GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P05198	P18848	1	transcriptional regulation	down-regulates quantity	0.64	ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery	SIGNOR-260169
Q13976	Q14847	1	phosphorylation	down-regulates activity	0.359	Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.	SIGNOR-97946
P12931	P09619	0	phosphorylation	up-regulates activity	0.604	The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.	SIGNOR-247979
P50281	P00748	1	cleavage	down-regulates quantity by destabilization	0.331	The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377\|However, no activity of Factor XII can be observed after MMPinduced cleavage.	SIGNOR-263610
Q9Y4K3	Q8N2H9	0	ubiquitination	down-regulates quantity	0.63	Finally, we used coexpression studies to directly demonstrate that Pellino3 inhibits the ability of wild-type TRAF6 to stabilize HIF-1alpha but not the stabilizing effects of the K124A TRAF6 mutant that is resistant to ubiquitination.\|In the present study, Pellino3 ubiquitinates TRAF6 with lysine 63-linked polyubiquitin chains to block the interaction of TRAF6 with HIF-1\u03b1.	SIGNOR-278707
P30260	P06493	0	phosphorylation	up-regulates	0.704	Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation	SIGNOR-119873
P01137	P08253	0	cleavage	up-regulates	0.555	We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-beta (tgf-beta), which constitutes a novel mechanism of tgf-beta activation	SIGNOR-74384
Q9UGJ0	Q13586	1	phosphorylation	down-regulates activity	0.2	STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE	SIGNOR-277297
P48736	P12931	1	phosphorylation	up-regulates activity	0.365	PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.	SIGNOR-277225
Q9Y4L5	P01106	1	ubiquitination	down-regulates quantity by destabilization	0.448	These results suggest that Rabring7 antagonizes function of c-Myc possibly through degradation of c-Myc.\|Unexpectedly, we found that Rabring7 more strongly binds to c-Myc than to MM-1 (XREF_FIG) and that Rabring7 stimulates poly-ubiquitination of c-Myc in a T58 dependent manner (XREF_FIG).	SIGNOR-278662
Q96AQ6	Q00987	0	polyubiquitination	down-regulates quantity by destabilization	0.29	. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1.	SIGNOR-272850
P12004	P08069	0	phosphorylation	up-regulates activity	0.2	In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination.	SIGNOR-277252
Q5VZV1	P55072	1	methylation	up-regulates activity	0.308	We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo.	SIGNOR-255918
P11308	Q14258	0	ubiquitination	down-regulates quantity	0.301	We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG.\|Our previous discovery of USP9X as an ERG stabilizing deubiquitinase suggests that reduction of ERG protein levels by TRIM25 mediated proteasomal degradation is prevented by expression of USP9X in fusion positive prostate cancer cells.\|Using several biochemical assays we show that TRIM25 mediates the polyubiquitination of full-length ERG as well as N-terminally truncated ERG.	SIGNOR-278732
O43318	O14733	1	phosphorylation	up-regulates activity	0.645	Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK	SIGNOR-274146
Q15759	P05787	1	phosphorylation	up-regulates	0.427	Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-114063
Q9UQM7	P41134	1	phosphorylation	up-regulates activity	0.2	Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy.	SIGNOR-277367
P06213	P10586	0	dephosphorylation	down-regulates	0.577	Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product.	SIGNOR-76005
Q05925	P55075	1	transcriptional regulation	down-regulates quantity by repression	0.452	Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription	SIGNOR-265776
P31749	Q8N5S9	0	phosphorylation	up-regulates activity	0.379	Protein kinase B (PKB) was recently reported to be activated on the phosphorylation of Thr(308) by Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaM-kinase kinase alpha), suggesting that PKB was regulated through not only the phosphoinositide 3-kinase pathway but also the Ca(2+)/calmodulin protein kinase pathway.	SIGNOR-252609
Q14012	P18846	1	phosphorylation	up-regulates activity	0.512	Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.	SIGNOR-250611
P17948	Q12913	0	dephosphorylation	down-regulates	0.362	Vegf acts by binding to two high affinity receptor tyrosine kinases: vegf receptor (vegfr)* 1 also called flt-1, and vegfr-2, also called flk-1/kdr a dominant-negative mutant of high cell densityenhanced ptp 1 (dep-1)//cd148 as well as reduction of its expression by rna interference partially restore vegfr-2 phosphorylation and map kinase activation.	SIGNOR-101272
Q14896	Q05655	0	phosphorylation	up-regulates	0.2	The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment.	SIGNOR-150355
P18848	O43776	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269422
P31749	O14757	1	phosphorylation	down-regulates	0.43	The chk1 protein phosphorylated by pkb on serine 280 does not enter into protein complexes after replication arrest. Moreover, chk1 phosphorylated by pkb fails to undergo activating phosphorylation on serine 345 by atm/atr. Phosphorylation by atm/atr and association with other checkpoint proteins are essential steps in activation of chk1.	SIGNOR-124365
Q9C029	Q5TA31	1	ubiquitination	up-regulates quantity by stabilization	0.269	Taken together, these data suggest that Trim7 directly ubiquitinates RACO-1.	SIGNOR-278536
P10398	Q13153	0	phosphorylation	up-regulates	0.267	Phosphorylation of endogenous a-raf, b-raf and raf-1 on the homologous pak phosphorylation sites (serine 299, serine 445, or serine 338 respectively)we found that the phosphorylation of a-raf on serine 299 was also stimulated by egf, although the duration of phosphorylation on this site was much shorter than for raf-1. Thus, by analogy with raf-1, phosphorylation of this site may play an important role in the a-raf activation mechanism.	SIGNOR-236342
P04637	P62714	0	dephosphorylation	up-regulates quantity by stabilization	0.437	A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55\| In this study, we reported that the specific B regulatory subunits of PP2A B56gamma1 and B56gamma3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis	SIGNOR-248583
Q13049	Q96EV8	1	ubiquitination	down-regulates quantity	0.537	TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation.	SIGNOR-265658
Q99816	P17542	0	polyubiquitination	down-regulates quantity by destabilization	0.2	These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.	SIGNOR-271636
P78362	Q07955	1	phosphorylation	up-regulates activity	0.616	In contrast, SRPK1 or SRPK2 overexpression upregulated the phosphorylation and nucleus accumulation of SRSF1.\|Therefore, SRPK1 and SRPK2 may directly phosphorylate SRSF1 and promote it nucleus translocation, subsequently modulate MKNK2 alternative splicing.	SIGNOR-279660
P0DOX3	Q99856	0	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
Q8TDY4	Q9P289	0	phosphorylation	up-regulates activity	0.2	Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545\|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.	SIGNOR-272238
P01111	Q06124	0	dephosphorylation	up-regulates activity	0.673	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-255754
P24394	O60674	1	phosphorylation	up-regulates activity	0.624	Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.	SIGNOR-249530
Q13887	Q9HAU4	0	ubiquitination	down-regulates quantity by destabilization	0.37	Consistent with these observations, another study documented that Smurf2 specifically destabilizes KLF5, that the degradation of KLF5 by Smurf2 is disrupted by the proteasome inhibitor MG132, and that Smurf2 ubiquitinates KLF5 .	SIGNOR-278781
P00451	Q8NEV1	0	phosphorylation	down-regulates activity	0.2	Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II-like kinase may downregulate the activity of the two cofactors.\| Recombinant human factor VIII also showed incorporation of radioactivity in the presence of purified casein kinase II at the acidic NH2-terminal portion of factor VIII light chain (residues 1648 through 1689). Based on all the considerations reported above Se1657 is the most likely candidate within this region capable of incorporation of radioactivity	SIGNOR-263649
P45974	P0CG47	1	cleavage	up-regulates quantity	0.767	Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.	SIGNOR-270821
P00519	P12004	1	phosphorylation	up-regulates activity	0.333	In the current study, we are able to establish a new pathway in which the Ron receptor tyrosine kinase activates c-Abl which in turn catalyzes Y211 phosphorylation of PCNA.\|We previously showed that Y211 phosphorylation stabilized chromatin bound PCNA, which in turn promoted cell proliferation, and that c-Abl functioned to enhance chromatin association of PCNA in cancer cells.	SIGNOR-279389
Q96GD4	Q9H0H5	1	phosphorylation	up-regulates activity	0.78	It was found that the 5A fragment in which five Ser/Thr residues were substituted with Ala (S144A/T145A/S185A/T186A/S187A) fully prevented phosphorylation (Fig. 5B), confirming that Aurora B primarily phosphorylates five Ser/Thr residues in the basic region of MgcRacGAP. \| the strong phosphorylation of the basic region of MgcRacGAP by Aurora B kinase was demonstrated, and this phosphorylation prevents the inhibition of MgcRacGAP GAP activity by PRC1	SIGNOR-250590
Q13188	P31751	0	phosphorylation	down-regulates	0.261	Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.	SIGNOR-164302
P04637	Q9HCI7	0	ubiquitination	down-regulates activity	0.37	Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.	SIGNOR-271774
P50750	Q9H0D6	1	phosphorylation	up-regulates activity	0.278	Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro.	SIGNOR-277194
P49023	Q15256	0	dephosphorylation	down-regulates activity	0.2	Here, we show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88 (Y88) in colorectal cancer (CRC) cells. We engineered CRC cells homozygous for a paxillin Y88F knock-in mutant and found that these cells exhibit significantly reduced cell migration and impaired anchorage-independent growth,	SIGNOR-248720
O14641	P53350	0	phosphorylation	up-regulates	0.465	Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment	SIGNOR-167858
O43524	Q15831	1	transcriptional regulation	down-regulates quantity	0.634	SGK-1 Negatively Regulates LKB1 Expression via FOXO3 Transcription Factor	SIGNOR-255758
P17612	P11137	1	phosphorylation	down-regulates activity	0.36	CAMP-dependent protein kinase activity disrupts the MAP2-microtubule interaction in living HeLa cells. S319, S350, and S382 were thus identified as preferred targets of PKA	SIGNOR-250003
Q16566	P56524	1	phosphorylation	down-regulates activity	0.62	CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. \| Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. \| Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.	SIGNOR-250712
Q13315	O14757	1	phosphorylation	up-regulates	0.845	Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation.	SIGNOR-163106
P10586	P56945	1	dephosphorylation	down-regulates quantity by destabilization	0.339	LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.\|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.	SIGNOR-276998
O14672	P04626	1	cleavage	up-regulates activity	0.344	The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.	SIGNOR-259845
P31749	Q96IZ0	1	phosphorylation	down-regulates activity	0.39	Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy	SIGNOR-279668
P50542	P28328	0	ubiquitination	down-regulates quantity by destabilization	0.579	Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.	SIGNOR-253021
P41279	P45985	1	phosphorylation	up-regulates	0.559	Furthermore, we found that immunoprecipitated tpl-2 could directly phosphorylate and activate both mek-1 and mkk4 (also known as sek-1)	SIGNOR-196744
P27986	Q12913	0	dephosphorylation	down-regulates	0.261	As reduction of pi3k activity by cd148 or shp-1 [32] is not large (2540%), it is likely that these ptps may function as modulators of the pi3k pathway rather than suppressors.	SIGNOR-178049
P08151	Q16539	0	phosphorylation	down-regulates quantity by destabilization	0.27	Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling.	SIGNOR-277916
Q9P2P5	O15350	1	ubiquitination	up-regulates quantity by stabilization	0.37	P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.	SIGNOR-269457
P10071	P48729	0	phosphorylation	down-regulates	0.6	In principle, pka, ck-1 and gsk3 can phosphorylate as many as 19 serine residues in gli3: fourpkasites, three primarygsk3sites, four primary ck-1 sites and eight secondary gsk3 and ck-1 sites	SIGNOR-116512
P06493	Q9UPT9	1	phosphorylation	up-regulates activity	0.47	On the other hand, CDK1 enhances USP22 activity to stabilize CCNB1 during the G2/M phase.\|Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1.	SIGNOR-278241
Q14676	O76064	1	relocalization	up-regulates	0.757	Rnf8 relocalizes to dna damage sites via a phospho-dependent interaction with mdc1	SIGNOR-179820
P51911	P06241	0	phosphorylation	down-regulates activity	0.333	We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin	SIGNOR-251157
Q9NPC2	P17612	0	phosphorylation	up-regulates	0.2	Patch clamp analysis, flow cytometry, and immunocytochemistry studies of hek293 transfected with wt hk2p3.1 and cultured in the presence of pka activators or inhibitors all confirm that activation of pka resulted in an increase in hk2p3.1 current expression (figs. 4_4?6) and demonstrate the dynamic regulatory effect of pka activity on k2p3.1 channel expression.	SIGNOR-172466
P05412	P15407	1	transcriptional regulation	up-regulates quantity by expression	0.826	Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.	SIGNOR-261604
P53396	O14874	0	phosphorylation	up-regulates activity	0.2	BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.\|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.	SIGNOR-280194
P12931	P53801	1	phosphorylation	up-regulates activity	0.2	Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS.	SIGNOR-273810
Q8IYA7	Q13950	1	transcriptional regulation	up-regulates quantity by expression	0.301	MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).	SIGNOR-267215
Q16695	Q92830	0	acetylation	down-regulates activity	0.2	The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.	SIGNOR-269604
Q9H410	Q96GD4	0	phosphorylation	down-regulates	0.653	To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).	SIGNOR-165546
Q14643	P06241	0	phosphorylation	up-regulates	0.487	We have identified tyrosine 353 (tyr353) in the ip3-binding domain of type 1 ip3r (ip3r1) as a phosphorylation site for fyntyrosine phosphorylation of ip3r1 increased ip3 binding at low ip3 concentrations (<10 nm).	SIGNOR-121795
P49327	P04626	0	phosphorylation	up-regulates activity	0.442	Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).\|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.	SIGNOR-278399
Q13535	Q13315	1	phosphorylation	up-regulates activity	0.747	Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment	SIGNOR-150870
P08581	Q05397	1	phosphorylation	up-regulates	0.497	Met-mediated fak phosphorylation could further activate fak. Indeed, we found that met phosphorylates fak at its known phosphorylation sites, including tyr-576 and tyr-577, both of which are located in the activating loop within the catalytic domain	SIGNOR-147199
P68400	P18858	1	phosphorylation	up-regulates activity	0.34	Moreover, these data confirmed the occurrence of Ser66 phosphorylation, which was previously studied with a specific monoclonal antibody (23).	SIGNOR-103258
P40763	P00533	0	phosphorylation	up-regulates activity	0.879	The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.	SIGNOR-121965
P17612	P16144	1	phosphorylation	down-regulates	0.2	Additionally, we show that s1360 and s1364 of beta4 are the only residues phosphorylated by pkc and pka in cells, respectivelywe have defined three regions on beta4 that together harbor all the serine and threonine phosphorylation sites and show that three serines (s1356, s1360, and s1364), previously implicated in hd regulation, prevent the interaction of beta4 with the plectin actin-binding domain when phosphorylated	SIGNOR-156873
Q13043	Q15424	1	phosphorylation	down-regulates activity	0.2	In the present study, we demonstrate that the chromatin scaffold protein SAFB1 interacts with and is phosphorylated by MST1 and is a novel regulator of AR capable of integrating signaling between the AR and MST1 networks.	SIGNOR-279296
P17252	P04083	1	phosphorylation	up-regulates	0.2	The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.	SIGNOR-202780
P28698	O96013	0	phosphorylation	up-regulates activity	0.2	Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1). Phosphorylation of MZF1-S27 is an early response to ErbB2 activation and results in increased transcriptional activity of MZF1.The phosphorylation of MZF1-S27 is preceded by poly-SUMOylation of K23, which can make S27 accessible to efficient phosphorylation by PAK4.	SIGNOR-277422
P17612	O14965	1	phosphorylation	up-regulates activity	0.512	Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.	SIGNOR-250337
Q13315	Q9Y6K9	1	phosphorylation	down-regulates activity	0.739	Atm phosphorylates serine-85 of nemo to promote its ubiquitin-dependent nuclear export.	SIGNOR-144813
Q86YT6	P63162	1	ubiquitination	down-regulates quantity by destabilization	0.2	These data indicate that Mib1 reduces SMN protein stability by targeting it for degradation by the proteasome and represents a new modifier of the SMA phenotype.\|Through this study, we provide evidence that the E3 ligase Mib1 ubiquitinates and catalyzes SMN protein degradation.	SIGNOR-278632
Q13501	O75385	0	phosphorylation	down-regulates quantity by destabilization	0.567	ULK1 phosphorylates p62 at the Ser403 site.	SIGNOR-278349
Q14872	Q9NRM7	0	phosphorylation	down-regulates activity	0.2	The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1\|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1\|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression	SIGNOR-275475
O75688	O43318	1	dephosphorylation	down-regulates activity	0.551	In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1.	SIGNOR-277154
Q06413	P23409	1	transcriptional regulation	up-regulates quantity by expression	0.565	Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.	SIGNOR-238652
Q9Y2X9	Q9UKB1	0	ubiquitination	down-regulates quantity by destabilization	0.2	E3 ligase the beta-transducin repeat-containing protein 2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281.	SIGNOR-264897
Q9BXH1	P04626	0	phosphorylation	down-regulates quantity by destabilization	0.281	HER2 phosphorylates and destabilizes pro-apoptotic PUMA. Using an intracellular assay, we found PUMA to be phosphorylated in breast cancer cells with activated HER2. Via cell-free HER2 kinase assay, we observed that PUMA was directly phosphorylated by HER2. Activation of HER2 decreased PUMA protein half-life.	SIGNOR-276474
Q9Y6D9	P33981	0	phosphorylation	up-regulates activity	0.819	Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization.\|Indeed, Mps1 can phosphorylate Mad1 in vitro.	SIGNOR-279000
P51812	P11362	1	phosphorylation	down-regulates quantity	0.357	Both in vitro and in vivo experiments confirmed the interaction and we show that phosphorylated RSK2 binds to and phosphorylates serine 789 in the C-terminal tail of FGFR1.prevention of FGFR1 phosphorylation by inhibition of RSK2 activity or mutation of serine 789 to alanine reduced FGFR1 endocytosis and ubiquitination explaining mechanistically the prolonged signaling activity.	SIGNOR-276599
Q16539	P49918	1	phosphorylation	up-regulates	0.262	G1-s control by p38/hog1 sapks upon osmostress. Upon osmostress, activated p38 and hog1 sapks phosphorylate the s/cdk inhibitor p57 or sic1 respectively at one single residue. In mammalian cells (left panel), p57 phosphorylation on thr143 leads to an increase of the affinity of p57 towards the cyclin a/cdk2 complex leading to a g1 arrest.	SIGNOR-198390
O15105	Q09472	0	acetylation	up-regulates	0.464	Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300	SIGNOR-95169
Q01196	P10147	1	transcriptional regulation	up-regulates quantity by expression	0.2	We show that RUNX1 can specifically bind to both RUNX sites but that only the proximal RUNX site is essential for PMA/ PHA stimulation of the MIP-1a promoter in Jurkat T-cells. We also show that the endogenous MIP-1a promoter is constitutively bound by RUNX1.	SIGNOR-251738
Q04759	Q9BWT7	0	relocalization	up-regulates activity	0.435	TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation	SIGNOR-272471
P35247	P17676	0	transcriptional regulation	up-regulates quantity by expression	0.251	Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells\| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.	SIGNOR-254045
P27361	P51170	1	phosphorylation	down-regulates quantity by destabilization	0.28	Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.	SIGNOR-249449
P07996	Q9Y222	0	transcriptional regulation	up-regulates quantity by expression	0.2	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-261587
Q93008	P06493	0	phosphorylation	up-regulates activity	0.279	Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.	SIGNOR-275608
O43791	Q9HCU9	1	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
Q96T51	P61106	0	relocalization	up-regulates activity	0.63	Here, we have demonstrated that Rab14 interacts with RUFY1, previously identified as a Rab4 effector, and is required for RUFY1 recruitment onto endosomes and efficient recycling of Tfn.	SIGNOR-261279
O75431	O15033	0	ubiquitination	down-regulates quantity by destabilization	0.2	Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2.	SIGNOR-267674

P05198

P18848

1

transcriptional regulation

down-regulates quantity

0.64

ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery

SIGNOR-260169

Q13976

Q14847

1

phosphorylation

down-regulates activity

0.359

Studies with human lasp mutants identified serine 146 as a specific phosphorylation site for cgk and cak in vivo. Lasp is an actin-binding protein, and the phospho-lasp-mimicking mutant s146d showed reduced binding affinity for f-actin in cosedimentation experiments.

SIGNOR-97946

P12931

P09619

0

phosphorylation

up-regulates activity

0.604

The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.

SIGNOR-247979

P50281

P00748

1

cleavage

down-regulates quantity by destabilization

0.331

The data presented in this study show for the first time the degradation of Factor XII of the blood clotting system by matrix metalloproteinases. MMP-12, MMP-13, and MMP-14 cleave at Gly376Leu377|However, no activity of Factor XII can be observed after MMPinduced cleavage.

SIGNOR-263610

Q9Y4K3

Q8N2H9

0

ubiquitination

down-regulates quantity

0.63

Finally, we used coexpression studies to directly demonstrate that Pellino3 inhibits the ability of wild-type TRAF6 to stabilize HIF-1alpha but not the stabilizing effects of the K124A TRAF6 mutant that is resistant to ubiquitination.|In the present study, Pellino3 ubiquitinates TRAF6 with lysine 63-linked polyubiquitin chains to block the interaction of TRAF6 with HIF-1\u03b1.

SIGNOR-278707

P30260

P06493

0

phosphorylation

up-regulates

0.704

Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation

SIGNOR-119873

P01137

P08253

0

cleavage

up-regulates

0.555

We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-beta (tgf-beta), which constitutes a novel mechanism of tgf-beta activation

SIGNOR-74384

Q9UGJ0

Q13586

1

phosphorylation

down-regulates activity

0.2

STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE

SIGNOR-277297

P48736

P12931

1

phosphorylation

up-regulates activity

0.365

PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.

SIGNOR-277225

Q9Y4L5

P01106

1

ubiquitination

down-regulates quantity by destabilization

0.448

These results suggest that Rabring7 antagonizes function of c-Myc possibly through degradation of c-Myc.|Unexpectedly, we found that Rabring7 more strongly binds to c-Myc than to MM-1 (XREF_FIG) and that Rabring7 stimulates poly-ubiquitination of c-Myc in a T58 dependent manner (XREF_FIG).

SIGNOR-278662

Q96AQ6

Q00987

0

polyubiquitination

down-regulates quantity by destabilization

0.29

. Accordingly, we identified the microtubule-associated HPIP, a positive regulator of oncogenic AKT signaling, as a novel MDM2 substrate. MDM2-dependent HPIP degradation occurs in breast cancer cells on its phosphorylation by the estrogen-activated kinase TBK1.

SIGNOR-272850

P12004

P08069

0

phosphorylation

up-regulates activity

0.2

In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination.

SIGNOR-277252

Q5VZV1

P55072

1

methylation

up-regulates activity

0.308

We reveal that METTL21C trimethylates p97 on the Lys315 residue and found that loss of this modification reduced p97 hexamer formation and ATPase activity in vivo.

SIGNOR-255918

P11308

Q14258

0

ubiquitination

down-regulates quantity

0.301

We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG.|Our previous discovery of USP9X as an ERG stabilizing deubiquitinase suggests that reduction of ERG protein levels by TRIM25 mediated proteasomal degradation is prevented by expression of USP9X in fusion positive prostate cancer cells.|Using several biochemical assays we show that TRIM25 mediates the polyubiquitination of full-length ERG as well as N-terminally truncated ERG.

SIGNOR-278732

O43318

O14733

1

phosphorylation

up-regulates activity

0.645

Upon TNFα stimulation, MEKK1, ASK1, and TAK1 phosphorylate and activate MKK7, which in turn activates JNK

SIGNOR-274146

Q15759

P05787

1

phosphorylation

up-regulates

0.427

Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-114063

Q9UQM7

P41134

1

phosphorylation

up-regulates activity

0.2

Here we show that CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy.

SIGNOR-277367

P06213

P10586

0

dephosphorylation

down-regulates

0.577

Lar ptpase shows strong preference for dephosphorylation first at py5 (at tri-, di-, and monophosphotyrosyl levels). Initially this regioselectivity gives the y5(py9)(py10) diphospho regioisomer, followed by equal dephosphorylation at py9 or py10 to give the corresponding monophosphoryl species on the way to fully dephosphorylated product.

SIGNOR-76005

Q05925

P55075

1

transcriptional regulation

down-regulates quantity by repression

0.452

Our results in ES cells suggest that Engrailed inhibits Fgf8 expression in the absence of Pbx1. We identified single Engrailed- and Pbx-binding sites in the Fgf8 intron that inhibit expression of Fgf8 in mouse ES cells, but that together can allow full Fgf8 expression. Our data support the model that Engrailed heterodimerized with Pbx might activate transcription, while Engrailed or Pbx proteins alone might repress transcription

SIGNOR-265776

P31749

Q8N5S9

0

phosphorylation

up-regulates activity

0.379

Protein kinase B (PKB) was recently reported to be activated on the phosphorylation of Thr(308) by Ca(2+)/calmodulin-dependent protein kinase kinase alpha (CaM-kinase kinase alpha), suggesting that PKB was regulated through not only the phosphoinositide 3-kinase pathway but also the Ca(2+)/calmodulin protein kinase pathway.

SIGNOR-252609

Q14012

P18846

1

phosphorylation

up-regulates activity

0.512

Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.

SIGNOR-250611

P17948

Q12913

0

dephosphorylation

down-regulates

0.362

Vegf acts by binding to two high affinity receptor tyrosine kinases: vegf receptor (vegfr)* 1 also called flt-1, and vegfr-2, also called flk-1/kdr a dominant-negative mutant of high cell densityenhanced ptp 1 (dep-1)//cd148 as well as reduction of its expression by rna interference partially restore vegfr-2 phosphorylation and map kinase activation.

SIGNOR-101272

Q14896

Q05655

0

phosphorylation

up-regulates

0.2

The triple aspartic acid mutation shows greater distance between the two thick myosin filaments (affects the steric arrangement of the filament distances) in heart tissue. Mutation is cardioprotective during stress (ischemia-reprofusion injury) against apoptosis similar to isoproterenol treatment.

SIGNOR-150355

P18848

O43776

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269422

P31749

O14757

1

phosphorylation

down-regulates

0.43

The chk1 protein phosphorylated by pkb on serine 280 does not enter into protein complexes after replication arrest. Moreover, chk1 phosphorylated by pkb fails to undergo activating phosphorylation on serine 345 by atm/atr. Phosphorylation by atm/atr and association with other checkpoint proteins are essential steps in activation of chk1.

SIGNOR-124365

Q9C029

Q5TA31

1

ubiquitination

up-regulates quantity by stabilization

0.269

Taken together, these data suggest that Trim7 directly ubiquitinates RACO-1.

SIGNOR-278536

P10398

Q13153

0

phosphorylation

up-regulates

0.267

Phosphorylation of endogenous a-raf, b-raf and raf-1 on the homologous pak phosphorylation sites (serine 299, serine 445, or serine 338 respectively)we found that the phosphorylation of a-raf on serine 299 was also stimulated by egf, although the duration of phosphorylation on this site was much shorter than for raf-1. Thus, by analogy with raf-1, phosphorylation of this site may play an important role in the a-raf activation mechanism.

SIGNOR-236342

P04637

P62714

0

dephosphorylation

up-regulates quantity by stabilization

0.437

A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55| In this study, we reported that the specific B regulatory subunits of PP2A B56gamma1 and B56gamma3 mediate dephosphorylation of p53 at Thr55. Ablation of the B56gamma protein by RNAi, which abolishes the Thr55 dephosphorylation in response to DNA damage, reduces p53 stabilization, Bax expression and cell apoptosis

SIGNOR-248583

Q13049

Q96EV8

1

ubiquitination

down-regulates quantity

0.537

TRIM32 is an E3 ubiquitin ligase for dysbindin. TRIM32 targets dysbindin for degradation.

SIGNOR-265658

Q99816

P17542

0

polyubiquitination

down-regulates quantity by destabilization

0.2

These data suggest that Tal mediates polyubiquitylation of the lysine residues in the VPS28-binding region of TSG101, leading to subsequent degradation of TSG101.

SIGNOR-271636

P78362

Q07955

1

phosphorylation

up-regulates activity

0.616

In contrast, SRPK1 or SRPK2 overexpression upregulated the phosphorylation and nucleus accumulation of SRSF1.|Therefore, SRPK1 and SRPK2 may directly phosphorylate SRSF1 and promote it nucleus translocation, subsequently modulate MKNK2 alternative splicing.

SIGNOR-279660

P0DOX3

Q99856

0

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

Q8TDY4

Q9P289

0

phosphorylation

up-regulates activity

0.2

Here we show that MST4 phosphorylates ACAP4, an ARF6 GTPase-activating protein, at Thr545|Significantly, phosphorylation of Thr545 enables ACAP4 to interact with ezrin. Given the location of Thr545 between the GTPase-activating protein domain and the first ankyrin repeat, we reason that MST4 phosphorylation elicits a conformational change that enables ezrin-ACAP4 interaction.

SIGNOR-272238

P01111

Q06124

0

dephosphorylation

up-regulates activity

0.673

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-255754

P24394

O60674

1

phosphorylation

up-regulates activity

0.624

Downstream intracellular signaling from the IL-4IL-4Rc complex involves activation of the Jak1 and Jak3 kinases, phosphorylation of the Stat6 transcription factor, and activation of the insulin receptor substrate (IRS)-2 and Dok2-signaling intermediates. IL-13 initially binds to IL-13R1 with intermediate affinity, and then heterodimerizes with IL-4R. The IL-13IL-13R1IL-4R complex activates the Tyk2, Jak2, and Jak1 kinases and Stat6.

SIGNOR-249530

Q13887

Q9HAU4

0

ubiquitination

down-regulates quantity by destabilization

0.37

Consistent with these observations, another study documented that Smurf2 specifically destabilizes KLF5, that the degradation of KLF5 by Smurf2 is disrupted by the proteasome inhibitor MG132, and that Smurf2 ubiquitinates KLF5 .

SIGNOR-278781

P00451

Q8NEV1

0

phosphorylation

down-regulates activity

0.2

Our findings suggest that phosphorylation of factors Va and VIIIa by a platelet casein kinase II-like kinase may downregulate the activity of the two cofactors.| Recombinant human factor VIII also showed incorporation of radioactivity in the presence of purified casein kinase II at the acidic NH2-terminal portion of factor VIII light chain (residues 1648 through 1689). Based on all the considerations reported above Se1657 is the most likely candidate within this region capable of incorporation of radioactivity

SIGNOR-263649

P45974

P0CG47

1

cleavage

up-regulates quantity

0.767

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

SIGNOR-270821

P00519

P12004

1

phosphorylation

up-regulates activity

0.333

In the current study, we are able to establish a new pathway in which the Ron receptor tyrosine kinase activates c-Abl which in turn catalyzes Y211 phosphorylation of PCNA.|We previously showed that Y211 phosphorylation stabilized chromatin bound PCNA, which in turn promoted cell proliferation, and that c-Abl functioned to enhance chromatin association of PCNA in cancer cells.

SIGNOR-279389

Q96GD4

Q9H0H5

1

phosphorylation

up-regulates activity

0.78

It was found that the 5A fragment in which five Ser/Thr residues were substituted with Ala (S144A/T145A/S185A/T186A/S187A) fully prevented phosphorylation (Fig. 5B), confirming that Aurora B primarily phosphorylates five Ser/Thr residues in the basic region of MgcRacGAP. | the strong phosphorylation of the basic region of MgcRacGAP by Aurora B kinase was demonstrated, and this phosphorylation prevents the inhibition of MgcRacGAP GAP activity by PRC1

SIGNOR-250590

Q13188

P31751

0

phosphorylation

down-regulates

0.261

Akt phosphorylates mst2 at thr117 in vitro and in vivo, which leads to mst2 cleavage and kinase activity as well as nuclear translocation.

SIGNOR-164302

P04637

Q9HCI7

0

ubiquitination

down-regulates activity

0.37

Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.

SIGNOR-271774

P50750

Q9H0D6

1

phosphorylation

up-regulates activity

0.278

Among the RNA processing factors phosphorylated by Cdk9 was the 5'-to-3' "torpedo" exoribonuclease Xrn2, required in transcription termination by Pol II, which we validated as a bona fide P-TEFb substrate in vivo and in vitro. Phosphorylation by Cdk9 or phosphomimetic substitution of its target residue, Thr439, enhanced enzymatic activity of Xrn2 on synthetic substrates in vitro.

SIGNOR-277194

P49023

Q15256

0

dephosphorylation

down-regulates activity

0.2

Here, we show that paxillin is a direct substrate of PTPRT and that PTPRT specifically regulates paxillin phosphorylation at tyrosine residue 88 (Y88) in colorectal cancer (CRC) cells. We engineered CRC cells homozygous for a paxillin Y88F knock-in mutant and found that these cells exhibit significantly reduced cell migration and impaired anchorage-independent growth,

SIGNOR-248720

O14641

P53350

0

phosphorylation

up-regulates

0.465

Dvl2 bound to and was phosphorylated at thr206 by a mitotic kinase, polo-like kinase 1 (plk1), and this phosphorylation was required for spindle orientation and stable microtubule (mt)-kt attachment

SIGNOR-167858

O43524

Q15831

1

transcriptional regulation

down-regulates quantity

0.634

SGK-1 Negatively Regulates LKB1 Expression via FOXO3 Transcription Factor

SIGNOR-255758

P17612

P11137

1

phosphorylation

down-regulates activity

0.36

CAMP-dependent protein kinase activity disrupts the MAP2-microtubule interaction in living HeLa cells. S319, S350, and S382 were thus identified as preferred targets of PKA

SIGNOR-250003

Q16566

P56524

1

phosphorylation

down-regulates activity

0.62

CaMKIV phosphorylates HDAC4 in vitro and promotes its nuclear-cytoplasmic shuttling in vivo. | Thus, CaMKIV can phosphorylate HDAC4 at Ser-467 and/or Ser-632 in vitro. | Collectively, our results suggest that CaMKIV reverses the transcriptional repression activity of HDAC4 by stimulating the mobilization of HDAC4 out of the nucleus.

SIGNOR-250712

Q13315

O14757

1

phosphorylation

up-regulates

0.845

Atr (predominantly) or atm (to a lesser extent) phosphorylates chk1 at ser317/345, directly leading to activation.

SIGNOR-163106

P10586

P56945

1

dephosphorylation

down-regulates quantity by destabilization

0.339

LAR specifically dephosphorylates and destabilizes p130Cas and may play a role in regulating cell adhesion-mediated cell survival.|Transmembrane tyrosine phosphatase LAR induces apoptosis by dephosphorylating and destabilizing p130Cas.

SIGNOR-276998

O14672

P04626

1

cleavage

up-regulates activity

0.344

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

SIGNOR-259845

P31749

Q96IZ0

1

phosphorylation

down-regulates activity

0.39

Prostate apoptosis response protein-4 (Par-4) sensitizes cells to chemotherapy

SIGNOR-279668

P50542

P28328

0

ubiquitination

down-regulates quantity by destabilization

0.579

Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.

SIGNOR-253021

P41279

P45985

1

phosphorylation

up-regulates

0.559

Furthermore, we found that immunoprecipitated tpl-2 could directly phosphorylate and activate both mek-1 and mkk4 (also known as sek-1)

SIGNOR-196744

P27986

Q12913

0

dephosphorylation

down-regulates

0.261

As reduction of pi3k activity by cd148 or shp-1 [32] is not large (2540%), it is likely that these ptps may function as modulators of the pi3k pathway rather than suppressors.

SIGNOR-178049

P08151

Q16539

0

phosphorylation

down-regulates quantity by destabilization

0.27

Here, we show that SHH inactivates p38α (MAPK14) in a smoothened-dependent manner, conversely, p38α directly phosphorylates GLI1 on Ser937/Ser941 (human/mouse) to induce GLI1's proteasomal degradation and negates the transcription of SHH signaling.

SIGNOR-277916

Q9P2P5

O15350

1

ubiquitination

up-regulates quantity by stabilization

0.37

P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.

SIGNOR-269457

P10071

P48729

0

phosphorylation

down-regulates

0.6

In principle, pka, ck-1 and gsk3 can phosphorylate as many as 19 serine residues in gli3: fourpkasites, three primarygsk3sites, four primary ck-1 sites and eight secondary gsk3 and ck-1 sites

SIGNOR-116512

P06493

Q9UPT9

1

phosphorylation

up-regulates activity

0.47

On the other hand, CDK1 enhances USP22 activity to stabilize CCNB1 during the G2/M phase.|Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1.

SIGNOR-278241

Q14676

O76064

1

relocalization

up-regulates

0.757

Rnf8 relocalizes to dna damage sites via a phospho-dependent interaction with mdc1

SIGNOR-179820

P51911

P06241

0

phosphorylation

down-regulates activity

0.333

We identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. we have localized the tyrosines phosphorylated without actin to Tyr261 in calponin h3 and to Tyr261 and Tyr182 in calponin h1. Tyrosine phosphorylation of calponins inhibits their binding to F-actin

SIGNOR-251157

Q9NPC2

P17612

0

phosphorylation

up-regulates

0.2

Patch clamp analysis, flow cytometry, and immunocytochemistry studies of hek293 transfected with wt hk2p3.1 and cultured in the presence of pka activators or inhibitors all confirm that activation of pka resulted in an increase in hk2p3.1 current expression (figs. 4_4?6) and demonstrate the dynamic regulatory effect of pka activity on k2p3.1 channel expression.

SIGNOR-172466

P05412

P15407

1

transcriptional regulation

up-regulates quantity by expression

0.826

Members of the AP1 family distinctly regulated the fra-1 promoter. In particular, coexpression of c-Jun, Jun-D, and Fra-2 up-regulated fra-1 transcription.

SIGNOR-261604

P53396

O14874

0

phosphorylation

up-regulates activity

0.2

BCKDK can activate ACLY and promote the cleavage of citric acid into acetyl-CoA, and oxaloacetate.|BCKDK can phosphorylate BCKDHA and ATP citrate lyase (ACLY), exerting opposing effects on both.

SIGNOR-280194

P12931

P53801

1

phosphorylation

up-regulates activity

0.2

Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS.

SIGNOR-273810

Q8IYA7

Q13950

1

transcriptional regulation

up-regulates quantity by expression

0.301

MKX is a meniscus-enriched transcription factor. In human meniscus cells, MKX regulates the expression of meniscus marker genes, OA-related genes, and other transcription factors, including Scleraxis (SCX), SRY Box 5 (SOX5), and Runt domain-related transcription factor 2 (RUNX2).

SIGNOR-267215

Q16695

Q92830

0

acetylation

down-regulates activity

0.2

The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14.

SIGNOR-269604

Q9H410

Q96GD4

0

phosphorylation

down-regulates

0.653

To determine whether the combinatorial regulation of the kmn network by aurora b observed in vitro is critical to controlling kinetochore-microtubule attachments in vivo, we next investigated the effect of the phosphomimetic (to aspartate) and nonphosphorylatable (to alanine) mutants of dsn1, knl1, and ndc80 in vertebrate cells. We predicted that both types of mutations in critical phosphorylation sites would affect chromosome segregation, since preventing the inactivation of inappropriately attached kinetochores by aurora b (in the nonphosphorylatable mutant) or constitutively inactivating this attachment (in the phosphomimetic mutant).

SIGNOR-165546

Q14643

P06241

0

phosphorylation

up-regulates

0.487

We have identified tyrosine 353 (tyr353) in the ip3-binding domain of type 1 ip3r (ip3r1) as a phosphorylation site for fyntyrosine phosphorylation of ip3r1 increased ip3 binding at low ip3 concentrations (<10 nm).

SIGNOR-121795

P49327

P04626

0

phosphorylation

up-regulates activity

0.442

Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression ( xref ; xref ).|Conversely, HER2 directly phosphorylates and activates FASN, while it also promotes FASN gene expression.

SIGNOR-278399

Q13535

Q13315

1

phosphorylation

up-regulates activity

0.747

Atr-dependent phosphorylation and activation of atm in response to uv treatment or replication fork stalling. Here, we show that atm phosphorylation at ser1981, a characterised autophosphorylation site, is atr-dependent and atm-independent following replication fork stalling or uv treatment

SIGNOR-150870

P08581

Q05397

1

phosphorylation

up-regulates

0.497

Met-mediated fak phosphorylation could further activate fak. Indeed, we found that met phosphorylates fak at its known phosphorylation sites, including tyr-576 and tyr-577, both of which are located in the activating loop within the catalytic domain

SIGNOR-147199

P68400

P18858

1

phosphorylation

up-regulates activity

0.34

Moreover, these data confirmed the occurrence of Ser66 phosphorylation, which was previously studied with a specific monoclonal antibody (23).

SIGNOR-103258

P40763

P00533

0

phosphorylation

up-regulates activity

0.879

The transcription factors stat1, stat3, and stat5 are directly phosphorylated by erbb-1, subsequent to which they dimerize through phosphotyrosine-sh2 domain interactions and translocate to the nucleus to activate gene trascription critical for proliferation.

SIGNOR-121965

P17612

P16144

1

phosphorylation

down-regulates

0.2

Additionally, we show that s1360 and s1364 of beta4 are the only residues phosphorylated by pkc and pka in cells, respectivelywe have defined three regions on beta4 that together harbor all the serine and threonine phosphorylation sites and show that three serines (s1356, s1360, and s1364), previously implicated in hd regulation, prevent the interaction of beta4 with the plectin actin-binding domain when phosphorylated

SIGNOR-156873

Q13043

Q15424

1

phosphorylation

down-regulates activity

0.2

In the present study, we demonstrate that the chromatin scaffold protein SAFB1 interacts with and is phosphorylated by MST1 and is a novel regulator of AR capable of integrating signaling between the AR and MST1 networks.

SIGNOR-279296

P17252

P04083

1

phosphorylation

up-regulates

0.2

The authors identified several phosphorylated residues by a combination of peptide mapping and sequence analysis and showed that recombinant pp60c-src phosphorylates annexin a1 near its amino terminus, at tyrosine 21 (tyr21). Also polyoma virus middle t/pp60c-src complex, recombinant pp50v-abl, and the egf receptor/kinase phosphorylated the same tyrosine residue. It was also shown that serine 27 residue of anxa1 is the primary site phosphorylated by protein kinase c (pkc). In the same study, the threonine 41 residue has been identified as a pkc substrate as well. The adenosine cyclic 3_,5_-phosphate dependent protein kinase a (pka) phosphorylates anxa1 in its carboxyl-terminal core at the threonine 216 residue (thr216) [2].The phosphorylation of serine 27 is essential for annexin a1 membrane localization.

SIGNOR-202780

P28698

O96013

0

phosphorylation

up-regulates activity

0.2

Here, we link ErbB2 activation to invasion via ErbB2-induced, SUMO-directed phosphorylation of a single serine residue, S27, of the transcription factor myeloid zinc finger-1 (MZF1). Phosphorylation of MZF1-S27 is an early response to ErbB2 activation and results in increased transcriptional activity of MZF1.The phosphorylation of MZF1-S27 is preceded by poly-SUMOylation of K23, which can make S27 accessible to efficient phosphorylation by PAK4.

SIGNOR-277422

P17612

O14965

1

phosphorylation

up-regulates activity

0.512

Aurora2 is regulated by phosphorylation. phosphorylation occurs on a conserved residue, Threonine 288, within the activation loop of the catalytic domain of the kinase and results in a significant increase in the enzymatic activity. Threonine 288 resides within a consensus motif for the cAMP dependent kinase and can be phosphorylated by PKA in vitro.

SIGNOR-250337

Q13315

Q9Y6K9

1

phosphorylation

down-regulates activity

0.739

Atm phosphorylates serine-85 of nemo to promote its ubiquitin-dependent nuclear export.

SIGNOR-144813

Q86YT6

P63162

1

ubiquitination

down-regulates quantity by destabilization

0.2

These data indicate that Mib1 reduces SMN protein stability by targeting it for degradation by the proteasome and represents a new modifier of the SMA phenotype.|Through this study, we provide evidence that the E3 ligase Mib1 ubiquitinates and catalyzes SMN protein degradation.

SIGNOR-278632

Q13501

O75385

0

phosphorylation

down-regulates quantity by destabilization

0.567

ULK1 phosphorylates p62 at the Ser403 site.

SIGNOR-278349

Q14872

Q9NRM7

0

phosphorylation

down-regulates activity

0.2

The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1|the Hippo pathway kinase LATS phosphorylates and inhibits MTF1|LATS phosphorylates MTF1 at S152 and disrupts its association with the promoters of heavy metal response genes, resulting in the loss of heavy metal response gene expression

SIGNOR-275475

O75688

O43318

1

dephosphorylation

down-regulates activity

0.551

In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1.

SIGNOR-277154

Q06413

P23409

1

transcriptional regulation

up-regulates quantity by expression

0.565

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

SIGNOR-238652

Q9Y2X9

Q9UKB1

0

ubiquitination

down-regulates quantity by destabilization

0.2

E3 ligase the beta-transducin repeat-containing protein 2 (beta-TrCP2) governs the ubiquitination and degradation of ZNF281. In human CRC specimens, endogenous beta-TrCP2 were inversely correlated with ZNF281.

SIGNOR-264897

Q9BXH1

P04626

0

phosphorylation

down-regulates quantity by destabilization

0.281

HER2 phosphorylates and destabilizes pro-apoptotic PUMA. Using an intracellular assay, we found PUMA to be phosphorylated in breast cancer cells with activated HER2. Via cell-free HER2 kinase assay, we observed that PUMA was directly phosphorylated by HER2. Activation of HER2 decreased PUMA protein half-life.

SIGNOR-276474

Q9Y6D9

P33981

0

phosphorylation

up-regulates activity

0.819

Furthermore, although catalytically inactive Mps1 can restore kinetochore localization of Mad1, only the active kinase restores Mad2 localization.|Indeed, Mps1 can phosphorylate Mad1 in vitro.

SIGNOR-279000

P51812

P11362

1

phosphorylation

down-regulates quantity

0.357

Both in vitro and in vivo experiments confirmed the interaction and we show that phosphorylated RSK2 binds to and phosphorylates serine 789 in the C-terminal tail of FGFR1.prevention of FGFR1 phosphorylation by inhibition of RSK2 activity or mutation of serine 789 to alanine reduced FGFR1 endocytosis and ubiquitination explaining mechanistically the prolonged signaling activity.

SIGNOR-276599

Q16539

P49918

1

phosphorylation

up-regulates

0.262

G1-s control by p38/hog1 sapks upon osmostress. Upon osmostress, activated p38 and hog1 sapks phosphorylate the s/cdk inhibitor p57 or sic1 respectively at one single residue. In mammalian cells (left panel), p57 phosphorylation on thr143 leads to an increase of the affinity of p57 towards the cyclin a/cdk2 complex leading to a g1 arrest.

SIGNOR-198390

O15105

Q09472

0

acetylation

up-regulates

0.464

Here we present evidence that smad7 interacts with the transcriptional coactivator p300, resulting in acetylation of smad7 on two lysine residues in its n terminus. Acetylation or mutation of these lysine residues stabilizes smad7 and protects it from tgfbeta-induced degradation. we have recently shown that smad7 is acetylated on lysine residues 64 and 70 by p300

SIGNOR-95169

Q01196

P10147

1

transcriptional regulation

up-regulates quantity by expression

0.2

We show that RUNX1 can specifically bind to both RUNX sites but that only the proximal RUNX site is essential for PMA/ PHA stimulation of the MIP-1a promoter in Jurkat T-cells. We also show that the endogenous MIP-1a promoter is constitutively bound by RUNX1.

SIGNOR-251738

Q04759

Q9BWT7

0

relocalization

up-regulates activity

0.435

TBKBP1 recruits TBK1 to protein kinase C-theta (PKCθ) through a scaffold protein, CARD10. This enables PKCθ to phosphorylate TBK1 at Ser 716, a crucial step for TBK1 activation

SIGNOR-272471

P35247

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.251

Cotransfection of C/EBPalpha, C/EBPbeta, or C/EBPdelta cDNA in H441 lung adenocarcinoma cells significantly increased the luciferase activity of a wild-type SP-D promoter construct containing 698 bp of upstream sequence (SS698). Transfection of C/EBP also increased the level of endogenous SP-D mRNA in H441 cells| Thus, interactions among C/EBP elements in the near-distal promoter can modulate the promoter activity of SP-D.

SIGNOR-254045

P27361

P51170

1

phosphorylation

down-regulates quantity by destabilization

0.28

Using a number of different approaches it was demonstrated that the protein kinase acting on betaThr-613 and gammaThr-623 is the extracellular regulated kinase (ERK). It is suggested that an ERK-mediated phosphorylation of betaThr-613 and gammaThr-623 down-regulates the channel by facilitating its interaction with Nedd4.

SIGNOR-249449

P07996

Q9Y222

0

transcriptional regulation

up-regulates quantity by expression

0.2

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-261587

Q93008

P06493

0

phosphorylation

up-regulates activity

0.279

Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis.

SIGNOR-275608

O43791

Q9HCU9

1

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

Q96T51

P61106

0

relocalization

up-regulates activity

0.63

Here, we have demonstrated that Rab14 interacts with RUFY1, previously identified as a Rab4 effector, and is required for RUFY1 recruitment onto endosomes and efficient recycling of Tfn.

SIGNOR-261279

O75431

O15033

0

ubiquitination

down-regulates quantity by destabilization

0.2

Therefore, these results implied that AREL1 ubiquitinates and promotes the degradation of MTX2.

SIGNOR-267674