GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13950	P46531	2	binding	down-regulates	0.38	Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.	SIGNOR-167627
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
Q15208	P01106	1	phosphorylation	down-regulates activity	0.282	Previously, we demonstrated that STK38 kinase mediates MYC phosphorylation.\|STK38-WT overexpression dramatically reduced MYC half-life (4-fold), compared to control un induced cells (XREF_FIG), while STK38-KD overexpression led to increased MYC half-life (1.7 fold), illustrating an involvement in MYC protein turnover regulation (XREF_FIG).	SIGNOR-280142
Q16539	Q15075	1	phosphorylation	up-regulates activity	0.458	We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes	SIGNOR-140082
P35222	P48729	0	phosphorylation	down-regulates	0.791	Specifically, ck1_ phosphorylates _-catenin at s45, which primes this n-terminal region for subsequent phosphorylations by gsk3 at t41, s37 and s33 [7]. These latter two phosphorylations are recognized by the e3-ligase component, _-trcp, for ultimate ubiquitylation and destruction by the proteosome	SIGNOR-165022
P09132	O76094	2	binding	up-regulates activity	0.942	Mammalian SRP comprises the highly base-paired SRP RNA (also referred to as 7SL RNA) of ∼300 nt and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) (Figure (Figure1A).1A). The hierarchy of protein addition always starts with the scaffolding protein SRP19 (together with SRP9/14 for the entire SRP) followed by SRP68/72 and finally by SRP54.	SIGNOR-261166
P07948	Q04760	1	phosphorylation	up-regulates activity	0.2	We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).	SIGNOR-276186
P24941	O60318	1	phosphorylation	up-regulates activity	0.2	To study the inducible regulation of GANP DNA-primase during cell activation, we examined phosphorylation induced by various kinds of kinases.We observed that the cell cycle-associated kinase Cdks induced phosphorylation of GANP in vitro. Examination of immunoprecipitates of Cdk2 from B cells revealed phosphorylation of GANP-PD at a consensus sequence of Cdk phosphorylation at Ser502 (S/T-P-X-K/R) (Fig. (Fig.1C1C Left; ref. 22).	SIGNOR-262734
P27361	Q9UQ13	1	phosphorylation	down-regulates quantity by destabilization	0.335	Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.	SIGNOR-277443
Q6AZZ1	Q92734	1	ubiquitination	down-regulates quantity by destabilization	0.451	Our results suggest that TRIM68 degrades TFG at a point of pathway convergence in which downstream events lead to the activation of both NF-kappaB and IRF3.\|TRIM68 polyubiquitinates TFG leading to its degradation via its RING domain which also plays an important role in TRIM68 negative inhibition on IFN-beta production.	SIGNOR-278737
P41229	O95628	0	ubiquitination	down-regulates quantity by destabilization	0.545	In our study, we show that the protein level of the yeast histone H3 Lys 4 (H3 K4) demethylase Jhd2/Kdm5 is modulated through polyubiquitination by the E3 ubiquitin ligase Not4 and turnover by the proteasome. Finally, we show that human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism. We propose that Not4 is an E3 ubiquitin ligase that monitors and controls a precise amount of Jhd2 protein so that the proper balance between histone demethylase and histone methyltransferase activities occur in the cell, ensuring appropriate levels of H3 K4 trimethylation and gene expression.	SIGNOR-271468
P09471	Q13639	2	binding	up-regulates activity	0.253	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-257242
P58400	Q8N2Q7	2	binding	up-regulates activity	0.84	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264149
P38936	P12004	2	binding	down-regulates	0.765	P21 exerts its effect on the cell cycle not only by inhibiting cyclin/cdk complexes, but also by inhibiting proliferating cell nuclear antigen (pcna)	SIGNOR-191939
Q8IZQ8	P17252	0	phosphorylation	down-regulates activity	0.2	PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues.	SIGNOR-279099
Q8TAE6	Q13418	0	phosphorylation	up-regulates activity	0.546	Pka predominantly phosphorylated a site distinct from the inhibitory t73 in kepi. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c	SIGNOR-101835
P12821	P01019-PRO_0000032458	1	cleavage	up-regulates quantity	0.2	Ang I is subsequently converted into the major RAS effector peptide Ang II or Ang (1–8), through activity of the zinc-dependent protease ACE, which hydrolyzes two amino acids from the carboxy terminus of Ang I	SIGNOR-260236
P49023	P45983	0	phosphorylation	up-regulates activity	0.676	JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion.	SIGNOR-250129
O95180	P17612	0	phosphorylation	down-regulates activity	0.2	Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity.	SIGNOR-263110
P04626	P15514	0	phosphorylation	up-regulates	0.628	Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor	SIGNOR-31199
O00468	O75096	2	binding	up-regulates activity	0.849	AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer.	SIGNOR-273849
P13861	P22694	2	binding	down-regulates activity	0.896	Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets	SIGNOR-258757
O14640	P31431	2	binding	up-regulates	0.356	Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.	SIGNOR-199632
Q9NRM7	P46937	1	phosphorylation	down-regulates	0.821	Lats1/2 inhibit yap by direct phosphorylation at s127, which results in yap binding to 14-3-3 and cytoplasmic sequestration	SIGNOR-198514
Q13145	Q13467	2	binding	up-regulates	0.583	These data together suggest that bambi may form a ternary coreceptor complex with fzd5 and lrp6	SIGNOR-23040
P11142	Q99933	2	binding	up-regulates activity	0.895	Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.	SIGNOR-254115
P35236	Q05513	0	phosphorylation	up-regulates activity	0.26	HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.	SIGNOR-276047
P30679	P20309	2	binding	up-regulates activity	0.397	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-257224
P35916	P35916	2	phosphorylation	up-regulates activity	0.2	Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail.	SIGNOR-104088
Q09472	Q9Y6B2	2	binding	down-regulates activity	0.421	Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.	SIGNOR-253379
P28222	P09471	2	binding	up-regulates activity	0.48	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-256999
O43815	P67775	2	binding	up-regulates activity	0.638	The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms	SIGNOR-261698
Q9NQC3	Q96FE5	2	binding	up-regulates	0.666	Nogo-a, myelin-associated glycoprotein (mag), and oligodendrocyte myelin glycoprotein (omgp)...signal through a common receptor complex in neurons, which includes the ligand binding nogo-66 receptor (ngr), and two signal-transducing binding partners, p75 and lingo-1,	SIGNOR-133752
P19338	P60484	0	dephosphorylation	up-regulates activity	0.27	The fact that PTEN\u03b2 interacts with nucleolin and dephosphorylates nucleolin at Thr84 raised a question as to whether nucleolin mediates PTEN\u03b2 regulation of rDNA transcription, and thus represents a direct mechanism by which PTEN\u03b2 controls ribosomal biogenesis.	SIGNOR-277166
Q9UJY1	P27361	0	phosphorylation	up-regulates activity	0.34	Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation	SIGNOR-107680
P52333	P40763	1	phosphorylation	up-regulates	0.792	Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated	SIGNOR-256254
P20941	P25098	0	phosphorylation	down-regulates activity	0.2	Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability\|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).	SIGNOR-279411
Q15465	Q16878	2	binding	up-regulates	0.2	Cdo and boc bind shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where cdo and boc enhance shh signaling within its target field.	SIGNOR-146461
Q8IUQ4	Q6IE81	1	polyubiquitination	down-regulates quantity by destabilization	0.291	Siah-1 decreases Jade-1 abundance and enhances Jade-1 ubiquitination	SIGNOR-272915
P06493	P16949	1	phosphorylation	up-regulates activity	0.641	null	SIGNOR-279803
O00505	P46531	1	relocalization	up-regulates	0.324	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.	SIGNOR-165280
P07947	Q969T9	1	phosphorylation	up-regulates activity	0.304	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273582
P78527	P03372	1	phosphorylation	up-regulates quantity by stabilization	0.386	DNA-PK phosphorylates ERalpha at Ser-118.\|Phosphorylation resulted in stabilization of ERalpha protein as inhibition of DNA-PK resulted in its proteasomal degradation.	SIGNOR-279561
P28482	Q9BZI1	1	phosphorylation	up-regulates activity	0.2	We tested the transcriptional properties of Irx2 by dividing it into amino- and carboxy terminal parts and found that Mek1-mediated phosphorylation activates and derepresses the amino and carboxyl parts, respectively. When Ser46 and Ser65 were mutated to alanine (S46A and S65A), phosphorylation was reduced, whereas substitution of Ser83 and Ser103 (S83A and S103A) did not affect phosphorylation.	SIGNOR-263052
P09619	P25098	2	phosphorylation	up-regulates activity	0.2	The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2.\|We conclude that the activated PDGFRbeta itself phosphorylates GRK2 tyrosyl residues and thereby activates GRK2, which then serine phosphorylates and desensitizes the PDGFRbeta.	SIGNOR-278972
P55957	Q07817	2	binding	down-regulates activity	0.859	Overexpression of antiapoptotic proteins including Bcl-XL and/or Bcl-2 contributes to tumor initiation, progression, and resistance to therapy by direct interactions with proapoptotic BH3 proteins. Release of BH3 proteins from antiapoptotic proteins kills some cancer cells and sensitizes others to chemotherapy. Binding of Bcl-XL and Bcl-2 to the BH3 proteins Bad, Bid, and the three major isoforms of Bim was measured for fluorescent protein fusions in live cells using fluorescence lifetime imaging microscopy and fluorescence resonance energy transfer.	SIGNOR-209675
O96013	O94806	0	phosphorylation	up-regulates activity	0.252	PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)	SIGNOR-275931
Q05513	O15530	0	phosphorylation	up-regulates	0.577	Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylationcytoskeletal reorganization;tnni1(induces);desmin(induces);tpm1(induces);myo1c(induces);tnnt1(induces);	SIGNOR-85501
Q13557	P56524	1	phosphorylation	up-regulates	0.358	These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2	SIGNOR-151418
P48729	Q9BQN1	2	binding	up-regulates quantity	0.2	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-273752
Q15256	P40763	1	dephosphorylation	down-regulates activity	0.2	Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.	SIGNOR-248719
P14735	P01308	1	cleavage	down-regulates quantity by destabilization	0.719	IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds	SIGNOR-260986
Q99801	P17252	0	phosphorylation	up-regulates	0.2	Phosphorylation of wild-type nkx3.1 decreased the apparent binding affinity of the protein for the consensus sequence by 3-fold relative to the nonphosphorylated protein (fig. 3) _ .	SIGNOR-86723
P35348	P29992	2	binding	up-regulates activity	0.573	In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11.	SIGNOR-278121
P62330	P48426	1	null	up-regulates activity	0.338	Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.	SIGNOR-264911
Q9BQE4	Q9BUN8	2	binding	up-regulates activity	0.2	VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97.	SIGNOR-261370
P27986	Q9Y6W8	2	binding	up-regulates activity	0.497	ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling.	SIGNOR-272539
Q8WWF5	O43353	1	ubiquitination	down-regulates quantity by destabilization	0.2	Collectively, ZNRF4 degrades RIP2 protein by targeting the RIP2CARD domain in an E3-ubiquitin ligase activity dependent manner.\|Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation.	SIGNOR-278684
O95747	P55011	1	phosphorylation	up-regulates	0.524	The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.	SIGNOR-90927
Q96PY5	P53350	2	binding	up-regulates activity	0.2	Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles.	SIGNOR-273614
Q9H165	P69891	1	transcriptional regulation	down-regulates quantity by repression	0.446	Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching.	SIGNOR-269067
Q05513	P49841	1	phosphorylation	down-regulates	0.597	Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.	SIGNOR-119889
P17096	Q03135	0	relocalization	up-regulates activity	0.265	CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.	SIGNOR-254428
P56704	Q9UP38	2	binding	up-regulates activity	0.796	Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have a complex and partially overlapping pattern of expression in different regions of the embryo, and many of them (fz1, 3, 7, 8 and 9) have specific expression in the epithelial somites as well as in the newly formed myotomes.	SIGNOR-169651
P08575	P41240	0	phosphorylation	up-regulates	0.469	Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.	SIGNOR-26785
Q15046	P00441	2	binding	down-regulates quantity by destabilization	0.2	In the presence of mutant SOD1, mitoKARS displays a high propensity to misfold and aggregate prior to its import into mitochondria, becoming a target for proteasome degradation.	SIGNOR-262800
Q969H0	Q5VWQ8	1	ubiquitination	down-regulates quantity by destabilization	0.327	DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1	SIGNOR-254774
Q8IYM9	Q8IYM9	2	polyubiquitination	down-regulates quantity by destabilization	0.2	Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase.	SIGNOR-271780
P08754	O00398	2	binding	up-regulates activity	0.2	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256869
Q00535	P62136	1	phosphorylation	down-regulates activity	0.395	Pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.	SIGNOR-92269
Q14155	Q9ULV8	2	binding	down-regulates	0.2	Here, we show that activation of cdc42 protects the egf receptor from the negative regulatory activity of the c-cbl ubiquitin ligase. Activated cdc42 binds to p85cool-1 (for cloned-out-of-library)/beta-pix (for pak-interactive exchange factor), a protein that directly associates with c-cbl. This inhibits the binding of cbl by the egf receptor and thus prevents cbl from catalyzing receptor ubiquitination	SIGNOR-118135
P06239	P28482	0	phosphorylation	up-regulates activity	0.583	Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.\|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.	SIGNOR-249412
P60484	P08047	1	dephosphorylation	down-regulates activity	0.421	Moreover, PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1 .\|PTEN dephosphorylates the Sp1 transcription factor , the phosphorylation status of which directly impacts its ability to bind to some DNA promoter regions , .	SIGNOR-277119
P03956	P02461	1	cleavage	down-regulates quantity by destabilization	0.35	In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.	SIGNOR-272339
Q92769	P29475	0	s-nitrosylation	down-regulates activity	0.265	we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation	SIGNOR-236919
Q92823	P29323	0	phosphorylation	up-regulates activity	0.298	EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.	SIGNOR-262863
P29350	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.287	Interaction between SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated Cdk2 phosphorylated SHP-1 protein.	SIGNOR-279147
Q9H461	Q9ULT6	0	ubiquitination	down-regulates quantity	0.539	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260111
P53350	O14965	0	phosphorylation	up-regulates	0.665	We find that aurora a (aurka) can directly phosphorylate plk1 on thr 210;activation of plk1 requires phosphorylation of a conserved threonine residue (thr 210).	SIGNOR-179422
P52333	P29350	0	dephosphorylation	up-regulates	0.688	The expression of shp-1 protein was associated with dephosphorylation of the jak3 kinase.	SIGNOR-82764
Q92915	Q9UQD0	2	binding	down-regulates activity	0.547	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253413
Q13153	P18669	1	phosphorylation	down-regulates	0.2	Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity.	SIGNOR-91594
P35368	P63092	2	binding	up-regulates activity	0.506	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 ‚â• -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 ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256807
Q15761	P10082	2	binding	up-regulates	0.643	Maml3 forms complexes in vivo with icn and csl and functiosn as transcriptional coactivators for notch signaling.	SIGNOR-114749
P46531	O14672	0	cleavage	up-regulates activity	0.782	ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development	SIGNOR-259838
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
O75581	P49841	0	phosphorylation	up-regulates activity	0.794	Glycogen synthase kinase 3 (gsk3), which is known for its inhibitory role in wnt through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of lrp6. We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.	SIGNOR-143041
P63000	O60716	2	binding	up-regulates	0.585	We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn	SIGNOR-198938
O00329	O00329	2	phosphorylation	down-regulates	0.2	Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo in vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity.	SIGNOR-65186
P10415	O43521	2	binding	down-regulates	0.819	Bim can induce apoptosis by interacting with anti-apoptotic members of the bcl2 family, including bcl2, bcl-xl and mcl-1.. Bim binds prosurvival proteins comparably. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1	SIGNOR-133823
O60716	P12931	0	phosphorylation	up-regulates activity	0.922	Identification of Src phosphorylation sites in the catenin p120ctn.Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.combinations of Tyr _ Phe mutations at residues 96, 112, 228, 257, 280, 291, 296, and 302	SIGNOR-246484
Q16611	P55957	2	binding	up-regulates	0.822	We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome c. these data support a two-class model for bh3 domains: bid-like domains that activate bax, bak and bad-like domains that sensitize by occupying the pocket of antiapoptotic members.	SIGNOR-92942
P50148	P50052	2	binding	up-regulates	0.504	These neuropeptide gpcrs are coupled to the activation of phospholipase c, and therefore to calcium ele- vation and protein kinase c (pkc) activation, through g proteins of the alfaq family	SIGNOR-106995
P24394	P31785	2	binding	up-regulates	0.83	Il-2r gamma was demonstrated to be a component of the il-4 receptor on the basis of chemical cross-linking data, the ability of il-2r gamma to augment il-4 binding affinity, and the requirement for il-2r gamma in il-4-mediated phosphorylation of insulin receptor substrate-1.	SIGNOR-37362
Q14258	Q7Z2W4	1	ubiquitination	up-regulates activity	0.398	Our data demonstrates that TRIM25 triggers ubiquitination of ZAP and enhances its antiviral activity through inhibition of viral translation, highlighting the importance of cofactors in the mechanisms of broadly antiviral proteins.	SIGNOR-278565
Q14493	P58876	1	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-265378
P23508	P78527	0	phosphorylation	up-regulates activity	0.2	MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.	SIGNOR-273530
Q9H190	P30408	0	relocalization	up-regulates activity	0.402	TM4SF1 functions as a membrane adaptor connecting DDR1 to syntenin2.	SIGNOR-272401
P35354	P07948	0	phosphorylation	up-regulates activity	0.385	We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro.	SIGNOR-276643
P24941	P49736	1	phosphorylation	up-regulates	0.735	In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2	SIGNOR-144000

Q13950

P46531

2

binding

down-regulates

0.38

Runx2 is an inhibitor of the notch1 signaling pathway during normal osteoblast differentiation. The n-terminal domain of runx2 was crucial to the binding and inhibition of the the n-terminus of the notch1 intracellular domain.

SIGNOR-167627

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

Q15208

P01106

1

phosphorylation

down-regulates activity

0.282

Previously, we demonstrated that STK38 kinase mediates MYC phosphorylation.|STK38-WT overexpression dramatically reduced MYC half-life (4-fold), compared to control un induced cells (XREF_FIG), while STK38-KD overexpression led to increased MYC half-life (1.7 fold), illustrating an involvement in MYC protein turnover regulation (XREF_FIG).

SIGNOR-280142

Q16539

Q15075

1

phosphorylation

up-regulates activity

0.458

We found that p38alpha can phosphorylate the rab5 effectors eea1 and rabenosyn-5 on thr-1392 and ser-215, respectively, and these phosphorylation events regulate the recruitment of eea1 and rabenosyn-5 to membranes

SIGNOR-140082

P35222

P48729

0

phosphorylation

down-regulates

0.791

Specifically, ck1_ phosphorylates _-catenin at s45, which primes this n-terminal region for subsequent phosphorylations by gsk3 at t41, s37 and s33 [7]. These latter two phosphorylations are recognized by the e3-ligase component, _-trcp, for ultimate ubiquitylation and destruction by the proteosome

SIGNOR-165022

P09132

O76094

2

binding

up-regulates activity

0.942

Mammalian SRP comprises the highly base-paired SRP RNA (also referred to as 7SL RNA) of ∼300 nt and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72) (Figure (Figure1A).1A). The hierarchy of protein addition always starts with the scaffolding protein SRP19 (together with SRP9/14 for the entire SRP) followed by SRP68/72 and finally by SRP54.

SIGNOR-261166

P07948

Q04760

1

phosphorylation

up-regulates activity

0.2

We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D).

SIGNOR-276186

P24941

O60318

1

phosphorylation

up-regulates activity

0.2

To study the inducible regulation of GANP DNA-primase during cell activation, we examined phosphorylation induced by various kinds of kinases.We observed that the cell cycle-associated kinase Cdks induced phosphorylation of GANP in vitro. Examination of immunoprecipitates of Cdk2 from B cells revealed phosphorylation of GANP-PD at a consensus sequence of Cdk phosphorylation at Ser502 (S/T-P-X-K/R) (Fig. (Fig.1C1C Left; ref. 22).

SIGNOR-262734

P27361

Q9UQ13

1

phosphorylation

down-regulates quantity by destabilization

0.335

Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.

SIGNOR-277443

Q6AZZ1

Q92734

1

ubiquitination

down-regulates quantity by destabilization

0.451

Our results suggest that TRIM68 degrades TFG at a point of pathway convergence in which downstream events lead to the activation of both NF-kappaB and IRF3.|TRIM68 polyubiquitinates TFG leading to its degradation via its RING domain which also plays an important role in TRIM68 negative inhibition on IFN-beta production.

SIGNOR-278737

P41229

O95628

0

ubiquitination

down-regulates quantity by destabilization

0.545

In our study, we show that the protein level of the yeast histone H3 Lys 4 (H3 K4) demethylase Jhd2/Kdm5 is modulated through polyubiquitination by the E3 ubiquitin ligase Not4 and turnover by the proteasome. Finally, we show that human NOT4 can polyubiquitinate human JARID1C/SMCX, a homolog of Jhd2, suggesting that this is likely a conserved mechanism. We propose that Not4 is an E3 ubiquitin ligase that monitors and controls a precise amount of Jhd2 protein so that the proper balance between histone demethylase and histone methyltransferase activities occur in the cell, ensuring appropriate levels of H3 K4 trimethylation and gene expression.

SIGNOR-271468

P09471

Q13639

2

binding

up-regulates activity

0.253

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-257242

P58400

Q8N2Q7

2

binding

up-regulates activity

0.84

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264149

P38936

P12004

2

binding

down-regulates

0.765

P21 exerts its effect on the cell cycle not only by inhibiting cyclin/cdk complexes, but also by inhibiting proliferating cell nuclear antigen (pcna)

SIGNOR-191939

Q8IZQ8

P17252

0

phosphorylation

down-regulates activity

0.2

PKCalpha directly promoted the basal phosphorylation of endogenous myocardin at serine and threonine residues.

SIGNOR-279099

Q8TAE6

Q13418

0

phosphorylation

up-regulates activity

0.546

Pka predominantly phosphorylated a site distinct from the inhibitory t73 in kepi. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c

SIGNOR-101835

P12821

P01019-PRO_0000032458

1

cleavage

up-regulates quantity

0.2

Ang I is subsequently converted into the major RAS effector peptide Ang II or Ang (1–8), through activity of the zinc-dependent protease ACE, which hydrolyzes two amino acids from the carboxy terminus of Ang I

SIGNOR-260236

P49023

P45983

0

phosphorylation

up-regulates activity

0.676

JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion.

SIGNOR-250129

O95180

P17612

0

phosphorylation

down-regulates activity

0.2

Here, we identify protein kinase A (PKA) as a molecular switch that allows Gbeta(2)gammax dimers to effect voltage-independent inhibition of Ca(v)3.2 channels. Inhibition requires phosphorylation of Ser(1107), a critical serine residue on the II-III loop of the channel pore protein. S1107A prevents inhibition of unitary currents by recombinant Gbeta(2)gamma(2) dimers but does not disrupt dimer binding nor change its specificity.

SIGNOR-263110

P04626

P15514

0

phosphorylation

up-regulates

0.628

Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor

SIGNOR-31199

O00468

O75096

2

binding

up-regulates activity

0.849

AGRN is released by the nerve and binds to LRP4, which then binds to MuSK. This interaction leads to MuSK autophosphorylation and activation of its kinase function, leading to anterograde signalling by subsequent phosphorylation of DOK7 (not shown), which binds MuSK as a dimer.

SIGNOR-273849

P13861

P22694

2

binding

down-regulates activity

0.896

Inactive PKA exists as a holoenzyme, comprised of two regulatory (R) subunits and two catalytic subunits . In the presence of cAMP, the holoenzyme becomes active by binding two cAMP molecules cooperatively to each R subunit, resulting in a conformational change in the R subunits, thus releasing the two C subunits to phosphorylate downstream targets

SIGNOR-258757

O14640

P31431

2

binding

up-regulates

0.356

Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.

SIGNOR-199632

Q9NRM7

P46937

1

phosphorylation

down-regulates

0.821

Lats1/2 inhibit yap by direct phosphorylation at s127, which results in yap binding to 14-3-3 and cytoplasmic sequestration

SIGNOR-198514

Q13145

Q13467

2

binding

up-regulates

0.583

These data together suggest that bambi may form a ternary coreceptor complex with fzd5 and lrp6

SIGNOR-23040

P11142

Q99933

2

binding

up-regulates activity

0.895

Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.

SIGNOR-254115

P35236

Q05513

0

phosphorylation

up-regulates activity

0.26

HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.

SIGNOR-276047

P30679

P20309

2

binding

up-regulates activity

0.397

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-257224

P35916

2

phosphorylation

up-regulates activity

0.2

Trans-phosphorylation of activated, dimerized receptor tyrosine kinases is known to be critical for the regulation of kinase activity and for receptor interaction with signal transduction molecules. In this study, we have identified five tyrosyl phosphorylation sites in the vegfr-3 carboxyl-terminal tail.

SIGNOR-104088

Q09472

Q9Y6B2

2

binding

down-regulates activity

0.421

Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 (and the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity.

SIGNOR-253379

P28222

P09471

2

binding

up-regulates activity

0.48

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-256999

O43815

P67775

2

binding

up-regulates activity

0.638

The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms

SIGNOR-261698

Q9NQC3

Q96FE5

2

binding

up-regulates

0.666

Nogo-a, myelin-associated glycoprotein (mag), and oligodendrocyte myelin glycoprotein (omgp)...signal through a common receptor complex in neurons, which includes the ligand binding nogo-66 receptor (ngr), and two signal-transducing binding partners, p75 and lingo-1,

SIGNOR-133752

P19338

P60484

0

dephosphorylation

up-regulates activity

0.27

The fact that PTEN\u03b2 interacts with nucleolin and dephosphorylates nucleolin at Thr84 raised a question as to whether nucleolin mediates PTEN\u03b2 regulation of rDNA transcription, and thus represents a direct mechanism by which PTEN\u03b2 controls ribosomal biogenesis.

SIGNOR-277166

Q9UJY1

P27361

0

phosphorylation

up-regulates activity

0.34

Hsp22 is phosphorylated by protein kinase c (at residues ser(14) and thr(63)) and by p44 mitogen-activated protein kinase (at residues ser(27) and thr(87)). Concerning the possible function of hsp22, no definitive conclusions can be drawn with the available data, although its function might be to bind to and modulate the activity of hsp27.Some Studies claimed that phosphorylation is required for the translocation

SIGNOR-107680

P52333

P40763

1

phosphorylation

up-regulates

0.792

Since Jak-STAT pathway primarily activated in IL-15-me- diated cell proliferation, we tested whether it is also participates in IL-15-mediated proliferation of FAPs. Interestingly, we found the expression of phospho-Jak3 and phospho-Tyk2, as well as their downstream, phospho- STAT3 and phospho-STAT5, was significantly upregulated

SIGNOR-256254

P20941

P25098

0

phosphorylation

down-regulates activity

0.2

Phosphorylation of phosducin by GRK2 markedly reduces its G beta gamma binding ability|The phosphorylation of purified phosducin and PhLP by recombinant GRK2 proceeds rapidly and stoichiometrically (0.82 +/- 0.1 and 0.83 +/- 0.09 mol of P(i)/mol of protein, respectively).

SIGNOR-279411

Q15465

Q16878

2

binding

up-regulates

0.2

Cdo and boc bind shh through a high-affinity interaction with a specific fibronectin repeat that is essential for activity. We propose a model where cdo and boc enhance shh signaling within its target field.

SIGNOR-146461

Q8IUQ4

Q6IE81

1

polyubiquitination

down-regulates quantity by destabilization

0.291

Siah-1 decreases Jade-1 abundance and enhances Jade-1 ubiquitination

SIGNOR-272915

P06493

P16949

1

phosphorylation

up-regulates activity

0.641

null

SIGNOR-279803

O00505

P46531

1

relocalization

up-regulates

0.324

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.

SIGNOR-165280

P07947

Q969T9

1

phosphorylation

up-regulates activity

0.304

Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.

SIGNOR-273582

P78527

P03372

1

phosphorylation

up-regulates quantity by stabilization

0.386

DNA-PK phosphorylates ERalpha at Ser-118.|Phosphorylation resulted in stabilization of ERalpha protein as inhibition of DNA-PK resulted in its proteasomal degradation.

SIGNOR-279561

P28482

Q9BZI1

1

phosphorylation

up-regulates activity

0.2

We tested the transcriptional properties of Irx2 by dividing it into amino- and carboxy terminal parts and found that Mek1-mediated phosphorylation activates and derepresses the amino and carboxyl parts, respectively. When Ser46 and Ser65 were mutated to alanine (S46A and S65A), phosphorylation was reduced, whereas substitution of Ser83 and Ser103 (S83A and S103A) did not affect phosphorylation.

SIGNOR-263052

P09619

P25098

2

phosphorylation

up-regulates activity

0.2

The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2.|We conclude that the activated PDGFRbeta itself phosphorylates GRK2 tyrosyl residues and thereby activates GRK2, which then serine phosphorylates and desensitizes the PDGFRbeta.

SIGNOR-278972

P55957

Q07817

2

binding

down-regulates activity

0.859

Overexpression of antiapoptotic proteins including Bcl-XL and/or Bcl-2 contributes to tumor initiation, progression, and resistance to therapy by direct interactions with proapoptotic BH3 proteins. Release of BH3 proteins from antiapoptotic proteins kills some cancer cells and sensitizes others to chemotherapy. Binding of Bcl-XL and Bcl-2 to the BH3 proteins Bad, Bid, and the three major isoforms of Bim was measured for fluorescent protein fusions in live cells using fluorescence lifetime imaging microscopy and fluorescence resonance energy transfer.

SIGNOR-209675

O96013

O94806

0

phosphorylation

up-regulates activity

0.252

PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)

SIGNOR-275931

Q05513

O15530

0

phosphorylation

up-regulates

0.577

Our findings suggest that insulin, via pip(3), provokes increases in pkc-zeta enzyme activity through (a) pdk-1-dependent t410 loop phosphorylation, (b) t560 autophosphorylationcytoskeletal reorganization;tnni1(induces);desmin(induces);tpm1(induces);myo1c(induces);tnnt1(induces);

SIGNOR-85501

Q13557

P56524

1

phosphorylation

up-regulates

0.358

These results demonstrate that camkiideltab preferentially targets hdac4, and this involves serine 210overexpression of camkiideltab in primary neonatal cardiomyocytes increases the activity of the mef2 transcription factor and completely rescues hdac4-mediated repression of mef2

SIGNOR-151418

P48729

Q9BQN1

2

binding

up-regulates quantity

0.2

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-273752

Q15256

P40763

1

dephosphorylation

down-regulates activity

0.2

Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

SIGNOR-248719

P14735

P01308

1

cleavage

down-regulates quantity by destabilization

0.719

IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds

SIGNOR-260986

Q99801

P17252

0

phosphorylation

up-regulates

0.2

Phosphorylation of wild-type nkx3.1 decreased the apparent binding affinity of the protein for the consensus sequence by 3-fold relative to the nonphosphorylated protein (fig. 3) _ .

SIGNOR-86723

P35348

P29992

2

binding

up-regulates activity

0.573

In this report, we demonstrate that in transfected cos-7 cells Gal4 and Ga16, like Gaq and Ga11, can activate PIPLC j3l and that all three al-ARs, alA, alB and alC, can activate endogenous PI-PLC by coupling to Gaq or Ga11.

SIGNOR-278121

P62330

P48426

1

null

up-regulates activity

0.338

Effects of ARF6 upon Axonogenesis Are Mediated by Phosphatidyl-inositol-4-phosphate 5-Kinase α. activated ARF6 stimulates the lipid-modifying enzyme PI(4)P 5-Kinase, leading to local increases in plasma membrane PIP2 and changes in actin dynamics. Alternatively, activation of Rac1 by upstream Rac1 activators or indirectly by ARF6-GTP results in stimulation of actin polymerization.

SIGNOR-264911

Q9BQE4

Q9BUN8

2

binding

up-regulates activity

0.2

VIMP mediates p97 binding to hDerlin-1. these data suggest that Derlin-1 and VIMP form a membrane protein complex that serves as a receptor for p97.

SIGNOR-261370

P27986

Q9Y6W8

2

binding

up-regulates activity

0.497

ICOS ligation in concert with TCR stimulation results in strong PI3K activation in T lymphocytes. The ICOS cytoplasmic tail contains an YMFM motif that binds the p85alpha subunit of class IA PI3K, similar to the YMNM motif of CD28, suggesting a redundant function of the two receptors in PI3K signaling.

SIGNOR-272539

Q8WWF5

O43353

1

ubiquitination

down-regulates quantity by destabilization

0.2

Collectively, ZNRF4 degrades RIP2 protein by targeting the RIP2CARD domain in an E3-ubiquitin ligase activity dependent manner.|Here we show that ZNRF4 induces K48-linked ubiquitination of RIP2 and promotes RIP2 degradation.

SIGNOR-278684

O95747

P55011

1

phosphorylation

up-regulates

0.524

The secretory na-k-cl cotransporter nkcc1 is activated by secretagogues through a phosphorylation-dependent mechanism. three phosphoacceptor sites were identified in the n-terminal domain of the protein (at thr184, thr189, and thr202) none of these residues occurs in the context of strong consensus sites for known ser/thr kinases.

SIGNOR-90927

Q96PY5

P53350

2

binding

up-regulates activity

0.2

Phosphorylation of hCenexin1 at S796 is critical for the hCenexin1-Plk1 interaction.Here we show that a splice variant of hODF2 called hCenexin1, but not hODF2 itself, efficiently localizes to somatic centrosomes via a variant-specific C-terminal extension and recruits Plk1 through a Cdc2-dependent phospho-S796 motif within the extension. This interaction and Plk1 activity were important for proper recruitment of pericentrin and gamma-tubulin, and, ultimately, for formation of normal bipolar spindles.

SIGNOR-273614

Q9H165

P69891

1

transcriptional regulation

down-regulates quantity by repression

0.446

Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching.

SIGNOR-269067

Q05513

P49841

1

phosphorylation

down-regulates

0.597

Phospho-gsk3b-specific antibodies also revolved that lkb1 regulates gsk3b phosphorylation at a known inhibitory site, serine-9. This localized phosphorylation is cdc42 and pkc-zeta-dependent.

SIGNOR-119889

P17096

Q03135

0

relocalization

up-regulates activity

0.265

CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.

SIGNOR-254428

P56704

Q9UP38

2

binding

up-regulates activity

0.796

Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.All the frizzled genes studied have a complex and partially overlapping pattern of expression in different regions of the embryo, and many of them (fz1, 3, 7, 8 and 9) have specific expression in the epithelial somites as well as in the newly formed myotomes.

SIGNOR-169651

P08575

P41240

0

phosphorylation

up-regulates

0.469

Tyrosine phosphorylation of cd45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

SIGNOR-26785

Q15046

P00441

2

binding

down-regulates quantity by destabilization

0.2

In the presence of mutant SOD1, mitoKARS displays a high propensity to misfold and aggregate prior to its import into mitochondria, becoming a target for proteasome degradation.

SIGNOR-262800

Q969H0

Q5VWQ8

1

ubiquitination

down-regulates quantity by destabilization

0.327

DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1

SIGNOR-254774

Q8IYM9

2

polyubiquitination

down-regulates quantity by destabilization

0.2

Importantly, TRIM22 was conjugated with poly-ubiquitin chains and stabilized by the proteasome inhibitor in 293T cells, suggesting that TRIM22 targeted itself for proteasomal degradation through the poly-ubiquitylation. We also found that TRIM22 was located in the nucleus, indicating that TRIM22 might function as a nuclear E3 ubiquitin ligase.

SIGNOR-271780

P08754

O00398

2

binding

up-regulates activity

0.2

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

SIGNOR-256869

Q00535

P62136

1

phosphorylation

down-regulates activity

0.395

Pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.

SIGNOR-92269

Q14155

Q9ULV8

2

binding

down-regulates

0.2

Here, we show that activation of cdc42 protects the egf receptor from the negative regulatory activity of the c-cbl ubiquitin ligase. Activated cdc42 binds to p85cool-1 (for cloned-out-of-library)/beta-pix (for pak-interactive exchange factor), a protein that directly associates with c-cbl. This inhibits the binding of cbl by the egf receptor and thus prevents cbl from catalyzing receptor ubiquitination

SIGNOR-118135

P06239

P28482

0

phosphorylation

up-regulates activity

0.583

Phosphorylation at Ser-59 (or alternatively, its mutation to Glu) reverses the inhibition and allows interaction of the p56lck SH2 domain with p62.|phosphotyrosine-independent binding of p62 to the p56lck SH2 domain appears to provide an alternative pathway for p56lck signaling that is regulated by Ser-59 phosphorylation.

SIGNOR-249412

P60484

P08047

1

dephosphorylation

down-regulates activity

0.421

Moreover, PTEN downregulates p75NTR expression by decreasing DNA-binding activity of Sp1 .|PTEN dephosphorylates the Sp1 transcription factor , the phosphorylation status of which directly impacts its ability to bind to some DNA promoter regions , .

SIGNOR-277119

P03956

P02461

1

cleavage

down-regulates quantity by destabilization

0.35

In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775–Ile776 or Gly775–Lys776 in native type I, II or III collagen molecules3,4.

SIGNOR-272339

Q92769

P29475

0

s-nitrosylation

down-regulates activity

0.265

we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation

SIGNOR-236919

Q92823

P29323

0

phosphorylation

up-regulates activity

0.298

EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.

SIGNOR-262863

P29350

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.287

Interaction between SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated Cdk2 phosphorylated SHP-1 protein.

SIGNOR-279147

Q9H461

Q9ULT6

0

ubiquitination

down-regulates quantity

0.539

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260111

P53350

O14965

0

phosphorylation

up-regulates

0.665

We find that aurora a (aurka) can directly phosphorylate plk1 on thr 210;activation of plk1 requires phosphorylation of a conserved threonine residue (thr 210).

SIGNOR-179422

P52333

P29350

0

dephosphorylation

up-regulates

0.688

The expression of shp-1 protein was associated with dephosphorylation of the jak3 kinase.

SIGNOR-82764

Q92915

Q9UQD0

2

binding

down-regulates activity

0.547

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253413

Q13153

P18669

1

phosphorylation

down-regulates

0.2

Activated pak1 inhibits glycolysis by association of its catalytic domain with pgam-b and subsequent phosphorylation of the enzyme on serine residues 23 and 118, thereby abolishing pgam activity.

SIGNOR-91594

P35368

P63092

2

binding

up-regulates activity

0.506

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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256807

Q15761

P10082

2

binding

up-regulates

0.643

Maml3 forms complexes in vivo with icn and csl and functiosn as transcriptional coactivators for notch signaling.

SIGNOR-114749

P46531

O14672

0

cleavage

up-regulates activity

0.782

ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development

SIGNOR-259838

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

O75581

P49841

0

phosphorylation

up-regulates activity

0.794

Glycogen synthase kinase 3 (gsk3), which is known for its inhibitory role in wnt through the promotion of beta-catenin phosphorylation and degradation, mediates the phosphorylation and activation of lrp6. We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.

SIGNOR-143041

P63000

O60716

2

binding

up-regulates

0.585

We demonstrate that p120-catenin participates in the stimulation of rac1 activity, binding directly to this protein. In addition we show that vav2 also binds to p120-catenin and is required for rac1 activation and for beta-catenin translocation to the nucleus.Vav2 And rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by ck1 and inhibited by tyrosine phosphorylation by src or fyn

SIGNOR-198938

O00329

2

phosphorylation

down-regulates

0.2

Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo in vitro autophosphorylation of p110delta completely down-regulates its lipid kinase activity.

SIGNOR-65186

P10415

O43521

2

binding

down-regulates

0.819

Bim can induce apoptosis by interacting with anti-apoptotic members of the bcl2 family, including bcl2, bcl-xl and mcl-1.. Bim binds prosurvival proteins comparably. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1

SIGNOR-133823

O60716

P12931

0

phosphorylation

up-regulates activity

0.922

Identification of Src phosphorylation sites in the catenin p120ctn.Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.combinations of Tyr _ Phe mutations at residues 96, 112, 228, 257, 280, 291, 296, and 302

SIGNOR-246484

Q16611

P55957

2

binding

up-regulates

0.822

We find short peptides representing the alpha-helical bh3 domains of bid or bim are capable of inducing oligomerization of bak and bax to release cytochrome c. these data support a two-class model for bh3 domains: bid-like domains that activate bax, bak and bad-like domains that sensitize by occupying the pocket of antiapoptotic members.

SIGNOR-92942

P50148

P50052

2

binding

up-regulates

0.504

These neuropeptide gpcrs are coupled to the activation of phospholipase c, and therefore to calcium ele- vation and protein kinase c (pkc) activation, through g proteins of the alfaq family

SIGNOR-106995

P24394

P31785

2

binding

up-regulates

0.83

Il-2r gamma was demonstrated to be a component of the il-4 receptor on the basis of chemical cross-linking data, the ability of il-2r gamma to augment il-4 binding affinity, and the requirement for il-2r gamma in il-4-mediated phosphorylation of insulin receptor substrate-1.

SIGNOR-37362

Q14258

Q7Z2W4

1

ubiquitination

up-regulates activity

0.398

Our data demonstrates that TRIM25 triggers ubiquitination of ZAP and enhances its antiviral activity through inhibition of viral translation, highlighting the importance of cofactors in the mechanisms of broadly antiviral proteins.

SIGNOR-278565

Q14493

P58876

1

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-265378

P23508

P78527

0

phosphorylation

up-regulates activity

0.2

MCC is phosphorylated at the ATM/ATR consensus sites Ser118 and Ser120. Finally, mutation of S118/120 to alanine did not affect MCC nuclear shuttling following UV but did impair MCC G2/M checkpoint activity.

SIGNOR-273530

Q9H190

P30408

0

relocalization

up-regulates activity

0.402

TM4SF1 functions as a membrane adaptor connecting DDR1 to syntenin2.

SIGNOR-272401

P35354

P07948

0

phosphorylation

up-regulates activity

0.385

We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity. FYN and LYN kinases phosphorylate COX2 on two distinct residues in vitro.

SIGNOR-276643

P24941

P49736

1

phosphorylation

up-regulates

0.735

In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2

SIGNOR-144000