destabilization

0.427

F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells

SIGNOR-273452

P19484

P05771

0

phosphorylation

up-regulates activity

0.33

This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor.

SIGNOR-255315

Q00987

P46934

0

ubiquitination

up-regulates quantity by stabilization

0.466

NEDD4 promotes MDM2 ubiquitination in a dose- and time-dependent manner, whereas depletion of NEDD4 reduced the half-life of endogenous MDM2 [ xref ].

SIGNOR-278769

P48730

P27707

1

phosphorylation

up-regulates activity

0.339

Site-directed mutagenesis demonstrated that only Ser-74 phosphorylation was involved in Deoxycytidine kinase activation by CKI delta, strengthening the key role of this residue in the control of Deoxycytidine kinase activity.|We showed that recombinant CKI delta phosphorylated several residues of bacterially overexpressed Deoxycytidine kinase: Ser-74, but also Ser-11, Ser-15, and Thr-72.

SIGNOR-280233

Q16659

Q9Y6Q9

1

phosphorylation

up-regulates

0.481

Here, we report that erk3 interacted with and phosphorylated steroid receptor coactivator 3 (src-3), an oncogenic protein overexpressed in multiple human cancers at serine 857 (s857)

SIGNOR-196957

Q92502

P60953

1

gtpase-activating protein

down-regulates activity

0.511

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

SIGNOR-260520

Q5VTY9

Q15465

1

palmitoylation

up-regulates

0.683

Our molecular analysis of knockout mice deficient in skn, the murine homolog of the drosophila ski gene, which catalyzes hh palmitoylation, and gene-targeted mice producting a non palmitoylated form of shh indicates that hh palmitoylation is essential for its activity as well as the generation of a protein gradient in the developing embryos

SIGNOR-124118

P62987

Q93009

0

cleavage

up-regulates quantity

0.735

Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.

SIGNOR-270823

P01137

P02452

1

transcriptional regulation

up-regulates quantity by expression

0.485

COL1A1 expression is regulated by upstream genes and the binding of regulatory elements at multiple binding sites upstream of its promoter. During cancer progression, CAFs reorganize and cross-link COL1A1, which accumulates and stiffens in the tumor stroma [12], [18]. This process may involve fibrogenic factors, especially transforming growth factor-beta (TGF-β1). Indeed, a TGF-β1 response sequence was identified 174 nucleotides upstream of the COL1A1 transcription start site, and was shown to up-regulate COL1A1 promoter activity

SIGNOR-277678

O75398

Q05925

1

transcriptional regulation

up-regulates quantity by expression

0.2

Deaf1 is the first transcription factor implicated in the regulation of En1, a critical determinant of eccrine fate, within keratinocytes.

SIGNOR-269062

P01112

Q07890

0

guanine nucleotide exchange factor

up-regulates

0.79

Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.

SIGNOR-175262

P68400

Q13133

1

phosphorylation

down-regulates

0.2

Ck2? Also phosphorylated lxr? At s198 in vitro, suggesting that ck2 may be a bona fide s198 kinase. our results show that macrophage lxr? Phosphorylation at s198 affects the transcriptional activity of the receptor in a gene-specific manner (fig. ?(Fig.3a)3a) and restricts the repertoire of genes regulated by lxr?

SIGNOR-160640

Q9BX66

P00519

0

phosphorylation

up-regulates activity

0.424

We have here identified Tyr360 in CAP as a major phosphorylation site by c-Abl, although Tyr 632 also might contribute since its substitution in combination with the Y360F mutation reduced the phosphorylation of CAP to a very low level. Y360 in CAP is the major phosphorylation site of c-Abl. Since Tyr326 was not a major c-Abl phosphorylation site, we sought to identify a putative other kinase that might be involved in the phosphorylation of Y326 in CAP.

SIGNOR-278153

P23396

P31749

0

phosphorylation

up-regulates activity

0.368

Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.

SIGNOR-259815

P06213

Q9Y4H2

1

phosphorylation

down-regulates activity

0.757

Tyr624 and Tyr628 are involved in the interaction between the IR and the KRLB domain of IRS-2, including tyrosine phosphorylation, and Tyr628 seems to be more important than Tyr624 in this process. the binding between the insulin receptor and the KRLB domain of IRS-2 results in tyrosine phosphorylation of the KRLB domain, and this leads to decreased binding of IRS-2 to the insulin receptor.

SIGNOR-251319

Q9NR19

Q14457

1

transcriptional regulation

up-regulates quantity by expression

0.2

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276561

Q9Y365

P68400

0

phosphorylation

down-regulates

0.409

Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity

SIGNOR-155740

Q14703

Q96BA8

1

cleavage

up-regulates

0.571

Cleavage of oasis by site-1 and site-2 proteases / oasis is cleaved at the membrane under er stress conditions and that its cleaved n-terminal domain translocates into the nucleus;and then activates transcription of target genes

SIGNOR-143785

O96028

P38398

0

ubiquitination

down-regulates quantity by destabilization

0.2

Proteomic data analysis revealed interaction between NSD2 and BRCA1 and further study revealed that BRCA1 ubiquitinates NSD2 at K292 residue.|These results suggested that BRCA1 interacts with and promotes degradation of NSD2 via polyubiquitination .

SIGNOR-278745

O15530

P17252

1

phosphorylation

up-regulates

0.417

One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.

SIGNOR-126066

O75385

P06733

1

phosphorylation

down-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274029

Q9UQB3

P49841

0

phosphorylation

down-regulates quantity

0.347

Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin.

SIGNOR-279719

Q12879

Q13627

0

phosphorylation

up-regulates quantity

0.397

DYRK1A enhances the surface expression of GluN1 and GluN2A receptors.|Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser 1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons.

SIGNOR-279327

O00141

P42858

1

phosphorylation

down-regulates

0.372

The serum- and glucocorticoid-induced kinase sgk inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin.

SIGNOR-121349

P42684

P00519

0

phosphorylation

up-regulates

0.517

The results show that arg is stabilized in response to 0.1 mm h2o2 by autophosphorylation of y-261, consistent with involvement of the arg kinase function in regulating arg levels. The results further demonstrate that c-abl-mediated phosphorylation of arg on y-261 similarly confers arg stabilization

SIGNOR-134396

P19784

P13349

1

phosphorylation

up-regulates activity

0.307

Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites at serine49 and serine133, both of which seem to be necessary for Myf-5 activity.

SIGNOR-251016

Q02156

P17302

1

phosphorylation

down-regulates activity

0.44

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-144465

P45983

Q96LC9

1

phosphorylation

up-regulates activity

0.689

Activated JNK causes BimL and Bmf phosphorylation in vivo. It is known that UV radiation causes the release of Bim and Bmf from dynein and myosin V motor complexes and that these proteins cause Bax/Bak-dependent apoptosis . The results of this study demonstrate that JNK can engage this apoptotic pathway by phosphorylation of BH3-only proteins, including Bim and Bmf.

SIGNOR-250116

Q96T68

P84243

1

methylation

up-regulates activity

0.2

Here, we have characterized a previously undescribed member of the histone H3K9 methyltransferase family named CLLD8 (or SETDB2 or KMT1F). This protein contributes to the trimethylation of both interspersed repetitive elements and centromere-associated repeats and participates in the recruitment of heterochromatin protein 1 to centromeres. Methylation of histone H3 at lysine 9 (H3K9) has emerged as an important player in the formation of heterochromatin, chromatin condensation, and transcriptional repression.

SIGNOR-263894

P78362

P23443

0

phosphorylation

up-regulates activity

0.355

Altogether, these results identify S6K1-phosphorylated SRPK2 as an essential mediator of IGF1-stimulated SG formation in hPDAC cells.|The nodes of the core SG network are known to contribute to SG formation to varying degrees and it is possible that S6K1-stimulated SRPK2 may impact their contribution; this is consistent with the predicted model whereby SG assembly is subject to regulation by positive and negative cooperativity of extrinsic factors with the core network interactions (14).

SIGNOR-280121

Q7Z6J0

O14964

1

ubiquitination

down-regulates quantity

0.246

Importantly, ubiquitination of Hrs mediated by POSH caused the reduction of Hrs level via the ubiquitin-proteasome pathway.

SIGNOR-278575

P78352

P00519

0

phosphorylation

up-regulates activity

0.441

Moreover, c-Abl phosphorylates PSD-95 at tyrosine 533.|c-Abl modulates the synaptic contact number and PSD-95 clustering.

SIGNOR-278391

P22612

Q14896

1

phosphorylation

up-regulates

0.275

Phosphorylation of cmybp-c by pka speeds actomyosin interactions and contributes to increased cardiac contractility following _-adrenergic stimulation.7, 8 phosphorylation by pka is essential for proper cardiac function /for the human isoform, three pka sites were previously identified (ser275, ser284, and ser304) /our results indicate that pka phosphorylates up to four sites in both the murine and human m-domains including a novel site not previously described for either protein (ser307 for mouse and ser311 for human).

SIGNOR-163788

P11309

P68431

1

phosphorylation

down-regulates activity

0.2

Pim1-dependent phosphorylation of histone h3 at serine 10 is required for myc-dependent transcriptional activation and oncogenic transformation.

SIGNOR-156946

P35232

P10721

0

phosphorylation

up-regulates activity

0.2

In this study, we showed that c-Kit associates with PHB to upregulate phospho-PHB in the lipid raft of the plasma membrane.|c-Kit phosphorylates PHB at the Tyr259 residue.

SIGNOR-278362

Q6U7Q0

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.2

CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction.

SIGNOR-264891

P31749

P23588

1

phosphorylation

up-regulates

0.393

Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.

SIGNOR-252520

P17302

Q02156

0

phosphorylation

down-regulates activity

0.44

Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication.|These data strongly suggest that PKC directly phosphorylates Cx43 on S368 in vivo, which results in a change in single channel behavior that contributes to a decrease in intercellular communication.

SIGNOR-144465

O95628

Q96T37

1

ubiquitination

down-regulates quantity by destabilization

0.359

We demonstrate that RBM15 is methylated by protein arginine methyltransferase 1 (PRMT1) at residue R578, leading to its degradation via ubiquitylation by an E3 ligase (CNOT4).

SIGNOR-271466

Q9H4B6

O00506

0

phosphorylation

down-regulates activity

0.28

STK25 inhibits the ability of SAV1 to counteract STRIPAK.|Using this antibody, we confirmed that SAV1 WT was indeed phosphorylated by STK25 at T26 in human cells (XREF_FIG).

SIGNOR-278369

Q9HAU4

P25490

1

ubiquitination

down-regulates quantity by destabilization

0.364

In addition, Smurf2 decreased the protein half-life and transcriptional activity of YY1.|Wild type Smurf2, but not the E3 ubiquitin ligase defective mutant, increased the poly-ubiquitination of YY1.

SIGNOR-278544

P05067

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.267

These include a significant increase in APP phosphorylation at Thr 668 by cdk2, cdk4, and cdk5, which increases its beta-amyloid production and APP proteolysis by the activated caspases during cell cycle ( xref ; xref ; xref ; xref ).

SIGNOR-280210

O75182

Q5VTB9

0

polyubiquitination

down-regulates quantity by destabilization

0.429

Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B.

SIGNOR-271943