GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q00987	P27695	1	ubiquitination	down-regulates quantity by destabilization	0.416	Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.	SIGNOR-278555
Q96F44	Q99453	1	ubiquitination	down-regulates	0.485	The e3 ubiquitin ligasetrim11mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expandedphox2b.	SIGNOR-195878
P68400	Q9H2G2	1	phosphorylation	down-regulates	0.2	Slk down-regulation by v-src is indirect and is accompanied by slk hyperphosphorylation on serine residues. Deletion analysis revealed that casein kinase ii (ck2) sites at position 347/348 are critical for v-src-dependent modulation of slk activity.	SIGNOR-147879
P36956	Q9H5J4	1	transcriptional regulation	up-regulates quantity by expression	0.45	These data demonstrated that Elovl-6 is regulated directly and primarily by SREBP-1c.	SIGNOR-267943
P53350	Q9H6R7	1	phosphorylation	up-regulates activity	0.2	PLK1 Phosphorylates MMAP to Promote Its Interaction with KIF2A and MRE11. we performed in vitro kinase assays followed by mass spectrometry and found that two sites (S686 and S695) in this cluster were phosphorylated. Thus, all of these results are in agreement that this cluster is phosphorylated by PLK1.	SIGNOR-273730
P50613	P13631	1	phosphorylation	up-regulates activity	0.418	RARg Is Phosphorylated by cdk7 in Its B and F Regions \| Mutation into alanine of Ser-77 and Ser-79 located in the A/B region reduced the transcriptional activity of hRARg1 (Fig. 9A), confirming that these phosphorylation sites are required for optimal transcription.	SIGNOR-259853
P29350	P40763	1	dephosphorylation	down-regulates	0.457	Stat3 may also be a substrate of shp1	SIGNOR-178699
P68400	Q16543	1	phosphorylation	up-regulates activity	0.397	Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. \| In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.	SIGNOR-250838
P17542	P62256	1	transcriptional regulation	up-regulates quantity by expression	0.326	Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.\|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.	SIGNOR-269000
O14874	P12694	1	phosphorylation	down-regulates	0.609	Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.	SIGNOR-25084
Q12778	Q8IW41	0	phosphorylation	up-regulates activity	0.422	The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.	SIGNOR-280037
P17252	P35222	1	phosphorylation	down-regulates	0.413	As shown in Fig. 1 B, PKCalpha readily phosphorylated Ser33 and Ser37 / Thr41 on full-length beta-catenin (beta-catenin 1 - 781) and CTD deletion mutant (beta-catenin 1-682).\|To examine the effect of the armadillo repeats 1-5 on PKCalpha mediated beta-catenin degradation, DNA constructs expressing beta-catenin 1 - 781 and beta-catenin deletion mutants (beta-catenin 1-422 and beta-catenin 1-138) were transfected into HEK293 cells, followed by treatment with increasing concentrations of A23187 and CGK062, which are known activators of PKCalpha.	SIGNOR-278492
P24752	P29803	1	acetylation	down-regulates activity	0.2	We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)	SIGNOR-267634
P08581	Q04206	0	transcriptional regulation	up-regulates quantity	0.25	Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.	SIGNOR-241929
O15530	P31749	1	phosphorylation	up-regulates	0.748	We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.	SIGNOR-67367
P42345	P08069	1	phosphorylation	up-regulates activity	0.494	Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.\|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR.	SIGNOR-280044
Q16539	P78536	1	phosphorylation	up-regulates activity	0.405	We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding	SIGNOR-163970
Q14145	Q16236	1	ubiquitination	down-regulates quantity	0.813	Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation	SIGNOR-259335
Q9Y5X2	P23458	0	phosphorylation	up-regulates activity	0.341	IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.	SIGNOR-273647
O95747	Q13621	1	phosphorylation	up-regulates activity	0.502	We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).	SIGNOR-276309
O00418	O15264	0	phosphorylation	down-regulates activity	0.578	eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]	SIGNOR-250089
Q99626	Q9HAW8	1	transcriptional regulation	up-regulates quantity by expression	0.257	Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.	SIGNOR-253968
P53350	Q9UKT4	1	phosphorylation	down-regulates	0.783	We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.	SIGNOR-142949
Q13315	P46527	1	phosphorylation	up-regulates quantity by stabilization	0.419	We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.	SIGNOR-279392
P07550	P31749	0	phosphorylation	down-regulates	0.354	Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation.	SIGNOR-252470
P68400	P52655	1	phosphorylation	up-regulates activity	0.379	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-250877
Q9UQM7	Q05469	1	phosphorylation	down-regulates	0.2	Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.	SIGNOR-58251
P41743	Q6P1M3	1	phosphorylation	up-regulates activity	0.687	This finding indicates that both mLgl-2 and mLgl-1 are phosphorylated in vivo in an aPKC lambda activity-dependent manner.	SIGNOR-263180
P31749	P10276	1	phosphorylation	down-regulates	0.602	We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt.	SIGNOR-252489
P20393	P37231	0	transcriptional regulation	up-regulates quantity by expression	0.277	Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation.	SIGNOR-268022
P68431	O75151	0	demethylation	down-regulates activity	0.2	PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark.	SIGNOR-264521
P31321	O43164	0	polyubiquitination	down-regulates quantity by destabilization	0.2	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271857
P10412	P50750	0	phosphorylation	down-regulates activity	0.2	These data provide further evidence that CDK9 phosphorylates H1.4-S187, and that the level of pS187-H1.4 at genes is directly related to the extent of co-enrichment of CDK9.\|that enrichment of pS187-H1.4 at genes is positively related to their transcription.	SIGNOR-279691
Q14807	Q96EP1	0	ubiquitination	down-regulates quantity by destabilization	0.399	Chfr ubiquitinates Kif22 and promotes its degradation.	SIGNOR-271469
O15530	P12931	0	phosphorylation	up-regulates activity	0.585	Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.	SIGNOR-109533
P61586	Q7Z6I6	0	gtpase-activating protein	down-regulates activity	0.449	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-260485
Q9UNE7	Q16665	1	ubiquitination	down-regulates quantity by destabilization	0.376	the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.	SIGNOR-271426
Q13393	P54646	0	phosphorylation	up-regulates	0.2	Ampk-wild type (wt) stimulates pld activity, while ampk-dominant negative (dn) inhibits it. Ampk regulates pld1 activity through phosphorylation of the ser-505 and this phosphorylation is increased by the presence of amp.	SIGNOR-164293
P51617	Q9NWZ3	0	phosphorylation	up-regulates activity	0.687	In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1.	SIGNOR-117315
P26367	Q9H2X6	0	phosphorylation	up-regulates activity	0.463	HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373.	SIGNOR-251271
P54646	P28562	1	phosphorylation	down-regulates quantity by destabilization	0.273	Taken together, these results imply that nicotine acts via AMPKα2 to phosphorylate MKP1 at Ser334, instigating MKP1 ubiquitination and proteasome-mediated degradation.	SIGNOR-276890
Q05655	P48995	1	phosphorylation	up-regulates activity	0.2	Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.	SIGNOR-279559
P25098	P21731-2	1	phosphorylation	down-regulates activity	0.2	These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.	SIGNOR-274088
Q13153	Q99523	1	phosphorylation	down-regulates activity	0.2	PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.	SIGNOR-273718
Q9Y2K2	O15055	1	phosphorylation	down-regulates quantity by destabilization	0.2	In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation.	SIGNOR-279570
P23471	Q9UM73	1	dephosphorylation	down-regulates	0.545	Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation.	SIGNOR-157227
Q05209	O43586	1	dephosphorylation	down-regulates activity	0.61	We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. \|The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.\|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl	SIGNOR-248656
Q16659	Q8IW41	1	phosphorylation	up-regulates activity	0.69	ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5.	SIGNOR-279073
Q15678	Q03135	1	dephosphorylation	down-regulates activity	0.2	Finally, PTPN14 overexpression in B16F10 cells reduced the ability of CAV1 to induce metastasis in vivo.\|Moreover, the CAV1 (Y14F) mutant protein was shown to co-immunoprecipitate with PTPN14 even in the absence of E-cadherin, and overexpression of PTPN14 reduced CAV1 phosphorylation on tyrosine 14, as well as suppressed CAV1 enhanced cell migration, invasion and Rac-1 activation in B16F10, metastatic colon [HT29 (US)] and breast cancer (MDA-MB-231) cell lines.	SIGNOR-277054
Q9NX09	P49841	0	phosphorylation	down-regulates quantity by destabilization	0.339	It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.	SIGNOR-279526
Q9HCU9	O43791	0	ubiquitination	down-regulates quantity	0.402	Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells.	SIGNOR-268857
P12277	Q96DX5	0	polyubiquitination	down-regulates quantity by destabilization	0.683	We demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.	SIGNOR-271623
Q14106	P24941	0	phosphorylation	up-regulates activity	0.246	Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.	SIGNOR-273601
Q16549	P49715	1	phosphorylation	down-regulates	0.2	Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21	SIGNOR-186202
Q13164	Q14814	1	phosphorylation	up-regulates	0.705	Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b. the sites phosphorylated by activated bmk1 were mapped to ser-355, thr-312, and thr-319 of mef2a and ser-179 of mef2d both in vitro and in vivo.	SIGNOR-236041
P32754	Q96FA3	0	ubiquitination	down-regulates quantity by destabilization	0.2	Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.	SIGNOR-272959
Q9NQG5	P14635	1	transcriptional regulation	up-regulates quantity by expression	0.2	These results indicated that CREPT regulates the Cyclin B1 expression via directly targeting its promoter region during transcription.	SIGNOR-265500
P06493	Q9Y6X9	1	phosphorylation	down-regulates quantity by destabilization	0.2	Mechanically, PTX and VCR activate cyclin-dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone-mediated autophagy (CMA) mechinery, resulting in its autophagic degradation.	SIGNOR-277837
Q8N6T7	Q00987	0	ubiquitination	down-regulates quantity	0.415	These results suggest that MDM2 degrades SIRT6 in a proteasome dependent manner.\|USP10 has been shown to deubiquitinate and stabilize p53, a well-known substrate of MDM2, suggesting a mechanism whereby SIRT6 is ubiquitinated and destabilized by MDM2, which could be reversed by USP10 mediated deubiquitination.	SIGNOR-278702
P35869	P04798	1	transcriptional regulation	up-regulates quantity by expression	0.684	Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.	SIGNOR-259909
O43524	Q13547	0	deacetylation	up-regulates activity	0.368	The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a	SIGNOR-256486
Q14934	P45983	0	phosphorylation	up-regulates activity	0.467	Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.\|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.	SIGNOR-280033
P51608	P18031	1	transcriptional regulation	down-regulates quantity by repression	0.2	In this study, we have demonstrated that the PTPN1 gene, which encodes PTP1B, was a direct target of MECP2 and that PTP1B protein levels were dramatically increased in Mecp2-mutant mice and in fibroblasts derived from patients with RTT.	SIGNOR-264546
Q9HAU4	P36894	1	ubiquitination	down-regulates	0.552	Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps	SIGNOR-192898
P42568	O00141	0	phosphorylation	down-regulates activity	0.509	In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.\|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation.	SIGNOR-279111
O60381	P14598	1	transcriptional regulation	down-regulates quantity by repression	0.265	Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene.	SIGNOR-261614
O43791	P10070	1	ubiquitination	down-regulates quantity	0.71	RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins	SIGNOR-268860
Q9ULV8	P12931	0	phosphorylation	up-regulates	0.537	Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c.	SIGNOR-165862
P17275	Q9Y222	0	transcriptional regulation	up-regulates quantity by expression	0.265	Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.	SIGNOR-261585
Q13621	Q9UEW8	0	phosphorylation	up-regulates activity	0.577	We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).	SIGNOR-276308
P00519	P49759	0	phosphorylation	down-regulates	0.259	Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3	SIGNOR-181031
P12931	P35222	1	phosphorylation	down-regulates activity	0.761	beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation.	SIGNOR-106458
Q96T88	P24941	0	phosphorylation	down-regulates quantity by destabilization	0.303	UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant	SIGNOR-277192
Q16549	Q92945	1	phosphorylation	down-regulates	0.2	Ksrp phosphorylated by p38 displays compromised binding to are-containing transcripts and fails to promote their rapid decay,although it retains the ability to interact with the mrna degradation machinery.	SIGNOR-143167
P17275	Q16539	0	phosphorylation	up-regulates	0.502	These results clearly demonstrate that phosphorylation by p38 kinase is essential for the regulation of dmp1 transcription by junb and p300. phosphorylation of junb at ser-79 was found to be essential for its interaction with p300.	SIGNOR-127545
O00444	Q969U6	1	phosphorylation	down-regulates activity	0.543	The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6.	SIGNOR-275476
O75379	P68400	0	phosphorylation	up-regulates	0.446	The r-snare vamp4, which contains a dileucine motif, binds to the ap-1 or the ggas. Serine 20 and leucines 25,26 are essential for this binding. Ap-1 association with vamp4 is enhanced when serine 30 is phosphorylated by casein kinase 2. This phosphorylation-dependent modulation of ap-1 binding is mediated by pacs-1 (phosphofurin acidic cluster sorting protein). Ablation of both the dileucine motif and serine 30 results in a dramatic mislocalization of vamp4 in the regulated secretory pathway.	SIGNOR-119090
Q14289	Q02535	1	phosphorylation	up-regulates quantity	0.2	Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.\|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.	SIGNOR-278496
Q13409	Q8NG06	0	polyubiquitination	down-regulates quantity by destabilization	0.298	Trim58 ubiquitinates dynein and promotes its proteasomal degradation. Trim58 binds DIC directly, polyubiquitinates it in vitro, and induces proteasomal degradation of the dynein holocomplex in vivo.	SIGNOR-272841
Q99856	P0DOX3	1	transcriptional regulation	up-regulates quantity by expression	0.2	In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.\| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene.	SIGNOR-268531
Q92915	O60674	0	phosphorylation	up-regulates activity	0.2	JAK2 regulates Nav1.6 channel function via FGF14Y158 phosphorylation\|Patch-clamp electrophysiology revealed that through Y158, JAK2 controls FGF14-dependent modulation of Nav1.6 channels. In hippocampal CA1 pyramidal neurons, the JAK2 inhibitor Fedratinib reduced firing by a mechanism that is dependent upon expression of FGF14.	SIGNOR-275747
Q8TDC3	Q8N5S9	0	phosphorylation	up-regulates activity	0.307	In transfected COS-7 cells, kinase activity and Thr (189) phosphorylation of overexpressed SAD-B were significantly enhanced by coexpression of constitutively active CaMKKalpha (residues 1-434) in a manner similar to that observed with coexpression of LKB1, STRAD, and MO25.\|Taken together, these results indicate that CaMKKalpha is capable of activating SAD-B through phosphorylation of Thr (189) both in vitro and in vivo and demonstrate for the first time that CaMKK may be an alternative activating kinase for SAD-B.	SIGNOR-280202
A8K4G0	P06241	0	phosphorylation	up-regulates activity	0.308	As CD300b phosphorylation was occurring only in the presence of both c-Fyn and DAP-12, we addressed whether tyrosine phosphorylation was required for association of CD300b and DAP-12. For this purpose, we generated a set of HA-tagged CD300b mutants affecting the transmembrane lysine (K158L), the cytoplasmic tyrosine (Y188F) or both residues.\|As expected, the CD300b double mutant could neither recruit DAP-12 nor become phosphorylated in the presence of c-Fyn kinase (Fig. 5⇑C). Association between CD300b and DAP-12 was maintained in absence of the c-Fyn kinase, indicating that phosphorylation of the adaptor was not essential for the formation of the complex (data not shown)	SIGNOR-264771
Q15717	P06493	0	phosphorylation	down-regulates activity	0.407	Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.\|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.	SIGNOR-279014
Q92973	O15534	1	relocalization	up-regulates activity	0.268	The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization	SIGNOR-262102
Q13131	O60825	1	phosphorylation	up-regulates activity	0.464	Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.	SIGNOR-84061
Q96EB6	P04637	1	deacetylation	down-regulates	0.803	Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.	SIGNOR-182515
Q8WTR2	P45983	1	dephosphorylation	down-regulates	0.421	Skrp1 was highly specific for c-jun n-terminal kinase (jnk) in vitro and effectively suppressed the jnk activation in response to tumor necrosis factor alpha or thapsigargin skrp1 does not bind directly to its target jnk, but co-precipitation of skrp1 with the mapk kinase mkk7, a jnk activator, was found in vitro and in vivo.	SIGNOR-117260
P35568	Q02750	0	phosphorylation	down-regulates	0.352	Thus, at least three kinases mediate phosphorylation of ser307, including jnk, serine kinases in the pi 3-kinase cascade that are activated byinsulinor igf-1, and mek1-sensitive kinase cascades during tnf-alfa stimulation.	SIGNOR-236611
O75385	Q86WV6	1	phosphorylation	down-regulates activity	0.2	Collectively, our data indicates that cGAS is essential for the activation of AMPK and ULK1 suppression of STING (XREF_FIG) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity (XREF_FIG).\|Collectively, our data indicates that cGAS is essential for the activation of AMPK/ULK1 suppression of STING ( xref ) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity ( xref ).	SIGNOR-279316
Q02156	Q9H9S0	1	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
P23443	P36956	1	phosphorylation	up-regulates activity	0.424	Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation.\|Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element-binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation ( xref ).	SIGNOR-280120
Q92830	P11802	0	phosphorylation	up-regulates activity	0.36	Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5\|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)	SIGNOR-275494
P17480	P24941	0	phosphorylation	up-regulates activity	0.372	Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity	SIGNOR-235419
P43250	P08069	1	phosphorylation	down-regulates quantity by destabilization	0.306	GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation	SIGNOR-276412
P28482	P09917	1	phosphorylation	up-regulates activity	0.381	Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.	SIGNOR-264409
Q8WYQ5	P00519	0	phosphorylation	up-regulates activity	0.2	The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267).	SIGNOR-262604
Q15772	Q9BR39	1	phosphorylation	up-regulates activity	0.36	Studies in HEK293 cells confirmed that SPEG overexpression increases JPH2 phosphorylation .	SIGNOR-279759
P01116	Q5VWQ8	0	gtpase-activating protein	down-regulates activity	0.518	The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.	SIGNOR-254746
O60566	Q96SN8	0	transcriptional regulation	up-regulates quantity by expression	0.27	These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter	SIGNOR-260312

Q00987

P27695

1

ubiquitination

down-regulates quantity by destabilization

0.416

Once the reaction proceeds beyond the monoubiquitination stage, MDM2 polyubiquitinates APE1 for degradation.

SIGNOR-278555

Q96F44

Q99453

1

ubiquitination

down-regulates

0.485

The e3 ubiquitin ligasetrim11mediates the degradation of congenital central hypoventilation syndrome-associated polyalanine-expandedphox2b.

SIGNOR-195878

P68400

Q9H2G2

1

phosphorylation

down-regulates

0.2

Slk down-regulation by v-src is indirect and is accompanied by slk hyperphosphorylation on serine residues. Deletion analysis revealed that casein kinase ii (ck2) sites at position 347/348 are critical for v-src-dependent modulation of slk activity.

SIGNOR-147879

P36956

Q9H5J4

1

transcriptional regulation

up-regulates quantity by expression

0.45

These data demonstrated that Elovl-6 is regulated directly and primarily by SREBP-1c.

SIGNOR-267943

P53350

Q9H6R7

1

phosphorylation

up-regulates activity

0.2

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

SIGNOR-273730

P50613

P13631

1

phosphorylation

up-regulates activity

0.418

RARg Is Phosphorylated by cdk7 in Its B and F Regions | Mutation into alanine of Ser-77 and Ser-79 located in the A/B region reduced the transcriptional activity of hRARg1 (Fig. 9A), confirming that these phosphorylation sites are required for optimal transcription.

SIGNOR-259853

P29350

P40763

1

dephosphorylation

down-regulates

0.457

Stat3 may also be a substrate of shp1

SIGNOR-178699

P68400

Q16543

1

phosphorylation

up-regulates activity

0.397

Phosphorylation of serine 13 is required for the proper function of the Hsp90 co-chaperone, Cdc37. | In this report, we demonstrate that mammalian Cdc37 is phosphorylated on Ser13 in situ in rabbit reticulocyte lysate and in cultured K562 cells and that casein kinase II is capable of quantitatively phosphorylating recombinant Cdc37 at this site.

SIGNOR-250838

P17542

P62256

1

transcriptional regulation

up-regulates quantity by expression

0.326

Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.

SIGNOR-269000

O14874

P12694

1

phosphorylation

down-regulates

0.609

Phosphorylation sites and inactivation of branched-chain alpha-ketoacid dehydrogenase isolated from rat heart, bovine kidney, and rabbit liver, kidney, heart, brain, and skeletal muscle.

SIGNOR-25084

Q12778

Q8IW41

0

phosphorylation

up-regulates activity

0.422

The kinase MK5 phosphorylates and activates Foxo1 at serine 215, and this modification is required for Foxo1 to induce Rag transcription.

SIGNOR-280037

P17252

P35222

1

phosphorylation

down-regulates

0.413

As shown in Fig. 1 B, PKCalpha readily phosphorylated Ser33 and Ser37 / Thr41 on full-length beta-catenin (beta-catenin 1 - 781) and CTD deletion mutant (beta-catenin 1-682).|To examine the effect of the armadillo repeats 1-5 on PKCalpha mediated beta-catenin degradation, DNA constructs expressing beta-catenin 1 - 781 and beta-catenin deletion mutants (beta-catenin 1-422 and beta-catenin 1-138) were transfected into HEK293 cells, followed by treatment with increasing concentrations of A23187 and CGK062, which are known activators of PKCalpha.

SIGNOR-278492

P24752

P29803

1

acetylation

down-regulates activity

0.2

We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)

SIGNOR-267634

P08581

Q04206

0

transcriptional regulation

up-regulates quantity

0.25

Together, these results indicate that the Met gene is a direct target of NFkappaB and that Met participates in NFkappaB-mediated cell survival.

SIGNOR-241929

O15530

P31749

1

phosphorylation

up-regulates

0.748

We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies.

SIGNOR-67367

P42345

P08069

1

phosphorylation

up-regulates activity

0.494

Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR.

SIGNOR-280044

Q16539

P78536

1

phosphorylation

up-regulates activity

0.405

We show that p38 MAP kinase, which is activated in response to inflammatory or stress signals, directly activates TACE, a membrane-associated metalloprotease that is also known as ADAM17 and effects shedding in response to growth factors and Erk MAP kinase activation. p38alpha MAP kinase interacts with the cytoplasmic domain of TACE and phosphorylates it on Thr(735), which is required for TACE-mediated ectodomain shedding

SIGNOR-163970

Q14145

Q16236

1

ubiquitination

down-regulates quantity

0.813

Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation

SIGNOR-259335

Q9Y5X2

P23458

0

phosphorylation

up-regulates activity

0.341

IFNγ induced JAK1-mediated phosphorylation of SNX8 at Tyr95 and Tyr126, which promoted the recruitment of IKKβ to the JAK1 complex.

SIGNOR-273647

O95747

Q13621

1

phosphorylation

up-regulates activity

0.502

We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).

SIGNOR-276309

O00418

O15264

0

phosphorylation

down-regulates activity

0.578

eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. eEF2K[S359A] was phosphorylated (presumably at Ser396) by the high concentrations of SAPK4/p38 used in this experiment. However, the inhibition of eEF2K under these conditions was reduced from 82% in the wild-type enzyme to 19% in eEF2K[S359A]

SIGNOR-250089

Q99626

Q9HAW8

1

transcriptional regulation

up-regulates quantity by expression

0.257

Using gel shift and functional assays, HNF1alpha was demonstrated to bind to and activate the UGT1A8, -1A9, and -1A10 promoters. In contrast, Cdx2 bound to and activated the UGT1A8 and -1A10 promoters but could not activate the UGT1A9 promoter.

SIGNOR-253968

P53350

Q9UKT4

1

phosphorylation

down-regulates

0.783

We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.

SIGNOR-142949

Q13315

P46527

1

phosphorylation

up-regulates quantity by stabilization

0.419

We also uncovered that ATM phosphorylates p27Kip1 on a previously uncharacterized residue (Ser-140), which leads to its stabilization after induction of DNA double-strand breaks.

SIGNOR-279392

P07550

P31749

0

phosphorylation

down-regulates

0.354

Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation.

SIGNOR-252470

P68400

P52655

1

phosphorylation

up-regulates activity

0.379

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-250877

Q9UQM7

Q05469

1

phosphorylation

down-regulates

0.2

Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.

SIGNOR-58251

P41743

Q6P1M3

1

phosphorylation

up-regulates activity

0.687

This finding indicates that both mLgl-2 and mLgl-1 are phosphorylated in vivo in an aPKC lambda activity-dependent manner.

SIGNOR-263180

P31749

P10276

1

phosphorylation

down-regulates

0.602

We report that akt, which is constitutively activated in nsclc cells, phosphorylates raralpha and inhibits its transactivation. / mutation of ser96 to alanine abrogated the suppressive effect of akt.

SIGNOR-252489

P20393

P37231

0

transcriptional regulation

up-regulates quantity by expression

0.277

Mutations of the 5' or 3' half-sites of the response element totally abrogated PPARgamma binding and transcriptional activation, identifying this site as a novel type of functional PPARgamma response element. Finally, ectopic expression of Rev-Erbalpha in 3T3-L1 preadipocytes potentiated adipocyte differentiation induced by the PPARgamma ligand rosiglitazone. These results identify Rev-Erbalpha as a target gene of PPARgamma in adipose tissue and demonstrate a role for this nuclear receptor as a promoter of adipocyte differentiation.

SIGNOR-268022

P68431

O75151

0

demethylation

down-regulates activity

0.2

PHF2, a jmjC demethylase, is enzymatically inactive by itself, but becomes an active H3K9Me2 demethylase through PKA-mediated phosphorylation. This modification leads to targeting of the PHF2–ARID5B complex to its target promoters, where it removes the repressive H3K9Me2 mark.

SIGNOR-264521

P31321

O43164

0

polyubiquitination

down-regulates quantity by destabilization

0.2

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271857

P10412

P50750

0

phosphorylation

down-regulates activity

0.2

These data provide further evidence that CDK9 phosphorylates H1.4-S187, and that the level of pS187-H1.4 at genes is directly related to the extent of co-enrichment of CDK9.|that enrichment of pS187-H1.4 at genes is positively related to their transcription.

SIGNOR-279691

Q14807

Q96EP1

0

ubiquitination

down-regulates quantity by destabilization

0.399

Chfr ubiquitinates Kif22 and promotes its degradation.

SIGNOR-271469

O15530

P12931

0

phosphorylation

up-regulates activity

0.585

Using site-directed mutants, we show that, although phosphorylation on tyr-373/376 is important for pdk1 activity, phosphorylation on tyr-9 has no effect on the activity of the kinase. Both of these residues can be phosphorylated by v-src tyrosine kinase in vitro, and co-expression of v-src leads to tyrosine phosphorylation and activation of pdk1.

SIGNOR-109533

P61586

Q7Z6I6

0

gtpase-activating protein

down-regulates activity

0.449

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-260485

Q9UNE7

Q16665

1

ubiquitination

down-regulates quantity by destabilization

0.376

the ubiquitin ligase activity of CHIP regulates HIF-1α degradation.

SIGNOR-271426

Q13393

P54646

0

phosphorylation

up-regulates

0.2

Ampk-wild type (wt) stimulates pld activity, while ampk-dominant negative (dn) inhibits it. Ampk regulates pld1 activity through phosphorylation of the ser-505 and this phosphorylation is increased by the presence of amp.

SIGNOR-164293

P51617

Q9NWZ3

0

phosphorylation

up-regulates activity

0.687

In addition, IRAK-4 is able to phosphorylate IRAK-1, and overexpression of dominant-negative IRAK-4 is blocking the IL-1-induced activation and modification of IRAK-1, suggesting a role of IRAK-4 as a central element in the early signal transduction of Toll/IL-1 receptors, upstream of IRAK-1.

SIGNOR-117315

P26367

Q9H2X6

0

phosphorylation

up-regulates activity

0.463

HIPK2 phosphorylates the activation domain of Pax6, which augments Pax6 transactivation by enhancing its interaction with p300. Mass spectrometric analysis identified three Pax6 phosphorylation sites as threonines 281, 304, and 373.

SIGNOR-251271

P54646

P28562

1

phosphorylation

down-regulates quantity by destabilization

0.273

Taken together, these results imply that nicotine acts via AMPKα2 to phosphorylate MKP1 at Ser334, instigating MKP1 ubiquitination and proteasome-mediated degradation.

SIGNOR-276890

Q05655

P48995

1

phosphorylation

up-regulates activity

0.2

Taken together, these results indicate that store depletion induces interactions between TRPC1 and PKC\u03b4 in VSMCs, and that these interactions cause PKC\u03b4\u2010dependent phosphorylation of TRPC1.

SIGNOR-279559

P25098

P21731-2

1

phosphorylation

down-regulates activity

0.2

These data suggest a model whereby agonist-induced PKC phosphorylation of Ser(145) partially impairs TPbeta signalling while GRK2/3 phosphorylation at both Ser(239) and Ser(357) within its IC(3) and C-tail domains, respectively, sterically inhibits G-protein coupling, profoundly desensitizing signalling, and promotes beta-arrestin association and, in turn, facilitates TPbeta internalization.

SIGNOR-274088

Q13153

Q99523

1

phosphorylation

down-regulates activity

0.2

PAKs specifically phosphorylate Ser15 of the sortilin-cd and alter its trafficking. It can be concluded that PAK1-3 may indeed instigate the phosphorylation of sortilin and that they target a single serine residue (Ser15) located in the kinase domain-binding site of the sortilin-cd. Full-length sortilins with the serine at position 793 (residue 15 in the cytoplasmic domain) (for the sequence, see Fig. 2). Phosphorylation (Ser15) downregulates the sortilin–AP-1 interaction.

SIGNOR-273718

Q9Y2K2

O15055

1

phosphorylation

down-regulates quantity by destabilization

0.2

In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation.

SIGNOR-279570

P23471

Q9UM73

1

dephosphorylation

down-regulates

0.545

Rptpbeta/zeta dephosphorylates alk at the site(s) in alk that is undergoing autophosphorylation through autoactivation.

SIGNOR-157227

Q05209

O43586

1

dephosphorylation

down-regulates activity

0.61

We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. |The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl

SIGNOR-248656

Q16659

Q8IW41

1

phosphorylation

up-regulates activity

0.69

ERK3, ERK4 and p38 MAPK can all phosphorylate MK5 at Thr 182 , , , - ], but it is not known whether these enzymes also can phosphorylate Ser 115 and whether this modification contributes to ERK3-, ERK4-, or p38 MAPK -regulated subcellular localization of MK5.

SIGNOR-279073

Q15678

Q03135

1

dephosphorylation

down-regulates activity

0.2

Finally, PTPN14 overexpression in B16F10 cells reduced the ability of CAV1 to induce metastasis in vivo.|Moreover, the CAV1 (Y14F) mutant protein was shown to co-immunoprecipitate with PTPN14 even in the absence of E-cadherin, and overexpression of PTPN14 reduced CAV1 phosphorylation on tyrosine 14, as well as suppressed CAV1 enhanced cell migration, invasion and Rac-1 activation in B16F10, metastatic colon [HT29 (US)] and breast cancer (MDA-MB-231) cell lines.

SIGNOR-277054

Q9NX09

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.339

It has been reported that GSK3beta phosphorylates REDD1 at residues Thr23 and Thr25, resulting in REDD1 recruitment to the Cullin 4a-beta-Trcp E3 ligase complex.

SIGNOR-279526

Q9HCU9

O43791

0

ubiquitination

down-regulates quantity

0.402

Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3-SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells.

SIGNOR-268857

P12277

Q96DX5

0

polyubiquitination

down-regulates quantity by destabilization

0.683

We demonstrate that creatine kinase B (CKB) interacts with Asb-9 in a specific, SOCS box-independent manner. This interaction increases the polyubiquitylation of CKB and decreases total CKB levels within the cell. The targeting of CKB for degradation by Asb-9 was primarily SOCS box-dependent and suggests that Asb-9 acts as a specific ubiquitin ligase regulating levels of this evolutionarily conserved enzyme.

SIGNOR-271623

Q14106

P24941

0

phosphorylation

up-regulates activity

0.246

Taken together, these observations strongly support the notion that several different CDK-cyclin complexes are involved in the phosphorylation of Tob2 at S254.A more detailed regulatory context of Tob2 phosphorylation at S254 is provided by our findings from mass-spec and in vitro kinase analyses that suggest connections to PP2B and PP2C phosphatases and CDK-cyclin complexes, particularly CDK1, CDK2, and CDK4 (Table 1; Supplemental Table S2).One possibility is that the phosphorylation of S254 helps stabilize the interaction of Tob2 with the Ccr4–Not complex, which could contribute to Tob2's ability to recruit the entire Ccr4–Not complex and thus further enhances deadenylation.

SIGNOR-273601

Q16549

P49715

1

phosphorylation

down-regulates

0.2

Addition of active p38a induced phosphorylation of wild-type c/ebp_? (c/ebp_?WT) on serine 21

SIGNOR-186202

Q13164

Q14814

1

phosphorylation

up-regulates

0.705

Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b. the sites phosphorylated by activated bmk1 were mapped to ser-355, thr-312, and thr-319 of mef2a and ser-179 of mef2d both in vitro and in vivo.

SIGNOR-236041

P32754

Q96FA3

0

ubiquitination

down-regulates quantity by destabilization

0.2

Decreased expression of 4-hydroxyphenylpyruvic acid dioxygenase (HPD), a key enzyme for tyrosine metabolism, is a cause of human tyrosinemia. However, the regulation of HPD expression remains largely unknown. Here, we demonstrate that molecular chaperone TTC36, which is highly expressed in liver, is associated with HPD and reduces the binding of protein kinase STK33 to HPD, thereby inhibiting STK33-mediated HPD T382 phosphorylation. The reduction of HPD T382 phosphorylation results in impaired recruitment of FHA domain-containing PELI1 and PELI1-mediated HPD polyubiquitylation and degradation.

SIGNOR-272959

Q9NQG5

P14635

1

transcriptional regulation

up-regulates quantity by expression

0.2

These results indicated that CREPT regulates the Cyclin B1 expression via directly targeting its promoter region during transcription.

SIGNOR-265500

P06493

Q9Y6X9

1

phosphorylation

down-regulates quantity by destabilization

0.2

Mechanically, PTX and VCR activate cyclin-dependent kinase 1, which in turn induces MORC2 phosphorylation at threonine 717 (T717) and T733. Phosphorylated MORC2 enhances its interation with HSPA8 and LAMP2A, two essential components of the chaperone-mediated autophagy (CMA) mechinery, resulting in its autophagic degradation.

SIGNOR-277837

Q8N6T7

Q00987

0

ubiquitination

down-regulates quantity

0.415

These results suggest that MDM2 degrades SIRT6 in a proteasome dependent manner.|USP10 has been shown to deubiquitinate and stabilize p53, a well-known substrate of MDM2, suggesting a mechanism whereby SIRT6 is ubiquitinated and destabilized by MDM2, which could be reversed by USP10 mediated deubiquitination.

SIGNOR-278702

P35869

P04798

1

transcriptional regulation

up-regulates quantity by expression

0.684

Kaempferol proved to be capable of inhibiting binding of agonist and agonist-induced formation of the AHR/ARNT DNA-binding complex and upregulation of the AHR target gene, CYP1A1.

SIGNOR-259909

O43524

Q13547

0

deacetylation

up-regulates activity

0.368

The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a

SIGNOR-256486

Q14934

P45983

0

phosphorylation

up-regulates activity

0.467

Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser(213) and Ser(217), which are located in the conserved SP motif.|Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose dependent manner by JNK1 or JNK2.

SIGNOR-280033

P51608

P18031

1

transcriptional regulation

down-regulates quantity by repression

0.2

In this study, we have demonstrated that the PTPN1 gene, which encodes PTP1B, was a direct target of MECP2 and that PTP1B protein levels were dramatically increased in Mecp2-mutant mice and in fibroblasts derived from patients with RTT.

SIGNOR-264546

Q9HAU4

P36894

1

ubiquitination

down-regulates

0.552

Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps

SIGNOR-192898

P42568

O00141

0

phosphorylation

down-regulates activity

0.509

In addition to Nedd4-2, Sgk1 also phosphorylates Af9, forkhead like transcription factor FOXO3a and several other substrates.|Sgk1 impairs the ability of Af9 to interact with Dot1a at these subregions without impacting Af9 DNA binding activity, leading to targeted histone H3 K79 hypomethylation.

SIGNOR-279111

O60381

P14598

1

transcriptional regulation

down-regulates quantity by repression

0.265

Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene.

SIGNOR-261614

O43791

P10070

1

ubiquitination

down-regulates quantity

0.71

RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins

SIGNOR-268860

Q9ULV8

P12931

0

phosphorylation

up-regulates

0.537

Phosphorylation of a critical tyrosine (tyr-341) in the linker region of cbl-c by src or a phosphomimetic mutation of this tyrosine (y341e) is sufficient to increase the e3 activity of cbl-c.

SIGNOR-165862

P17275

Q9Y222

0

transcriptional regulation

up-regulates quantity by expression

0.265

Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.

SIGNOR-261585

Q13621

Q9UEW8

0

phosphorylation

up-regulates activity

0.577

We establish that the SPAK and OSR1 kinases activated by WNK interact with an RFQV motif on NKCC2 and directly phosphorylate Thr95, Thr100, Thr105 and, possibly, Ser91.Using these phosphorylation-specific antibodies we establish that hypotonic low-chloride stimulation induces marked phosphorylation of overexpressed NKCC2 in HEK-293 cells at Ser91, Thr100, Thr105 and Ser130 (Fig. 3A).

SIGNOR-276308

P00519

P49759

0

phosphorylation

down-regulates

0.259

Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3

SIGNOR-181031

P12931

P35222

1

phosphorylation

down-regulates activity

0.761

beta-catenin is a good substrate of pp60c- srctyrosine kinase in vitro;this kinase modifies specifically tyr-86 and tyr-654although consistently detected, this negative effect of tyr-86 phosphorylation on tbp binding was clearly less important than the positive effect observed after tyr-654 phosphorylation.

SIGNOR-106458

Q96T88

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.303

UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant

SIGNOR-277192

Q16549

Q92945

1

phosphorylation

down-regulates

0.2

Ksrp phosphorylated by p38 displays compromised binding to are-containing transcripts and fails to promote their rapid decay,although it retains the ability to interact with the mrna degradation machinery.

SIGNOR-143167

P17275

Q16539

0

phosphorylation

up-regulates

0.502

These results clearly demonstrate that phosphorylation by p38 kinase is essential for the regulation of dmp1 transcription by junb and p300. phosphorylation of junb at ser-79 was found to be essential for its interaction with p300.

SIGNOR-127545

O00444

Q969U6

1

phosphorylation

down-regulates activity

0.543

The activity of SCF-FBXW5 is in turn negatively regulated by Polo-like kinase 4 (PLK4), which phosphorylates FBXW5 at Ser 151 to suppress its ability to ubiquitylate HsSAS-6.

SIGNOR-275476

O75379

P68400

0

phosphorylation

up-regulates

0.446

The r-snare vamp4, which contains a dileucine motif, binds to the ap-1 or the ggas. Serine 20 and leucines 25,26 are essential for this binding. Ap-1 association with vamp4 is enhanced when serine 30 is phosphorylated by casein kinase 2. This phosphorylation-dependent modulation of ap-1 binding is mediated by pacs-1 (phosphofurin acidic cluster sorting protein). Ablation of both the dileucine motif and serine 30 results in a dramatic mislocalization of vamp4 in the regulated secretory pathway.

SIGNOR-119090

Q14289

Q02535

1

phosphorylation

up-regulates quantity

0.2

Taken together these findings demonstrated that Pyk2 mediates the expression of ID3 protein.|Together these findings from the combined MS+MS/MS data confirm that Flag tagged ID3 is phosphorylated by active recombinant Pyk2 kinase; and support the phospho-Tyr band that was detected at the corresponding MW ~ 13 kDA for Flag-ID3 by immunoblot.

SIGNOR-278496

Q13409

Q8NG06

0

polyubiquitination

down-regulates quantity by destabilization

0.298

Trim58 ubiquitinates dynein and promotes its proteasomal degradation. Trim58 binds DIC directly, polyubiquitinates it in vitro, and induces proteasomal degradation of the dynein holocomplex in vivo.

SIGNOR-272841

Q99856

P0DOX3

1

transcriptional regulation

up-regulates quantity by expression

0.2

In this work, we show that TFII-I directly interacts with human Bright through amino acids in Bright's protein interaction domain and that specific tyrosine residues of TFII-I are essential for Bright-induced activity of an immunoglobulin reporter gene. Moreover, inhibition of TFII-I function in a B-cell line resulted in decreased heavy-chain transcript levels.| Figure 3 shows that both anti-Bright and anti-TFII-I precipitated the bf150 Bright binding site from the B-cell line but not from a T-cell line that contains but does not express the V1 gene.

SIGNOR-268531

Q92915

O60674

0

phosphorylation

up-regulates activity

0.2

JAK2 regulates Nav1.6 channel function via FGF14Y158 phosphorylation|Patch-clamp electrophysiology revealed that through Y158, JAK2 controls FGF14-dependent modulation of Nav1.6 channels. In hippocampal CA1 pyramidal neurons, the JAK2 inhibitor Fedratinib reduced firing by a mechanism that is dependent upon expression of FGF14.

SIGNOR-275747

Q8TDC3

Q8N5S9

0

phosphorylation

up-regulates activity

0.307

In transfected COS-7 cells, kinase activity and Thr (189) phosphorylation of overexpressed SAD-B were significantly enhanced by coexpression of constitutively active CaMKKalpha (residues 1-434) in a manner similar to that observed with coexpression of LKB1, STRAD, and MO25.|Taken together, these results indicate that CaMKKalpha is capable of activating SAD-B through phosphorylation of Thr (189) both in vitro and in vivo and demonstrate for the first time that CaMKK may be an alternative activating kinase for SAD-B.

SIGNOR-280202

A8K4G0

P06241

0

phosphorylation

up-regulates activity

0.308

As CD300b phosphorylation was occurring only in the presence of both c-Fyn and DAP-12, we addressed whether tyrosine phosphorylation was required for association of CD300b and DAP-12. For this purpose, we generated a set of HA-tagged CD300b mutants affecting the transmembrane lysine (K158L), the cytoplasmic tyrosine (Y188F) or both residues.|As expected, the CD300b double mutant could neither recruit DAP-12 nor become phosphorylated in the presence of c-Fyn kinase (Fig. 5⇑C). Association between CD300b and DAP-12 was maintained in absence of the c-Fyn kinase, indicating that phosphorylation of the adaptor was not essential for the formation of the complex (data not shown)

SIGNOR-264771

Q15717

P06493

0

phosphorylation

down-regulates activity

0.407

Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.

SIGNOR-279014

Q92973

O15534

1

relocalization

up-regulates activity

0.268

The non-classical nuclear import carrier Transportin 1 modulates circadian rhythms through its effect on PER1 nuclear localization

SIGNOR-262102

Q13131

O60825

1

phosphorylation

up-regulates activity

0.464

Heart 6-phosphofructo-2-kinase activation by insulin results from ser-466 and ser-483 phosphorylation and requires 3-phosphoinositide-dependent kinase-1, but not protein kinase b.

SIGNOR-84061

Q96EB6

P04637

1

deacetylation

down-regulates

0.803

Sirt1 has been shown to regulate cell fate in part by deacetylating the p53 protein at lysine 382 and inhibiting p53-mediated transcriptional activation and apoptosis.

SIGNOR-182515

Q8WTR2

P45983

1

dephosphorylation

down-regulates

0.421

Skrp1 was highly specific for c-jun n-terminal kinase (jnk) in vitro and effectively suppressed the jnk activation in response to tumor necrosis factor alpha or thapsigargin skrp1 does not bind directly to its target jnk, but co-precipitation of skrp1 with the mapk kinase mkk7, a jnk activator, was found in vitro and in vivo.

SIGNOR-117260

P35568

Q02750

0

phosphorylation

down-regulates

0.352

Thus, at least three kinases mediate phosphorylation of ser307, including jnk, serine kinases in the pi 3-kinase cascade that are activated byinsulinor igf-1, and mek1-sensitive kinase cascades during tnf-alfa stimulation.

SIGNOR-236611

O75385

Q86WV6

1

phosphorylation

down-regulates activity

0.2

Collectively, our data indicates that cGAS is essential for the activation of AMPK and ULK1 suppression of STING (XREF_FIG) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity (XREF_FIG).|Collectively, our data indicates that cGAS is essential for the activation of AMPK/ULK1 suppression of STING ( xref ) and that cGAMPs are responsible for triggering the dephosphorylation of AMPK T172 and activation of ULK1 which phosphorylates STING on S366 to impede its activity ( xref ).

SIGNOR-279316

Q02156

Q9H9S0

1

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

P23443

P36956

1

phosphorylation

up-regulates activity

0.424

Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation.|Besides promoting protein synthesis, S6K1 also phosphorylates and activates sterol regulatory element-binding protein 1 and 2 (SREBP and SREBP2), which promotes de novo lipid synthesis that is critical for cell growth and proliferation ( xref ).

SIGNOR-280120

Q92830

P11802

0

phosphorylation

up-regulates activity

0.36

Activated cyclin D1-Cdk4 kinase phosphorylates and activates GCN5|GCN5 T272A/S372A (AA) phosphorylation by cyclin D1-CDK4 kinase is diminished compared to GCN5 wild-type (WT)

SIGNOR-275494

P17480

P24941

0

phosphorylation

up-regulates activity

0.372

Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity

SIGNOR-235419

P43250

P08069

1

phosphorylation

down-regulates quantity by destabilization

0.306

GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation

SIGNOR-276412

P28482

P09917

1

phosphorylation

up-regulates activity

0.381

Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.

SIGNOR-264409

Q8WYQ5

P00519

0

phosphorylation

up-regulates activity

0.2

The kinase ABL phosphorylates the microprocessor subunit DGCR8 to stimulate primary microRNA processing in response to DNA damage. When coexpressed in HEK293T cells, ABL phosphorylated DGCR8 at Tyr(267).

SIGNOR-262604

Q15772

Q9BR39

1

phosphorylation

up-regulates activity

0.36

Studies in HEK293 cells confirmed that SPEG overexpression increases JPH2 phosphorylation .

SIGNOR-279759

P01116

Q5VWQ8

0

gtpase-activating protein

down-regulates activity

0.518

The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP hydrolysis to GDP.

SIGNOR-254746

O60566

Q96SN8

0

transcriptional regulation

up-regulates quantity by expression

0.27

These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter

SIGNOR-260312