GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P04637	Q70YC5	1	transcriptional regulation	up-regulates quantity by expression	0.29	Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability\| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy	SIGNOR-272476
P11274	P07332	0	phosphorylation	down-regulates activity	0.368	In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.	SIGNOR-251137
Q8NEM2	P04626	0	phosphorylation	up-regulates activity	0.2	Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].\|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site.	SIGNOR-280009
P23528	Q96S53	0	phosphorylation	down-regulates activity	0.503	Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.	SIGNOR-108753
P49662	Q63HK5	0	transcriptional regulation	down-regulates quantity by repression	0.27	Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD.	SIGNOR-264815
P22455	P42224	1	phosphorylation	up-regulates activity	0.348	Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.	SIGNOR-251141
Q9BT67	P46934	1	relocalization	up-regulates activity	0.589	Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.	SIGNOR-260997
Q8WU20	Q06124	1	phosphorylation	up-regulates	0.78	In addition to the direct interactions with grb2, tyrosine-phosphorylated frs2 forms a complex with the sh2 domain-containing protein tyrosine phosphatase shp2. This interaction results in tyrosine phosphorylation of shp2 and complex formation between shp2 and grb2. the catalytic activity of shp2 is essential for a sustained map kinase response and for potentiation of fgf-induced neurite outgrowth in pc12 cells	SIGNOR-58196
Q9H9S0	Q02156	0	phosphorylation	up-regulates activity	0.329	Taken together, our results demonstrate that PKC\u03b5-mediated phosphorylation at T200 and T280 enhances Nanog protein stability in head and neck squamous cell carcinoma.\|These observations confirm that PKCepsilon modulates Nanog transcriptional activity and demonstrate that Nanog is phosphorylated by PKCepsilon at T200 and T280 in vivo.	SIGNOR-278203
O00327	Q14995	0	transcriptional regulation	down-regulates quantity by repression	0.467	A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription.	SIGNOR-268006
O15111	Q8N3F0	1	phosphorylation	down-regulates activity	0.2	INKIT interacted with IKKα/β and TBK1/IKKɛ, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.	SIGNOR-273612
O75496	P00519	0	phosphorylation	up-regulates activity	0.355	Taken together, suggests that c-Abl binds and phosphorylates geminin on Y150 in G2/M/early G1 phases.	SIGNOR-278505
P01178-PRO_0000020496	P16519	0	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270337
Q5TKA1	Q00526	0	phosphorylation	up-regulates	0.2	In this report, we demonstrate that cyclin e1/cdk3 phosphorylates lin-9 on thr-96. Mutating thr-96 to alanine inhibits activation of cyclins a2 and b1 promoters, whereas a phosphomimetic asp mutant strongly activates their promoters and triggers accelerated entry into g2/m phase in 293t cells.	SIGNOR-204529
P13498	Q05655	0	phosphorylation	up-regulates	0.2	Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. \| Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro	SIGNOR-260892
Q9BV73	Q68D86	1	relocalization	up-regulates activity	0.2	CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.	SIGNOR-275625
P48163	Q96HS1	0	dephosphorylation	up-regulates activity	0.2	PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation.	SIGNOR-275569
P05771	P11388	1	phosphorylation	up-regulates activity	0.359	Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. \| Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.	SIGNOR-249195
P63000	Q53QZ3	0	gtpase-activating protein	down-regulates activity	0.581	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-260470
P13611	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.29	By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.	SIGNOR-255441
Q13002	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.\|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.	SIGNOR-278541
Q9Y5Z0	P05067	1	cleavage	up-regulates activity	0.544	BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.\|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating Î±- and Î²-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform.	SIGNOR-261773
Q99814	Q9H3R0	1	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271585
P36956	P17676	0	transcriptional regulation	up-regulates quantity	0.41	These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis	SIGNOR-251645
Q9C0C9	O43541	1	ubiquitination	down-regulates	0.464	We showed that ube2o functions as an e2-e3 hybrid to monoubiquitinate smad6 at lysine 174	SIGNOR-192255
P68400	O14737	1	phosphorylation	up-regulates	0.2	Programmed cell death 5 (pdcd5), a protein involved in cell death and down-regulated in different forms of human tumors. Pdcd5 is phosphorylated in vitro by both ck2alpha subunit and by the ck2 holoenzyme at a residue, s118, which is found phosphorylated in vivo. Transfection of the non-phosphorylatable mutant (s118a) impairs the pdcd5 acceleration of either doxorubimicin- or uv-induced apoptosis in u2os cells	SIGNOR-187106
Q14934	P27361	0	phosphorylation	up-regulates	0.289	The formation of rsk-nfatc4-dna transcription complex is also apparent upon adipogenesis. Bound rsk phosphorylates ser(676) and potentiates nfatc4 dna binding by escalating nfat-dna association. Ser(676) is also targeted by the erk map kinase, which interacts with nfat at a distinct region than rsk. Thus, integration of the erk/rsk signaling pathway provides a mechanism to modulate nfatc4 transcription activity.	SIGNOR-133276
Q9NYY3	Q969H0	1	phosphorylation	down-regulates	0.483	Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176	SIGNOR-196448
P08670	P06493	0	phosphorylation	down-regulates	0.362	These results strongly suggest that cdc2 kinase is the kinase which phosphorylates vimentin ser55 in the entire cytoplasm during mitosis and that the appearance of immunoreactivities with antibody 4a4 in cell staining indeed reflect the vimentin phosphorylation by cdc2 kinase. immunofluorescent evidence using antibody 4a4 and biochemical analysis using vimentin ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase.	SIGNOR-35492
O60674	Q12913	0	dephosphorylation	down-regulates activity	0.323	These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.\|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation.	SIGNOR-277094
O14672	P26378	0	post transcriptional regulation	up-regulates quantity	0.2	Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure	SIGNOR-266865
P11802	P19532	1	phosphorylation	up-regulates activity	0.2	CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .\|We found that CDK4 and CDK6 interact with and phosphorylate nuclear TFEB and TFE3, thereby promoting their shuttling to the cytoplasm.	SIGNOR-279514
O75385	Q15437	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting SEC23B degradation.	SIGNOR-265285
Q13501	Q9UHD2	0	phosphorylation	up-regulates	0.709	Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance.	SIGNOR-191944
P08235	P28482	0	phosphorylation	down-regulates quantity by destabilization	0.286	Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.	SIGNOR-276101
Q14457	O75385	0	phosphorylation	up-regulates activity	0.771	In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex.	SIGNOR-278503
P45983	P04637	1	phosphorylation	up-regulates	0.796	Activated jnk phosphorylates p53	SIGNOR-59812
P35368	P17252	0	phosphorylation	down-regulates activity	0.39	Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.	SIGNOR-248988
P61244	P68400	0	phosphorylation	down-regulates	0.361	Here, we have mapped the nh2-terminal in vivo phosphorylation sites of max to ser2 and ser11[...]	SIGNOR-35772
P04004	P05129	0	phosphorylation	up-regulates quantity by stabilization	0.285	Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.	SIGNOR-248964
P40763	Q99558	0	phosphorylation	up-regulates activity	0.26	Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays.\|When we transfected NIK into LNCaP cells, NIK was able to phosphorylate Stat3 at both tyrosine 705 and serine 727 residues ( Fig. 3 A).	SIGNOR-279341
P52655	P19784	0	phosphorylation	up-regulates activity	0.374	We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.	SIGNOR-250996
O14980	Q13485	1	relocalization	down-regulates	0.3	We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.	SIGNOR-84247
P12931	P49789	1	phosphorylation	up-regulates activity	0.466	The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.	SIGNOR-247134
O95295	P17612	0	phosphorylation	up-regulates activity	0.307	PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation	SIGNOR-250053
P43354	Q13164	0	phosphorylation	up-regulates activity	0.2	Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.\|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.\|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.\|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase.	SIGNOR-279215
Q9H1K1	P42345	0	phosphorylation	up-regulates	0.2	Here, we demonstrate that mtorc1 associates with iscu and phosphorylates iscu at serine 14. This phosphorylation stabilized iscu protein.	SIGNOR-201595
Q09472	P31749	0	phosphorylation	up-regulates	0.697	We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity	SIGNOR-148983
Q2M1Z3	P60953	1	gtpase-activating protein	down-regulates activity	0.673	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-260490
P29401	Q8N531	0	ubiquitination	up-regulates activity	0.2	Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.	SIGNOR-277843
P27986	P06239	0	phosphorylation	down-regulates activity	0.623	the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.	SIGNOR-251383
Q12913	P36888	1	dephosphorylation	down-regulates activity	0.49	Moreover, activated FLT3 could be dephosphorylated by recombinant DEP-1 in vitro.\|The data indicate that DEP-1 is negatively regulating FLT3 signaling activity and that its loss may contribute to but is not sufficient for leukemogenic cell transformation.	SIGNOR-277092
Q13464	P60484	1	phosphorylation	up-regulates	0.656	In addition, active rhoa is able to stimulate the phospholipid phosphatase activity of pten in human embryonic kidney cells and leukocytes, and this regulation seems to require rhoa's downstream effector, rhoa-associated kinase (rock). together with the observation that individual substitution of ser 229 and thr 223 restored some of the rescuing ability (fig. 4b), we conclude that effective regulation of pten by sdf-1 may require more than one of these residues.	SIGNOR-134855
Q01484	Q92823	0	relocalization	up-regulates quantity	0.737	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266719
Q9Y4D1	P12931	0	phosphorylation	up-regulates activity	0.325	Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.\|PTPN3 suppresses lung cancer cell invasiveness by counteracting Src mediated DAAM1 activation and actin polymerization.	SIGNOR-280128
P37840	P53355	0	phosphorylation	up-regulates quantity	0.27	We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.	SIGNOR-278440
O15530	Q05513	1	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
P49841	Q13144	1	phosphorylation	down-regulates activity	0.579	The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535).	SIGNOR-251236
Q9UHD2	Q92630	0	phosphorylation	down-regulates quantity by destabilization	0.413	We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1.	SIGNOR-276939
P15923	P49137	0	phosphorylation	up-regulates	0.52	Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2	SIGNOR-166643
Q15418	P78371	1	phosphorylation	up-regulates	0.249	Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process.	SIGNOR-172986
Q14469	P04150	1	transcriptional regulation	down-regulates quantity by repression	0.2	HES1 binding to the promoter of the NC3C1 gene inhibits its expression and results in insufficient production of the encoded glucocorticoid receptor- rendering these cells resistant to treatment with dexamethasone	SIGNOR-251674
P67775	P27361	1	dephosphorylation	down-regulates	0.647	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).	SIGNOR-103162
Q9HB96	O14757	0	phosphorylation	up-regulates	0.716	Chk1 directly phosphorylates the fance subunit of the fa core complex on two conserved sites (threonine 346 and serine 374). chk1-mediated phosphorylation of fance is required for the fanconi anemia/brca pathway.	SIGNOR-153023
Q9H9Z2	P28482	0	phosphorylation	down-regulates activity	0.262	Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200.	SIGNOR-277338
O43303	P24941	0	phosphorylation	down-regulates activity	0.515	GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)	SIGNOR-265956
P49841	Q9Y6K9	1	phosphorylation	down-regulates quantity	0.431	For analysis of phosphorylation of NEMO on Ser8 and Ser17 by GSK-3, we generated phospho-specific antibodies (anti-phospho-NEMO-Ser8 and anti-phospho-NEMO-Ser17) while anti-phospho-NEMO-Ser31 and anti-phospho-NEMO-Ser43 were commercially available. Indeed, GSK-3\u03b2 was able to phosphorylate all four serines of rhNEMO in a time-dependent manner in an in vitro kinase assay (Fig. 3a).\|In this study, we identified NEMO as a GSK-3\u03b2 substrate that is phosphorylated at several serine residues located within the N-terminal domain.\|The kinase forms a complex with wild-type NEMO while point mutations of NEMO at the specific serines abrogated GSK-3Œ≤ binding and subsequent phosphorylation of NEMO resulting in its destabilization	SIGNOR-279527
P17252	P15311	1	phosphorylation	up-regulates	0.547	Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567.	SIGNOR-133223
P28482	Q99967	1	phosphorylation	up-regulates activity	0.454	CITED2 coactivation is enhanced by activation of MAPK1 and requires T166.\|CITED2 is phosphorylated by MAPK1 at S85, T166 and T175.	SIGNOR-278410
P28562	P45983	1	dephosphorylation	down-regulates	0.789	Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2.	SIGNOR-46079
Q00535	P07197	1	phosphorylation	down-regulates quantity	0.42	Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.\|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression.	SIGNOR-279683
P16104	O76064	0	ubiquitination	up-regulates	0.2	Rnf8 can ubiquitylate histone h2a and h2ax,	SIGNOR-159309
Q13882	P51692	1	phosphorylation	up-regulates	0.429	Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.	SIGNOR-159066
P24941	Q01196	1	phosphorylation	up-regulates activity	0.2	We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein.	SIGNOR-138932
Q12772	Q8WU17	0	ubiquitination	down-regulates quantity	0.477	Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner	SIGNOR-271958
P12931	P10398	1	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
Q96PX1	P24941	0	phosphorylation	up-regulates activity	0.287	CDK2 promotes phosphorylation of RNF157 at the same Ser 660-663 residues that become phosphorylated downstream of combined PI3K and MAPK pathway activity.	SIGNOR-279016
Q15208	P49841	0	phosphorylation	down-regulates activity	0.278	GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress.	SIGNOR-276392
Q8IVT5	Q7Z569	0	ubiquitination	down-regulates quantity by destabilization	0.661	Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.	SIGNOR-272028
P41229	P78317	0	sumoylation	up-regulates activity	0.2	Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015).	SIGNOR-271576
Q9NZ42	P49768	1	cleavage	up-regulates	0.959	Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.	SIGNOR-97113
Q16549	P30305	1	phosphorylation	down-regulates	0.2	We propose that regulation of cdc25b phosphorylation by p38 is a critical event for initiating the g2/m checkpoint after ultraviolet radiation	SIGNOR-107423
P24941	P25205	1	phosphorylation	up-regulates	0.796	In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722.	SIGNOR-176656
Q99962	O75116	0	phosphorylation	down-regulates	0.439	We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85.	SIGNOR-140466
Q16537	Q9P2K6	0	polyubiquitination	down-regulates quantity by destabilization	0.2	PPP2R5ϵ is a KLHL42 substrate and affects TGF-β signaling in SSc. Lys-84 is a candidate ubiquitin acceptor site within PPP2R5ϵ.	SIGNOR-272205
O75592	P49815	1	ubiquitination	down-regulates quantity by destabilization	0.356	We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain.	SIGNOR-278704
P16885	P43405	0	phosphorylation	up-regulates activity	0.753	Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).\|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).	SIGNOR-278995
P62714	P05771-2	1	dephosphorylation	down-regulates activity	0.469	Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.	SIGNOR-248587
P49760	Q9UBK2	1	phosphorylation	down-regulates activity	0.2	Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .\|Clk2 phosphorylates and represses PGC-1\u03b1.	SIGNOR-278228
P06493	Q12778	1	phosphorylation	down-regulates	0.511	Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1.	SIGNOR-178202
Q05513	Q5JVS0	1	phosphorylation	down-regulates activity	0.292	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249257
P29466	P49768	1	cleavage	up-regulates activity	0.385	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261755
P02458	P03956	0	cleavage	down-regulates quantity by destabilization	0.445	MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.	SIGNOR-256341
P49407	P27361	0	phosphorylation	down-regulates	0.716	Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation	SIGNOR-67634
P09668	P02818	1	cleavage	down-regulates quantity by destabilization	0.283	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256325
Q16566	Q9UNW9	1	phosphorylation	up-regulates quantity	0.255	CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. Conversely, Nova-2 with single or double mutations to alanine (2A and 1A2A) was predominantly nuclear, like the WT (Figures 5H and and5I).5I). In contrast, glutamate mutations at site 3 had no effect on Nova-2 localization (Figures 5H and and5I)5I) or on Nova-2 binding to RNA (Figure S5E). These results showed that active CaMKIV reduces Nova-2 nuclear localization by phosphorylating sites 1 and 2 (S25, T27).	SIGNOR-273521
Q14643	Q96K19	0	polyubiquitination	down-regulates activity	0.431	In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.	SIGNOR-271913
O75116	Q9UBR4	1	phosphorylation	up-regulates activity	0.2	Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.	SIGNOR-280110
O15350	Q05655	0	phosphorylation	up-regulates	0.307	The results show that pkcdeltacf phosphorylates the p73beta transactivation and dna-binding domains. pkcdeltacf-mediated phosphorylation of p73beta is associated with accumulation of p73beta and induction of p73beta-mediated transactivation.	SIGNOR-90279
Q9Y4I1	P31751	0	phosphorylation	up-regulates activity	0.458	Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton.Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.	SIGNOR-262632

P04637

Q70YC5

1

transcriptional regulation

up-regulates quantity by expression

0.29

Here, analysis of p53-regulated genes activated in the setting of telomere dysfunction identified Zfp365 (ZNF365 in humans) as a direct p53 target that promotes genome stability| Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. We provide evidence that loss of ZNF365 leads to increased expression of CFS and dysfunctional telomeres, aberrant sister telomere recombination, and increased aneuploidy

SIGNOR-272476

P11274

P07332

0

phosphorylation

down-regulates activity

0.368

In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.

SIGNOR-251137

Q8NEM2

P04626

0

phosphorylation

up-regulates activity

0.2

Blocking HER2 activation using trastuzumab effectively abolished EGF-induced nuclear localization of SHCBP1 in gastric cancer cells [7].|In addition, nuclear translocation of SHCBP1 is a downstream consequence of HER2 activation, which is dependent on phosphorylation of SHCBP1 at the Ser273 site.

SIGNOR-280009

P23528

Q96S53

0

phosphorylation

down-regulates activity

0.503

Like tesk1, tesk2 phosphorylated cofilin specifically at ser-3 and induced formation of actin stress fibers and focal adhesions.

SIGNOR-108753

P49662

Q63HK5

0

transcriptional regulation

down-regulates quantity by repression

0.27

Chromatin immunoprecipitation showed a direct interaction of FE65 and Teashirt3 with the promoter region of CASP4. The results were consistent with a model in which reduced expression of Teashirt3, mediated by genetic or other causes, increases caspase-4 expression, leading to progression of AD.

SIGNOR-264815

P22455

P42224

1

phosphorylation

up-regulates activity

0.348

Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.

SIGNOR-251141

Q9BT67

P46934

1

relocalization

up-regulates activity

0.589

Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB function and impede the degradation of mature hERG proteins mediated by Nedd4-2.

SIGNOR-260997

Q8WU20

Q06124

1

phosphorylation

up-regulates

0.78

In addition to the direct interactions with grb2, tyrosine-phosphorylated frs2 forms a complex with the sh2 domain-containing protein tyrosine phosphatase shp2. This interaction results in tyrosine phosphorylation of shp2 and complex formation between shp2 and grb2. the catalytic activity of shp2 is essential for a sustained map kinase response and for potentiation of fgf-induced neurite outgrowth in pc12 cells

SIGNOR-58196

Q9H9S0

Q02156

0

phosphorylation

up-regulates activity

0.329

Taken together, our results demonstrate that PKC\u03b5-mediated phosphorylation at T200 and T280 enhances Nanog protein stability in head and neck squamous cell carcinoma.|These observations confirm that PKCepsilon modulates Nanog transcriptional activity and demonstrate that Nanog is phosphorylated by PKCepsilon at T200 and T280 in vivo.

SIGNOR-278203

O00327

Q14995

0

transcriptional regulation

down-regulates quantity by repression

0.467

A retinoic acid receptor-related orphan receptor (ROR) response element within the BMAL1 promoter is responsive to both ROR and REV-ERB (encoded by the genes NR1D1 and NR1D2); ROR activates the transcription of BMAL1, whereas REV-ERB suppresses its transcription.

SIGNOR-268006

O15111

Q8N3F0

1

phosphorylation

down-regulates activity

0.2

INKIT interacted with IKKα/β and TBK1/IKKɛ, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.

SIGNOR-273612

O75496

P00519

0

phosphorylation

up-regulates activity

0.355

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

SIGNOR-278505

P01178-PRO_0000020496

P16519

0

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270337

Q5TKA1

Q00526

0

phosphorylation

up-regulates

0.2

In this report, we demonstrate that cyclin e1/cdk3 phosphorylates lin-9 on thr-96. Mutating thr-96 to alanine inhibits activation of cyclins a2 and b1 promoters, whereas a phosphomimetic asp mutant strongly activates their promoters and triggers accelerated entry into g2/m phase in 293t cells.

SIGNOR-204529

P13498

Q05655

0

phosphorylation

up-regulates

0.2

Phosphorylation of p22phox on threonine 147 enhances NADPH oxidase activity by promoting p47phox binding. | Threonine 147 of p22phox Is Phosphorylated by PKC-α and PKC-δ in Vitro

SIGNOR-260892

Q9BV73

Q68D86

1

relocalization

up-regulates activity

0.2

CCDC102B is recruited to the centrosome by C-Nap1 (also known as CEP250) and interacts with the centrosome linker components rootletin and LRRC45. CCDC102B decorates and facilitates the formation of rootletin filaments. Furthermore, CCDC102B is phosphorylated by Nek2A (an isoform encoded by NEK2) and is disassociated from the centrosome at the onset of mitosis.

SIGNOR-275625

P48163

Q96HS1

0

dephosphorylation

up-regulates activity

0.2

PGAM5-mediated dephosphorylation of malic enzyme 1 (ME1) at S336 allows increased ACAT1-mediated K337 acetylation, leading to ME1 dimerization and activation, both of which are reversed by NEK1 kinase-mediated S336 phosphorylation. SIRT6 deacetylase antagonizes ACAT1 function in a manner that involves mutually exclusive ME1 S336 phosphorylation and K337 acetylation.

SIGNOR-275569

P05771

P11388

1

phosphorylation

up-regulates activity

0.359

Here, we have shown that the enzymatic activity of topoisomerase II alpha protein purified from HeLa cell nuclei was strongly enhanced following phosphorylation by protein kinase C. | Site-directed mutagenesis studies indicated that phosphorylation of serine 29 generated both of these phosphopeptides.

SIGNOR-249195

P63000

Q53QZ3

0

gtpase-activating protein

down-regulates activity

0.581

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-260470

P13611

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.29

By using in vitro and in vivo assays, we showed CSPG2 to be directly transactivated by p53.

SIGNOR-255441

Q13002

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.

SIGNOR-278541

Q9Y5Z0

P05067

1

cleavage

up-regulates activity

0.544

BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein.|Figure 6 Preferred BACE1 and BACE2 cleavage sites. (A) Sequence of APP indicating Î±- and Î²-cleavage sites, BACE1- and BACE2-cleavage sites, and the location of mutations analyzed here. APP numbering is that of the 770-aa isoform.

SIGNOR-261773

Q99814

Q9H3R0

1

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271585

P36956

P17676

0

transcriptional regulation

up-regulates quantity

0.41

These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis

SIGNOR-251645

Q9C0C9

O43541

1

ubiquitination

down-regulates

0.464

We showed that ube2o functions as an e2-e3 hybrid to monoubiquitinate smad6 at lysine 174

SIGNOR-192255

P68400

O14737

1

phosphorylation

up-regulates

0.2

Programmed cell death 5 (pdcd5), a protein involved in cell death and down-regulated in different forms of human tumors. Pdcd5 is phosphorylated in vitro by both ck2alpha subunit and by the ck2 holoenzyme at a residue, s118, which is found phosphorylated in vivo. Transfection of the non-phosphorylatable mutant (s118a) impairs the pdcd5 acceleration of either doxorubimicin- or uv-induced apoptosis in u2os cells

SIGNOR-187106

Q14934

P27361

0

phosphorylation

up-regulates

0.289

The formation of rsk-nfatc4-dna transcription complex is also apparent upon adipogenesis. Bound rsk phosphorylates ser(676) and potentiates nfatc4 dna binding by escalating nfat-dna association. Ser(676) is also targeted by the erk map kinase, which interacts with nfat at a distinct region than rsk. Thus, integration of the erk/rsk signaling pathway provides a mechanism to modulate nfatc4 transcription activity.

SIGNOR-133276

Q9NYY3

Q969H0

1

phosphorylation

down-regulates

0.483

Plk2 regulates centriole duplication through phosphorylation-mediated degradation of fbxw7 (human cdc4).Plk2 phosphorylates fbxw7 on serine 176

SIGNOR-196448

P08670

P06493

0

phosphorylation

down-regulates

0.362

These results strongly suggest that cdc2 kinase is the kinase which phosphorylates vimentin ser55 in the entire cytoplasm during mitosis and that the appearance of immunoreactivities with antibody 4a4 in cell staining indeed reflect the vimentin phosphorylation by cdc2 kinase. immunofluorescent evidence using antibody 4a4 and biochemical analysis using vimentin ser55 peptide showed that the degree of disassembly of vimentin filament of various cell types at early mitotic phase correlated well with the amount of mitotically activated cdc2 kinase.

SIGNOR-35492

O60674

Q12913

0

dephosphorylation

down-regulates activity

0.323

These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation.

SIGNOR-277094

O14672

P26378

0

post transcriptional regulation

up-regulates quantity

0.2

Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure

SIGNOR-266865

P11802

P19532

1

phosphorylation

up-regulates activity

0.2

CDK4 and CDK6 interact with TFEB and TFE3 in the nucleus We next investigated how CDK4 and CDK6 activate TFEB and TFE3 .|We found that CDK4 and CDK6 interact with and phosphorylate nuclear TFEB and TFE3, thereby promoting their shuttling to the cytoplasm.

SIGNOR-279514

O75385

Q15437

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting SEC23B degradation.

SIGNOR-265285

Q13501

Q9UHD2

0

phosphorylation

up-regulates

0.709

Tbk-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on ser-403, a residue essential for its role in autophagic clearance.

SIGNOR-191944

P08235

P28482

0

phosphorylation

down-regulates quantity by destabilization

0.286

Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation.

SIGNOR-276101

Q14457

O75385

0

phosphorylation

up-regulates activity

0.771

In the nucleation step of autophagy, The ULK1 complex phosphorylates and activates the Beclin-1-VPS34 complex.

SIGNOR-278503

P45983

P04637

1

phosphorylation

up-regulates

0.796

Activated jnk phosphorylates p53

SIGNOR-59812

P35368

P17252

0

phosphorylation

down-regulates activity

0.39

Phorbol ester-induced phosphorylation of the Ser394 and Ser400 as well as GRK2-mediated phosphorylation of the Ser404, Ser408, and Ser410, resulted in the desensitization of alpha1BAR-mediated inositol phosphate response.

SIGNOR-248988

P61244

P68400

0

phosphorylation

down-regulates

0.361

Here, we have mapped the nh2-terminal in vivo phosphorylation sites of max to ser2 and ser11[...]

SIGNOR-35772

P04004

P05129

0

phosphorylation

up-regulates quantity by stabilization

0.285

Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.

SIGNOR-248964

P40763

Q99558

0

phosphorylation

up-regulates activity

0.26

Activation of Stat3 by NIK requires NIK kinase activity as showed by kinase assays.|When we transfected NIK into LNCaP cells, NIK was able to phosphorylate Stat3 at both tyrosine 705 and serine 727 residues ( Fig. 3 A).

SIGNOR-279341

P52655

P19784

0

phosphorylation

up-regulates activity

0.374

We now show that human TFIIA is phosphorylated in vivo on serine residues that are partially conserved between yeast and human TFIIA large subunits. Alanine substitution mutation of serine residues 316 and 321 in TFIIA alphabeta reduced TFIIA phosphorylation significantly in vivo. Additional alanine substitutions at serines 280 and 281 reduced phosphorylation to undetectable levels. Mutation of all four serine residues reduced the ability of TFIIA to stimulate transcription in transient transfection assays with various activators and promoters, indicating that TFIIA phosphorylation is required globally for optimal function.

SIGNOR-250996

O14980

Q13485

1

relocalization

down-regulates

0.3

We demonstrate that inhibition of crm1-mediated nuclear export by treatment of cells with leptomycin b results in endogenous smad4 accumulating very rapidly in the nucleus.

SIGNOR-84247

P12931

P49789

1

phosphorylation

up-regulates activity

0.466

The human tumor suppressor Fhit is a homodimeric histidine triad (HIT) protein of 147 amino acids which has Ap3A hydrolase activity. We have recently discovered that Fhit is phosphorylated in vivo and is phosphorylated in vitro by Src kinaseMALDI-TOF and HPLC-ESI tandem mass spectrometry of intact Fhit and proteolytic peptides of Fhit demonstrated that Fhit is phosphorylated on Y114 on either one or both subunitsThe decreases in the values of Km and kcat for the phosphorylated forms in comparison to those of unphosphorylated Fhit favor the formation and lifetime of the Fhit_Ap3A complex, which may enhance the tumor suppressor activity of Fhit.

SIGNOR-247134

O95295

P17612

0

phosphorylation

up-regulates activity

0.307

PKA-phosphorylation of Snapin significantly increases its binding to synaptosomal-associated protein-25 (SNAP-25). Mutation of Snapin serine 50 to aspartic acid (S50D) mimics this effect of PKA phosphorylation

SIGNOR-250053

P43354

Q13164

0

phosphorylation

up-regulates activity

0.2

Activation of MEK, which in turns activates ERK5, does enhance the ERK5 induced nurr1 activity, while no increase is observed in the presence of a dn MEK5 or of the unphosphorylated ERK5 AEF, in which amino acids phosphorylated by MEK5 are mutated.|The A/B domain of nurr1 is highly phosphorylated in the presence of ERK5 and mutations of two amino acids in this same domain decrease significantly the ERK5 mediated nurr1 transcriptional response.|These data would suggest once again that the basal activity of ERK5 is responsible for the phosphorylation of nurr1.|As shown in XREF_FIG, nurr1 A/B domain was significantly phosphorylated by ERK5, while the GST protein alone was not a substrate for this kinase.

SIGNOR-279215

Q9H1K1

P42345

0

phosphorylation

up-regulates

0.2

Here, we demonstrate that mtorc1 associates with iscu and phosphorylates iscu at serine 14. This phosphorylation stabilized iscu protein.

SIGNOR-201595

Q09472

P31749

0

phosphorylation

up-regulates

0.697

We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity

SIGNOR-148983

Q2M1Z3

P60953

1

gtpase-activating protein

down-regulates activity

0.673

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-260490

P29401

Q8N531

0

ubiquitination

up-regulates activity

0.2

Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation.

SIGNOR-277843

P27986

P06239

0

phosphorylation

down-regulates activity

0.623

the regulatory p85 subunit of phosphatidylinositol 3-kinase is phosphorylated on tyrosine residues. We report that this phosphorylation event is readily catalyzed by the Abl and Lck protein-tyrosine kinases in vitro, by Bcr-Abl or a catalytically activated Lck-Y505F in co-transfected COS cells. we have mapped a major phosphorylation site to Tyr-688 in the C-terminal SH2 domain of p85. Tyrosine phosphorylation of p85 in vitro or in vivo was not associated with detectable change in the enzymatic activity of the phosphatidylinositol 3-kinase heterodimer, but correlated with a strong reduction in the binding of some, but not all, phosphoproteins to the SH2 domains of p85.

SIGNOR-251383

Q12913

P36888

1

dephosphorylation

down-regulates activity

0.49

Moreover, activated FLT3 could be dephosphorylated by recombinant DEP-1 in vitro.|The data indicate that DEP-1 is negatively regulating FLT3 signaling activity and that its loss may contribute to but is not sufficient for leukemogenic cell transformation.

SIGNOR-277092

Q13464

P60484

1

phosphorylation

up-regulates

0.656

In addition, active rhoa is able to stimulate the phospholipid phosphatase activity of pten in human embryonic kidney cells and leukocytes, and this regulation seems to require rhoa's downstream effector, rhoa-associated kinase (rock). together with the observation that individual substitution of ser 229 and thr 223 restored some of the rescuing ability (fig. 4b), we conclude that effective regulation of pten by sdf-1 may require more than one of these residues.

SIGNOR-134855

Q01484

Q92823

0

relocalization

up-regulates quantity

0.737

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266719

Q9Y4D1

P12931

0

phosphorylation

up-regulates activity

0.325

Our findings reveal a novel mechanism by which reversible tyrosine phosphorylation of DAAM1 by Src and PTPN3 regulates actin dynamics and lung cancer invasiveness.|PTPN3 suppresses lung cancer cell invasiveness by counteracting Src mediated DAAM1 activation and actin polymerization.

SIGNOR-280128

P37840

P53355

0

phosphorylation

up-regulates quantity

0.27

We demonstrated that DAPK1 directly phosphorylates \u03b1-synuclein at Ser129, and induces the formation of insoluble \u03b1-synuclein aggregates.

SIGNOR-278440

O15530

Q05513

1

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

P49841

Q13144

1

phosphorylation

down-regulates activity

0.579

The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535).

SIGNOR-251236

Q9UHD2

Q92630

0

phosphorylation

down-regulates quantity by destabilization

0.413

We further found that DYRK2 phosphorylated Ser527 of TBK1, which is essential for the recruitment of NLRP4 and for the E3 ubiquitin ligase DTX4 to degrade TBK1.

SIGNOR-276939

P15923

P49137

0

phosphorylation

up-regulates

0.52

Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2

SIGNOR-166643

Q15418

P78371

1

phosphorylation

up-regulates

0.249

Furthermore, both the s260a and s260d mutants showed a decreased folding capacity as compared to cells expressing the wild-type cct_ subunit ( fig.?_5e), suggesting that a cyclic phosphorylation of the s260 site by s6k1 is likely to be important for chaperonin function and that mutation of this site interferes with this process.

SIGNOR-172986

Q14469

P04150

1

transcriptional regulation

down-regulates quantity by repression

0.2

HES1 binding to the promoter of the NC3C1 gene inhibits its expression and results in insufficient production of the encoded glucocorticoid receptor- rendering these cells resistant to treatment with dexamethasone

SIGNOR-251674

P67775

P27361

1

dephosphorylation

down-regulates

0.647

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).

SIGNOR-103162

Q9HB96

O14757

0

phosphorylation

up-regulates

0.716

Chk1 directly phosphorylates the fance subunit of the fa core complex on two conserved sites (threonine 346 and serine 374). chk1-mediated phosphorylation of fance is required for the fanconi anemia/brca pathway.

SIGNOR-153023

Q9H9Z2

P28482

0

phosphorylation

down-regulates activity

0.262

Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200.

SIGNOR-277338

O43303

P24941

0

phosphorylation

down-regulates activity

0.515

GST-tagged recombinant CP110 (GST-wt) was robustly phosphorylated by cyclin E/CDK2 (Figure 2A). Expression of a mutant derivative of CP110 refractory to CDK phosphorylation provokes marked polyploidy. We localized the majority (nine of ten) of potential CDK2 phosphorylation sites in CP110 to an amino-terminal fragment (GST-ΔN1; Figure 1B)

SIGNOR-265956

P49841

Q9Y6K9

1

phosphorylation

down-regulates quantity

0.431

For analysis of phosphorylation of NEMO on Ser8 and Ser17 by GSK-3, we generated phospho-specific antibodies (anti-phospho-NEMO-Ser8 and anti-phospho-NEMO-Ser17) while anti-phospho-NEMO-Ser31 and anti-phospho-NEMO-Ser43 were commercially available. Indeed, GSK-3\u03b2 was able to phosphorylate all four serines of rhNEMO in a time-dependent manner in an in vitro kinase assay (Fig. 3a).|In this study, we identified NEMO as a GSK-3\u03b2 substrate that is phosphorylated at several serine residues located within the N-terminal domain.|The kinase forms a complex with wild-type NEMO while point mutations of NEMO at the specific serines abrogated GSK-3Œ≤ binding and subsequent phosphorylation of NEMO resulting in its destabilization

SIGNOR-279527

P17252

P15311

1

phosphorylation

up-regulates

0.547

Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567.

SIGNOR-133223

P28482

Q99967

1

phosphorylation

up-regulates activity

0.454

CITED2 coactivation is enhanced by activation of MAPK1 and requires T166.|CITED2 is phosphorylated by MAPK1 at S85, T166 and T175.

SIGNOR-278410

P28562

P45983

1

dephosphorylation

down-regulates

0.789

Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2.

SIGNOR-46079

Q00535

P07197

1

phosphorylation

down-regulates quantity

0.42

Converse to the effect of PKA overexpression, overexpression of CDK5 and its activator, p35, decreased the association between spinophilin and NF-M as well as the expression of NF-M.|Moreover, CDK5 phosphorylates NF-M [ xref ], and this was also apparent in our data, given a dramatic molecular weight shift in the NF-M band following CDK5 overexpression.

SIGNOR-279683

P16104

O76064

0

ubiquitination

up-regulates

0.2

Rnf8 can ubiquitylate histone h2a and h2ax,

SIGNOR-159309

Q13882

P51692

1

phosphorylation

up-regulates

0.429

Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.

SIGNOR-159066

P24941

Q01196

1

phosphorylation

up-regulates activity

0.2

We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein.

SIGNOR-138932

Q12772

Q8WU17

0

ubiquitination

down-regulates quantity

0.477

Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner

SIGNOR-271958

P12931

P10398

1

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

Q96PX1

P24941

0

phosphorylation

up-regulates activity

0.287

CDK2 promotes phosphorylation of RNF157 at the same Ser 660-663 residues that become phosphorylated downstream of combined PI3K and MAPK pathway activity.

SIGNOR-279016

Q15208

P49841

0

phosphorylation

down-regulates activity

0.278

GSK-3β phosphorylated STK38 on residues S6 and T7 in vitro, depending largely on a PKA-mediated priming phosphorylation of STK38 on residues S10 and S11, respectively. Our results indicate that that GSK-3β inhibits STK38's full activation, and suggest that STK38 activation is required to prevent cell death in response to oxidative stress.

SIGNOR-276392

Q8IVT5

Q7Z569

0

ubiquitination

down-regulates quantity by destabilization

0.661

Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.

SIGNOR-272028

P41229

P78317

0

sumoylation

up-regulates activity

0.2

Hendriks and coworkers showed that, in response to alkylation damage by methyl methanesulfonate (MMS), SUMOylated JARID1B (KDM5B) is ubiquitylated by the SUMOtargeted ubiquitin ligase RNF4 and degraded by the proteasome, whereas JARID1C (KDM5C) is SUMOylated and recruited to the chromatin to demethylate histone H3K4 (Hendriks et al., 2015).

SIGNOR-271576

Q9NZ42

P49768

1

cleavage

up-regulates

0.959

Our data reveal a direct role of pen-2 in proteolytic cleavage of ps1 and a regulatory function of aph-1, in coordination with pen-2, in the biogenesis of the ps1 complex.

SIGNOR-97113

Q16549

P30305

1

phosphorylation

down-regulates

0.2

We propose that regulation of cdc25b phosphorylation by p38 is a critical event for initiating the g2/m checkpoint after ultraviolet radiation

SIGNOR-107423

P24941

P25205

1

phosphorylation

up-regulates

0.796

In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722.

SIGNOR-176656

Q99962

O75116

0

phosphorylation

down-regulates

0.439

We identified the phosphorylation site of endophilin a1 at thr-14 endophilin t14d inhibited egf receptor internalization. Furthermore, phosphorylation of endophilin by rho-kinase inhibited the binding to cin85.

SIGNOR-140466

Q16537

Q9P2K6

0

polyubiquitination

down-regulates quantity by destabilization

0.2

PPP2R5ϵ is a KLHL42 substrate and affects TGF-β signaling in SSc. Lys-84 is a candidate ubiquitin acceptor site within PPP2R5ϵ.

SIGNOR-272205

O75592

P49815

1

ubiquitination

down-regulates quantity by destabilization

0.356

We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain.

SIGNOR-278704

P16885

P43405

0

phosphorylation

up-regulates activity

0.753

Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase C\u03b32 (PLC\u03b32).|Syk in turn phosphorylates and activates the B cell linker protein (BLNK), phosphoinositide 3-kinase (PI3K) and phospholipase Cgamma2 (PLCgamma2).

SIGNOR-278995

P62714

P05771-2

1

dephosphorylation

down-regulates activity

0.469

Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C beta II are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme.

SIGNOR-248587

P49760

Q9UBK2

1

phosphorylation

down-regulates activity

0.2

Clk2 could also repress PGC-1alpha activation of Foxo1 on the IRS response element , as well as repress the Pepck promoter .|Clk2 phosphorylates and represses PGC-1\u03b1.

SIGNOR-278228

P06493

Q12778

1

phosphorylation

down-regulates

0.511

Overexpression of cdk1 inhibits the transcriptional activity of foxo1 in pca cells through s249 phosphorylation on foxo1.

SIGNOR-178202

Q05513

Q5JVS0

1

phosphorylation

down-regulates activity

0.292

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249257

P29466

P49768

1

cleavage

up-regulates activity

0.385

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

SIGNOR-261755

P02458

P03956

0

cleavage

down-regulates quantity by destabilization

0.445

MMP-1 cleaves type II collagen at the peptide bond Gly906-Leu907 Proteolysis of triple-helical collagen is an important step in the progression toward irreversible tissue damage in osteoarthritis. Earlier work on the expression of enzymes in cartilage suggested that collagenase-1 (MMP-1) contributes to the process.

SIGNOR-256341

P49407

P27361

0

phosphorylation

down-regulates

0.716

Erk1 and erk2 phosphorylate beta-arrestin1 at ser-412 in vitro. . in the resting state, cytosolic arrestin1 proteins are constitutively phosphorylated by extracellular signal-regulated kinase (erk) at ser412, located within their distal c terminus. erk-phosphorylated arrestin1 is unable to associate with clathrin cages, whereas this constraint is removed upon its dephosphorylation

SIGNOR-67634

P09668

P02818

1

cleavage

down-regulates quantity by destabilization

0.283

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

SIGNOR-256325

Q16566

Q9UNW9

1

phosphorylation

up-regulates quantity

0.255

CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. CaMKIV Phosphorylates Nova-2 and Regulates Its Nuclear Localization. Conversely, Nova-2 with single or double mutations to alanine (2A and 1A2A) was predominantly nuclear, like the WT (Figures 5H and and5I).5I). In contrast, glutamate mutations at site 3 had no effect on Nova-2 localization (Figures 5H and and5I)5I) or on Nova-2 binding to RNA (Figure S5E). These results showed that active CaMKIV reduces Nova-2 nuclear localization by phosphorylating sites 1 and 2 (S25, T27).

SIGNOR-273521

Q14643

Q96K19

0

polyubiquitination

down-regulates activity

0.431

In summary, here we present evidence that RNF170 is an E3 ligase that mediates IP3 receptor ubiquitination and processing by the UPP and that it is recruited to activated IP3 receptors by the erlin1/2 complex to which it is constitutively bound.

SIGNOR-271913

O75116

Q9UBR4

1

phosphorylation

up-regulates activity

0.2

Rok-\u03b1 phosphorylates and activates LIM kinase, which in turn phosphorylates and inactivates cofilin.

SIGNOR-280110

O15350

Q05655

0

phosphorylation

up-regulates

0.307

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

SIGNOR-90279

Q9Y4I1

P31751

0

phosphorylation

up-regulates activity

0.458

Here we identify an Akt consensus phosphorylation motif in the actin-based motor protein myosin 5a and show that insulin stimulation leads to phosphorylation of myosin 5a at serine 1650. This Akt-mediated phosphorylation event enhances the ability of myosin 5a to interact with the actin cytoskeleton.Taken together, these data indicate that myosin 5a is a newly identified direct substrate of Akt2 and, upon insulin stimulation, phosphorylated myosin 5a facilitates anterograde movement of GLUT4 vesicles along actin to the cell surface.

SIGNOR-262632